Patai S., Rappoport Z. 2000 The chemistry of functional groups. The chemistry of dienes and polyenes. V. 2 / 0739 884

transforms into 2-benzyl-6-methylphenol 328 (AcOH C 1% H2SO4, or aqueous dioxane C HCl, 25 °C, 20 min) (equation 115)173. The migration of a benzyl group to the C(2) position can proceed even if the latter is occupied by a tert-butyl group. The rearrangement of the dienone 329 (in 2N HCl in 80% aqueous methanol) results in partial elimination of the tert-butyl group to provide 2-benzyl-6-methylphenol 328 and 5-benzyl-2-tert-butyl-6- methylphenol 330 in a 5 : 7 ratio (equation 116)173.

Me

(326)

Various mechanisms are discussed for the migration of a benzyl group including, e.g., a two-stage Cope or reverse Claisen rearrangement as well as a preference of direct [1,5]-shift over successive Wagner – Meerwein migrations (equation 115)173.

Besides catalyzed rearrangements, thermal isomerizations in a series of linearly-conju- gated cyclohexadiene systems, which are accompanied by migrations of various groups having a complex structure, are also known. The thermal sigmatropic migrations of methoxycarbonyl groups proceed upon pyrolysis of the acetoxydiene 331 to give dimethyl isophthalate 332 without a change in the isotope distribution (equation 117)174. This excluded a radical-chain mechanism and confirms the complete intramolecularity of the rearrangement. By using NMR spectral analysis the behavior of the deuterium labeled

triester 333 was investigated in order to distinguish two possible pathways: (1) direct [1,3]- methoxycarbonyl migration, and (2) direct [1,5]- or two successive [1,3]-shifts. Path (1), which involves a single [1,3]-shift, was excluded in this way, whereas the [1,5]-shift mechanism was found to fit the observations without special assumptions (equation 118).

The presence of an acetoxy group is not a necessary condition for the methoxycarbonyl rearrangement. Thus, the pyrolysis of diene 334 (300 – 320 °C, 1 h, 97% conversion) gave the diester 335 as the major product (equation 119)174. Dicarboxylates like 334 were suggested to be the intermediates in pyrolysis (420 °C, flow system) of dimethyl and diethyl 2-acetoxycyclohex-3-ene 1,1-dicarboxylates175.

Besides the dienone – phenol rearrangement there are also several types of a related dienol –benzene rearrangement in which the intermediate cyclohexenyl cation 341 is generated from cyclohexadienols 340 by elimination of the appropriate nucleofuge, e.g. hydroxy group, rather than by addition of an electrophile as above (equation 122)178. Such nucleofuge can also be a chlorine atom (see also equation 101). The mechanism of the dienol –benzene rearrangement in a series of steroides was studied by using 2H NMR spectroscopy during the transformations of the steroid alcohol 342 (equation 123)179. The

H OH

(340)(341)

R = Me, CCl3

DBr

AcOD +

HO

H

(342)

OAc

Me

Me

+

+

(123)

H

OAc

−H+

AcO

(343)

Me

absence of a deuterium label in the aliphatic fragment of the final structure 343 suggests that the rearrangement proceeds by a cleavage of the C(3) O bond rather than through a prior dehydration to 1,3,5(6)-triene and subsequent reprotonation179.

A related dienediol –phenol rearrangement which can occur by different pathways was reported as a new method for synthesis of the oxepine system180. Protonation of the starting diol 344 produces a cation 345 which can follow ‘normal’ dienone –phenol rearrangement (path a) when the substituents R2 D Me, Ph and R1 D t-Bu are eliminated in the step 346 ! 347. However, when R1 D t-Bu and R2 is a substituted phenyl which decreases the nucleophility, the cationoid intermediate 345 cyclizes to the oxonium ion 348 (path b) which then undergoes deprotonation to give the oxepine 349 (equation 124)180.

R1 = Me, Ph, t-Bu; R2 = Me, Ph, Ar; R3 = t-Bu, Ph, Ar

Various transformations take place upon interaction of acid reagents with hydroxycyclohexadienones containing both hydroxy and carbonyl groups. Thus, treatment of compound 350 with an Ac2O C H2SO4 mixture leads to elimination of the OH group and substitution of a tert-butyl moiety (equation 125)181. An analogous behavior of 4-alkyl-substituted dienones 351 in the presence of Ac2O or other acidic reagents was described a few year later (equation 126)182.

A two-step transformation of conjugated dienes into non-conjugated ones was proposed for the synthesis of the difficult to-obtain lapachol (355) (a member of a class of antimalarial agents having an activity against the Walker carcinosarcoma 256) from the more available isolapachol 352183. This method consists in an oxidative cyclization of isolapachol 352 by 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) to form a mixture of the products 353 and 354 (equation 127). Treatment of this mixture with dilute acid in