Conjugated 1,2-disubstituted

This chapter, therefore, ends the monograph with a potpourri of reactions all of which occur without a change in oxidation state. In many cases, the reaction is one of nucleophilic attack at an electrophilic C-atom. The result is often hydrolytic bond cleavage (e.g., in carbohydrate conjugates, disubstitut-ed methylene and methine groups, imines, oximes, isocyanates, and nitriles, and various ring systems) or a nucleophilic substitution (e.g., hydrolytic de-halogenation of halocarbons and chloroplatin derivatives, and cyclization reactions). The formation of multiple bonds by dehydration is a special case to be discussed separately. 

Initial studies on the Jacobsen-Katsuki epoxidation reaction identified conjugated eyelie and acyelic cw-disubstituted olefins as the class of olefins best suited for the epoxidation reaetion. " Indeed a large variety of c/s-disubstituted olefins have been found to undergo epoxidation with a high degree of enantioselectivity. 2,2"-Dimethylehromene derivatives are especially good substrates for the epoxidation reaetion. Table 1.4.1 lists a variety of examples with their corresponding reference. 

It would be expected that the stabilization of the adsorbed species by an extended conjugated system should increase with the number of aromatic rings in the adsorbed azahydrocarbon. However, data suitable for comparison are available only for phenanthridine, benzo-[/]quinoline, and benzo[h] quinoline. The large difference in the yields of biaryl obtained from the last two bases could be caused by steric interaction of the 7,8-benz-ring with the catalyst, which would lower the concentration of the adsorbed species relative to that with benzo[/]quinoline. The failure of phenanthridine to yield any biaryl is also noteworthy since some 5,6-dihydrophenanthridine was formed. This suggests that adsorption on the catalyst via the nitrogen atom is possible, but that steric inhibition to the combination of the activated species is involved. The same effect could be responsible for the exclusive formation of 5,5 -disubstituted 2,2 -dipyridines from 3-substi-tuted pyridines, as well as for the low yields of 3,3, 5,5 -tetramethyl-2,2 -bipyridines obtained from 3,5-lutidine and of 3,3 -dimethyl-2,2 -... 

Conjugate addition [2] to Midiael acceptors is die most important and usefid reaction in orgatiocopper diemistiy, and die reaction is ofien used as die key step in die syndiesis of numerous natural and unnatural products. Perhaps one of die most efficient methods for die syndiesis of quaternary carbon centers is organo-copper-mediated conjugate addidon to /, / -disubstituted enones. 

Amides are very weak nucleophiles, far too weak to attack alkyl halides, so they must first be converted to their conjugate bases. By this method, unsubstituted amides can be converted to N-substituted, or N-substituted to N,N-disubstituted, amides. Esters of sulfuric or sulfonic acids can also be substrates. Tertiary substrates give elimination. O-Alkylation is at times a side reaction. Both amides and sulfonamides have been alkylated under phase-transfer conditions. Lactams can be alkylated using similar procedures. Ethyl pyroglutamate (5-carboethoxy 2-pyrrolidinone) and related lactams were converted to N-alkyl derivatives via treatment with NaH (short contact time) followed by addition of the halide. 2-Pyrrolidinone derivatives can be alkylated using a similar procedure. Lactams can be reductively alkylated using aldehydes under catalytic hydrogenation... 

The reaction of crotonaldehyde and methyl vinyl ketone with thiophenol in the presence of anhydrous hydrogen chloride effects conjugate addition of thiophenol as well as acetal formation. The resulting j3-phenylthio thioacetals are converted to 1-phenylthio-and 2-phenylthio-1,3-butadiene, respectively, upon reaction with 2 equivalents of copper(I) trifluoromethanesulfonate (Table I). The copper(I)-induced heterolysis of carbon-sulfur bonds has also been used to effect pinacol-type rearrangements of bis(phenyl-thio)methyl carbinols. Thus the addition of bis(phenyl-thio)methyllithium to ketones and aldehydes followed by copper(I)-induced rearrangement results in a one-carbon ring expansion or chain-insertion transformation which gives a-phenylthio ketones. Monothioketals of 1,4-diketones are cyclized to 2,5-disubstituted furans by the action of copper(I) trifluoromethanesulfonate. ... 

