Stereochemistry vinylic substitution

Vinylic and divinylic tellnrides react with alkenes in MeOH in the presence of a combination of catalytic amounts of PdCl2 together with AgOAc and EtjN to afford the corresponding vinyl-substituted alkenes The products result respectively from the coupling of the styryl and phenyl moieties of the starting telluride with retention of its double-bond stereochemistry. 

Investigations158 of the stereochemistry of vinylic substitutions on nitroolefins revealed that the lifetime of the carbanion (73) of Scheme 34 is sufficiently long to enable rotation around the C=C bond faster than the leaving-group departure156. 

Vinylic substitution of bromine by noncyclic primary and secondary amines in 3-bromo-4,4-dimethoxy-2-butenoates and corresponding nitriles occurs in a stereocontrolled fashion. Regardless of the starting stereochemistry, the product possesses trans amino and ester (or nitrile) groups (equation 20)174. Also, displacement of bromine from 5-bro-mouracils, by cyclic amines, has been used as a preparation of novel pyrimidine inhibitor intermediates1. This reaction has been shown to be assisted by the presence of fluoride ion... 

The vinylic substitution by tellurolate anions has not been extensively investigated. It is, however, an efficient method for synthesizing vinylic tellurides of defined stereochemistry. (E)-/3-bromostyrene 79 reacts with organo-tellurolate anions to give ( )-vinylic tellurides 80 (Scheme 49).34,144... 

Functionalized P-amino-a, -unsaturated lactones, esters and nitriles can be prepared by nucleophilic vinylic substitution of halogen atoms by amines on the corresponding 3-halo-a,3-unsaturated compounds (12), (13) and (15) (Scheme 9). 3-Bromo-2-butenoates ( )-(13) and (Z)-(13) reacted with secondary amines to give ( )-p-aminopropenoates ( )-(14) regardless of the initial stereochemistry, while the reaction with primary amines yielded a mixture of ( )- and (Z)-(14), when R = H, with the latter predominant. In contrast, the substitution of ( )- and (Z)-nitriles, ( )-(15) and (Z)-(15), with second-... 

This review deals with the replacement of substituents in the vinylic position hy anionic or neutral nucleophiles. Its division according to mechanistic routes suffers from the fact that for many systems there is a strong connection and mutual intercalation between several routes, but we will try to show the similarities in the behaviour of different systems and to discuss the various criteria which have been used for differentiation between the mechanistic pathways. Some topics, e.g. the stereochemistry and the element effect, are discussed in greater detail than others, especially when the data could be collected in convenient tables. No attempt has been made to cover all the synthetically used vinylic substitution reactions of which reviews are available, e.g. on /3-chloro-vinyl ketones (Kochetkov, 1952, 1961 Kochetkov et al., 1961 Pohland and Benson, 1966), fluoro-olefins (Chambers and Mobbs, 1965) or tetracyanoethylene (Cairns et al., 1958 Cairns and McKusick, 1961). 

The stereochemistry of nucleophilic vinylic substitution via the AdN-E mechanism ranges from retention of configuration to stereoconvergence. For SnV 1-type reactions, often partial inversion has been observed. The inversion has been attributed to nucleophilic attack on an ion pair intermediate.As illustrative examples, results of the acetolysis of the vinyl triflates la-c in the presence of sodium acetate are given in Scheme The fraction of inversion ranges from 40 to 80%, and is smaller the more stable the intermediate cation /3-alkyl substitution... 

Previously, we have discussed that the inversion of the stereoehemistry in the solvolysis product of vinyl iodonium salt 2 could be explained by an in-plane S 2 vinylic substitution. The same arguments can be employed now to explain how the minor isomer 6Z is formed (Scheme 35.6). Direct attack of acetic acid to the a-carbon should lead to the observed reaction product in a one-step proeess through transition state 9. The position of the deuterium atom should not change (no scrambling), only the stereochemistry of the product has been reversed during the reaction. 

Possibly, the most striking aspect of the vinylic substitution of bromides 1 is the stereospecificity of the reaction. In fact, the retention of the stereochemistry during the process is decisive in deciding among the diverse mechanisms proposed. Let us use vinyl bromide E-1 as a substrate to discuss the different options. 

In fact, the hyperconjugative stabilizing effect is the net result of the destahiUzing interaction of the occupied anionic C2p and the filled Oc-nu orbitals and the stabilizing interaction of the C2p with the 0 c-Nu orbital. A complete study of the stereochemistry in nucleophilic vinylic substitution reactions has been reported by Apeloig Y, Rappoport Z (1979) J. Am. Chem. Soc. 101 5095-5098. 

The stereochemistry of addition is usually anti for alkyl-substituted alkynes, whereas die addition to aryl-substituted compounds is not stereospecific. This suggests a termo-iecular mechanism in the alkyl case, as opposed to an aryl-stabilized vinyl cation mtermediate in the aryl case. Aryl-substituted alkynes can be shifted toward anti addition by including bromide salts in the reaction medium. Under these conditions, a species preceding the vinyl cation must be intercepted by bromide ion. This species can be presented as a complex of molecular bromine with the alkyne. An overall mechanistic summary is shown in the following scheme. 

A valuable feature of the Nin/Crn-mediated Nozaki-Takai-Hiyama-Kishi coupling of vinyl iodides and aldehydes is that the stereochemistry of the vinyl iodide partner is reflected in the allylic alcohol coupling product, at least when disubstituted or trans tri-substituted vinyl iodides are employed.68 It is, therefore, imperative that the trans vinyl iodide stereochemistry in 159 be rigorously defined. Of the various ways in which this objective could be achieved, a regioselective syn addition of the Zr-H bond of Schwartz s reagent (Cp2ZrHCl) to the alkyne function in 165, followed by exposure of the resulting vinylzirconium species to iodine, seemed to constitute a distinctly direct solution to this important problem. Alkyne 165 could conceivably be derived in short order from compound 166, the projected product of an asymmetric crotylboration of achiral aldehyde 168. 

More mechanistic work undoubtedly will be done on the stereochemistry of solvolysis, particularly of simple alkyl-substituted acyclic vinyl systems. The questions of concerted anchimerically assisted or nonconcerted rearrangements both to the double bond and across the double bond need further development. 

Stereochemistry can be interpreted in terms of conformation effects in the 1,4-biradical intermediates.199 Vinyl enol ethers and enamides add to aromatic ketones to give 3-substituted oxetanes, usually with the cis isomer preferred.200... 

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