Domino Reactions E-Book
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- Herausgeber: Wiley-VCH
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
The follow-up to the successful "Domino Reaction in Organic Synthesis", this ready reference brings up to date on the original concept. The chapters have been arranged according to the name of well-known transformations of the first step and in combination with the formed products. Each chapter is written by an internationally renowned expert, and the book is edited by L. F. Tietze, who established the concept of domino reactions.
The one-stop source for all synthetic chemists to improve the synthetic efficiency and allow an ecologically and economically beneficial preparation of every chemical compound.
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Seitenzahl: 870
Veröffentlichungsjahr: 2013
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Table of Contents
Related Titles
Title Page
Copyright
Preface
List of Contributors
List of Abbreviations
Introduction
References
Chapter 1: Transition-Metal-Catalyzed Carbonylative Domino Reactions
1.1 Introduction
1.2 Transition-Metal-Catalyzed Carbonylative Domino Reactions
1.3 Outlook
References
Chapter 2: Metathesis Reactions in Domino Processes
2.1 Domino Processes Featuring Solely Metathesis Events
2.2 Domino Processes Featuring Metathesis and Non-metathesis Events
2.3 Conclusion and Outlook
Acknowledgments
References
Chapter 3: C–H Activation Reactions in Domino Processes
3.1 Heck Reactions/C–H Activations
3.2 Carbopalladations and Aminopalladations of Alkynes/C–H Activations
3.3 Palladium-Catalyzed/Norbornene-Mediated ortho C–H Activations
3.4 Domino Reactions Involving Heteroatom-Directed C–H Activations
3.5 Conclusions
References
Chapter 4: Domino Reactions Initiated by Nucleophilic Substitution
4.1 Domino SN/Michael Addition and Related Reactions
4.2 Domino Reactions Initiated by Nucleophilic Ring Opening of Aziridines, Epoxides, and Activated Cyclopropanes
4.3 Domino SN/Brook Rearrangements
References
Chapter 5: Radical Reactions in Domino Processes
5.1 Introduction
5.2 Radical/Cation Domino Processes
5.3 Radical/Anionic Domino Processes
5.4 Domino Radical/Radical Process
5.5 Radical/Pericyclic Domino Processes
5.6 Asymmetric Radical Domino Processes
5.7 Conclusion and Outlook
Acknowledgments
References
Chapter 6: Pericyclic Reactions in Domino Processes
6.1 Introduction
6.2 Cycloadditions
6.3 Sigmatropic Rearrangements
6.4 Electrocyclizations
6.5 Mixed Transformations
6.6 Concluding Remarks
Acknowledgments
References
Chapter 7: Modern Domino Reactions Containing a MichaelAddition Reaction
7.1 Introduction
7.2 Formation of Acyclic Products
7.3 Formation of Carbocycles
7.4 Formation of O-Heterocycles
7.5 Formation of N-Heterocycles
7.6 Formation of S-Heterocycles
7.7 Formation of Heterocycles Containing Nitrogen and Oxygen
References
Chapter 8: Aldol Reactions in Domino Processes
8.1 Introduction
8.2 Domino Processes with the Aldol Reaction as First Step
8.3 Domino Processes with the Aldol Reaction as Subsequent Step
8.4 Conclusion and Outlook
References
Chapter 9: Oxidations and Reductions in Domino Processes
9.1 Introduction
9.2 Domino Reactions Initiated by Oxidation or Reduction Reaction
9.3 Domino Reactions Having Oxidation in Middle of the Sequence
9.4 Domino Reactions Terminated by Oxidation or Reduction Reaction
9.5 Conclusion
Acknowledgments
References
Chapter 10: Organocatalysis in Domino Processes
10.1 Introduction
10.2 One- and Two-Component Domino Reactions
10.3 Multicomponent Reactions
10.4 Conclusions
References
Chapter 11: Metal-Catalyzed Enantio- and Diastereoselective C–C Bond-Forming Reactions in Domino Processes
11.1 Domino Reaction Initiated by C–C Bond Formation
11.2 Domino Reaction Initiated by C–H Bond Formation
11.3 Domino Reaction Initiated by C–N Bond Formation
11.4 Domino Reaction Initiated by C–O Bond Formation
11.5 Domino Reaction Initiated by C–B and C–Si Bond Formation
11.6 Conclusion and Outlook
References
Chapter 12: Domino Processes under Microwave Irradiation, High Pressure, and in Water
12.1 Introduction
12.2 Microwave-Assisted Domino Reactions
12.3 Aqueous Domino Reactions
12.4 High-Pressure-Promoted Domino Reactions
12.5 Conclusion and Outlook
Acknowledgments
References
Chapter 13: Domino Reactions in Library Synthesis
13.1 Introduction
13.2 Domino Reactions in Natural-Product-Inspired Compound Collection Syntheses
13.3 Domino Approaches Targeting Scaffold Diversity
13.4 Solid-Phase Domino Syntheses of Compound Collections
13.5 Conclusion
References
Chapter 14: Domino Reactions in the Total Synthesis of Natural Products
14.1 Cationic Domino Reactions
14.2 Anionic Domino Reactions
14.3 Radical Domino Reactions
14.4 Pericyclic Domino Reactions
14.5 Transition-Metal-Catalyzed Domino Reactions
14.6 Domino Reactions Initiated by Oxidation or Reduction
14.7 Conclusion
References
Chapter 15: Multicomponent Domino Process: Rational Designand Serendipity
15.1 Introduction
15.2 Basic Considerations of MCRs
15.3 Substrate Design Approach in the Development of Novel MCRs
15.4 Conclusion
References
Index
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Editor
Prof. Dr. Lutz F. Tietze
Georg-August University
Institute of Organic and Biomolecular Chemistry
Tammannstr. 2
37077 Göttingen
Germany
Cover
Jungle Photo. Source: Fotolia © Chakka
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Preface
The synthesis of chemical compounds is a key issue in chemistry, both in academia and industry. A simple statement of general relevance is the saying “you cannot investigate a compound which you do not have in your hands and you cannot sell a substance which you did not make.” However, the aspects of synthesis have changed over the years. At the beginning, the development of synthetic methods such as the electrophilic aromatic substitution, the aldol reaction or the Diels–Alder cycloaddition was in the focus. Then the selectivity as the chemo-, regio-, diastereo-, and enantioselectivity was the main concern. Now, new aspects in synthesis have arisen, which are part of green chemistry: efficiency, reduction of waste, saving our resources, protecting our environment, and, finally, also economic advantages by reducing the transformation time and the amount of chemicals needed. To meet all these requirements, the domino concept was introduced by me, which, since its presentation and the first reviews, has grown immensely in the last years. In this book, experts in the different fields of domino reactions have put together their knowledge, and I am very grateful to all of them for their excellent contributions. Moreover, I would like to thank Martina Pretor for her fabulous help in preparing the book. I am also grateful to the publishers Wiley/VCH, especially Dr. Elke Maase and Dr. Bernadette Gmeiner, for their support.
Finally, I would like to express my deep thanks to the University of Göttingen, the State of Lower Saxony, the German Research Foundation (DFG), the Volkswagen Foundation, the German Ministry of Education and Research (BMBF), the European Community and the Fonds der Chemischen Industrie as well as the Alexander von Humbold Foundation, the Konrad–Adenauer–Foundation and the German National Academic Foundation for their continuous support of our work on domino reactions and other topics. I am also very thankful to many Chemical Companies worldwide, in particular the BASF and the Bayer AG.
