Reactions at unsaturated carbon

When a Br nsted base functions catalytically by sharing an electron pair with a proton, it is acting as a general base catalyst, but when it shares the electron with an atom other than the proton it is (by definition) acting as a nucleophile. This other atom (electrophilic site) is usually carbon, but in organic chemistry it might also be, for example, phosphorus or silicon, whereas in inorganic chemistry it could be the central metal ion in a coordination complex. Here we consider nucleophilic reactions at unsaturated carbon, primarily at carbonyl carbon. Nucleophilic reactions of carboxylic acid derivatives have been well studied. These acyl transfer reactions can be represented by... 

III. NUCLEOPHILIC REACTIONS AT UNSATURATED CARBONS A. Olefinic Carbon Centers... 

Since thiols and thiyl radicals are known to readily undergo addition reactions at unsaturated carbon centers (199, 202, 204), a possible mechanism for this inactivation reaction is shown in Scheme 43. Addition of the active site nucleophilic or radical species followed by protonation or electron transfer, respectively, would yield the thioacrylate derivative and inactive enzyme. Of course, addition to C-2 of propargylic acid is also possible, forming a 2-substituted acrylate derivative instead. 

It appears that SN reactions at saturated carbon atoms, free radical substitutions (again at saturated carbon) and S Ar reactions at unsaturated carbon have all been claimed to occur with aliphatic y- and -sultones, although documentation of evidence seems in some... 

It is the coupling of the bond making between Y and C with the unbonding of X- from C in the transition structure which makes the process possible and the poorer the nucleofuge, the more necessary the coupling. Discussion of these matters was enormously facilitated by the introduction of two-dimensional reaction maps by More O Ferrall [26]. A simple case for substitution at unsaturated carbon, i.e. acetyl transfer from one Lewis base to another, is shown in Fig. 1.2. 

In view of the observed inactivity of a, a-disubstituted olefins towards polymerisation with Ziegler-Natta catalysts, it is interesting to note that a, co-diolefins substituted at unsaturated carbon atoms, such as e.g. 2,5-dimethyl-l,5-hexa-diene, also undergo cyclopolymerisation, analogously to unsubstituted parent monomers [2,446], This can be interpreted in terms of a reaction pathway analogous to that shown in scheme (89). The insertions in the cyclopolymerisation appear to be facilitated by the nature of such a process. 

The value of AH is large for reactions at the carbon atom (AH 40 kcal./mole), and hence this determines the reactivity at both saturated and unsaturated carbon atoms. (K 1 and K ->- 1 respectively). The contribution of K A H is much smaller for the reaction at phosphorus, hence the first term determines the relative reactivity in reaction (d), (particularly in the non-polar solvents used in such reactions). These examples are sufficient to illustrate the inadequacy of the SHAB rule when conjugated nucleophiles are considered. 

The introduction of a halogen atom into the nucleus of an unsaturated heterocycle serves at once as a valuable synthetic route to heterocyclic derivatives and as a revealing probe of substitution processes at unsaturated carbon.1 From a synthetic standpoint, aromatic and heterocyclic halides have become more attractive starting materials in recent years. Traditionally considered to be rather unreactive, these vinylic halides had been found suitable only in certain reactions... 

However, the similar silylation of the P-chlorophosphaalkene 6a with two equivalents of the trichlorosilane/triethylamine reagent does not proceed with formation of a P=P double bond. The main product of this reaction is the stable bis(trimethylsilyl)methylbis(trichlorosilyl)phosphane 2d, which indicates a hydrosilylation of the P=C double bond by trichlorosilane, like the known Benkeser additions at unsaturated carbon-carbon bond systems [8]. 

In principle nitroalkenes should be available from direct nitration of vinyl carbanions. However, this reaction is not practical due to the potential anionic polymerization. But vinylstannanes obtained from ketones can be used instead of vinyl carbanions. Tetranitromethane is effective in replacing tin by nitro at unsaturated carbon. This method has been used to prepare several alkyl-substituted 1-nitrocyclo-hexenes and 1-nitrocycloheptenes (Scheme 2). ... 

