Abstract
A case of spontaneous chirality generation was observed during a synthetic project studying the allylboration of 1,2,3-triazolic aldehydes. Here, we present computational studies supported by experimental findings targeting the elucidation of border conditions required for the observation of spontaneous chirality generation in the reaction of 1-Ar-1H-1,2,3-triazole-4-carbaldehydes 1a,b with triallylborane. Three possible sources of symmetry breaking were found computationally. Thus, dimerization of the initial reaction products, alcoholates 4a,b, gives dimers 5a,b (homochiral) and 6a,b (heterochiral). The latter were computed to be more stable thermodynamically, which can lead to amplification of the initial stochastic imbalance of the enantiomers of 4a,b via the reservoir mechanism. Furthermore, enantiomeric excess can be increased during the transfer of the second allylic group in the reaction of optically active boronates 4a,b with 1a,b, which was computed to be enantioselective due to the strong activating and stereoregulating properties of the 1,2,3-triazole group. In addition, reactions of borinic esters 8a,b, products of the previous reaction with triallylborane, recovered in each case two molecules of 4a,b of the same handedness, which can lead to additional chirality amplification. Experimentally, reactions of optically active alcohols (+)-R-2a,b with triallylborane provided chiral alcoholates 4a,b, which were reacted with equivalent amounts of corresponding aldehydes 1a,b. Unexpectedly, in two series of 10 experiments each, preferential formation of both enantiomers of the newly formed product was observed: seven times S and three times R in the case of 1a and six times S and four times R in the case of 1b.