Göttingen, June 6th, 2013
Lutz F. Tietze
List of Contributors
List of Abbreviations
(
S
,
S
)-MeDuPhos
(+)-1,2-bis[(2
S
,5
S
)-2,5-dimethylphospholano]benzene
(TMS)
2
NH
hexamethyldisilazane or bis(trimethylsilyl)amine
[Bmim]
1-butyl-3-methylimidazolium
Ac
acetyl
acac
acetylacetone
ACCN
1,1′-azobis(cyclohexanecarbonitrile)
Ac
2
O
acetic anhydride
AcOH
acetic acid
AIBN
2,2′-azobisisobutyronitrile
All
allyl
Ar
aryl
ARC
anionic relay chemistry
ASG
anion stabilizing group
ATBT
allyltri-
n
-butyltin
atm
standard atmosphere
BAIB
(diacetoxyiodo)benzene
BER
borohydride exchange resin
BF
3
·OEt
2
boron trifluoride–diethyl ether complex
BHT
butylhydroxytoluene
BINAP
2,2′-bis(diphenylphosphino)-1,1′-binaphthalene
BINAPO
2-diphenylphosphino-2′-diphenylphosphinyl-1,1′-binaphthalene
BINOL
1,1′-bi-2-naphthol
Biphep
1,1′-biphenyl-2,2′-diphenylphosphine
Bn
benzyl
Boc
tert
-butoxycarbonyl
borsm
based on recovered starting material
bpz
2,2′-bipyrazine
Bu
butyl
Bz
benzoyl
CA
cycloaddition
CAN
ceric ammonium nitrate
Cbz
carbonylbenzyloxy
CD
circular dichroism
cf
.
compare (lat.
confer
)
CM
cross-metathesis
cod
1,5-cyclooctadiene
coe
cyclooctene
Cp
cyclopentadienyl
CR
cycloreversion
CSA
camphorsulfonic acid
Cy
cyclohexyl
d
day
DA
Diels–Alder reactions
DABCO
1,4-diazabicyclo[2.2.2]octane
DAIB
(diacetoxyiodo)benzene
dba
dibenzylidenacetone
DBU
1,8-diazabicyclo[5.4.0]undec-7-ene
DCB
1,2-dichloroisobutane
DCE
1,2-dichloroethane
DCM
dichloromethane
DDQ
2,3-dichloro-5,6-dicyano-1,4-benzoquinone
de
diastereomeric excess
DFT
density functional theory
DHQ
hydroquinine
DHQD
dihydroquinidine
DIBAL
diisobutylaluminum hydride
DIOP
4,5-bis(diphenylphosphinomethyl)-2,2-dimethyl-1,3-dioxolane
DIPEA
diisopropylethylamine
DKP
diketopiperazine
DLP
1,2-dichloroethane with lauroyl peroxide
DMA
N
,
N
-dimethylacetamide
DMAD
dimethyl acetylenedicarboxylate
DME
dimethoxyethane
DMF
N
,
N
-dimethylformamide
DMP
Dess–Martin-periodinane
DMPU
1,3-dimethyl-3,4,5,6-tetrahydro-2(1
H
)-pyrimidinone,
N
,
N
-dimethyl propylene urea
DMSO
dimethyl sulfoxide
DOS
diversity-oriented synthesis
dpm
dipivaloylmethane
dppe
1,2-bis(diphenylphosphino)ethane
dppf
1,2-bis(diphenylphosphino)ferrocene
dppp
1,3-bis(diphenylphosphino)propane
dr
diastereomeric ratio
DTBP
2,6-di-
tert
-butylpyridine
E
electrophile
EC
electrocyclization
ee
enantiomeric excess
equiv
equivalent
ERO
electrocyclic ring-opening
et al
.
and others (lat.
et alii
)
Et
ethyl
EWG
electron-withdrawing group
Fmoc
9-fluorenylmethoxycarbonyl
fod
(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyloctane-3,5-dionate
GAP
group-assisted purification
h
hour
HAT
hydrogen atom transfer
HFIP
hexafluoroisopropanol
HIV
human immunodeficiency virus
HMPA
hexamethylphosphortriamide
HOMO
highest occupied molecular orbital
i.e.
that means (lat.
id est
)
IBX
2-iodoxybenzoic acid
IMDA
intramolecular Diels–Alder reaction
L
ligand
LDA
lithium diisopropylamide
LiHMDS
lithium hexamethyldisilazide
LUMO
lowest unoccupied molecular orbital
MAOS
microwave-assisted organic synthesis
MBH
Morita–Baylis–Hillman
MDRs
multicomponent domino reactions
Me
methyl
MeCN
acetonitrile
MEK
methyl ethyl ketone
MEM
(2-methoxyethoxy)methyl
Mes
mesityl
MOM
methoxymethyl
MTM
methylthiomethyl
MW
microwave
NADH
nicotinamide adenine dinucleotide
NBS
N
-bromosuccinimide
NCS
N
-chlorosuccinimide
NMM
N
-methyl morpholine
NMO
N
-methylmorpholine-
N
-oxide
NMP
N
-methyl-2-pyrrolidinone
Ns
p
-nitrobenzenesulfonyl
Nu
nucleophile
Oct
octyl
o
-DCB
ortho
-dichlorobenzene
PCC
pyridinium chlorochromate
PET
photochemical electron transfer
PEG
polyethylene glycol
PFBA
pentafluorobenzoic acid
PG
protecting group
Ph
phenyl
Phen
9,10-phenanthroline
PhMe
toluene
PIDA
phenyliodine diacetate
Piv
pivalate
PMB
p
-methoxybenzyl
PNO
pyridine-
N
-oxide
PPh
3
triphenylphosphine
PPTS
pyridinium
p
-toluenesulfonate
Pr
propyl
PS–BEMP
polystyrene–(2-
tert
-butylimino-2-diethylamino-1,-dimethyl-perhydro-1,3,2-diazaphosphorine)
PS–DMAP
polystyrene–dimethylaminopyridine
p
-TsOH or
p
-TSA
p
-toluenesulfonic acid
PVE
propargyl vinyl ether
Py
pyridine
R
rest
rac
racemic
RCM
ring-closing metathesis
ROM
ring-opening metathesis
RRM
ring-rearrangement metathesis
rt
room temperature
SEM
2-trimethylsilylethoxymethyl
SET
single electron transfer
sigR
sigmatropic rearrangement
S
N
nucleophilic substitution
S
N
1
substitution nucleophilic unimolecular
S
N
2
substitution nucleophilic bimolecular
SolFC
solvent free condition
SOMO
singly occupied molecular orbital
SPPS
solid-phase peptide synthesis
t
tert
TADDOL
(−)-(4
R
,5
R
)- or (+)(4
S
,5
S
)-2,2-dimethyl-α,α,α′,α′-tetraphenyl-1,3-dioxolane-4,5-dimethanol
TBA
tetra-
n
-butylammonium
TBA
tribromoacetic acid
TBAB
tetra-
n
-butylammonium bromide
TBAF
tetra-
n
-butylammonium fluoride
TBAI
tetra-
n
-butylammonium iodide
TBCHD
2,4,4,6-tetrabromo-2,5-cyclohexadienone
TBD
1,5,7-triazabicyclo[4.4.0]dec-5-ene
TBDMS or TBS
tert
-butyldimethylsilyl
TBDPS or TBPS
tert
-butyldiphenylsilyl
t
-Bu
tert
-butyl
t
-BuOH
tert
-butyl alcohol
t
-BuOK
tert
-butylate potassium
TC
thiophene-2-carboxylate
TEA
triethylamine
TEBA
benzyltriethylammonium chloride
TEMPO
(2,2,6,6-tetramethylpiperidin-1-yl)oxy
TES
triethylsilyl
TESOTf
triethylsilyltrifluoromethanesulfonate
Tf
trifluoromethanesulfonyl
TFA
trifluoroacetic acid
TFE
2,2,2-trifluorethanol
TfO
trifluoromethanesulfonate
TFP
tri-(2-furyl)phosphine
THF
tetrahydrofuran
TMSOTf
trimethylsilyl trifluromethanesulfonate
Thio
thiophene
TIPS
triisopropylsilyl
TMEDA
tetramethylethylendiamine
TMS
trimethylsilyl
TMSI
trimethylsilyl iodide or iodotrimethylsilane
Tol
tolyl
Ts
4-toluenesulfonyl (tosyl)
TS
transition state
TsOH
p
-toluenesulfonic acid
TTMSS
tris(trimethylsilyl)silane
VAPOL
2,2′-diphenyl-(4-biphenanthrol)
vs
.
