3- Pyridyl alkanols

As described, pyrimidyl alkanols 2 act as highly efficient asymmetric autocatalysts with significant amplification of chirality. 3-Quinolyl alkanoland 5-carbamoyl-3-pyridyl alkanol also serve as efficient asymmetric autocatalysts with amplification of chirality. 

Meanwhile, asymmetric autocatalysis of 3-quinolyl alkanol 84-86167,173 and 5-carbamoyl-3-pyridyl alkanol 77174 also proceed with amplification of . Quinolyl alkanols 84 with 9% increases its to 88%173 and the of 5-carbamoyl-3-pyridyl alkanol 77 increased from 14% to 87%174. 

Pyridyl alkanol [41], diol [42], and ferrocenyl alcohol [43] were the first asymmetric autocatalysts found by Soai and co-workers in the enantioselective alkylation of pyridine-3-carbaldehyde, dialdehyde, and ferrocenecarbaldehyde, respectively, with dialkylzincs. 

Moreover, when these alkanols with low ee are utilized as asymmetric autocatalysts, 5-pyrimidyl alkanol 28 [48], 3-quinolyl alkanol [49],and 5-carbamoyl-3-pyridyl alkanols [50] with higher ees were obtained. The successive reactions were performed in order to make the best use of the autocatalysis, that is, the products of one round served as the asymmetric autocatalysts for the next. In the case of pyrimidyl alkanol, staring from (S)-alkanol 28a with only 2% ee, the ee reached almost 90% after four rounds [48] without the assistance of any other chiral auxiliary (Scheme 14). 2-Alkynyl-5-pyrimidyl alkanol 28b [5] and 2-... 

One of the reasons that the enantioselectivity of 5-pyrimidyl alkanol is higher than that of 3-pyridyl alkanol may be due to the presence of symmetry in the pyrimidine ring. When the bond between the asymmetric carbon and the pyridine ring rotates, conformational isomers of pyridyl alkanol will be formed (Figure 9.2). However, with pyrimidyl alkanol, the rotation does not form conformational isomers. Thus, the reduced number of possible conformational isomers may enable 5-pyrimidyl alkanol to serve as a highly enantioselective asymmetric autocatalyst. 

The introduction of a carbamoyl group to the 5-position of chiral 3-pyridyl alkanol enhances its efficacy as asymmetric autocatalyst. (S)-5-Carbamoyl-3-pyridyl alkanols 61 are automulti-plied with up to 86% ee in the enantioselective addition of i-Pr2Zn to 5-carbamoyl-3-pyridine-carbaldehyde 60 (Scheme 9.32) [60]. The enantioselectivity depends on the structure of the substituent on the nitrogen atom of the amide. A bulky t-Pr substituent is efficient for achieving high enantioselectivity. The amplification of the enantiopurity of 61 to a certain degree is also observed [61]. 

After studying various nitrogen-containing compounds, we found that the zinc alkoxide of 2-methyl-l-(3-quinolyl)propan-l-ol 5 (Fig. 1) catalyzes the enantioselective formation of itself with the same configuration in the reaction between quinoline-3-carbaldehyde and z-P Zn to produce the product 5 in high ee (up to 94% ee) [58]. In addition, the 5-carbamoyl-3-pyridyl alkanol 6 (Fig. 1) can act as an efficient autocatalyst to catalyze its own production in a highly enantioselective manner (up to 86% ee) [59]. 

We found that chiral 5-pyrimidyl alkanol, 3-quinolyl alkanol and 5-carbamoyl-3-pyridyl alkanol are highly enantioselective asymmetric autocatalysts for the addition of z-Pr2Zn to the corresponding aldehydes, respectively. Among these, 2-alkynyl-5-pyrimidyl alkanol is a highly efficient asymmetric auto-... 

Soai K, Niwa S, Hori H Asymmetric self-catalytic reaction — Self-production of chiral l-(3-pyridyl)alkanols as chiral self-catalysts in the enantioselective addition of dialkylzinc reagents to pyridine-3-carbaldehyde. J Chem Soc Chem Common 1990, (l4) 982-983. 

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. 

As described, it took us for 5 years to find pyrimidyl alkanol since the initial asymmetric autocatalysis of pyridyl alkanol of 1990. Soon after pyrimidyl alkanol, we also found efficient systems of asymmetric autocatalysis with 3-quinolyl alkanol [27] and 5-carbamoyl-3-pyridyl alkanol [28]. 

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