Absolute Asymmetric Photocyclization of Triisopropylbenzophenone Derivatives in Crystals and Their Morphological Changes

Although 4-(2,4,6-triisopropylbenzoyl)­benzyl­benzamide
is
an achiral molecule, chiral crystals can form through spontaneous
crystallization in a methanol solution. In the M crystal,
twofold helical hydrogen-bond chains form in a counterclockwise direction
among the molecules along the a axis to generate
crystal chirality. The solid-state circular dichroism spectra of the
two enantiomorphous crystals as Nujol mulls show a good mirror-image
relationship. UV irradiation of the M crystal at
>290 nm caused highly enantioselective Norrish type II photocyclization
to yield the (R)-cyclobutenol with 94% ee in 100%
yield as the sole product, resulting in successful absolute asymmetric
synthesis. In contrast, the (S)-cyclobutenol was
obtained from the P crystal with 95% ee in 100% yield.
The high enantiodifferentiation in the crystalline-state photocyclization
is attributed to the shorter distance between the carbonyl oxygen
atom and one of the methine γ-hydrogen atoms of the two o-isopropyl groups as well as the smooth transformation
with minimum molecular motion because of the similar shapes of the
reactant and product molecules. UV irradiation of the platelike crystals
resulted in a crack in the direction perpendicular to the long axis
(the a axis of the unit cell), likely because the
hydrogen-bond chains were broken during the photocyclization.

4-(2,4,6-三异丙基苯甲酰基)苄基苯甲酰胺（4-(2,4,6-triisopropylbenzoyl)benzylbenzamide）虽为非手性分子，但可通过甲醇溶液中的自发结晶过程形成手性晶体。在M晶体中，分子沿晶胞a轴方向形成逆时针走向的二重螺旋氢键链，由此赋予晶体手性。以石蜡油糊（Nujol mulls）法测试两种对映异构晶体的固态圆二色谱，二者呈现出良好的镜像对称关系。对M晶体施加波长大于290 nm的紫外辐照，可引发高对映选择性的Norrish II型光环合反应，仅以100%产率得到对映体过量值（ee）为94%的(R)-环丁烯醇，成功实现绝对不对称合成。与之相对，从P晶体中可得到对映体过量值为95%的(S)-环丁烯醇，产率同样为100%。晶体态光环合反应所展现的高对映区分能力，可归因于羰基氧原子与两个邻位异丙基其中一个的次甲基γ-氢原子之间更短的距离，同时反应物与产物分子形状相近，使得反应仅需最小程度的分子运动即可顺利进行。对片状晶体进行紫外辐照后，其会沿垂直于长轴（即晶胞的a轴）的方向产生裂纹，这大概率是由于光环合反应过程中氢键链发生断裂所致。