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. 2006 Mar 1;128(8):2751-6.
doi: 10.1021/ja056018x.

Metallophosphite-catalyzed asymmetric acylation of alpha,beta-unsaturated amides

Mary R Nahm  1 , Justin R Potnick, Peter S White, Jeffrey S Johnson
Affiliations

Metallophosphite-catalyzed asymmetric acylation of alpha,beta-unsaturated amides

Mary R Nahm et al. J Am Chem Soc. .

Abstract

The l-menthone-derived TADDOL phosphite 6b catalyzes highly enantioselective conjugate additions of acyl silanes to alpha,beta-unsaturated amides. p-Methoxybenzoyl cyclohexyldimethylsilane adds to a variety of N,N-dimethyl acrylamide derivatives in the presence of the lithium salt of 6b. In many instances the alpha-silyl-gamma-ketoamide product undergoes facile enantioenrichment (to 97-99% ee) upon recrystallization. Desilylation with HF.pyr affords the formal Stetter addition products. Baeyer-Villiger oxidation of the desilylated gamma-ketoamides affords useful ester products. An X-ray diffraction study of 6b reveals that the isopropyl group of the menthone ketal influences the position of the syn-pseudoaxial phenyl group in the TADDOL structure. Through a crossover experiment, the silicon migration step in the reaction mechanism is shown to be strictly intramolecular.

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Figures

Figure 1
Figure 1
TADDOL-phosphites containing the l-menthone ketal.
Figure 2
Figure 2
X-ray structures of phosphites 1-Ph and 6b.
Figure 3
Figure 3
Proposed model for anti diastereoselectivity.
Scheme 1
Scheme 1
Alkene Acylation Catalyzed by Phosphites 1-Ar
Scheme 2
Scheme 2
Enantioselective Acylation of N,N-Dimethylcinnamide
Scheme 3
Scheme 3
Recrystallization and Enantiomeric Excess Upgrade of α-Silyl-γ-ketoamide 11
Scheme 4
Scheme 4
Synthetic Operations Involving 13a
Scheme 5
Scheme 5
Crossover Experiment to Determine Silyl Group Transfer Pathway
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References

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    1. For an exception using PBu3, see Gong JH, Im YJ, Lee KY, Kim JN. Tetrahedron Lett. 2002;43:1247–1251.

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