.
Angewandte
Communications
DOI: 10.1002/anie.201206551
Asymmetric Catalysis
Dirhodium Carboxylates Catalyzed Enantioselective Coupling
Reactions of a-Diazophosphonates, Anilines, and Electron-Deficient
Aldehydes**
Cong-Ying Zhou, Jing-Cui Wang, Jinhu Wei, Zhen-Jiang Xu, Zhen Guo, Kam-Hung Low, and
Chi-Ming Che*
Ammonium ylides are versatile intermediates that are
frequently used in the synthesis of complex and diverse
nitrogen-containing compounds.[1,2] Transition-metal com-
plexes, including dirhodium(II,II) carboxylates, copper(II)
acetylacetonate, and ruthenium(II) porphyrins, are effective
Scheme 1. Ammonium ylide formation by the reaction of metal carbe-
catalysts for the generation of ammonium ylides through
noid with amine. L=ligand, M=metal.
decomposition of diazo compounds in the presence of
amines.[2] While highly enantioselective alkene cyclopropa-
[4–8]
nation,[2,3] carbene X H (X = C, Si, N, O) insertion,
and
À
transformation reactions of oxygen ylides[9,10] and sulfur
ylides[11] have been achieved by decomposition of diazo
compounds in the presence of chiral transition-metal com-
plexes, transition-metal-catalyzed asymmetric reactions of
ammonium ylides are rare. The major challenge in developing
highly enantioselective metal-catalyzed ammonium ylide
reactions is the equilibrium between the metal-bound/stabi-
lized ylide (referred to as metal-bound ylide) and the free
ylide; the latter leads to the formation of racemic product
(Scheme 1).
Scheme 2. Three-component coupling reaction to syn-4a and anti-4a.
At the outset, the reaction of dimethyl a-diazo(benzyl)
phosphonate 1a, aniline 2a, 4-nitrobenzaldehyde 3a, and
[Rh2(OAc)4] catalyst (2 mol%) in CH2Cl2 at 408C for
15 hours afforded the two diastereomers syn-4a and anti-4a
in 57% overall yield and with a syn/anti ratio of 86:14
(Scheme 2). The structure of the major isomer syn-4a was
determined by X-ray crystallography (see the Supporting
Information).
A proposed mechanism for this Rh-catalyzed three-
component reaction is shown in Scheme 3. With reference
to previous work on Brønsted acid/[Rh2(OAc)4]-catalyzed
coupling reaction of diazoester, carbamate, and imine,[14c] the
rhodium catalyst decomposes a-diazophosphonate to gener-
ate Rh–carbene species A, which is trapped by aniline to give
In this study, we examined the three-component coupling
reaction of a-diazophosphonates, anilines, and electron-
deficient aldehydes to give a-amino-b-hydroxyphosphonate
compounds (Scheme 2).[12] a-Amino phosphonic acid com-
pounds are key substrates used in the synthesis of phospho-
nopeptides and could act as enzyme inhibitors, antibiotics,
plant growth regulators, and haptens of catalytic antibodies.[13]
[*] J.-C. Wang[+,+], Z.-J. Xu, Prof. Dr. C.-M. Che
Shanghai-Hong Kong Joint Laboratory in Chemical Synthesis,
Shanghai Institute of Organic Chemistry
354 Feng Lin Road, Shanghai (China)
C.-Y. Zhou[+,+], J. Wei, Z. Guo, K.-H. Low
Department of Chemistry, State Key Laboratory of Synthetic
Chemistry and Open Laboratory of Chemical Biology of the Institute
of Molecular Technology for Drug Discovery and Synthesis
University of Hong Kong, Pokfulam Road (Hong Kong, China)
[+] These authors contributed equally to this work.
[**] We are thankful for financial support from the University of Hong
Kong (University Development Fund), Hong Kong Research Grants
Council (HKU 700708P, HKU1/CRF/08), CAS-GJHZ200816 and
CAS-Croucher Funding Scheme for Joint Laboratory, and the Areas
of Excellence Scheme established under the University Grants
Committee of the Hong Kong Special Administrative Region, China
(AoE/P- 10/01). We thank Chen Yang (HKU) for the X-ray
crystallographic structural determination.
Supporting information for this article is available on the WWW
Scheme 3. Proposed mechanism for the three-component coupling
reaction.
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ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 11376 –11380