Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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.

PubMed Disclaimer

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.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Puentes CO, Kouznetsov V. J Heterocyclic Chem. 2002;39:595.
    2. Ding H, Friestad GK. Synthesis. 2005:2815.
    3. Friestad GK, Mathies AK. Tetrahedron. 2007;63:2541. - PMC - PubMed

    1. For general reviews that cover allyl additions to imines, see: Yamamoto Y, Asao N. Chem Rev. 1993;93:2207.Enders D, Reinhold U. Tetrahedron: Asymmetry. 1997;8:1895.Bloch R. Chem Rev. 1998;98:1407.Kobayashi S, Ishitani H. Chem Rev. 1999;99:1069.

    1. For examples involving enantiomerically enriched allylboron reagents, see: With N-trimethylsilaimines: Itsuno S, Watanabe K, Ito K, El-Shehawy AA, Sarhan AA. Angew Chem, Int Ed Engl. 1997;36:109.With aldimine-trialkylborane adducts: Ramachandran PV, Biswas D. Org Lett. 2007;9:3025.With cyclic imines: Wu TR, Ching JM. J Am Chem Soc. 2006;128:9646.For transformations with enantiomerically enriched allylsilane reagents, see: With N-acylhydrazones: Berger R, Rabbat PMA, Leighton JL. J Am Chem Soc. 2003;125:9596.With o-anisidylimines: Rabbat PMA, Corey Valdez S, Leighton JL. Org Lett. 2006;8:6119.With a range of heterocyclic aldimines: Perl NR, Leighton JL. Org Lett. 2007;9:3699.With N-heteroaryl hydrazones: Feske MI, Santanilla AB, Leighton JL. Org Lett. 2010;12:688.

    1. For example, see: Cogan DA, Liu G, Ellman J. Tetrahedron Lett. 1999;55:8883.Miyabe H, Yamaoka Y, Naito T, Takemoto Y. J Org Chem. 2004;69:1415.Vilaivan T, Winotapan C, Banphavichit V, Shinada T, Ohfune Y. J Org Chem. 2005;70:3464.Friestad GK, Korapala CS, Ding H. J Org Chem. 2006;71:281.Grigg R, McGaffrey S, Sridharan V, Fishwick CWG, Kilner C, Korn S, Bailey K, Blacker J. Tetrahedron. 2006;62:12159.Sun XW, Liu M, Xu MH, Lin GQ. Org Lett. 2008;10:1259.Reddy LR, Hu B, Prashad M, Prasad K. Org Lett. 2008;10:3109.Delaye PO, Pradhan TK, Lambert E, Vasse JL, Szymoniak J. Eur J Org Chem. 2010:3395.For a review, see: Alvaro G, Savoia D. Synlett. 2002:651.

    1. For Cu-catalyzed allyl additions to α-amino esters, see: With allylstannanes: Fang X, Johannsen M, Yao S, Gathergood N, Hazell RG, Jørgensen KA. J Org Chem. 1999;64:4844.With alkenes: Ferraris D, Young B, Cox C, Dudding T, Drury WJ, III, Ryzhkov L, Taggi AE, Lectka T. J Am Chem Soc. 2002;124:67.With allylsilanes: Kiyohara H, Nakamura Y, Matsubara R, Kobayashi S. Angew Chem, Int Ed. 2006;45:1615.

Publication types