Oxazolyl carbonates, rearrangements

Smith and co-workers have employed NHC 81 to catalyse the 0- to C-carboxyl transfer of a range of oxazolyl carbonates 80, forming 82 with the generation of a C-C bond at a quaternary centre with good catalytic efficiency [27], This transformation presumably proceeds via the generation of an intermediate carboxyazolium species, and has been utihsed as a component of domino multi-component reactions [28], as well as the rearrangement of indolyl and benzofuranyl carbonates (Scheme 12.15) [29]. 

Reactions that exploit the nucleophilicity of NHC without involving a Breslow intermediate (101) are often encountered in the literature. For instance, a series of chiral NHCs has been evaluated for their catalytic ability to promote the Steglich rearrangement of oxazolyl carbonates (133) to C-carboxyazalactones (134) (Scheme 1) This NHC-catalysed version, involving azolium species (135) as non-Breslow intermediate, has been realized with only moderate levels of enantioselectivities. 

The evaluation of a range of enantiomerically pure NHCs to promote the catalytic enantioselective Steglich rearrangement of oxazolyl carbonates to... 

The rearrangement of O-aqrlated azlactones (or of oxazolyl carbonates) to a C-acyl-(or to a C-carboxy) azlactone takes place easily at room temperature in the presence of catalytic amounts of 4-(dimethylamino)pyridine (DMAP) or of 4-(l-pyrrolidinyl) pyridine (PPY), as first disclosed by Stegtich and Hofle in 1969 (Scheme 40.1) [9]. Although the product is usually a 4-acyl- (or a 4-alkoxycarbonyl)azlactone, if the R2 substituent is electron-donating the rearrangement at C2 can take place. 

Another chiral isothiourea, HBTM (S)-ll, previously developed by Birman and Li for the kinetic resolution of aryl cycloalkanols [23], was found by A.D. Smith and coworkers [24] to give excellent yields and enantioselectivities in the Steglich rearrangement of oxazolyl carbonates (Scheme 40.17). The related catalyst (S,R)-12 gave very similar results. 

Scheme 40.19 Isothlourea 13 promoted Steglich rearrangement of oxazolyl carbonates.

The structurally related isothiourea (S)-13 was synthesized by Okamoto and coworkers, and used as a catalyst in the Steglich rearrangement of oxazolyl carbonates [26]. As shown in Scheme 40.19, yields and enantioselectivities ranged from good to excellent. The same compound can also catalyze the O- to C-carbonyl rearrangement of benzofuranone and oxindole-derived carbonates, but with poor... 

In the laboratory of D.R. Williams, a carbanion methodology for the alkylations and acylations of substituted oxazoles was investigated. The study showed that the monoalkylation of the dianion generated from 2-(5-oxazolyl)-1,3-dithiane exclusively led to the substitution of the carbon adjacent to sulfur. However, acylation reactions of the dianion afforded 4,5-disubstituted oxazoles. These new products presumably arose from carbonyinitrile ylide intermediates, which were generated by the selective C-acylation of a ring-opened dianion tautomer. This is the first example of a base-induced, low-temperature Cornforth rearrangement. 

This reaction has been extended to the translocation of the acyl group for indole derivatives. In addition, a chiral planar DMAP derivative has been developed and applied for the enantioselective rearrangement of 0-acylated azlactone and the same catalyst recently has been used for an intermolecular reaction to form 1,3-diketones. Moreover, 3-(2,2,2-triphenyl-1 -acetoxyethyl)-4-(dimethylamino) pyridine (TADMAP) has been applied as a chiral nucleophilic catalyst to catalyze the carboxyl migration of oxazolyl, furanyl, and benzofuranyl enol carbonates with good to excellent levels of enantioselec-tivity. The rearrangement for oxazole derivatives are particularly efficient for giving chiral lactams and lactones. ... 

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