Asymmetric synthesis mismatched double

In general, as the aldehyde a-substituents become more sterically demanding, it becomes more difficult to obtain useful levels of diastereoselection for the product expected from reagent control in mismatched double asymmetric reactions between chiral aldehydes and chiral allyl- and crotylboronates [203]. For this reason, in natural product synthesis, mismatched double asymmetric reactions should be designed to occur early rather than late in a synthetic sequence. 

We began these studies with the intention of applying this tandem asymmetric epoxidation/asymmetric allylboration sequence towards the synthesis of D-olivose derivative 63 (refer to Figure 18). As the foregoing discussion indicates, our research has moved somewhat away from this goal and we have not yet had the opportunity to undertake this synthesis. This, as well as the synthesis of the olivomycin CDE trisaccharide, remain as problems for future exploration. Because it is the enantioselectivity of the tartrate ester allylboronates that has limited the success of the mismatched double asymmetric reactions discussed here, as well as in several other cases published from our laboratorythe focus of our work on chiral allyiboronate chemistry has shifted away from synthetic applications and towards the development of a more highly enantioselective chiral auxiliary. One such auxiliary has been developed, as described below. 

Review on matched and mismatched pairing in double asymmetric synthesis Masamune, S, Choy, W. Petersen, J.S. Sita, L. R., Angew. Chem., Int. Ed. Engl., 1985, 1-30. 

From the many examples of reactions with imines activated in various ways, we select the asymmetric synthesis of pipecolic acids by double diastereomeric induction using an activated imine 87 with two chiral auxiliaries - a-methylbenzylamine on the nitrogen atom and 8-phenylmenthol as esterifying group. Both these auxiliaries were discussed in earlier chapters (22 and 27). Acid-catalysed cycloaddition with normal dienes gives excellent asymmetric induction and reasonable yield. We show the matched case - the mismatched case is obviously worse.13... 

In studies directed toward the total synthesis of tedanolide [38], the addition of y-substituted ketene acetal 60 to aldehyde 84 generated unsaturated ester 85 in 62% yield (Scheme 30). The resulting double bond could be further functionalized by applying Sharpless asymmetric dihydroxylation conditions. Hence diol 86, which represents the mismatched case due to unfavorable... 

When two of the reaction components are chiral (any combination of substrate, reagent, catalyst, or solvent), the chirality elements of each reactant will operate either in concert (matched pair) or in opposition (mismatched pair) and together influence the stereochemical outcome of the reaction. In this case, the reaction is subject to double asymmetric induction. Unless the diastereofadal selectivities of both chiral reactants are in opposition and identical in magnitude, the ratio C D 1. Applications of double asymmetric induction in synthesis will be discussed in Chapter 5. 

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