Stereodirecting auxiliary

The selenophenyl substituent, which served as stereodirecting auxiliary (Section 4.2), was then removed to give the 2 -deoxy disaccharide 62. 

Tan and coworkers [28] developed an alternative scaffolding strategy [27]. The stereodirecting auxiliary was generated from 2-alkoxy-l,3-azaphospholidines (Scheme 4.118). The latter were available by a three-step sequence starting from Af-methyl aniline without using any chromatographic separations. 

The first attempts to develop reactions offering control over the absolute stereochemistry of a chiral center, created by y-selective substitution of an achiral allylic alcohol-derived substrate, involved the use of chiral auxiliaries incorporated in the nucleofuge. The types of stereodirecting groups utilized vary, and have included sulfoximines [15], carbamates [16], and chiral heterocyclic sulfides [17-19]. 

A new camphor-derived auxiliary was developed by Dixon and coworkers as a stereodirecting group for highly diastereoselective alkylations of an attached glycinamide residue... 

In the sections that follow, the discussions progress through simple diastereoselection, control from indigenous chirality present in the substrate, control from a removable chiral auxiliary, ultimately to absolute stereodirection from an external species not formally bound in a covalent fashion to the substrate. There have been several previous reviews of the ene reaction, although none has focused on both relative and absolute stereochemical aspects 6-14 20. 

Br, or I) (equation 1). Another method relies on alkylation of a-hydroxy or a-alkoxy carbonyl compounds. The induction of diastereoselectivty, in these cases, is achieved through the use of chiral auxiliaries and other stereodirecting groups (equation 2). The third method frequently utilizes the nucleophilic addition of hydride or other carbanions to a-dicarbonyl compounds (equation 3). In addition to being laborious, nonoxidative methods are limited to the synthesis of acyclic compounds, which greatly reduces the magnitude of their synthetic practicality. 

The main features of an efficient chiral auxiliary are (i) Commercial availability at low cost in both enantiomeric forms (ii) the facility of insertion on the substrate and removal from the product in high yields and non-racemizing conditions and, obviously, (iii) powerful and predictable stereodirecting ability. 

Chiral lithium diphenylbinaphtholate (2) has been found to be an effective catalyst for the enantioselective aldol-Tishchenko reaction, affording 1,3-diol derivatives with three contiguous chiral centres and high stereoselectivities (up to 99% ee) ° A direct, highly enantioselective alkylation of arylacetic acids via enediolates using a readily available chiral lithium amide (3) as a stereodirecting reagent has been developed. This approach circumvents the traditional attachment and removal of chiral auxiliaries used currently for this type of transformation. 

Both procedures normally give (Z)-enolates in greater than 99% selectivity. These react with aldehydes via a cychc six-membered transition state of the Zimmerman-Traxler type, with one face of the imide enolates hindered by the auxiliary, forcing attack of the aldehyde at the opposite face. As with diastereoselective a-alkylations (previous section), the stereodirecting influence of the auxiliaries generally overrides that imposed by ancillary stereogenic centers in the aldehyde substrates . 

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