Organophosphorus Chemistry E-Book

• Herausgeber: Wiley-VCH Verlag GmbH & Co. KGaA
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 951

Veröffentlichungsjahr: 2019

Beschreibung

Filling the gap for an up-to-date reference that presents the field of organophosphorus chemistry in a comprehensive and clearly structured way, this one-stop source covers the chemistry, properties, and applications from life science and medicine. Divided into two parts, the first presents the chemistry of various phosphorus-containing compounds and their synthesis, including ylides, acids, and heterocycles. The second part then goes on to look at applications in life science and bioorganic chemistry. Last but not least, such important practical aspects as 31P-NMR and protecting strategies for these compounds are presented.

For organic, bioinorganic, and medicinal chemists, as well as those working on organometallics, and for materials scientists. The book, a contributed work, features a team of renowned scientists from around the world whose expertise spans the many aspects of modern organophosphorus chemistry.

Leseprobe

Table of Contents

Cover

1 Phosphines and Related Tervalent Phosphorus Systems

1.1 Introduction

1.2 Synthesis of Phosphorus Ligands

1.3 Ligand Properties

1.4 Rhodium‐Catalyzed Hydroformylation with Xantphos‐Type Ligands

1.5 Cross‐Coupling Catalysis with Mono‐ and Bidentate Phosphines

1.6 Decomposition Reactions

References

2 Recent Developments in Phosphonium Chemistry

2.1 Introduction

2.2 Synthesis of Phosphonium Salts

2.3 Phosphonium Salts as a Tool for Organic Synthesis

2.4 Phosphonium Salts for Biological and Medical Applications

2.5 Conclusion

References

3 Phosphorus Ylides and Related Compounds

3.1 Introduction

3.2 Preparation of Phosphorus Ylides

3.3 Applications of Phosphorus Ylides in Organic Synthesis

3.4 Conclusions

Acknowledgments

References

4 Low‐Coordinate Phosphorus Compounds with Phosphaorganic Multiple Bond Systems

4.1 Introduction

4.2 General Considerations on Structure and Bonding of PC Multiple Bond Systems

4.3 Synthetic Approaches

4.4 Reactivity

4.5 Applications of Phosphorus–Carbon Multiple Bond Systems

References

5 Pentacoordinate Phosphorus Compounds

5.1 History of Pentacoordinate Phosphorus Compounds

5.2 Preparation of Pentacoordinate Phosphorus Compounds

5.3 Structure of Trigonal Bipyramid and Square Pyramid

5.4 Interconversion of Pentacoordinate Phosphorus Compounds

5.5 Apicophilicity

5.6 Hydrolysis of Phosphate Esters

References

6 Hexacoordinate Phosphorus Compounds

6.1 Preparation and Structure of Hexacoordinate Phosphorus Compounds

6.2 Stereochemistry of Hexacoordinate Phosphorus Compounds

6.3 Hexacoordinate Compounds with Intramolecular Coordination

6.4 Theoretical Studies on Hexacoordinate Phosphorus Compounds

6.5 Hexacoordinate Phosphates as Counter Anions for Complex Ligands

References

7 Methods for the Introduction of the Phosphonate Moiety into Complex Organic Molecules

7.1 Introduction

7.2 PC (sp) Bond Formation

7.3 PC (sp) Bond Formation

7.4 PC (sp) Bond Formation

7.5 Conclusion

References

8 Phosphorus Heterocycles

8.1 Introduction

8.2 Five‐Membered Phosphorus Heterocycles

8.3 Five‐Membered Phosphorus Heterocycles with One Phosphorus Atom: 1

H

‐Phospholes and Fused Aromatic Systems Containing Phosphole Ring

8.4 Aromaticity of 1

H

‐Phospholes and 1

H

‐Phosphole‐Containing Heterocyclic Systems

8.5 1

H

‐Phospholes

8.6 Synthesis of 1

H

‐Phospholes Following [4+1] and [2+2+1] Synthetic Strategies

8.7 Synthesis of Phospholes by [3+2] Cyclization Reaction

8.8 Synthesis of 1

H

‐Phospholes by Intramolecular Cyclization Reactions

8.9 Synthesis of Phosphorus‐Containing Porphyrin Hybrids

8.10 Fused Heterocycles with 1

H

‐Phosphole Structural Fragment

8.11 Synthesis‐Fused 1

H

‐Phospholes Following [4+1] and [2+2+1] Synthetic Strategies

8.12 Synthesis of Fused Phospholes Following [3+2] Synthetic Strategies

8.13 Synthesis of Fused Phospholes Following Intramolecular Cyclization Strategies

8.14 Application of CH Bond Activation Protocols for the Synthesis of Benzo[

b

]phosphindoles via Intramolecular Cyclization

8.15 Synthesis of π‐Conjugated Benzo[

b

]phosphindoles Following [2+2+2] Cycloaddition Synthetic Strategy

8.16 Five‐Membered Phosphorus Heterocycles with One Heteroatom

8.17 Synthesis of 1,2‐ and 1,3‐Heterophospholes: General Overview

8.18 1,2‐Azaphospholes

8.19 Synthesis of 1,2‐Azaphospholes Following [3+2] Synthetic Strategies

8.20 Synthesis of Fused 1,2‐Azaphospholes via Intramolecular Cyclization Strategy

8.21 Synthesis of 1,2‐Oxophospholes, 1,2‐Thiaphosphols, and 1,2‐Selenophosphols

8.22 1,3‐Azaphospholes

8.23 Synthesis of 1,3‐Azaphospholes by Intramolecular Cyclization Reactions

8.24 Synthesis of 1,3‐Oxaphospholes, 1,3‐Thiaphospholes, and 1,3‐Selenophospholes

8.25 Six‐Membered Phosphorus Heterocycles

8.26 Phosphinines: General Overview

8.27 Synthesis of λ‐ and λ‐Phosphenines: General Overview

8.28 Synthesis of Phosphenines Following [5+1] Synthetic Strategy

8.29 Synthesis of Phosphenines Following [4+2] Synthetic Strategy

8.30 Synthesis of Phosphenines from Phospholes

8.31 Synthesis of Phosphenines Following 1,6‐Electrocyclization Strategy

8.32 Synthesis of Fused λ‐ and λ‐Phosphenines: General Overview

8.33 Synthesis of Fused Phosphenines Following [4+2] Synthetic Strategy

8.34 Synthesis of Fused Phosphenines by Intramolecular Cyclization

8.35 Synthesis of Fused Phosphenines Following [5+1] Synthetic Strategy

8.36 Six‐Membered Phosphorus Heterocycles with One Heteroatom

8.37 Synthesis 1,2‐, 1,3‐, and 1,4‐Heterophosphinines

8.38 1,2‐Azaphosphenines

8.39 Synthesis of 1,2‐Azaphosphenines Following [3+1+1+1] Synthetic Strategy

8.40 Synthesis of 1,2‐Azaphosphenines Following [3+3] Synthetic Strategy

8.41 Synthesis of 1,2‐Azaphosphenines Following [3+2+1] Synthetic Strategies

8.42 Synthesis of 1,2‐Azaphosphenines Following [5+1] Synthetic Strategies

8.43 Synthesis of 1,2‐Azaphosphenines Following [4+2] Synthetic Strategies

8.44 Synthesis of 1,2‐Azaphosphenines Following Intramolecular Cyclization Strategies

8.45 1,3‐Azaphosphenines

8.46 Synthesis of 1,3‐Azaphosphenines Following [5+1] Synthetic Strategy

8.47 Synthesis of 1,3‐Azaphosphenines Following [4+2] Synthetic Strategies

8.48 1,4‐Azaphosphenines

8.49 Oxygen‐ and Sulfur‐Containing Heterophosphinines

8.50 Application and Synthesis of Phosphoborine Systems

8.51 Application and Synthesis of 1,4‐Phosphasiline System

8.52 Synthesis of Germanium‐ and Tin‐Containing Heterophosphinines

References

9 Modern Aspects of

31

P NMR Spectroscopy

9.1 Introduction

9.2 Chemical Shifts

9.3 Coupling Constants

9.4 Two‐Dimensional (2D) P NMR Techniques

9.5 Analytical Methods

9.6 Diffusion‐Ordered NMR Spectroscopy (DOSY)

9.7 Solid‐State (SS) P NMR

9.8 Physical and Chemical Processes of Organophosphorus Compounds

9.9 Identification of Intermediates and Monitoring Their Reactivity

9.10 Conclusion

Acknowledgment

References

10 Phosphorus in Chemical Biology and Medicinal Chemistry

10.1 Phosphorus and Life: An Introduction

10.2 Unnatural Nucleotides as Chemical Tools in Biology

10.3 Prodrugs of Nucleoside Phosphates and Phosphonates

10.4 Synthesis and Medical Applications of Bisphosphonates

10.5 Conclusion: The Future of Phosphorus in Chemical Biology and Medicinal Chemistry

References

11 Future Trends in Organophosphorus Chemistry

11.1 Introduction

11.2 Facile CP Bond Formation Methods

Utilization of Organophosphorus Compounds

References

Index

End User License Agreement

List of Tables

Chapter 1

Table 1.1 Typical

χ

‐values of ligands PR

3

.