as opposed to (lat.
versus
)
XPhos
2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl
Introduction
The beginning of organic synthesis can be dated back to the year 1824 when Wöhler, later professor of chemistry at the Georg-August University in Göttingen, showed that inorganic matter could be transformed into organic matter without the vis vitalis, the so-called power of life. At that time, he prepared the natural product oxalic acid from dicyan by simple hydrolysis. Better known is the transformation of ammonium cyanate into urea by simple heating, in 1828 (Scheme 1) [1].
Scheme 1 Synthesis of oxalic acid and urea without a vis vitalis by Whler.
A second milestone in organic synthesis is the total synthesis of the indole alkaloid reserpine by Woodward in 1956 [2] using a Diels–Alder reaction as the key step (Scheme 2), and finally with the total synthesis of palytoxin in 1994, the toxin of dinoflagellate Ostreopsis siamensis, with 64 stereogenic centers and several (E)- and (Z)-double bonds, Kishi [3] has shown that chemists can prepare any organic compound (Scheme 3).
Scheme 2 Synthesis of the indole alkaloid reserpine by Woodward 1956.
Scheme 3 Synthesis of palytoxin by Kishi 1994.
However, the synthesis of such a big molecule as palytoxin using a conventional stepwise approach with more than 100 steps is a singular great feat and can almost not be repeated. Thus, a 100-step synthesis with 80% yield per step would lead to only 0.00 000 002% as the total yield.
In contrast, a much better efficiency could be accomplished using domino reactions, which have been defined by us as processes of two or more bond forming reactions under identical reaction conditions, in which the latter transformations take place at the functionalities obtained in the former bond forming reactions [4]. In the processes one, two, three, or more substrates can be involved. Thus, multicomponent transformations are domino reactions per definition. In the meantime, several excellent reviews have also been published by other authors on this topic [5].
The quality and the usefulness of domino reactions are related to the increase of complexity and diversity in the final product compared to the starting material. Thus, the more steps a domino-process includes the greater is the probability to transform simple substrates to huge compounds. A further great advantage of the domino concept is its benefit to our environment and our natural resources, as it allows reducing the waste produced compared to normal procedures and minimize the amount of chemicals required for the preparation of a product. This also makes them economically favorable; moreover, they grant a decrease of the production time, which altogether would reduce furthermore the costs of any product.
Domino reactions usually show a good stereocontrol and good overall yields. Also very important is the fact that novel pathways can be developed, which cannot be followed in a stepwise approach, as in domino reactions intermediates can be unstable compounds, which are consumed as they are formed in a further step.
In our previous book on domino reactions [4h], we have classified domino reactions according to the mechanism of the different steps. This organizing principal will also be used in this book, and you will find chapters about transition metal catalysis including carbonylation, metathesis and CH-activation, nucleophilic substitutions, radical reactions, pericyclic reactions, Michael reactions, aldol reactions, oxidations, and reductions.
In addition, we have also included chapters that are related to the type of process as organocatalysis, enantio- and diastereoselective reactions, and multicomponent reactions as well as domino processes under microwave irradiation, high pressure, and in water. Finally, two chapters that are more product oriented have been included on the synthesis of compound collections and the synthesis of natural products and analogs.
This arrangement clearly leads to some overlap, which we have tried to minimize by discussing related subjects in-depth only in one chapter. However, to allow a correlation, some domino-processes are mentioned in more than one chapter.
Besides giving information to the reader about the development of domino reactions in the past years, the main purpose of this book is also to stimulate the design of novel domino reactions and use them in the synthesis of natural products and analogs, pharmaceuticals, agrochemicals, polymers, and materials not only in academic institutions but also in industry.
Per definition, all domino reactions take place in one reaction vessel without isolating any intermediates; however, they are much more than the so-called one-pot reactions, where you just put together different substrates and reagents after each other. The planning of domino reactions is like playing chess, where to be a reasonable player you will have to analyze four to five steps in advance. Thus, you have to predict the reaction pathways of all substrates and intermediates in your reaction mixture and in contrast to chess, where the movement of the different chess pieces is fixed, the reactivity of the chemical compounds can even be altered, for instance, by changing the pH-value or using different catalysts.
For the use and design of domino reactions in the synthesis of natural products, it is sometimes useful to look at the biosynthesis of these compounds. Thus, Nature is also using the concept of domino reactions and one of the most impressive examples is the biosynthesis of lanosterol from (S)-2,3-oxidosqualene, in which four new rings and six new stereogenic centers are formed [6]. This concept has later been exploited by developing a biomimetic synthesis of steroids [7] (Scheme 4).
Scheme 4 Biosynthesis of lanosterol from (S)-2,3-oxidosqalene.
Another well-known example is the biosynthesis of atropine within the formation of the central skeleton tropinone. Using a twofold Mannich reaction, tropinone has been prepared in a single process [8] (Scheme 5).
Scheme 5 Biomimetic synthesis of tropinone.
It should be stated that the book does not aim at comprehensiveness but the authors of the different chapters have looked for the most impressive examples and for clarifying the concept.
References
1. (a) Wöhler, F. (1828) Ann. Phys. Chem., 88, 253–256;(b) Wöhler, F. (1824) Z. Physiol., 1, S. 125–290.
