Intramolecular reactions Wittig reactions

Phenylcyclopent[c]azcpine (33a) and 6,7-fused cyclopentazepines 33b-d are formed in moderate yields in a one-pot, two-stage process involving initial condensation of triphenyl-[(l-phenylvinyl)imino]phosphoranes 32 with 6-(dimethylamino)fulvene-2-carbaldehyde (30), followed by an intramolecular aza-Wittig reaction of the iminophosphorane with the pendant aldehyde function.5 The method fails with the unsubstituted vinylphosphorane 32 (R1 = R2 = H). 

Two intramolecular aza-Wittig reactions leading to 1,3-benzoxazepines have been described. In the first,19 ethyl (Z)-3-(2-acyloxyphenyl)-2-azidoprop-2-enoates 1 are treated with triphenyl-phosphane under argon at 20°C for 3-4 hours when 2-substituted ethyl 1,3-benzoxazepine-4-carboxylates 2 are obtained in 85-90% yield. 

Alkoxy-3//-l,4-benzodiazepin-5(4//)-ones by Intramolecular Aza-Wittig Reactions... 

An intramolecular aza-Wittig reaction of the imino-A5-phosphancs 4, prepared by the action of triphenylphosphane on the corresponding azido compounds, affords l//-l,2,4-benzo-triazepines 5.346 The reactions were carried out by heating compounds 4 in acetonitrile or 2-hydroxyethyl methyl ether for the time indicated. No further details were reported. 

The synthesis of pyrrolo[3,4-c]pyridazines 20 is achieved by intramolecular aza-Wittig reactions of the phosphazines 19 <95JHC1457>. 

In a similar sense, the intramolecular aza-Wittig reaction of azide 135 resulted in quinazolinone-containing product 136 in good yield <00H1765>. Compound 136 then underwent acid-promoted cleavage through intermediate 137 to yield fused quinazolinones 138 after tautomerization. 

The only example known for the formation of azetidine 82 by direct intramolecular aza-Wittig reaction is the reaction of the /3-azidoketone 81 with triphenylphosphane (Scheme 41). Attempts to transfer this reaction to 83 and 84 were not successful (87NKK1250). This failure can be attributed to the formation of intermediates with highly energetic transition states, where the rate of intramolecular attack on the carbonyl function is so slow that oligo- and polymeric compounds are preferentially formed. 

The simplest available derivatives of pyrrole in this sense are pyrrolines (97) which are accessible by simple intramolecular aza-Wittig reaction of iminophosphorane 96, the latter being formed by a Staudinger reaction from -y-azidoketones (95), as shown in Scheme 44. The process occurs under neutral conditions, so that once the double bond is formed, it cannot isomerize (86TL1031 87NKK1250). 

An intramolecular aza-Wittig reaction of 1,3-diketones (134) and hydra-zinobis(iminophosphoranes) (133) gives pyrazole (135) on elimination of two equivalents of triphenylphosphane oxide, as shown in Scheme 53 (75CB623). 

Imidazoles are synthesized from A-(2-azidoethyl)phthalimide (136) via the Staudinger reaction to obtain an initial intermediate iminophosphorane 137, which is then converted by an intramolecular aza-Wittig reaction and... 

Access to pyridines from aza-l,3,5-triene units, achieved by an intramolecular aza-Wittig reaction and thermal electrocyclic cyclization with a subsequent 1,3-H shift, was mentioned in Section V,B (cf. Scheme 28) as an... 

Fully unsaturated 1,3-benzoxazepine system (319) can be obtained by intramolecular aza-Wittig reaction (90S455) of the esters (318) induced by triethyl phosphite (90S455,92CC81). 

An intramolecular aza-Wittig reaction of the /3-lactam carbonyl group with azide present at the o-position of the A -benzyl substituent in azetidin-2-ones 377 gives the fused tricyclic heterocyclic compound 378 (Equation 150) <1998SL1288>. 

Exposure of the substrate 174 to dimethyl acetal of azidoacetaldehyde in the presence of TMSOTf gives the intermediate 175, which affords the pyrrole 176 under conditions of intramolecular aza-Wittig reaction (Scheme 98) <2005JOC4751>. 

The intramolecular aza-Wittig reaction of azidothioesters provides a new approach to functionalized thiazolines <07AG(E)2701>. Coupling of protected amino acids 79 with azido thiols 80 provides thioesters 81, which are treated with triphenyl phosphine to afford thiazolines 17 in good yields. Similarly, the bis(thioester) 82 is converted into the bis(thiazoline) 19. These thiazolines are readily oxidized to the corresponding thiazoles (vide supra). 

