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. 2011 Mar 16;133(10):3332-5.
doi: 10.1021/ja200311n. Epub 2011 Feb 22.

Enantioselective synthesis of homoallylic amines through reactions of (pinacolato)allylborons with aryl-, heteroaryl-, alkyl-, or alkene-substituted aldimines catalyzed by chiral C1-symmetric NHC-Cu complexes

Erika M Vieira  1 , Marc L Snapper, Amir H Hoveyda
Affiliations

Enantioselective synthesis of homoallylic amines through reactions of (pinacolato)allylborons with aryl-, heteroaryl-, alkyl-, or alkene-substituted aldimines catalyzed by chiral C1-symmetric NHC-Cu complexes

Erika M Vieira et al. J Am Chem Soc. .

Abstract

A catalytic method for enantioselective synthesis of homoallylamides through Cu-catalyzed reactions of stable and easily accessible (pinacolato)allylborons with aryl-, heteroaryl-, alkyl-, or alkenyl-substituted N-phosphinoylimines is disclosed. Transformations are promoted by 1-5 mol % of readily accessible NHC-Cu complexes, derived from C(1)-symmetric imidazolinium salts, which can be prepared in multigram quantities in four steps from commercially available materials. Allyl additions deliver the desired products in up to quantitative yield and 98.5:1.5 enantiomeric ratio and are amenable to gram-scale operations. A mechanistic model accounting for the observed selectivity levels and trends is proposed.

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Figures

Figure 1
Figure 1
Nuclear Overhauser effect (nOe) experiments and X-ray structure, indicating the identity of the major isomer of imidazolinium salt 6d (5:1, see the Supporting Information for details).
Figure 2
Figure 2
Model for origin of enantioselectivity in NHC–Cu-catalyzed allyl additions to N-phosphinoylimines.
Scheme 1
Scheme 1
Catalytic Cycle for Reaction of (Pinacolato)allylboron with Aldimines Promoted by an NHC–Cu Complexa a B(pin) = pinacolatoboron.
Scheme 2
Scheme 2
NHC–Cu-Catalyzed Enantioselective Allyl Addition to Heteroaryl-Substituted Phosphinoyliminesa aPerformed under the conditions shown in Table 2 with 6b (for 9 and 11) or 6d (for 10) as the imidazolinium salt. Conversions and selectivities determined as indicated in Table 2; yields of isolated and purified products (±5%).
Scheme 3
Scheme 3
NHC–Cu-Catalyzed Enantioselective Allyl Addition to Alkyl-Substituted Phosphinoyliminesa aPerformed under identical conditions for R-13. Conversions and selectivities determined as indicated in Table 2; yields are of the purified products (±5%). b With catalyst derived from 6d. c Performed with 5.0 mol % of 6d and CuCl and 12 mol % NaOt-Bu.
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References

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