First Organocatalyzed Asymmetric Michael Addition of Aldehydes to Vinyl Sulfones

Abstract

[reaction: see text] The first asymmetric direct Michael addition of aldehydes to vinyl sulfones catalyzed by N-iPr-2,2'-bipyrrolidine is described. 1,4-Adducts are obtained in good yields and enantioselectivities. The determination of absolute configuration allowed us to postulate a Si,Si transition state model, as shown previously for nitroolefins.

Aminal–Pyrrolidine Organocatalysts – Highly Efficient and Modular Catalysts for α‐Functionalization of Carbonyl Compounds

“…1 H NMR (400 MHz, CDCl 3 ): δ = 0.94 (d, J = 6.8 Hz, 3 H, Me), 0.99 (d, J = 7.1 Hz, 3 H, Me), 2.11–2.17 (m, 2 H, CH 2 ), 2.47–2.54 (m, 1 H, OH), 2.90–2.94 (m, 1 H, CHCO), 4.68–4.71 (dd, J = 9.1, 3.1 Hz, 1 H, CHSO 2 ), 7.53–7.60 (m, 4 H, Ph), 7.67–7.73 (m, 2 H, Ph), 7.88–7.96 (m, 4 H, Ph), 9.59 (s, 1 H, CHO) ppm. Spectroscopic data are in agreement with those in the literature 11a…”

Aminal–Pyrrolidine Organocatalysts – Highly Efficient and Modular Catalysts for α‐Functionalization of Carbonyl Compounds

“…1 H NMR (400 MHz, CDCl 3 ): δ = 0.94 (d, J = 6.8 Hz, 3 H, Me), 0.99 (d, J = 7.1 Hz, 3 H, Me), 2.11–2.17 (m, 2 H, CH 2 ), 2.47–2.54 (m, 1 H, OH), 2.90–2.94 (m, 1 H, CHCO), 4.68–4.71 (dd, J = 9.1, 3.1 Hz, 1 H, CHSO 2 ), 7.53–7.60 (m, 4 H, Ph), 7.67–7.73 (m, 2 H, Ph), 7.88–7.96 (m, 4 H, Ph), 9.59 (s, 1 H, CHO) ppm. Spectroscopic data are in agreement with those in the literature 11a…”

Skeletal Transformations Observed in the Reaction of a Tricyclic Thymine Nucleoside with Dicarbonyl Compounds

“…Interestingly, a second C–C bond is formed in this reaction, resulting in a new six-membered ring. Our own work, together with literature precedents showing the participation of enamines in asymmetric conjugate additions to a vinyl sulfone (Michael acceptor), gives strong support to this attack. ,− …”

3,3‘-Bimorpholine Derivatives as a New Class of Organocatalysts for Asymmetric Michael Addition

“…The preferred diastereo- and enantioselectivity could be explained in terms of the potential transition states Re , Re or Si , Si for the 1,4-addition using i PBM 2a as organocatalyst (Scheme ). The anti enamine would be formed selectively and would react with nitroolefins via an acyclic synclinal transition state described by Seebach, in which there are favorable electrostatic interactions between the nitrogen of the enamine and the nitro group, as shown previously with 2,2‘-bipyrrolidine derivatives. ,

2 Proposed Transition State Model

…”

“…Finally, the results of a preliminary study have demonstrated that i PBM 2a has also catalyzed Michael addition of aldehydes to 1,1-bis(benzenesulfonyl)ethylene 8 . Under the reaction conditions described previously, addition of isovaleraldehyde 3a to vinyl sulfone 8 resulted in the formation of the adduct 9 in 79% yield and 55% ee (Scheme ).

3 Asymmetric Conjugate Addition of Isovaleraldehyde 3 a to Vinyl Sulfone 8 Catalyzed by i PBM

…”

Aminal–Pyrrolidine Organocatalysts – Highly Efficient and Modular Catalysts for α‐Functionalization of Carbonyl Compounds

“…1 H NMR (400 MHz, CDCl 3 ): δ = 0.94 (d, J = 6.8 Hz, 3 H, Me), 0.99 (d, J = 7.1 Hz, 3 H, Me), 2.11–2.17 (m, 2 H, CH 2 ), 2.47–2.54 (m, 1 H, OH), 2.90–2.94 (m, 1 H, CHCO), 4.68–4.71 (dd, J = 9.1, 3.1 Hz, 1 H, CHSO 2 ), 7.53–7.60 (m, 4 H, Ph), 7.67–7.73 (m, 2 H, Ph), 7.88–7.96 (m, 4 H, Ph), 9.59 (s, 1 H, CHO) ppm. Spectroscopic data are in agreement with those in the literature 11a…”

