Rh-Catalyzed Intermolecular Reactions of Cyclic α-Diazocarbonyl Compounds with Selectivity over Tertiary C–H Bond Migration

Intermolecular Rh-catalyzed reactions of cyclic α-diazocarbonyl compounds with chemoselectivity over β-hydride elimination are described. These methods represent the first general intermolecular reactions of Rh-carbenoids that are selective over tertiary β-C–H bond migration. Successful transformations include cyclopropanation, cyclopropenation, and various X–H insertion reactions with a broad scope of substrates. We propose that the intermolecular approach of substrates to carbenes from acyclic diazo precursors may be relatively slow due to a steric interaction with the ester function, which is perpendicular to the π-system of the carbene. For carbenes derived from five- and six-membered cyclic α-diazocarbonyls, it is proposed that the carbene is constrained to be more conjugated with the carbonyl, thereby relieving the steric interaction for intermolecular reactions, and accelerating the rate of intermolecular reactivity relative to intramolecular β-hydride migration. However, attempts to use α-diazo-β-ethylcaprolactone in intermolecular cyclopropanation with styrene were unsuccessful. It is proposed that the conformational flexibility of the seven-membered ring allows the carbonyl to be oriented perpendicular to Rh-carbene. The significant intermolecular interaction between the carbonyl and approaching substrate is in agreement with the poor ability of α-diazo-β-ethylcaprolactone to participate in intermolecular cyclopropanation reactions. DFT calculations provide support for the mechanistic proposals that are described

Rh-Catalyzed Intermolecular Reactions of Cyclic α-Diazocarbonyl Compounds with Selectivity over Tertiary C–H Bond Migration

Intermolecular Rh-catalyzed reactions of cyclic α-diazocarbonyl compounds with chemoselectivity over β-hydride elimination are described. These methods represent the first general intermolecular reactions of Rh-carbenoids that are selective over tertiary β-C–H bond migration. Successful transformations include cyclopropanation, cyclopropenation, and various X–H insertion reactions with a broad scope of substrates. We propose that the intermolecular approach of substrates to carbenes from acyclic diazo precursors may be relatively slow due to a steric interaction with the ester function, which is perpendicular to the π-system of the carbene. For carbenes derived from five- and six-membered cyclic α-diazocarbonyls, it is proposed that the carbene is constrained to be more conjugated with the carbonyl, thereby relieving the steric interaction for intermolecular reactions, and accelerating the rate of intermolecular reactivity relative to intramolecular β-hydride migration. However, attempts to use α-diazo-β-ethylcaprolactone in intermolecular cyclopropanation with styrene were unsuccessful. It is proposed that the conformational flexibility of the seven-membered ring allows the carbonyl to be oriented perpendicular to Rh-carbene. The significant intermolecular interaction between the carbonyl and approaching substrate is in agreement with the poor ability of α-diazo-β-ethylcaprolactone to participate in intermolecular cyclopropanation reactions. DFT calculations provide support for the mechanistic proposals that are described

Rh(II)-Catalyzed Reactions of Diazoesters with Organozinc Reagents

Rh­(II)-catalyzed reactions of diazoesters with organozinc reagents are described. Diorganozinc reagents participate in reactions with diazo compounds by two distinct, catalyst-dependent mechanisms. With bulky diisopropylethyl acetate ligands, the reaction mechanism is proposed to involve initial formation of a Rh-carbene and subsequent carbozincation to give a zinc enolate. With Rh₂(OAc)₄, it is proposed that initial formation of an azine precedes 1,2-addition by an organozinc reagent. This straightforward route to the hydrazone products provides a useful method for preparing chiral quaternary α-aminoesters or pyrazoles via the Paul–Knorr condensation with 1,3-diketones. Crossover and deuterium labeling experiments provide evidence for the mechanisms proposed

Selective Syntheses of Δ^α,β and Δ^β,γ Butenolides from Allylic Cyclopropenecarboxylates via Tandem Ring Expansion/[3,3]-Sigmatropic Rearrangements

Allylic cyclopropenecarboxylates undergo ring expansion reactions to give 2-allyloxyfuran intermediates, which subsequently rearrange to Δ^β,γ butenolides via a Claisen rearrangement or to the corresponding Δ^α,β butenolides via further Cope rearrangement. Also described are methods for chirality transfer in the rearrangement of nonracemic allylic esters

Selective Syntheses of Δ^α,β and Δ^β,γ Butenolides from Allylic Cyclopropenecarboxylates via Tandem Ring Expansion/[3,3]-Sigmatropic Rearrangements

Allylic cyclopropenecarboxylates undergo ring expansion reactions to give 2-allyloxyfuran intermediates, which subsequently rearrange to Δ^β,γ butenolides via a Claisen rearrangement or to the corresponding Δ^α,β butenolides via further Cope rearrangement. Also described are methods for chirality transfer in the rearrangement of nonracemic allylic esters

Rh-Catalyzed Intermolecular Reactions of Cyclic α-Diazocarbonyl Compounds with Selectivity over Tertiary C–H Bond Migration

