The Barton‐McCombie Reaction

Abstract

Deoxygenations of alcohols, i.e., processes that replace a hydroxyl group with hydrogen at a saturated carbon, find applications in both total synthesis and the systematic modifications of natural products. They may also be employed to introduce deuterium or tritium in a site‐specific manner. Reductive methods that involve ionic or highly polarized reagents or intermediates can be limited in their applicability: for example, competing reaction pathways including cationic rearrangements and anionic eliminations may be encountered in sterically hindered systems with substrates bearing heteroatoms close to the center undergoing reduction. As evidenced by developments over the last few decades, methods that involve the generation and direct quenching via hydrogen atom abstraction of the derived, carbon‐centered radical typically show the greatest tolerance for the presence of other functional groups and for variations in both the steric acid and the electronic environment in the vicinity of the center undergoing deoxygenation. Derivatization of the hydroxyl is a prerequisite, the determinant factors for efficient formation of the deoxygenated product lies in the ability of the combination of the substrate and reagents to induce homolysis of the C‐O bond coupled with the induction of homolysis to rapidly reduce a free radical by hydrogen donation, thereby propagating an efficient chain process. A high‐yielding way to realize this sequence was first described by Barton McCombie using the free‐radical chain reaction of O ‐thioacyl derivatives of secondary alcohols with tri‐ n ‐butylstannane. This chapter provides a detailed description and comparison of the combinations of substrates and reagents that will bring about these processes and provides a summary and evaluation of alternative deoxygenation methods. Mechanistic and stereochemical issues set out the scope and limitations of these processes with respect to both the thioacylation and reduction steps and exemplify some applications to both total synthesis and the modification of natural products.

Visible‐Light Photocatalysis as an Enabling Tool for the Functionalization of Unactivated C(sp3)‐Substrates

“…The Barton-McCombie deoxygenation reaction [77][78][79] is one of the best-known radical reactions and most important synthetic tools for deoxygenation of complex molecules. Like the related Barton decarboxylation reaction described above, it requires the preparation of an active xanthate ester and the use of toxic, expensive, or hazardous radical initiators.…”

Convenient Access to 2‐β‐d‐Glucopyranosylpyridines by Using Bohlmann–Rahtz Heteroannulation

“…With substrates, 24g – i , no benzylic deoxygenation and debenzylation were observed under the same reaction conditions. With these substrates, we adopted a two‐step reaction sequence involving Barton–McCombie deoxygenation method and Lewis acid mediated debenzylation . The alcohol 24f was converted into the thiocarbonyl derivative using 1,1‐thiocarbonyldiimidazole (TCDI), followed by treatment with n Bu 3 SnH in the presence of catalytic amount of AIBN.…”

Diastereoconvergent Synthesis of (–)‐Paroxetine

“…Attempts to carry out the deoxygenation of tertiary alcohols 2 and 6 under classical Barton–McCombie conditions failed, because the respective xanthates (not shown) either decomposed or hydrolyzed to give the respective alcohol precursors. Therefore, the deoxygenation was carried out via cyclic thiocarbonates .…”