Diphenyl methanol enantioselective addition

Design of chiral catalysis and asymmetric autocatalysis for diphenyl-(l-methyl-pyrrolidin-2-yl) methanol-catalyzed enantioselective additions of organozinc reagents 97YGK994. 

In the course of the continuing study [9a,b] on the enantioselective addition of dialkylzincs to aldehydes by using chiral amino alcohols such as diphenyl(l-methyl-2-pyrrolidinyl)methanol (45) (DPMPM) [48] A. A -dibutylnorephedrine 46 (DBNE) [49], and 2-pyrrolidinyl-l-phenyl-1-propanol (47) [50] as chiral catalysts, Soai et al. reacted pyridine-3-carbaldehyde (48) with dialkylzincs using (lS,2/ )-DBNE 46, which gave the corresponding chiral pyridyl alkanols 49 with 74-86% ee (Scheme 9.24) [51]. The reaction with aldehyde 48 proceeded more rapidly (1 h) than that with benzaldehyde (16 h), which indicates that the product (zinc alkoxide of pyridyl alkanol) also catalyzes the reaction to produce itself. This observation led them to search for an asymmetric autocatalysis by using chiral pyridyl alkanol. 

The asymmetric catalytic hydrogenation of 2-(6 -methoxy-2 -naphthyl)propenoic acid to (S)-naproxen was monitored in both methanol- and C02-expanded methanol.f The catalyst used was [dichloro-(S)-(-)-2,2 -bis(diphenyl-phosphino)-1, l -binapthyl]ruthenium(II). Addition of CO2 to the methanol produced strong retardation of the reaction rate. An average reduction in enantioselectivity of 6%i was observed compared to that in methanol. The enantioselectivity was found to increase as the temperature decreased in both neat methanol and C02-expanded methanol systems, indicating that the underlying mechanisms were similar. Insufficient oxygen removal may have prevented the... 

The chiral catalysts 1 to 4 are highly enantioselective in the addition of di(prira-alkyl)zincs to aromatic aldehydes. (IS, 2i )-iV,iV-dibutylnorephedrine [1 (DBNE)] [5] possesses the advantage of its utility as a highly enantioselective catalyst even for the alkylation of aliphatic aldehydes to afford aliphatic sec-alcohols with up to 93% ee [5]. DBNE is also an appropriate chiral catalyst for the addition of diisopropylzinc [di(sec-alkyl)zinc] (98% ee) [15]. (S)-Diphenyl(l-meth-ylpyrrolidin-2-yl)methanol [2 (DPMPM) [6] catalyzes the enantioselective ethylation of aromatic aldehydes to afford almost enantiomerically pure sec-alcohols... 

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