Short, Convergent Synthesis of Locked Retinals

Abstract

We report a short and convenient synthesis of two configurationally locked retinals that are important for applications in the context of optogenetics. The C11–C15 cyclopentyl fragments of both retinals were obtained by palladium‐catalysed alkoxycarbonylation and merged with the rest of the carbon skeleton through Wittig olefination. The preparation of the required and known ylide precursor was revisited and optimised. This synthetic route enables gram‐scale preparation of both retinal derivatives.

Aluminum Chloride-Mediated Dieckmann Cyclization for the Synthesis of Cyclic 2-Alkyl-1,3-alkanediones: One-Step Synthesis of the Chiloglottones

“…Cyclic 2-alkyl-1,3-alkanediones ( 7 , R = alkyl) constitute key synthetic building blocks for the construction of heterocycles, complex molecules, and natural products (Figure A). Two of the most prominent examples derived from these structural motifs are the Wieland–Miescher and Hajos–Parrish ketones, 3 and 4 , which represent crucial synthetic intermediates in strategies toward steroid and terpene natural products .…”

Phosphonium salts and P-ylides

“…281 The result offered a new approach to the synthesis of chiral S1P1 agonists. Many other applications of the Wittig reaction were reported in the literature; they include for example, the synthesis of eushearilide, 282 (þ)-chloriolide, 283 1,3-di-O-cinnamoyl-glycerol, 284 locked retinals, 285 and (þ)monanchorin. 286 The Wittig protocol was used also for the preparation of polymers 287 and donor-acceptor 1,4-fluorenylene chromophores.…”

Phosphonium salts and P-ylides

“…281 The result offered a new approach to the synthesis of chiral S1P1 agonists. Many other applications of the Wittig reaction were reported in the literature; they include for example, the synthesis of eushearilide, 282 (þ)-chloriolide, 283 1,3-di-O-cinnamoyl-glycerol, 284 locked retinals, 285 and (þ)monanchorin. 286 The Wittig protocol was used also for the preparation of polymers 287 and donor-acceptor 1,4-fluorenylene chromophores.…”