Chiral compounds diastereoselective reductive

The stereoselective epoxidation of chalcones, followed by acid-catalysed ring closure and concomitant cleavage of the epoxide ring, provides a very efficient route to chiral flavon-3-ols and, subsequently, by borohydride reduction to produce flavan-3,4-diols [13, 14], It has been shown that diastereoselective reduction of the chiral flavon-3-ols by sodium borohydride in methanol yields the trans-2,3-dihydroxy compounds, whereas borohydride reduction in dioxan produces the cis-isomers [14] the synthetic procedure confirms the cis configuration of the 2,3-hydroxy groups of naturally occurring leucodelphinidins [14]. 

Stereospecific Reductive Amination of Carbonyl Compounds. Catalytic or chemical reduction of chiral imines derived from (1) often proceeds with high diastereoselectivity. Reductive removal of the a-methylbenzyl group yields chiral primary amines (eq 18 and 19). - ... 

There are many other examples of drugs based on an amino acid backbone. Stoner et al. recently reported a synthesis of the HIV protease inhibitor ABT-378 (Lopinavir) (84) (133). In a similar synthesis to that of the related compound. Ritonavir, key intermediate (85)is prepared by stepwise diastereoselective reduction of enaminone (86).This means that the existing chiral center, derived from natural L-phenylalanine (protected to 87), controls the formation of the two new stereocenters as... 

Both carbonyl groups of p-diketones 32 are reduced and the two reductions are independently enantioselective in the same sense so that the chiral (C2 symmetric) product 33 predominates by 99 1 over the meso compound 34. This makes symmetrical 1,3-diols such as 33 readily available.12 Elsewhere you will meet methods that use one centre to induce another in a 1,3-relationship, maybe by diastereoselective reduction - this is a quite different strategy. 

Recent employment of optically active fluorinated compounds for biologically active substances (7-2) or ferroelectric liquid crystals (3-5) has emphasized the versatility of these chiral molecules, while few methods have been reported for the preparation of such materials in a highly diastereo- as well as enantioselective manner. On the other hand, recent investigations in this field have opened the possibility for the introduction of chirality via asymmetric reduction or optical resolution by employing biocatalysts such as baker s yeast (6-75) or hydrolytic enzymes (16-20), respectively (27-23), along with the conventional chemical methodology (24-27). Chiral materials thus obtained may also be utilized in diastereoselective reactions which create new chiral centers (77). In this paper, the authors would like to discuss our recent progress in the preparation of optically active fluorinated compoounds and the effect of fluorine atom(s) on the reactivity and selectivity. 

An example of the diastereoselective reduction of a chiral iminium ion compound has recently been reported. The diastereomers were formed, in this case, in a 3 1 ratio20. Chiral iminium ions21,22 derived from chiral (lS)-l-arylethylamines (Ar = phenyl, 2-chlorophenyl, or 2,6-dichlorophenyl) have been reduced stereo selectively with sodium borohydride in 61 77% yield. Diastereoselection of the C=N reduction ranged from 88 12 to 100 0. 

As for the diols, the symmetric compounds have found most uses for nonsymmetric diols, a versatile synthesis via silyl ketones using the SAMP/RAMP methodology has been developedl5. Both enantiomers of the simplest symmetric diol, 2,3-butanediol (11), are often used in asymmetric synthesis, mostly for the formation of acetals and ketals with carbonyl compounds and subsequent reactions with acidic catalysts (Section D. 1.1.2.2.), Grignard reagents (Section D. 1.3.1.4.) and other carbanions (Sections D. 1.5.1., D. 1.5.2.4.), and diastereoselective reductions (Section D.2.3.3.). Precursors of chiral alkenes for cycloprotonations (Section D.1.6.1.5.) and for chiral allenes (Section B.I.), and chiral haloboronic acids (Section D. 1.1.2.1.) are other applications. The free diol has been employed as a chiral ligand in molybdenum peroxo complexes used for enantioselective epoxidation of alkenes (Section D.4.5.2.2.). 