This method provides a convenient synthesis of alkenes with the double bond in a relatively unstable position. Thus reduction of the p-toluenesulfonylhydrazones of a,(3-unsaturated aryl ketones and conjugated dienones gives rise to nonconjugated olefins. Unsaturated ketones with endocyclic double bonds produce olefins with double bonds in the exocyclic position. The reduction of p-toluenesulfonylhydrazones of conjugated alkynones furnishes a simple synthesis of 1,3-disubstituted allenes. ... 

Rovis and co-workers further extended the scope of the reaction to the enantio-and diastereoselective cyclisation of a,P-disubstituted Michael acceptors 137. The high diastereoselectivity of the process relies on selective protonation of the resnltant enolate after conjugate addition. It was found that HMDS (formed dnring deprotonation of the triazolium salt pre-catalyst) was detrimental to the... 

More generally, many combinations of EWG substituents can serve as the anion-stabilizing and alkene-activating groups. Conjugate addition has the potential to form a bond a to one group and (3 to the other to form a a,y-disubstituted system. 

This strategy is applied to a general method for the preparation of 2,2-disubstituted 1-ni-troalkenes. Conjugate 1,4-addition of complex zinc cuprates to l-nitroalkenes, followed by trapping with phenylselenyl bromide and subsequent oxidative elimination, affords the corresponding 2,2-disubstituted l-nitroalkenes in good yields (Eq. 5.82).132... 

Nenajdenko et al. described the first example of addition of a 1,2-dication to C-C mutiple bonds. The only S-S dication found to participate in this reaction was the highly strained dication 115 derived from 1,4-dithiane. The reaction with alkenes 119 proceeded under mild conditions and led to derivatives of dithioniabicyclo[2.2.2]octane 120 as shown in Equation (33) and Table 21 <1998JOC2168>. This reaction was sensitive to steric factors and proceeded only with mono and 1,2-disubstituted ethylenes. Only alkenes conjugated with aromatic or cyclopropane moieties underwent this reaction. For the 1,2-disubstituted alkenes used in this study, the relative configuration of substitutents at the double bond was preserved and only one diastereomer was formed (see entries 2 and 3). 

Only a few results are available concerning competitive cyclopropanation of non-conjugated dienes. The case of 1,4-hexadiene72 (mixture of Z and E isomers) illustrates the reactivity difference between a monosubstituted and a 1,2-disubstituted double bond, whereas in limonene (24)47, a 1,1-disubstituted and a trisubstituted double bond compete for the carbenoid derived from ethyl diazoacetate. In both cases, the less substituted double bond reacts preferentially (Scheme 8). 

In an extension of previous work on conjugated enamine carbonyl derivatives, reaction of the pyrazolone 91 with IV.lV-disubstituted hydrazines on heating in an alcohol solvent afforded the hexahydropyrazolo[4,3-Michael-type addition of the alcohol to a pre-formed pyrazolo-diazepine, was excluded <06T8126>. 

In line with its importance in characterization, this section has been expanded and updated and includes a more detailed analysis than that in CHEC-II(1996) and CHEC(1984), which contain, nonetheless, important data on proton NMR shifts of C-3- and C-5-unsubstituted fully conjugated 1,2,4-oxadiazoles. A major advance since CHEC-II(1996) is the appearance of a large amount of fully assigned 13C data for C-3/C-5-disubstituted fully conjugated 1,2,4-oxadiazoles <1996JHC1583,... 

Reaction with alkenes is sensitive to steric factors - in the case of dication 49, only reaction with mono- and 1,2-disubstituted ethylenes afforded identifiable reaction products. Only alkenes conjugated with aromatic or cyclopropane moiety undergo this reaction. In the case of 1,2-disubstituted alkenes, the relative configuration of substitutents at the double bond is preserved and only one diastereomer is formed. 

Acyclic S-S dications 51 and 52 also give 1,2-disulfonium salts 90 in reactions with olefins.79 Formation of a mixture of diastereomers is observed in the case of 1,2-disubstituted alkenes. Reaction with conjugated dienes leads exclusively to the product of 1,4-addition 89 as mixtures of E- and Z-products whose ratio depends on steric factors (Scheme 34).79... 

When located at opposite ends (or at conjugated positions) in a molecular system, a donor and an acceptor do more than simply add up their separate effects. A cooperative phenomenon shows up, involving the entire disubstituted molecule, known as charge transfer (C.T.). Such compounds are colored (from pale yellow to red, absorption from 3,000 to 5,000 A) and show high U.V. absorption oscillator strength. "Figure 2 helps understand the enhancement of optical nonlinearity in such a system. 

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