Chiral Building Blocks in Asymmetric Synthesis E-Book
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- Herausgeber: Wiley-VCH GmbH
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
The work presents achievements in the field of preparation and applications of building blocks in asymmetric synthesis. An indispensable resource for every academic and industrial researcher working in the field.
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Veröffentlichungsjahr: 2022
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Table of Contents
Cover
Title Page
Copyright
Preface
Foreword
1 Enantioselective Synthesis of Cyclopropenes
1.1 Introduction
1.2 Metal‐Catalyzed Enantioselective Syntheses of Cyclopropenes
1.3 Other Synthetic Routes and Derivatizations of Enantioenriched Cyclopropenes
1.4 Summary and Prospect
References
2 Chiral Heterocycles for Asymmetric Synthesis
2.1 Introduction
2.2 Small‐Ring Heterocycles
2.3 Medium‐Ring Aliphatic Heterocycles
2.4 Other Heterocyclic Building Blocks
2.5 Conclusions
References
3 Saturated Heterocycles as Chiral Auxiliaries
3.1 Introduction
3.2 Proline‐Derived Chiral Auxiliaries
3.3 2,5‐
trans
‐Disubstituted Pyrrolidines
3.4 Heterocyclic Hydrazones
3.5 Oxazolidine‐Based Chiral Auxiliaries
3.6 Camphor‐Based Chiral Heterocyclic Auxiliaries
3.7 Phosphonamide‐Based Chiral Auxiliaries
3.8 Schöllkopf's Chiral Auxiliaries and Related Heterocycles for the Asymmetric Synthesis of α‐Amino Acids
3.9 Conclusions
References
4
trans‐
1,2‐Diaminocyclohexane and Its Derivatives in Asymmetric Organocatalysis
4.1 Introduction
4.2
trans‐
1,2‐Diaminocyclohexane‐Based Organocatalysts
4.3 Application of
trans‐
1,2‐Diaminocyclohexane Derivatives in Asymmetric Organocatalysis
4.4 Conclusions
References
5 Diketopiperazines as Chiral Building Blocks
5.1 Introduction
5.2 A Brief Overview of the Synthesis of 2,5‐Diketopiperazines
5.3 2,5‐Diketopiperazines in Drug Synthesis
5.4 Natural Product Synthesis
5.5 Conclusions
References
6 Amino Acids as Chiral Building Blocks
6.1 Introduction
6.2 Chiral Substrates/Reagents
6.3 Chiral Auxiliaries
6.4 Oxazaborolidines
6.5 Organocatalysts
6.6 Conclusions
References
7 Carbohydrate‐Based Catalysts and Auxiliaries in Organic Synthesis
7.1 Chiral Auxiliaries
7.2 Chiral Catalysts
References
8 Monoterpenes as Chiral Building Blocks
8.1 Introduction
8.2 Acyclic Monoterpene Building Blocks
8.3 Monocyclic Terpene Building Blocks
8.4 Bicyclic Terpene Building Blocks
8.5 Conclusions
References
9 Diterpene Acids as Starting Materials for the Synthesis of Biologically Active Compounds
9.1 Zamoranic Acid 1 as a Precursor of Interesting Compounds
9.2
Ent
‐halimic Acid as a Precursor of Biologically Active Compounds and Other Interesting Derivatives
Acknowledgments
References
10 Alkaloids as Chiral Building Blocks, Auxiliaries, Ligands, and Molecular Diversity
10.1 Introduction
10.2 Ephedra Alkaloids
10.3 Tobacco Alkaloids (Nicotine and Anabasine)
10.4 Lupin Alkaloids
10.5
Cinchona
Alkaloids
10.6 Tropane Alkaloids
10.7 Alkaloids as Building Blocks in the Syntheses of Chiral Polymers and Their Application
Acknowledgments
References
11 Chiral Building Blocks for Total Steroid Synthesis and the Use of Steroids as Chiral Building Blocks in Organic Synthesis
11.1 Introduction
11.2 Chiral Building Blocks for the Construction of Steroids
11.3 Steroids as Chiral Building Blocks
References
12 Chiral Organophosphorus Compounds in Asymmetric Synthesis
12.1 Introduction
12.2 Organophosphorus Compounds with Incorporated Chiral Terpene Moieties
12.3 Organophosphorus Compounds with Axial Chirality
12.4 Chiral Aminophosphonic Acids and Their Analogs
12.5 Stereogenic Organophosphorus Compounds with P—N and/or P—O Bonds
12.6 Summary
References
13 Organosulfur Compounds as Chiral Building Blocks
13.1 State of the Art
13.2 Introduction
13.3 The Tradition
13.4 Ideas for the Future
13.5 Conclusions
References
14 Organoselenium Compounds as Chiral Building Blocks
14.1 Introduction
14.2 Asymmetric Selenofuctionalization Reactions Promoted by Electrophilic Selenium Reagents
14.3 Vinyl Selenones as Important Building Blocks in Asymmetric Processes
14.4 Asymmetric Synthesis by Michael‐Initiated Ring Closure Reactions from Vinyl Selenones
14.5 Functionalization of Vinyl Selenones of Carbohydrates and Nucleotides
14.6 Asymmetric Organocatalytic Transformations Starting with Vinyl Selenones
14.7 Conclusion
References
15 Allenes as Chiral Building Blocks in Asymmetric Synthesis
15.1 Introduction
15.2 Nucleophilic Addition and Substitution
15.3 Allenylzinc and Indium Reagents, Allenylsilanes and Allenylstannanes
15.4 Epoxidation, Aziridination, and Silacyclopropanation of Allenes
15.5 Nazarov Cyclization of Allenyl Vinyl Ketones
15.6 Nucleophilic Cyclization and Addition Promoted by Electrophiles
15.7 Cycloisomerization and Other Reactions Catalyzed by Transition Metals
15.8 Cycloaddition of Allenes
Acknowledgments
References
16 The Synthesis and Application of BINOL Derivatives as Effective Building Blocks for Catalysts Employed in Enantioselective Synthesis
16.1 Introduction
16.2 BINOL Derivatives with Free Hydroxyl Groups
16.3 Onium Salts as Charged Catalysts in PTC
16.4 Chiral Phosphoric Acids Derived from BINOL Platform
Acknowledgments
References
17 Chiral Acenes: Synthesis and Applications
17.1 Introduction
17.2 Chiral Carbo[
n
]helicenes
17.3 Twistacenes
17.4 Chiral Nanobelts
17.5 Concluding Remarks
References
18 2‐Aza‐21‐Carbaporphyrin in Construction of Chiral Supramolecular Assemblies
18.1 Preface
18.2 Monomers
18.3 Dimers and Oligomers
18.4 Summary and Outlook
References
19 Catenane, Rotaxane, and Molecular Knot Chiral Building Blocks
19.1 Introduction
19.2 Elements of Molecular Topology
19.3 Topological Chirality and Chiral Catenanes
19.4 Chiral [2]Rotaxanes
19.5 Topologically Chiral Molecular Knots
19.6 Catenanes, Rotaxanes, and Knots as Chiral Building Blocks
19.7 Conclusions
References
Index
End User License Agreement
List of Tables
Chapter 7
Table 7.1 The 1,4‐addition to oxazolidinone‐conjugated sugar‐auxiliaries.
Table 7.2 The 1,4‐addition to ester type sugar‐auxiliaries.
Table 7.3 The Diels–Alder reaction of crotonic acid esters bearing carbohydr...
Table 7.4 The asymmetric aldol reaction catalyzed by
135–139
.
List of Illustrations
Chapter 1
Scheme 1.1 Catalytic stereoselective functionalization of cyclopropenes.
Scheme 1.2 Asymmetric cyclopropenation of terminal alkynes with
catalyst....
Scheme 1.3 Asymmetric cyclopropenation of terminal alkynes with
.
Scheme 1.4 Asymmetric cyclopropenation of terminal alkynes with
.
Scheme 1.5 Enantioselective [2+1]‐cycloaddition reactions of ethyl diazoacet...
Scheme 1.6 Asymmetric cyclopropenation of terminal alkynes using
.
Scheme 1.7
‐catalyzed cyclopropenation of terminal alkynes with diacceptor ...
Scheme 1.8 First enantioselective synthesis of fluorinated cyclopropenes and...
Scheme 1.9 Macrocyclization via cyclopropenation of alkynes using copper cat...
Scheme 1.10 Iridium‐catalyzed enantioselective cyclopropenation of terminal ...
Scheme 1.11 Enantioselective cyclopropenation with a cobalt–porphyrin comple...
Scheme 1.12 Enantioselective cyclopropenation reaction catalyzed by a gold–s...