Table 1.2 Typical

θ

values of phosphorus ligands PR

3

.

Table 1.3 Diphosphines and their natural bite angles

β

n

.

Chapter 6

Table 6.1

31

P NMR chemical shifts of phosphorus chlorides.

Chapter 7

Table 7.1 Regioselectivity of Rh‐catalyzed hydrophosphonylation.

Table 7.2 Ni‐catalyzed Michaelis–Arbuzov reaction of aryl bromide

45

.

Chapter 9

Table 9.1 Typical chemical shifts for noncyclic three‐ and four‐coordinate organ...

List of Illustrations

Chapter 1

Scheme 1.1 Reaction 1, alkylation of PCl bonds.

Scheme 1.2 Reaction 2, synthesis of Josiphos.

Scheme 1.3 Reaction 3, aryl–methyl exchange.

Scheme 1.4 Reaction 4, P‐chiral phosphines.

Scheme 1.5 Reaction 5, Buchwald's synthetic scheme.

Scheme 1.6 Reaction 6, phosphole synthesis.

Scheme 1.7 Reaction 7.

Scheme 1.8 Reaction 8 [14], P–C cleavage by sodium.

Scheme 1.9 Reaction 9, P–C cleavage by lithium [14].

Scheme 1.10 Reaction 10, P–Cl reduction.

Scheme 1.11 Reaction 11, P–C cleavage in diphosphines.

Scheme 1.12 Reaction 12, reactions of 1,2‐diphospholane.

Scheme 1.13 Reaction 13, synthesis of DIOP via tosylate.

Scheme 1.14 Reactions 14. P–C coupling after conversion of tosylate to halide.

Scheme 1.15 Reaction 15, synthesis of diphosphines from tosylates via phosphide...

Scheme 1.16 Reaction 16, synthesis of the SHOP ligand.

Scheme 1.17 Reaction 17, substitution of fluoride by phosphide base.

Scheme 1.18 Reaction 18, the use of SPOs in diphosphine synthesis.

Scheme 1.19 Reaction 19, Michael addition of phosphide anion.

Scheme 1.20 Reaction 20, radical addition of R

2

PH to alkenes.

Scheme 1.21 Reaction 21, addition of hypophosphorus acid.

Scheme 1.22 Reaction 22, reduction of PO [31, 32].

Scheme 1.23 Reaction 23, reduction of PO.

Scheme 1.24 Reaction 24, reduction of PS.

Scheme 1.25 Reaction 25, reduction of PO.

Scheme 1.26 Reaction 26, conversion of PH into PCl.

Scheme 1.27 Reaction 27, cross‐coupling PC bond formation.

Scheme 1.28 Reaction 28, cross‐coupling PC bond formation.

Scheme 1.29 Reaction 29, Cu‐catalyzed cross‐coupling PC bond formation.

Scheme 1.30 Reaction 30, synthesis of Shell's polyketone ligand.

Scheme 1.31 Reaction 31, DIPAMP synthesis.

Scheme 1.32 Reaction 32, stereoselective lithiation.

Scheme 1.33 Reaction 33, application of Reaction 32.

Figure 1.1 Ligand effect on the CO‐stretching frequency.

Figure 1.2 Tolman's method for determining the cone angle.

Scheme 1.34 Bidentate ligands and their natural bite angles.

Scheme 1.35 “

Trans

” ligands.

Scheme 1.36 Ligands for bimetallic complexes and metal nanoparticles.

Scheme 1.37 Chiral ligands by Knowles.

Scheme 1.38 Monophos asymmetric hydrogenation.

Scheme 1.39 Duphos ligands, chiral substituents at phosphorus.

Scheme 1.40 Atropisomeric bisphosphines.

Scheme 1.41 Spiro bisphosphines.

Scheme 1.42 Phanephos.

Scheme 1.43 Synthesis of Josiphos ligands.

Scheme 1.44 BTA ligands for helical symmetry.

Scheme 1.45 Structure of BISBI.

Scheme 1.46 Xantphos‐type ligands.

Scheme 1.47 Dibenzophosphole‐ and phenoxaphosphino‐substituted Xantphos ligands...

Scheme 1.48 Simplified mechanism for Pd‐catalyzed cross‐coupling.

Scheme 1.49 Suitable catalysts (precursors) for cross‐coupling catalysis.

Scheme 1.50 Convenient synthesis of PdL

2

complexes.

Scheme 1.51 The first “Buchwald” ligands.

Scheme 1.52 One of the Shell ligands, dtbpp, and the Lucite ligand, dtbpx, for ...

Scheme 1.53 Ligands studied by Hartwig et al.

Scheme 1.54 Meisenheimer intermediates in migratory reductive elimination.

Scheme 1.55 Phosphino–alkene ligand enhancing reductive elimination.

Scheme 1.56 Oxidative addition of arylphosphines after creating a vacancy.

Scheme 1.57 Heck reaction with PPh

3

as the aryl donor.

Scheme 1.58 Polymer end‐capping by phosphonium salts.

Scheme 1.59 Alkyl/aryl exchange at Pd/P under mild conditions.

Scheme 1.60 Incorporation of phenyl groups of PPh

3

in the product.

Scheme 1.61 Formation of Ph

5

FcP

t‐

Bu

2

(Q‐Phos) via phenylation with PhCl.

Scheme 1.62 Various decomposition pathways for phosphite ligands.

Scheme 1.63 Typical bulky monophosphites and diphosphites.

Scheme 1.64 Metal‐catalyzed Arbuzov reaction leading to phosphite decomposition...

Scheme 1.65 Reactions of phosphites and aldehydes.

Scheme 1.66 Reactivity of various phosphites toward C5‐aldehyde [206]. Percenta...

Scheme 1.67 Phosphite metalation followed by Arbuzov‐like reaction.

Chapter 2

Scheme 2.1 Synthesis of phosphonium salt by reaction of tertiary phosphine with...

Scheme 2.2 Synthesis of phosphonium salts in low polar solvent or without solve...

Scheme 2.3 Synthesis of phosphonium salts from mesylate and tosylate derivative...

Scheme 2.4 Synthesis of phosphonium salts from alkyl triflates.

Scheme 2.5 Synthesis of phosphonium salts from ammonium salts.

Scheme 2.6 Synthesis of phosphonium salts from alcohol, lactone, or carbonate i...

Scheme 2.7 Monoalylation of chiral diphosphine.

Scheme 2.8 Illustration of the synthesis of polyphosphonium derivatives by reac...

Scheme 2.9 Illustration of the synthesis of bisphosphonium derivative by reacti...

Scheme 2.10 First methods reported for the synthesis of tetraarylphosphonium sa...

Scheme 2.11 Reaction of phosphine with aryl halide catalyzed by nickel salts.

Scheme 2.12 Palladium (1 and 2) and nickel (3) catalysis for the synthesis of t...

Scheme 2.13 Synthesis of triarylvinylphosphonium salts.

Scheme 2.14 Synthesis of

ortho

‐functionalized tetrarylphosphonium.

Scheme 2.15 Synthesis of tetraarylphosphonium salts via aryne intermediate and ...

Scheme 2.16 Synthesis of benzyltrialkylphosphonium salt by base‐induced 1,3‐sig...

Figure 2.1 High thermostable tetraarylphosphonium salts.

Scheme 2.17 Homocoupling of aryl and alkynyl Grignard reagents in phosphonium‐b...

Scheme 2.18 Carbonylation‐based reaction carried out in phosphonium‐based ionic...

Scheme 2.19 Diels–Alder reaction in trihexyl‐tetradecylphosphonium bis(trifluor...

Scheme 2.20 Possible mechanism of degradation of phosphonium salt that could ex...

Figure 2.2 Polyfluorinated phosphonium salts used as an extractant or PTC.

Scheme 2.21 First asymmetric synthesis catalyzed by chiral phosphonium salts.

Scheme 2.22 First chiral spiranic phosphonium salts used as a chiral phase tran...

Figure 2.3 Recent chiral phosphonium salts used as chiral phase transfer cataly...

Scheme 2.23 Formation of oxazolone intermediate and racemization of amino acid ...

Scheme 2.24 Formation of an amide bond from HMPA and via an acyloxyphosphonium ...

Figure 2.4 Structure of some typical peptide‐coupling reagents.

Scheme 2.25 Synthesis of some phosphonium reagents aminophosphine (1) and amino...

Scheme 2.26 Synthesis of PyCloP and PyBroP, and BOP reagents.

Scheme 2.27 Synthesis of substituted PyOxP and PyOxB reagents and example of tw...

Scheme 2.28 Mechanism of amide bond formation using a BOP reagent.

Scheme 2.29 Mechanism of amide bond formation using a BOP reagent.