2. Woodward, R.B. (1958) Tetrahedron, 2, 1–57.
3. Suh, E.M. and Kishi, Y. (1994) J. Am. Chem. Soc., 116, 11205–11206.
4. For domino reactions, see: (a) Tietze, L.F. and Beifuss, U. (1993) Angew. Chem. Int. Ed., 105, 137–170 ; Angew. Chem., Int. Ed. Engl. 1993, 32, 131–163;(b) Tietze, L.F. (1996) Chem. Rev., 96, 115–136;(c) Tietze, L.F. (1997) Nachr. Chem. Tech. Lab., 45, 1181–1187;(d) Tietze, L.F. and Lieb, M. (1998) Curr. Opin. Chem. Biol., 2, 363–37;(e) Tietze, L.F. and Haunert, F. (2000) in Stimulating Concepts in Chemistry (eds M. Shibasaki, J.F. Stoddart, and F. Vögtle), Wiley-VCH Verlag GmbH, Weinheim, pp. 39–64;(f) Tietze, L.F. and Modi, A. (2000) Med. Res. Rev., 20, 304–322;(g) Tietze, L.F. and Rackelmann, N. (2004) Pure Appl. Chem., 76, 1967–1983;(h) Tietze, L.F. and Rackelmann, N. (2005) in Multicomponent Reactions (eds J. Zhu and H. Bienaymé), Wiley-VCH Verlag GmbH, Weinheim, pp. 121–168;(i) Tietze, L.F., Brasche, G., and Gericke, K.M. (2006) Domino Reactions in Organic Synthesis, Wiley-VCH Verlag GmbH, Weinheim.(j) Tietze, L.F. and Levy, L. (2009) in The Mizoroki–Heck Reaction (ed. M. Oestreich), Wiley-VCH Verlag GmbH, Weinheim, pp. 281–344;(k) Tietze, L.F., Spiegl, D.A., and Brazel, C.C. (2009) in Experiments in Green and Sustainable Chemistry (eds H.W. Roesky and D.K. Kennepohl), Wiley-VCH Verlag GmbH, Weinheim, pp. 158–167;(l) Tietze, L.F. and Düfert, A. (2010) in Catalytic Asymmetric Conjugate Reactions (ed. A. Cordova), Wiley-VCH Verlag GmbH, Weinheim, pp. 321–350;(m) Tietze, L.F. and Düfert, A. (2010) Pure Appl. Chem., 82, 1375–1392;(n) Tietze, L.F., Stewart, S., and Düfert, A. (2012) in Modern Tools for the Synthesis of Complex Bioactive Molecules (eds J. Cossy and S. Arseniyades), John Wiley & Sons, Inc, Hoboken, NJ, pp. 271–334;(o) Tietze, L.F., Düfert, M.A., and Schild, S.-C. (2012) in Comprehensive Chirality, Vol. 2 (eds E.M. Carreira and H. Yamamoto), Elsevier, Amsterdam, pp. 97–121.
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Chapter 1
Transition-Metal-Catalyzed Carbonylative Domino Reactions
Xiao-Feng Wu, Helfried Neumann, and Matthias Beller
1.1 Introduction
“Sustainable development” has become one of the hottest terms in the twenty-first century. Of particular relevance in organic chemistry are the reaction efficiency and the avoidance of waste generation. With regard to sustainability, methodologies based on domino reactions, including multicomponent reactions, are a highly efficient strategy to synthesize complicated organic compounds. Domino reactions are defined as processes of two or more bond-forming reactions under identical conditions, in which the subsequent transformations take place at the functionalities that are obtained in the previous bond-forming transformations. Using domino reactions, complicated compounds can be relatively easily prepared from simple substrates. No tedious preparation of intermediates and purification processes are needed, which are the most energy-consuming and waste-generating steps in organic synthesis [1]. One prominent example is the domino Knoevenagel/hetero-Diels–Alder reaction, in which dihydropyrans could be straightforwardly synthesized from readily available starting materials [2].
Transition-metal catalysts play an ever-increasing and important role in modern chemistry [3]. Numerous transition-metal-catalyzed coupling reactions have been developed and applied in the total synthesis of natural products, such as the Suzuki reaction, the Negishi reaction, the Heck reaction, and many others [4]. Interestingly, the power of transition-metal catalysts is even more visible in the area of domino reactions, where terms such as palladium walking show the value of transition metals in bond formations.
Carbonylation reactions are interesting and important with regard to both industrial and academic research [5]. In these reactions, carbon monoxide (CO) can be used as one of the cheapest C1 sources. By introducing one or even more CO units into the parent molecules, carbonyl-containing products are easily prepared, which can be further modified to yield important chemicals for organic synthesis. Following the definition of domino reactions, we realized to our surprise that all the carbonylative coupling reactions belong to domino reactions, in which at least two C–C bonds were formed under the same reaction conditions.
In order to assess the value of domino and carbonylation reactions, and also to differentiate them from normal transition-metal-catalyzed carbonylation reactions, in this chapter we will only describe the carbonylation reactions that produce at least three bonds under the same conditions.
1.2 Transition-Metal-Catalyzed Carbonylative Domino Reactions
Transition-metal-catalyzed carbonylation reactions have shown impressive progress during past few decades; especially, the use of ruthenium, rhodium, and palladium as catalysts is widespread. More recently, iron and copper catalysts have also been attracting the attention of synthetic chemists because of their low cost and environmentally benign properties.
1.2.1 Ruthenium-Catalyzed Carbonylative Domino Reactions
Compared with metathesis [6], the ability of ruthenium catalysts in carbonylation is also impressive.
In 1998, the first ruthenium-catalyzed cyclocarbonylation of yne-aldehydes was studied by the group of Murai [7]. Bicyclic α,β-unsaturated γ-butyrolactones were synthesized in good to excellent yields (Scheme 1.1a), and two proposed reaction mechanisms were discussed for this transformation. One involved a five-membered metalacycle formed via a [2+2+1] cycloaddition, and the other proceeded through a ruthenium acyl intermediate that was generated from the oxidative addition of an aldehyde C–H bond to ruthenium. Later on, Kang and coworkers [8] developed a ruthenium-catalyzed cyclocarbonylation of allenyl aldehydes and allenyl ketones to synthesize various α-methylene-γ-butyrolactones in 48–85% yields (Scheme 1.1b). More recently, Snapper and Finnegan prepared polycyclic lactones in moderate to good yields through ruthenium catalysis, in which a ring-closing metathesis/hetero-Pauson–Khand reaction mechanism was proposed (Scheme 1.1c) [9]. This strategy was also adopted for the preparation of cyclopentenones [10].
Scheme 1.1 (a–c) Ruthenium-catalyzed hetero-Pauson–Khand reactions.
Some intermolecular carbonylative cycloaddition reactions were developed as well. In 1999, the group of Murai published a ruthenium-catalyzed intermolecular cyclocoupling of ketones, ethylene, and CO, producing lactones in good yields (Scheme 1.2) [11a]. This reaction showed the catalytic synthesis of heterocycles via an intermolecular carbonylative [2+2+1] cycloaddition for the first time. Many different ketones, such as α-dicarbonyl compounds and N-heterocyclic ketones, are used in this cycloaddition, and the addition of phosphines promotes the reactions of α-dicarbonyl compounds. Among the tested phosphines, P(4-CF3C6H4)3 has proved to be the ligand of choice. Beside ethylene cyclic olefins, unpolarized terminal olefins and internal alkynes could also be employed successfully in the synthesis, yielding highly functionalized lactones. An aromatic keto ester substituted with a CF3 group accelerated the reaction of the keto ester with ethylene. On the other hand, by using aromatic N-heterocyclic ketones, the rate of the reaction with ethylene slowed down when the phenyl ring contained a CF3 and went up when CF3 was replaced by a methoxy group [11b]. An increase in the pressure of ethylene or a lowering of the pressure of CO had a positive influence on the rate of the reaction in the case of the keto ester. Interestingly, a reversed behavior of the pressure rate was observed with N-heterocyclic ketones when using ethene.
Scheme 1.2 Ruthenium-catalyzed intermolecular carbonylative cycloaddition reaction.