Scheme 1.13 Directed evolution catalysis for enantioselective synthesis of c...
Scheme 1.14 Enantioselective desymmetrization of bis‐pentafluorophenylesters...
Scheme 1.15 Synthesis of (
)‐pentalenene via Pauson–Khand cycloaddition invo...
Scheme 1.16 Post‐functionalization of enantioenriched mono‐substituted cyclo...
Chapter 2
Scheme 2.1 Sharpless' epoxidation in the total synthesis of (+)‐disparlure....
Scheme 2.2 Epoxidation of allyl alcohol yielding an industrial building bloc...
Scheme 2.3 Synthesis of epoxide building block 7 in the total synthesis of b...
Scheme 2.4 Organocatalytic epoxidation of alkenes. DIC, diisopropylcarbodiim...
Scheme 2.5 Organocatalytic epoxidation of unsaturated aldehydes and ketones ...
Scheme 2.6 Epoxidation of an unsaturated ketone with a primary amine catalys...
Scheme 2.7 Use of chiral aziridine
28
in the total synthesis of teleocidin B...
Scheme 2.8 Cu‐catalyzed aziridination in the total synthesis of agelastatin ...
Scheme 2.9 Aziridine formation via nucleophilic displacement in the synthesi...
Scheme 2.10 Aziridination of imines with sulfur ylides in the total synthesi...
Scheme 2.11 Synthesis of azetidines using azabicyclo[1.1.0]butyllithium. THF...
Scheme 2.12 Organocatalytic desymmetrizing opening of racemic azetidines.
Scheme 2.13 Cu‐catalyzed Kinugasa reaction for the synthesis of azetidinones...
Scheme 2.14 Rh–Pd‐catalyzed formation of β‐lactams via C‐H activation and al...
Scheme 2.15 Formation of chiral pyrrolidine building block
79
. DCE, 1,2‐Dich...
Scheme 2.16 Preparation of chiral pyrrolidine
86
by dipolar cycloaddition....
Scheme 2.17 Pyrrolidine building block
90
obtained by Au‐catalyzed cycloizom...
Scheme 2.18 Synthesis of spirooxindol pyrrolidine
95
. DCE, 1,2‐Dichloroethan...
Scheme 2.19 Organocatalytic synthesis of chiral pyrrolidines with antibacter...
Scheme 2.20 Rh‐catalyzed synthesis of pyrrolidine building block
105
.
Scheme 2.21 Ir‐catalyzed dearomatization of indoles in the total synthesis o...
Scheme 2.22 Organocatalytic synthesis of spirooxindol intermediate
116
.
Scheme 2.23 Spirooxindol
122
in the total synthesis of (−)‐strychnofoline....
Scheme 2.24 Chiral pyrrolidine building block
125
obtained via enantioselect...
Scheme 2.25 Chiral lactone
130
in the total syntheses of amprenavir and empa...
Scheme 2.26 Chiral pyrrolidine
135
in the total synthesis of swainsonine. TE...
Scheme 2.27 Building block
143
for peptide ligation.
Scheme 2.28 Intermediate
146
in the total synthesis of (−)‐deoxoapodine.
Scheme 2.29 Pd‐catalyzed allylic substitution for the synthesis of derivativ...
Scheme 2.30 Ni‐catalyzed synthesis of piperidine building block
156
.
Scheme 2.31 General preparation of bisalkaloid ligands (a) and its applicati...
Figure 2.1 Examples of chiral catalysts derived from
Cinchona
alkaloids.
Chapter 3
Scheme 3.1 Alkylation of (
S
)‐prolinolamides.
Scheme 3.2 Stereoselective acyl‐Claisen rearrangement as a key step in synth...
Scheme 3.3 Rearrangement of chiral amide
8
to butyrolactone
9
.
Scheme 3.4 Asymmetric Michael addition to conjugated amides.
Scheme 3.5 Synthesis of (−)‐α‐elemene (
19
).
Scheme 3.6 Diastereoselective Eschenmoser–Claisen rearrangement of glycine d...
Scheme 3.7 Diastereoselective thio‐Claisen rearrangement of glycine derivati...
Scheme 3.8 Asymmetric acyl‐Claisen rearrangement of allylamines.
Scheme 3.9 Asymmetric radical reactions.
Scheme 3.10 Conformations of aza‐enolates and stereochemical model of the re...
Scheme 3.11 α‐Functionalization of Enders' hydrazones with various electroph...
Scheme 3.12 Cleavage of hydrazine moiety.
Scheme 3.13 Nucleophilic addition of organometallic species to C<span class=...
Scheme 3.14 Alkylation of α‐heteroatom substituted hydrazones.
Scheme 3.15 Total synthesis of 2‐
epi
‐deoxoprosopinine (
50
).
Scheme 3.16 Tandem aza‐Michael addition/α‐ester enolate alkylation or aldol ...
Scheme 3.17 Diastereoselective Staudinger [2+2] cycloaddition.
MMPP
=
magnes
...
Scheme 3.18 Nucleophilic addition to indoline‐derived chiral hydrazone.
Scheme 3.19 Diastereoselective radical addition to
N
‐acyl hydrazones.
Scheme 3.20 Evans' oxazolidinone as asymmetry inducer in a diastereoselectiv...
Scheme 3.21 Total synthesis of baulamycin A: synthesis of fragment
88
.
Scheme 3.22 Total synthesis of baulamycin A: synthesis of fragment
95
.
Scheme 3.23 Diels–Alder reaction of dienophile
107
.
Scheme 3.24 1,4‐Addition/enolate trapping of unsaturated amides bearing Oppo...
Scheme 3.25 Aldol reaction of
N
‐acylated Oppolzer's sultam with aldehydes....
Scheme 3.26 Examples of electrophilic α‐addition to
N
‐acylated Oppolzer's su...
Scheme 3.27 Aziridination with
N
‐alkoxycarbonyl imines with diazo reagent
11
...
Scheme 3.28 Alkylation of 2‐aza (
120
) and 3‐aza (
125
) camphor imides.
Scheme 3.29 Aldol reaction of
N
‐acyl camphor imide
128
.
Scheme 3.30 Alkylation reactions of
131
,
134,
and
135
with alkyl halides....
Scheme 3.31 Aldol reaction of
N
‐acylated camphor‐based oxazolidines.
Scheme 3.32 Asymmetric olefination of chiral phosphonamides.
Scheme 3.33 Alkylation of chiral phosphonamides.
Scheme 3.34 Asymmetric conjugated 1,4‐addition of phosphonamides to Michael ...
Scheme 3.35 Asymmetric 1,4‐addition of P‐chiral phosphonoamide to Michael ac...
Scheme 3.36 Nucleophilic addition to chiral
N
‐phosphonyl imines.
Scheme 3.37 Synthesis of the anti‐cancer drug velcade (
164
).
Scheme 3.38 Synthesis of Schöllkopf's chiral auxiliary.
Scheme 3.39 Asymmetric alkylation of bis‐lactim
166
.
Figure 3.1 Proline‐based chiral auxiliaries.
Figure 3.2 Examples of 2,5‐disubstituted pyrrolidine chiral auxiliaries.
Figure 3.3 Selected analogs of SAMP/RAMP hydrazines.
Figure 3.4 Selected analogs of Enders' proline‐based hydrazines.
Figure 3.5 Structure of
N
‐acyl hydrazones. LA = Lewis acid.
Figure 3.6 Selected Evans‐type chiral auxiliaries.
Figure 3.7 Structure of baulamycin A (
81
).
Figure 3.8 Camphor‐derived chiral auxiliaries.
Figure 3.9 Examples of phosphonamide chiral auxiliaries.
Figure 3.10 Heterocyclic analogs of Schöllkopf's auxiliary.
Chapter 4
Scheme 4.1 Resolution of the racemic
trans
‐1,2‐diaminocyclohexane.
Scheme 4.2 Asymmetric cyanation reactions.
TFAA
,
trifluoroacetic anhydride
...
Scheme 4.3 Michael additions of malonate to nitrostyrenes.
Scheme 4.4 Michael additions of other 1,3‐dicarbonyls to nitrostyrene.
Scheme 4.5 Michael additions of ketones to nitrostyrene.
Scheme 4.6 Michael additions of other carbon nucleophiles to nitrostyrene....
Scheme 4.7 Michael additions of heteroatom‐centered nucleophiles to nitrosty...
Scheme 4.8 Michael reactions of enones.
Scheme 4.9 Michael reactions of benzylidene pyruvates.
Scheme 4.10 Reactions of isatin‐derived Michael acceptors.
Scheme 4.11 Michael reactions of maleimides.
