Catalytic asymmetric cycloaddition reactions of enoldiazo compounds

Abstract

Review of recent advances in asymmetric catalytic cycloaddition reactions of silyl-protected enoldiazo compounds.

Synthesis of Chiral Tetrasubstituted Azetidines from Donor–Acceptor Azetines via Asymmetric Copper(I)‐Catalyzed Imido‐Ylide [3+1]‐Cycloaddition with Metallo‐Enolcarbenes

“…Analysis of substituent effects revealed the influence of the three variable substitution patterns on reactivity and enantioselectivity for [3+ +1]-cycloaddition as af unction of either or both electronic and steric factors.Increasing the size of the aliphatic chain at the g-position of enoldiazoacetate 1 led to an improvement in yield and enantiocontrol of the reaction [82 %yield, 75 % ee (Me, 3bb)to92% yield, 90 % ee (Et, 3cb); entries 1a nd 4i nT able 1].However,introduction of octyl, benzyl and isopropyl substituents resulted in reduced reactivity (70-78 %yield after 3days,entries [16][17][18], but with excellent enantioselectivity (90-95 % ee). These results suggest as ignificant steric effect by the g-substituent on enantiocontrol for cycloaddition, and the Et substituent at the g-position was chosen for further studies (diazo com- Ap roposed mechanism for [3+ +1]-cycloaddition of enoldiazoacetates with imido-sulfur ylides,c onsistent with our previous report on carbonyl-sulfur ylides [12] (Scheme 2) includes aC u I -catalyzed generation of Z-metallo-enolcarbene A that, depending on reaction conditions,can form the corresponding stable donor-acceptor cyclopropene B,w hich serves as ar esting state for Z-metallo-enolcarbene A, [13] or undergo an irreversible proto-decupration to produce diene C.T he major reaction pathway proceeds by nucleophilic addition of imido-sulfur ylide 2 onto the electrophilic vinylogous carbon of Z-metallo-enolcarbene A to generate vinylcopper-carbene intermediate D.D isplacement of the diphenyl sulfide,ag ood leaving group,f orms cyclic inter-mediate E,w hich upon dissociation of the copper catalyst produces donor-acceptor azetine 3.T he facility of N-arylimidosulfur ylides for this cycloaddition compared to Nacylimidosulfur ylides does not appear to be due to enhanced electron donation from the aryl group because of the limited influence by substituents on product yields and selectivities but, instead, on the inherently low nucleophilicity of the imido nitrogen of acylimidosulfur ylides.…”

Synthesis of Chiral Tetrasubstituted Azetidines from Donor–Acceptor Azetines via Asymmetric Copper(I)‐Catalyzed Imido‐Ylide [3+1]‐Cycloaddition with Metallo‐Enolcarbenes

“…Analysis of substituent effects revealed the influence of the three variable substitution patterns on reactivity and enantioselectivity for [3+ +1]-cycloaddition as af unction of either or both electronic and steric factors.Increasing the size of the aliphatic chain at the g-position of enoldiazoacetate 1 led to an improvement in yield and enantiocontrol of the reaction [82 %yield, 75 % ee (Me, 3bb)to92% yield, 90 % ee (Et, 3cb); entries 1a nd 4i nT able 1].However,introduction of octyl, benzyl and isopropyl substituents resulted in reduced reactivity (70-78 %yield after 3days,entries 16-18), but with excellent enantioselectivity (90-95 % ee). These results suggest as ignificant steric effect by the g-substituent on enantiocontrol for cycloaddition, and the Et substituent at the g-position was chosen for further studies (diazo com- Ap roposed mechanism for [3+ +1]-cycloaddition of enoldiazoacetates with imido-sulfur ylides,c onsistent with our previous report on carbonyl-sulfur ylides [12] (Scheme 2) includes aC u I -catalyzed generation of Z-metallo-enolcarbene A that, depending on reaction conditions,can form the corresponding stable donor-acceptor cyclopropene B,w hich serves as ar esting state for Z-metallo-enolcarbene A, [13] or undergo an irreversible proto-decupration to produce diene C.T he major reaction pathway proceeds by nucleophilic addition of imido-sulfur ylide 2 onto the electrophilic vinylogous carbon of Z-metallo-enolcarbene A to generate vinylcopper-carbene intermediate D.D isplacement of the diphenyl sulfide,ag ood leaving group,f orms cyclic inter-mediate E,w hich upon dissociation of the copper catalyst produces donor-acceptor azetine 3.T he facility of N-arylimidosulfur ylides for this cycloaddition compared to Nacylimidosulfur ylides does not appear to be due to enhanced electron donation from the aryl group because of the limited influence by substituents on product yields and selectivities but, instead, on the inherently low nucleophilicity of the imido nitrogen of acylimidosulfur ylides.…”

“…[12] This transformation was the first example in which the dipolar intermediate underwent nucleophilic displacement of aleaving group (R 2 S) to achieve product formation in am etal carbene [3 + n]-cycloaddition reaction. [13] Thehigh yields and enantioselectivities achieved in these reactions prompted us to investigate whether [3+ +1]-cycloaddition could also occur with "nitrene" donor species. However, N-acyl-imido sulfur ylides, [14] used in place of the N-acylsulfur ylides,w ith the same catalysts and under the same conditions,w ere unreactive even at elevated temperatures due to al ack of reactivity of the imido ylide.A ryl-, sulfonyl-, and acyl-azides were,s imilarly,u nable to undergo cycloaddition with metal carbenes formed from enoldiazoacetates and, instead, formed imine products.…”

Strain‐Induced Nucleophilic Ring Opening of Donor–Acceptor Cyclopropenes for Synthesis of Monosubstituted Succinic Acid Derivatives

“…1 [c] dichloromethane 92 2 [c] chloroform 90 3 [c] 1,2-dichloroethane84 4 [d] tetrahydrofuran 28 5 [d] tetrahydrofuran (50 8C, 30 min) 46 6 [d] tetrahydrofuran (50 8C, 60 min) 33 7 [c] diethyl ether 15 8 [c] toluene 54 9 [c] acetonitrile nd [e] [a] Reactions were carried out on a0 .30 mmol scale of 1a with 0.30 mmol of benzylaminea nd 0.30 mmol of water. [ b] ring opening could be performed enantioselectively via enantiomerically enriched DACP.A sp reviously reported, [19] donoracceptorc yclopropenes as the restings tate of metal carbenes undergo asymmetricc ycloaddition using transition metal complexes with chiral ligands to form structurally diverse carboand heterocycleswith high levels of enantiocontrol. We initially attempted to prepare the chiral cyclopropenes, but their two enantiomers were not clearly separated chromatographically.…”