P(CH3NCH2CH2)3N as a dehydrobromination reagent:: Synthesis of vitamin A derivatives revisited

Although P(CH3NCH2CH2)(3)N (1) was found to be less effective than 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in the removal of hydrogen bromide from vitamin A intermediates 13-cis-10-bromo-9,10-dihydroretinyl acetates (6) and 14-bromo-9,14-dihydroretinyl acetate (11) when the reaction was carried out in refluxing benzene, in acetonitrile at room temperature it was superior to DBN and DBU.A P-31 NMR study of this reaction suggests that the carbanion generated from acetonitrile-d(3) in the presence of 1 is the basic species that initiates the elimination step. Diastereoselectivity of the nucleophilic addition of (Z)-HCdropC(CH3)=CHCH2OH to the carbonyl group of (E)-2-methyl-4-(2',6',6'-trimethyl-1'-cyclohexen-1'-yl)-3-butenal (2) was only moderate (20%), and (9R*,10S*)-13-cis-11,12-didehydro-9,10-dihydro-10-hydroxyretinol (3b) predominated. The LiAlH4 reduction of the CdropC bond in the diastereoisomeric diols 3 afforded 13-cis-9,10-dihydro-10-hydroxyretinols 4a and 4b as major products together with 11-cis-13-cis-isomers and the deoxygenated compound (3EZ,5EZ,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1,3,5,8-nonatetraene (9). Reaction of 15-acetates of the pure diastereoisomeric allylic alcohols 4a and 4b with PBr3 occurred with significant but not identical retention of configuration, and with concomitant formation of the rearranged bromide 11.