Figure 2.5 Uptake of TPP (triphenylphosphonium)‐delocalized cations into mitoch...

Scheme 2.30 General scheme for the synthesis of cationic lipophilic phosphonium...

Figure 2.6 Phosphonium salts exhibiting antiproliferative activity against MDA‐...

Figure 2.7 Phosphonium salts exhibiting antiproliferative activity against huma...

Figure 2.8 Examples of phosphonium salts evaluated regarding their antiprolifer...

Figure 2.9 Betulonic acid and phosphonium‐based betulonic acid analogs.

Figure 2.10 Ammonium‐ and phosphonium‐based ionic liquids exhibiting anticancer...

Figure 2.11 Structure of ionic liquids with anticancer properties against Sarco...

Figure 2.12 Structure of triphenylpyrylium salt (TPP) used for imaging HEK‐293 ...

Scheme 2.31 Oxidation of MitoPY1 120 with H

2

O

2

.

Figure 2.13 Structure of TPP fluorescent and [

18

F]TPP PET/CT probe.

Figure 2.14 Phosphonium‐based cationic lipids and cationic polymers used for nu...

Figure 2.15 Examples of some phosphonium salts presenting antibacterial activit...

Figure 2.16 Examples of some phosphonium pyridoxine salts presenting antibacter...

Scheme 2.32 Examples of some phosphobetaine salts presenting antibacterial acti...

Figure 2.17 Examples of phosphonium polymer salts presenting antibacterial acti...

Figure 2.18 Structures of ubiquinone and MitoQ

10

170.

Figure 2.19 Examples of phosphonium salts presenting antiparasitic activity.

Chapter 3

Scheme 3.1 Wittig and Geissler first olefination of carbonyl compounds in 1953.

Scheme 3.2 Canonical structures of a general ylide:

A

– ylene and

B

– ylide.

Figure 3.1 (

C

) Description of the PC bond as a σ‐bond and a π‐bond. (

D

) Descri...

Scheme 3.3 Resonance structures of the phosphorus ylides

1a‐d

.

Scheme 3.4 Preparation of phosphorus ylides by using DBU as a strong base.

Scheme 3.5 Preparation of

C

‐phosphanyl phosphorus ylides

5

and the correspondin...

Scheme 3.6 Synthesis of

C

‐amino phosphorus ylides via carbenoid intermediates.

Figure 3.2 Structure of the phosphatranes ylide.

Scheme 3.7 Synthesis of cumulene phosphorus ylides

7

derived from 9‐fluorenone.

Scheme 3.8 Synthesis of

N

‐heterocyclic β‐keto‐ylides by sequential deprotonatio...

Scheme 3.9 Synthesis of phosphorus ylides

12

and

14

from tetramethylpentalenyl ...

Scheme 3.10 Synthesis of phosphorus cyclic bis‐ylides

16

and

17

.

Scheme 3.11 Synthesis of Rh(I)‐coordinated phosphorus yldiide by deprotonation ...

Scheme 3.12 Synthesis of phosphorus ylides via one‐pot three‐component reaction...

Scheme 3.13 Formation of phosphorus ylides using dimethyl methoxymalonate as Nu...

Scheme 3.14 Synthesis of phosphorus ylides via three‐component reactions and co...

Scheme 3.15 Tebby's rearrangement and reaction of phosphole

28

with dimethyl ac...

Scheme 3.16 Synthesis of phosphorus ylides via

inverse Wittig‐type

reacti...

Scheme 3.17 Preparation of

o

‐phosphanoaryl‐ylide.

Scheme 3.18 Synthesis of new phosphorus ylides by direct chemical modification ...

Scheme 3.19 (1) Synthesis of phosphorus ylides via carbene‐transfer protocol. (...

Scheme 3.20 Alkylation of lithio[bis(diphenylphosphanyl)acetonitrile] to synthe...

Scheme 3.21 Proposed mechanism for the synthesis of alkylphosphonium triphenylc...

Scheme 3.22 Synthesis of phosphorus ylides by transylidation reactions with

in

...

Scheme 3.23 Synthesis of phosphorus ylides and bis‐ylides via phospha‐Michael a...

Scheme 3.24 Synthesis of α‐sulfanyl‐α‐phosphonyl phosphonium ylides

43

.

Scheme 3.25 Synthesis of cyclic phosphorus ylides from diphosphanylketenimines ...

Scheme 3.26 Formation of CC bonds observed by Staudinger and coworkers.

Scheme 3.27 Wittig and Geissler first olefination of carbonyl compounds in 1953...

Scheme 3.28 Synthesis of alkenes via carbanion

47

stabilized by a

electron with

...

Scheme 3.29 The mechanism of the Wittig reaction.

Scheme 3.30 The stereoselectivity of the Wittig reaction.

Figure 3.3 Structure of dibenzylic bis(triphenyl‐phosphonium)‐stoppered [2]rota...

Scheme 3.31 Inter‐ and intramolecular Wittig olefination reaction.

Scheme 3.32 One‐pot synthesis of coumarins via intramolecular Wittig cyclizatio...

Scheme 3.33 Intramolecular Wittig cyclization of

in situ

‐generated phosphorus y...

Scheme 3.34 Synthesis of phosphorus ylides via three‐component reactions and co...

Scheme 3.35 Synthesis of carlosic acid via intermediate

H

.

Scheme 3.36 Synthesis of β‐functionalized terthiophenes.

Scheme 3.37 Wittig olefination and Pd‐catalyzed reactions for the synthesis of

Scheme 3.38 One‐pot Cu(II)‐catalyzed tandem acylation/Wittig lactonization of a...

Scheme 3.39 Asymmetric organocatalytic Michael addition followed by a Wittig re...

Scheme 3.40 Synthesis of discodermolide based on a Wittig olefination reaction.

Scheme 3.41

In situ

Wittig reaction of nonstabilize phosphorus ylides with alde...

Scheme 3.42 Synthesis of polycyclic compound

75

via

in situ

deprotonation and W...

Scheme 3.43 Wittig reaction in aqueous medium.

Scheme 3.44 Gram‐scale synthesis of the anticancer agent DMU‐212 in water.

Scheme 3.45 1,4‐Addition of the nonstabilized phosphorus ylides

77

to α‐phenyls...

Scheme 3.46 Cascade reaction of phosphorus ylides

79

under flash vacuum pyrolys...

Scheme 3.47 Wittig‐type olefination of alcohols with several phosphorus ylides.

Scheme 3.48 Nucleophilic addition of phosphorus ylides to mesoionic compounds

8

...

Chapter 4

Scheme 4.1 Prototypes of phosphaorganic multiple bond systems.

Scheme 4.2 Prototypic low‐coordinate phosphorus compounds.

Scheme 4.3 Formation of planar (“classical”) and

trans

‐bent (“nonclassical”)

EE

Scheme 4.4 Formation of linear and

trans

‐bent

EE

′ triple bonds from a combinati...

Scheme 4.5 Schematic orbital interaction diagram illustrating the mesomeric eff...

Scheme 4.6 An example of an inversely polarized phosphaalkene.

Scheme 4.7 Isolable π‐stabilized anionic PC multiple bond systems.

Scheme 4.8 PC bond polarization in a diphosphabutadiene (

13

) and a diamino phos...

Scheme 4.9 Syntheses of phosphaalkenes by 1,2‐elimination (R = Me, Et).

Scheme 4.10 Syntheses of phosphaalkenes via rearrangement reactions (R = Ph, th...

Scheme 4.11 Syntheses of phosphaalkenes via condensation reactions.

Scheme 4.12 Multifunctional phosphaalkenes (R = H, Ph, OSiMe

3

).

Scheme 4.13 Syntheses of phosphaalkynes.

Scheme 4.14 Syntheses of phosphinines via ring atom metathesis.

Scheme 4.15 Multifunctional 2,4,6‐triarylphosphinines with mixed P,N‐donor sets...

Scheme 4.16 Phosphinine syntheses via cycloaddition (and cycloreversion) reacti...

Scheme 4.17 Synthesis of functional phosphinines by ring expansion of phospholi...

Scheme 4.18 Syntheses of phospholides.

Scheme 4.19 Addition reactions of phosphaorganic multiple bond systems.

Scheme 4.20 Schematic representation of cycloadditions involving phosphaalkenes...

Scheme 4.21 Synthesis of benzo‐phosphabarrellenes from benzyne and phosphinines...

Scheme 4.22 Exemplary reactions of phosphaalkenes with electrophiles.

Scheme 4.23 Exemplary reactions of phosphaalkenes and phosphinines with nucleop...

Scheme 4.24 A stable phosphaalkene derived radical cation.

Scheme 4.25 Exemplary metathesis reaction of an inversely polarized phosphaalke...

Scheme 4.26 Reported coordination modes of phosphaalkenes and phosphaalkynes.

Scheme 4.27 Reported coordination modes of phosphinines and phospholides.

Scheme 4.28 Calculated s‐ and p‐orbital contributions to the lone pairs in prot...

