Double-asymmetric synthesis

Double asymmetric synthesis and a new strategy for stereochemical control in organic synthesis [95]... 

When an optically active substrate reacts with an optically active reagent to form two new chiral centers, it is possible for both centers to be created in the desired sense. This type of process is called double asymmetric synthesis (for an example, see p. 1222). 

Double asymmetric synthesis was pioneered by Horeau et al.,87 and the subject was reviewed by Masamune et al.88 in 1985. The idea involves the asymmetric reaction of an enantiomerically pure substrate and an enantiomerically pure reagent. There are also reagent-controlled reactions and substrate-controlled reactions in this category. Double asymmetric reaction is of practical significance in the synthesis of acyclic compounds. 

This chapter has introduced the aldol and related allylation reactions of carbonyl compounds, the allylation of imine compounds, and Mannich-type reactions. Double asymmetric synthesis creates two chiral centers in one step and is regarded as one of the most efficient synthetic strategies in organic synthesis. The aldol and related reactions discussed in this chapter are very important reactions in organic synthesis because the reaction products constitute the backbone of many important antibiotics, anticancer drugs, and other bioactive molecules. Indeed, study of the aldol reaction is still actively pursued in order to improve reaction conditions, enhance stereoselectivity, and widen the scope of applicability of this type of reaction. 

Among the syntheses of complicated natural products, the total synthesis of rifamycin S (44) is another example that shows how a complicated structure can be constructed by applying the concept of double asymmetric synthesis (see Section 1.5.3 for double asymmetric synthesis). Rifamycin S is one of the an-samycin antibiotics, characterized by a distinct structural feature a macro-... 

The poor diastereoselectivity of the reactions of chiral aldehydes and achiral allylboronates appeared to be a problem that could be solved by recourse to the strategy of double asymmetric synthesis.f Our studies thus moved into this new arena of asymmetric synthesis, our objective being the development of a chiral allylboron reagent capable of controlling the stereochemical outcome of reactions with chiral aldehydes independent of any diastereofacial preference on the part of the carbonyl reaction partner. 

These reactions can also be made enantioselective (in which case only one of the four isomers predominates) by using539 chiral enol derivatives,540 chiral aldehydes or ketones,541 or both.542 Since both new chiral centers are formed enantioselectively, this kind of process is called double asymmetric synthesis.543 A single one of the four stereoisomers has also been produced where both the enolate derivative and substrate were achiral, by carrying out the reaction in the presence of an optically active boron compound544 or a diamine coordinated with a tin compound.545... 

Masamune, S., Choy, W., Peterson, J.S., and Sita, L.R. (1985). Double asymmetric synthesis and a new strategy for stereochemical control in organic synthesis. Angewandte Chemie, International Edition in English, 24, 1-30. 

S. Masamune, W. Choy, J. S. Petersen, L. R. Sita, Double Asymmetric Synthesis and a New Strategy for Stereochemical Control in Organic Synthesis", Angew. Chem. Int. Ed. Engl. 1985, 24, 1-30. 

Review "Double Asymmetric Synthesis and a New Strategy for Stereochemical Control In Organic Synthesis"... 

Asymmetric Crotylboration . Reagents for crotylboration are prepared from 2,5-dimethyl-S-methoxyborolane (eq 5) by addition of (Z)- or ( )-crotylpotassium under standard conditions. Reactions with representative achiral aldehydes are 93-96% diastereoselective and 86-97% enantioselective for the major diastereomer (eqs eq 12 and eq 13). Results with chiral aldehydes conform to the rule of double asymmetric synthesis. ... 

The recognition of chiral carbonyl compounds, especially the substrates having a chiral stereogenic center at the a-carbon, have been a main subject of research for long time [81], since Curtin [82] and Cram [83] initially proposed a structural model for the diastereoselective addition to these molecules. There are in-depth studies related to this subject including chiral enolate addition, i.e., double asymmetric synthesis [84]. In this section, therefore, some other impressive topics of current interest are discussed briefly. 

DOUBLE ASYMMETRIC SYNTHESIS REACTIONS OF CHIRAL C—X ELECTROPHILES AND CHIRAL ALLYL ORGANOMETALLICS... 

Methods that involve C—C bond formation with the establishment of two new stereogenic centers are of considerable interest in this context. The aldol reaction has proven very useful in this regard, particularly in view of die development of powerful chiral enolates capable of controlling the stereochemical course of reactions with chiral aldehydes via the principle of double asymmetric synthesis. ... 

We have seen in Section 1.1.3 that reactions of many allyl organometallics and chiral C=X electrophiles proceed with only modest levels of relative diastereoselection. Significant improvement in dia-stereoselectivity is possible, however, by using double asymmetric synthesis, that is, by using the highly enantioselective allyl metal reagents described in Section 1.1.4 rather than the less diastereoface-selec-tive achiral allyl metal compounds discussed in Section 1.1.3. Double asymmetric synthesis is also... 

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