Enantioselective Gold‐Catalyzed Functionalization of Unreactive sp³ CH Bonds through a Redox–Neutral Domino Reaction

Abstract

Selectivity is golden: The first asymmetric redox-neutral domino reaction catalyzed by gold that results in the direct functionalization of unreactive sp(3) C-H bonds has been reported. This method consists of a heterocyclization/1,5-hydride transfer/cyclization reaction and provides synthetically valuable azepines with high enantioselectivities and in high yields (Tf = triflate; see scheme).

Au‐ and Pt‐Catalyzed CH Activation/Functionalizations for the Synthesis of Heterocycles

“…The resulting furanfused azepines 154 could be obtained in good to excellent yields with satisfactory enantioselectivity (Scheme 12.67) [71]. …”

Transition-Metal-Catalyzed Functionalization of C(sp3)&singleBond;H Bonds of Amines

“…Transition-metal catalysts such as complexes of gold [132,133] and platinum, [134] as well as those of cobalt [135] and palladium, [136] are used efficiently in cyclization reactions involving the intramolecular [1,5] transfer of a hydride onto a terminal alkyne or an electron-deficient alkene, followed by ring closure on the resulting stabilized carbocation (iminium-type) intermediate (Scheme 61). [132][133][134][135][136] The most typical examples of this internal redox process involve the coupling of C(sp 3 )-H bonds with double bonds (Scheme 61). [133,135,[137][138][139][140][141][142][143][144] In this process, activation of an electron-deficient alkene by a Lewis acid or transition metal initiates a 1,5-hydride transfer and the formation of a stabilized cation, which induces cyclization to form a C-C bond.…”

“…[132][133][134][135][136] The most typical examples of this internal redox process involve the coupling of C(sp 3 )-H bonds with double bonds (Scheme 61). [133,135,[137][138][139][140][141][142][143][144] In this process, activation of an electron-deficient alkene by a Lewis acid or transition metal initiates a 1,5-hydride transfer and the formation of a stabilized cation, which induces cyclization to form a C-C bond. This strategy has also been extended to the coupling of C(sp 3 )-H bonds with triple bonds (Scheme 61).…”

“…[132][133][134]136] Unactivated terminal alkynes also serve as hydride acceptors in the through-space hydride transfer and undergo catalytic intramolecular hydroalkylation at the a-position of amines, providing rapid access to bicyclic products (Scheme 61). [134] Scheme 61 Transition-Metal-Catalyzed Cyclization of C(sp 3 )-H Bonds via Hydride Transfer [132][133][134][135][136][137][138][139][140][141][142][143][144] The catalytic alkenylation of cyclic amines via through-space hydride transfer affords products of high synthetic value. Out of various platinum salts tested for the alkenylation of pyrrolidine derivatives 183 (n = 1) to give the products 184 (n = 1), best results are obtained by using platinum(IV) iodide as catalyst (Table 38).…”

Recent achievements in intermolecular sp3 C–H bond functionalization of organic compounds by superelectrophilic trihalomethyl metal complex

“…Examples of intramolecular functionalization initiated by Lewis acids and occurring via hydride shift/ring closure sequences are presented in Ref. [8][9][10].…”