Pyridine Is an Organocatalyst for the Reductive Ozonolysis of Alkenes

Abstract

Whereas the cleavage of alkenes by ozone typically generates peroxide intermediates that must be decomposed in an accompanying step, ozonolysis in the presence of pyridine directly generates ketones or aldehydes through a process that neither consumes pyridine nor generates any detectable peroxides. The reaction is hypothesized to involve nucleophile-promoted fragmentation of carbonyl oxides via formation of zwitterionic peroxyacetals.

An enantioselective enzymatic desymmetrization route to hexahydro-4H-furopyranol, a high-affinity ligand for HIV-1 protease inhibitors

“…Oxidative cleavage of the olefin by ozonolysis in the presence of pyridine as the organocatalyst 26 in CH 2 Cl 2 at −78 °C, followed by reduction of the resulting crude dialdehyde with sodium borohydride at 0 °C to 23 °C afforded diol 13 . Treatment of diol 13 with a catalytic amount (30 mol %) of CSA in CH 2 Cl 2 at 23 °C for 2 h furnished bicyclic acetal 14 via lactol intermediate 13A in 56% yield over 3 steps.…”

Rh(III)-Catalyzed C–H Bond Addition/Amine-Mediated Cyclization of Bis-Michael Acceptors

“…Ozonolysis of 6 in the presence of pyridine yielded the 1,4-dicarbonyl 7 in good yield. 11 Paal- Knorr furan and pyrrole synthesis then afforded the piperidine-fused furan 8 and pyrrole 9 in 80% and 91% yield, respectively.…”

Short Stereoselective Synthesis of the Phytophthora Universal Mating Hormone α1 Using Lithiation/Borylation Reactions

“…Selective ozonolysis of the electron-rich trisubstituted olefin in 7 in the presence of the enone was achieved using pyridine as an additive. [11] In the presence of pyridine, the chemoselectivity of the reaction was easier to control, and since ozonides are not intermediates in the ozonolysis it is also safer. Chemoselective reduction of the aldehyde with LiAlH(OtBu) 3 gave the desired alcohol 10 in 74 % yield from 7 in a one-pot operation.…”