There has been recent interest in naphtho-fused dithiepines as chiral acyl anion equivalents, particularly since the starting dithiol 128 can be obtained in enan-tiomerically pure form (89TL2575). This is transformed using standard methods into the dithiepine 129, but showed only moderate diastereoselectivity in its addition to carbonyl compounds. On the other hand, as we have seen previously for other systems, formation of the 2-acyl compound 130 and reduction or addition of a Grignard reagent gave the products 131 with much better stereoselectivity (91JOC4467). 

As with the reduction of aldehydes and ketones (16-23), the addition of organometallic compounds to these substrates can be carried out enantioselectively and diastereoselectively. Chiral secondary alcohols have been obtained with high ee values by addition to aromatic aldehydes of Grignard and organolithium compounds in the presence of optically active amino alcohols as ligands. ... 

Chloromethylphosphonamide 104 has been alkylated with diastereoselectivities up to >95%. The corresponding azido compounds 106 were obtained by nucleophilic displacement, with partial to full stereospecificity <2000HA528>. This two-step process can lead to aminophosphonic acids after reduction of the azido group and hydrolysis of the chiral appendage (Scheme 7). 

Johnson in 1993 described an approach to racemic p-amyrin involving application of a biomimctic polyene cyclization.7 In the same year Corey accomplished the enantioseleetive synthesis of compound 4. a key intermediate that opened the way to stereoselective preparation of compounds I, 2. and 3 8 A key step in the synthesis of P-amyrin (1) was the introduction of chiral oxazaboroli-dines for enantioseleetive carbonyl reduction. Ba ed on these methods, generation of an enantiomerically pure epoxide and its stereoselective cationic cyclization led to the pentacyclic system of structure 1 Diastereoselective cyclopropanation and an intramolecular protonation of a carbanion represent other interesting steps in this total synthesis. 

Reductive aldol reaction of an allenic ester (52) to a ketone such as acetophenone can give y- (53-y) or a-product (53-cy).159 Using as catalysts a copper salt and a range of chiral phosphines, together with phosphine additives such as the triphenyl or tricy- clohexyl compounds, a highly selective set of outcomes can be achieved, e.g. (53-y) almost exclusively cis- with 99% ee, or - without additive - significant amounts of (53-a) can be formed (as a syn-anti mixture). A diastereoselective implementation of the latter has also been developed. 

The synthesis of enantiopure amino-functionalized compounds such as a- and (3-amino acids or nonfunctionalized amines can be envisaged by the use of aldehydes, ketones, a- or (3-keto acids, or derivatives thereof as substrates for imine formation followed by, for example, diastereoselective Strecker reactions, reductions, or organometallic addition reactions. In the literature, diastereoselective syntheses based on a large variety of chiral auxiliaries, such as a-arylethylamines,4... 

In this chapter, recent applications of (W)-phcnylglycine amide (1) in asymmetric synthesis are presented (Figure 25.2). The first section deals with diastereoselective Strecker reactions for the preparation of a-amino acids and derivatives, whereas the second section focuses on diastereoselective allylation of imines for preparation of enantiomerically pure homoallylamines. This latter class of compounds is a well-known intermediate for the synthesis of, for example, many types of amines, amino alcohols, and P-amino acids. The final section describes reduction of imines providing enantiomerically pure amines. (S)-3,3-Dimethyl-2-butylamine and (S)-l-aminoindane will be presented as leading examples. The results described in this chapter originate from a longstanding cooperation in the field of chiral technology development between DSM Pharma Chemicals and Syncom B.V. 

If, for example, the mild Lewis acid LiAlH4—it is mildly acidic because its acidic moiety is Li+—is used as a hydride donor, the diastereoselectivity of the reduction of a-chiral carbonyl compounds with a heteroatom in the a position can be controlled by... 

Of course, the highest diastereoselectivities in the reduction of a-chiral a-oxygenated carbonyl compounds are expected when the reducing agent and the protecting group direct in one and the same direction that is, when both make possible or both prevent... 

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