Scheme 4.29 Phosphaalkenes with π‐conjugating C‐aryl substituents.

Scheme 4.30 Syntheses of π‐conjugated alkynyl phosphaalkenes.

Scheme 4.31 Unusual conjugation: ferrocenyl‐substituted bis‐phosphaalkenes and ...

Scheme 4.32 Phosphaalkene‐based π‐conjugated materials.

Scheme 4.33 Computationally predicted molecular structures of stable phosphaalk...

Scheme 4.34 Exemplary transition metal‐mediated 1,3‐diphosphete syntheses.

Scheme 4.35 Proposed mechanism for the synthesis of pentaphosphaferrocenes from...

Scheme 4.36 Formation and conversion of a zirconia‐diphospha‐tricyclopentane.

Scheme 4.37 Aluminum‐mediated cyclo‐oligomerization of

t

BuCP.

Scheme 4.38 Metal‐mediated syntheses of 1,3,5‐triphosphinines.

Scheme 4.39 Reductive conversion of

t

BuCP into di‐ and triphospholides.

Scheme 4.40 Synthesis of penta‐ and hexamers of

t

BuCP and P

5

‐deltacyclenes.

Scheme 4.41 Synthesis of phosphaalkene‐decorated polymers by phospha‐Cope rearr...

Scheme 4.42 Addition and insertion polymerization of a phosphaalkene.

Scheme 4.43 Phosphorus analogs of poly‐phenylene vinylenes (PPV).

Scheme 4.44 Enantiomerically pure phosphaalkenes and phosphinines with chiral s...

Scheme 4.45 Atropisomeric phosphinines (only one enantiomer shown).

Scheme 4.46 Planar chiral phosphametallocenes.

Scheme 4.47 Phosphaferrocenes deriving their chirality exclusively from chiral ...

Scheme 4.48 Syntheses of reduced 2,2′‐bisphosphine metal complexes.

Scheme 4.49 Metal‐centered reactivity of reduced 2,2′‐bisphosphine metal comple...

Scheme 4.50 Redox‐active complexes of silacalix‐[4]‐phosphinines.

Scheme 4.51 Catalytically active Rh(I) and Pd(II) phosphacyclohexadienyl comple...

Scheme 4.52 Amination and alkylation of allylic alcohols using a DCPB‐Y‐based P...

Scheme 4.53 Catalytic application of chiral phosphine‐phosphaferrocene hybrid l...

Scheme 4.54 Enantioselective conjugate addition catalyzed by chiral phosphaferr...

Scheme 4.55 Catalytically active π‐ and σ‐phospholyl complexes.

Scheme 4.56 Functionalization of the surfaces of Au nanoparticles and modified ...

Scheme 4.57 OH‐functionalized phosphinines used for surface functionalization.

Chapter 5

Scheme 5.1

Figure 5.1 X‐ray structure of

2

of trigonal bipyramid configuration [3].

Scheme 5.2

Scheme 5.3

Scheme 5.4

Figure 5.2 X‐ray structure of

12

[12].

Scheme 5.5

Scheme 5.6

Scheme 5.7

Scheme 5.8

Scheme 5.9

Figure 5.3 Molecular structure of

25

[20].

Scheme 5.10

Figure 5.4 X‐ray structure of

29

in KANVUS drawing [23].

Scheme 5.11

Figure 5.5 A simple valence orbital description for a hypervalent X–P–Y bonding...

Figure 5.6

Trigonal bipyramid

(

TBP

) and

square pyramid

(

SP

).

Figure 5.7 Molecular structure of

31

of nearly SP structure [27].

Figure 5.8 Interconversion between apical and equatorial bonds by Berry pseudor...

Scheme 5.12

Figure 5.9 Chirality symbols

C

and

A

around TBP phosphorus [32].

Scheme 5.13

Figure 5.10 X‐ray structure of

40‐

A

[35].

Scheme 5.14

Scheme 5.15

Scheme 5.16

Scheme 5.17

Figure 5.11 TBP structures proposed for the transition state of phosphoryl tran...

Chapter 6

Scheme 6.1

Scheme 6.2

Scheme 6.3

Scheme 6.4

Scheme 6.5

Scheme 6.6

Figure 6.1 Schematic view of

10

with some selected bond lengths (in roman) and ...

Scheme 6.7

Scheme 6.8

Figure 6.2 X‐ray structure of

11

[15].

Scheme 6.9

Figure 6.3 X‐ray structure of

19

[17].

Scheme 6.10

Chapter 7

Scheme 7.1 The Michaelis–Arbuzov reaction.

Scheme 7.2 The Michaelis–Becker reaction.

Scheme 7.3 S

N

P(V) on diethyl chlorophosphate.

Scheme 7.4 Microwave‐assisted Michaelis–Arbuzov reaction.

Scheme 7.5 Microwave‐assisted synthesis of diisopropyl chloroethylphosphonate

1

...

Scheme 7.6 Conversion of benzylic alcohol

13

into the corresponding phosphonate...

Scheme 7.7 ZnBr

2

‐catalyzed Michaelis–Arbuzov reaction at room temperature.

Scheme 7.8 Formation of β‐ketophosphonates

20

from epoxy sulfones

18

.

Scheme 7.9 Lanthanum‐catalyzed Pudovik reaction.

Scheme 7.10 Yamamoto's asymmetric Pudovik reaction.

Scheme 7.11 Mg

II

binaphtholate‐catalyzed Pudovik reaction of ketone

25

.

Scheme 7.12 InCl

3

‐catalyzed formation of α‐aminophosphonate

29

.

Scheme 7.13 Hydrophosphonylation of diethyl phosphite to imines using quinine a...

Scheme 7.14 Pd‐catalyzed coupling of benzyl halide

31

and diethyl H‐phosphonate...

Scheme 7.15 Mechanism of Pd‐catalyzed dialkyl benzylphosphonate

14

formation.

Scheme 7.16 Pd‐catalyzed hydrophosphonylation of olefins.

Scheme 7.17 Synthesis of phosphonic acid

39

using olefins and hypophosphorous a...

Scheme 7.18 Enantioselective Michael addition of diphenyl phosphite

6e

to nitro...

Scheme 7.19 Mechanism of the Ni‐catalyzed Michaelis–Arbuzov reaction of aryl tr...

Scheme 7.20 Michaelis–Arbuzov reaction of arenediazonium salt

53

.

Scheme 7.21 Synthesis of arylphosphonates

46

from

in situ

‐generated arynes.

Scheme 7.22 Stereospecific synthesis of vinylphosphonate

59

from vinylboronate

Scheme 7.23 Pd‐catalyzed cross‐coupling of aryl halide

45

and dialkyl H‐phospho...

Scheme 7.24 Synthesis of phosphonylated pyrimidines, pyrazines, and anilines.

Scheme 7.25 Proposed mechanism for the Pd‐catalyzed formation of arylphosphonat...

Figure 7.1 Palladacycles

66

and

67

synthesized by Xu et al.

Scheme 7.26 Pd‐catalyzed coupling of aryl bromides and iodide

45

with dialkyl H...

Scheme 7.27 Microwave‐assisted synthesis of complex phosphonate

89

from aryl br...

Scheme 7.28 Synthesis of arylphosphonates from arylboronates and dialkyl H‐phos...

Scheme 7.29 Mechanism of Pd

II

‐catalyzed synthesis of arylphosphonate

65

from ar...

Scheme 7.30 Formation of complex phosphonate

80

as backbone‐modified nucleic ac...

Scheme 7.31 Synthesis of (

E

)‐ and (

Z

)‐vinylphosphonate

82

by kinetic resolution...

Scheme 7.32 Cu‐catalyzed synthesis of arylphosphonate

46

.

Figure 7.2 Pyrrolidine‐2‐phosphonic acid phenyl monoester

83

.

Scheme 7.33 Cu‐catalyzed synthesis of vinylphosphonate

85

from vinyliodonium sa...

Scheme 7.34 Synthesis of arylphosphonates from aryl bromides and chlorides.

Scheme 7.35 Regioselective hydrophosphonylation of alkynes.

Scheme 7.36 Putative hydrophosphonylation mechanism according to Ananikov et al...

Scheme 7.37 Regioselective hydrophosphonylation of alkyne

87

, leading to linear...

Scheme 7.38 Pd‐catalyzed

cis

double phosphonylation of alkyne

87

with dialkyl H...

Scheme 7.39 Insertion of alkynes into phosphonylated zirconacycles and subseque...

Scheme 7.40 Hydrostannation and carbometallation of fluorinated alkynylphosphon...

Scheme 7.41 Ortholithiation and subsequent S

N

P(V) of aryl bromides.

Scheme 7.42 Radical generation and consecutive trapping with trimethyl phosphit...

Scheme 7.43 Electrochemical formation of arylphosphonates.

Scheme 7.44 Horner–Wadsworth–Emmons reaction of aldehyde 110 and tetramethyl me...

