Reagent-based stereocontrol

An instance of the enantiofacial preference of the reacting partner overwhelming that of the reagent is shown in the case of the reagent s reaction with the tartrate-derived allyl boronates shown. Even in the mismatched case, this example of reagent-based stereocontrol affords a greater than 10 1 selectivity for the syn product (eq ). ... 

Figure 1.6. Reagent-based stereocontrol in double asymmetric induction.

Scheme 1.6. Matched and mismatched double asymmetric induction demonstrating Reagent-Based Stereocontrol (a) The diethylzinc addition catalyzed by titanium TADDOLates (Chapter 4, [52]). (b) The Sharpless asymmetric epoxidation (Chapter 8,...

Scheme 5.24. Reagent-based stereocontrol in aldol additions using Evans imide enolates [125],...

Whereas the thermodynamic route described above relied on reagent control to establish the spongistatin C19 and C21 stereocentres, the discovery of highly stereoselective 1,5-anti aldol reactions of methyl ketones enabled us to examine an alternative,16 substrate-based stereocontrol route to 5. Regioselective enolisation of enantiomerically pure ketone 37, derived from a readily available biopolymer, gave end... 

Further addition of the Grignard reagent can take place to give -hydroxy silanes with high diastereoselectivity (Scheme 103)12,165. The hydroxy silanes can of course undergo subsequent stereocontrolled acid or base catalysed elimination of trialkylsilanol to give alkenes. 

Stereocontrolled ethynylation of methyl 2,3,4-tri-O-benzyl-a-D-g/Hco-hexodialdo-l,5-pyranoside (52) with a Grignard reagent formed from trimethylsilylacetylene, followed by a multistep procedure afforded the aminouronic acid 53, the a-amino acid on which miharamycin A is based.168 Uronic acid derivatives have also been produced by the Wittig reaction on the aldehydic side chain of dialdofuranose compounds.169... 

Indeed, the forwards reaction uses a boron triflate and a bulky base of the type we have seen in order to make the cis boron enolate and achieve exactly this control. There are, of course, two. wn-aldol products possible here, 58 and 60, by virtue of the chiral centres present in the aldehyde fragment, and both do indeed form (in a 16 84 ratio). Trying to achieve selective formation of one of these syn diastereomers rather than the other syn diastereomer is beyond the scope of this chapter, even though that too is relative stereocontrol. It is complicated because it involves enantio-merically pure reagents in combination with the enantiomerically pure aldehyde and a match/mis-match issue. These issues are explored more fully in Chapter 30. Examples include combinations of chiral or achiral aldehydes with both achiral and chiral boron reagents. 

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