Internal diastereoselective induction

In all the examples commented upon so far, we have dealt with reactions with internal diastereoselective induction. However, when a chiral centre is already present in one of the components [12] we must refer then to a relative diastereoselective induction, and Cram s rule [13] must be taken into account when the chiral centre is present at the a-position of the aldehyde (28). For instance, in the reaction shown in Scheme 9.7 of the four possible diastereomers only two are formed, the Cram-i yn-aldol 30a being the predominant diastereomer (see below 9.3.3). 

Carbonyl-Ene Reaction. BINOL-TiX2 reagent exhibits a remarkable level of asymmetric catalysis in the carbonyl-ene reaction of prochiral glyoxylates, thereby providing practical access to a-hydroxy esters. These reactions exhibit a remarkable positive nonlinear effect (asymmetric amplification) that is of practical and mechanistic importance (eq 19). The desymmetrization of prochiral ene substrates with planar symmetry by the enantiofacial selective carbonyl-ene reaction provides an efficient solution to remote internal asymmetric induction (eq 20). The kinetic resolution of a racemic allylic ether by the glyoxylate-ene reaction also provides efficient access to remote but relative asymmetric induction (eq 21). Both the dibromide and dichloride catalysts provide the (2R,5S)-syn product with 97% diastereoselectivity and >95% ee. 

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 most important feature of the Ireland variant is the control of the enolate geometry which allows the internal asymmetric induction (simple diastereoselectivity) of the rearrangement to be controlled (see Section 1.6,3.1.1.4.1.2. p 3412). 

Therefore, the internal asymmetric induction (simple diastereoselectivity) in these types of rearrangement is related to control of the vinyl and allyl double bond in the transition state. 

It is possible to control the internal asymmetric induction (simple diastereoselectivity) in ortho ester rearrangements by using special substitution patterns in the substrate. Thus, starting materials obtained from allylic alcohols 6 with a C-5 substituent R2 preferentially yield syn-diastereomers 7 due to 1,3-diaxial interactions of the substituents R2 and R3, which disfavor the transition state B, The necessity of a C-5 substituent for achieving diastereocontrol in ortho ester rearrangements is shown in Table 7, entry 1 in comparison to entry 3455. 

A chiral 2-alkyl-4,5-dihydrooxazole 7 is obtained by the use of (+)-( 5, 2 S)-1-phenyl-2-aminopropane-1,3-diol, available from the chiral pool (see p 115). From this, the methyl ether 8 is prepared using sodium hydride and iodomethane. As a result of internal asymmetric induction, the alkylation of its lithium derivative occurs diastereoselectively. In the case of = Me, = Et, hydrolysis yields the (+)-( S)-enantiomer of 2-methylbutanoic acid 9, with ee = 67 %, as the main product ... 

Discussing the stereochemical outcome of the Claisen rearrangements, two aspects had to be considered. On one hand, the relative configuration of the new stereogenic centers was found to be exclusively syn in 308 and 309 suggesting a chair-like transition state c-a and c-fS, respectively, including a Z acyl ammonium enolate structure (complete simple diastereoselectivity/internal asymmetric induction, Scheme 10.64). 

Radical cyclization reaction often proceeds with high diastereoselectivity and high asymmetric induction when chiral precursors are used. Internal alkynes... 

Deprotonation of the (S)-phenylalaninol derivative (S)-181 in the presence of the achiral Hgand TMEDA produces the diastereomers 182 and 183 in a ratio of 90 10 [Eq. (47,see Sect 2.4) [68]. Here,due to internal substrate-inherent induction, the pro-R-H is removed preferentially ( / induction [ 118]). In the presence of (-)-sparteine, which has a high preference for the pro-S protons Ik induction), the diastereomer 183 is formed with an opposite 90 10 diastereoselectivity obviously the substrate-inherent diastereoselectivity is overridden by the reagent-induced selectivity. 

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