Scheme 7.45 Proposed mechanisms for alkynylphosphonate synthesis via the Michae...

Scheme 7.46 Alkynylphosphonate synthesis from alkynyliodonium salt

119

and tria...

Scheme 7.47 Synthesis of fosfomycin

126

using dibutyl chlorophosphate

124

with ...

Scheme 7.48 Synthesis of alkynylphosphonate

118

using lithium bis‐(diisopropyla...

Scheme 7.49 Synthesis of alkynylphosphonate

132

from dibromoalkenes and diethyl...

Scheme 7.50 Aerobic oxidative coupling of terminal alkyne

87

and dialkyl H‐phos...

Scheme 7.51 Proposed mechanism of aerobic oxidative coupling of terminal alkyne...

Figure 7.3 Silica‐supported Cu

II

‐NHC catalyst.

Scheme 7.52 Decarboxylative synthesis of alkynylphosphonate

118

using carboxyli...

Scheme 7.53 Pd‐catalyzed synthesis of alkynylphosphonate

118

from dibromoalkene...

Scheme 7.54 Proposed mechanism according to Meurillon et al. for the Pd‐catalyz...

Scheme 7.55 Isomerization of allenylphosphonate

148

to alkynylphosphonate

118

.

Scheme 7.56 Synthesis of alkynylphosphonate by heating vinylselenoxide

149

.

Chapter 8

Scheme 8.1 The scope of the five‐membered phosphorus heterocycles discussed in ...

Scheme 8.2 Material‐relevant 1

H

‐phospholes and 1

H

‐phosphole‐containing heterocy...

Scheme 8.3 Photochromic transformation of benzothienophospholes.

Scheme 8.4 1

H

‐Phospholes with planar or near‐to‐planar geometry.

Scheme 8.5 General overview of synthetic routes toward functionalized 1

H

‐phosph...

Scheme 8.6 [2+2+1] Synthesis of 1

H

‐phospholes via zirconiacyclopentadienes.

Scheme 8.7 [4+1] Synthesis of 1

H

‐phospholes from 1,4‐diiodo‐1,3‐butadiens.

Scheme 8.8 [2+2+1] Synthesis of α‐ethynylphospholes and modulation of their π‐c...

Scheme 8.9 [4+1] Synthesis of 2,5‐diferrocenyl‐1‐phenyl‐1

H

‐phosphole.

Scheme 8.10 Lithium‐mediated [2+2+1] synthesis of

P

‐aryl‐tetraphenyl‐1

H

‐phospho...

Scheme 8.11 Synthesis of 3,4‐dimethyl‐1‐phenyl‐1

H

‐phosphole via the base‐mediat...

Scheme 8.12 Synthesis of bis‐3‐oxo‐λ

5

‐phospholes by the formal [2+2+1] cascade ...

Scheme 8.13 [3+2] Synthesis of carbaborane‐fused alkynylphosphone‐substituted 1

Scheme 8.14 A Wrackmeyer 1,1‐carboboration route toward 3‐boryl‐substituted 1

H

‐...

Scheme 8.15 Synthesis of 1

H

‐phospholes from open‐chain precursors by reductive ...

Scheme 8.16 Synthesis of 2,5‐dihydro‐1

H

‐phospholes using the ring‐closing olefi...

Scheme 8.17 General strategy for the synthesis of phosphoporphyrins and analogs...

Scheme 8.18 General overview of the synthetic routes toward fused 1

H

‐phospholes...

Scheme 8.19 General overview of the synthetic routes toward fused 1

H

‐phospholes...

Scheme 8.20 [4+1] Synthesis of dibenzophospholes.

Scheme 8.21 [4+1] Synthesis of π‐extended benzo[

b

]phospholes.

Scheme 8.22 [2+2+1] Synthesis of benzo[

b

]phospholes via zirconium benzyne‐media...

Scheme 8.23 One‐pot multicomponent [2+2+1] synthesis of benzo[

b

]phosphole oxide...

Scheme 8.24 The formal one‐pot [3+2] synthesis of 11

H

‐dibenzo[

b

,

g

]phosphindoles...

Scheme 8.25 The [3+2] synthesis of benzo[

b

]phospholes via the silver‐ or mangan...

Scheme 8.26 [3+2] Stereoselective synthesis of P‐chirogenic dibenzophosphole–bo...

Scheme 8.27 Base‐mediated intramolecular cyclization reaction of 2‐alkynylpheny...

Scheme 8.28 Lithium‐promoted synthesis of 1

H

‐phosphindoles via cyclization of 2...

Scheme 8.29 Transition‐metal‐catalyzed synthesis of 1

H

‐phosphindoles via cycliz...

Scheme 8.30 Intramolecular cascade phospho‐cyclization of bis(2‐bromophenyl)ace...

Scheme 8.31 Synthesis of phosphonium‐ and borate‐bridged zwitterionic ladder‐ty...

Scheme 8.32 Synthesis of phosphorus‐ and silica‐bridged ladder‐type stilbenes v...

Scheme 8.33 Synthesis of 2,3‐dihydro‐1‐phenylbenzo[

b

]phosphole derivatives.

Scheme 8.34 Synthesis of 2,3‐dihydro‐1

H

‐phosphindole.

Scheme 8.35 Synthetic route to benzo[

b

]phosphole oxides via TBAI‐catalyzed radi...

Scheme 8.36 Synthesis of benzo[

b

]phosphindoles via intramolecular CH bond acti...

Scheme 8.37 Rhodium‐catalyzed double [2+2+2] synthesis of aromatic‐extended dib...

Scheme 8.38 Relevant 1,2‐ and 1,3‐heterophospholes.

Scheme 8.39 General overview of synthetic strategies toward 1,2‐azaphospholes.

Scheme 8.40 General overview of synthetic strategies toward 1,3‐heterophosphole...

Scheme 8.41 [4+1] Synthesis of 1,2‐benzazaphosphole 1‐oxides and azaphosphole 1...

Scheme 8.42 [4+1] Synthesis of 1,2‐azaphospholes by direct phosphorylation reac...

Scheme 8.43 Formal [3+2] synthesis of 1,2‐azaphospholes from photochemically ge...

Scheme 8.44 Reaction between 1

H

‐1,3,2‐diazaphosphole‐4,5‐dicarbonitrile and alk...

Scheme 8.45 Synthesis of 1

H

‐1,2‐azaphospholes from

in situ

‐generated 1‐aza‐2‐ph...

Scheme 8.46 Synthesis of 1,2‐azaphosphole derivatives through the polar [3+2] c...

Scheme 8.47 Metal‐free cyclization of phosphonamides through intramolecular oxi...

Scheme 8.48 Benzazaphosphol‐3‐one 1‐oxides as by‐products in Lopez‐Ortiz olefin...

Scheme 8.49 Lopez‐Ortiz synthesis of stereogenic γ‐aminophosphonic acids, which...

Scheme 8.50 Synthesis of cumulene‐fused 1,2‐oxophospholes by the reaction of si...

Scheme 8.51 Iodine‐ or copper dibromide‐mediated synthesis of 2,5‐dihydro‐1,2‐o...

Scheme 8.52 Strategies for [3+2] synthesis of 1,2‐oxophospholes, 1,2‐thiaphosph...

Scheme 8.53 [4+1] Synthesis of 1,3‐benzazaphospholes from 2‐phosphinoanilines.

Scheme 8.54 [4+1] Synthesis of 1,3‐benzazaphospholes from 2‐phosphinoanilines.

Scheme 8.55 Reaction of 4‐methyl‐2‐phosphinoaniline with

ortho

‐phthalic dicarba...

Scheme 8.56 Synthesis of phosphaindolizines following the [4+1] cyclocondensati...

Scheme 8.57 Synthesis of 1,3‐benzazaphospholes by intramolecular thermal cycloc...

Scheme 8.58 Synthesis of bis‐3

H

‐1,3‐azaphosphole ferrocene sandwich compounds.

Scheme 8.59 Synthesis of 1,3‐oxaphospholes by [4+1] cyclization reaction.

Scheme 8.60 Synthesis of 1,3‐thiaphospholes and 1,3‐selenophospholes by [4+1] c...

Scheme 8.61 [3+2] Synthesis of 1,3‐oxaphospholes by the reaction of phosphaalky...

Scheme 8.62 [3+2] Synthesis of 1,3‐oxaphospholes from phosphaalkynes and isomün...

Scheme 8.63 Synthesis of 1,3‐thiaphosphols and 1,3‐selenaphosphols by [3+2] cyc...

Scheme 8.64 Synthetic route to 2,3‐dihydrobenzo[

d

][1,3]oxaphosphole, a precurso...

Scheme 8.65 Relevant phosphinines and fused derivatives.

Scheme 8.66 General overview of synthetic routes toward λ

3

‐ and λ

5

‐ phosphenine...

Scheme 8.67 [5+1] Synthesis of 4‐methyl‐λ

3

‐phosphinine.

Scheme 8.68 [5+1] Synthesis of tetrahydro λ

3

‐phosphinines from penta‐1,4‐dien‐3...

