Addition-rearrangement sequence

It is noteworthy that the reaction of phenylallene with dichlorocarbene under basic conditions has been reported to lead to the pentachloride (281) 210 a). However, the structure of the product has now been reassigned as (282), the formation of which appears to involve a similar addition-rearrangement sequence to that described for the formation of (279), the intermediate cyclobutenylcation being trapped by chloride 210b). 

Similar results were obtained on application of the related Tiffeneau-Demjanov reaction. This semipi-nacol-type reaction, an extension of the Demjanov rearrangement, involves the rearrangement of a diazonium ion (25 Scheme 7), which is generated by the diazotization of the corresponding amino alcohol (24).The amino alcohol is obtained from the ketone by reduction of a nitrome ane adduct (23a), cyanohydrin (23b) or trimethylsilyl cyanohydrin (23c). This procedure allows for a controlled addition-rearrangement sequence in cases where the use of diazomethane is complicated by the further reaction of the product ketone. 

MacMillan has developed a Lewis acid-catalyzed addition-rearrangement sequence which facilitates the conjugate addition of allylamine 408 to allenoate ester 409 to generate the zwitterionic intermediate for the Claisen rearrangement. The minimization of steric interactions between the ammonium species and the y-allenyl substituent led... 

One further addition-rearrangement sequence which should be mentioned is the reaction of phase transfer generated dichlorocarbene with spirocyclopropylindene. The initial carbene adduct is unstable under the reaction conditions and undergoes ring expansion and dehydrochlorination to yield a mixture of l-(2-chloroethyl)-3-chloronaphthalene and l-vinyl-3-chloronaphthalene [23]. The reaction is formulated in equation 2.24. 

The fragmentation of alkoxyl radicals is especially favorable because the formation of a carbonyl bond makes such reactions exothermic. Rearrangements of radicals frequently occur by a series of addition-fragmentation steps. The following two reactions involve radical rearrangements that proceed through addition-elimination sequences. 

A new multistep synthesis of ( )-reserpine (109) has been published by Wender et al. (258). The key building block of the synthesis is cw-hexahydroiso-quinoline derivative 510, prepared by the extension of the previously elaborated (259) Diels-Alder addition-Cope rearrangement sequence. Further manipulation of 510 gave 2,3-secoreserpinediol derivative 512, which already possesses the required stereochemistry in ring E. Oxidative cyclization of 512 yielded 3-isoreserpinediol (513), which was transformed by the use of simple reaction... 

Additionally, uracil 6-iminophosphorane, isocyanate, and o-methyl-e-caprolactim ether join to form the intensely yellow pyrimido[4 5 4,5] pyrimido[6,l-n]azepine (360), as shown in Scheme 130. Upon ring closure, methanol is spontaneously eliminated. Diethyl azodicarboxylate affords with the other components pyrimido[4,5-e][l,2,4]triazoline (361), which is closely related to the alkaloid isofervenuline. The imidazo[5, -/][ ,2,4]tria-zine (362) results in a known Michael-type rearrangement sequence by treatment with diethyl acetylenedicarboxylate (86JOC149, 86JOC2787) in this latter case, the Michael-type addition occurs much faster than the expected three-component reaction [93H(35)1055]. 

Derivatives of trifluoroethanethiol have limited though interesting chemistry. Unfortunately, metallated difluorothioenol chemistry has not been reported, because rapid nucleophilic attack occurs even by hindered bases such as LDA. Nakai et al. exploited this high electrophilicity in a tandem addition/elimina-tion-rearrangement sequence [146], but more recent applications have concerned free radical chemistry (Eq. 46). Chlorination of trifluoroethyl phenyl sulfide followed by exposure to tin hydride in the presence of an allylstannane resulted in C-C bond formation with a reasonable level of stereocontrol [147]. 

Stiasni, N. and Kappe, C.O., A tandem intramolecular Michael-addition/elimination sequence in dihydropy-rimidone to quinoline rearrangements, ARKIVOC, 2002, 71-79. 

Polysubstituted 1,3-oxazolidines were prepared in a one-pot diversity oriented four-component reaction (4-MCR), comprising two linked domino processes. Thus, domino synthesis of enol ethers 9 was followed by a sequential amine addition-cyclization sequence [74]. While strong microwave irradiation (900 W) of silica-gel absorbed conjugated alkynoates 9 and amines afforded tetrasubstituted pyrroles (via the skeletal rearrangement of 1,3-oxazolidines, see Sect. 2.1 and Scheme 5) [24], the use of milder microwave conditions (160 W power, 90 min) furnished 1,3-oxazolidines. Under these mild conditions the 1,3-oxazolidines did not rearrange to pyrroles and with respect to diastereoselectivity, the 1,3-oxazolidines were obtained as mixtures of syn/anti isomers. Overall, the formation of one C-C bond, one C-0 bond, two C - N bonds and a ring in this MCR required less than 3 hours and utilized simple and commercially available reagents (Scheme 26). 

The alkane and alkene intermediates have been isolated, which supports the contention that an addition/elimination sequence has been followed. After the first addition, which yields the saturated compound, two elimination reactions occur to give the alkyne derivative. This then undergoes a second addition to result in the final, rearranged, substitution product. 

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