Organocatalytic Asymmetric Additions to meso‐Anhydrides and Azlactones

Abstract

This review charts the recent progress of two related, yet distinct organocatalytic processes: the desymmetrisation of meso‐anhydrides and the dynamic kinetic resolution of azlactones. Driven by recent advances in catalyst design, both these processes have undergone something of a renaissance in recent years and are now becoming very powerful and versatile synthetic methodologies. The material is presented in a critical fashion and the material is organised by reaction type and catalyst class.

Catalytic enantioselective reductive desymmetrisation of achiral and meso compounds

“…The functionalised chiral (bi)cyclic hydroxyamides 24 were obtained with excellent ees (from 93 to 97%; four examples). The substituents on the ring system did not 25 interfere with the catalytic activity. The -hydroxycarboxamides 26 were efficiently obtained by hydrogenating monocyclic achiral six-membered imides 25 (ees: 88 to 98%), whilst products 28 were prepared from five-membered imides 27 with lower enantioselectivities than the ones previously mentioned: when Ru 30 complexes with n = 1 or 2 (depending on the substrate) were used, the ees ranged from 62 to 92%.…”

“…up to 99%) were obtained in some of the examples indicated in Scheme 3, 51,52 although at the 20 expense of having to perform one or two additional synthetic steps. The same strategy has been used by Jones et al 53 and Bach et al 54 for the transformation of imides into lactams: they employed chiral oxazaborolidine catalysts derived from both enantiomeric series of 1-amino-indan-2-ol (42 53 and ent-42 54 ; see 25 Scheme 3 (c) and (d)), and borane as the reducing agent, to reduce the carbonyl group into the hydroxyl group. Subsequent deoxygenation of the hydroxyl group with Et 3 SiH furnished the corresponding lactams in ees up to 99%.…”

“…BH 3 ). This 1,2-monoreduction leads to the corresponding hydroxylactams, which are very interesting 25 building blocks for various biologically significant molecules. The most efficient results within this chemistry are summarised in Scheme 1.…”

“…the choice of one enantiotopic atom or functional group over the other), which is 20 provided by a chiral reagent or catalyst. Compared to asymmetric catalytic methods or (dynamic) kinetic resolution procedures on standard substrates, 32 enantioselective desymmetrisation offers several advantages, namely: (i) the possibility to simultaneously establish several stereogenic elements, which may be distant to 25 the site of the reaction; and (ii) in certain desymmetrisations, in which the substrate may undergo multiple transformations, the final enantioselectivity can be enhanced by coupling kinetic resolution to the desymmetrisation process. The great potential of enantioselective desymmetrisation has been 30 widely exploited in a topologically diverse array of achiral and meso substrates (Fig.…”

A Practical Aryl Unit for Azlactone Dynamic Kinetic Resolution: Orthogonally Protected Products and A Ligation‐Inspired Coupling Process

“…[2][3][4] This focus has resulted in a number of bifunctional, [5] Brønsted basic/ nucleophilic, [6] and Brønsted acidic [7] catalytic systems capable of promoting the highly efficient and enantioselective addition of low-molecular-weight alcohols to azlactones under mild reaction conditions. [8][9][10] These reactions provide easy access to bis(protect)ed amino acids of potential importance: for instance Song et al…”