Bis(iminophosphorane) 9 affords 2-substituted quinazolin-4(3//)-one 10 on heating in anhydrous toluene at reflux temperature. This conversion involves an intramolecular aza-Wittig reaction where an amidocarbonyl group acts as the carbonyl partner. ... 

Treatment of thiol ester azide 212 with PPhs in anhydrous THF (under reflux) provided thiazoline 213 in good yield (Scheme 84). In situ generation of a phosphinimine by Staudinger reaction of the azide with PPh3 allowed an intramolecular aza-Wittig reaction to take place with the thioester under the neutral and anhydrous conditions <2004PNA12067>. 

Nitrogen Heterocycles.- Reactions of iminophosphoranes have been used to prepare a wide range of heterocycles. Examples of compounds prepared by intramolecular aza-Wittig reactions include 3,4-dihydroquinazolines (191) and quinazolines (192), quinazoline derivatives (e.g. 193),pyrrolo( 1,2-a)quinoxalines (194), indolo[3,2-clquinolines (195), and indolo[l,2-c]quinazolines (196),"8 imidazolinones (197),"9 quinazolinones (198),"9, 120 pyrido[2,3-d]pyrimidine derivatives (199), 21 and 4,5-dihydropyrazolo(3,4-d]pyrimidine derivatives (200). 22 Tributyl(cyclohepta-1,3,5-trienylimino)phosphorane (201), prepared by thermal isomerization of the 2,4,6-derivative, reacts with a,p-unsaturated ketones to give 9H-cyclohepta[b]pyridine derivatives (202). 23 a synthesis of (2,4)pyridinophanes (204) by the reaction of N-vinyliminophosphoranes (203) with a,P-unsaturated ketones has been reported. 24... 

Sugimori, T., Okawa, T., Eguchi, S., Kakehi, A., Yashima, E., Okamoto, Y. The first total synthesis of (-)-benzomalvin A and benzomalvin B via the intramolecular aza-Wittig reactions. Tetrahedron 1998, 54, 7997-8008. 

Azeto[2,l-bjquinazolines. The intramolecular aza-Wittig reaction by treatment of A/-(o-azidobenzyl)azetidinones (also the A/-benzoyl analogs) with triorganophosphines R3P is only successful when R = Me (when R = Bu, Ph, complex reaction mixtures are generated which do not contain the desired products). 

A third variation involves formation of the C-N bond and hence the heterocyclic ring as a result of an intramolecular aza-Wittig reaction. The azidocinnamate (85) yields the substituted benzo[d,e]quinoline (87) on treatment with triethyl phosphite, presumably via the iminophosphorane (86) (D,M.B. Hickey et at, Chem. Comm., 198A, 776). 

A new synthesis of 2-imidazolin-5-ones (194) utilizes an intramolecular aza-Wittig reaction. Readily available azidoimides are treated with triphenylphosphine to give (194) by sequential Staudinger and intramolecular aza-Wittig processes (Scheme 130) <89T6375>. 

IH(32)1913>. Intramolecular aza-Wittig reaction was facilitated by triphenyl phosphine to transform 3-O-azidophenyl isoxazole (57) to isoxazolo isoquinolinone (58) (Equation (12)). N-Alkylation of 5-substituted isoxazole (59) with ethylbromoacetate resulted in the isoxazolium bromide salt (60) (Equation (13)). Isoxazolium salts are very useful in making the synthon, jS-ketoamide <83JOC1149>. 

JOC43i>. An intramolecular aza-Wittig reaction ensues upon treatment of the azides with phosphorus(III) reagents (Scheme 65). Yields of oxazoles, including furyl- and pyridyl-substituted... 

Compounds 21 react with triphenyl phosphine to give the corresponding phosphazines. When the starting diazocompound carries a vinyl group substituted by a carbonyl function, an intramolecular Aza-Wittig reaction provides an interesting entry to CF3-substituted pyridazines 24 (Scheme 41, ref. 33). 

Scheme 7.2 Some reaction types which are characterized by large, negative volumes of activation (a) Diels-Alder and other cycloaddition reactions, including heterocyclic and intramolecular examples (b) ionogenic reactions, such as Menshutkin quaterniza-tions (c) additions to double bonds, for example, aldol reactions, Wittig reactions and, chiral-borane reductions (in the last type of reaction, pressure both accelerates the reduction and retards decomposition of the Alpine borane to achiral 9-BBN) (d) sequential...

An interesting isoquinoline synthesis uses an intramolecular aza-WiTTiG reaction to establish the C=N bond in o-acylstyryl ylides 72, producing 1-substituted isoquinoline-3-carboxylic esters 73 [117] ... 

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