Diastereo mers

FIGURE 7 10 Stereo isomeric 2 3 butanediols shown in their eclipsed con formations for convenience Stereoisomers (a) and (b) are enantiomers of each other Structure (c) is a diastereo mer of (a) and (b) and is achiral It is called meso 2 3 butanediol... 

An expedient and stereoselective synthesis of bicyclic ketone 30 exemplifies the utility and elegance of Corey s new catalytic system (see Scheme 8). Reaction of the (R)-tryptophan-derived oxazaboro-lidine 42 (5 mol %), 5-(benzyloxymethyl)-l,3-cyclopentadiene 26, and 2-bromoacrolein (43) at -78 °C in methylene chloride gives, after eight hours, diastereomeric adducts 44 in a yield of 83 % (95 5 exo.endo diastereoselectivity 96 4 enantioselectivity for the exo isomer). After reaction, the /V-tosyltryptophan can be recovered for reuse. The basic premise is that oxazaborolidine 42 induces the Diels-Alder reaction between intermediates 26 and 43 to proceed through a transition state geometry that maximizes attractive donor-acceptor interactions. Coordination of the dienophile at the face of boron that is cis to the 3-indolylmethyl substituent is thus favored.19d f Treatment of the 95 5 mixture of exo/endo diastereo-mers with 5 mol % aqueous AgNC>3 selectively converts the minor, but more reactive, endo aldehyde diastereomer into water-soluble... 

It is particularly appealing that the configuration at the a-carbon atom in the w-diastereo-mers m-18 can be inverted by trifluoroacetylation and migration of the 2,2-dimethylpropanoyl group24. Furthermore, A-deprotection is possible through simple operations24. 

The lithium cnolate generated by deprotonation of 2-/m-butyl-6-methyl-l,3-dioxan-4-onc, readily available from polyhydroxybutyric acid (PHB), predominantly affords the diastereo-mers 7 when reacted with aldehydes. The diastereomeric ratios of aldol adducts 7/8, produced by reactions with aliphatic aldehydes, range from 87.5 12.5 to >99 1. Pure diastereoiners7are obtained by recrystallization in 25-74% yield116-118. Only marginal diastereoselectivities with respect to the carbinol center are obtained with aromatic aldehydes111-119. Benzoylation of the dioxanones 7, followed by reduction with lithium aluminum hydride, affords enan-tiomerically and diastereomerically pure triols 9 in >85% yield 11. ... 

Chang, A.Y. and P.B. Dervan. Strand selective cleavage of DNA by diastereo-mers of hairpin polyamide-seco-CBl conjugates. /. Am. Chem. Soc. 2000, 122, 4856-4864. 

The same reaction sequence performed in methanol affords a mixture of diastereo-mers of the phosphorylated phosphinic ester 48b, of which one pure isomer can be isolated32 . In the presence of piperidine, reductive elimination of nitrogen 28,29) from 45 to give bis(diphenylphosphoryI)methane competes with the prevailing formation of the phosphinic piperidide 48c32). Expected trapping of 47 by [2 + 2]-cycloaddition with benzaldehyde fails to occur in place of 1,2k5-oxaphosphetanes, products are obtained which arise mainly by way of the benzoyl radical32,33). 

Very recently, Reetz, Ma and Goddard reported phosphoramidites based on BINOL bearing a single ortho-substituent (Scheme 28.10) [69]. These ligands are also chiral on phosphorus, such that the synthesis results mostly in diastereo-mers which have to be separated. In several cases, however, one of the diaster-eomers was formed exclusively. Some of the ligands afford high ee-values in the hydrogenation of methyl N-acyl dehydroalanine and dimethyl itaconate. 

One of the key features of such stereocontrolled aldol reactions is the predictability of the absolute stereochemistry of the enantiomers (or diastereo-mers) that will be formed as the major products. The preferred intermediate for an archetypal aldol reaction, proceeding by way of a metal enolate, can be tracked using the Zimmerman Traxler transition state and the results from the different variations of the aldol reaction can be interpreted from similar reasoning, and hence predictions made for analogous reactions1129]. 

In situ magnesiation of an allenyl iodide with isopropylmagnesium bromide gives rise to a transient allenyl Grignard reagent, which adds to aldehydes and ketones to afford mainly homopropargylic alcohol adducts (Table 9.8) [18]. The anti diastereo-mers are favored, especially with sterically demanding aldehydes. Additions to ketones are less selective. 

Thermolysis of 164 bearing a pendent olefin at 150 °C also allows the aryl radical in 167 to be captured in a 5-exo fashion, leading to 165 as a 1 1 mixture of diastereo-mers (Scheme 20.33). The corresponding Lewis acid-catalyzed [3,3]-sigmatropic rearrangement promoted by AgBF4 was facile at room temperature, making it possible for 166 to be isolated. Thermolysis of 166 at 75 °C afforded 165 in 80% yield. 

