Substitution at Unsaturated Atoms

Substitution at certain unsaturated centers has little direct stereochemical interest, because there is no choice, e.g. substitution at aromatic, acetylenic, and carbonyl carbons must go with retention. On the other hand, stereoselection is possible at ethylenic and allenic carbon, phosphorus (P—O, P=S) and sulfur (S=0) centers. There appear to be important mechanistic differences between substitutions at unsaturated carbon and phosphorus or sulfur. All SE, SH, SN substitutions at such carbon atoms appear to proceed in at least two steps, while those at phosphorus and sulfur may go in one or more steps. For the SN process, comparative data are available here, substitution at unsaturated carbon proceeds with retention, while at phosphorus and sulfur inversion predominates. Substitution at unsaturated phosphorus and sulfur sites was sufficiently similar to other saturated centers that it was considered with them. Because of these mechanistic differences, we shall examine substitutions at unsaturated carbon more closely. 

So effective was the collinear three-center transition state in clarifying the Walden inversion problem, that concerted backside attacks were proposed or considered for the Beckman rearrangement, isomerization of alkenes, etc. (Olson, 1933 Marvel, 1943), as well as substitution in alkenes (Gold, 1951 Ross et al., 1952). Since an appropriate arrangement of hybrid orbitals is available, some of the transition states did not 

The oxygen derivatives of three centers, carbon, phosphorus, sulfur, can be compared with respect to the AO s available for nucleophilic substitution. Unlike 45, participation of the 77-system in the process is possible for 53 and 54. In 49, we have sp3 bonds and the tetrahedral intermediate in 53 and 54, which may be transition states or intermediates, we can have pd overlap between the orbital covering the three collinear atoms and sp2d orbitals to oxygen. 

Over the last two decades Russian workers have uncovered a host of interesting SE reactions with retention at an alkene center (Reutov, 1967b). These have involved exchanges with mercury, lead, tin, thallium, etc. attached to an alkene carbon  

Numerous other stereospecific conversions have been reported, e.g. (137) (Zweifel and Steele, 1967). 

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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. 

In contrast to saturated hydrocarbons, the unsaturated hydrocarbons react with atomic fluorine by two pathways, i.e. (atomic fluorine addition at >C=C< double bond and hydrogen substitution by fluorine atoms. The reaction of fluorine with aromatic hydrocarbons proceeds with the formation of F-derivatives and hydrogen atoms break off ... 

Bromolactonization of /3,y-unsaturated acids has proven to be a much more satisfactory method of synthesis of /3-lactones, giving good yields of stable crystalline -y-bromo-/3-lactones, except when the substitution at the -y-carbon atom can favor development of carbonium character there. Thus 1,4-dihydrobenzoic acid and 2-methyl-l,4-dihydrobenzoic acid form /3-lactones (equation 95), while 3-methyl-l,4-dihydrobenzoic acid forms the -y-lactone (75JOC2843). The reaction of the sodium salt of a-methylcinnamic acid with bromine in water or methanol also gives /3-lactone, but the yield is low (78JOC3131). 

Cyclisation of pent-4-en-l-ols features in a variety of guises in pyran syntheses. Reaction of the unsaturated alcohol with iodine reagents affords the tetrahydropyran with high diastereoselectivity associated with the bulky silyl substituent and which is enhanced by substitution at the terminal carbon atom (95SL663). 

Consideration of the degree of metal substitution at the carbons of the C2 fragment and the separations of the two carbon atoms, has led to the formulation of polymetallic species as permetallated ethyne (E), ethene (F), or ethane (G) (Chart 2).35 Addition of metal fragments to the unsaturated species E leads to sequential formation of F and G and progressive saturation of the C=C triple bond. These ideas are broadly consistent with the results of computational studies (Section IX.D). Compounds of type E are described below, while the more highly metallated species are discussed in Sections VII, VIII, and IX. 

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... 

We may consider now the effect of substitution at C-4 of testosterone (0=C—C=C system). If there is a hydrogen atom at C-4, the large electronegativity of the oxygen atom gives an acceptor character to the carbonyl group and a donor character to the unsaturated bond. Therefore, the resonance contributing structures depicted below are important ... 

Several possible explanations have been offered. One is that the ground state of the nucleophile is destabilized by repulsion between the adjacent pairs of electrons another is that the transition state is stabilized by the extra pair of electrons a third is that the adjacent electron pair reduces solvation of the nucleophile. Evidence supporting the third explanation is that there was no alpha effect in the reaction of HOj with methyl formate in the gas phase, although HOj shows a strong alpha effect in solution. The a-efifect has been demonstrated to be remarkably dependent on the nature of the solvent. The a-effect is substantial for substitution at a carbonyl or other unsaturated carbon, at some inorganic atoms, and for reactions of a nucleophile with a carbocation, but is generally smaller or absent entirely for substitution at a saturated carbon. ... 

In most cases the regiochemistry of the Shapiro reaction is controlled by steric factors, with the second metalation occurring at the less-substituted a-carbon atom of the hydrazone.2 For example, a-methyl ketone 10 was transformed to disubstituted alkene 11 in 69% yield as a single regioisomer via conversion to a tosylhydrazone followed by treatment with -BuLi. However, the regiochemical outcome of Shapiro reactions involving a,p-unsaturated hydrazones is difficult to predict in the absence of data obtained from reactions of structurally related substrates, as the second metalation can occur at either the a - or y-position. 

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