Skeletal Transformations Observed in the Reaction of a Tricyclic Thymine Nucleoside with Dicarbonyl Compounds

“…Interestingly, a second C–C bond is formed in this reaction, resulting in a new six-membered ring. Our own work, together with literature precedents showing the participation of enamines in asymmetric conjugate additions to a vinyl sulfone (Michael acceptor), gives strong support to this attack. ,− …”

3,3‘-Bimorpholine Derivatives as a New Class of Organocatalysts for Asymmetric Michael Addition

“…The preferred diastereo- and enantioselectivity could be explained in terms of the potential transition states Re , Re or Si , Si for the 1,4-addition using i PBM 2a as organocatalyst (Scheme ). The anti enamine would be formed selectively and would react with nitroolefins via an acyclic synclinal transition state described by Seebach, in which there are favorable electrostatic interactions between the nitrogen of the enamine and the nitro group, as shown previously with 2,2‘-bipyrrolidine derivatives. ,

2 Proposed Transition State Model

…”

“…Finally, the results of a preliminary study have demonstrated that i PBM 2a has also catalyzed Michael addition of aldehydes to 1,1-bis(benzenesulfonyl)ethylene 8 . Under the reaction conditions described previously, addition of isovaleraldehyde 3a to vinyl sulfone 8 resulted in the formation of the adduct 9 in 79% yield and 55% ee (Scheme ).

3 Asymmetric Conjugate Addition of Isovaleraldehyde 3 a to Vinyl Sulfone 8 Catalyzed by i PBM

…”

Aminal–Pyrrolidine Organocatalysts – Highly Efficient and Modular Catalysts for α‐Functionalization of Carbonyl Compounds

“…1 H NMR (400 MHz, CDCl 3 ): δ = 0.94 (d, J = 6.8 Hz, 3 H, Me), 0.99 (d, J = 7.1 Hz, 3 H, Me), 2.11–2.17 (m, 2 H, CH 2 ), 2.47–2.54 (m, 1 H, OH), 2.90–2.94 (m, 1 H, CHCO), 4.68–4.71 (dd, J = 9.1, 3.1 Hz, 1 H, CHSO 2 ), 7.53–7.60 (m, 4 H, Ph), 7.67–7.73 (m, 2 H, Ph), 7.88–7.96 (m, 4 H, Ph), 9.59 (s, 1 H, CHO) ppm. Spectroscopic data are in agreement with those in the literature 11a…”

Skeletal Transformations Observed in the Reaction of a Tricyclic Thymine Nucleoside with Dicarbonyl Compounds

“…Interestingly, a second C–C bond is formed in this reaction, resulting in a new six-membered ring. Our own work, together with literature precedents showing the participation of enamines in asymmetric conjugate additions to a vinyl sulfone (Michael acceptor), gives strong support to this attack. ,− …”

3,3‘-Bimorpholine Derivatives as a New Class of Organocatalysts for Asymmetric Michael Addition

“…The preferred diastereo- and enantioselectivity could be explained in terms of the potential transition states Re , Re or Si , Si for the 1,4-addition using i PBM 2a as organocatalyst (Scheme ). The anti enamine would be formed selectively and would react with nitroolefins via an acyclic synclinal transition state described by Seebach, in which there are favorable electrostatic interactions between the nitrogen of the enamine and the nitro group, as shown previously with 2,2‘-bipyrrolidine derivatives. ,

2 Proposed Transition State Model

…”

“…Finally, the results of a preliminary study have demonstrated that i PBM 2a has also catalyzed Michael addition of aldehydes to 1,1-bis(benzenesulfonyl)ethylene 8 . Under the reaction conditions described previously, addition of isovaleraldehyde 3a to vinyl sulfone 8 resulted in the formation of the adduct 9 in 79% yield and 55% ee (Scheme ).

3 Asymmetric Conjugate Addition of Isovaleraldehyde 3 a to Vinyl Sulfone 8 Catalyzed by i PBM

…”