Diastereomeric excess

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],... 

When chiral enolates are allowed to react with W-fluoro-2,4,6-trimethyl-pyridinium triflate (K, Table 3b), moderate diastereomeric excesses are achieved [79] (equation 44)... 

The [2 + 2] cycloaddition reaction of A -benzyl-l,4-dihydropyridine 34b with acrylonitrile, followed by catalytic reduction gave two pairs of diastereoisomeric amides 36 and 37 with a low diastereomeric excess, probably due to the large distance between the asymmetric center and the site of acrylonitrile attack. Compounds 36 and 37 were resolved into the four individual diastereoisomers (ca 5% for compound 36 and 15% for 37) [97JCR(M)321], Irradiation of 1,4-dibenzyl-1,4,5,6-tetrahydropyridine 38 in the presence of 29 gave two stereoisomers. 

Treatment of bis-lactim ether 420 with BuLi, then with cw-l,4-dichloro-2-butene in the presence of Nal afforded 3,4,9,9n-tetrahydro-6//-pyrido[l,2-fl]pyrazin-4-one (421) with 96% diastereomeric excess (97TA1855). Reaction of l,2-diphenyl-6-methyl-quinoxaline with 1,4-dichlorobutane in THF in the presence of Na at —78°C afforded a 3 1 mixture of 4a,5-diphenyl-9-methyl-l,2,3,4-tetrahydro-4a//-pyrido[l,2-n]quinoxaline and 4-(4-chlorobutyl)-2,3-diphenyl-6-methyl-1,4-dihydroquinoxaline (98JHC1349). 

The titaniated (25)-2,5-dihydro-2-isopropyl-3,6-dimethoxypyrazines derived from cyclo(L-Val, Gly) or cyclo(L-Val, Ala) (1, R1 = H, CH3) react with a,/I-unsaturatcd aldehydes exclusively by 1.2-addition (cf. nearly exclusive 1,4-addition of ,//-unsaturated ketones with cuprate complexes of 2,5-dialkoxy-3,6-dihydropyrazines, see Section D. 1.5.2.3.1.4.) in a highly diastereoselective mode to give virtually only the (l S,2R)-diastereoniers 2 ". In reactions with the corresponding lithiated pyrazines both regioselectivity and diastereofacial differentiation at C-2 are also remarkably high (dc 95 %), but the diastereomeric excess at C-l is substantially smaller (30 50%) ... 

In a manner similar to carbonyl compounds, thioketones react with lithiated (2,S )-2,5-dihvdro-2-isopropyl-3,6-dimethoxypyrazines to give the 2,5-trun.s-adducts 2 with the diastereomeric excess exceeding 95% 12. The adducts can be further modified to give vinylglycine derivatives12. 

The reaction of propargylic chiral acetals with a catalytic copper reagent (RMgX/5% CuX) provides the expected alkoxy allenes in quantitative yield (Table 3)61. The diastereomeric excess is highly dependent on the size of the ring of the acetal and on the type of substituents it contains. The best diastereomeric excess is 85% with the acetal derived from cyclooctanediol. The use of lithium dimethylcuprate results in 1,2-addition lo the triple bond and the resulting lithium alkenyl cuprate bearing a cyclic acetal does not eliminate even at reflux temperature ( + 35°C). 

More recently, the Lewis acid promoted asymmetric 1,4-addition of trimethyl(2-propenyl)silane to chiral a,/ -unsaturated /V-acylamides has been published33. Lewis acid mediated reactions of trimethyl(2-propenyl)silanes with a,/I-unsatu rated AT-acyloxazolidinones or iV-enoylsultams show high chemical yield with good diastereomeric excess. The absolute configuration of the new asymmetric center is controlled by the nature of the Lewis acid used. 

Charlton121 has recently reported the asymmetric induction in the reaction of dimethyl fumarate and l,3-dihydrobenzo[c]thiophene 2,2-dioxide (198) containing a chiral a-alkoxy group at the 2-position (equation 128). A diastereomeric excess of 2.8 1 of 199 to 200 is achieved by using 198 derived from optically active a-methylbenzyl alcohol. 

The cycloaddition of chiral, racemic and non-racemic alkoxybutadienes 109 with phenyltriazolinedione led to aza compounds [110] in high yield, with good facial selectivity (diastereomeric excess 87-92%) (Equation 2.31). The cycloadditions of the same dienes with N-phenylmaleimide require Lewis acid catalysis. 

