Allene synthesis by an asymmetric Baylis–Hillman style reaction on vinylphosphine oxides

Abstract

A novel reaction has been discovered with a mechanism similar to the Baylis-Hillman reaction. Reaction of a vinylic phosphine oxide with (R)-N-lithio-α-methylbenzylbenzylamine 2 in the presence of an aldehyde gave hydroxyphosphine oxides in good to moderate yields and moderate to poor enantioselectivities. The hydroxyphosphine oxides undergo the Horner-Wittig elimination reaction to produce allenes. Baylis-Hillman reactions of vinylic phosphine oxides with tertiary amines were also investigated.

Recent Contributions from the Baylis−Hillman Reaction to Organic Chemistry

“…(Figure ). Several interesting publications ,,,,,,,,,,,,,− appeared during the last 25 years addressing the problem of mechanism of the Baylis−Hillman reaction.…”

“…Taking into account all the mechanistic proposals reported in the literature, it is proposed that the most reasonable mechanism involves the Michael, aldol/Michael, and elimination as shown in the Scheme . ,,,,,,− Despite several studies in this direction, many aspects of the rate-limiting step (RLS) are not yet clearly understood. This might be attributed to the fact that most of the mechanistic studies were investigated using acrylates as activated alkenes and aldehydes as electrophiles, although different kinds of activated alkenes and electrophiles were employed in a number of Baylis−Hillman reactions.…”

Recent Advances in the Baylis−Hillman Reaction and Applications

“…Subsequently, Warren and co-workers 260 used chiral lithium amide methodology (developed by Davies 259 ) for synthesizing enantiomerically enriched Baylis-Hillman-type molecules starting from vinyl phospho- nates. They also converted these allyl alcohols into allenes (Scheme 80).…”

Synthesis of Allenes by 1,2-Elimination

“…An interesting application to asymmetric synthesis has been reported by the Warren group, who showed that vinylic phosphine oxide 38 could be reacted with chiral lithium amide 39 and pivaldehyde providing enantioenriched βhydroxy phosphonates 40 (Scheme 11). [28] This reaction was proposed to take place via an addition elimination mechanism analogous to the Baylis-Hillman reaction. Subsequent treatment of intermediate 40 with NaH in DMF resulted in stereospecific syn-elimination to form the corresponding allene 41 which was isolated in good yield albeit with modest enantioenrichment.…”