O-Vinyl derivatives

The oxygen analogue of the Fischer cyclization requires the formation of O-vinyl derivatives of N-aryIhydroxylarnincs. These are readily converted to indoles but are less readily accessible than the arylhydrazones used for the Fischer cyclization. 

One route to O-vinyl derivatives involves LiPdCl4-catalysed exchange with vinyl acetate[l]. Rearrangement and cyclization occur concurrently to give 1-acylindoles. 

Addition of arylhydroxylamines to electrophilic allenes such as methyl propadienoate or l-methancsulfonyl-l,2-propadiene is another route to O-vinyl derivatives[2]. The addition step is carried out by forming the salt of the hydroxylamine using NaH and the addition is catalysed with LiO,CCF3. The intermediate adducts are cyclized by warming in formic acid. Yields are typically 80% or better. 

The first mechanism is favored at present (see Sections IV.A-C) in many cases the formation of pyrroles clearly involves O-vinyl derivatives. 

Reactions of both 4 and 5 lead to the same products, tra s-[Pt(PH3)2Cl2] and buta-1,3-diene. Therefore, the difference in reaction energies (AE) reflects the relative stabiUty of initial bis-o-vinyl derivatives 5 Init is thermodynamically more stable by 7.2 kcal/mol than 4 Init. Very Ukely, destabilization of 4 Init due to mutual trans orientation of vinyl and phosphine hgands is responsible for facilitating the reductive ehmination process 4 Init—>4 TS— 4 Prod. 

Another reaction comprises the interception of intermediate adduct of ketone and hydroxylamine C by acetylene to afford O-vinyl derivative D, further dehydration of which leads to O-vinyl oxime B (Scheme 1.21). Such interception can be more preferable than vinylation of the corresponding ketoxime, since the hydroxyl group is bonded to less electronegative nitrogen atom than nitrogen atom in ketoxime. 

The data on interaction of oximes with acetylenes are quite discrepant [4,7]. For example, according to the work [304], ketoximes are added to dimethyl acetylenedi-carboxylate across the hydroxyl group to form O-vinyl derivatives. At the same time, it is known that such reactions lead to N-vinylnitrones [305-308] or N-vinyl zwit-terion intermediates [305,309,310], which further, attaching the second molecule of acetylene, are converted to oxazole [306-308] or pyridine [305,309] derivatives. 

It has been mentioned [311] that non-cataly tic thermolysis of O-vinyl derivatives of aliphatic ketoximes does not result in pyrroles. At the same time, 0-vinylaryl(hetaryl) ketoximes upon heating ( 100°C, 1.5 h) in the system KOH/DMSO are transformed into the corresponding pyrroles (Scheme 1.137) [315]. 

Thermally reversible gels can be prepared from poly (vinyl alcohol) and alkali metal salts of o-hydroxybenzal derivatives having benzenoid groups at both ends 24). Colored gels can be obtained, depending on the type of ketone used (Figure 4). 

Frejd and co-workers utilized a different tactic for aniline cyclization by first employing a Heck-Jeffery protocol under solvent-free conditions to prepare o-amino dehydrophenylalanine derivatives from o-aminoaryl iodides with the former undergoing a spontaneous la cyclization-elimination sequence to afford 2-methoxycarbonyl indoles <06S1183>. Dimethyl(methylthio)sulfonium trifluoromethanesulfonate (DMTST) was used by the Okuma group to promote the cyclization of o-vinyl-A-p-toluenesulfonylanilide to N-tosylindole <06CL1122>. 

As these acetals could be converted into the 4,6-O-ethylidene derivatives on treatment with acid, it was reasoned that use of a cyclic vinyl ether, namely, 3,4-dihydro-2H-pyran, might prevent this second process, thus leading to a more useful method of selective acetalation.338 An equimolar reaction with methyl a-D-glu-copyranoside for 4 days in N,N-dimethylformamide led to utilization of 88% of the glycoside, and the 6-(tetrahydropyran-2-yl) ether constituted —85% of the crude reaction-product. In contrast to the steric control apparent in this instance, reaction of 3,4-dihydro-2H-pyran with the axial and equatorial hydroxyl groups in dl-1,4,5,6-tetra-O-acetyl-mi/o-inositol was completely unselective,339 a fact that has been rationalized310 in terms of the probable mechanism of these reactions. 

Intramolecular vinyl substitutions are commonly used to form cyclic products. In a typical reaction, p-in-doleacetic acid has been prepared in up to 43% yield from an o-bromoaniline derivative, as shown in equation (23).74... 

In preparing the highly neuroexcitatory o-anisyl derivative 26, Shira-hama and co-workers utilized a photoinduced intramolecular Diels-Al-der reaction of precursor 32, itself derived from optically active vinyl glycinol (Scheme 8).32 Although an attractive and relatively short synthetic route, the possibilities for modification of the C-4 aryl substituent were felt too limited for our purposes. 

Several ruthenium complexes are able to promote the classical Markovnikov addition of O nucleophiles to alkynes via Lewis-acid-type activation of triple bonds. Starting from terminal alkynes, the anti-Markovnikov addition to form vinyl derivatives of type 1 (Scheme 1) is less common and requires selected catalysts. This regioselectivity corresponding to the addition of the nucleophile at the less substituted carbon of the C=C triple bond is expected to result from the formation of a ruthenium vinylidene intermediate featuring a highly reactive electrophilic Ca atom. 

The lithiation of an O-vinyl carbamate with rAr-BuLi followed by transmetallation with zinc bromide provides the convenient acyl anion derivative, which undergoes smooth Pd(0)-catalyzed cross-coupling reactions (Equation (24)).67 This reaction sequence has been extended to lithium enolates. The deprotonation of the aminoester with LDA followed by a transmetallation with zinc bromide in ether furnishes a zinc enolate, which readily adds to the double... 

The UV-spectrum of the second compound (LXXXIV), C21H29N2O+, has an indoline UV-spectrum which shows no shift in alkali but which in 1 N hydrochloric acid is characteristic of the indolinium cation. The IR-spectrum shows the presence of a hydroxyl but no vinyl group. In contrast to LXXXV, which cannot be acetylated, the alcohol LXXXIV with acetic anhydride in pyridine gives a crystalline O-acetyl derivative. 

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