Addition of Chloroprene Grignards to Aromatic Aldehydes: Synthesis of Homoallenyl Alcohols

Abstract

A general procedure for the one-pot synthesis of racemic homoallenyl alcohols from the corresponding aldehyde and chloroprene-derived Grignards is described. Employing bis[2dimethylaminoethyl]ether (BDMAEE) as an additive at low temperatures shifts the selectivity of the chloroprene Grignard addition to aldehydes such that it is almost exclusive toward allene formation. In a set of follow-up experiments, simple and more elaborate methods for further derivatization have been demonstrated, allowing quick access to more complex structures.

Synthesis of β-Allenylamines by Addition of Chloroprene Grignards to N-Boc Imines

“…11 Taking on the work of Matsumoto, 12 we recently developed a method for the regioselective addition of 2-(1,3-butadienyl)magnesium chloride (chloroprene Grignard) and substituted 1,3-butadiene Grignards to aldehydes. 13 To expand the scope of electrophiles, we envisioned the addition reaction of chloroprene Grignards to imines.…”

“…We further subjected imines 1a and 1r to an addition reaction with substituted chloroprene Grignards, that we established in an earlier work (Scheme 4). 13 Addition of 2methyl chloroprene Grignard (R 2 = Me, R 3 = H) in the presence of DMDEE to imine 1a gave the 1,1-disubstituted allene 4 in 78% yield. The reaction with trimethyl substituted Grignard (R 2 = Me, R 3 = Me) allowed synthesis of the challenging tetrasubstituted allene 5.…”