Exploring Border Conditions for Spontaneous Emergence of Chirality in Allylboration of 1,2,3-Triazolic Aldehydes

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-1<i>H</i>-1,2,3-triazole-4-carbaldehydes <b>1a,b</b> with triallylborane. Three possible sources of symmetry breaking were found computationally. Thus, dimerization of the initial reaction products, alcoholates <b>4a,b</b>, gives dimers <b>5a,b</b> (homochiral) and <b>6a,b</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 <b>4a,b</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 <b>4a,b</b> with <b>1a,b</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 <b>8a,b</b>, products of the previous reaction with triallylborane, recovered in each case two molecules of <b>4a,b</b> of the same handedness, which can lead to additional chirality amplification. Experimentally, reactions of optically active alcohols (+)-<i>R</i>-<b>2a,b</b> with triallylborane provided chiral alcoholates <b>4a,b,</b> which were reacted with equivalent amounts of corresponding aldehydes <b>1a,b</b>. Unexpectedly, in two series of 10 experiments each, preferential formation of both enantiomers of the newly formed product was observed: seven times <i>S</i> and three times <i>R</i> in the case of <b>1a</b> and six times <i>S</i> and four times <i>R</i> in the case of <b>1b</b>.