Large-Scale Green Chemical Synthesis of Adjacent Quaternary Chiral Centers by Continuous Flow Photodecarbonylation of Aqueous Suspensions of Nanocrystalline Ketones

To
demonstrate the ease of scale-up and synthetic potential of some organic
solid state reactions, we report the synthesis, crystallization, and
solid state photochemistry of acyclic, homochiral, hexasubstituted
(+)-(2R,4S)-2-carbomethoxy-4-cyano-2,4-diphenyl-3-pentanone 1. We demonstrate that solid state photodecarbonylation of
(+)-(2R,4S)-1 affords
(+)-(2R,3R)-2-carbomethoxy-3-cyano-2,3-diphenyl-butane 2 with two adjacent stereogenic, all-carbon substituted quaternary
centers, in quantitative chemical yield and 100% diastereoselectivity
and enantiomeric excess. The efficient multigram photodecarbonylation
of (+)-(2R,4S)-1 as
a nanocrystalline suspension in water using a continuous flow photoreactor
shows that the large-scale synthesis of synthetically challenging
compounds using photochemical synthesis in the solid state can be
executed in a remarkably simple manner.