Intermolecular Rh-catalyzed reactions of cyclic α-diazocarbonyl compounds with chemoselectivity over β-hydride elimination are described. These methods represent the first general intermolecular reactions of Rh-carbenoids that are selective over tertiary β-C–H bond migration. Successful transformations include cyclopropanation, cyclopropenation, and various X–H insertion reactions with a broad scope of substrates. We propose that the intermolecular approach of substrates to carbenes from acyclic diazo precursors may be relatively slow due to a steric interaction with the ester function, which is perpendicular to the π-system of the carbene. For carbenes derived from five- and six-membered cyclic α-diazocarbonyls, it is proposed that the carbene is constrained to be more conjugated with the carbonyl, thereby relieving the steric interaction for intermolecular reactions, and accelerating the rate of intermolecular reactivity relative to intramolecular β-hydride migration. However, attempts to use α-diazo-β-ethylcaprolactone in intermolecular cyclopropanation with styrene were unsuccessful. It is proposed that the conformational flexibility of the seven-membered ring allows the carbonyl to be oriented perpendicular to Rh-carbene. The significant intermolecular interaction between the carbonyl and approaching substrate is in agreement with the poor ability of α-diazo-β-ethylcaprolactone to participate in intermolecular cyclopropanation reactions. DFT calculations provide support for the mechanistic proposals that are described

Rh-Catalyzed Intermolecular Reactions of Cyclic α-Diazocarbonyl Compounds with Selectivity over Tertiary C–H Bond Migration

Intermolecular Rh-catalyzed reactions of cyclic α-diazocarbonyl compounds with chemoselectivity over β-hydride elimination are described. These methods represent the first general intermolecular reactions of Rh-carbenoids that are selective over tertiary β-C–H bond migration. Successful transformations include cyclopropanation, cyclopropenation, and various X–H insertion reactions with a broad scope of substrates. We propose that the intermolecular approach of substrates to carbenes from acyclic diazo precursors may be relatively slow due to a steric interaction with the ester function, which is perpendicular to the π-system of the carbene. For carbenes derived from five- and six-membered cyclic α-diazocarbonyls, it is proposed that the carbene is constrained to be more conjugated with the carbonyl, thereby relieving the steric interaction for intermolecular reactions, and accelerating the rate of intermolecular reactivity relative to intramolecular β-hydride migration. However, attempts to use α-diazo-β-ethylcaprolactone in intermolecular cyclopropanation with styrene were unsuccessful. It is proposed that the conformational flexibility of the seven-membered ring allows the carbonyl to be oriented perpendicular to Rh-carbene. The significant intermolecular interaction between the carbonyl and approaching substrate is in agreement with the poor ability of α-diazo-β-ethylcaprolactone to participate in intermolecular cyclopropanation reactions. DFT calculations provide support for the mechanistic proposals that are described

Rh-Catalyzed Intermolecular Reactions of Cyclic α-Diazocarbonyl Compounds with Selectivity over Tertiary C–H Bond Migration

Intermolecular Rh-catalyzed reactions of cyclic α-diazocarbonyl compounds with chemoselectivity over β-hydride elimination are described. These methods represent the first general intermolecular reactions of Rh-carbenoids that are selective over tertiary β-C–H bond migration. Successful transformations include cyclopropanation, cyclopropenation, and various X–H insertion reactions with a broad scope of substrates. We propose that the intermolecular approach of substrates to carbenes from acyclic diazo precursors may be relatively slow due to a steric interaction with the ester function, which is perpendicular to the π-system of the carbene. For carbenes derived from five- and six-membered cyclic α-diazocarbonyls, it is proposed that the carbene is constrained to be more conjugated with the carbonyl, thereby relieving the steric interaction for intermolecular reactions, and accelerating the rate of intermolecular reactivity relative to intramolecular β-hydride migration. However, attempts to use α-diazo-β-ethylcaprolactone in intermolecular cyclopropanation with styrene were unsuccessful. It is proposed that the conformational flexibility of the seven-membered ring allows the carbonyl to be oriented perpendicular to Rh-carbene. The significant intermolecular interaction between the carbonyl and approaching substrate is in agreement with the poor ability of α-diazo-β-ethylcaprolactone to participate in intermolecular cyclopropanation reactions. DFT calculations provide support for the mechanistic proposals that are described

Rh(II)-Catalyzed Reactions of Diazoesters with Organozinc Reagents

Rh­(II)-catalyzed reactions of diazoesters with organozinc reagents are described. Diorganozinc reagents participate in reactions with diazo compounds by two distinct, catalyst-dependent mechanisms. With bulky diisopropylethyl acetate ligands, the reaction mechanism is proposed to involve initial formation of a Rh-carbene and subsequent carbozincation to give a zinc enolate. With Rh₂(OAc)₄, it is proposed that initial formation of an azine precedes 1,2-addition by an organozinc reagent. This straightforward route to the hydrazone products provides a useful method for preparing chiral quaternary α-aminoesters or pyrazoles via the Paul–Knorr condensation with 1,3-diketones. Crossover and deuterium labeling experiments provide evidence for the mechanisms proposed

Facially Selective Cu-Catalyzed Carbozincation of Cyclopropenes Using Arylzinc Reagents Formed by Sequential I/Mg/Zn Exchange

Described is a Cu-catalyzed directed carbozincation of cyclopropenes with organozinc reagents prepared by I/Mg/Zn exchange. This protocol broadens the scope with respect to functional group tolerance and enables use of aryl iodide precursors, rather than purified diorganozinc precursors. Critical to diastereoselectivity of the carbozincation step is the removal of magnesium halide salts after transmetalation with ZnCl₂