Amides intramolecular vinylations

Muratake et al. reported the intramolecular a-arylation of ketones [55,56]. Thus, polycyclic compounds are readily obtained from aromatic keto-bromides and keto-triflates (Eq. 16). Bromo-amides can give the corresponding cycliza-tion products (Eq. 17) [52]. Related intramolecular vinylation reactions to give aliphatic polycyclic compounds have also been reported (Eq. 18) [57,581. The intramolecular cyclization of aromatic halo-ketones under carbon monoxide, which proceeds by mechanism C, gives the corresponding a-acylated products (Eq.l9) [321. 

Zhao, Q. W. and Li, C. Z. 2008. Preference of P-lactam formation in Cu(l)-catalyzed intramolecular coupling of amides with vinyl bromides. Org. Lett. 10(18) 4037-4040. 

It is known that the oxidative addition of aryl or vinyl halides to a low-valent palladium complex produces an aryl- or vinylpalladium complex, which reacts with carbon monoxide to afford an acylpalladium complex. If alcohol and amine are added to this reaction system, we can obtain ester or amide. " Intramolecular reactions of aryl or... 

Scheme 29 Copper-catalyzed intramolecular vinylations of amides...

The reaction of alkenyl mercurials with alkenes forms 7r-allylpalladium intermediates by the rearrangement of Pd via the elimination of H—Pd—Cl and its reverse readdition. Further transformations such as trapping with nucleophiles or elimination form conjugated dienes[379]. The 7r-allylpalladium intermediate 418 formed from 3-butenoic acid reacts intramolecularly with carboxylic acid to yield the 7-vinyl-7-laCtone 4I9[380], The /i,7-titisaturated amide 421 is obtained by the reaction of 4-vinyl-2-azetidinone (420) with an organomercur-ial. Similarly homoallylic alcohols are obtained from vinylic oxetanes[381]. 

Many synthetic water-soluble polymers are easily analyzed by GPC. These include polyacrylamide,130 sodium poly(styrenesulfonate),131 and poly (2-vinyl pyridine).132 An important issue in aqueous GPC of synthetic polymers is the effect of solvent conditions on hydrodynamic volume and therefore retention. Ion inclusion and ion exclusion effects may also be important. In one interesting case, samples of polyacrylamide in which the amide side chain was partially hydrolyzed to generate a random copolymer of acrylic acid and acrylamide exhibited pH-dependent GPC fractionation.130 At a pH so low that the side chain would be expected to be protonated, hydrolyzed samples eluted later than untreated samples, perhaps suggesting intramolecular hydrogen bonding. At neutral pH, the hydrolyzed samples eluted earlier than untreated samples, an effect that was ascribed to enlargement... 

Finally, the intramolecular coupling reaction between an olefin and a pyrrole ring has been examined (Scheme 40). In this example, a 66% isolated yield of the six-membered ring product was obtained. A vinyl sulfide moiety was used as the olefin participant and the nitrogen protected as the pivaloyl amide in order to minimize the competition between substrate and product oxidation. Unlike the furan cyclizations, the anodic oxidation of the pyrrole-based substrate led mainly to the desired aromatic product without the need for subsequent treatment with acid. 

Radical cyclizations are often used in ring formations and are an effective methodology in the synthesis of piperidines. The intramolecular cyclization of an oxime ether, such as 63 onto an aldehyde or ketone gives a new entry into cyclic amino alcohols <99JOC2003, 99H(51)2711>. Similarly, reaction of a terminal acetylene with BujSnH generates a vinyl radical, which will cyclize with an imine moiety to give 3-methylenepiperidine <99TL1515>. The indolizidine alkaloid ipalbidine was prepared by a sulfur-controlled 6-exo-selective radical cyclization of an a/p/ia-phenylthio amide <99H(50)31>. 

Reaction of the dilithio anion of 1-vinylbenzotriazole 90 with 2equiv of an aryl isocyanate led to a fused 1,4-diazepine ring formation via an intramolecular Michael addition of the intermediate aryl amide to the vinyl moiety, a type c ring closure that proceeded in good overall yield (Scheme 44) <2003JOC5713>. 

Diketones or P-oxocarboxylic add esters and amides react with amino add salts to yield the corresponding enamines 123 (Scheme 59).1 .729] jjjese derivatives are stable to basic reaction conditions and can be used for peptide couplings. Cleavage of the A/-vinyl derivatives is readily achieved with mild acids. The enamines are usually stabilized by an intramolecular hydrogen bond, as has been confirmed by NMR and IR spectroscopy.1 1... 

Vinyl oxazolidinone 148 has been shown to be a good precursor to rra r-oxazolines (Scheme 38). Under palladium(O) catalysis, an intermediate 7t-allyl complex is formed with the loss of CO2. Intramolecular attack by the amide oxygen forms the thermodynamically favored /ra r-oxazoline 149. This oxazoline was then converted to the natural product balanol <19990L615>. 

The synthesis of unnatural (+)-mesembrine (387) through the asymmetric synthesis of methyl (i )-l-[(3,4-dimethoxy)phenyl]-4-oxocyclohex-2-enyl acetate (390) by cycloaddition of enantiomerically pure vinyl sulfoxide with dichloroketene has been performed 189) (Scheme 43). Vinyl sulfoxide 388 [prepared by conjugate addition of enantiopure acetylenic sulfoxide with (3,4-dimethoxy)phenylcopper] reacted with trichloroacetyl chloride in the presence of freshly prepared zinc-copper couple in THF at 0°C to produce a mixture of mono- and dichloro lactones 389. Reduction of 389 with zinc in acetic acid followed by cyclization and methylation afforded methyl IR-[(3,4-dimethoxy)phenyl]-4-oxocyclohex-2-enyl acetate (390), treatment of which with methylamine brought about amidation and concomitant intramolecular Michael addition to provide 2-oxo-mesembrine (391). Successively, 391 was transformed to (+)-mesembrine (387) in 79% yield (three steps ketalization of an oxo group, reduction of lactam, and deketali-zation)(/S9). 

The intramolecular acylation of the vinyl lithium derivative of 63, prepared by exchange of iodine with lithium (chapter 8) with the Weinreb amide on the side chain gives the five-membered heterocyclic ring in 64, an intermediate on the way to (-)-brunsvigine 65, an alkaloid of the montanine group.14... 

More recently, a tandem Heck/allylic substitution cascade was used as a route toward various lactams. The reaction of 631a,b with 2-isopropenyl bromide in the presence of Pd(OAc)2 and (o-tolyl)3P gave the Heck adduct 632 that reacted further with H-Pd-Br to give the 71-allylpalladium complex 633. Intramolecular attack of the amide anion on the 7i-allyl complex followed by reductive elimination of Pd(0) afforded 634a,b in 77 and 75% yield, respectively (03OL259). Other vinyl bromides were also examined and found to give substituted pyrrolidinones and piperidones in moderate to good yields (50-82%). 

Various examples of intramolecular stereoselective carboamination have been reported28 "30. Asymmetric synthesis of key intermediates for capnellenols is achieved via a Heck-type intramolecular carbopalladation of an alkene with a vinyl halide and amide anion capture in the presence of Chiraphos- or BINAP-modified palladium catalysts31. 

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