Scheme 8.69 [5+1] Synthesis of λ

3

‐phosphinines starting from 2,4,6‐substituted ...

Scheme 8.70 Preparation of phosphinane‐1‐oxides via nickel‐catalyzed hydrophosp...

Scheme 8.71 [5+1] Synthesis of phosphinanes.

Scheme 8.72 [4+2] Synthesis of λ

3

‐phosphinines by the reaction between 1,3‐buta...

Scheme 8.73 [4+2] Synthesis of λ

3

‐phosphinines by the reaction between 2‐pyrano...

Scheme 8.74 1,3,2‐Diazaphosphinines in double‐fold [4+2] cycloaddition reaction...

Scheme 8.75 Preparation of 2‐hydroxy‐ and 2‐bromo λ

3

‐phosphinine via [4+2] cycl...

Scheme 8.76 Synthesis of λ

3

‐phosphinines via [2+2+2] cycloaddition of diynes wi...

Scheme 8.77 Synthesis of λ

3

‐phosphinines from λ

3

‐phospholes via [4+2] cycloaddi...

Scheme 8.78 Transformation of 1‐phosphanorbornadiene cycloadducts to λ

3

‐phosphi...

Scheme 8.79 Synthesis of λ

3

‐phosphinines via expansion of the 1

H

‐phosphole fram...

Scheme 8.80 One‐pot conversion of α‐unsubstituted phospholide ions into 3‐acyl‐...

Scheme 8.81 Synthesis of λ

3

‐phosphinines through the reaction of λ

3

‐phospholes ...

Scheme 8.82 Three possible 1,6‐electrocyclization modes of phosphohexatrienes a...

Scheme 8.83 Synthesis of λ

3

‐phosphinine through flash thermolysis of vinyldiall...

Scheme 8.84 Synthesis of λ

5

‐phosphinines via electrocyclization of phosphohexat...

Scheme 8.85 Phospha‐Wulff–Dötz reaction, synthesis of λ

3

‐phosphinines.

Scheme 8.86 General overview of synthetic routes toward fused λ

3

‐ and λ

5

‐phosph...

Scheme 8.87 Synthesis of λ

5

‐phosphinolines via formal [4+2] cycloaddition of be...

Scheme 8.88 Resonance structures of phosphonium–iodonium ylides.

Scheme 8.89 Photochemical synthesis of λ

5

‐phosphinolines from mixed phosphonium...

Scheme 8.90 Formal [4+2] synthesis of λ

5

‐isophosphinolines.

Scheme 8.91 [4+2] Synthesis of 2‐phosphanaphthalene via the reaction of methyle...

Scheme 8.92 Synthesis of phosphanthridines.

Scheme 8.93 Assembly of λ

5

‐phosphanthridine framework via the cyclization of 2′...

Scheme 8.94 [5+1] Synthesis of dithieno[2,3‐

b

;3′,2′‐

e

]‐4‐keto‐1,4‐dihy‐drophosp...

Scheme 8.95 Synthesis of phosphaperylenes.

Scheme 8.96 Synthesis of phospha‐fluorescein.

Scheme 8.97 Synthesis of phospha‐rhodamine.

Scheme 8.98 Synthesis of the phospho‐double helicene.

Scheme 8.99Scheme 8.99 Relevant heterophosphinines and fused derivatives.

Scheme 8.100 Consecutive [3+1+1+1] synthesis of 1,2λ

5

‐azaphosphinines starting ...

Scheme 8.101 The synthesis of 1,2λ

5

‐azaphosphinines via [3+3] cycloaddition bet...

Scheme 8.102 [3+2+1] Synthesis of 1,2λ

3

‐azaphosphinines via direct phosphorylat...

Scheme 8.103 [5+1] Synthesis of 5,6‐dihydrodibenzo[

c

,

e

]‐1,2λ

5

‐azaphosphinine 6‐...

Scheme 8.104 Synthesis of 1,2λ

5

‐azaphosphinines via the [4+2] cycloaddition bet...

Scheme 8.105 [4+2] Synthesis of 2,1λ

5

‐benzazaphosphinines via the Ru‐catalyzed ...

Scheme 8.106 [4+2] Synthesis of 1,2‐dihydro‐2,1‐benzazaphosphinine‐1‐oxide with...

Scheme 8.107 [4+2] Synthesis of 1,2λ

5

‐azaphosphinin‐6‐ones from

N

‐alkoxycarbony...

Scheme 8.108 Reaction of bis[bis(diisopropylamino)phosphinolcarbodiimide with d...

Scheme 8.109 [4+2] Synthesis of 2‐λ

3

‐phosphachinolines from phosphantriylammoni...

Scheme 8.110 Synthesis of 5,6‐dihydrodibenzo[

c

,

e

]‐1,2λ

5

‐azaphosphinines via ena...

Scheme 8.111 Synthesis of 1,2‐dihydro‐2,1λ

5

‐benzazaphosphinines via Pd(II)‐cata...

Scheme 8.112 [5+1] Synthesis of 1,3λ

3

‐azaphosphinines via the reaction of 1,3‐o...

Scheme 8.113 Synthesis of 1,3λ

3

‐azaphosphinine following the [4+2] cycloadditio...

Scheme 8.114 [5+1] Synthesis of 5,10‐dihydrophenophosphazine ring system throug...

Scheme 8.115 The formal [4+2] synthesis of 1,4‐benzazaphosphorinium triflates.

Scheme 8.116 The palladium‐catalyzed synthesis of 5,10‐dihydrophenophosphazines...

Scheme 8.117 Synthesis of phosphorus‐centered 4,8,12‐triazatriangulenes.

Scheme 8.118 Phosphine ligands containing 1,4‐oxaphosphinines (POP) architectur...

Scheme 8.119 [5+1] Synthesis of 1,4‐oxaphosphinines.

Scheme 8.120 The palladium‐catalyzed synthesis of phenoxaphosphines via carbon

Scheme 8.121 Synthesis of phosphangulene system containing three 10

H

‐phenoxapho...

Scheme 8.122 Synthesis of phosphorus‐centered and sulfur‐bridged concave molecu...

Scheme 8.123 Six‐membered BCP heterocyclic compounds.

Scheme 8.124 Photolytic reaction between cyclic phosphine oligomer [PPh]

5

and p...

Scheme 8.125 Synthesis 1,4‐phosphaboratabenzene ring system by the [5+1] cycliz...

Scheme 8.126 [5+1] Synthesis of 1,4‐dihydro‐1,4‐phosphasiline.

Scheme 8.127 Formal [5+1] synthesis of 1‐phospha‐4‐silabicyclo[2.2.2]octanes by...

Scheme 8.128 Triptycene‐type phosphine ligands: formal [5+1] synthesis of the 9...

Scheme 8.129 Germanium‐ and tin‐containing heterophosphinines.

Scheme 8.130 Synthesis of 1,4‐dihydro 1,4‐phosphagermines and 1,4‐phosphastanni...

Scheme 8.131 Synthesis of biferrocene‐fused 1,4‐phosphastannines.

Chapter 9

Figure 9.1 Typical

31

P NMR chemical shift ranges for organophosphorus compounds...

Figure 9.2

31

P NMR chemical shifts for heterocyclic phenylphosphines.

Figure 9.3 The effect of phosphorus stereochemistry on

31

P NMR chemical shifts ...

Figure 9.4

31

P{

1

H} NMR spectrum (C

6

D

6

) of a chlorophospholane, showing isotope...

Figure 9.5

31

P NMR spectra before and after intercalation of a Rh complex into ...

Figure 9.6

31

P NMR chemical shifts as a metric for bonding in carbene‐phosphini...

Figure 9.7

31

P NMR chemical shifts for related phosphine‐boranes.

Scheme 9.1 Experimental and computed

31

P NMR chemical shifts for a product in L...

Figure 9.8 Cyclic triphosphenium ions.

Figure 9.9 Experimental and calculated

31

P NMR chemical shifts in bicyclic tung...

Figure 9.10

31

P NMR spectrum (in C

6

D

6

,

2

Ad = 2‐adamantyl, Mes = mesityl) of a d...

Figure 9.11

31

P NMR shifts and

1

J

PH

values in isomeric octahedral organophospho...

Figure 9.12 Calculated and observed

J

PH

values in the chlorophosphines Me

2

NPCl

2

Figure 9.13

31

P NMR data for isomeric phosphiranes (Mes = mesityl = 2,4,6‐Me

3

C

6

Figure 9.14

J

PP

coupling constants in symmetrical and unsymmetrical bis(phospho...

Figure 9.15

31

P{

1

H} NMR spectrum (DMSO‐d

6

) of

RR

/

SS

‐

5

, showing the

13

C satellit...

Figure 9.16 (a) Experimental

31

P NMR spectrum of bis(primary phosphine)

6

in CD

Figure 9.17 Diphosphines containing polarized PP bonds.

