DAVIES Asymmetric Synthesis

K. T. Wan and M. E. Davis, Asymmetric Synthesis of Naproxen by Supported Aqueous-Phase... 

H.M.L. Davies, Asymmetric synthesis using rhodium-stabilized vinylcarbenoid intermediates, Aldrichimica Acta 30 (1997) 107-114. 

The Darzens condensation reaction has been used with a wide variety of enolate equivalents that have been covered elsewhere. A recent application of this important reaction was appljed toward the asymmetric synthesis of aziridine phosphonates by Davis and coworkers.In this application, a THF solution of sulfinimine 34 (0.37 mmol, >98% ee) and iodophosphonate 35 (0.74 mmol) was treated with LiHMDS (0.74 mmol) at -78 °C to give aziridine 36 in 75% yield. Treatment of 36 with MeMgBr removed the sulfinyl group to provide aziridine 37 in 72% yield. 

An aza-Darzens reaction, involving the addition of chloromethylphosphonate anions to enantiopure N-sulfinimines, has also been developed by Davis and others for the asymmetric synthesis of aziridine-2-phosphonates [81-84], As an example, treatment of the lithium anion generated from dimethyl chloromethylphos-phonate (93 Scheme 3.30) with N-sulfmimine (Ss)-92 gave the a-chloro-P-amino phosphonate 94, which could be isolated in 51% yield. Cyclization of 94 with n-BuLi gave cis-N-sulfmylaziridine-2-phosphonate 95 in 82% yield [81],... 

The Rh2(DOSP)4 catalysts (6b) of Davies have proven to be remarkably effective for highly enantioselective cydopropanation reactions of aryl- and vinyl-diazoacetates [2]. The discovery that enantiocontrol could be enhanced when reactions were performed in pentane [35] added advantages that could be attributed to the solvent-directed orientation of chiral attachments of the ligand carboxylates [59]. In addition to the synthesis of (+)-sertraline (1) [6], the uses of this methodology have been extended to the construction of cyclopropane amino acids (Eq. 3) [35], the synthesis of tricyclic systems such as 22 (Eq. 4) [60], and, as an example of tandem cyclopropanation-Cope rearrangement, an efficient asymmetric synthesis of epi-tremulane 23 (Eq. 5) [61]. 

Recent efforts in the development of efficient routes to highly substituted yS-ami-no acids based on asymmetric Mannich reactions with enantiopure sulfmyl imine are worthy of mention. Following the pioneering work of Davis on p-tolu-enesulfmyl imines [116], Ellman and coworkers have recently developed a new and efficient approach to enantiomerically pure N-tert-butanesulfmyl imines and have reported their use as versatile intermediates for the asymmetric synthesis of amines [91]. Addition of titanium enolates to tert-butane sulfmyl aldimines and ketimines 31 proceeds in high yields and diastereoselectivities, thus providing general access to yS -amino acids 32 (Scheme 2.5)... 

As another extension of this process, Davies et al. have developed highly regio-, diastereo- and enantioselective C-H insertions of methyl aryldiazoace-tates into cyclic A-Boc-protected amines catalysed by rhodium(II) S)-N- p-dodecylphenyl)sulfonylprolinate. The best results were obtained in the case of the C-H insertion of methyl aryldiazoacetates into A-Boc-pyrrolidine, which gave, in all cases, a diastereoselectivity and an enantioselectivity greater than 90% de and 90% ee respectively (Scheme 10.77). The synthetic utility of this method was demonstrated by means of a two-step asymmetric synthesis of a novel class of C2-symmetric amines. 

William R. Roush is Warner Lambert/Parke Davis Professor of Chemistry at the University of Michigan. He received his B.S. from the University of California, Los Angeles, in 1974 and his Ph.D. from Harvard University in 1977. His research area is organic chemistry, with specialized interests in organic synthesis and natural products chemistry, stereochemistry of organic reactions, development of new methods and regents, asymmetric synthesis, and oligosaccharide synthesis. 

Davis et al. [88] described the asymmetric synthesis of a-substituted primary sulfonamides involving the diastereoselective a-alkylation of N-sulfonylcamphor-imine dianions, while Huart and Ghosez reported an enantioselective synthesis of bicyclic cyclopentenones via a stereoselective 1,4-addition of metallated enan-tiopure sulfonamides to cyclic enones [89]. 

If you want to read more about these discoveries we suggest Practical asymmetric synthesis , i.W. Davies and P. J. Relder, Chemistry and Industry (London, 1,1996,412-15. The reference far the Parma work is G. Casiraghi. G. Caenati, G. Puglia, and G. Terengtii, J. Chert . Soc., Perkin Trans. 

A particularly effective method for the asymmetric synthesis of both aldehyde-and ketone-derived sulfinimines recently introduced by Davis and co-workers is the condensation of (5)-(+)-p-toluenesulfinamide (63) with aldehydes and ketones using activated 4-A molecular sieves or titanium ethoxide [Ti(OEt)4].46 This procedure avoids the problem of removing the menthol by-product of the one-pot procedure (see Section II.D) which is sometimes problematic.23 Importantly, this methodology affords ketone derived sulfinimines 66 which are difficult to prepare by other means. 

Davis and Andermichael recently described a new method for the asymmetric synthesis of 3-substituted-1 -(2//)-isoquinolones which are important chiral building blocks for alkaloid synthesis.83 This procedure involved the highly diastereose-... 

Soon after Kuhn s photodestruction experiments around 1930, Karagunis and Drikos tried to perform an asymmetric synthesis with an asymmetrically substituted triphenylmethyl radical, but there was no optical activity created [107]. In 1935 Davis and Heggie [108] reported a total asymmetric synthesis by addition of bromine to 2,4,6-trinitrostilbene (they found, however, a maximum curve of... 

With the enantioselective intramolecular benzoin reaction established as a synthetic tool, and in combination with our efforts in the synthesis of bioactive natural products bearing a quaternary a-hydroxy ketone unit (Davis and Weismiller 1990 Heller and Tamm 1981), such as the 4-chromanone derivative (S)-eucomol (Bohler and Tamm 1967 Crouch et al. 1999), a catalytic asymmetric synthesis of various 3-hydroxy-4-chromanones brought about by the chiral triazolium salts 127, 123b and 102 as pre-catalysts was investigated (Enders et al. 2006d). The sterically different pre-catalysts were chosen in order to adjust the catalyst system to the steric and electronic properties of the substrates 128. A screening of the reaction conditions indicated 10 mol% of the... 

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