Stereoselectivity enantiofacial selectivity

With C2-symmetric reagents (5,5)-2,5-dimethyl-l-trifluoromethylsulfonylborolane34 and (R,R)-l-chloro-2,5-diphenylborolane , (S)-(3-ethylpent-3-yl) thiopropanoate is added, via the corresponding enolates, to aldehydes with remarkable auxiliary-induced stereoselectivity. Thus, /1-hydroxy thioestcrs arc obtained with 87-94% ee when the borolanyl triflate auxiliary reagent is used. These ee values do not exactly reflect the enantiofacial selectivity since the borolane is not available in enantiomerically pure form (see Section 1.3.4.2.2.2.). Use of the chiral chloroborolane auxiliary gives the thioestcrs with 95-96% cc70,11. o... 

Not only does acetone undergo a highly enantioselective aldol reaction, but hydroxy acetone exhibits excellent stereoselectivity to produce the anti-aldol products 75 (Scheme 2.3d). For example, L-proline catalyzed the aldol reaction between hydroxy acetone and cyclohexanecarbaldehyde to furnish the anti -diol in 60% yield with a greater than 20 1 diastereomeric ratio. The enantiofacial selectivity of the anti-isomer was higher than >99%. Diastereoselectivities are very high with a-substituted aldehydes, whereas low selectivities are recorded in reactions with aromatic aldehydes and with a-unsubstituted aliphatic aldehydes. It is noteworthy that the levels of enantiofacial selectivity for the anti -aldol products... 

Asymmetric Desymmetrization. Desymmetrization of an achiral, symmetrical molecule is a potentially powerful but relatively unexplored concept for the asymmetric catalysis of carbon-carbon bond formation. While the ability of enzymes to differentiate between enantiotopic functional groups is well known, little is known about the similar ability of nonenzymatic catalysts to effect carbon-carbon bond formation. The desymmetrization by the enantiofacial selective carbonyl-ene reaction of prochiral ene substrates with planar symmetry provides an efficient access to remote internal asymmetric induction which is otherwise difficult to attain (eq 6). The (2R,5S)-xyn product is obtained in >99% ee along with more than 99% diastereoselectivity. The desymmetrized product thus obtained can be transformed stereoselectively by a more classical diastereoselective reaction (e.g., hydroboration). 

The highest degree of diastereoselectivity is between the mismatched pairs. The normal low dia-stereoselectivity of the (-)-menthyloxy diene is completely reversed and enhanced by using the chiral catalyst with opposite enantiofacial selectivity. Since Ae primary cycloadducts also contain the chiral auxiliary, the major stereoisomers can be purified and subsequently eliminated to give optically pure dihy-dropyrones. Tliis method can, therefore, be used as a general method for synthesis of a variety of optically pure dihydropyrones. 

JV-Phenyl- or A-methyl-C-phenyl nitrones with (/ )-4-vinylsulfmyltoluene react with complete stereoselection in a process involving only the. Si-face of the alkene88. Cycloaddition of 4,5-dihydro-3//-pyrrole 1-oxide to unsaturated esters of chiral alcohols derived from camphor occurs with poor enantiofacial selection on the nitrone, but high diastereofacial preference on the alkene89. 

As shown in Table 26, the same selectivities were observed in the reactions of other 3-acyl-l,3-oxazolidin-2-ones. Thus, by using the same chiral source ((R)-(+)-binaphthol), both enantiomers of the Diels-Alder adducts between 3-acyl-l,3-oxazolidin-2-ones and cyclopentadiene were prepared. Traditional methods have required both enantiomers of chiral sources in order to prepare both enantiomers stereoselectively [74], but the counterparts of some chiral sources are of poor quality or are hard to obtain (for example, sugars, amino acids, alkaloids, etc.). It is noted that the chiral catalysts with reverse enantiofacial selectivities could be prepared by using the same chiral source and a choice of achiral ligands. 

A stereochemical analysis has predicted the distribution of isotactic stereoblocks present in isotactic-hemiisotactic polypropylene. For an ideal case (without site epimerization and with perfect enantiofacial selectivity at the more stereoselective site), the derived equations depend only on... 

Interestingly, the stereoselectivity of reactions of cyclohexanone vith iso-butyraldehyde and benzaldehyde vere first predicted by using density functional theory calculations on models based on Houk s calculated transition state of the Hajos-Parrish-Eder-Sauer-Wiechert reaction [125]. The transition states of inter- and intramolecular aldol reactions are almost super-imposable and readily explain the observed enantiofacial selectivity. Relative transition state energies vere then used to predict the diastereo- and enan-tioselectivity of the proline-catalyzed reactions of cyclohexanone vith iso-butyraldehyde and benzaldehyde. The predictions are compared vith the experimental results in Scheme 4.30. The good agreement clearly validates the theoretical studies, and provides support for the proposed mechanism. Additional density functional theory calculation also support a similar mechanism [126, 127]. 

The asymmetric cyclisation of achiral olefinic organohthium reagents by a stereogenic alkah metal centre can be modulated by ( )-sparteine, which confers enantiofacial selectivity on the reaction such that the anionic cyclisation process discriminates between the enantiotopic faces of an unactivated C=C bond. Recently, modifications have been made to the well known hthium-ene cyclisation reaction whereby the subsequent expulsion of a thiophenoxide group yields a fused vinylcyclopropane. Moreover, allylic lithium oxyanion-induced reactivity and stereoselectivity in this intramolecular carbometallation has been demonstrated in the highly stereoselective synthesis of a natural bicyclo[3.1.0] hexane. ... 

The remarkable advantage of this C—C bond formation is that the reaction proceeds in a stereoselective manner. From the screening of microorganisms [71,74,80-81,86], two types of PDase that show complementary enantiofacial selectivity have been found. PDase from yeast (Saccharomyces) catalyzes the attack of TPP-thiazoUum intermediate on the si face of the aldehyde acceptor as shown in Eq. (23). In contrast, the enz)me from Zymo-monas mobilis shows re face selectivity to result in the opposite enantiomer of hydroxy... 

The breakthrough came in 1980, when Ryoji Noyori (Fig. 3.29) showed that rhodium(I)-catalysed double bond migrations could proceed stereoselectively at or below room temperatrue. BINAP served as the ligand. [127] It is obtainable in both enantiomeric forms. The rhodium complex catalyses very selectively the double bond migration. Here occurs an interesting stereochemical connection the (S)-BINAP-rhodium complex converts diethylnerylamine into the (S)-en-antiomer, but converts diethylgeranylamine into its (R)-enantiomer. The (R)-BINAP complex reacts vice versa. Obviously, the catalyst very efficiently differentiates between the enantiofacial sides of the A -double bond, and thereby between the two enantiotopic H-atoms at C-1. 

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