Samarium Diiodide Mediated Reactions in Total Synthesis

Abstract

Introduced by Henri Kagan more than three decades ago, samarium diiodide (SmI 2 ) has found increasing applications in chemical synthesis. This single-electron reducing agent has been particularly useful in C-C bond formations, including those found in total synthesis endeavors. This Review highlights selected applications of SmI 2 in total synthesis, with special emphasis on novel transformations and mechanistic considerations. The examples discussed are both illustrative of the power of this reagent in complex molecule construction and inspirational for the design of synthetic strategies toward such targets, both natural and designed.

An Oxidative Prins–Pinacol Tandem Process and its Application to the synthesis of (−)‐Platensimycin

“…Aldehydes 28 are known synthetic intermediates for (À)-platensimycin. [8] Hence, they were subjected to the action of Kagans reagent (SmI 2 ), [19] whereupon stereoselective cyclization to alcohols 29 occurred (Scheme 10). Finally, the olefin regioisomers of 29 converged to the same final product 31 upon treatment with TFA.…”

Recent developments in transition-metal photoredox-catalysed reactions of carbonyl derivatives

“…1, 2 Among the strategies reported in the literature, the formation of ketyl radicals via single electron reduction of carbonyl derivatives has emerged as an appealing route to access a wide range of valuable molecular architectures. 3 However, a widespread application of ketyl radicals in synthesis has been hindered by (i) the highly negative reduction potential 4 of aldehydes ( E 1/2 red = −1.93 V vs. SCE for benzaldehyde), 5 ketones ( E 1/2 red = −2.11 V vs. SCE for acetophenone), 5 and imines ( E 1/2 red = −1.91 V vs. SCE for N -benzylideneaniline) 5 (Scheme 1) and (ii) the requirement to employ toxic, air- and moisture-sensitive reducing agents, and harsh reaction conditions to generate the ketyl and α-aminoalkyl anion radical intermediates. Accordingly, early examples of reductive coupling reactions between carbonyl derivatives and alkenes/alkynes were performed using very strong reductants such as alkali 6 and alkali earth 7 metals, tin, 8-13 zinc, 14, 15 titanium, 16 and samarium reagents, 17-22 as well as under electrochemical 23-26 and photochemical 27-32 conditions.…”

“…In order to address these issues, a number of reductive coupling reactions of carbonyl derivatives involving a catalytic amount of early transition (e.g., Ti, V) or lanthanide metals (e.g., Sm) have been developed over the years and applied in natural product synthesis. 3, 33-38 Nonetheless, complementary strategies to generate ketyl and α-aminoalkyl anion radical intermediates and to harness their unusual reactivity are still highly sought after.…”

Total Synthesis of Jiadifenolide

“…[15] At this stage, with a view to effecting the crucial reductive cyclization reaction to close the central B-ring, alcohols 13 were oxidized to provide tricarbonyl 14. Disappointingly however, no productive cyclization of 14 could be induced under a range of conditions utilizing either SmI 2 [16] or alternative reagents, [17] returning only starting material or, under more forcing conditions, decomposition products. A similar situation was observed for alcohols 13.…”