In 2002, a novel and rapid ruthenium-catalyzed synthesis of pyranopyrandiones was developed by the group of Mitsudo [12]. Single cyclopropenones and cyclopropenones in combination with internal alkynes could be converted, in the presence of Ru3(CO)12 as catalyst, to pyranopyrandiones by cross-carbonylation of 2 equiv of CO in good yields (Scheme 1.3a,b). Interestingly, this reaction was successful when simple NEt3 was used as an efficient ligand. In contrast to other amine ligands (NBu3, N-methylpiperidine, pyridine, and N,N-diethylaniline), phosphorus ligands (PCy3 and PBu3) gave only moderate catalytic activity in this transformation. The right choice of the ruthenium precursor is very important, since the use of RuCl2(PPh3)3, RuH2(CO)(PPh3)3, and RuCl3·3H2O was ineffective even in the presence of NEt3. In addition, Ryu and coworkers [13] developed a synthesis of α-pyrones based on a ruthenium-catalyzed intermolecular carbonylative cycloaddition of α,β-unsaturated ketones with silylacetylenes and CO. Moderate yields were achieved by this new transformation (Scheme 1.3c).
Scheme 1.3 (a–c) Ruthenium-catalyzed carbonylative synthesis of pyrones.
The group of Murai [14] could demonstrate that ruthenium-catalyzed cyclocarbonylation of yne-imines resulted in formation of lactams (Scheme 1.4a). Catalytic amounts of Ru3(CO)12 promote this cyclocarbonylation of 1,6- and 1,7-yne-imines, giving bicyclic α,β-unsaturated lactams. Similar to the Pauson–Khand reaction, the lactam is formed in a [2+2+1] cycloaddition in which the acetylene π-bond, the imine π-bond, and the carbon atom of CO are involved. The acetylenic terminal carbon has to consist of an alkyl, an aryl, or silyl groups in order to give bicyclic α,β-unsaturated lactams via cyclocarbonylation of yne-imines. If the acetylenic terminal carbon has no substituents instead of the corresponding lactam, a dihydropyridine derivative will be generated without the incorporation of CO. Later on, the authors also showed that the cyclocarbonylation of imines, alkenes, or alkynes and CO gives γ-butyrolactams in good yields (Scheme 1.4b) [15].
Scheme 1.4 (a, b) Ruthenium-catalyzed carbonylative synthesis of lactams.
In 2000, a selective cycloaddition of cyclopropyl imines, derived from cyclopropyl phenyl ketone and tert-butylamine and CO (2 bar), was developed by the same group (Scheme 1.5) [16]. The reaction was allowed to proceed in toluene (3 ml) in presence of a catalytic amount of Ru3(CO)12 (0.02 mmol) at 160 °C for 60 h, giving the pyridinone derivative in 76% isolated yield.
Scheme 1.5 Ruthenium-catalyzed carbonylative reaction of cyclopropyl imines.
Moreover, in 2008, a novel ruthenium-catalyzed cyclization based on a combination of isocyanates, alkynes, and CO was developed by the group of Kondo et al. [17]. Polysubstituted maleimides could be obtained in excellent yields under CO at atmospheric pressure with low catalyst loading (Scheme 1.6).
Scheme 1.6 Ruthenium-catalyzed carbonylative synthesis of maleimides.
In 1997, Murai's [18] group developed the first ruthenium-catalyzed Pauson–Khand reaction, which originally was carried out by a cobalt catalyst. They showed that good yields of cyclopentenones could be achieved in an intramolecular, ruthenium-catalyzed cyclocarbonylation of 1,6-enynes (Scheme 1.7a). Later on, the cyclocarbonylation was extended to an intermolecular version in which alkynes, CO, and alkenes were converted into many cyclopentenones with excellent regioselectivity (Scheme 1.7b) [19]. Different substituted alkynes could be employed, showing the tolerance of the reaction. Notably, when a 2-PyMe2Si-substituted alkyne was used, the leaving group could be cleaved after the reaction. In 2000, Mitsudo and coworkers [20] reported another synthesis of cyclopentenones, which relied on a combination of allylic carbonates, alkenes, and CO. Here, the cyclocarbonylation was performed with either [RuCl2(CO)3]2/NEt3 or (η3-C3H5)RuBr(CO)3/NEt3, which constitutes a highly effective catalyst systems (Scheme 1.7c).
Scheme 1.7 (a–c) Ruthenium-catalyzed carbonylative synthesis of cyclopentenones.
Starting from the same substrates, even hydroquinones can be prepared by insertion of two molecules of CO. In 1998, Mitsudo and coworkers [21a] demonstrated that hydroquinones could be achieved in a ruthenium-catalyzed cyclocarbonylation by using alkynes and 2-norbornenes. Unsymmetrically substituted hydroquinones were obtained in high yields by this novel ruthenium-catalyzed transformation. For the preparation of higher substituted hydroquinones, functionalized alkenes could also be employed as starting material. Here, [Cp*RuCl2]2 was used as the catalyst (Scheme 1.8) [21b].
Scheme 1.8 Ruthenium-catalyzed carbonylative synthesis of hydroquinones.
1.2.2 Rhodium-Catalyzed Carbonylative Domino Reactions
In 2006, the group of Artok showed that 5-aryl-2(5H)-furanones could be prepared in moderate to good yields by a rhodium-catalyzed carbonylative arylation of internal alkynes with aryl boronic acids (Scheme 1.9a) [22]. α,β-Unsaturated ketones (chalcone derivatives) were formed as the major product when some TFA (trifluoroacetic acid) was added under the same reaction conditions [23a]. By varying the catalytic system, indanones could be produced as the main product [23b]. The chemical behavior of terminal alkynes is different, and either α,β-unsaturated ketones or furans starting from propargylic alcohols can be achieved (Scheme 1.9b) [24, 25]. In the case of vinyl ketones, 1,4-diketones were obtained by rhodium-catalyzed coupling of arylboronic acids in the presence of 20–40 bar of CO [26]. In 2007, Chatani demonstrated that indenones could be accessed by a carbonylative rhodium-catalyzed cyclization of alkynes with 2-bromophenylboronic acids (Scheme 1.9c) [27]. Here, the key intermediate is a vinylrhodium(I) species that is formed by transmetallation of RhCl with 2-bromophenylboronic acid followed by insertion of an alkyne. Next, the C–Br bonds on the adjacent phenyl ring were oxidatively added to provide a benzorhodacyclopentene species. After CO insertion and reductive elimination, the desired indenone was obtained. With regard to the regioselectivity, an alkyne substituted with a bulky and electron-withdrawing group favors the α-position of indenones. The highest regioselectivity was achieved in the case of silyl- or ester-substituted alkynes in the order SiMe3 > COOR aryl alkyl. Similarly, also indanone derivatives could be obtained when 2-bromophenylboronic acid was reacted with norbornene under 1 bar of CO. On conducting the reaction without CO, two molecules of alkynes were incorporated during the reaction sequence with 2-bromophenylboronic acid to give naphthalene derivatives. With the aid of carbonylative rhodium-catalyzed cyclization of 1-(2-bromophenyl)-hept-2-yn-1-one and PhB(OH)2, indan-1,3-dione derivatives were obtained.
Scheme 1.9 (a–c) Rhodium-catalyzed carbonylation of alkynes and boronic acids.
