Nucleophilic vinylic substitution reactions

The nucleophilic vinylic substitution reaction of ( )-a-haloenyne sulfones with sodium alkoxides proceeds regioselectively to give ( )-a-alkoxyenyne sulfones. These conqioimds are versatile intermediates for the preparation of iiirans (Scheme 15, <96TL7381>). 

In 2008 Yang and coworkers have reported an efficient synthesis of substituted a-alkilidene-fi-lactams via aNaOH- promoted intramolecular aza-Michael addition of a-carbamoyl, a-(l-chlorovinyl) ketene-S,S-acetals and subsequent nucleophilic vinylic substitution reaction in alcoholic media (Scheme 90), [198]. 

Inversion (top) and retention (bottom) of configuration in nucleophilic vinylic substitution reactions. 

Study of structure-activity relationships in nucleophilic vinylic substitution reactions (S nV) that proceed by the addition-elimination mechanism has been furthered by the study of acid-catalysed breakdown of alkoxide and thiolate ion adducts of benzylidene Meldrum s acid (36a), methoxybenzylidene Meldrum s acid (36b), and thiomethoxybenzylidene Meldrum s acid (36c). Catalysis of alkoxide or thiolate expulsion is in competition with protonation of the a-carbon or one of the carbonyl oxygens to form an enolate. The positive Ag values for H+-catalysed RO and RS departure imply an imbalanced transition state in which proton transfer leads C-O or C-S bond cleavage. The pA values of the various adducts are much lower than for Meldrum s acid, in view of the stabilizing influence of OR, SR, and OMe groups on the carbanion. 

An NaOH-promoted intramolecular aza-Michael addition of a-carbamoyl,a-(l-chlorovinyl)ketene-S,S-acetals 85 followed by the nucleophilic vinylic substitution reaction yielded substituted ( )-3-alkylidene- 3-lactams 86a (Scheme 3.32) [67]. The reaction was completely diastereoselective except in the case of N-methyl amides in which some (Z)-isomer 86b was also formed. 

If we think about the stepwise alternatives, the more likely for a nucleophilic vinylic substitution reaction are either an elimination-addition or an addition-elimination process. In the elimination-addition sequence (Scheme 38.4), the losts of HBr during the first step of the reaction would form phenylacetylene, which after nucleophilic attack would lead to anion 5. The protonation of this species should yield the substitution products 2, but as a Z+E mixture. It is evident that the stereospecificity of the reaction cannot be justified by this route. Furthermore, we know from the experimental data that phenylacetylene was virtually unreactive when treated with MeSNa under the reaction conditions employed for the vinylic substrates 1. In view of these results, the elimination-addition mechanism should not be considered. 

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. 

Nucleophilic vinylic substitution and vinyl cation intermediates in the reactions of vinyl iodonium salts. 37, 1... 

Nucleophilic substitution, in phosphate esters, mechanism and catalysis of, 25, 99 Nucleophilic substitution, single electron transfer and, 26, 1 Nucleophilic substitution reactions in aqueous solution, 38, 161 Nucleophilic vinylic substitution, 7, 1... 

The work of Ochiai s group on nucleophilic vinylic substitution of phenyliodonium salts (see previous section) has been extended to examining the behaviour of allenyl (aryl)iodine(III). Ratios of nucleophilic substitution to [3,3]-sigmatropic rearrangement for the collapse of allenyl(aryl)iodine(III), generated from the reactions of aryliodanes... 

Evidence for a Michael addition of a nucleophile to alkenyl(phenyl)iodonium salts at the Cp atom has now been reported for the first time. Nucleophilic vinylic substitutions of (Z)-(/3-bromoalkenyl)iodonium tetrafiuoroborates (161) and its (Z)-(/3-chloroalkenyl) analogue with sodium benzenesulfinate in THE afforded stereoselectively (Z)-l,2-bis(benzenesulfonyl)alkene (163) with retention of configuration. Intermediate formation of (Z)-[/3-(benzenesulfonyl)alkenyl]iodonium salt (162) in these reactions was established by NMR experiments in CDCI3. The formation of (Z)-(162) involves a hitherto unobserved Michael addition of benzenesulfinate anion to the alkenyliodonium salts at the Cp atom, followed by halogen extrusion. ... 