Scheme 9.2

Cis–trans

isomerization of a cyclometalated Pt–phosphine compl...

Figure 9.18 Dependence of

1

J

P–Se

in phosphine selenides on P–Ar substitue...

Figure 9.19

Trans

influence series from determination of

J

Pt–P

.

Figure 9.20 HPP‐4 COSY spectrum of SR‐12813 (C

6

D

6

). The H‐P‐C‐P‐H connectivity ...

Figure 9.21 2D semiconstant time

31

P,

1

H COSY NMR spectrum of phospholipids from...

Figure 9.22 Yttrium phosphine oxide complex studied by 2D

31

P‐

89

Y NMR.

Figure 9.23 Part of the

1

H–

31

P HOESY spectrum of the Ti–neopentyl complex Ti(PN...

Figure 9.24 Structure of the glyphosate‐induced metabolite MEcPP.

Scheme 9.3 Phosphitylation of O–H groups in lignin as an analytical method [63]...

Figure 9.25 Determination of enantiomeric purity of chiral phosphines or phosph...

Scheme 9.4

31

P NMR probe for enantioselectivity of alkylation of a diphenylphos...

Figure 9.26

31

P NMR probe for diastereomer ratio in acylphosphonium salts.

Figure 9.27

31

P NMR probe for enantiopurity of amino acids.

Scheme 9.5

31

P NMR probe for enantiopurity of a chiral alcohol without an added...

Scheme 9.6

31

P NMR probe of borane Lewis acidity.

Figure 9.28

31

P‐DOSY spectra (a) of a mixture of phosphine oxides and (b) after...

Figure 9.29 Ion pairing in a cationic dicopper complex was studied by

31

P DOSY.

Figure 9.30

31

P DOSY NMR spectrum (C

6

D

6

) of a mixture of mononuclear and dinucl...

Figure 9.31 Polymers characterized by

31

P NMR DOSY.

Figure 9.32

31

P DOSY spectrum of a cationic manganese–phosphine complex with th...

Scheme 9.7

31

P NMR probe of diffusion behavior in lubricating oil.

Scheme 9.8

31

P NMR probe of enzyme diffusion via derivatization with a phosphor...

Scheme 9.9

31

P NMR analysis of anchoring a phosphine on silica.

Scheme 9.10 Decomposition of Sarin on activated carbon observed by SS

31

P NMR.

Figure 9.33 Structures of adsorbed PMe

3

on solid acids.

Figure 9.34 SS

31

P NMR chemical shifts for PPh

3

Cl

2

and its hydrolysis products.

Figure 9.35 Isomers of a Pt–phosphaalkene complex.

Figure 9.36 Solid‐state

31

P NMR spectra provided evidence for the dinuclear str...

Figure 9.37 Measurement of

31

P‐

11

B scalar spin–spin interactions by SS

31

P NMR.

Figure 9.38 A titanium phosphinidene complex that was characterized by solution...

Figure 9.39 Two‐dimensional solid‐state

31

P‐

15

N TEDOR spectrum of a RNA–protein...

Figure 9.40

31

P{

1

H} NMR spectrum of Rh complex

19

(CD

2

Cl

2

).

Figure 9.41 Phosphido portion of the

31

P{

1

H} NMR spectrum of Pt((

R,R

)‐Me‐DuPhos...

Figure 9.42

31

P{

1

H} NMR spectrum (toluene‐d

8

, 183 K) of a lead–phosphido comple...

Figure 9.43 Variable temperature

31

P{

1

H} NMR spectra of FeCp–phosphorane comple...

Figure 9.44 Tautomerization of a secondary phosphine oxide.

Scheme 9.11 Tautomerization of a P–NH group.

Scheme 9.12 Isomerization of bis(triazinyl)phosphines.

Figure 9.45 Variable temperature

31

P{

1

H} NMR spectra for the phosphine tellur...

Scheme 9.13 The rate of phosphine dissociation from Grubbs metathesis catalys...

Scheme 9.14 Formation and decomposition of an intermediate in phosphine oxidati...

Scheme 9.15 Identification of diastereomeric phosphonium intermediates in asymm...

Scheme 9.16 Enhanced

31

P NMR signals from a Ru–phosphine complex via PHIP.

Chapter 10

Figure 10.1 A few examples of organophosphorus compounds in biological systems.

Scheme 10.1 Ludwig synthesis of modified (d)NTPs.

Scheme 10.2 Ludwig–Eckstein method.

Scheme 10.3 Preparation of (d)NTPs by nucleophilic ring opening.

Scheme 10.4 Chemical activation of a (d)NMP with an imidazolylimidazolinium gro...

Scheme 10.5 Borch method for the synthesis of (d)NTPs.

Scheme 10.6 Synthesis of [α]5′-(α-

P

‐thio)triphosphates.

Scheme 10.7 Synthesis of 5′‐(α‐

P

‐borano)triphosphates.

Scheme 10.8 Synthesis of nucleoside 5′‐(α‐

P

‐seleno)triphosphates.

Scheme 10.9 Synthesis of 2′‐deoxynucleoside 5′‐(α,β)‐NH‐triphosphate analogs.

Scheme 10.10 Synthesis of α,β‐CXY-dNTP analog.

Scheme 10.11 Elongation of oligophosphate chains by CE phosphorimidazolides.

Scheme 10.12 Synthesis of fluorinated deoxynucleotide analogs.

Scheme 10.13 Synthesis of non-fluorinated (α,β),(β,γ)‐bis(CH

2

)‐dNTPs.

Scheme 10.14 Synthesis of (α,β),(β,γ)-CH

2

/NH‐dTTP isomers via “flip chemistry”.

Scheme 10.15 Synthesis of β,γ‐CXY NTP analogs via morpholidates.

Scheme 10.16 Synthesis of (β,γ)‐CXY‐(d)NTP analogs via

N

‐methylimidazolides.

Figure 10.2 Isolated diastereomers of (β,γ)‐CHX‐dGTP analogs.

Scheme 10.17 Synthesis of (β,γ)‐CHX‐dNTP diastereomers.

Scheme 10.18 Synthesis of (α,β)‐CHX‐ATP diastereomers.

Scheme 10.19 Synthesis of a 5′‐CH

2

analog of dUTP.

Scheme 10.20 Synthesis of nucleoside 5′‐(γ‐

P

‐thio)triphosphates.

Scheme 10.21 Synthesis of NTPγF.

Scheme 10.22 Synthesis of dNTP dye and spin-label conjugates.

Figure 10.3 Structure of tenofovir disoproxil fumarate (

95

) and adefovir dipivo...

Scheme 10.23 Synthesis of prodrugs of adefovir and tenofovir using a chlorometh...

Figure 10.4 Structure of two prodrugs utilizing the ProTide strategy.

Scheme 10.24 Diastereoselective synthesis of aryloxy phosphoramidate prodrugs o...

Scheme 10.25 Synthesis of brincidofovir.

Scheme 10.26 Strategies to mask the negative charges on ANPs.

Figure 10.5 Next‐generation peptidomimetic prodrugs of HPMPC.

Scheme 10.27 AZT diphosphate prodrug synthesis.

Scheme 10.28 d4T prodrug synthesis.

Figure 10.6 Examples of earlier types of simple BPs (

128

and

129

), and the more...

Figure 10.7 Structures of some of the phosphonocarboxylate cognates of BPs.

Scheme 10.29 Synthesis of α‐hydroxymethylene N‐BPs.

Scheme 10.30 Synthesis of α‐hydroxymethylene N‐BPs using catecholborane.

Scheme 10.31 Synthesis of α‐hydroxymethylene N‐BPs using Grignard reagents.

Scheme 10.32 Synthesis of α‐hydroxymethylene N‐BPs using

in situ

generated ally...

Scheme 10.33 Synthesis of a BP analog of glutamic acid.

Scheme 10.34 Synthesis of dye‐conjugated risedronate using the “magic linker” m...

Scheme 10.35 Synthesis of [

18

F]‐chlorofluoromethylene‐BP.

Figure 10.8 BPs being used as delivery agents for 5′‐fluorouracil (

160

), ciprof...

Figure 10.9 Examples of lipophilic bisphosphonates.

Scheme 10.36 Synthesis of lipophilic BP

164

.

Chapter 11

Figure 11.1 Structure of ionic liquids.

Figure 11.2 Perfluoroalkylated phosphines.

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E1

Organophosphorus Chemistry

From Molecules to Applications

Edited by Viktor Iaroshenko

Copyright

Editor

Dr. Viktor Iaroshenko

Polish Academy of Sciences, Center of

Molecular and Macromolecular

Studies in Lodz, Laboratory of

Homogeneous Catalysis and

Molecular Design, Sienkiewicza 112,

90‐363 Łódź, Poland

Cover

Various organophosphorus molecules.

Background image taken from

© Photodisc.

