Application of the lithiation-borylation reaction to the preparation of enantioenriched allylic boron reagents and subsequent in situ conversion into 1,2,4-trisubstituted homoallylic alcohols with complete control over all elements of stereochemistry

Martin Althaus; Adeem Mahmood; José Ramón Suárez; Stephen P Thomas; Varinder K Aggarwal

doi:10.1021/ja910593w

Application of the lithiation-borylation reaction to the preparation of enantioenriched allylic boron reagents and subsequent in situ conversion into 1,2,4-trisubstituted homoallylic alcohols with complete control over all elements of stereochemistry

J Am Chem Soc. 2010 Mar 24;132(11):4025-8. doi: 10.1021/ja910593w.

Authors

Martin Althaus¹, Adeem Mahmood, José Ramón Suárez, Stephen P Thomas, Varinder K Aggarwal

Affiliation

¹ School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.

PMID: 20192266
DOI: 10.1021/ja910593w

Abstract

The reactions of Hoppe's lithiated carbamates with vinylboranes and boronic esters give allylic boranes/boronic esters, and subsequent addition of aldehydes provides a new route to enantioenriched homoallylic alcohols with high enantiomeric ratios and diastereomeric ratios. Specifically, reactions of sparteine-complexed lithiated carbamates with trans-alkenyl-9-BBN derivatives followed by addition of aldehydes gave (Z)-anti-homoallylic alcohols in greater than 95:5 er and 99:1 dr. However, in the special case of the methyl-substituted lithiated carbamate, diamine-free conditions were required to achieve high selectivity. Reactions of sparteine-complexed lithiated carbamates with (Z)-alkenyl pinacol boronic esters and (E)-alkenyl neopentyl boronic esters gave (E)-syn- and (E)-anti-homoallylic alcohols, respectively, in greater than 96:4 er and 98:2 dr. In these reactions, a Lewis acid (MgBr(2) or BF(3) x OEt(2)) was required to promote both the 1,2-metalate rearrangement and the addition of the intermediate allylic boronic ester to the aldehyde. This methodology provides a general route to each of the three classes of homoallylic alcohols with high selectivity.