1,2-prototropic shift

A simple preparative route to the previously unknown lH-3-pyrazolines via azomethine imines was developed. Olefins of the type R cH=CHR react with hexafiuoroacetone azine to give azomethine mines, which undergo a sequence of prototropic shifts to form 17/-3-pyrazolines [196, 202], On heating, the latter are transformed into 3-trifluoromethylpyrazoles [196, 206] and, on treatment with bases, into 1,2,5,6-tetrahydropynmidines [206] (equation 45)... 

In the case of alkenes simply substituted by an electron-withdrawing group (without a y-hydroxy group), the stabilized ylides give first a Michael addition and most often a subsequent prototropic shift resulting in new functionalized ylides (Scheme 8). Then a possible evolution of the resulting ylides can occur to give the final products [40-44]. 

Simple acetylenic allylic alcohols can be cyclized easily by tarf-butoxide, and since this base initiates prototropic shifts the vinylic link may.be E or Z such cyclizations proceed via exomethylene furans similar to 15.65 If necessary, UV irradiation can effect both the isomerization of an to a Z-alkene and the cyclization, leaving only the final adjustments to be made chemically.66 In a variation, methoxide plays the role of leaving group allowing very good yields to be attained (Scheme 10).67... 

Furylcarbinols with protic acids (fluoroboric acid) may merely give car-benium (furylium) salts.171 Similar cations are accessible via 2-furyldiazo-methane derivatives,172 but in many cases ring opening and prototropic shifts ensue as in Marckwald reactions (Scheme 30).173 A recent development controls solution acidity by using magnesium or zinc ions instead of protons... 

That the intermediate formed in Scheme 35 C must be the exomethylene compound shown in Scheme 36 had been recognized long before it was isolated and found to be unexpectedly stable except to bases.197 Cyanide ion induces isomerization to the furonitrile by prototropic shift. Other bases cannot be used in place of cyanide ion because they displace the cyano group already present in a substitution of an unusual kind (Scheme 36).197... 

On the other hand, the cation radical of the kinetic ESE+ is readily converted to the thermodynamic cation radical by a 1,3-prototropic shift in the course of the photoinduced electron transfer with chloranil.41 As such, the efficient isomerization of the kinetic ESE cation radical as an intermediate in equation (19) accounts for the observed lack of regioselectivity in equation (18).37... 

Vinylcyclopropanes bearing a cis alkyl substituent undergo a competitive prototropic shift accompanying ring opening (Eq. 14)14). In such cases, temperature... 

Formation of Acyclic Fragments by Homodiene Prototropic Shift... 

The vinylcyclopropenes that bear an alkyl group cis to the double bond relieve the strain of the three membered via prototropic shift. Because of the geometric constraints, olefin geometry is controlled (Eq. 99). Olefination of the bifunctional... 

Scheme 7.19). Prototropic shift of the initial adduct to produce ROCHCl2 and, subsequently, the formate ester is a less favourable pathway. Alternatively, the carbon monoxide-separated ion-pair can lose a proton leading to an alkene, or cycloadducts derived from further reaction with the carbene. The formation of rearranged products from the reaction of 1 -hydroxymethyladamantane suggests that a relatively unencumbered carbenium cation can also be generated, which leads to a Nametkin rearrangement of the system [4]. 

The major product (21-37%) from the reaction of benzyne with N-phenylpyrrole is the 2 1 adduct (167), the formation of which is explicable in terms of the cyclization of either one of two intermediate zwitterions, 165 or 166. Alternatively, prototropic shift within the intermediate (166) accounts for the formation of the a-naphthylamine (147) (4-6% yield). Other benz[o]carbazole derivatives (168 and 169)... 

An exhaustive series of reports by Grigg et al. (28) outlined two basic methods for the generation of azomethine ylides proceeding via either a 1,2-prototropic shift, or by a decarboxylative approach (29). The decarboxylative route to azomethine ylides can be exemplified by the condensation of benzaldehyde with the cyclic amino acid tetrahydroisoquinoline (108) (30), in DMF at 120 °C, to generate the intermediate awfi-dipole 109, which underwent subsequent cycloaddition with N-methyl maleimide to furnish a 1 1 endo/exo mixture of adducts 110 (R = Ph), in 82% yield (Scheme 3.30). 

Yhde generation by this method involves a 1,2-prototropic shift of the proton a to the imine, furnishing, in this instance, a mixture of yhdes 124 and 125, which undergo subsequent ent o-cycloaddition. Due to the highly reactive nature of the dipolarophile, it is unlikely that a single ylide is initially formed, followed by dipole transmutation (Scheme 3.36). 

A samrated 5(2//)-oxazolone, also known as a 3-oxazolin-5-one or a pseudox-azolone, can be considered as the tautomer of a saturated 5(4//)-oxazolone (or 2-oxazohn-5-one) by a 1,3-prototropic shift (Scheme 7.1). 

On treatment with camphorsulfonic acid/pyridine, methyl ( )-1-[(.S )-4-mcthylphcnylsuirinyl]-2-alkenoates undergo, enantioselectively, a sequential prototropic shift and allylic sulfoxide/ sulfenate rearrangement to produce methyl (R,/f)-4-hydroxy-2-alkcnoates in 64- 72% optical purity63a. 

Not unexpectedly the 5a,9a-dihydro-l-benzazepine (64) on heating isomerizes to the conjugated 2,3-dihydro isomer (78JOC315). Likewise, 19F NMR spectra reveal that after 24 hours at 25 °C, 30% of the unconjugated bis-(trifluoromethyl)dihydroazepine (65) (see Section 5.16.4.2.1(ii)) is converted via prototropic shift to the conjugated 2,3-dihydro-3iT-azepine (67JA605). 

Alcoholysis of hydrazides [59] and epimerization of the 7a-epimers of cephalosporin analogues [60] can be effected with the aid of chloral. Because of the donor chlorine atoms the imines formed initially are conducive to conjugate dehydrochlorination or prototropic shift. It is likely that acylazo compounds are intermediates for the ester synthesis. 

Oxidation of alkyl halides via reaction with A -triflyl hydrazides exploits the facile elimination of triflinic acid [74]. Acidification of N-H and C-H by a P-donor is essential to the elimination and the prototropic shift. 

Of particular interest is the syn-l,6-imino-8,13-methano[14]annulene (59) which represents the first authenticated example of a stable If/-azepine with a free NH group (80AG(E)1015>. The annulene with aluminum oxide undergoes a remarkable isomerization to the anti isomer (61). Investigation shows that the isomerization is not a thermal reaction but involves alumina-catalyzed prototropic shifts via the 3f/-azepine tautomer (60). This system is unique in that it is the first example of a 3H -> If/ azepine tautomerism, and is a consequence of the high degree of strain in the anti-Bredt 3f/-azepine (60). 

Michael acceptors which carry a good leaving group at the a-carbon atom or whose electron-withdrawing group itself can serve as the leaving group may be cyclopropanated by active methylene compounds under basic conditions via a prototropic shift subsequent to the Michael addition as outlined in equation 139. Thus, the basicity of the carbanions involved must be balanced to allow the requisite prototropic shift otherwise, the reaction will be very slow or will not work. 

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