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

• Published in: Journal of the American Chemical Society Vol. 137; no. 4; pp. 1679 - 1684
• Main Authors: Hernández-Linares, María Guadalupe, Guerrero-Luna, Gabriel, Pérez-Estrada, Salvador, Ellison, Martha, Ortin, Maria-Mar, Garcia-Garibay, Miguel A
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 04.02.2015; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; RADICAL PAIRS; REARRANGEMENT; DECARBONYLATION; CHEMISTRY; REACTIVITY; ENGINEERING REACTIONS; PHOTOCHEMICAL-REACTIONS; CYCLOADDITION REACTION; COMBINATION; CRYSTALLINE SOLIDS
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja512524j

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.