Reagent controlled asymmetric synthesis chirality

Reagent-controlled asymmetric cyclopropanation is relatively more difficult using sulfur ylides, although it has been done. It is more often accomplished using chiral aminosulfoxonium ylides. Finally, more complex sulfur ylides (e.g. 64) may result in more elaborate cyclopropane synthesis, as exemplified by the transformation 65 66 ... 

Asymmetric ylide reactions such as epoxidation, cyclopropanation, aziridination, [2,3]-sigmatropic rearrangement and alkenation can be carried out with chiral ylide (reagent-controlled asymmetric induction) or a chiral C=X compound (substrate-controlled asymmetric epoxidations). Non-racemic epoxides are significant intermediates in the synthesis of, for instance, pharmaceuticals and agrochemicals. 

According to the general principles of asymmetric synthesis, chiral induction can be effected via substrate, reagent, or external (catalyst) control. Effective substrate control in the sense of induced diastereoselectivity requires a preformed stereogenic center within the substrate. For organometallic catalytic conversions a stereospecific reaction course and simple diastereoselectivity, as outlined above, is prerequisite. 

In principle, asymmetric synthesis involves the formation of a new stereogenic unit in the substrate under the influence of a chiral group ultimately derived from a naturally occurring chiral compound. These methods can be divided into four major classes, depending on how this influence is exerted (1) substrate-controlled methods (2) auxiliary-controlled methods (3) reagent-controlled methods, and (4) catalyst-controlled methods. 

The substrate-controlled reaction is often called the first generation of asymmetric synthesis (Fig. 1-30, 1). It is based on intramolecular contact with a stereogenic unit that already exists in the chiral substrate. Formation of the new stereogenic unit most often occurs by reaction of the substrate with an achiral reagent at a diastereotopic site controlled by a nearby stereogenic unit. 

Lewis acids of chiral metal aryloxides prepared from metal reagents and optically active binaphthol derivatives have played a significant role in asymmetric synthesis and have been extensively studied.23 However, in Diels-Alder reactions, the asymmetric induction with chiral metal aryloxides is, in most cases, controlled by steric interaction between a dienophile and a chiral ligand. This kind of interaction is sometimes insufficient to provide a high level of enantioselectivity. 

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. 

Chiral synthesis, also called asymmetric synthesis, is synthesis which preserves or introduces a desired chirality. Principally, there are three different methods to induce asymmetry in reactions. There can be either one or several stereogenic centres embedded in the substrate inducing chirality in the reaction (i.e. substrate control) or an external source providing the chiral induction (i.e. reagent control). In both cases the obtained stereoselectivity reflects the energy difference between the diastereomeric transition states. 

Asymmetric synthesis (1) Use a chiral auxiliary (chiral acetal—the synthetic equivalent of an aldehyde chiral hydrazone—the synthetic equivalent of a ketone) covalently attached to an achiral substrate to control subsequent bond formations. The auxiliary is later disconnected and recovered, if possible. (2) Use a chiral reagent to distinguish between enantiotopic faces or groups (asymmetric induction) to mediate formation of a chiral product. The substrate and reagent combine to form diastereomeric transition states. (3) Use a chiral catalyst to discriminate enantiotopic groups or faces in diastereomeric transition states but only using catalytic amounts of a chiral species. 

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. 

Asymmetric synthesis introduces one or more new features of chirality in a molecule. Several approaches are possible. In general, preferential formation of an enantiomer or diastereoisomer is achieved as a result of the influence of a chiral element present in the substrate, a reagent, catalyst or the environment. Chirality control is also possible in the electronically excited state,584 as demonstrated in the following examples. 

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