Wittig cyclization

Reaction of anthanilic acid 112 with acid anhydrides afforded the corresponding imide derivatives 113. Subjecting 113 to intramolecular Wittig cyclization has been achieved by treatment with A-phenyl(triphe-nylphosphoranylidene)etheneimine in toluene or dioxane whereby the corresponding pyrroloquinolines 116 were obtained (94TL9229). The intermediate 115 resulting from the rearrangement of 114 could be isolated when the reaction was done at room temperature (Scheme 22). 

B-Lactams.- The now standard intramolecular Wittig cyclization procedure has been used110,111 to prepare a number of... 

Table 32 Aza-Wittig cyclization of azinoiminophosphorane intermediates with benzaldehydes to give 1,2,4-triazoles derivatives (Scheme 14) ...

For the synthesis of base-sensitive oxazoles (Scheme 52), /3-acyloxyvinyl azides (130) react with triethyl phosphite via an aza-Wittig-cyclization. Phosphorimidate 131 is converted to 1,3-oxazole 132 with spontaneous elimination of triethyl phosphate (89JOC431). Benzoxazoles are also available by this synthetic route (71CC1608). 

A direct aza-Wittig cyclization to triazolotriazine 176 (Scheme 67) takes place when triazinone 174 is treated with diphenylthiourea, the latter being substituted on the nitrogen. Elimination of triphenylphosphane sulfide from 175 makes 1,2,4-triazole accessible [86JCS(P1)2037]. When the nucleophilic attack continues on the sulfur, thiadiazoles are formed [86JCS(P1)2037]. 

Kurita et al. reacted a-azidocinnamate 327 with benzoyl chloride (Scheme 119) to form benzoate 328, which upon conversion of the azide group into an iminophosphorane (329) underwent an aza-Wittig cyclization to yield 1,3-benzoxazepine (330) (92CC81). 

As Scheme 120 shows, more benzoxazepines are available by aza-Wittig cyclization of o-acyloxy-2-azidoacetophenone (331). The benzoyloxy derivatives, however, eliminate triphenylphosphane oxide but afford an acyclic product (332) for steric reasons (90S455). 

The Staudinger-aza-Wittig cyclization methodology for imine formation can also be applied to the synthesis of oxazolines under essentially neutral conditions.Thus, an azido ester such as 281 reacts with triphenylphosphine to give the oxazoline 283 in excellent yield. There was no evidence for cychzation at the benzoate presumably because cyclization to a five-membered ring is faster than... 

The pyrido[2,3- pyrimidinones 380 and 381 were thermally obtained from boiling the ethyl acrylate derivatives 378 and 379, respectively, with l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and EtNHPd in THF (Scheme 13) <2001W02001055148, 2004USP2004009993>. The acrylates were obtained from reaction of the corresponding pyrimidine-5-carbaldehyde with (carbethoxymethylene)triphenylphosphorane. On the other hand, acrylate 382 was converted into 383 via aza-Wittig cyclization (Equation 32) <1997LA1619>. 

Enantioselective Intramolecular Wittig Reaction. Asymmetric induction has been reported to accompany intramolecular Wittig cyclization of a phosphonium ylide performed in the presence of (/J,5)-CAMPHOS catalyst. However, this reaction proceeds to afford the corresponding cyclization product with only 10% ee (eq 4) ... 

Researchers at Merck have studied the synthesis of the simple carbapenem system (94) through Wittig cyclization of the keto ylide (93). This interesting precursor was prepared directly from the thiol ester... 

Davis and coworkers carried out a Wittig-cyclization sequence with the partially protected 2-deoxyamino sugar 191 using an amino acid based phosphonate. Reaction of 191 with the cesium enolate 192 gave a 53% yield of epimers 193 and 194 (1 1 ratio) in which epimerization of the 2-amino group had taken place. The maimo isomer 194 was then epimerized to the more stable gluco 193 derivative by simple treatment with t-BuOLi in methanol (Scheme 38) [54]. 

Methods for the formation of the six-membered ring of oxacephalosporins (336) include the intramolecular Wittig cyclization of azetidinonyl ylides (335) and the rhodium(II) acetate generation of carbene intermediates from 4-alkoxylactams (337) bearing a diazoketone unit in the side chain. Once formed, the carbenes insert into the N—H bond of the lactam unit thereby effecting ring closure (Scheme 95) <90H(3i)79i, 90H(3i)797>. 

A new class of compounds (13a-f) has been prepared from (12a-f) by a Staudinger reaction with PhaP followed by an intramolecular aza-Wittig cyclization. Compounds (13) are cruciform 7i-systems with the phenyloxazole arms almost perpendicular to the terphenyl system. ... 

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