In 2001, a novel rhodium-catalyzed cyclohydrocarbonylation of imino alkynes was developed by Alper and Van den Hoven [28]. The reaction was catalyzed by a zwitterionic rhodium complex and P(OPh)3, giving aldehyde-substituted pyrrolinones in 67–82% yield (Scheme 1.10a). Imino alkynes with alkyl, alkoxyl, vinyl, and aryl substituents can be used in this unique transformation. This synthetic approach is a convenient way for the synthesis of highly functionalized pyrrolinones, which constitute often biologically active compounds. In 2001, the group of Saito reported on the intramolecular carbonylation of alkyne-carbodiimides, giving 4,5-dihydro-1H-pyrrolo[2,3-b]pyrrolin-2-ones and 1H-pyrrolo[2,3-b]indol-2-ones in reasonably good yields (Scheme 1.10b) [29]. Later on, they could apply their methodology on N-[2-(2-alkyn-1-yl)phenyl]carbodiimides to synthesize 2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-2-ones in good yields (Scheme 1.10c) [30].
Scheme 1.10 (a–c) Rhodium-catalyzed cyclocarbonylation reactions.
In 2004, the synthesis of indazolo[2,1-a]indazole-6,12-diones was carried out by a rhodium-catalyzed cyclocarbonylation of azobenzenes by the group of Takahashi [31]. To get good yields, nitrobenzene was added as a hydrogen acceptor (Scheme 1.11a). But on running the carbonylation of azobenzene via cobalt catalysis, quinazoline was obtained as the terminal product. Furthermore, Chatani and coworkers described a rhodium-catalyzed synthesis of maleimides starting from a combination of alkynes and pyridine-2-ylmethylamine in the presence of CO (Scheme 1.11b) [53].
Scheme 1.11 (a, b) Rhodium-catalyzed carbonylative C–H activation.
Lautens and coworkers investigated an asymmetrical ring-opening reaction in which meso-diazabicycles were opened by acyl anion nucleophiles in a catalytic manner to give functionalized trans-1,2-hydrazinoacyl cyclopentenes stereoselectively [32]. Under very mild conditions, an acyl anion is generated in situ, starting from readily available organoboron precursors (Scheme 1.12).
Scheme 1.12 Rhodium-catalyzed carbonylative ring-opening of diazabicycles.
In 2007, a series of 3-methylcyclopent-2-enones were synthesized by a rhodium-catalyzed carbonylation of spiropentanes [33]. Here, two different types of carbon–carbon bond cleavage processes were involved to get the product in good yield (Scheme 1.13)
Scheme 1.13 Rhodium-catalyzed carbonylation of spiropentanes.
1.2.3 Palladium-Catalyzed Carbonylative Domino Reactions
The outstanding ability of palladium catalysts was demonstrated in the area of carbonylative coupling reactions mainly with activated arenes. Nevertheless, palladium catalysts can also be used in oxidative cyclization chemistry. The group of Gabriele succeeded in producing substituted furans from the corresponding alkynols under oxidative conditions (Scheme 1.14a) [34]. Here, in the presence of catalytic amounts of [PdI4]2− in conjunction with an excess of KI, 4-yn-1-ols containing a terminal triple bond undergo oxidative cyclization/alkoxycarbonylation in methanol at 70 °C and 100 bar of a 9 : 1 mixture of CO and air to give 2E-[(methoxycarbonyl)methylene]tetrahydrofurans in good yield. A side reaction, producing 2-methoxy-2-methyltetrahydrofurans via a cycloisomerization/hydromethoxylation sequence, could be easily prevented by increasing the KI excess. Without KI excess and in the absence of carbon monoxide, the latter product can be formed from 4-yn-1-ols and methanol in high yields using the same catalytic system. Another system that needs no KI and high pressure leading to different products was developed by Akita and coworkers [35] (Scheme 1.14b). Following this procedure, they were able to perform the reaction in an asymmetric manner by applying chiral bisoxazolines as ligands.
Scheme 1.14 (a, b) Palladium-catalyzed carbonylative synthesis of tetrahydrofurans.
Gabriele and coworkers [36] showed that, besides lactones, furans could also be prepared by a similar process starting from different substrates. Here, a variety of (Z)-2-en-4-yn-1-ols have been carbonylated under oxidative conditions to give substituted furan-2-acetic esters in good yields (Scheme 1.15a). The cyclization/alkoxycarbonylation sequence was carried out in alcoholic media at 50–70 °C under 100 bar pressure of a 9 : 1 mixture of CO and air. As catalyst system, PdI2 in combination with KI was used. The proposed reaction pathway involves the in situ isomerization of the initially formed (E)-2-[(alkoxycarbonyl)methylene]-2,5-dihydrofuran species, which in some cases have been isolated and proved to be the intermediates. Under similar reaction conditions, 3-yne-1,2-diols were transformed into the corresponding furan-3-carboxylic esters in good yield (Scheme 1.15b).
Scheme 1.15 (a, b) Palladium-catalyzed carbonylative synthesis of furans.
The palladium-catalyzed carbonylation of alkynols resulted in the formation of synthetically interesting lactones and furans. In 1994, Sakamoto and coworkers showed that the palladium-catalyzed carbonylation reaction of 2-alkynylanilines and 2-alkynylphenols in methanol could give the corresponding indoles and benzofurans in moderate yields. Starting from 2-alkynylbenzamides, 3-alkylidenisoindoles were obtained (Scheme 1.16) [37a]. A similar methodology was applied by Scammells for the synthesis of XH-14 and its derivatives, which contain a benzofuran as the main skeleton [37b].
Scheme 1.16 Palladium-catalyzed carbonylative synthesis of benzofurans and indoles.
Costa and coworkers [38] used an oxidative Pd-catalyzed cyclization/alkoxycarbonylation sequence for the synthesis of 1-(alkoxycarbonyl)methylene-1,3-dihydroisobenzofurans and 4-(alkoxycarbonyl)benzo[c]-pyrans starting from 2-alkynylbenzyl alcohols and 2-alkynylbenzaldehydes or 2-alkynylphenyl ketones. The reactions were run in ROH or CH3CN/ROH (R = Me, i-Pr) mixtures as solvent at 70–105 °C in the presence of catalytic amounts of PdI2 in combination with KI under a CO/air mixture in the ratio 4 : 1 or 3 : 1 (20 or 32 bar total pressure at 25 °C). The reaction proceeds via an intramolecular attack of nucleophilic oxygen atom (either already present in the starting material or generated in situ by ROH attack on carbonyl group) directed to the triple bond which is coordinated to Pd(II). The reaction sequence is closed by a subsequent alkoxycarbonylation. The presence of substituents at the alkyne terminal position and at the carbon atom α to the hydroxy group control the selectivity of the process by forming a five- or six-membered ring (Scheme 1.17). Alternatively, the reaction of alkynyloxiranes could also lead to 1,3-dihydroisobenzofurans and tetrahydrofurans. Moderate to good yields of the products were obtained under similar reaction conditions (PdI2/KI/CO/O2).
Scheme 1.17 Palladium-catalyzed carbonylative synthesis of furans and pyrans.
