Stereoconvergent reaction

A stereoconvergent reaction without any correlation between the geometry of the enolate and simple diastereoselectivity occurs when fluoride ions are used to induce an aldol addition of enolsilanes to aldehydes. For example, both a 99 1 and a 9 91 mixture of the following (Z)/( )-enolsilane lead predominantly to the formation of the. un-adduct in a highly selective manner, when the addition is mediated by tris(diethylamino)sulfonium difluorotrimethylsili-conate27,28. 

Fig. 3.9. A pair of stereoconvergent reactions (using the glucoside syntheses from Figure 2.23 as an example).

Protiodesilylation of endo- and e o-trimethylsilyl-3-phenyl-2-thiabicy-clo[2.2. l]hept-5-enes 19, endo-trimethylsilyl-ea o-5-oxide 39, and the corresponding 5,5-dioxide 40 with fluoride gave the endo-phenyl derivatives through a stereoconvergent reaction. These results were rationalized by hypothesizing a common carbanionic intermediate33 (Scheme 24). 

In two recent publications Curran et al. described the theoretical as well as the mathematical background of stereoconvergent reactions [2]. They give further evidence for their analysis by providing some examples from the field of radical chemistry to demonstrate this strategy called complex stereoselection. The process of stereoconver-... 

The Mukaiyama aldol reaction of ethyl ketones can lead to the controlled introduction of two adjacent stereocenters. While enolate geometry may not be trans-fened faithfully to the relative stereochemistry of the aldol product syn versus anti), stereoconvergent reactions are possible. In the example shown in Scheme 9-5, it should be noted that 7i-facial control from the chiral aldehyde is strong as both products 7 and 8 arise from Felkin selectivity [5]. 

Scheme 1.10 Ni-catalyzed stereoconvergent reaction of a racemic a-halonitrile.

Allylic trimethoxysilanes are activated by a catalytic combination of CuCl and TBAF.118 The mechanism of this reaction is not entirely clear, but it seems to involve fluoride activation of the silane. These reactions are stereoconvergent for the isomeric 2-butenyl silanes, indicating that reaction occurs through an acyclic TS. 

The multi-component procedure is also effective for the chromium-catalyzed addition of organic halides to aldehydes (the Nozaki-Hiyama-Kishi reaction) [73]. The active Cr(II) species is recycled by redox interaction with Mn powder as the stoichiometric co-reductant in the presence of MesSiCl (Scheme 34), which mainly liberates the chromium catalyst from the alkoxide adduct. The chemo- and diastereo-selective addition reaction is performed with a variety of organic halides and alkenyl triflates. In the case of crotyl bromide, the addition is highly stereoconvergent, i.e., the respective anti-... 

Bromination is less stereoselective, and the reactions of cis- and trans-olefins tend to be stereoconvergent. The stereospecific formation of the mixed bromoadducts in protic media, such as methanol or acetic acid, could be interpreted in the light of the recent finding (Ruasse et al., 1991) that these solvents assist the formation of the ionic intermediate nucleophilically. If a solvent molecule is close to the cationic part of the transition state in the rate-limiting step, the intermediate can be trapped by this solvent molecule in a necessarily trans mode with respect to the first bromine, before the two components of the ion-pair diffuse away from each other (15). This would... 

These palladium- or nickel-catalyzed reactions are radical reactions leading to an organometallic product. By using a precursor such as 37 as a 1 1 mixture of diastereoisomers, the palladium-catalyzed cyclization provides in a stereoconvergent way the cyclopentylmethylzinc derivative 38 which, after allylation, produces the unsaturated ester 39 in 71% yield". The intermediate radical cyclizes via a transition state A where all the substituents are in an equatorial position. Interestingly, the analogous reaction using Ni(acac)2 as a catalyst allows the preparation of heterocyclic compounds such as 40. The... 

Evans [369] and Masamune [370,371] have pioneered the use of thioesters for stereocontrol of the aldol reaction. The accompanying scheme summarizes the reactions of boron and silicon enolates of t-butyl thiopropanoate with aldehydes [372]. Both reactions are stereoconvergent. (Z) and (E)-enolates afford the same diastereoisomer syn with the boron... 

Reactions which are apparently stereospecific occur in the nucleophilic displacement of vinylic iodide [31] in the electron-deficient alkenes E- and Z-24 shown in Scheme 9.14. With ethanolic toluenethiolate, the sole detectable product from the reaction of -24 is -25. However, -25 is also the sole detectable product from the reaction of Z-24. This stereoconvergence demands that the stereoisomers react through a common intermediate, and it was reasonably suggested that initial nucleophilic addition of the thiolate anion yields a resonance-stabilised carbanion (26) whose stereoisomerisation, again by rotation about a carbon-carbon single bond, is much faster than the loss of iodide to yield the substitution product ( fy). 

Backvall et al. utilized a stereoconvergent palladium-catalyzed SN2 reaction of a-allenic acetates 39 for the synthesis of (Z, )-2-bromo-l,3-dienes 40 [29]. 

The concept of stereospecificity has been introduced to characterize the stereochemical course of pairs of highly stereoselective reactions. Another term, stereoconvergence, is also very useful in this connection. 

In a parallel study, it was found that chelating chiral diamines 208 or 209 are well suited as ligands to promote Kumada-type couplings of primary and secondary alkyl halides 202 with aryl Grignard reagents 203 (entry 4) [281]. This reaction was applicable to alkyl bromides and alkyl iodides, while alkyl chlorides gave only low yields. Acetal and ester functions are tolerated. A notable feature is the stereoretentive arylation of fra s-a-bromo acetals with excellent diastereo-selectivity. The involvement of radicals is supported by the stereoconvergent formation of cxo-phenvI norbornane from both endo- or exo-bromonorbomane (cf. Part 1, Fig. 9) and radical 5-exo cyclizations (see below). 

This reaction also gave the opportunity to open an access to various polycyclic derivatives, as illustrated by the transformation of the mixture of diaster eomers 133 into tricyclic derivative 134 as a single diastereomer, thanks to a completely stereoconvergent process. An interesting entry into carene 136 and carone derivatives 137 has also been disclosed by Fiirstner [88]. 1,5-Enynes have proven to be versatile precursors for the preparation of perfumery agents such as sabina ketone (Scheme 45). 

Although the subsequent discussion describes the stereoselection at the steady state through the example of radical reactions, the analysis and principles are general for any reaction profile that fits into the scheme of complex stereoselective reactions. In the process proposed and analyzed by Curran et al., the activation of compounds of type 1 is done, for example, by radical formation. The group selectivity in this first step has again no effect on the stereomeric nature of the product. To obtain a stereoconvergent process it is crucial, however, that the reaction is operating at the steady state. This means that the concentrations of the radial intermediates (compounds in brackets in Scheme 2) is low and stationary, while their absolute concentrations are determined by the different rates of reaction. 

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