Diastereotopic substituents

Scheme 15. Allylic C-H activation via hydroboration on side-chains bearing diastereotopic substituents.

The motion of ji 3-alkyne and ji 3-aryne ligands in trimetallic clusters has been observed and discussed in several papers. " " Use of diastereotopic substituents (-PMe2Ph, " -C//2CH3, " " -CHA/e2 " ) at the organic ligands has confirmed that their rotation (Scheme 16) requires... 

Highly diastereoface selective Michael additions to chiral cycloalkenones and lactones have been developed264. The selectivity is, in general, due to the shielding of one of the diastereotopic faces by a substituent R at the stereogenic center in the y- or -position (steric effect). 

In the discussion of the stereochemistry of aldol and Mukaiyama reactions, the most important factors in determining the syn or anti diastereoselectivity were identified as the nature of the TS (cyclic, open, or chelated) and the configuration (E or Z) of the enolate. If either the aldehyde or enolate is chiral, an additional factor enters the picture. The aldehyde or enolate then has two nonidentical faces and the stereochemical outcome will depend on facial selectivity. In principle, this applies to any stereocenter in the molecule, but the strongest and most studied effects are those of a- and (3-substituents. If the aldehyde is chiral, particularly when the stereogenic center is adjacent to the carbonyl group, the competition between the two diastereotopic faces of the carbonyl group determines the stereochemical outcome of the reaction. 

The fluorine substituent at the 2-position of a trifluorovinyl group is much more highly shielded than the other two fluorines, and its presence gives rise to an enhanced split of the diastereotopic fluorines at the 1-position and enhanced coupling constants, both geminal and vicinal. 

For purposes of illustration, consider the erythro selective reaction illustrated in eq. [69]. For aldehydes containing an adjacent asymmetric center (R, Rl = medium and large alkyl substituents), the bias for nucleophilic addition from a given diastereotopic face of the aldehyde is predicted empirically by Cram s rule (the open-chain... 

Eliel et al. equilibrated the diastereotopic 2-iPr-5-R-l,3-dioxanes, determined their conformational preferences (Table VII) (77JOC1533), and discussed the results in terms of solvent effects and various repulsive and attractive interactions between the 5-substituent and the ring oxygen atoms (as visualized in Scheme 9). 

The spectral data provide information about the structure of a-acetoxydibenzylnitrosamine (VII). The high frequency (1780 cm ) for the carbonyl group in the infrared spectrum (Fig. 9) is consistent with this structure ( ) and the introduction of the chiral center at the benzylic position causes the methylene of the other benzyl ic substituent to be diastereotopic and appear in the nmr spectrum as an AB quartet. The center of the quartet... 

Regioselectivc endo deprotonation and alkylation of 4,5-dihydroisoxazoles proceeds under asymmetric induction controlled by the substituent(s) in position 5. These substituents shield one of the diastereotopic faces of the 4,5-dihydroisoxazole, such that alkylation provides the trans-diastereomers in excess (see Table 1). 

As a theoretical model, diastereotopically distinct isotopic substitution in 1,3-butadiene was utilized by Bach and coworkersl9b to provide an independent test of the ability of high-level ab initio calculations to accurately predict a transition structure for epoxidation. The calculated KIE for deuterium substitution at the a-carbon in the TS for epoxidation of 1,3-butadiene (Figure 24) (Ha) is 0.99, in excellent agreement with the experimental value for an aryl-substituted styrene. The KIE for diastereotopically distinct hydrogen (Ht,) on the /J-carbon cis to the vinyl substituent is 0.80, while that for Hc is predicted to be 0.82. The calculated KIE is 0.66 for this transition structure with Hc, reflecting the extensive... 

A different experimental approach to the relative importance of one-center and two-center epimerizations in cyclopropane itself was based on the isomeric l-13C-l,2,3-d3-cyclopropanes165"169. Here each carbon has the same substituents, one hydrogen and one deuterium, and should be equally involved in stereomutation events secondary carbon-13 kinetic isotope effects or diastereotopically distinct secondary deuterium kinetic isotope effects may be safely presumed to be inconsequential. Unlike the isomeric 1,2,3-d3-cyclo-propanes (two isomers, only one phenomenological rate constant, for approach to syn, anti equilibrium), the l-13C-l,2,3-d3-cyclopropanes provide four isomers and two distinct observables since there are two chiral forms as well as two meso structures (Scheme 4). Both chiral isomers were synthesized, and the phenomenological rate constants at 407 °C were found to be k, = (4 l2 + 8, ) = (4.63 0.19)x 10 5s l and ka = (4kl2 + 4, ) = (3.10 0.07) x 10 5 s 1. The ratio of rate constants k, kl2 is thus 1.0 0.2 both one-center and two-center... 

On the basis of the above-mentioned studies, trimesitylmethane (7) is expected to have a propeller geometry in the ground state, and to exist in two enantiomeric forms, differing only in their sense of twist (helicity). Consequently, each of the three equivalent mesityl rings has two diastereotopic ortho methyl substituents, in addition to the para methyl group. In the absence of rapid stereoisomerization, the 1H-nmr spectrum of 7 in an achiral solvent should display three methyl resonances of equal intensity. This expectation is in fact realized at 37 °C,... 

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