Studies on electrophilic reaction of tertiary 2,3-allenols with NBS in H2O or aqueous MeCN: an efficient selective synthesis of 2-bromoallylic ketones, 1,2-allenyl ketones, or 3-bromo-2,5-dihydrofurans.

Previously, we observed that the electrophilic reaction of 2,3-allenols with X(+) (X = Br, I) affords 3-halo-2-alkenals or 2-halo-2-alkenyl ketones in aqueous MeCN (MeCN/H(2)O = 15:1). However, the reaction of tertiary 2,3-allenols with NBS under these reaction conditions affords a mixture of rearrangement products (aldehydes or ketones) together with 1-bromovinyl epoxides in a low selectivity. Due to the synthetic potential of 2-haloallylic ketones, we decided to explore this reaction further. After screening, we observed that the electrophilic reaction of terminal tertiary 2,3-allenols with NBS in water affords 2-bromoallylic ketones highly selectively in up to 97% yields via a sequential electrophilic interaction of Br(+) with the allene moiety to form a possible three-membered bromonium intermediate with the more substituted C=C bond, which would be followed by 1,2-aryl or 1,2-alkyl shift to open the strained three-membered ring and proton elimination to form the carbonyl functionality. When both R(1) and R(2) (the substituents on the carbon atom connected to the hydroxyl groups) are alkyl groups, one of these two groups is migrated; with 1,2-propadienyl cycloalkanols, a ring expansion reaction was observed; with R(1) being an aryl group, R(1) would be transferred exclusively to form the 2-bromoallylic ketones. Interestingly, these 2-bromo-1-aryl-2-propenyl ketones may easily be converted into 1,2-allenyl ketones after column chromatography on silica gel pre-eluented with 10 drops of Et(3)N; when there is at least an alkyl substituent on the 4-position of the tertiary 2,3-allenols, their electrophilic reaction with NBS in CH(3)CN/H(2)O = 15/1 or H(2)O, under the same reaction conditions as above, affords 3-bromo-2,5-dihydrofurans in 61-84% yields, indicating that the electronic effect and the steric effect of the two C=C bonds determine the reaction pathway, i.e., the Br(+) interacts with the C=C bond at the 3-position.