The organoalkali route to vitamin A and β-carotene

Article abstract of DOI:10.1002/1099-0690(200110)2001:20<3903::AID-EJOC3903>3.0.CO;2-R

The reductive cleavage of methyl vinyl-β-ionyl ether (1) or the deprotonation of 3,2′,6′,6′-tetramethyl-5-(1-cyclohexenyl)-1, 3-pentadiene (2) gives rise to an organometallic C₁₅ species that combines selectively with a variety of electrophiles at the terminal chain position. Its reaction with aldehydes, however, is less clean. In particular, (E)-β-formyl-2-butenyl acetate gives the expected adduct 7a and, after dehydration, vitamin A acetate only in poor yield. The same is true for the analogous reaction with 2,7-dimethyl-2,4,6-octatriendial, which ultimately affords βcarotene. Vitamin A acetate can also be prepared, this time in moderate yield, by functionalization through consecutive deprotonation, borylation, oxidation and acetylation of a C₂₀ pentaene hydrocarbon having the required skeleton. Both the C₁₅ and the C₂₀ organometallic key intermediates adopt spontaneously a zigzag-like outstretched conformation which, upon electrophilic trapping, directly and exclusively leads to the all-(E) configuration.