Transformation of Racemic Azlactones into Enantioenriched Dihydropyrroles and Lactones Enabled by Hydrogen‐Bond Organocatalysis

Abstract

Azlactones, a potent building block for the synthesis of complex molecules, have been explored in an organocatalytic Mannich reaction with protected imines. In this study, azlactones containing a propargyl substituent were employed for the first time in organocatalysis so far. The catalytically active species responsible for high enantioselectivity with substrate containing such a small linear substituent is assembled in situ from a bifunctional thiourea, prone to dimerization, and an organic acid, as evidenced by DOSY NMR. The resulting α,β‐diamino acid derivatives were subjected to further derivatization: as an example, gold‐catalyzed intramolecular hydroamination of alkynes gave chiral spirocyclic dihydropyrrole. Alternatively, related squaramide catalyst enabled a Mannich reaction of azlactones with N‐aryl or alkyl glyoxylate imines. Reduction of these adducts gave access to 2,3‐diaminobutyrolactones or 2,3‐diamino‐1,4‐diol with a tertiary and a quaternary stereocenter.

Towards an Asymmetric β-Selective Addition of Azlactones to Allenoates

“…Azlactones 1 and allenoates 3 were synthesized according to previously published procedures [18,[42][43][44].…”

Towards an asymmetric β-selective addition of azlactones to allenoates

“…All reactions were carried out under argon atmosphere unless stated otherwise. Azlactones 1 and allenoates 3 were synthesized according to previously published procedures [ 18 , 42 – 44 ].…”

Bi-functional and mono-component organocatalysts for the ring-opening alternating co-polymerisation of anhydride and epoxide

“…A similar catalyst-acid adduct has been described for a thiourea amine bi-functional catalyst. 41,46 Thus, BA initiates the ROAC by ring-opening of PA in the presence of the bi-functional catalyst (cf. Scheme 3a) even at room temperature at the lower concentration used for the NMR study.…”