Cis/trans selectivity

Ni(C104)2 6H2O showed a litde better enantioselectivity than the anhydrous complex. Although the uncatalyzed reaction was highly exo selective (cis/trans=i 97), the catalyzed reactions were very poor in diastereoselectivity, a mixture of endo and exo cycloadducts being formed. We expected that this poor diastereoselectivity would not be a serious problem since the same enantioface should be involved at the 2-position of the diastereomeric cycloadducts (Scheme 7.27). The best enantioselectivity (cis > 99% ee, trans 94% ee) was observed when the reaction was catalyzed by l ,J -DBFOX/Ph-Ni(SbF6)2 (50 mol%). With the decreased amount of catalyst (10 mol%) still a satisfactory level of enantioselectivity was observed for the cis cycloadduct (94% ee). 

Motherwell and Whitehead et al. reported a similar intramolecular reductive aldol reaction of aldehyde-enoate derivatives. The cyclization of 6-oxo-ester 23 was catalyzed by RhCl(PPh3)3 (1 mol%) with Et3SiH (210 mol%) as terminal reductant (Scheme 9) [17,18]. The cyclization proceeded at 50 °C for 18 h to give the aldol product 24 in 81% yield with ds-selectivity (cis trans =... 

Mononuclear oxazolines have been less studied. Moderate enantioselectivities (up to 60%) were obtained using PyrOx as ligands for the copper(l)-catalyzed carbene-transfer reaction of ethyl diazoacetate to styrene." " " However, the diastereo-selectivities (cis/trans) in these reactions were generally poor. 

The aldehydes 42 and 43 were subjected to the key intramolecular aldol-type cyclization to afford the c/.s-fused quinolinone 44 selectively (cis trans=6.5 1, 52% isolated yield) or 45 exclusively (51% yield). The stereochemistry of 44 and 45 was determined by NOE experiments as shown in Scheme 17. 

Catalyst Time a h b Conv. % Epoxide Yield (%) Selectivity (%) cis trans e.e. trans (%) ... 

Styrene cyclopropanation continues to attract much interest. Cationic complex CpFe(CO)2(THF) BF4" mediates carbene transfer from ethyl diazoacetate with high cis selectivity cis trans = 85 15) [38]. On the other hand, Tp Cu(C2H4), where Tp is hydrotris(3,5-dimethyl-l-pyrazolyl)borate, is one of the rare catalysts to promote carbene transfer from ethyl diazoacetate to alkenes and also to alkynes. While cyclopropanes are formed in high yield, cyclopropenes are obtained only in moderate yield [39]. The same complex also catalyzes nitrene transfer from PhI=NTs to alkenes to produce aziridines in high yields. 

Wei CC, Gao G and Kispert LD (1997) Selected cis/trans isomers ofcarotenoids formed by bulk electrolysis and iron(III) chloride oxidation. J Chem Soc Perkin Trans 2 pp 783-786 WolffC and Witt HT (1969) On metastable states ofcarotenoids in primary events ofphotosynthesis. Z Naturforsch 24b 1031-1037... 

Catalyst Selectivity ketol (%) diol (%) ring-opened product %) stereo- selectivity (cis/trans)... 

In N-acyliminium ion-mediated functionalization of 2- or 6-alkoxy-substituted piperidines, Sc(OTf)3 was found to be an excellent Lewis acid with a silyl enol ether nucleophile, and moderate diastereoselectivities were obtained (trans/cis = 26/74 and 78/22, respectively) [158]. Sc(OTf)3 was found to be a more efficient metal tri-flate in the nucleophilic substitution of N-benzyloxycarbonyl-2-methoxypiperidine and 3-substituted-2-acyloxy-N-benzyloxy-carbonylpiperidine with silylicon enolates [159]. 2-Acetoxy-3-benzyloxy-N-benzyloxycarbonylpiperidine afforded the 2-alkylat-ed adducts in high cis selectivity (cis/trans = 71/29), while 2,3-diacyloxy-N-benzyl-oxycarbonylpiperidines showed trans selectivity (trans/cis = 80/20-100/0). Febri-fugine, a potent malarial alkaloid, was successfully synthesized from 2,3-diacetoxy car bony Ipiperidine on the basis of these diastereoselective nucleophilic substitution reactions. 

Figure B2.4.2. Eyring plot of log(rate/7) versus (1/7), where Jis absolute temperature, for the cis-trans isomerism of the aldehyde group in fiirfiiral. Rates were obtained from tln-ee different experiments measurements (squares), bandshapes (triangles) and selective inversions (circles). The line is a linear regression to the data. The slope of the line is A H IR, and the intercept at 1/J = 0 is A S IR, where R is the gas constant. A and A are the enthalpy and entropy of activation, according to equation (B2.4.1)...

Accumulating evidence makes it increasingly clear that there is no single dominant Wittig transition state geometry and, therefore, no simple scheme to explain cis/trans selec-tivities. The conventional betaine pathway may not occur at all, the stabilized ylides, e,g., PhsP—CH —C02Et, can be ( )- or (Z)-selective, depending on the solvent and substrate (E. Vedejs, 1988 A, B, 1990). 

Selenourea [630-10-4] ]5k.e urea and thiomea can form channel inclusion compounds (87) with a variety of hydrocarbons. Though the difference in channel diameter between thiourea and selenourea is small, selenourea seems to be much more selective for the inclusion of certain guest molecules (eg, cis/trans isomers). 