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1Phosphines and Related Tervalent Phosphorus Systems: Organophosphorus Compounds as Ligands in Organometallic Catalysis

Piet W. N. M. van Leeuwen

LPCNO, INSA‐Toulouse, 135 Av. de Rangueil, 31077 Toulouse, France

1.1 Introduction

1.1.1 History

Phosphines and related phosphorus‐containing molecules play a major role in homogeneous catalysis. The history of homogeneous metal complex catalysis, as we know it today, started in the 1960s, although there had been even industrial applications long before that. In the 1920s, a catalytic process was used for the addition of water to acetylene. The metal mercury was used in a sulfuric acid solution. The reaction was very slow and large volumes were needed; thus, this was far from attractive. A related process still in operation is the zinc‐salt‐catalyzed addition of carboxylic acids to acetylene. With the introduction of petrochemistry, the feedstock for acetaldehyde production changed to ethene. The reaction used until today is a stoichiometric oxidation of ethene by palladium, the so‐called Wacker process, in which palladium is reoxidized with oxygen and a copper catalyst. Carbonylation catalysis came on stream in the 1930s and 1940s, although its application was retarded by World War II (WWII). Initially, the metals of choice were nickel, e.g. work by Reppe, and cobalt, especially hydroformylation by Roelen, and methanol carbonylation. Probably, Reppe (1948) was the first to use triphenylphosphine as a modifying ligand in a catalytic reaction, which concerned the addition of nickel‐cyanide‐catalyzed carbonylative alcohol addition to alkynes, leading to acrylates [1]. He used nickel cyanide also in the synthesis of polyketone from carbon monoxide and ethene in those early years. As of the 1960s, all these “leads” were greatly improved by ligand effects and by changing to the more active second‐row transition metals palladium and rhodium. Cobalt was also modified by phosphine ligands, and in this instance, the catalyst produced more of the linear oxygenate product, which now is mainly the alcohol rather than the aldehyde (Shell) [2]. Early examples of triphenylphosphine‐modified group 10 hydrogenation catalysis are due to Bailar and Itatani [3]. Ever since, more publications have appeared that reported phosphine effects on catalytic reactions.

1.1.2 Alternative Ligands

Before concentrating only on phosphorus ligands, we should mention that in the past three decades, ligands based on other donor atoms have become equally important and, in some areas, even more important than phosphines. In the mid‐1980s, the metallocene era started for the early transition metals especially in polymerization catalysis, followed by alkoxides, amides, and salen ligands. Meanwhile, metallocene catalysts have found industrial applications. In the late transition metal area, the diimine ligands stand out together with a shift to the first‐row metals for alkene polymerization, and they almost made it to a replacement of the nickel catalyst in the oligomerization of ethene. They were followed a little later by the outburst of the NHC ligands, which have beaten, in several instances, the best phosphines used so far in certain reactions. They have found commercial applications in metathesis reactions. A combination of all donor ligands in bidentates has further enriched the toolbox of homogeneous catalysis. One should not forget that the “ligand‐free” systems are attractive, as they do not suffer from ligand decomposition, but their life can still be limited because of precipitation or formation of a compound with the wrong valence state. The stabilizing ligands in these cases are, for example, carbon monoxide, alkenes, halides, and other anions, for example, the Wacker process, cobalt‐catalyzed hydroformylation (Exxon), nickel‐catalyzed oligomerization of butene to 3‐methylheptane (IFP, Dimersol process), rhodium‐catalyzed carbonylation of methanol (Monsanto, now BP), and ditto for iridium (BP, Cativa process).

1.1.3 Aim of the Chapter

The aim of this chapter is to give an introduction to the use of tervalent phosphorus compounds as ligands in homogeneous catalysis. Several chapters in this work refer to that area and have their own introductions. We have tried to avoid overlap and provide some basic concepts in a nutshell while referring to those chapters that deal in more detail with this topic. In Section 1.2, we deal with the most common elementary steps used for the synthesis of phosphorus ligands. In more specific chapters, synthesis will be dealt with in much more detail than what we were able to cover here. The overview is very limited, as, for example, in our laboratories students are introduced to phosphorus ligand synthesis with a series of about 200 synthetic steps of which we think they are worthwhile for a starter in this area! In Section 1.3, the properties of phosphorus ligands will be discussed by presenting the most common yardsticks used, such as Tolman's χ and θ values for the electronic and steric parameters, respectively, and Casey's βn, the natural bite angle for bidentate ligands. For the steric and electronic parameters, several alternatives have been developed, and all the parameters have found use particularly in catalysis [4]. Studies on the use of parameters in Linear Free Energy Relations and QUALE will be mentioned.

In Section 1.4, chiral phosphorus ligands will be introduced focusing on the types of chiral ligands available, involving the most typical phosphorus and diphosphorus ligands, and heterobidentate ligands.

The next two sections will deal with two examples of ligand effects, namely a few highlights in hydroformylation and the next one on modern cross‐coupling chemistry. As both are huge areas, these parts also serve as a brief introduction to the fields. We will highlight the crucial issues concerning monodentate and bidentate ligands.

Section 1.6 includes the main decomposition pathways of phosphorus ligands, which are also discussed in dedicated chapters in books and reviews.

1.2 Synthesis of Phosphorus Ligands

1.2.1 Introduction

Clearly, the synthesis of phosphorus ligands involves a library of organic phosphorus chemistry to which one cannot do justice in just a few pages. Chapter 7 by Stevens deals with the most important routes for the introduction of phosphonates into complex organic molecules, and more details and references can be found there. Phosphonates can be converted into phosphines, of which there exist many examples. Here, we will deal with a simple summary of the common elementary steps for making phosphorus ligands. Phosphaalkenes will not be discussed as they are not yet of proven interest in catalysis. Although phosphinines have been exploited occasionally in catalysis and have shown interesting properties, for instance, in rhodium‐catalyzed hydroformylation [5], we will not discuss their synthesis. We will confine ourselves to a series of elementary steps thought to be useful for our purposes. Even that will rather be a short list of less than 40, as, for example, in my group, the students acquainted themselves in phosphine synthesis using a set of about 150–200 reactions. Although one could bring down the number as there are less reaction types, it would still be too large to list for the present purposes. Below we have ordered the reactions according to the main reaction types, which are still feasible, because the number of ways to make a PC bond is far less numerous than that for making CC bonds!

1.2.2 Nucleophilic Substitution by Carbanions at Pδ+

The ionic approach to the formation of a carbon–phosphorus bond has two possibilities, namely the use of phosphorus as a nucleophile or as an electrophile. The latter seems more in accord with the electronic properties of phosphorus, as a slightly positively charged phosphorus species is common and stable, whereas phosphido anions (Section 1.2.3) tend to show electron transfer reactions in addition to and before entering a nucleophilic attack. Indeed, nucleophilic substitution is the most common reaction used, although both routes have their pros and cons. One might not often directly see potential cons for a certain route. For example, an attack of a benzylic anion at a phosphorus electrophile will proceed smoothly, but the product formed, PhCH2PR2, has an acidic proton at the benzylic position, and the remaining benzyl anion may be consumed via a simple proton abstraction and, at best, the yield is only half of the expected amount. The nucleophile will often be a relatively simple Grignard or a hydrocarbyllithium reagent, and it can be used in excess, as during the workup by hydrolysis, it can be easily removed. If the nucleophile is a more complicated molecule, of which the remains can be removed only with difficulty, the use of a large excess must be avoided. Also, the carbonucleophile may substitute other hydrocarbyl groups at phosphorus (Scheme 1.3). Reaction 3 shows a less common nucleophilic substitution, but it shows its versatility.

Perfluoroalkyl groups are far less frequently used than simple aromatics, which we will encounter below. The first example shows pentafluoroethyl groups, which are not the most common substituents at phosphorus, but they are highly desirable in the studies of electronic effects in catalysis (Scheme 1.1) [6]. In this case, the diphosphine was obtained in an excellent yield. It should be borne in mind that the formation of LiF of such lithium fluoroalkyl intermediates is a highly exothermic decomposition reaction. Occasionally, such decomposition reactions take place. For instance, dry spots in the reaction vessel, caused by a flow of an inert gas, might initiate an explosive formation of LiF. Several accidents have occurred, even on a large scale, but few have been adequately reported (a safe synthesis of fluoroalkyl‐containing organometallics has been reported) [7]. The phosphorus precursor is not a common reagent either; it is difficult to synthesize, but it is commercially available.

Scheme 1.1 Reaction 1, alkylation of PCl bonds.

A more elaborate lithium reagent that one might not want to spoil is shown in Scheme 1.2, Reaction 2 [8]. In the next step, the amino group can be replaced by a phosphide anion under mild acidic conditions to give the so‐called Josiphos ligands. Lithiation at the upper ring is facilitated by the amino group and will proceed mainly on one side to give a certain diastereoisomer if the amine consists of just one enantiomer.

Scheme 1.2 Reaction 2, synthesis of Josiphos.

Examples of hydrocarbyl/hydrocarbyl substitution are given in Scheme 1.3, Reaction 3 [9]. Thus, on the way to the formation of the lithium nucleophiles of 10H