Practically Perfect Asymmetric Autocatalysis with (2-Alkynyl-5-pyrimidyl)alkanols

Abstract

Extremely high enantioselectivity (>99.5% ee) and chemical yield (>99%) are achieved in an asymmetric autocatalytic reaction. A (5-pyrimidyl)alkanol with a tert-butylethynyl group at its 2-position (1) is a very efficient asymmetric autocatalyst in the enantioselective alkylation in Equation (1).

Natural Abundance Isotopic Chirality in the Reagents of the Soai Reaction

“…The reagents of the most efficient variant [17] of the Soai reaction include an N-heterocyclic aldehyde, 4-[2-(tert.-butyl)ethynyl]pyrimidylaldehyde (1), di(iso-propyl)zinc (2) and the autocatalyst, which is the alkylation product of 1 by 2, leading to the secondary alcohol (3), as shown in Figure 1 [41,42]. These molecules are formed from H, C, N, O and Zn, which are present in nature as mixtures of their stable isotopes; the H, C, N, and O with dominance of the lighter nuclei, while Zn as a more equable mixture of five isotopes [12] (Table S1).…”

“…These data show that even if the expectable e.e. values are very low, according to experimental evidence [16][17][18][19][20] and theoretical considerations [21][22][23][24], the isotope chirality in the tert.-butyl group in compounds 1 and/or 3 could influence the outcome of the most sensitive variant of the Soai reaction, however, taking into regard that it is separated from the pyrimidyl unit by the rigid C 2 moiety, and thus from the decisive molecular events around the new stereocenter, this option appears as scarcely probable, but cannot be excluded.…”

“…This, obviously, is due to the asymmetric natural abundance of the isotopes of H and C. However, even so, the percentages of expected enantiomeric excesses are much higher than the experimentally documented sensitivity threshold of the Soai reaction [16][17][18][19][20][37][38][39]41,42].…”

“…Let us denote 64 Zn as a, 65 Zn as b, 66 Zn as c, 67 Zn as d, and 68 Zn or 70 Zn as e (we shall later use similar notation for oxygen isotopes: 16 O u, 17 O v, and 18 O w). Simple case (all O atoms are regarded equal, or isotopic differences in these O atoms are disregarded).…”

“…The Soai reaction shows extreme sensitivity towards the chiral induction exerted by even very low quantities both of the autocatalyst [16][17][18][19][20][21][22][23][24] and of added (enantiomerically pure or enriched) "foreign" chiral molecules [25][26][27][28][29][30][31]. It has also been proved experimentally that such inductor molecules may include enantiomers of simple chiral organic compounds with chirality due only to stable isotopic substitution [32][33][34][35][36][37][38][39].…”