The rational design and mechanistic understanding of catalytic systems capable of generating quaternary stereocenters in an asymmetric fashion is a recognized challenge in synthesis.[1] A number of asymmetric Lewis base mediated processes have been developed within this area, [2] in which enantiomerically pure derivatives of 4-(pyrrolidino)pyridine (PPY) and 4-dimethylaminopyridine (DMAP) are elegantly employed by the Fu, [3] Vedejs, [4] and Richards groups, [5] as asymmetric catalysts for the rearrangement of 5-oxazolyl carbonates into 4-carboxyazlactones (Scheme 1).[6] This process delivers C-carboxyazlactones bearing a quaternary stereocenter with excellent enantiocontrol. [7] Among the recent developments in Lewis base catalysis, the ability of isothioureas to efficiently promote alcohol acylation has been demonstrated. Birman and Li first showed that tetramisole and its benzannulated analogue BTM could catalyze effective kinetic resolution [8] and desymmetrization protocols (Scheme 2).[9] Independent studies by Kobayashi and Okamoto, and Birman et al. subsequently introduced DHPB, [10] before Birman and Li developed HBTM (1) for the kinetic resolution of aryl cycloalkanols.[11] Building upon these studies, [12,13] Dietz and Gröger have utilized tetramisole (32 mol %) to promote a modestly enantioselective rearrangement of an oxazolyl acetate (63 % ee at 80 % conversion), [14] and we have shown that DHPB represents the optimal catalyst substructure for the carboxyl group transfer reaction of oxazolyl carbonates in the racemic series. [15] As part of a research program concerned with utilizing Lewis bases as catalysts, [16] we hoped to build upon these precedents by using chiral isothioureas, such as 1, to promote the Steglich rearrangement with high enantioselectivity. The incorporation of a stereodirecting group at C4, adjacent to the nucleophilic nitrogen atom, is imperative in these catalyst architectures; this contrasts the recognized derogatory effect of the 2-substitution of DMAP or PPY derivatives upon catalytic turnover in acylation reactions. [4a, 17] Upon formation of an N-carboxy derivative within the Steglich reaction, this stereodirecting group was predicted to adopt a pseudoaxial conformation.[18] It was anticipated that asymmetric induction would arise from discrimination between the prochiral faces of an azlactone enolate upon addition to this intermediate, preferably anti to the C4 stereodirecting unit, with the axial C3 À H aiding differentiation between the planar aromatic and aliphatic quadrants (Figure 1).Initial studies evaluated isothiourea 1 to promote the asymmetric O-to C-carboxyl group transfer of a range of alkyl and aryl oxazolyl carbonates 2-4, with the transfer of the

The catalytic activity and enantioselectivity in the kinetic resolution of (±)-1-naphthylethanol with a range of structurally related 3,4-dihydropyrimido[2,1-b]benzothiazole-based catalysts is examined. Of the isothiourea catalysts screened, (2S,3R)-2-phenyl-3-isopropyl substitution proved optimal, giving good levels of selectivity in the kinetic resolution of a number of secondary alcohols (S values up to >100 at ~50% conversion). Low catalyst loadings (0.10-0.25 mol%) of the optimal isothiourea can be used to generate enantiopure alcohols (>99% ee) in good yields.

The choice of the anion of an achiral TBD-derived guanidinium salt, used as cocatalyst for proline, allows reacting cycloketones with aromatic aldehydes and preparing either anti- or syn-aldol adducts with very high enantioselectivity. As a proof of principle, we show how the judicious choice of an additive allows individual access to all possible products, thus controlling the stereochemical outcome of the asymmetric aldol reaction. The origin of the syn diastereoselectivity unfolds from an unusual equilibrium process coupled to the enamine-based catalytic cycle standard for proline.

Samarium metal and samarium diiodide have become important tools as selective cyclopropanating agents in organic synthesis due to their high chemo- and stereoselectivity. Therefore, Sm and SmI(2) are the ideal reagents to prepare cyclopropane derivatives. This tutorial review highlights C-C multiple bond cyclopropanation processes promoted by samarium or samarium diiodide.

The combined activity of (S)-proline and an achiral cocatalyst (a TBD-derived guanidinium salt) allow direct aldol reactions to be carried out with high diastereoselectivity and enantioselectivity under solvent-free conditions with a rather simple reaction setup where stirring is not required.