Because of the interesting biological properties of 3(2H)-furanone derivatives, many methodologies have been developed for their syntheses [39a]. In 1988, Inoue and coworkers described the coupling of α-ethynyl tertiary alcohols and acyl chlorides to give 3(2H)-furanones in the presence of a palladium catalyst and CO2. Next, they started with the same reaction conditions with CO and CO2 under pressure but using aryl halides instead of acyl chlorides [39b]. They showed that acetylenic ketone was formed as an intermediate by a combination of acetylenic alcohol, CO, and the aryl halides. Subsequent reaction with CO2 resulted in the formation of a cyclic carbonate, which was decarboxylated to 3(2H)-furanones with the release of CO2 (Scheme 1.18a). Alternatively, Kiji and coworkers [39c] showed that, in the absence of CO2, 3-isopropylidene-5-phenyl-2(2H)-furanone could be achieved as the main product. Carbonylative coupling of iodobenzene and 2-methyl-3-butyn-2-ol in aqueous biphasic NaOH/benzene system was carried out by using Pd(OAc)2/PPh3/Bu4PBr as catalyst. This biphasic solvent system gave, in sharp contrast to a homogeneous Et3N solution, 3-isopropylidene-5-phenyl-2(2H)-furanone in moderate yield accompanied by 2,2-dimethyl-5-phenyl-3(2H)-furanone and benzoic acid as side products. The formation of the main product was explained by a carbonylative coupling of iodobenzene with 2-methyl-3-butyn-2-ol, forming 4-hydroxy-4-methyl-1-phenyl-2-pentyn-1-one, which underwent hydrogenolysis to yield 4-methyl-1-phenyl-2,3-pentadien-1-one. Subsequent cyclocarbonylation yielded 3-isopropylidene-5-phenyl-2(2H)-furanone as the final product (Scheme 1.18b). Concerning the formation of 3-alkylidenefuran-2-ones, the group of Alper [39d] established a palladium catalyst system for the carbonylative coupling of aryl iodides with benzyl acetylenes. More recently, our group developed a general and efficient method for the synthesis of furanones starting from aryl bromides and aryl triflates [39e]. After double carbonylation with benzyl acetylenes, furanones were produced in good yields. Methylated BE-23372M, a kinase inhibitor, was also produced in a one-pot sequence with 65% yield (Scheme 1.18c).
Scheme 1.18 (a–c) Palladium-catalyzed carbonylative synthesis of furanones.
In 2005, Chatani and coworkers [40a] reported on the carbonylation of yne esters giving lactones in good yields under 1 bar of CO (Scheme 1.19a). It turned out that the 2-pyridinyloxy moiety was a good leaving group among the groups tested. Similarly, the cyclocarbonylation of 2-propynyl-1,3-dicarbonyls with organo halides or triflates gave rise to the formation of furans in good yields (Scheme 1.19b) [40b]. Kato and coworkers [40c] developed a palladium-mediated oxidative cyclocarbonylation of 2-alkyl-2-propargylcyclohexane-1,3-diones, generating bicyclic-β-alkoxyacrylates in 51–74% yield with 72–82% ee (Scheme 1.19c). The authors were able to extend their palladium-catalyzed cyclocarbonylation to propargylic esters, propargylic acetates, 4-yn-1-ones, and allenyl ketones. Mukai and coworkers [40d] were able to apply this methodology in the total synthesis of naturally occurring diacetylenic spiroacetal enol ethers. A related mechanistic study supported by both experiment and DFT (density functional theory) study was carried out by Carfagna and coworkers [40e]. They proposed that, under the carbonylative conditions of Gabriele et al., the concatenation occurs between a Pd(0)-promoted deallylation and a Pd(II)-promoted heterocyclization catalytic cycle to convert 1-(2-allyloxyphenyl)-2-yn-1-ols to 2-benzofuran-2-ylacetic esters and β,γ-unsaturated esters in high yields. This reaction sequence is named sequential homobimetallic catalysis [40f]. Owing to the theoretical and synthetic importance of the process, a closer look at the mechanism and scope of the reaction revealed that the experimental results fit to the sequential homobimetallic mechanism. In place of the esters, under the same conditions, amides could also be produced in the presence of amines [40g]. The methodology could be extended to the synthesis of coumarins by using similar reaction conditions [40h]. Here, 3-[(methoxycarbonyl)-methyl]coumarins were prepared starting from readily available 2-(1-hydroxyprop-2-ynyl)phenols. In the presence of catalytic amounts of PdI2 and an excess of KI in MeOH at room temperature and under 90 bar of CO, the product was obtained in good to high isolated yields (62–87%).
Scheme 1.19 (a–c) Palladium-catalyzed cyclocarbonylation of alkynones.
Moreover, Shim and coworkers [41a] studied the cyclocarbonylation of 2-(2-bromophenyl)-2-oxazolines to the corresponding isoindolinones. By using a palladium–nickel catalyst under 3 bar of CO, the products were produced in high yields (Scheme 1.20a). Later on, isoindolinones could also be achieved by coupling 2-iodobenzoyl chloride with imines in moderate yields using NEt3 and Pd(PPh3)2Cl2/PPh3 (Scheme 1.20b) [41b]. The same group could synthesize even more complex isoindolinones through a palladium-catalyzed carbonylative coupling of 2-bromobenzaldehydes with aminoalcohols or diamines [41c]. At lower temperature and lower catalyst loading, the corresponding isoindolinones were achieved in good isolated yields (Scheme 1.20c). Interestingly, when primary amines were used for the palladium-catalyzed coupling of 2-bromobenzaldehydes or 2-bromocyclohex-1-enecarbaldehydes, no base was needed (Scheme 1.20d) [41d]. The mechanism is believed to start with the condensation of the aldehyde and the primary amine, forming an imine. After the oxidative addition of the carbon–bromide bond of the imine to the active palladium(0) catalyst and subsequent CO insertion, an aroylpalladium(II) intermediate is formed. Next, an intramolecular acylpalladation to the imine gives the alkylpalladium(II) intermediate, which is decomposed to isoindolin-1-one by hydrogenolysis with molecular hydrogen. It is assumed that hydrogen is produced by the water-gas shift reaction of CO and H2O which comes from the initial condensation stage.
Scheme 1.20 (a–d) Palladium-catalyzed carbonylative synthesis of isoindolin-1-ones.
The group of Arndtsen developed a number of elegant multicomponent reactions that introduce one or two CO groups into the parent molecules [42]. A combination of alkynes, imines, acid chlorides, and CO gives pyrroles as the terminal products in the presence of a palladium catalyst (Scheme 1.21a). By using α-amidoesters and alkynes, the reaction proceeds to give the same products (Scheme 1.21b). Even imidazoles could be formed when the reaction was carried out with imines and acid chlorides. Interestingly, by simply changing the reaction sequence of adding the substrates, imidazolinium salts or imidazolines could be produced. In general, these methods offer convenient pathways for the production of heterocycles from easily available substrates.
Scheme 1.21 (a, b) Palladium-catalyzed carbonylation of imines.
Recently, Alper and coworkers [43] reported on novel processes for the synthesis of carbonylated indole derivatives via a palladium-catalyzed N–C coupling/carbonylation sequence. 2-Carboxyindoles with a variety of functional groups were achieved in good yields (Scheme 1.22a). Similarly, 2-aroylindoles could also be obtained from the same substrates in moderate yields (Scheme 1.22b). In 2011, Alper and Zeng [43c] published a facile and selective palladium-catalyzed domino synthesis of carbonylated benzothiophenes. By a carbonylative intramolecular C–S coupling/intermolecular cascade sequence, 2-carbonylbenzo[b]thiophene derivatives were produced from 2-gem-dihalovinylthiophenols in 24–73% yield (Scheme 1.22c). This protocol allows access to various highly functionalized benzo[b]thiophenes.
Scheme 1.22 (a–c) Palladium-catalyzed carbonylative synthesis of indoles and thiophenes.
In 2000, a palladium-catalyzed decarboxylative carbonylation of 5-vinyloxazolidin-2-ones was studied by Knight and coworkers [44]. By a palladium-catalyzed decarboxylative carbonylation process, 5-vinyloxazolidin-2-ones, which are prepared from amino acids, reacted to form 3,6-dihydro-1H-pyridin-2-ones in good yields (Scheme 1.23).
