Abstract
There have been extensive studies in recent years on two-carbon ring expansion via rearrangement of the 1-vinylcycloalkanol system with an activating group attached to C-2. In spite of a large variation of activating groups studied, the process does not appear to be highly useful in general. With the exception of the strained cyclobutanol system and a few conformationally rigid molecules, the reaction often led to the formation of a complex mixture. We have now observed that the cyano group can serve as an effective activating group. With the assistance of this functionality, a variety of 1-vinylcycloalkanols were shown to undergo two-carbon ring expansion with facility. This two-carbon ring expansion process is apparently general. Upon exposure to potassium hydride in THF in the presence of 18-crown-6, a variety of 2-cyano-1-vinylcycloalkanols with diverse ring sizes (5-, 6-, 7- and 12-membered rings) were found to undergo ring enlargement to give the corresponding γ-cyano cycloalkanones in synthetically useful yields (51-86%). It is noteworthy that the rearrangement of the 5-membered ring compounds was extremely facile; each reaction was shown to be complete within 10 min. Even for the formation of mid-sized 8- and 9-membered rings respectively from 6- and 7-membered starting substrates, the reaction also took place rather smoothly within a short period of time (2-6 h) with the exception of the transformation of compound 57 to 71 which took about one day. The process is also applicable to the preparation of large ring ketones. A case in evidence is the rearrangement of 1-vinyl-1-cyclododecanol 65 which gave the corresponding 14-membered ring ketone 80. The above results suggest that the cyano group is a useful activating group which makes the two-carbon ring expansion via the 1-vinyl-1-cycloalkanol system a viable general synthetic process. The cyano group appears to be quite unique in this regard. In sharp conrtast to compound 54 which gave the ring enlargement product 68 in good yield, the corresponding carbomethoxy derivative 54a underwent extensive decomposition upon exposure to potassium hydride under similar conditions.