Selectivities to various isomers are more difficult to predict when metal oxides are used as catalysts. ZnO preferentially produced 79% 1-butene and several percent of i7j -2-butene [624-64-6] (75). CdO catalyst produced 55% 1-butene and 45% i7j -2-butene. It was also reported that while interconversion between 1-butene and i7j -2-butene was quite facile on CdO, cis—trans isomeri2ation was slow. This was attributed to the presence of a TT-aHyl anion intermediate (76). High i7j -2-butene selectivities were obtained with molybdenum carbonyl encapsulated in 2eohtes (77). On the other hand, deuteration using H1O2 catalyst produced predominantly the 1,4-addition product, trans-2-huX.en.e-d2 with no isotope scrambling (78). 

Alternatively, epoxides can be formed with concomitant formation of a C-C bond. Reactions between aldehydes and various carbon nucleophiles are an efficient route to epoxides, although the cis. trans selectivity can be problematic (see Section 9.1.4). Kinetic resolution (see Section 9.1.5.2) or dihydroxylation with sequential ring-closure to epoxides (see Section 9.1.1.3) can be employed when asymmetric epoxidation methods are unsatisfactory. 

An excellent method for the diastereoselective synthesis of substituted amino acids is based on optically active bislactim ethers of cyclodipeptides as Michael donors (Schollkopf method, see Section 1.5.2.4.2.2.4.). Thus, the lithium enolates of bislactim ethers, from amino acids add in a 1,4-fashion to various a,/i-unsaturated esters with high diastereofacial selectivity (syn/anti ratios > 99.3 0.7-99.5 0.5). For example, the enolate of the lactim ether derivative 6, prepared from (S)-valine and glycine, adds in a highly stereoselective manner to methyl ( )-3-phenyl-propenoate a cis/trans ratio of 99.6 0.4 and a syn/anti ratio of 91 9, with respect to the two new stereogenic centers, in the product 7 are found105, los. 

In a modified procedure, these additions lead to / ,y- and ) <5-unsaturated amino acid derivatives with cis/trans selectivity >99 1 and syn/anti diastereoselectivity >99 1 (see Section I.5.2.4.2.2.4.)108. 

Electrochemical oxidation of 4-aryl-substituted thiane in aqueous organic solvents containing various halide salts as electrolytes gave selectively the trans-sulfoxide (lOe). Under acidic conditions a preferential formation of the cis-sulfoxide was attained328. The stereoselective potential of this method for the oxidation of cyclic sulfides139,329 is apparent (equation 123). 

Trienone 124 underwent intramolecular cycloaddition affording hydrobenzo-suberone 125. Thermal reaction was poorly diastereoselective (62 38 cis trans stereoisomers). When the cycloaddition was carried out in the presence of LiBF4, trienone 124 was converted into cA-adduct 125 quantitatively and stereo selectively [118] (Equation 2.35). 

The isomerization takes place because the excited states, both 5i and T, of many alkenes have a perpendicular instead of a planar geometry (p. 311), so cis-trans isomerism disappears upon excitation. When the excited molecule drops back to the So state, either isomer can be formed. A useful example is the photochemical conversion of c/s-cyclooctene to the much less stable trans isomer." Another interesting example of this isomerization involves azo crown ethers. The crown ether (5), in which the N=N bond is anti, preferentially binds NH4, Li, and Na, but the syn isomer preferentially binds and Rb (see p. 105). Thus, ions can be selectively put in or taken out of solution merely by turning a light source on or off." ... 

Rhodium complexes with chelating bis(oxazoline) ligands have been described to a lesser extent for the cyclopropanation of olefins. For example, Bergman, Tilley et al. [32] have prepared a family of bis(oxazoline) complexes of coordinatively unsaturated monomeric rhodium(II) (see 20 in Scheme 13). Interestingly, the use of complex 20 in the cyclopropanation reaction of styrene afforded mainly the cis cyclopropane cis/trans = 63137), with 74% ee and not the thermodynamically favored trans isomer. No mechanistic suggestions are proposed by the authors to explain this unusual selectivity. 

The selectivity in the hydrogenation of di-substituted benzenes such as xylene, methylanisole, cresol was also reported. In all cases, the czs-compound is largely the major compound > 80%. The ratio cis/trans decreases with the position of the substituents o > m>p but the identity of the metal does not seem important with this surfactant-stabilized system [45,47]. 

In summary, all the experiments expressly selected to check the theoretical description provided fairly clear evidence in favour of both the basic electronic model proposed for the BMPC photoisomerization (involving a TICT-like state) and the essential characteristics of the intramolecular S and S, potential surfaces as derived from CS INDO Cl calculations. Now, combining the results of the present investigation with those of previous studies [24,25] we are in a position to fix the following points about the mechanism and dynamics of BMPC excited-state relaxation l)photoexcitation (So-Si)of the stable (trans) form results in the formation of the 3-4 cis planar isomer, as well as recovery of the trans one, through a perpendicular CT-like S] minimum of intramolecular origin, 2) a small intramolecular barrier (1.-1.2 kcal mol ) is interposed between the secondary trans and the absolute perp minima, 3) the thermal back 3-4 cis trans isomerization requires travelling over a substantial intramolecular barrier (=18 kcal moM) at the perp conformation, 4) solvent polarity effects come into play primarily around the perp conformation, due to localization of the... 

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