Synthesis of 11‐cis‐Retinoids by Hydrosilylation–Protodesilylation of an 11,12‐Didehydro Precursor: Easy Access to 11‐ and 12‐Mono‐ and 11,12‐Dideuteroretinoids

Abstract

An expeditious, highly efficient approach to 11-cis-retinoids was achieved by semihydrogenation of a readily available 11-yne precursor through a hydrosilylation-protodesilylation protocol. The complete chemo-, regio-, and syn-stereoselectivity of the method also allowed direct access to 11- and 12-monodeutero-, and 11,12-dideutero-11-cis-retinoids. The analogous trans series was not accessible by this route, and was synthesized by means of Hiyama coupling.

Synthesis of 9-CD3-9-cis-retinal cofactor of isorhodopsin

“…The ratio of the formed diastereomers was in favor of the desired E isomer ( E/Z : 12:1 based on isolated yields). Replacing the last step with an alternative published oxidation condition using MnO 2 at room temperature 32 afforded similar yield of the target aldehyde. The structure of the labeled retinal was fully characterized using IR, UV, 1 H NMR, 13 C NMR, and DART-MS (see Supplementary Data).…”

“…There are many reports available on using deuterium and carbon-13 enriched retinoids for investigating different aspects of the visual cycle, with the help of spectroscopic methods such as solid-state magic-angle-spinning NMR, Raman, or FTIR. 32–35 Studies have shown that the non-bonding interactions of the methyl group on C9 of 11- cis -retinal with opsin is necessary for rhodopsin activation. 11,36 Our synthesis of the 9-CD 3 -9- cis -retinal gives a new route to testing structure-function hypotheses for visual rhodopsin and other retinal proteins.…”

Cobalt-Catalyzed (E)-Selective Hydrosilylation of 1,3-Enynes for the Synthesis of 1,3-Dienylsilanes

“…On the other hand, silyl groups are easily converted to other important functional groups . Therefore, it is easy to imagine that silyl-substituted 1,3-dienes have diverse reactivity, and indeed, they have been applied in many organic transformations. − …”

“…Hydrosilylation of 1,3-enynes is a potentially efficient and atom-economic method for producing silyl-substituted 1,3-dienes, but the control of regio- and stereoselectivities is highly challenging, owing to the existence of four active sites of 1,3-enynes. At the moment, hydrosilylation of 1,3-enynes depends basically on noble transition metals, such as Pt, ,, Rh, , Ru, ,, and Pd, , although in most of the cases, the substrate scope was not studied. A typical example is the Pd-catalyzed cis -hydrosilylation of 1,3-enynes reported by Zhou and Moberg, affording a series of 1,3-dienes with an internal silyl group, while in that case, 1,3-enynes with a terminal double bond were not suitable (Scheme ).…”

Iron-Catalyzed Regio- and Stereoselective Hydrosilylation of 1,3-Enynes To Access 1,3-Dienylsilanes

“…In the past decades, several selective hydrosilylations of 1,3-enynes to access 1,3-dienylsilanes have been achieved based on precious transition metals, − such as Pt, Rh, Pd, and Ru. Early studies focused on the hydrosilylation of silicon-substituted butenynes, and the selectivity was influenced by the substitution pattern around the alkyne group .…”