Scheme 4.12 Reaction of 4‐nitrobenzaldehyde with cyclohexanone.
Scheme 4.13 Asymmetric reactions of aldehydes.
DIPEA
,
diisopropylethylamine
....
Scheme 4.14 Enantioselective reactions of isatins.
Scheme 4.15 Enantioselective reactions of imines.
DABCO
,
1,4‐diazabicyclo[2.
...
Scheme 4.16 Asymmetric Pictet–Spengler‐type reactions.
Scheme 4.17 Reactions of nitrogen electrophiles.
Scheme 4.18 Miscellaneous reactions.
LED
,
light emitting diode
;
Scheme 4.19 Miscellaneous cyclizations and cycloadditions.
Figure 4.1 Early examples of
trans
‐1,2‐diaminocyclohexane‐based organocataly...
Figure 4.2 Examples of protected DACH derivatives commonly used in the synth...
Figure 4.3 Selected
N
1,
N
1‐dialkyl‐cyclohexane‐1,2‐diamines used in organocat...
Figure 4.4 Mono‐amides (
4
) and sulfonamides (
5
).
Figure 4.5 Amine‐thiourea (
6
and
7
) and urea (
8
) derivatives.
Figure 4.6 Amine‐(thio)ureas containing two different chiral units.
Figure 4.7 Amine‐squaramide derivatives.
Figure 4.8 Organocatalysts containing a guanidine motif.
Figure 4.9 Non‐basic thiourea and urea organocatalysts activating via hydrog...
Figure 4.10 Tertiary ammonium salts‐ureas
17
for phase transfer catalysis....
Figure 4.11
C
2
‐
symmetric mono‐DACH organocatalysts.
Figure 4.12 Organocatalysts containing two diaminocyclohexane units.
Figure 4.13 Amides of DACH with
N
‐unprotected amino acids.
Figure 4.14 Miscellaneous DACH‐based organocatalysts (
21
).
Chapter 5
Figure 5.1 Representative natural products containing 2,5‐diketopiperazine c...
Figure 5.2 Main strategies for the synthesis of 2,5‐DKPs.
Figure 5.3 Synthesis of 2,5‐DKPs from dipeptide esters.
Figure 5.4 Strategies for the synthesis of 2,5‐DKPs on solid supports. (a) S...
Figure 5.5 Synthesis of 2,5‐DKPs via the Ugi reaction: general concept.
Figure 5.6 Synthesis of 2,5‐DKPs via the Ugi reaction: representative practi...
Figure 5.7 Synthesis of 2,5‐DKPs by intramolecular aza‐Wittig reactions.
Figure 5.8 Synthesis of 2,5‐DKPs coupled to Pictet–Spengler reactions.
Figure 5.9 Synthesis of 2,5‐DKPs by intramolecular amide alkylation.
Figure 5.10 Synthesis of 2,5‐DKPs by a domino Ugi‐aza‐Michael sequence.
Figure 5.11 Synthesis of 2,5‐DKPs by dimerization of α‐haloacetamides.
Figure 5.12 An example of the synthesis of 2,5‐DKPs by one‐pot formation of ...
Figure 5.13 Biosynthesis of 2,5‐DKPs from aminoacyl‐tRNAs catalyzed by cyclo...
Figure 5.14 Two synthetic approaches to tadalafil. Reagents and conditions: ...
Figure 5.15 Synthesis of NNZ‐2591. Reagents and conditions: (i) CHCl
3
, reflu...
Figure 5.16 Synthesis of aplaviroc. Reagents and conditions: (i) (a) MeOH, 5...
Figure 5.17 Synthesis of retosiban. Reagents and conditions: (i) Triethylami...
Figure 5.18 Asymmetric synthesis of amino acids from 2,5‐DKPs.
Figure 5.19 Synthesis of tryprostatin B from cyclo(
L
‐Trp‐
L
‐Pro).
Figure 5.20 Synthesis of spirotryprostatin based on an intramolecular Heck r...
Figure 5.21 Synthesis of stephacidin B from a functionalized diketopiperazin...
Figure 5.22 Synthesis of versicolamide B via an intramolecular Diels–Alder r...
Figure 5.23 Synthesis of variecolortide A via an intermolecular Diels–Alder ...
Figure 5.24 Synthesis of dideoxyverticillin A from a protected cyclo(
L
‐Trp‐
L
Figure 5.25 Total synthesis of ardeemin and
N
‐acetylardeemin.
Figure 5.26 Total synthesis of (+)‐phakellin based on an Overman rearrangeme...
Figure 5.27 Synthesis of sarcodonin ɛ and phellodonin from a common diketopi...
Figure 5.28 Fukaiyama's total synthesis of ecteinascidin 743 from an Ugi‐der...
Chapter 6
Scheme 6.1 Synthesis of (
S
)‐harmicine using
L
‐proline as a chiral pool subst...
Scheme 6.2 Synthesis of 4‐phosphothiophen‐2‐yl alanine using a serine‐derive...
Scheme 6.3 Synthetic pathway for the asymmetric synthesis of the (
R
)‐lacosam...
Scheme 6.4 Synthesis of a novel thiazoline derivative starting from
L
‐threon...
Scheme 6.5 Asymmetric synthesis of sarpagine and koumine alkaloids using
L
‐t...
Scheme 6.6 Retrosynthetic strategy to tubulysins starting from
L
‐valinol and...
Scheme 6.7 Stereoselective syntheses of (2
R
)‐pterosin B using the chiral aux...
Scheme 6.8 Stereoselective synthesis of novel FTY720 analogues using Schöllk...
Scheme 6.9 Synthesis of (+)‐ambrisentan using the diastereoselective Evans' ...
Scheme 6.10 Retrosynthesis of presaccharotriolide Z.
Scheme 6.11 Synthesis of the chiral aldehyde and vinyl iodide intermediates ...
Scheme 6.12 SuperQuat chiral auxiliaries introduced by Davies' group.
Scheme 6.13 Synthesis of α‐chiral bicyclo[1.1.1]pentanes, using the Davies' ...
Scheme 6.14 The proline‐derived Corey–Bakshi–Shibata (CBS) catalyst.
Scheme 6.15 The key proline‐catalyzed aldol reaction in the total synthesis ...
Scheme 6.16 The use of prolinate salts for a multi‐component Mannich reactio...
Scheme 6.17 Tandem‐type one‐pot process of an aldol proline‐amide‐catalyzed ...
Scheme 6.18 The use of ball milling in the proline‐based thiodipeptide catal...
Scheme 6.19 Organocatalyzed conjugate additions of aldehydes to nitroolefins...
Scheme 6.20 Novel diarylprolinol‐derived amino perfluoroalkanesulfonamide ca...
Scheme 6.21 The total synthesis of clinprost via a key diarylprolinol silyl ...
Scheme 6.22 Vinylogous Michael Aldol cascade for the synthesis of spirocycli...
Scheme 6.23 Enantioselective radical conjugate addition to enals using a org...
Scheme 6.24 One‐pot sequential bio‐catalyzed oxidation/organocatalyzed α‐ary...
Scheme 6.25 Highly stereoselective [4+2]‐cycloaddition reaction of activated...
Scheme 6.26 The key highly stereoselective organocatalyzed asymmetric epoxid...
Scheme 6.27 The synthesis of calcimimetic (
R
)‐(+)‐NPS R‐568 via a one‐pot im...
Scheme 6.28 Direct asymmetric aldol reaction between cycloalkanones and subs...
Scheme 6.29 Proline and visible‐light organophotoredox strategy for an enant...
Scheme 6.30 Postulated mechanism for the enantioselective Mannich reaction o...
Scheme 6.31 The key α‐arylation using an Olofsson diaryliodonium salt and a ...
Scheme 6.32 A flow‐chemistry‐assisted highly stereoselective 1,3‐dipolar cyc...
Scheme 6.33 Cascade cyclizations of α,β‐unsaturated thioesters leading to in...
Figure 6.1 The original Hajos, Parrish, Wiechert, Eder, and Sauer reaction, ...
Figure 6.2 (a) Birmann's first‐generation 2,3‐dihydroimidazo[1,2‐
a
]pyrimidin...
Chapter 7
Scheme 7.1 The variety of asymmetric reactions involving Kunz auxiliary as a...
Scheme 7.2 The Mannich reaction selectivity difference in relation to the ty...
Scheme 7.3 Stereoselective 1,4‐addiction combined with enolate
30
trapping v...
Scheme 7.4 Stereoselective Diels‐Alder reaction of
27b
and
28b.
Scheme 7.5 Stereoselective epoxidation of oxazolidine‐based alkene
34.
Scheme 7.6 The reversed selectivity for
36
that depends on R
1
substituent ty...