The preparation and characterization of several octahedral Ru(II) complexes containing s-trans coordinated dienes have been reported. The Zn mediated reduction of Ru(acac)3 in the presence of a 1,3-diene affords (diene)Ru(acac)2 complexes as a mixture of diastereo-mers (eg. 129)13a b. Reaction of [(trispyrazolylborate)RuCl]jt or [(NH3)4Ru(acetone)2]2+ [CIO4 ]2 with acyclic dienes yields complex 130 or cation 131 respectively130,14. Coordination of the ligand as an s-trans diene was indicated either by crystal structure or by determining C2v symmetry on the basis of NMR spectroscopy. 

In order to elucidate the nature of this mechanism further, Gibson (nee Thomas) studied134,136 the conversion of an optically pure sample of vinylke-tone 121.fi to the corresponding vinylketene (221.e). The vinylketone was resolved by carbonyl ligand substitution with (+)-neomenthyldiphenyl-phosphine, followed by subsequent separation of the resultant diastereo-mers to yield an optically enriched product.136,137 When 222.e, of known e.e., was treated with methyllithium under an atmosphere of carbon monoxide, the expected vinylketene complex 221.e was isolated and was found... 

Pritchard and co-workers (147) reported the preparation of an acyclic chiral sulfite, 98, which is formed as a mixture of diastereo-mers in the reaction between racemic methyl chlorosulfite and (+)-diphenacyl malate. The pure diastereomers of 98 were isolated by fractional crystallization. 

Unsaturated carboxylic acids can be de-carboxylated to alkyl radicals that undergo an intramolecular addition. The S-exo-trig-cyclization of fi-allyloxy radicals, generated from an appropriate carboxylic acid, combined with a final heterocoupling has been applied to synthesize a precursor of prostaglandine PGF2q (Fig. 47) [246] and a branched carbohydrate (ratio of diastereo-mers 1.8 1) (Fig. 48) [247]. A radical tandem cyclization of a doubly unsaturated monocyclic carbocyclic acid provides a... 

Though the rearrangements of the reactants 10c delivered single regioiso-mers, the products 12c (R=nBu/R =H) were isolated as a mixture of diastereo-mers after the rearrangement reduction sequence. Likewise, the 3,3-sigma-... 

Srinivas NR, Shyu WC, Barbhaiya RH. 1995. Gas chromatographic determination of enantiomers as diastereo-mers following pre-column derivatization and applications to pharmacokinetic studies a review. Biomed Chromatogr 9 1. 

The product esters could not be separated analytically, so we reduced the cmde product from the cyclizations to the corresponding alcohols. We observed both diastereo-mers 39 and 40 of the methine insertion product, and three of the four possible dia-stereomers 41a, 41b, and 41c of the methylene insertion product interestingly alcohol 41d was not detected. The five alcohols could be resolved by HPLC and by H-NMR. While the HPLC ratios were more precise, the H-NMR ratios tracked reasonably well, and could be sufficient if a new rhodium(II) catalyst was to be characterized. 

Scheme 40 Synthesis of the tetrahydro-/ -carboline scaffold 221. Two representative diastereo-mers of 221A are drawn in blue and cyan...

Further process optimization by Thiruvengadam and co-workers (Thimvengadam et al., 1999), led to a novel, stereoselective, scalable two-step process devoid of chromatography for chiral 2-azetidinone construction (Scheme 13.4). As above, the titanium-enolate of chiral oxazolidinone 11a was preformed, but now when reacted with well behaved imines of type 16, affords the unexpected anti-addition product. This surprising result was further supported by careful comparison to minor antiproducts obtained in the earlier aldol-addition methodology and determination that the major product was indeed 17a (undesired RSR series). Adjustment of the oxazolidinone absolute stereochemistry to the fortuitously less expensive 2S-series afforded the desired diastereo-mer 17b in 95% de and in 50-70% yield. Recrystallization improved the stereochemical purity to >99% de. 

This bromination at C-3 creates a second stereocentre and therefore gives rise to diastereo-mers. The two hydrogens at C-3 are diastereotopic and therefore give rise to diastereomers on substitution. 

Figure 4 A. Scheme showing the reaction of OPA with a chiral thiol and a chiral amine to form diastereo-mers. Either the thiol or the amine could act as the CDA (compare Table 1. Entry 27).

The same strategy has been used by Williams (90JA808) in his synthesis of brevianamide B. The aldehyde (82), prepared enantioselectively from L-proline, was converted to the silyl ether. Acylation of this (BuLi, ClC02Me) gave the carbomethoxy derivative as a mixture of diastereo-mers, which was alkylated by gramine. As before, an enolate alkylation (Sn2 ) on an allyl chloride derived from the above gave the tricyclic compound, which could be transformed to brevianamide B (Scheme 24). 

The reaction of sulfoximine 6 with ClC02CH(Cl)Me proceeded readily and gave, besides 54, the chlorohydrins 57, as mixtures of the anti and syn diastereo-mers in ratios of 78 22 and 73 27, respectively, in good yields. Treatment of the mixture of chlorohydrins with DBU furnished oxiranes 58 as mixtures of trans and as isomers in ratios of 78 22 and 73 27, respectively, in good yields. 

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