Scheme 1.23 Palladium-catalyzed carbonylative synthesis of pyridinones.
Alper and Xiao [45] synthesized thiochromanones by palladium-catalyzed carbonylative ring-forming reactions of 2-iodothiophenol derivatives, allenes, and CO. The thiochroman-4-ones were achieved in good to excellent isolated yields with high regioselectivity, which was probably caused by electronic effects (Scheme 1.24). This catalytic heteroannulation comprises the regioselective addition of the sulfur moiety on the more electrophilic carbon center of the allene, arylpalladium formation, CO insertion, subsequent intramolecular cyclization, and, finally, the reductive elimination.
Scheme 1.24 Palladium-catalyzed carbonylative synthesis of thiochromanones.
Recently, an efficient method for the synthesis of 1,4-benzo- and pyrido-oxazepinones was also disclosed [46]. This reaction proceeds via a domino process through one-pot ring-opening/carboxamidation reaction sequences of N-tosylaziridines with 2-halophenols/pyridinol under phase-transfer conditions (benzyltriethylammonium chloride, TEBA). A variety of 1,4-benzo- and pyrido-oxazepinones could be easily synthesized by using a range of N-tosylaziridines and 2-halophenols/pyridinol (Scheme 1.25a). Analogously, when 2-iodothiophenols were employed, 1,4-benzothiazepin-5-ones were obtained in good yields (Scheme 1.25b).
Scheme 1.25 (a,b) Palladium-catalyzed carbonylation of N-tosyl aziridines.
1.2.4 Iron-, Copper-, Nickel-, and Cobalt-Catalyzed Carbonylative Domino Reactions
Compared to palladium, rhodium, and ruthenium, iron and copper are less developed in carbonylation reactions. But the advantages of iron and copper are attracting more and more chemists to work in this area. Fe(CO)5 as a more easily available iron–carbonyl complex has found an important place in the stoichiometric and catalytic carbonylation reactions [47]. The group of Periasamy applied Fe(CO)5 as precursor for the in situ generation of NaHFe(CO)4 for double carbonylation of alkynes to cyclobutenediones. In their procedures, CuCl2 was needed as the oxidant reagent. The active species was [Fe(CO)4], which could be generated from various reagents, such as MeI, NaBH4, amines, Me3NO, and NaH. Additionally, using these methods, α,ß-unsaturated acids, benzoquinones, and cyclic anhydrides could also be produced as unexpected products (Scheme 1.26). In the mentioned reactions, stoichiometric amount of iron salts were still needed.
Scheme 1.26 Double carbonylation of alkynes.
Notably, Beller's group developed a series of iron-catalyzed aminocarbonylation of alkynes in 2009 [48a–d]. Starting from alkynes and amines, succinimides were prepared in good yields in the presence of carbon monoxide (Scheme 1.27). This methodology was also applied for the synthesis of himanimides A and B. Under the same conditions, cinnamides were also synthesized by adding 1,4-diazabutadiene as ligand or by using microwave irradiation. NEt3 was the ligand of choice [48e]. A combination of Fe(CO)5 and irradiation was also used for producing vinylesters and lactones from alkynes at 0 °C [48f].
Scheme 1.27 Iron-catalyzed carbonylative synthesis of amides and esters.
Additionally, the reactions with alkynes and iron catalyst were also applied to the carbonylative homocoupling of aryl iodides to give benzophenones [49]. As catalyst system, Fe(CO)5-Co2(CO)8 was used under phase-transfer conditions to give carbonylate aryl iodides in moderate yields.
In 2008, Bhanage and coworkers [50a] reported on a copper-catalyzed carbonylative Sonogashira reaction of aryl iodides. In this procedure, copper bis(2,2,6,6-tetramethyl-3,5-heptanedionate) [Cu(TMHD)2] was used as the catalyst for this transformation and NEt3 as base. Alkynones were produced in good yields. Recently, Xia and coworkers [50b] described a general and efficient copper-catalyzed double aminocarbonylation of aryl iodides (Scheme 1.28). Aryl iodides were double-carbonylated with amines in good yields by using the NHC–Cu catalyst (72–93%).
Scheme 1.28 Copper-catalyzed double carbonylation of aryl iodides.
Skoda-Földes and coworkers [51] investigated the domino reaction of ethyl diazoacetate, CO, and ferrocenylimines in the presence of Co2(CO)8 as catalyst (Scheme 1.29). In most cases, the main products were 2-(1-ferrocenylmethylidene) malonates formed by an N(1)–C(4) cleavage of the primarily derived β-lactams. The latter compounds could only be isolated when the reaction was carried out at relatively low CO pressure, using an excess of ethyl diazoacetate. Among these compounds, trans-N-(tert-butyl)-3-ethoxycarbonyl-4-ferrocenyl-b-lactam proved to be the most stable one and could be isolated in 55% yield. N-Alkyl β-lactams were shown to undergo an acidic cleavage, leading to the (E)-isomers of 2-(1-ferrocenylmethylidene)malonates as the main products. The structures of the two new compounds, namely (E)-2-ethoxycarbonyl-3-ferrocenyl-N-((R)-1-phenylethyl)-2-propenamide and trans-N-(tert-butyl)-3-ethoxycarbonyl-4-ferrocenyl-b-lactam, were confirmed by X-ray crystallography. The relative thermodynamic stability of the products as well as the energetics of the acid-mediated cleavage of the β-lactam ring was elucidated with DFT calculations.
Scheme 1.29 Cobalt-catalyzed carbonylative synthesis of malonic acid derivatives.
Even though Ni(CO)4 is called liquid death, this nickel catalyst has been applied in carbonylation reactions [52]. The group of Ricart reported a nickel-catalyzed carbonylative cycloaddition of alkynes and allyl halides to cyclopentanes. The desired products were obtained in high yields and with controlled stereoselectivity. Iron was used as a reductant. An extension of the reaction to new substrates led to the conclusion that, although the steric and electronic effects of the alkyne substituents are generally irrelevant in relation to the adducts and their yields, those of the allylic counterpart may have a significant influence on the outcome of the reaction. However, the presence of the amine moiety in the alkyne completely inhibited the reaction. The feasibility of a multicentered reaction was verified with a triacetylene, in which up to 12 bonds were created simultaneously and in good yield (Scheme 1.30).
Scheme 1.30 Nickel-catalyzed carbonylative synthesis of cyclopentanes.
1.3 Outlook
In summary, we have summarized representative examples of transition-metal-catalyzed carbonylative domino reactions. In the area of carbonylations, palladium, rhodium, and cobalt are still the main actors. The ability of palladium catalysts in carbonylative cross-coupling, rhodium catalysts in carbonylative C–H activation, and cobalt catalyst in carbonylative reactions with unsaturated bonds is impressive.
In the future, cheap catalysts such as iron and copper are expected to be explored and applied. In the case of noble metals, their reaction efficiency and selectivity should be improved. The use of nickel catalysts in carbonylation is potentially accompanied with the formation of Ni(CO)4, which is highly dangerous for the operators. Therefore, methods for stabilizing Ni must be developed before Ni can be used in catalytic reactions.
With regard to oxidative carbonylations, green oxidants, such as air or oxygen, are much more interesting than equal amounts of Cu(OAc)2 or BQ.
In conclusion, the main direction for methodology development in the future is looking at “sustainable development.”
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