1,2-Stereoinduction

In 2001, Imamoto et al. reported the preparation of novel chiral S/P-bidentate ligands containing a chirogenic centre at the phosphorus atom and their stereoinduction capability in palladium-catalysed asymmetric allylic substitution reactions (Scheme 1.14)." ... 

Simpler chiral pyrrolidine thioethers, reported in 2004 by Skarzewski et al., proved to be effective ligands in the test reaction. The sense of the stereoinduction was in agreement with the nucleophilic attack directed at the allylic carbon located trans to the sulfur atom in the intermediate complex (Scheme 1.40). 

Diastereoselectivity was observed as the result of stereoinduction (Equation (41)), giving preferential formation of the 1,2-trans products. Enhancement of the diastereoselectivity in the cycloisomerization of enyne 65a n= 1) was observed with the use of the catalyst bearing the sterically demanding Cp ligand 64. 

Stereoinduction was observed, as in the formation of 74 (Equation (46)) as a single diastereomer 1,3-stereo-induction was not successful. Most substrates contained only methyl-substituted olefins, leading to terminal alkenes. In the case of the cycloisomerization of an //-propyl-substituted enyne, a modicum of selectivity with respect to olefin geometry was exhibited 73 was produced in an isomeric ratio of 1 3.5. The authors do not specify whether the (E)- or (Z)-geometry was preferred. 

Stereoinduction was an efficient means to generate substituted cyclopentanes in a highly diastereo-selective manner using the Fe(acac)3 conditions. Gyclization of triene 81 gave trans- and cis-82 in a >99 1 ratio (Equation (51)). Unfortunately, 1,3-stereoinduction did not lead to useful amounts of diastereoselectivity. 

These examples (and others) indicate that trans-fused products are favored when the two dienes are joined by a four-carbon chain, whereas ds-fused products are favored by connection with a three-carbon chain. The first example also shows that high stereoinduction is possible in this intramolecular reaction. 

A stochiometric approach was applied by Van Koten and co-workers [29], who used chiral carbosilane dendrimers as soluble supports in the in situ ester enolate-imine condensation in the synthesis of /Mactams (e.g. 19, Scheme 20). The formation of the /Mactam products proceeded with high trans selectivity, and with the same level of stereoinduction as was earlier established in reactions without the dendritic supports, (i.e. the use of the enantiopure dendritic support did not affect the enantioselectivity of the C-C bond formation). After the reaction, the dendrimer species could be separated from the product by precipitation or GPC techniques and reused again. 

A model accounting for the observed sense of absolute stereoinduction is based upon the coordination mode revealed in the crystal structure of the cyclometallated C,0-benzoate complex [280]. It is postulated that aldehyde binding by the a-allyl haptomer occurs such that the allyl moiety is placed between the naphthyl and phenyl moieties of the hgand, allowing the aldehyde to reside in a more open enviromnent. In the favored mode of addition, the aldehyde C-H bond projects into... 

Fig. 3 Proposed stereochemical model accounting for the observed sense of absolute stereoinduction (chiral ligand = (5)-Cl,MeO-BIPHEP)...

Lactams were obtained in 80-95% conversion with high trans-selectivity (de >95%) but only moderate enantioselectivity ee ca. 30%). The stereoinduction results from the relatively remote stereocentres located at the linker units. For support recovery the authors performed nanofiltration experiments and it was found that the recovered dendrimers could be easily reused as substrate carriers. 

Interestingly, fundamentally different stereoinduction mechanisms have been proposed for the activation of a number of related imine substrates, studies that resulted in the development of simple and highly effective new catalytic systems (27) for the addition of silyl ketene acetals to Al-Boc-protected aldimines (Mannich reaction) (Scheme 11.12c). ... 

The synthesis of a-chiral isocyano amides has also been reported using various dehydration methods [47, 53-66]. Because of the lower acidity of the a-proton in a-isocyano amides, high stereoinductions can be obtained using relatively harsh dehydration methods (POCls/EtsN, —20°C) [62]. However, the triphosgene/NMM protocol remains the method of choice [53]. 

Scheme 2. Stereoinduction model for additions of E)-l to a-chiral aldehyde 39.

The stereoinductive effect of the a-substituent is often more powerful when this substituent is a polar group such as an alkoxy or amino gronp. In this instance as well, minimization of syn-pentane interactions with 3-monosnbstituted reagents is important, and the selectivity can be amplified if it acts in concert with other effects. Known models inclnde the stereoelectronic preference... 

Scheme 5. Model for absolute stereoinduction in additions of tartrate allylic boronate 53 to aldehydes.

One major advantage of chiral auxiliary reagents over chiral a-substituted reagents is the fact that the chiral diol or diamine unit is not modified in the bond-making process and is thus potentially recyclable. The preparation of enan-tiomerically pure a-substituted reagents requires a stereoinductive transformation... 

Scheme 8. Stereoinduction model for the additions of chiral a-chloro allylboronate 23.

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