An approach to the synthesis of chiral carbamates.
An attempt to obtain chiral induction across the carbamate linkage (-NCOO-), using chiral amines and the benzyl carbamate, was embarked upon. Initial studies centred around the benzyl carbamate protected form of a,a-diphenylpyrrolidinemethanol. The inability to protect the alcohol in this compound led to further investigations into differently structured molecules, these being 2-(1-phenylcyc1opentyl)-4,4,6-trimethyltetrahydro-l,3-oxazine and N-biphenyl benzyl carbamate. Chiral induction was not achieved, but the investigations therein led to two new fields of study. A trans-carbamation type cyclisation reaction was found to occur in the a,a-diphenyl-(2pyrrolidine- N-benzyl carbamate)methanol compound yielding the bicyclic 2-oxazolidone, 3-oxa-l-aza-4,4-diphenylbicyclo[3.3.0]octan-2-one, with nitrogen at the bridgehead position. Sodium hydride was the base used to facilitate this reaction. Further studies into this reaction and this class of compounds were inconclusive. The second field of study was the initial investigation into novel N-monosubstituted carbamate rearrangement reactions to yield a substituted alcohol, of the benzyl alcohol type. The rearrangement occurs when the carbamate is treated with butyllithium at O°C and the reaction allowed to warm to room temperature. The rearrangement was shown to occur when the substituent on the nitrogen is aromatic in nature, this group being able to contain a hetero-atom and be substituted. A positive result was also obtained when the 0-carbamate moiety was the benzyl or cinnamyl group and to a much lesser degree the allyl group. The products obtained from the rearrangement of the benzyl carbamates were a-aryl- a-phenylmethanols (substituted benzyl alcohols / benzhydrols), with the analogous product, l-aryl-3-phenylprop-2-en-l-ol, being obtained from the cinnamyl alcohol. A benzylic substituted benzyl carbamate rearranged to give the tertiary alcohol. It was found that the rearrangement occurred to the position on the aryl substituent to which the nitrogen had been attached. From the results obtained no conclusive mechanistic details could be determined, but it was proposed that the reaction intermediate contained a five-membered cyclic structure. It is assumed that the rearrangement occurs with concomitant loss of cyanic acid (HNCO).