Scheme 7.7 The conformational explanation of observed stereoselectivity diff...
Scheme 7.8 Stereoselective 1,4‐addition of a radical to
Aux
5d
crotonate (
38
...
Scheme 7.9 Stereoselective dihydroxylation of double bond of crotonate
38c.
...
Scheme 7.10 1,3‐dipolar cycloaddition involving the sugar‐auxiliary develope...
Scheme 7.11 Application of
allo
‐furanose derivative
56
as a chiral auxiliary...
Scheme 7.12 The aldol reaction supported by the sugar‐derived auxiliary
58
d...
Scheme 7.13 The stereoselective benzylation of ester
61
reported by Kakinuma...
Scheme 7.14 The Tadano's approach for alkylation of esters with auxiliary
Au
...
Scheme 7.15 The Tadano's approach for dialkylation of β‐ketoesters with auxi...
Scheme 7.16 Ferrocene selective iodination with application of sugar‐based a...
Scheme 7.17 Sugar‐based ether auxiliaries application in [2+1] cycloaddition...
Scheme 7.18 Sugar‐based ether auxiliaries application in [2 + 4] cycloadditi...
Scheme 7.19 Stereoselective singlet oxygen addition to naphthalene ring.
Scheme 7.20 Stereoselective hydrogenation of the double bond.
Scheme 7.21 Stereoselective reduction of the carbonyl group.
Scheme 7.22 Sugar‐based diphosphinite derivatives utilized in the asymmetric...
Scheme 7.23 Structures of catalysts
90a
and
90b
and their pseudo‐enantiomeri...
Scheme 7.24 The asymmetric addition of cyanide to a vinylnaphthalene promote...
Scheme 7.25 Structures of carbohydrate‐based Trost ligands
93–95
and t...
Scheme 7.26 The Woodward application of ligand
95
in the copper initiated Mi...
Scheme 7.27 The asymmetric cyanosiliation of ketones promoted by chiral comp...
Scheme 7.28 The asymmetric allylic alkylation of
103
and
104
catalyzed by su...
Scheme 7.29 Sugar‐derived BOX ligands and their application in the asymmetri...
Scheme 7.30 The asymmetric alkynylation of imines catalyzed by Cu/
113
compl...
Scheme 7.31 The asymmetric hydrogenation of olefins catalyzed by Ir/
116
com...
Scheme 7.32 The asymmetric Heck reaction catalyzed by Pd/
121
complexes.
Scheme 7.33 The NHC induced hydrosilylation of ketones.
Scheme 7.34 The Shi epoxidation of olefins initiated by chiral ketones
130
‐
Scheme 7.35 The asymmetric Michael addition to nitroolefins
147
catalyzed by...
Scheme 7.36 The asymmetric addition of
150
to imine
151
promoted by urea
145
...
Scheme 7.37 The asymmetric cyanosilylation of benzylophosphonates
153
cataly...
Scheme 7.38 The oxidative spirolactonization of
157
promoted by sugar‐derive...
Scheme 7.39 The phase transfer catalyzed epoxidation of chalcone
160
with su...
Figure 7.1 The pseudo‐enantiomeric relation of
D
‐galactose and
D
‐arabinose....
Figure 7.2 The examples of Kunz auxiliaries based on
D
‐galactose (
1
),
D
‐arab...
Figure 7.3 Examples of sugar‐derived auxiliaries used in ester forms.
Figure 7.4 Selected examples of sugar‐based organocatalysts containing a pr...
Figure 7.5 The examples of phase transfer catalysts
161–165
derived fr...
Chapter 8
Scheme 8.1 Biosynthesis of terpenes shown on the example of verbenone
5
, men...
Scheme 8.2 Synthesis of (+)‐artemone
22
and (−)‐cyclonerodiol
26
, chokol G
2
...
Scheme 8.3 Synthesis of ophiobolins A and N.
Scheme 8.4 Synthesis of (+)‐neopeltolide
53
employing citronellol
43
.
Scheme 8.5 Citronellol and citronellene as starting material in the synthesi...
Scheme 8.6 Synthesis of the tricyclic core
64
of the pseudopteroxazole.
Scheme 8.7 Examples of natural products obtained using carvone‐derived chira...
Scheme 8.8 Synthesis of (+)‐cubitene
85
through the SmI
2
‐induced cyclization...
Scheme 8.9 Synthesis of precursor
91
as the precursor of
Abies
sesquiterpeno...
Scheme 8.10 Synthesis of (+)‐cyperolone
97
utilizing (
R
)‐(−)‐carvone
72
as t...
Scheme 8.11 Transformation of (
R
)‐(−)‐carvone epoxide
99
to [3.3.1]bicyclic ...
Scheme 8.12 Synthesis of aciphyllene
111
based on the (
R
)‐(+)‐limonene
106
c...
Scheme 8.13 Diels–Alder cycloaddition of limonene‐derived ketone
114
leading...
Scheme 8.14 Limonene‐derived allylic alcohol
117
as a precursor of sesquiter...
Scheme 8.15 Transformation of (
S
)‐(−)‐limonene
123
to wine lactone
124
and (...
Scheme 8.16 (
S
)‐(−)‐perillyl alcohol
126
as starting material in the synthes...
Scheme 8.17 Utility of (
R
)‐(+)‐perillyl alcohol‐derived β‐ketoester
130
in t...
Scheme 8.18 (
R
)‐(+)‐Pulegone
134
as substrate in the synthesis of jiadifenol...
Scheme 8.19 (
S
)‐(−)‐Pulegone
139
as substrate in the synthesis of (+)‐ryanod...
Scheme 8.20 Synthesis of (−)‐englerin A
151
starting from (1
R
,3
R
,4
S
)‐(−)‐iso...
Scheme 8.21 (1
R
,3
R
,4
S
)‐(−)‐Isopulegol
139
as starting material in the synthe...
Scheme 8.22 (1
R
,3
R
,4
S
)‐(−)‐Isopulegol
146
transformation to an alkaloid benz...
Scheme 8.23 Utility of (−)‐menthone
161
as a chiral reactant.
Scheme 8.24 Transformation of (1
S
,6
R
)‐(+)‐3‐carene
167
to ingenane and tigli...
Scheme 8.25 Utility of (1
S
,6
R
)‐(+)‐2‐carene
174
to construct a
gem
‐dimethylc...
Scheme 8.26 Synthesis of guadials B
186
and C
187
using (+)‐α‐
184
and (−)‐β...
Scheme 8.27 Utility of (1
R
,5
R
)‐(+)‐verbenone
188
in the synthesis of (+)‐ono...
Scheme 8.28 Synthesis of (+)‐cardamon peroxide
203
commenced from (1
R
,5
S
)‐(−...
Scheme 8.29 Transformation of (1
S
,4
R
)‐(+)‐fenchone
204
to a 5,7‐fused ring p...
Figure 8.1 Acyclic monoterpenes most frequently used as chiral pool.
Figure 8.2 Monocyclic monoterpenes most frequently used as chiral pool.
Figure 8.3 Guaiane‐type sesquiterpenoides obtained from (
R
)‐(+)‐limonene
106
Figure 8.4 Bicyclic monoterpenes most frequently used as chiral pool.
Chapter 9
Scheme 9.1 Synthesis of chrysolic acid methyl esters
5
and isofregenedol
6
....
Scheme 9.2 Synthesis of labdane diterpenoids from zamoranic acid,
1
.
Scheme 9.3 Synthesis and synthetic plan of drimanes from zamoranic acid.
Scheme 9.4 Isodrimeninol synthesis from zamoranic acid.
Scheme 9.5 Limonidilactone,
49
, synthesis from zamoranic acid.
Scheme 9.6 Synthesis of angeloyl‐gutierrezianolic acid methyl ester from zam...
Scheme 9.7 Synthesis for tri‐ and tetracyclic diterpenes from zamoranic acid...
Scheme 9.8 Synthesis of tricyclic key intermediates from zamoranic acid.
Scheme 9.9 Synthesis of natural
ent
‐halimanolide from
ent
‐halimic acid,
2
.
Scheme 9.10 Synthesis of α and β‐hydroxyhalimanolides.
Scheme 9.11 Synthesis of furo‐
ent
‐halimanolides.
Scheme 9.12 Synthesis of chettaphanins from
ent
‐halimic acid.
Scheme 9.13 Synthesis of sesterterpenolides.
Scheme 9.14 Synthesis of sesterterpenolide analogues of dysidioide.
Scheme 9.15 Synthesis of
ent
‐labdanes from
ent
‐halimanes.
Scheme 9.16 Synthesis of pricrasane and abeopicrasane from
ent
‐halimic acid,...
