Aldehydes, alkylation autocatalysis

The enthalpies of trimers and tetramers were also calculated as part of this study. At the trimer level - important because this is the initial product of the reaction [dimer + zinc alkyl + aldehyde] - the most stable structures are macrocyclic. At the tetramer level there are two species of comparable enthalpy. One is the well-described cubic tetramer, and the other a barrel-like species that is conceptually related to two N - Zn lined dimers. The specific value derived from these calculations is only apparent when compared with the later computational work on the real diisopropylzinc-derived species. This highlights the importance of steric effects involving the more bulky isopropyl groups as a defining feature of asymmetric autocatalysis [80]. 

As described in the preceding sections, we already had experience on the enantioselective alkylation of aldehydes with dialkylzincs and the enantioselective synthesis of 3-pyridyl alkanol. In 1990, we found the first asymmetric autocatalysis of (5)-3-pyridyl alkanol 6 in the enantioselective addition of i-Pr2Zn to pyridine-3-carbaldehyde 7 to produce more of itself of 35% ee with the same S configuration (Scheme 6) [24]. Although the ee of product 6 decreased compared to that of the initial catalyst, the newly formed predominant enantiomer of the product is the same with that of asymmetric autocatalyst 6. We claim that this is the first asymmetric autocatalysis, that is, catalytic replication of chiral compound with the generation of new stereogenic centers. 

In 1953, Frank developed a mathematical model showing that spontaneous asymmetric synthesis is theoretically possible (21). If the chiral product of a catalytic reaction would act as a catalyst for its own formation and at the same time suppress the formation of its enantiomer, a basically enantiopirre product could be formed from near-racemic starling materials. About forty years later, Soai and coworkers provided the first experimental proof for this concept of asymmetric autocatalysis with the alkylation of pyrimidyl aldehydes with diallgrlzinc reagents (Figure 1) (22). 

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