SyManti ratios

A straightforward method for aldolizing unsymmetrical ketones on the more hindered side involves the use of catalytic titanium(lV) chloride in toluene at room temperature. For examples using acyclic and cyclic ketones, and linear, branched, and aromatic aldehydes, the regioselectivity varied from 7 1 to >99 1, while the symanti ratios were moderate to good, and yields were in the range 62-91%. In contrast to other methods, base is not required, and the ketone can be used as is (i.e. the silyl enol ether is not required). 

However, the Rh-catalysed hydrosilylation of terminal alkynes affords the thermodynamically unfavorable anti product 583 as the main product [224], The symanti ratio changes depending on the catalysts and solvents. The syn adduct 584 is obtained by a cationic Rh complex in MeCN [225]. The Ru catalyst gives the anti adduct. Formation of the anti adducts is explained by the following mechanism [224, 226]. Insertion of alkyne to the R3S-RI1 bond generates 585 which, due to steric repulsion, isomerizes to 588 via the carbene species 586, or the metallacyclopropene 587, and gives the anti adduct 583. 

Methyl substitution on the allylic system strongly affects the symanti ratio of adducts (Table 27). Both cyclic and acyclic transition states have been proposed to account for these observations. In general, (Z)-allylic alcohols tend to give mainly syn adducts, and vice-versa. 

By judicious choice of chiral auxiliary-reagent pairs, it has been possible to extend this chemistry to the enantioselective synthesis of p-hydroxy-a-methyl-carboxylic acid derivatives having either anti or syn stereochemistry (Schemes 24 and 25). For example, the boron azaenolate obtained upon reaction of (65) with diisopinocamphenylboryl triflate reacts with a series of aldehydes to provide adducts that are readily converted to the anti methyl esters (66) in good overall yields (Scheme 24). The anti.syn ratios for these reactions are typically >9 1, and the percentage enantiomeric excesses for the anti adducts are in the range of 77-85%. On the other hand, the boron azaenolate derived from oxazoline (61c) and 9-borabicyclononane triflate reacts with aldehydes to give adducts that can be converted into the methyl esters of the jyn-carboxylic acids (67 Scheme 25). The symanti ratios in these reactions are typically... 

Nakamura, Kuwajima and coworkers have recently shown that TBAF and TAS difluorotrimethylsili-conate-catalyzed reactions give identical sense and degree of stereoselection. As the stereoselectivity of the fluoride-catalyzed aldol reaction is independent of the countercation and of the type of silyl group,the open transition structures A (extended) and B (skew) have been proposed to account for the observed dependence of the symanti ratios on the steric hindrance of R , R and R (Figure 3). - ... 

Steric and conformational effects also play a significant role in determining the symanti ratio. With Al-(6,6-disubstituted-ethyl)-Al,Al,Al-trimethylammonium ions, syn elimination is more prevalent when the 6-substituents are aryl or branched. As the 6-groups become less bulky, the amount of syn elimination decreases. This effect is illustrated by the data below. ... 

Entry R R Lewis acid Mol% Yield (%) Ratio symanti... 

Another example of the all-TB-at-once protocol that gives excellent yields when the para position is occupied is summarized in Scheme 9 (05MI1). Starting from p-phenylenediamine 47 and the acid chloride 48, bis-TB 43 (40% symanti 1 2) was obtained in a 35% overall yield. Moreover, it was shown that the syn- to anti-bis-TB ratio strongly depends on medium, e.g. the solvent used, and can be significantly driven by a template (05MI1). 

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