Scheme 9.17 Synthesis of [4.3.3]propellanes from
ent
‐halimic acid,
2
.
Scheme 9.18 Synthesis of sesquiterpenes quinone/hydroquinone.
Scheme 9.19 Synthesis of (+)‐agelasine C.
Scheme 9.20 Synthesis of (+)‐thiersindole C,
131
, from
ent
‐halimic acid,
2
....
Scheme 9.21 Synthesis of sesquiterpenyl‐indoles from
ent
‐halimic acid.
Figure 9.1 Natural products zamoranic acid,
1
, and
ent
‐halimic acid,
2
, isol...
Figure 9.2 Synthesized compounds using zamoranic acid
1
as starting material...
Figure 9.3 Tri‐ and tetracyclic diterpene skeletons.
Figure 9.4 Synthesis of interesting compounds from
ent
‐halimic acid.
Figure 9.5 Sesterterpenolide and glycerol hybrids.
Figure 9.6 Natural quinone/hydroquinone sesquiterpenes.
Figure 9.7 Structures proposed and revised for (−)‐agelasine C and epi‐agela...
Figure 9.8 Sesquiterpene indoles, analogues of polyalthenol and pentacyclind...
Chapter 10
Scheme 10.1 Ring distortion of yohimbine with a subsequent decoration of fra...
Scheme 10.2 Synthesis of regulatory free pseudoephenamine substitute of pseu...
Scheme 10.3 Ephedrine isomers as chiral building blocks.
Scheme 10.4 Asymmetric addition of terminal alkynes to carbonyls mediated by...
Scheme 10.5 Selected examples of ligands and catalysts derived from ephedrin...
Scheme 10.6 Ephedrine‐derived amides
36
and
38
for enantio‐ or diastereosele...
Scheme 10.7 Selected applications of ephedrines‐derived heterocyclic chiral ...
Scheme 10.8 Synthesis of enantiomers of (
S
P
)‐
57
or (
R
P
)‐
59
from (−)‐ephedr...
Scheme 10.9 Regioselective substitution of pyridine ring in (
S
)‐nicotine
61
....
Scheme 10.10 (
S
)‐Nicotine as building block for related alkaloids: altinicli...
Scheme 10.11 Anabasine used as a chiral scaffold in various syntheses.
Scheme 10.12 Sparteine‐mediated asymmetric deprotonation of Hoppe carbamates...
Scheme 10.13 Aggarwal iterative asymmetric deprotonation mediated by spartei...
Scheme 10.14 Selected examples of (−)‐sparteine
88
‐mediated enantioselective...
Scheme 10.15 Sparteine‐mediated
ortho
‐lithiation for the synthesis of planar...
Scheme 10.16 (−)‐Sparteine
88
and (+)‐sparteine surrogate
91
‐mediated asymme...
Scheme 10.17 Synthesis of (+)‐sparteine surrogate
91
and other bispidines fr...
Scheme 10.18 Cytisine as a building block for synthesis of (+)‐hupeol
131
an...
Scheme 10.19 Major applications of Cinchona alkaloid derivatives
137
–
144
(i...
Scheme 10.20 Stoichiometric chiral sulfinyl transfer complex derived from qu...
Scheme 10.21 Ring cleavages and rearrangements of Cinchona alkaloids.
Scheme 10.22 Chiral building blocks from Cinchona alkaloids through an oxida...
Scheme 10.23 Ring distortion of quinine toward chiral molecular diversity....
Scheme 10.24 Nucleophilic substitution of Cinchona alkaloids.
Scheme 10.25 Baran's zinc sulfinates for radical regioselective modification...
Scheme 10.26 Selected examples of CH‐alkylation of Cinchona alkaloids using ...
Scheme 10.27 Formation of scopoline and epibatidine analog form scopolamine....
Scheme 10.28 Cocaine as a precursor of
cis
‐2,5‐disubstituted pyrrolidine der...
Scheme 10.29 Preparation of tropaquiniclidines
199–202
from cocaine by...
Scheme 10.30 Mizoroki–Heck polymerization of Cinchona alkaloid dimers with t...
Scheme 10.31 Quaternization of Cinchona bis 9‐
O
‐ethers toward polymers
206
....
Scheme 10.32 Immobilization of Cinchona organocatalysts onto poly(glycidyl m...
Figure 10.1 Selected alkaloids presented in this chapter and their applicati...
Figure 10.2 Ephedrine and its stereoisomers.
Figure 10.3 Selected applications of Myer's alkylation in total synthesis of...
Figure 10.4 Most common tobacco alkaloids.
Figure 10.5 Structural features and common representatives of lupin alkaloid...
Figure 10.6 Examples of biologically active compounds prepared with the use ...
Figure 10.7 Four major members of Cinchona alkaloids. Highlighted in gray ar...
Figure 10.8 Click chemistry Cinchona alkaloids‐derived 1,2,3‐triazoles and t...
Figure 10.9 Selected examples of biologically active diversified Cinchona al...
Figure 10.10 The most common members of tropane alkaloids.
Figure 10.11 Examples of hyperbranched polymers with Cinchona squaramide moi...
Figure 10.12 Helical poly(phenylacetylene)s
209–212
bearing Cinchona a...
Chapter 11
Scheme 11.1 The synthesis of
CBB 1
. Abbreviations:
NBS
=
N‐bromosuccinimide
...
Scheme 11.2 The synthesis of estrone.
Scheme 11.3 The synthesis of steroid system via
CBB 2
. Abbreviations: DIPEA ...
Scheme 11.4 The enantioselective synthesis of oxy‐functionalized steroids. A...
Scheme 11.5 The synthesis of cardiotonic steroids intermediate via
CBB 4
.
Scheme 11.6 The synthesis of cardenolide via
CBB 5
. Abbreviations: TPY = (tr...
Scheme 11.7 The synthetic approach to ouabagenin from
CBB 5
.
Scheme 11.8 The synthesis of
CBB 6
. Abbreviations: LDA = lithium diisopropyl...
Scheme 11.9 The synthesis of a tetracyclic steroidal core from
CBB 6
. Abbrev...
Scheme 11.10 The synthesis of an estrogenic skeleton from
CBB 7
.
Scheme 11.11 The synthesis of a steroid analogue via
CBB 8
; (a) (i) Phenylpr...
Scheme 11.12 The synthesis of
ent
‐steroids from
ent
‐
CBB 8
.
Scheme 11.13 The synthesis of a steroidal precursor from
CBB 9
[15].
Scheme 11.14 Possible mechanism of the oxidative rearrangement [14]. Abbrevi...
Scheme 11.15 (a) The structure of cyclopamine; (b) the structure of Comins r...
Scheme 11.16 The synthesis of cyclocitrinol. Abbreviation: Ts = tosyl, DMAP ...
Scheme 11.17 The synthesis of vulgarobufotoxin. Abbreviations:
TBS
=
tert‐bu
...
Scheme 11.18 The synthesis of pleurocin A/matsutakone. Abbreviations:
CSA
=
Scheme 11.19 The synthesis of strophasterol. Abbreviations: DMAP = 4‐dimethy...
Scheme 11.20 The synthesis of herbarulide. Abbreviation: MCPBA =
meta
‐chloro...
Scheme 11.21 The synthesis of pinnigorgiol E and pinnigorgiol B. Abbreviatio...
Scheme 11.22 The synthesis of clathsterol. Abbreviations: TBS =
tert
‐butyldi...
Scheme 11.23 The synthesis of propindilactone G. Abbreviations:
IBA
=
3‐iodo
...
Figure 11.1 (a) The steroid skeleton; (b) cholesterol structure with carbon ...
Figure 11.2 Examples of substrates from the chiral pool used to synthesize s...
Figure 11.3 The structure of (a) Hajos–Parish ketone and (b) Wieland–Miesche...
Chapter 12
Scheme 12.1 Synthesis of
H
‐Phosphinate (
R
P
)‐
7
.
Scheme 12.2
L
‐Menthyl
H
‐phosphinates in the construction of
P
‐stereogenic co...
Scheme 12.3 The utility of dimenthyl phosphite
26
in the synthesis of
28
and...
Scheme 12.4 The transformation of
30
leading to (−)‐menthyl phenylphosphinat...
Scheme 12.5 The synthesis of numerous chiral organophosphorus compounds from...
Scheme 12.6 Synthesis of
L
‐menthyl
H
‐phosphinite‐boranes and
L
‐menthyl
H
‐pho...
Scheme 12.7 Functionalization in the 3,3′‐positions.
Scheme 12.8 Functionalization in the 4,4′‐positions.
Scheme 12.9 Polymer supported 4,4′‐substituted‐BINAP‐based ligands. DVB, div...
