SmI2-catalysed cyclization cascades by radical relay

Abstract

Radical cyclization cascades are powerful tools used to construct the complex three-dimensional structures of some of society's most prized molecules. Since its first use forty years ago, SmI 2 has been used extensively for reductive radical cyclizations. Unfortunately, SmI 2 must almost always be used in significant excess thus raising issues of cost and waste. Here we have developed radical cyclization cascades that are catalyzed by SmI 2 and that exploit a radical relay/electron-catalysis strategy. The approach negates the need for a super-stoichiometric co-reductant and requires no additives. Complex cyclic products, including products of dearomatization, containing up to four contiguous stereocenters are obtained in excellent yield. Mechanistic studies support a single-electron transfer radical mechanism. Our strategy provides a long-awaited solution to the problem of how to avoid the need for stoichiometric amounts of SmI 2 and establishes a conceptual platform upon which other catalytic radical processes using the ubiquitous reducing agent can be built.

SmI2-Catalyzed Intermolecular Coupling of Cyclopropyl Ketones and Alkynes: A Link between Ketone Conformation and Reactivity

“…Attempted coupling with benzofuran was unsuccessful, and starting materials were recovered. 6 For ineffective coupling partners, it appears that trapping of the radical formed upon reversible fragmentation of the cyclopropyl ring is inefficient and starting ketone is recovered. See the Supporting Information for further details and a table of unsuccessful coupling partners.…”

“…We recently reported a radical-relay approach to catalysis with SmI 2 that negates the need for coreductants and additives: cyclopropyl ketones underwent catalytic radical cyclization to give complex bicyclic ketones. 6 We envisaged that unprecedented and more-challenging, intermolecular couplings might be possible using catalytic SmI 2 , as the reduction of radical intermediates A would be less-problematic at lower concentrations of the reagent.…”

Reversible electron transfer in organolanthanide chemistry

“…This is particularly interesting since it means that a reversible electron transfer has occurred. Such reactivity is not unique but is rare in organolanthanides [10]. It mostly shows that electron(s) can be selectively stored on ligand centers and re-used for further reactivity at an oxidized metal center.…”

“…The synthesis of more elaborated complexes such as substituted biscyclopentadienyl complexes [3, 4] allowed developing a very rich chemistry from small molecule activation (including N 2 ) [5], reversible C-C coupling reactions [6, 7], C-H activation [8] and many other useful reactions [9]. In agreement with their accessible redox potential, Yb and Sm are the two elements that are the mostly used and recently, efficient applications have been published [10]. Other divalent complexes with non-classical lanthanides [11] have also been reported, Tm being the next one on the list of the commonly used divalent lanthanides [12].…”

Recent advances in the chemistry of ketyl radicals

“…16 Against this backdrop, Procter and co-workers have recently reported efficient SmI 2 -catalyzed cyclizations that involve the generation of ketyl radical anions by SET reduction of ketone carbonyl groups by SmI 2 and that proceed under mild conditions and in the absence of stoichiometric co-reductants. 17 In 2012, Procter and co-workers reported the reductive cyclization of alkenyl-, alkynyl-, and allenyllactones to form oxygenated cycloheptanes using the SmI 2 -H 2 O system; allenyllactone substrates selectively produced cycloheptanes bearing three new stereocentres (Scheme 5). 18 A variety of substituents on the lactone ring, and on the allene, were tolerated in these processes and products were obtained in good yield and with excellent diastereocontrol.…”