Copper-Catalyzed Hydroamination: Enantioselective Addition of Pyrazoles to Cyclopropenes

Abstract

Chiral N-cyclopropyl pyrazoles and structurally related heterocycles are prepared using an earth-abundant copper catalyst under mild reaction conditions with high regio-, diastereo-, and enantiocontrol. The observed N 2 :N 1 regioselectivity favors the more hindered nitrogen of the pyrazole. Experimental and DFT studies support a unique mechanism that features a five-centered aminocupration.

Controlled and Regioselective Ring-Opening Polymerization for Poly(disulfide)s by Anion-Binding Catalysis

“…The fractional reaction order can be a result of off-cycle ground-state associations, − which is true in our current system that multiple association equilibrium exists, as depicted in Figure C. Although a rate law based on Figure C would not have a simple analytical expression as eq , we noticed that the experimental rate law presents positive reaction orders that do not exceed unity for all three species.…”

Borane-Catalyzed C–F Bond Functionalization of gem-Difluorocyclopropenes Enables the Synthesis of Orphaned Cyclopropanes

“…, C–F bond cleavage and C–C bond formation) would result in a net substitution reaction analogous to those published by Corey and Posner on dibromocyclopropane derivatives. The proposed C–F bond functionalization of difluorocyclopropenes stands in direct contrast to carbometallation and hydrogenation reactions of cyclopropenes, which functionalize the C–C double bond of cyclopropenes by virtue of strain, and provides an avenue to overcome deleterious ring-opening reactions of the highly reactive intermediates formed in such reactions.…”

Photoredox/Copper-Catalyzed One-Pot Aminoalkylation/Cyclization of Alkenes with Primary Amines to Synthesize Polysubstituted γ-Lactams

“…As a promising alternative, Cu−amido complexes, 9 which were first isolated and characterized by Gunnoe, 10 that catalyze the addition of primary amines to electron-deficient double bonds 11 (i.e., Michael acceptors, such as olefins, 12 allenes, 13 nitrostyrenes, 14 works, we envisioned that Cu−amido complexes formed by primary amines can be selectively trapped by orthoquinone intermediates, avoiding the alkylation of primary amines with α-Br-carbonyl esters, follow by cyclization to form γ-lactams (Scheme 1c). Herein, we report a photoredox/coppercatalyzed one-pot three-component reaction for the construction of γ-lactams via aminoalkylation/cyclization of alkenes with primary amines.…”

“…When 2-hydroxystyrene was replaced by styrene (6), only elimination product 7 could be obtained under the standard conditions (Scheme 2a). To further verify whether hydroxyl groups can serve as directing groups, 2-(2-vinylpheneyl)pyridine ( 9), 2-allyphenol (10), and 2-methoxystyrene (12) were evaluated, and no target products was generated. In addition, 3-hydroxystyrene (11) cannot give the corresponding products, while 4-hydroxystyrene produced branched product 4s (Table 2).…”

“…As a promising alternative, Cu–amido complexes, which were first isolated and characterized by Gunnoe, that catalyze the addition of primary amines to electron-deficient double bonds (i.e., Michael acceptors, such as olefins, allenes, nitrostyrenes, and azabenzonobornadienes) can offer the possibility of more ambient reaction conditions and enhanced control of reaction selectivity (Scheme b). Inspired by these works, we envisioned that Cu–amido complexes formed by primary amines can be selectively trapped by orthoquinone intermediates, avoiding the alkylation of primary amines with α-Br-carbonyl esters, follow by cyclization to form γ-lactams (Scheme c).…”