Scheme 12.10 Functionalization in the 5,5′‐positions. DMSO, dimethyl sulfoxi...
Scheme 12.11 Modification of MeO‐BIPHEP.
Scheme 12.12 Modification of HO‐BIPHEP.
Scheme 12.13 Modification of positions 6 and 6′ of biphenyl core. MW, microw...
Scheme 12.14 Modification of biphenyl‐derived phosphepines.
Scheme 12.15 The enzymatic transformation of
191
leading to dehydrophos (DHP...
Scheme 12.16 The synthesis of glucosides and galactosides
199–200
.
Scheme 12.17 The synthesis of
R
and
S
1,2,3,4‐tetrahydroisoquinoline‐3‐phosp...
Scheme 12.18 The synthesis of a library of α‐aminophosphonic acids
207
and
2
...
Scheme 12.19 The formation of deoxynucleotide derivatives
211–213
.
Scheme 12.20 The synthetic route to GGsTop
217
.
Scheme 12.21 The synthesis of aminophosphonic acids
222–223
.
Scheme 12.22 The synthesis of tRNASec mimic
228
.
Scheme 12.23 The synthetic route to receptor antagonists
240–242
and p...
Scheme 12.24 The steps of the synthesis of the inhibitor prodrug
246
.
Scheme 12.25 The synthesis of dipeptide
251
starting from
247
.
Scheme 12.26 The synthesis of a library of peptides
256–259
.
Scheme 12.27 Aminophosphonic acid
253
as a building block for peptide
261
.
Scheme 12.28 Fmoc‐
L
‐BrPmp(OMe
2
)‐OH
262
as a building block for the tripeptid...
Scheme 12.29
N
‐Fmoc‐F
2
Pmp‐OH
264
as a building block for peptides
265
and
26
...
Scheme 12.30 Formation of imine
269
starting from
267
.
Scheme 12.31 The synthesis of α‐epoxy‐δ‐aminophosphonate
273
.
Scheme 12.32 The synthesis of amino‐β‐ketophosphonate (
R
)‐
274
starting from...
Scheme 12.33 The synthesis of two natural peptides: Rhizocticin A and Plumbe...
Scheme 12.34 Synthesis chiral cyclic triamides or diamidochloridites.
Scheme 12.35 Total synthesis of estrone
289
.
Scheme 12.36 Synthesis of enantiopure phosphino‐phosphonites.
Scheme 12.37 Stereoselective formation of aminophosphines.
Scheme 12.38 The asymmetric synthesis of numerous chiral organophosphorus co...
Scheme 12.39 Synthesis of primary aminophosphines.
Scheme 12.40 Diastereoselective formation of
N
‐phosphinoyl oxazolidinones....
Scheme 12.41 Ephedrine‐assisted formation of chiral phosphorous stereocenter...
Scheme 12.42 Pseudoephedrine derived
bis
‐P‐chiral scaffolds.
Scheme 12.43 Acid‐dependent formation of secondary phosphine oxide antipodes...
Scheme 12.44 1‐Amino‐2‐indanol assisted synthesis of chiral
sec
‐Phosphine ox...
Scheme 12.45 Diastereoselective
ortho
‐lithiation of ferrocene
325
.
Figure 12.1 (−)‐
L-
Menthol in the synthesis of
P
‐stereogenic compounds.
Figure 12.2 Optically pure
L
‐menthyl phosphinates.
Figure 12.3
P
‐Stereogenic phosphonium salt and phosphine oxides.
Figure 12.4 (−)‐Menthol‐derived catalysts
48
–
57
.
Figure 12.5 Structures of atropisomeric phosphine ligands.
Figure 12.6 Polymeric and dendrimeric of 5,5′‐disubstituted BINAP derivative...
Figure 12.7 Modification of BINAPINE.
Figure 12.8 “Envelope” representation of aminophosphonate pentamolybdate uni...
Figure 12.9 Organophosphorus compound with P—N and/or P—O bonds.
Chapter 13
Scheme 13.1 Classical synthesis of menthyl (
S
S
)‐
p
‐toluenesulfinate.
Scheme 13.2 Alternative synthesis of menthyl (
S
S
)‐
p
‐toluenesulfinate.
Scheme 13.3 Synthesis of alkyl or aryl
p
‐tolyl sulfoxides by using menthyl (
Scheme 13.4 Highly successful synthetic strategies from past works involving...
Scheme 13.5 First steps involving chiral sulfinyl compounds in the synthesis...
Scheme 13.6 Relevant chiral intermediates in the synthesis of octalactins.
Scheme 13.7 Synthesis of chiral dihydropirans.
Scheme 13.8 Synthesis of (
R
)‐crispine A.
Scheme 13.9
ortho
‐Lithiation of activated aryl fragments as an innovative nu...
Scheme 13.10 Chiral sulfinyl intermediates in the synthesis of (
S
)‐tetrahydr...
Scheme 13.11 Chiral sulfinyl intermediates in the synthesis of xylopinine. S...
Scheme 13.12 Chiral sulfinyl quinonoid structures.
Scheme 13.13 Sulfinyl‐based synthesis of the core of ajudazol. Source: Essig...
Scheme 13.14 Chiral sulfoxides in the synthesis of atropisomeric structures....
Scheme 13.15 A sulfinyl route for the synthesis of steganone. Source: Dherba...
Scheme 13.16 Synthesis of chiral 2‐(
p
‐tolylsulfinyl)aniline.
Scheme 13.17 Homologation of boronic esters with chiral sulfinyl compounds....
Scheme 13.18 A sulfoxide‐oxazoline ligand.
Scheme 13.19 Synthesis of
p
‐toluenesulfinamide and its conversion into the c...
Scheme 13.20 First synthetic steps in the synthesis of (
S
)‐(+)‐cocaine.
Scheme 13.21 Application of the enolate of a Weinreb's amine in the synthesi...
Scheme 13.22 An early step in the synthesis of lirinine. Source: Hellal et a...
Scheme 13.23 An early step in the synthesis of lythranidine. Source: Gebauer...
Scheme 13.24 An early step in the synthesis of serine protease inhibitors.
Scheme 13.25 An early step in the synthesis of ibrexafungerp.
Scheme 13.26 A different menthyl arylsulfinate.
Scheme 13.27 Chiral sulfinyl ligands.
Scheme 13.28 Synthesis of (
S
)‐
tert
‐butyl
tert
‐butanethiosulfinate.
Scheme 13.29 Basic reactivity of the Ellman's reagent.
Scheme 13.30 Synthesis of a precursor of (+)‐yangambin with the aid of the E...
Scheme 13.31 Spiroketal intermediates with the aid of the Ellman's reagent....
Scheme 13.32 An early step in the synthesis of Almorexant.
Scheme 13.33 An early step in the synthesis of an inhibitor of
Pseudomonas a
...
Scheme 13.34 Chiral methyl phenyl sulfoximine as a precursor of thioureas.
Scheme 13.35 Chiral sulfoximines as a precursor of chiral cyclopropanes.
Scheme 13.36 Diacetone‐
D
‐glucose sulfinates and their employment in asymmetr...
Scheme 13.37 DAG‐sulfinates as precursor of rimatandine.
Scheme 13.38 Enantioselective oxidation of a large family of aryl benzyl sul...
Chapter 14
Scheme 14.1 Chiral diselenides in asymmetric synthesis.
Scheme 14.2 Selected examples of asymmetric methoxyselenylation of styrene....
Scheme 14.3 Chiral selenium‐mediated cyclization.
Scheme 14.4 Reagent‐controlled asymmetric selenocyclizations for the synthes...
Scheme 14.5 Selenium promoted synthesis of enantiopure pyrrolidines, octahyd...
Scheme 14.6 Possible conversions of selenium functionality.
Scheme 14.7 Asymmetric synthesis of substituted azetidines. THF, tetrahydrof...
Scheme 14.8 Synthesis of bioactive oligosaccharides.
Scheme 14.9 Asymmetric cyclopropanations of chiral methylene compounds with ...
Scheme 14.10 Synthesis of chiral 1,4‐dioxanes, morpholines, thiomorpholine, ...
Scheme 14.11 Synthesis of enantiopure pyrazino‐indoles and pyrroles. DCM, di...
Scheme 14.12 Functionalization of 2′,3′‐ene‐2′‐phenylselenonyl nucleosides t...
Scheme 14.13 A reactive selenosugar for the synthesis of enantiomerically pu...
Scheme 14.14 Vinyl selenones derived from
D
‐xylose and
D
‐fructose in diverse...
Scheme 14.15 Cycloaddition reactions of vinyl selenone‐modified carbohydrate...
