Asymmetric methodology

A review was published covering recent progress in the stereoselective synthesis of piperidines <00S1781>. Routes described in detail include those derived from the chiral-pool, chiral auxiliaries, and catalytic asymmetric methodology. 

Consequently, a number of stereoselective syntheses have been developed leading to a variety of paraconic acids either in racemic or in enantiopure form, using starting materials from the chiral pool, chiral auxiliaries or applying catalytic asymmetric methodology. Moreover, a number of strategies leading to paraconic acids in a non-stereoselective way have been reported, which will not be described in detail in this review [4, 5]. 

Asymmetric methodology should always be measured against the best existing alternatives for accessing the targeted compounds. In the case of hydrocy-anation of aromatic aldehydes, the bar is set very high, as both enantiomers of... 

Hudlicky T, Gonzalez D, Gibson DT (1999) Enzymatic Dihydroxylation of Aromatics in Enantioselective Synthesis Expanding Asymmetric Methodology. Aldrichimica Acta 32 35... 

The elegant asymmetrization methodology of a meso compound, achieved in high enantioexcess under chiral environment, was the highlight of the total synthesis of (+)-pancratistatin (94) reported by Trost and Pulley (31]. The synthesis commenced with ( )-conduritol-A (130), obtained from p-benzoquinone, (Scheme 18) which was converted into the acetonide 131 and thence, via the dialkoxide to the cis-bis carbonate 132 (Scheme 19). The chiral n-ailyl palladium complex A formed on treatment erf 132 with the catalyst generated from chiral bis-amide 133 and n-allyl palladium chloride underwent azide substitution from the less hindered face of the molecule to provide the monocarbonate 134 in excellent yield and with high optical induction. 

Since the discovery of cis-1 -amino-2-indanol as a ligand for human immunodeficiency virus protease inhibitors and the development of a practical industrial process for the synthesis of either ris-isomers in enantiopure form, the remarkable properties of the rigid indane platform have been used extensively in an ever-increasing number of asymmetric methodologies. In addition to the use of this amino alcohol as a chiral auxiliary and ligand for asymmetric synthesis, it has found application as a useful resolution agent. Applications include amines, carboxylic acids, and alcohols. 

The Diels-Alder reaction, now more than 60 years old, has regained new prominence with the ability to use asymmetric technology to control relative and absolute stereochemistry while creating two new carbon-carbon bonds.1 3-5 6 As a result of the diversity of dienes and dienophiles, the application of asymmetric methodology to the Diels-Alder reaction has lagged behind other areas such as aldol reactions.3 However, considerable advances have been made in recent years through the use of chiral dienophiles and catalysts.3 6 21... 

Hudlicky, T., Gonzalez, D., and Gibson, D. T. 1999. Enzymatic dihydroxylation of aromatics in enantioselective synthesis expanding asymmetric methodology. Aldrichimica Acta, 32(2), 35-62. 

Take particular note that two hydroxylations are done on the same substrate 111 at the same time. We will not dwell too much on this here, but from the point of view of enantiomeric excess this is an aspect of asymmetric methodology that can be very useful. See Double Methods in chapter 28. 

During the past three years, we have had excellent success in achieving some asymmetric syntheses O). We have focused attention specifically on faithful transfer of chirality from the sulfur atom of some a-carbonyl a,3-ethylenic sulfoxides to the 3-carbon atom during organometalllc 3-addition reactions. This type of high asymmetric induction in forming carbon-carbon bonds has led to successful preparation of several classes of optically active synthetic intermediates such as 3-methylalkanoic acids and 3-methylcycloalkanones. In addition, this asymmetric methodology has been applied successfully to preparation of more complex, enantiomerically pure molecules such as steroids and steroid intermediates. 

These studies are significant in two respects. Efficient or improving asymmetric methodology is of primary importance, especially in such a fundamental area. Additionally, this work provides new insights [3] into the complex solution behaviour of these commonplace but valuable main group reagents. 

Historical perspective C. H. Heathcock, Comp. Org. Syn. 2, 133-179 (1991). General review T. Mukaiyama, Org. React. 28,203-331 (1982). Application of lithium and magnesium enolates C. H. Heathcock, Comp. Org. Syn. 2, 181-238 (1991) of boron enolates B. M. Kim etal, ibid. 239-275 of transition metal enolates I. Paterson, ibid. 301-319. Stereoselective reactions of ester and thioester enolates M. Braun, H. Sacha, J. Prakt. Chem. 335,653-668 (1993). Review of asymmetric methodology A. S. Franklin, I. Paterson, Contemp. Org. Syn. 1,317-338 (1994). Cf. Claisen-Schmidt Condensation Henry Reaction Ivanov Reaction Knoevenagel Condensation Reformatskv Reaction Robinson Annulation. 

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