The reaction rate was increased when electron-donating groups were present in the benzylidene system (p = —0.62) and decreased when electron-attracting species were present. Introducing similar substituents to the phenylhydrazine system had a much more apparent effect (p = —2.17) similar to that found in the styrene system . The reaction evidently involves electrophilic attack it would be interesting to know the mechanism of the process in more detail since it apparently involves substitution at unsaturated carbon, which may proceed through an addition-elimination sequence (assumed here) or a one-step substitution process. 

Reaction mechanisms for hydrolysis can be classified according to the type of reaction center involved. The primary distinction is made between reaction at saturated and unsaturated centers. With respect to carbon-centered functional groups, which will be the primary focus of this chapter, hydrolysis involves reactions at sp (saturated) or sp (unsaturated) hybridized carbons. Nucleophilic reactions at sp carbons are termed nucleophilic substitution (2.7). The reaction at sp carbons is termed nucleophilic addition-elimination or acyl substitution (2.8). 

Hydrolysis at unsaturated carbon occurs by a two-step process (1) nucleophilic addition at the acyl group [RC(0)] to give a tetrahedral intermediate (2.52) and (2) elimination of the leaving group (2.53). This reaction mechanism is referred to as the addition-elimination mechanism or nucleophilic acyl substitution. 

The general course of aliphatic displacement at unsaturated carbon involves multistage mechanisms, which consist of a nucleophilic addition to a tt system followed by an elimination step (reaction 11). 

Mammals can add additional double bonds to unsaturated fatty acids in their diets. Their ability to make arachidonic acid from linoleic acid is one example (Figure 25.15). This fatty acid is the precursor for prostaglandins and other biologically active derivatives such as leukotrienes. Synthesis involves formation of a linoleoyl ester of CoA from dietary linoleic acid, followed by introduction of a double bond at the 6-position. The triply unsaturated product is then elongated (by malonyl-CoA with a decarboxylation step) to yield a 20-carbon fatty acid with double bonds at the 8-, 11-, and 14-positions. A second desaturation reaction at the 5-position followed by an acyl-CoA synthetase reaction (Chapter 24) liberates the product, a 20-carbon fatty acid with double bonds at the 5-, 8-, IT, and ITpositions. 

Van Leusen and co-workers also demonstrated the utility of dilithio-tosylmethyl isocyanide (dilithio-TosMIC) to extend the scope of the application. Dilithio-TosMIC is readily formed from TosMIC and two equivalents of n-butyllithium (BuLi) in THF at -70"C. Dilithio-TosMIC converts ethyl benzoate to oxazole 14 in 70% yield whereas TosMIC monoanion does not react. In addition, unsaturated, conjugated esters (15) react with dilithio-TosMIC exclusively through the ester carbonyl to provide oxazoles (16). On the other hand, use of the softer TosMIC-monoanion provides pyrroles through reaction of the carbon-carbon double bond in the Michael acceptor. 

Asymmetric induction by sulfoxide is a very attractive feature. Enantiomerically pure cyclic a-sulfonimidoyl carbanions have been prepared (98S919) through base-catalyzed cyclization of the corresponding tosyloxyalkylsulfoximine 87 to 88 followed by deprotonation with BuLi. The alkylation with Mel or BuBr affords the diastereomerically pure sulfoximine 89, showing that the attack of the electrophile at the anionic C-atom occurs, preferentially, from the side of the sulfoximine O-atom independently from the substituent at Ca-carbon. The reaction of cuprates 90 with cyclic a,p-unsaturated ketones 91 was studied but very low asymmetric induction was observed in 92. 

It has long been known that a, / -unsaturated sulfones resemble a, /i-unsaturated ketones and aldehydes in undergoing addition reactions with nucleophilic reagents43. These reactions are initiated by nucleophilic attack at the carbon to the sulfone group ... 

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