Scheme 14.16 Organocatalyzed reactions for the preparation of densely functi...
Scheme 14.17 Organocatalyzed reaction of 2‐aryl‐2‐cyanoacetates and vinyl se...
Scheme 14.18 Total synthesis of (+)‐Trigonoliimine A.
Scheme 14.19 A key step for the total synthesis of Hinckdentine A.
Scheme 14.20 One‐pot enantioselective synthesis of 1,3‐oxazinan‐2‐one. PTSA,...
Scheme 14.21 Triple role of phenylselenonyl group.
Scheme 14.22 Enantioselective synthesis of quaternary α‐amino acids employin...
Scheme 14.23 Enantioselective vinylogous Michael addition to vinyl selenones...
Scheme 14.24 Organocatalyzed enantioselective Michael addition/cyclization c...
Scheme 14.25 Organocatalyzed Michael additions of oxindoles to vinyl selenon...
Figure 14.1 Selenium‐heteroatom nonbonding interaction.
Figure 14.2 Vinyl selenones as building blocks in asymmetric synthesis.
Chapter 15
Scheme 15.1 Axial chirality of allenes as the source of central chirality of...
Scheme 15.2 Enantiospecific, dialkylzinc‐initiated cyclization of 2,3‐alleno...
Scheme 15.3 The catalytic cycle transforming chiral propargyl mesylates into...
Scheme 15.4 Stereospecific reactions of chiral allenylzinc reagents with ena...
Scheme 15.5 Allenylmetal‐based approach to the enantioselective synthesis of...
Scheme 15.6 Face‐selective 1,2‐addition of Grignard reagents to chiral allen...
Scheme 15.7 Late‐stage construction of the spiroketal fragment of pectenotox...
Scheme 15.8 Bis(spirodiepoxide) strategy for the erythrynolide macrolactone ...
Scheme 15.9 The synthesis of chiral phosphine oxides by allene epoxidation....
Scheme 15.10 CT in Rh‐catalyzed nitrene addition to allene.
Scheme 15.11 Stereospecific aziridination of chiral allene.
Scheme 15.12 Cyclization of sulfamate‐allenes to bicyclic aziridines for the...
Scheme 15.13 Silylene transfer to chiral allene and ring expansion in the re...
Scheme 15.14 The concept of torquoselectivity controlled by axial chirality ...
Scheme 15.15 The synthesis of chiral methoxymethyl allenes and their enantio...
Scheme 15.16 Application of silver‐promoted allenol cyclization in synthesiz...
Scheme 15.17 Regio‐ and diastereospecific cyclization of allenediol in the s...
Scheme 15.18 The synthesis of (−)‐malyngolide.
Scheme 15.19 Formation of an iodonium cation from allene and its sulfoxide‐a...
Scheme 15.20 Intramolecular hydroarylation of chiral benzylallenes.
Scheme 15.21 Silver‐promoted
exo
cyclization of allenylamine.
Scheme 15.22 Enantiosepecific cyclization of allenols to vinyltetrahydrofura...
Scheme 15.23 Total synthesis of (−)‐rhazinilam.
Scheme 15.24 CT in intermolecular Au‐catalyzed hydroamination of allenes....
Scheme 15.25 Asymmetric intermolecular hydroarylation of allenes with
N
‐meth...
Scheme 15.26 Titanium‐mediated cyclization of allene‐ynes with the formation...
Scheme 15.27 Allenic Pauson–Khand reaction leading to 5,7‐bicyclic systems....
Scheme 15.28 Allenic Pauson–Khand reaction catalyzed by a cationic rhodium c...
Scheme 15.29 CT in C–H activation of methoxybenzamides followed by allenol i...
Scheme 15.30 Origin of enantiospecificity in Ni‐catalyzed reaction of allene...
Scheme 15.31 Photoinduced intramolecular [2+2] cycloaddition of allenes and ...
Scheme 15.32 Allene–alkene Diels–Alder route to (+)‐sterpurene.
Scheme 15.33 Intramolecular allene–diene Diels–Alder cycloaddition.
Scheme 15.34 Photocatalytic deracemization of allene and its enantiospecific...
Chapter 16
Scheme 16.1 Pioneering application of organocatalytic allylboration of keton...
Scheme 16.2 Stereoselective propargyl‐ and allylboration of hydrazonoesters ...
Scheme 16.3 Application of BINOL in asymmetric conjugated addition of triflu...
Scheme 16.4 Organocatalytic 1,6‐addition of arylboronic acids to para‐quinon...
Scheme 16.5 Stereoselective Petasis reaction by Marques and Burke. DCM, dich...
Scheme 16.6 Organocatalytic synthesis of trifluoromethyl allylboronic acids ...
Scheme 16.7 Asymmetric Michael addition catalyzed by BINOL‐based crown ether...
Scheme 16.8 Enantioselective benzylation of glycine derivative by Maruoka's ...
Scheme 16.9 Maruoka's hybrid phase‐transfer catalysis.
Scheme 16.10 Nucleophilic aromatic substitution catalyzed by BINOL‐based pho...
Scheme 16.11 Asymmetric nucleophilic fluorination under hydrogen bonding PTC...
Scheme 16.12 Michael reaction of indanone derivatives by Akiyama.
Scheme 16.13 Michael reaction/iminium ion cyclization by Dixon.
Scheme 16.14 Phospha‐Michael‐type addition by Terada.
Scheme 16.15 Aza‐Friedel–Crafts reaction by Terada. DCE, dichloroethane.
Scheme 16.16 Aza‐Friedel–Crafts reaction by Bolm. TFA, trifluoroacetic acid....
Scheme 16.17 Aza‐Diels–Alder reaction by Akyiama.
Scheme 16.18 Oxo‐Diels–Alder reaction by Terada.
Scheme 16.19 1,3‐Dipolar cycloaddition by Gong. DCM, dichloromethane; PCC, p...
Scheme 16.20 1,3‐Dipolar cycloaddition of azlactones and methyleneindolinone...
Scheme 16.21 Mannich‐type reaction presented by Akiyama.
Scheme 16.22 Mannich reaction of acetylacetone by Terada. DCM, dichlorometha...
Scheme 16.23 Alkylation of α‐diazoesters with
N
‐acylimines by Terada and Pen...
Scheme 16.24 The Biginelli reaction by Gong.
Scheme 16.25 Strecker reaction by Rueping. HCN, hydrogen cyanide.
Scheme 16.26 Reductive amination by MacMillan. MS, molecular sieves.
Scheme 16.27 Pictet–Spengler reaction by List.
Figure 16.1 BINOL and its derivatives.
Chapter 17
Figure 17.1 (a) Molecular structures of carbo[
n
]helicenes and helicene numbe...
Figure 17.2 Helicene topological descriptors.
Figure 17.3 Helicene scaffold embedded into large polycyclic aromatic system...
Figure 17.4 (a) Topological descriptor of the helicene chirality and ECD spe...
Figure 17.5 Racemic synthesis of carbo[
n
]helicenes: metal‐free photocyclizat...
Figure 17.6 Racemic synthesis of carbo[
n
]helicenes through Pd‐catalyzed reac...
Figure 17.7 Intramolecular Co‐, Ni‐, Ru‐, and Pt‐catalyzed [2+2+2] cyclizati...
Figure 17.8 Optical resolution strategies. (a) chiral agents used for recrys...
Figure 17.9 Selected examples of asymmetric synthesis from optically pure su...
Figure 17.10 Helicenes in catalysis.
Figure 17.11 Helicenes used for organic electronics.
Figure 17.12 Top: Chiral twistacenes.
Figure 17.13 (A) synthesis of
116
. Reagents and conditions: (a) (i) 2,6‐dibr...
Chapter 18
Figure 18.1
meso
‐Tetraaryl porphyrins (a) and
meso
‐tetraaryl‐2‐aza‐21‐carbap...
Figure 18.2 Chiral porphyrins, their complexes, and dimers.
Figure 18.3 Substitution and addition sites in modified
NCP
.
Figure 18.4 Two projections of enantiomers of
meso‐
tetraphenyl‐2‐aza‐2...
Figure 18.5 Enantiomers of 21‐alkylated
NCP
and their CD spectra of dichloro...
Figure 18.6 21‐substituted
NCP
and solid‐state structures of enantiomers of ...
Figure 18.7 Formation and reactivity of 2,21‐alkoxy
NCP
[65].
Figure 18.8 Application of N‐fused porphyrin in the synthesis of 21‐substitu...
Figure 18.9 Stereoisomers of internally bridged
NCP
derivatives: with 21,22‐...
Figure 18.10 Solid‐state structures of enantiomers (a), schematic structure ...
