Oxazolyl carbonates

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]. 

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. ... 

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... 

While an array of 0- and iV-acylation processes catalyzed by Lewis bases have been developed, C-acylation or C-carboxylation processes are relatively unexplored. However, one C-carboxylation protocol, the O- to C-carboxyl transfer of oxazolyl carbonate derivatives to give the corresponding 4- or 2-carboxyazlactones, initially demonstrated in 1970 by Steglich and HOfle, is often used as the benchmark standard for assessing asymmetric Lewis... 

An interesting aspect of this reaction was reported by Movassaghi, who found that the preparation of amides from esters, expected to be possible under similar conditions, failed except for the special case of 1,2-amino alcohols. Similar procedures were also found to promote O- to C-carboxyl transfer reactions of oxazolyl carbonates (Scheme 14.4). " ... 

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... 

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