Rearrangements Steglich

Groger has also reported a preliminary study on enantioselective acetyl migration in the Steglich rearrangement using one of Fu s commercially available catalysts and Birman s tetramisole-based organocatalyst [108]. 

In 1970, Steglich reported that DMAP catalyzed the rearrangement of O-acylated azlactones to their C-acylated isomers (the Steglich rearrangement) [166, 167]. This process effects C-C bond formation and concomitant construction of a qua-... 

This reaction is related to the Steglich Rearrangement for benzofuran and indole derivatives. 

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... 

Scheme 10.8 Acetyl migration in a Steglich rearrangement reaction.

The commonly accepted mechanism for the Steglich rearrangement, depicted in Scheme 40.2, involves a fast and reversible attack of the nucleophilic catalyst to the acyl of alkoxycarbonyl group, leading to an ion pair that in a slow irreversible step leads to the formation of the C4- or C2-substituted azlactone. If the nucleophile is chiral, the acyl cation can discriminate between the two enantiotopic faces of the azlactone enolate, affording enantiomerically enriched products. 

In 1998, Ruble and Fu [10] reported on the use of ferrocene-derived chiral 4-aminopyridines [11] in the Steglich rearrangement of 2-aryl-4-alkyloxazolones (Scheme 40.3). After the systematic optimization of several reaction parameters, the authors found that the planar-chiral ferrocene derivative (S)-l catalyzed the rearrangement of an array of 0-benzyloxycarbonyl azlactones with total... 

Scheme 40.3 Enantioselective Steglich rearrangement of O-carbonylated aziactones catalyzed by a chiral 4-(pyrrolidino)pyridine (PPY) derivative.

Scheme 40.4 Conversion of the Steglich rearrangement products into quaternary a-amino acid derivatives.

Scheme 40.6 Enantioselective Steglich rearrangement with catalyst (R,R)-3.

Compound (S)-4, devised by Johanssen and coworkers as a new type of ferrocene-based planar chiral ferrocene-based DMAP analog and obtained in six steps from enantiopure Kagan s ferrocene sulfoxide, gave only marginal enantioselectivities in the Steglich rearrangement of an O-carbonylated oxazolone (Scheme 40.8) [16]. 

Scheme 40.8 Enantioselective Steglich rearrangement catalyzed by ferrocene (R)-4.

Scheme 40.9 Enantioselective Steglich rearrangement catalyzed by a chiral 3-substituted DMAP.

Scheme 40.10 Enantioselective Steglich rearrangement of Oorbonylated aziactones with Vedejs catalysts 6 and 7.

Scheme 40.16 Asymmetric acyl migration in the Steglich rearrangement.

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. 

Figure 40.3 Smith s transition state model for the Steglich rearrangement catalyzed by Isothiourea (S)-11.

Scheme 40.19 Isothlourea 13 promoted Steglich rearrangement of oxazolyl carbonates.

Zhang and coworkers have designed a new structural type of nitrogen-based nucleophilic catalyst, based on chiral bicyclic imidazoles. Compound (R)-14 was a good catalyst for the Steglich rearrangement of azlactone carbonates (Scheme 40.20) [27]. A limitation of this methodology is the rather difficult preparation of the catalyst in enantiopure form (low yield resolution of the racemic with tartaric acid or by preparative HPLC). 

Smith and coworkers have investigated the ability of chiral N-heterocychc carbenes (NHCs) to promote the asymmetric Steglich rearrangement [28]. After an extensive study, it was found that the carbene derived from the oxazoline-triazoUum salt 15 was the best catalyst (Scheme 40.21). 

Scheme 40.21 Asymmetric Steglich rearrangement catalyzed by a N-heterocyclic carbene.

In 2010, Ooi and coworkers proposed the use of chiral ammonium betaines as asymmetric ionic nucleophilic catalysts [29], They reasoned that an intramolecular alkoxonium salt could be an efficient catalyst for the Steglich rearrangement- since the alkoxide anion would displace the carbonyl substituent in the intermediate ion pair the ammonium cation would be engaged in an ionic interaction with the azlactone anion, enhancing both the rate and the stereoselectivity of the acyl transfer step (Scheme 40.22). 

Scheme 40.22 Ooi s working hypothesis for the Steglich rearrangement with an onium alkoxide as catalyst.

Seidel and coworkers have developed a new concept for asymmetric nucleophilic catalysis, in which an achiral nucleophile is used in combination with a chiral hydrogen-bonding catalyst. The application of this concept to the Steglich rearrangement implied the use of simple DMAP as the achiral nucleophile and of the thiourea 17 as the chiral hydrogen-bond donor co-catalyst (Scheme 40.24) [30]. 

Scheme 40.24 Dual-catalysis approach to the asymmetric Steglich rearrangement...

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