Figure 18.11 Enantiomers of 21‐(
o
‐carboxyphenyl)azo‐
NCP
(a) and 3‐amine‐21‐...
Figure 18.12 Enantiomers and CD spectra of 2‐methyl‐7,8‐(2′‐(2″,6″‐dichlorop...
Figure 18.13 Structures of chiral phlorins obtained by 1,3‐cycloadditions to...
Figure 18.14 Synthesis of 3‐P(O)(OEt)
2
–5‐H‐
NCP
(a), optical absorption (bla...
Figure 18.15 Examples of square planar and tetragonal bipyramid complexes of...
Figure 18.16 Schematic structures of chiral complexes of manganese, iron, co...
Figure 18.17 Schematic structure of zinc and cadmium complexes of 3‐P(O)(OR)...
Figure 18.18 Schematic representation and solid‐state enantiomers of the
NCP
Figure 18.19 Schematic structure and solid‐state enantiomers of
NCP
Ag(RuCp*)...
Figure 18.20 Schematic structures of 21‐ and 2,21‐alkylated derivatives of t...
Figure 18.21 Schematic structures and solid‐state enantiomers of selected
NC
...
Figure 18.22 Schematic and selected solid‐state structures of
NCP
dimers: bi...
Figure 18.23 Schematic and selected solid‐state structures of
NCP
dimers: bi...
Figure 18.24 Tetrakis(rhodium) bis(
NCP
) tetracarbonyl (a) and μ‐oxo‐dimer of...
Figure 18.25 Schematic structures of several chiral covalently bridged bis(
N
...
Figure 18.26 Schematic structures of silver(III) complex 2′,2″‐bis(3‐
NCP
Ag)...
Figure 18.27 Schematic and the solid state structures of 21,21′‐(
NCP
)
2
(a) a...
Figure 18.28 Definition of 3,3′‐(
NCP
)
2
chirality for the synclinal (a) and a...
Figure 18.29 Metal complexes of 3,3′‐(
NCP
)
2
with indication of their configu...
Chapter 19
Figure 19.1 Chemical structures of (a) the copper(I) complex [Cu(
1
)]
+
of...
Figure 19.2 Schematic representations and embedded presentations of the mole...
Figure 19.3 Chemical structure of porphyrin‐stoppered [2]rotaxane
3
.
Figure 19.4 Embeddings of the enantiomers of topologically chiral (a and b) ...
Figure 19.5 Chemical structures of conditionally topologically chiral [2]cat...
Figure 19.6 The chiral copper(I) [2]catenane complex [Cu(
7
)]
+
(one enant...
Figure 19.7 (a)
D
4
‐ and (b)
D
2
‐symmetric presentations of the Solomon rings ...
Figure 19.8 Schematical comparison of (a) a [2]catenane with oriented rings ...
Figure 19.9 Two isomers of the cyclodextrin‐based [2]rotaxane
10
:
10a
corres...
Figure 19.10 Inherently chiral [2]rotaxanes:
11
is based on the substitution...
Figure 19.11 The enantiomers of the “co‐conformationally point chiral” [2]ro...
Figure 19.12 Classical diagrams of the first five prime knots including the ...
Figure 19.13 Chemical structures of complexes of the molecular trefoil knots...
Figure 19.14 A molecular trefoil knot (
21
) obtained by hydrogen bond templat...
Figure 19.15 (a) Chiral and (b)
meso
diastereomers of a bis‐[2]catenane with...
Figure 19.16 (a) Chiral and (b)
meso
diastereomers of covalently linked tref...
Figure 19.17 A composite topologically chiral knot made by merging three ope...
Figure 19.18 A chiral bis[2]catenane (
22
) made by covalently bridging two to...
Figure 19.19 (a) A [3]rotaxane (
23
) incorporating two oriented macrocycles w...
Figure 19.20 Covalent bridging of trefoil knots produces knot‐stoppered dumb...
Figure 19.21 Chemical structure of the diastereomer of the branched tetrakno...
Figure 19.22 A covalent dimer of trefoil knots. The isomer shown (
27
) is chi...
Figure 19.23 A covalent trimer of trefoil knots. The isomer shown (
28
) is ch...
Figure 19.24 Copper(I) complexes of composite knots made by combining two do...
Figure 19.25 The dinuclear lutetium complex [Lu
2
(
30
)]
6+
of the composite...
Figure 19.26 Comparison of the structures of (a) the Fe
2+
complex of the...
Guide
Cover Page
Title Page
Copyright
Preface
Foreword
Table of Contents
Begin Reading
Index
Wiley End User License Agreement
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Chiral Building Blocks in Asymmetric Synthesis
Synthesis and Applications
Edited byElżbieta WojaczyńskaJacek Wojaczyński
Editors
Prof. Elżbieta WojaczyńskaWrocław University of Science and TechnologyFaculty of ChemistryWybrzeże Wyspiańskiego 1750 370 WrocławPoland
Dr. Jacek WojaczyńskiUniversity of WrocławFaculty of Chemistry14 F. Joliot‐Curie St.50 383 WrocławPoland
Cover Image: Courtesy of Prof. E. Wojaczyńska
All books published by WILEY‐VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.
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Print ISBN: 978‐3‐527‐34946‐3ePDF ISBN: 978‐3‐527‐83418‐1ePub ISBN: 978‐3‐527‐83419‐8oBook ISBN: 978‐3‐527‐83420‐4
Preface
The concept of chiral building blocks has emerged with the first total syntheses of natural products. Their complex architecture with a defined stereochemistry could be conveniently afforded with the use of enantiopure, easily available reactants: amino acids, carbohydrates, terpenes, simple alkaloids – compounds from a collection called a “chiral pool.” Their introduction at the early stage opens the route to stereoselective creation of subsequent stereogenic centers due to the possible chiral induction. The main drawbacks of this approach lie in the necessity of using stoichiometric amounts of chiral starting materials and in the fact that they are typically found in one enantiomeric form – limiting the accessible configuration of the target molecule.
Over the years, with the development of asymmetric synthesis, the attractiveness of building blocks has faded, as methods based on chiral, reusable auxiliaries, and catalysts (metal complexes, organic molecules, and enzymes) have gained popularity. Chirality multiplication resulting from the use of substoichiometric (“catalytic,” to use a common, but imprecise word) doses of such inducers, typically available as both optical antipodes, has captured the imagination of synthetic chemists. Their significance was also manifested by two Nobel Prizes awarded in 2001 to William S. Knowles, Ryōji Noyori, and K. Barry Sharpless for their work on stereoselective catalysis, and 20 years later to Benjamin List and David McMillan for the development of asymmetric organocatalysis.
It does not mean, however, that chiral pool concept has been completely forgotten or neglected. Perhaps pushed to the background by new discoveries and attracting less academic interest, it has always been of practical importance for the industry, in particular, for pharmaceutical companies exploiting all efficient and cheap routes for production of chiral drugs. For many preparations, the use of starting enantiomerically pure material is still the method of choice. And nowadays the chiral pool has been significantly enriched, to include not only compounds isolated from natural sources, but also simple synthetic building blocks, now available through efficient synthesis (sometimes combined with separation of enantiomers) or – more and more often – using biotechnological methods. They deliver both “natural,” traditional building blocks (amino‐ and hydroxyacids, terpenes, certain alkaloids) but also their less abundant enantiomers or diastereomers, and add new types of functionalities, e.g. amines or epoxides. A blend of approaches becomes common: reagents from the chiral pool often serve as the primary source of optical activity of many nonracemic compounds applied in catalytic processes, but, in turn, some of them are produced in asymmetric synthesis or with the use of enzymes. We hope that this book illustrates the current status of chiral building blocks in chemistry.
The book does not pretend to be comprehensive; instead of showing a full landscape, rather versatility and diversity of chiral building blocks are presented, from simple to complex ones, representing various types of chirality, originating from the presence of a stereogenic center (carbon atom or heteroatom), axis, or plane to helical and topological chirality. The authors – specialists in the field, some more experienced, and some at earlier stage of their careers – focus on the preparation of synthetic building blocks, and application of them as well as of natural chiral compounds in the construction of complex chiral scaffolds: drugs, agrochemicals, but also ligands and catalysts for organic synthesis.
We start with the smallest cyclic chiral building blocks, namely cyclopropene derivatives, whose stereoselective preparation is presented in Chapter 1. Two subsequent chapters focus on various ring systems containing heteroatoms: their preparation, and application as chiral reagents and auxiliaries. Again, there is no clear line between building blocks and auxiliaries: up to the moment when the chiral element remains in the product, it can be treated as a building block which may be eventually removed, but sometimes not entirely.
