Tandem Application of C–C Bond-Forming Reactions with Reductive Ozonolysis

Abstract

Several variants of reductive ozonolysis, defined here as the in situ generation of aldehydes or ketones during ozonolytic cleavage of alkenes, are demonstrated to work effectively in tandem with a number of C-C bond-forming reactions. For reactions involving basic nucleophiles (1,2-addition of Grignard reagents, Wittig or Horner-Emmons olefinations, and directed Aldol reactions of lithium enolates) the one-pot process offers a rapid and high-yielding alternative to traditional two-step protocols.

Design and Synthesis of New Withaferin A Inspired Hedgehog Pathway Inhibitors

“…Nevertheless, we observed only a slight yield improvement (20 % over the two steps, Table 1, Entry 2). We also tried to condense the two steps in one‐pot, performing an ozonolysis in the presence of pyridine, and adding the Grignard's reagent to the reaction mixture, upon alkene consumptions, [41] but the yield was again unsatisfactory (23 %, Table 1, Entry 3). Similar stability issues were observed during the oxidative cleavage of compound 3’ .…”

Synthesis and late stage modifications of Cyl-derivatives

“…Thus, macrocycle 11 was subjected to an ozonolysis with subsequent Wittig reaction in a one-pot manner (Scheme 4). Performing the ozonolysis in presence of pyridine led to immediate reduction of the primary ozonide formed during the reaction [59].…”

Alkene ozonolysis in the academic lab

“…18 Reductive ozonolysis (no work-up): Aprotic ozonolyses conducted in the presence of Noxides or pyridine directly output anhydrous solutions of ketones and aldehydes without formation of peroxide intermediates; 19,20, the products can be directly applied as substrates for C-C bond-forming processes. 21 Ozonolysis in the presence of solubilized water also provides moderate to good yields of ketones and aldehydes. 22…”