Stereocontrolled Synthesis of 1,3-Amino Alcohols by Reduction of Substituted 2-{1-[(tert-Butylsulfinyl)amino]alkyl}cyclohexanones

Abstract

Assembly of diethylzinc, cyclohex-2-en-1-one, and a chiral N-tert-butylsulfinyl imine in the presence of an appropriate phosphoramidite ligand yields a β-sulfinylamino cyclohexanone, which on reduction with sodium borohydride or lithium triethylborohydride provides access to a wide range of enantiomerically pure N-tert-butylsulfinyl 1,3-amino alcohols with five stereogenic centers.

Key words

amino alcohols - ketones - reduction - phosphoramidites - multicomponent reaction - stereoselectivity

References

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4

Synthetic (-)-pulegone is about ten times more expensive than its natural enantiomer.

8

Closely related examples are described in references 5a and 5b; attempts to improve the diastereoselectivity by using an excess of Et₂Zn were unsuccessful.

13

Crystallographic data (excluding structure factors) for the structure reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC 723111. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK [fax: [phone];
e-mail: [e-mail]].