Substituted 3,4-dihydropyranes were also prepared by Diels-Alder reactions between (E)-4-oxobutenoate 80 and vinylethers [80] under iron(III) 2-ethylhex-aonate, a mild and economical catalyst (Equation 3.26). Diastereomeric excess as high as 98 % was observed. Cycloadducts with a 2,4-cw-configuration were preferred. 

For this reaction, CALB catalyzes the amidation between a racemic P-hydroxyester and racemic amines, leading to the corresponding amide with very high enantiomeric and diastereomeric excesses. Besides, the remaining ester and amine are recovered from the reaction media, also showing good enantiomeric excesses. By this method, three enantioenriched interesting compounds are obtained from an easy one-step reaction. 

A related situation is found in the case of P-substituted cycloketones here, the electronic difference between the two a-carbons is almost insignificant, resulting in unselective migration upon chemical oxidation. BVMOs have a particularly different behavior, as they can influence the stereo- and/or regioselectivity of the biooxidation. In the latter case, the distribution of proximal and distal lactones is affected by directing the oxygen insertion process either into the bond close or remote to the position of the P-substituent. Consequently, a regioisomeric excess (re) can be defined for this biotransformation, similar to enantiomeric excess or diastereomeric excess values [143]. 

The diastereomeric excess (d.e.) of 76a reached 72% (epoxidation) and 98% (dihydroxylation). Nitro substitution on the aromatic ring (as in 77a) significantly reduced the selectivity (increased the syn proportion), although anti preference was stiU retained in epoxidation (20% d.e.) and in dihydroxylation (68% d.e.). 

Sulfonic peracids (66) have also been applied recently to the preparation of acid sensitive oxiranes and for the epoxidation of allylic and homoallylic alcohols, as well as relatively unreactive a, p - unsaturated ketones. These reagents, prepared in situ from the corresponding sulfonyl imidazolides 65, promote the same sense of diastereoselectivity as the conventional peracids, but often to a higher degree. In particular, the epoxidation of certain A -3-ketosteroids (e.g., 67) with sulfonic peracids 66 resulted in the formation of oxirane products (e.g., 68) in remarkably high diastereomeric excess. This increased selectivity is most likely the result of the considerable steric requirements about the sulfur atom, which enhances non-bonded interactions believed to be operative in the diastereoselection mechanism <96TET2957>. 

In the asymmetric version of the [1,2] -aWittig rearrangement (see Sect. 3.2), the deprotonation of S-methyl (ferf-butyl)arylphosphinothioate 103 followed by alkylation affords the corresponding (alkylthiomethyl)phosphine oxides 104 together with over-reacted products 105 (no diastereomeric excess is observed for this compound) and 106 [67] (Scheme 30). 

More recently, the addition of cyanide ion, generated from TMS cyanide and cesium fluoride, to a-aziridino N-siflfinyl imines, being chiral either at the a position or at sulfur, has been examined [87] (Scheme 28). The configuration of the newly formed stereocenter was determined only by the chiral (S)-sulfinyl group. In fact, the R configuration (diastereomeric excess, de, 98%) was obtained from either the Q -(ii)-imine 186 or the a-(S)-imine 188, giving 187 and 189, respectively. Acyclic 2,3-diaminonitriles can be obtained... 

Other types of new AT-containing ligands have been described as effective chiral inductors for copper-catalyzed asymmetric cyclopropanation. Hence, Fu and Lo [42] prepared a new planar-chiral hgand, namely the C2-symmetric bisazaferrocene (structure 34 in Scheme 18), which was fbimd to be efficient for the cyclopropanation of various olefins with large diastereomeric excesses and ee values up to 95%. 

When dealing with reactions leading to stereoisomeric products we have the additional complication that descriptors such as enantiomeric (diastereomeric) excess and enantiomeric (diastereomeric) ratio are used to describe product purities. The evaluation of RME for a specific stereoisomer, say the R enantiomer, is exactly as above using the connecting relationships for the fraction of each product shown below. 

Diethylaluminum cyanide mediates conjugate addition of cyanide to a, (3-unsaturated oxazolines. With a chiral oxazoline, 30-50% diastereomeric excess can be achieved. Hydrolysis gives partially resolved a-substituted succinic acids. The rather low enantioselectivity presumably reflects the small size of the cyanide ion. 

---