Chemistry Reference
In-Depth Information
S
[CD(+)310]-crystal of cytosine
34
N
OH
N
>99.5% ee
CHO
N
t
-Bu
(
S
)-
33
Asymmetric autocatalysis
N
R
t
-Bu
+
i
-Pr
2
Zn
N
OH
32
[CD(-)310]-crystal of cytosine
34
N
>99.5% ee
t
-Bu
(
R
)-
33
Scheme 12.40.
Highly enantioselective asymmetric autocatalysis using chiral crystal of cytosine.
asymmetric autocatalysis indicate the possibility that cytosine is the origin of biological
homochirality.
In addition, cocrystals of achiral tryptamine and
p
- chlorobenzoic acid, which belongs
to a chiral space group (
P
2
1
2
1
2
1
) and have both clockwise (
P
) and counterclockwise (
M
)
helicities in its crystal state, can act as a chiral source of asymmetric autocatalysis to
afford enantioenriched pyrimidyl alkanol whose absolute confi guration was controlled
by the chirality of the cocrystal [111]. The enantiomorphous crystals composed of achiral
hippuric acid, that is, naturally occurring
N
-benzoylglycine, have been used successfully
as chiral inducers in asymmetric autocatalysis [112].
12.4.5. Spontaneous Absolute Asymmetric Autocatalysis in Conjunction with
Asymmetric Autocatalysis
Spontaneous absolute asymmetric synthesis, that is, the formation of enantioenriched
compound without the intervention of any chiral factors, has been proposed as one of
the origins of biological homochirality in nature [71,95]. It has been well accepted that,
without the intervention of any chiral factor, the probability of the formation of
R
and
S
product is fi fty - fi fty (50:50); racemate is formed. However, according to the theory of
statistics, the numbers of
R
and
S
enantiomers are not exactly the same, that is, there is
almost always the fl uctuation in numbers of enantiomers [95,113]. We thought that, when
a reaction system involves asymmetric autocatalysis with amplifi cation of ee, the initial
small fl uctuation of ee in racemic mixtures that arises from the reaction of achiral reac-
tants can produce an enantiomerically enriched product. We anticipated that when
i
-
Pr
2
Zn was treated with pyrimidine - 5 - carbaldehydes
without
adding any chiral substance,
extremely slight enantioenrichment would be induced statistically in the initially formed
zinc alkoxide of the alkanol, and that the subsequent amplifi cation of chirality by asym-
metric autocatalysis would produce the pyrimidyl alkanol with detectable enantioenrich-
ment (Scheme 12.41 ).
The reaction of pyrimidine - 5 - carbaldehyde
28
and 2 - methylpyrimidine - 5 - carbalde-
hyde
30
with
i
- Pr
2
Zn without adding a chiral substance produced enantioenriched (
S
) - or
(
R
) - pyrimidyl alkanol
29
and 2-methylpyrimidyl alkanol
31
, respectively [114] . When
2 - alkynylpyrimidine - 5 - carbaldehyde
32
reacted with
i
- Pr
2
Zn in a mixed solvent of ether
and toluene, the subsequent one-pot asymmetric autocatalysis with amplifi cation of ee
gave enantiomerically enriched pyrimidyl alkanol
33
whose ee was well above the detec-
