Asymmetric Amplification and Asymmetric Induction for Alkylation
catalytic activity responsible for this unexpected behaviour.
Such profound effect can be illustrated by considering the
striking asymmetric amplification for compound (R)-4f
when compared to (R)-4e under identical reaction condi-
tions (Table 3, entries 5,6).
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Conclusions
In summary, we have presented a new chemical system
combining asymmetric amplification of autocatalyst 2
alongside a catalytic addition of Zn(iPr)2 to aldehydes 3.
Probably most important, even starting from very low en-
antiopurity, autocatalysts (R)-2 and (R)-4 exhibit efficient
cooperation and reveal a strong non-linear relationship.
Also, this catalytic system provides exceptional amplifi-
cation up to Ͼ98% ee in one reaction cycle for both com-
pounds (R)-2 and (R)-4, which adds complexity to the Soai
reaction when it is coupled to asymmetric induction, and
suggests a more advanced reaction network. Currently we
are conducting further investigations to delineate the nature
and the key role of reactive species in such a novel reaction
network.
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Experimental Section
General Procedures for the Asymmetric Alkylation: Standard pro-
cedures for the asymmetric alkylation catalysed by 2 in two step
one-pot: In an oven dried flask (R)-1-[2-(3,3-dimethylbut-1-yn-1-
yl)pyrimidin-5-yl]-2-methylpropan-1-ol (R)-2 (0.027 mmol, 99%
ee), is dissolved in 0.4 mL of dry toluene under nitrogen and di-
isopropylzinc 1 m (0.583 mmol) is added drop wise at 0 °C and
stirred for 30 min. The pyrimidyl aldehyde 3 (0.265 mmol) is dis-
solved in 1.6 mL of dry toluene and added slowly over three hours
at 0 °C to the reaction mixture. The advancement of the reaction
is monitored by HPLC. The reaction is quenched by the addition
of HCl 1 m in dioxane (0.265 mmol) and neutralized with saturated
aqueous NaHCO3. The mixture is extracted with ethyl acetate,
dried with anhydrous Na2SO4 and the solvents evaporated to dry-
ness under reduced pressure. The crude is further purified by flash
chromatography on silica gel to give the pure alcohol 4.
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Standard Procedure for the One-pot Asymmetric Autocatalysis of 2
and Asymmetric Alkylation: In an oven dried flask soai alcohol (R)-
2 (0.002 mmol, 11% ee), soai aldehyde 1 (0.02 mmol) and aldehyde
3 (0.200 mmol) are dissolved in 2 mL of dry toluene under nitrogen
atmosphere. A solution of diisopropylzinc 1 m in toluene (0.51 mL,
0.51 mmol) is added slowly over 3 h to the mixture, and is moni-
tored by TLC. The reaction is quenched by the addition of HCl 1 m
in dioxane (0.210 mmol) and neutralized with saturated aqueous
NaHCO3. The mixture is extracted with ethyl acetate, dried with
anhydrous Na2SO4 and the solvents evaporated to dryness under
reduced pressure. The crude was further purified by flash
chromatography on silica gel to give the pure alcohol 4.
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Acknowledgments
This work was supported by the Research Council of Norway
(FRIPRO program 205271), the University of Oslo, and COST Ac-
tion, Emergence and Evolution of Complex Chemical Systems
(CM 1304).
[12]
Eur. J. Org. Chem. 2015, 4087–4092
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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