Right- and left-handed circularly polarized light (CPL) has been proposed as one of the origins of homochirality of biomolecules. However, the enantiomeric excess induced by CPL has been only very low (<2% ee). We found the unprecedented example of asymmetric autocatalysis triggered directly by a chiral physical factor, that is, right- and left-handed CPL, leading to a near enantiopure compound. Asymmetric photolysis of racemic pyrimidyl alkanol by r-CPL irradiation followed by asymmetric autocatalysis affords (R)-pyrimidyl alkanol with >99.5% ee. On the other hand, irradiation with l-CPL affords (S)-pyrimidyl alkanol with >99.5% ee. Thus, chiral physical power, such as CPL, in conjunction with asymmetric autocatalysis, provides a highly enantioenriched compound.
Biomolecules such as amino acids and sugars occur in Nature overwhelmingly as l and d enantiomers, respectively. The origins of chirality and the processes leading to high enantiomeric enrichment of organic compounds have been intriguing puzzles.[1] Several factors have been proposed as the origins of chirality of organic molecules.[2] However, the enantiomeric excesses (ee) of organic compounds induced by these factors have usually been very low (from 10 À4 to < 2 % ee). Circularly polarized light (CPL) induces very low selectivity (< 2 % ee) in asymmetric photosynthesis, [2a,b] photoisomerization, [2c] photoequilibration, [2d,e] and photolysis. [2f,g] Asymmetric adsorption on and desorption from chiral surfaces induce a tiny imbalance (< 2 % ee) in enantiomers.[2h±k] These very low levels of enantiomeric excess require an efficient method of amplification in order to explain the very high enantiomeric enrichment of organic compounds. A tiny imbalance in the enantiomeric composition of a sterically encumbered olefin induces the twist of a nematic phase into a cholesteric phase in liquid crystals.[2d]The positive nonlinear effect of asymmetric catalysis, discovered by Kagan et al., [3a] explains how a product can have a higher ee than the chiral catalyst required for its production. [3] However, the selectivity of the reaction remains low to moderate when the chirality level of the asymmetric catalyst employed is low. For example, the product was produced with only 36 % ee when a catalyst with 3 % ee was used.[3b] On the other hand, we reported asymmetric autocatalysis in which the chiral product acts as a chiral catalyst for its own production. [4] The chirality level of the initial catalyst with 0.3±2 % ee was enhanced to 87±88 % ee.[5] However, considering the much lower levels of chirality induced by a physical factor, [2l] it is a challenge to develop a method for ™amplifying chirality∫ starting from extremely small enantiomeric imbalances to give practically enantiomerically pure product.Herein we report efficient chirality amplification by a catalyst with as low as 10 À5 % ee to give practically enantiomerically pure (> 99.5 % ee) product in only three consecutive cycles. The product formed in situ with enhanced ee serves as an asymmetric autocatalyst for the further formation of itself with much higher ee.The initial asymmetric autocatalysts with very low levels of chirality were prepared carefully by adding calculated amounts of standardized solutions of (S)-and (R)-(2-alkynyl-5-pyrimidyl)alkanol 1 (> 99.5 % ee) [6] to racemic 1 (Scheme 1).[7] The enantiomeric enrichment of these two solutions was roughly 0.00005 % ee (i.e. enantiomeric ratio of ca. 50.000025:49.999975).[8] We found that the first asymmetric autocatalysis with (S)-1 of approximately 0.00005 % ee in the enantioselective addition of diisopropylzinc [9] to 2-alkynylpyrimidine-5-carbaldehyde 2 gave (S)-1 in 96 % yield with an enhanced selectivity of 57 % ee (Table 1, run 1). To take advantage of asymmetric autocatalysis, the (S)-1 o...
Scheme 1. Alkylation of 2 catalyzed by and yielding (2-alkynyl-5-pyrimidyl)alkanol 1.
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