The nucleophilic vinylic substitution (S mV) of heteroatom-substituted alkylidene Meldrum s acids has been intensively studied and kinetics of the reaction <1998JOC6266, 1999CJC584, 2004JOC9248> as well as synthetic applications have been reported <19978567, 2002JHC15, 2005EJ04870> (cf. Section 8.11.4.2, Scheme 10). The preparation of the substrates and a sample application is shown in Scheme 90 <2001J(P2)1534>. 

Vinyl substitutions on alkenes not having their double bonds conjugated with carbonyl groups often proceed more rapidly and give better product yields when the reactions are conducted in the presence of an unhindered secondary amine. Conjugated and nonconjugated dienes are usually only minor products in these cases. The major products normally are allylic amines obtained by nucleophilic attack of the secondary amine upon the ir-allylpalladium intermediates. Since allylic amines may be quatemized and subjected to the Hoffmann elimination, this is a two-step alternative to the direct vinyl substitution reaction.90... 

Nucleophilic additions to alkenes 293 Nucleophilic vinylic substitution (SNV) Reactions 298 Nucleophilic substitution of Fischer carbene complexes 303 Reactions involving carbocations 309 Miscellaneous reactions 312... 

In 1991, we reported that a nucleophilic vinylic substitution of (E)-fi-alkylvinyl-AModanes with halides (BuN4X, X = C1, Br, I) in dichloromethane, methanol, or acetonitrile at room temperature proceeds with exclusive inversion of configuration [Eq. (100)] [176,177]. This is the first clear example of a vinylic Sn2 reaction. This reaction competes with an alkyne-forming reductive syn /3-elimination. 

Numerous reactions of alkenyl(phenyl)iodonium salts leading to the formation of new C-C bond have been reported in the literature. The most important and synthetically useful reactions include the generation and subsequent cyclization of alkylidenecarbenes, alkenylation of carbon substrates via nucleophilic vinylic substitution, and transition metal-mediated coupling reactions. 

Nucleophilic vinylic substitutions of 4//-pyran-4-onc and 2,6-dimethyl-4//-pyran-4-one with a hydroxide ion in aqueous solution were calculated by the density functional theory (B3LYP) and ab initio (MP2) methods using the 6-31+G(d) and 6-31G (d) basis sets. The aqueous solution was modelled by a supermolecular approach, where 11 water molecules were involved in the reaction system. The calculations confirmed a different addition-elimination mechanism of the reaction compared with that in the gas phase or non-polar solution. Addition of OH- at the C(2) vinylic carbon of the pyranone ring with an activation barrier of 10-11 kcalmol-1 (B3LYP) has been identified as the rate-determining step, in good quantitative and qualitative agreement with experimental kinetics. Solvent effects increase the activation barrier of the addition step and, conversely, decrease the barrier of the elimination step.138... 

Nucleophilic catalysis of ester hydrolysis and related reactions, 4, 237 Nucleophilic vinylic substitution, 7, 1... 

Nucleophilic vinylic substitutions are closely related to nucleophilic aromatic substitutions, as in both the leaving group leaves from an unsaturated carbon atom. However, the vinylic substitution routes are much more diverse, and disclose more of the details of the reaction. Stereochemical study of the reaction can give information on the lifetime of the intermediate and about the structure of the transition state... 

The addition-elimination route is the most studied one in Scheme 1. Since it involves a reaction of the nucleophile with the vinylic carbon atom, it is also the one which in actual fact is most correctly described as a nucleophilic vinylic substitution . We will therefore deal with it in the greatest detail. 

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