Chirality diastereoselectivity

Keywords. Chirality, Diastereoselectivity, Isotope labelling, Mass spectrometry, Stereochemistry... 

If the metal enolate contains a center of chirality, diastereoselection may be exhibited in the C—C bond formation process. Evans has identified three classes of metal enolates in which chirality transfer may occur (i) endo- and exo-cyclic enolates such as (27) or (28), which contain a chiral center ( ) in a ring bonded to the enolate at two points (ii) acyclic enolates such as (29) or (30), in which the moiety containing the chiral center ( ) is bonded to the enolate at only one point and (iii) chelated enolates such as (31) or (32), in which the chiral center is a part of the chelate ring. (Z)-Endocyclic enolates are also possible for large ring cyclic ketones. 

Note that this reaction is diastereoselective—but neither starting material nor products are chiral. Diastereoselectivity need have nothing to do with chirality ... 

Keywords Biotransformations / Chirality / Diastereoselectivity / Enantioselectivity / Microbial Reduction / Microbial Hydrolysis... 

When the Michael receptors are chiral, diastereoselective cyclopropanation reactions are possible. Treatment of an enan-tiomerically pure (+)-dicyclopentadienone with EDS A gave the eA o-cyclopropane product in 88% yield in >99% ee. Thermolysis of this adduct gave, via a retro-Diels-Alder reaction, an optically active (>99% ee) cyclopentenone in 82% yield (eq 8), ... 

By making the cyclic structure chiral, diastereoselective aldol and allylation reactions have been achieved to provide a novel access to optically active aldols and homoallyl alcohols (Schemes 3-124 and 3-125). 

Cram erythro-products" (G.E. Keck, 1984 A, B, C). [3-(Silyloxy)allyl]stannanes and O-pro-tected a- or y -hydroxy aldehydes yield 1,2,3- or 1,2,4-triols with three chiral centres with high regio- and diastereoselectivity (G.E. Keck, 1987). 

The cyclic 2,4-dienoate 184, formed by the Pd-catalyzed cyclization of the 1,6-enyne 183, reacted with 154 to form the azulene derivative 185[118], The 3-methylenepyrrolidine 188 is formed by the reaction of the Zn reagent 186 with the chiral imine 187 with high diastereomeric excess. The structure of the allylic ethers is important for obtaining high diastereoselectivity[l 19],... 

Chiral glyoxylates have been used to effect of/z o-hydroxyalkylation of phenols via coordinative complexes. In this way, optically active 2-hydroxymandehc esters have been obtained with up to 94% diastereoselectivity (36). 

High levels of asymmetric induction have been achieved in the hydroboration of 1,3-, 1,4-, and 1,5-dienes with thexylborane (482,483,489,490). The first chiral center is formed by an intermolecular reaction. In the second step, the organoborane intermediate undergoes an intramolecular hydroboration, creating the second chiral center with high diastereoselectivity. 

Industrial Synthetic Improvements. One significant modification of the Stembach process is the result of work by Sumitomo chemists in 1975, in which the optical resolution—reduction sequence is replaced with a more efficient asymmetric conversion of the meso-cyc. 02Lcid (13) to the optically pure i7-lactone (17) (Fig. 3) (25). The cycloacid is reacted with the optically active dihydroxyamine [2964-48-9] (23) to quantitatively yield the chiral imide [85317-83-5] (24). Diastereoselective reduction of the pro-R-carbonyl using sodium borohydride affords the optically pure hydroxyamide [85317-84-6] (25) after recrystaUization. Acid hydrolysis of the amide then yields the desired i7-lactone (17). A similar approach uses chiral alcohols to form diastereomic half-esters stereoselectivity. These are reduced and direedy converted to i7-lactone (26). In both approaches, the desired diastereomeric half-amide or half-ester is formed in excess, thus avoiding the cosdy resolution step required in the Stembach synthesis. 

The remarkable stereospecificity of TBHP-transition metal epoxidations of allylic alcohols has been exploited by Sharpless group for the synthesis of chiral oxiranes from prochiral allylic alcohols (Scheme 76) (81JA464) and for diastereoselective oxirane synthesis from chiral allylic alcohols (Scheme 77) (81JA6237). It has been suggested that this latter reaction may enable the preparation of chiral compounds of complete enantiomeric purity cf. Scheme 78) ... 

The frequent use of chiral controller or auxiliary groups in enantioselective synthesis (or diastereoselective processes) obviously requires the addition of such units retrosynthetically, as illustrated by the antithetic conversion 34 =i> 35. 

There are a number of powerful synthetic reactions which join two trigonal carbons to form a CC single bond in a stereocontrolled way under proper reaction conditions. Included in this group are the aldol, Michael, Claisen rearrangement, ene and metalloallyl-carbonyl addition reactions. The corresponding transforms are powerfully stereosimplifying, especially when rendered enantioselective as well as diastereoselective by the use of chiral controller groups. Some examples are listed in Chart 20. 

Since cbiral sulfur ylides racemize rapidly, they are generally prepared in situ from chiral sulfides and halides. The first example of asymmetric epoxidation was reported in 1989, using camphor-derived chiral sulfonium ylides with moderate yields and ee (< 41%) Since then, much effort has been made in tbe asymmetric epoxidation using sucb a strategy without a significant breakthrough. In one example, the reaction between benzaldehyde and benzyl bromide in the presence of one equivalent of camphor-derived sulfide 47 furnished epoxide 48 in high diastereoselectivity (trans cis = 96 4) with moderate enantioselectivity in the case of the trans isomer (56% ee). ... 

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). 

Diastereoselective synthesis of pyrrolidine derivatives using chiral and non-racemic A-cyanomethyloxazolidines 99CSR383. 

Chiral and nonracemic A-cyanomethyloxazolidines in diastereoselective synthesis, particularly of pyrrolidine and piperidine derivatives 99CSR383. 

Diastereoselective synthesis, particularly of piperidine derivatives using chiral and nonracemic A-cyanomethyloxazolidines 99CSR383. 

Chiral 3-alkenoyl-l,3-oxazolidin-2-ones have been developed and used in highly diastereoselective Diels-Alder reactions by Evans et al. [26] (Scheme 1.34). In this reaction these dienophiles are highly reactive compared with the corresponding... 

The chiral copper reagent 24 is an effective catalyst not only for intermolecular, hut also for intramolecular Diels-Alder reactions, as shown in the following schemes (Scheme 1.41, 1,42, 1.43). Synthetically useful octalin and decalin skeletons were synthesized in high enantio- and diastereoselectivity. The synthetic utility of this intramolecular Diels-Alder reaction has been demonstrated hy a short total synthesis of isopulo upone [23, 33d]. 

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