Organocatalytic Remote Stereocontrolled 1,8-Additions of Thiazolones to Propargylic Aza-p-quinone Methides

Abstract

A remote stereocontrolled 1,8-conjugate addition of thiazolones to propargylic aza-p-quinone methides formed from propargylic alcohols has been developed with the aid of a chiral phosphoric acid, and this represents the first report on organocatalytic stereocontrolled 1,8-addition of propargylic aza-p-quinone methides. Notably, the remote stereocontrolled activation protocol enables the construction of vicinal sulfur-containing quaternary carbon stereocenters and axially chiral tetrasubstituted allenes and promotes the chemistry of chiral phosphoric acids.

Recent Advances in Azlactone Transformations

“…[52] The further one-pot protection of the free hydroxyl group was also described, allowing the access to the desired products, bearing two contiguous stereogenic centers (one of them being fully-substituted) generated in a single reaction step, in low to good yields (ranging from 44 to 81 %) and with poor to excellent stereocontrol (ranging from 1.7:1 to 20:1 d.r. [53] The desired vicinal axially chiral tetrasubstituted allenes (126, 127 and 128) were obtained in moderate to excellent yields (ranging from 65 to 94 %) and low to excellent stereoselectivities (> 20:1 d.r. Although the protocol was success-Scheme 28.…”

“…In 2016, Xu and co-workers reported the first organocatalytic approach to the enantioselective hetero-Diels-Alder reaction between in situ generated γ-enolate of Erlenmeyer azlactone Scheme (53) and α-keto esters (54) or ,γ-unsaturated α-keto esters (55). [37] By the use of cinchonine derived tertiary aminethiourea catalyst, this approach allowed the access to highly functionalized dihydropyranones (56 and 57) bearing a new fully-substituted stereogenic center (Scheme 15).…”

Recent Advances in Catalytic Asymmetric Reactions of Thiazolones, Rhodanines and Their Derivatives

“…To explore the scope of remote stereocontrolled 1,8-addition, we then examined the reactions between 5H-thiazol-4-ones 65 and propargylic aza-p-quinone methides 66 (Scheme 19). [26] The chiral phosphoric acid C22 enabled the formation of the axially chiral tetrasubstituted allenes containing chiral thiazolone skeleton 67 in 80-96% yields with 80-> 99% ee and > 20:1 dr. Notably, the compete reaction of electronrich dienamine system was successfully inhibited.…”

Synthesis of Pyrrolo[1,2-a]indoles via (3+2)-Annulations of (Aza)-para-Quinone Methides with Indoles

“…[1][2][3] Chemically, compared with the fact that many methodologies have been extensively disclosed for the 1,6-conjugate addition of p-QMs, 4,5 however, less attention has been devoted to the more challenging 1,8-conjugate additions. [6][7][8][9] In 2017, the Sun group reported the asymmetric 1,8-conjugate addition of p-QMs, generated in situ from propargylic alcohols, in the first reported synthesis of chiral tetrasubstituted allenes (Scheme 1a). 6 Thereafter, the Sun and Li groups demonstrated the 1,8-conjugate addition of aza-para-quinone methides with 1,3-dicarbonyl nucleophiles 8 and thiazolones, 9 respectively.…”

“…[6][7][8][9] In 2017, the Sun group reported the asymmetric 1,8-conjugate addition of p-QMs, generated in situ from propargylic alcohols, in the first reported synthesis of chiral tetrasubstituted allenes (Scheme 1a). 6 Thereafter, the Sun and Li groups demonstrated the 1,8-conjugate addition of aza-para-quinone methides with 1,3-dicarbonyl nucleophiles 8 and thiazolones, 9 respectively. The Wang group realized the asymmetric catalytic 1,8-addition/Diels-Alder cascade reaction of para-quinone methides with -naphthols to construct complex polycyclic compounds (Scheme 1b).…”