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reaction of pyrimidine - 5 - carbaldehyde
32
with
i
- Pr
2
Zn in the presence of achiral silica
gel in toluene, followed by a one-pot asymmetric autocatalysis with amplifi cation of ee
gave the enantioenriched (
S
) - and (
R
) - 5 - pyrimidyl alkanol
33
with ee above the detec-
tion level. In order to examine the distribution of the absolute confi guration of the
predominantly formed enantiomers in each experiment, 84 experiments were run under
the same reaction conditions. In all cases, enantioenriched 5-pyrimidyl alkanols with
either
S
or
R
confi gurations were formed. The absolute confi gurations of the resulting
33
exhibited an approximate stochastic distribution, that is, the formation of the
S
form
occurred 45 times and the formation of the
R
form occurred 39 times (Fig. 12.6).
We have demonstrated the stochastic formation of (
S
) - and (
R
) - 5 - pyrimidyl alkanol
33
from pyrimidine - 5 - carbaldehyde
32
and
i
- Pr
2
Zn without the intervention of a chiral
auxiliary. Even in the reactions performed in toluene alone, stochastic behavior of the
formation of (
S
) - and (
R
) -
33
was observed in the presence of achiral silica gel. We
believe that the approximate stochastic behavior in the formation of alkanols fulfi lls one
of the conditions necessary for chiral symmetry breaking by spontaneous absolute asym-
metric synthesis.
12.5. CHIRAL DISCRIMINATION BY ASYMMETRIC AUTOCATALYSIS WITH
AMPLIFICATION OF EE
12.5.1. Introduction
Chirality plays a major role in many aspects of modern science. The fundamental pre-
requisite of a study on chirality is the availability of a method to discriminate between
enantiomeric forms. Signifi cant progress in chiral discrimination has been achieved in
recent decades; however, there remains a class of compounds whose chiral discrimina-
tion has been very diffi cult to establish, or has not been possible at all. The compound
is a chiral, but to all intents an optically inactive compound. Mislow called such hidden
chirality “cryptochirality” [95,117]. Herein, we demonstrate that the asymmetric auto-
catalysis has enormous power to recognize the hidden cryptochirality.
12.5.2. Discrimination of Cryptochirality in a Saturated Quaternary Hydrocarbon by
Asymmetric Autocatalysis
Chiral saturated hydrocarbons form a class of compounds whose chiral discrimination
has often been very diffi cult [118]. Unlike other functionalized compounds, chiral satu-
rated hydrocarbons do not bear heteroatoms,
- electrons, or chromophores; therefore,
the difference between the four substituents on the asymmetric carbon atom is very
small. An example of a compound whose chiral discrimination poses the utmost diffi culty
is a saturated quaternary hydrocarbon bearing similar substituents on the asymmetric
carbon atom, with a representative example being 5-ethyl-5-propylundecane, that is,
(
n
- butyl)ethyl(
n
- hexyl)(
n
- propyl)methane
35
[119]. The enantiomer of this hydrocarbon
exhibits the optical rotation (|
π
α
|
<
0.001) below the detection level between 280 and
580 nm.
We found that the chirality of the saturated quaternary hydrocarbon was successfully
discriminated using asymmetric autocatalysis [120]. The asymmetric autocatalysis initi-
ated by the chiral (
R
) - quaternary hydrocarbon using pyrimidine - 5 - carbaldehyde
32
and
i
- Pr
2
Zn produced (
S
) - pyrimidyl alkanol
33
with 97% ee and 93% yield. In contrast,
