An Intramolecular Wittig Reaction

The 5,8-dimethoxy-2(l//)-quinolinones 60 were obtained in moderate yield via an intramolecular Wittig reaction <95LA1895>. 

A solvent-free synthesis of benzo[b]furan derivatives 10-79, a class of compounds which is often found in physiologically active natural products, was described by Shanthan Rao and coworkers. These authors heated phosphorane 10-71 for 8 min in a microwave oven and obtained the benzo[b]furan 10-74 in 73% yield (Scheme 10.18) [25]. The sequence is initiated by an intramolecular Wittig reaction, providing alkyne 10-72 this underwent a subsequent Claisen rearrangement to give the intermediate 10-73. Also in this case, normal oil-bath heating gave much lower yields (5%) of the desired product the authors hypothesize that the micro-... 

Heterocycles.—The phosphonium salt (59) is an effective three-carbon synthon, as demonstrated by its reaction with enolates of /9-keto-esters (Scheme 20) to give cyclopentenyl sulphides via an intramolecular Wittig reaction.63 Ylides are also intermediates in the synthesis of dihydrofurans (60) from the cyclopropylphos-phonium salt (61) and sodium carboxylates (Scheme 21).64 Cumulated ylides are very useful for the synthesis of heterocyclic compounds, e.g. (62), from molecules which contain both an acidic Y—H bond and a carbonyl or nitroso-function, as shown in Scheme 22.65... 

The tricyclic 76 was obtained from an intramolecular Wittig reaction <98H2287>. The tricyclic 78 was obtained by reaction of 77 with benzyl bromoacetate in the presence of base followed by intramolecular Michael reaction <99T3427>. 

Three main synthetic routes have been used to prepare variously substituted carbapenems. Two involve an intramolecular Wittig reaction to form either the C(2)—C(3) bond (equation 1) or the C(l)—C(2) bond (equation 2). The third approach uses a carbene insertion step to form the C(3)—N(4) bond (equation 3). 

Benzoxepins are frequently synthesized by cyclization of alkyl aryl or diaryl ether precursors. An intramolecular Wittig reaction (equation 48) is used to provide the ring closure step in the synthesis of 1-benzoxepin (28) (68JOC2591). An internuclear cyclization reaction of an aromatic sulfonyl chloride (equation 49) occurred upon heating (250 °C) in the presence of a copper chloride catalyst to yield tribenz[6,d,/]oxepin (175). The analogous thiepin (see equation 71) may also be synthesized by this route (65T1299). 

Cyclopentenone amelation,1 A new method for this reaction involves Pd(0)-directed C-alkylation of 2-mcthyl-1,3-cyclopentanedione or 2-methyl-l,3intramolecular Wittig reaction (equation I). Of special interest, the cyclopentenone 1 can be obtained in optically active form by use of an optically active phosphine. Thus use of (R)-DIOP (4, 273 5, 360- 361 6, 309) leads to 1 as a 70 30 mixture of ( + )- and (-)-enantiomers. Similar results arc obtained with (R)-(-)-methylphenylprop>i-phosphine. 

The ring closure (83 — 84) involves an intramolecular Wittig reaction (81CC14). Another variation on the Madelung indole synthesis is provided by the cyclization of o-isocyanobenzenes (85 — 86) (77JA3532). 

The synthesis of the benzoxepin (167) involves an intramolecular Wittig reaction (Scheme 19) (68JOC2591). 

Diarylpyrroles have been constructed from a-amidonitriles and vinylphosphonium salts. The reaction presumably proceeds by nucleophilic addition to the vinylphosphonium salt followed by cyclization via an intramolecular Wittig reaction. Elimination of HCN accounts for the final aromatization (equation 118) (81JOC2570). 

The action of the base on the phosphonium salt generates the betaine (113) which is considered to exist in solution as the open form rather than the cyclic oxaphosphole (114). NMR evidence confirms the intermediacy of the phosphonium salt (115) and in some instances these salts have been isolated. Further treatment with base affords the ylide which undergoes an intramolecular Wittig reaction to yield the chromene (Scheme 12) (80T3409). 

The monophosphonium salt derived from l,2-di(bromomethyl)benzene reacts with sodium carboxylates to afford high yields of the ester (190). Generation of the ylide results in spontaneous cyclization via an intramolecular Wittig reaction to the isochromene (Scheme 35) (79TL2149). 

Carbanions stabilized by phosphorus and acyl substituents have also been frequently used in sophisticated cyclization reactions under mild reaction conditions. Perhaps the most spectacular case is the formation of an ylide from the /7-lactam given below using polymeric Hilnig base (diisopropylaminomethylated polystyrene) for removal of protons. The phosphorus ylide in hot toluene then underwent an intramolecular Wittig reaction with an acetyl-thio group to yield the extremely add-sensitive penicillin analogue (a penem I. Ernest, 1979). 

Butenolides. 21-Hydroxy-20-keto steroids react with 1 to form cardenolides by an intramolecular Wittig reaction (equation I).2... 

We have shown that the ylids 3 react with a number of nucleophiles (3). In particular 3a and 3b react quantitatively with the alkylidene phosphoranes 5 to give 3-pyrrolines 6a and 6b as a mixture of diastereoisomers. The cyclisation occurs via an intramolecular Wittig reaction on the carbonyl of an ester group (M. In the same conditions, 2c reacts with 5 to give quantitatively the pyrrolines 7c (two diastereoisomers) as a result of a Wittig reaction on the carbonyl of the keto group in 3c. 

Quinolinones can be made by the reaction of 2-aminophenones with a ketene ylide via an intramolecular Wittig reaction (Equation 122) <2003JOC4170>. The nucleoside unit in this example survives the reaction conditions. The reaction of (2-fluoromethyl)aniline with esters of arylacetic acid yielded 4-fluorinated 2-quinolinones (Scheme 66) <20040L4061 >. 

Salicylaldehyde derivatives react with dimethyl acetylenedicarboxylate in the presence of triphenylphosphine (PPh3) to afford di methyl-2//-chromene-2,3-dicarboxylates in high yield. The reaction proceeds via an intramolecular Wittig reaction of the ylide intermediate 71 (Scheme 23) <2003PS1457>. 

Treatment of a-hydroxymethylene ketones 646 with (triphenylphosphoranylidene)ethenone forms the intermediate ylide 647, which can undergo an intramolecular Wittig reaction to afford 2//-pyran-2-ones (Scheme 151) <1998T2161>. 

Substituted chromones can be synthesized in good yield from the corresponding silyl esters 764 via formation of the ylide intermediate 765, followed by an intramolecular Wittig reaction (Scheme 202) <20000L3821>. 

Treatment of keto alcohols 877 with (triphenylphosphonylidene)ethanone forms the intermediate ylide 878, which cyclizes via an intramolecular Wittig reaction to afford 5,6-dihydropyran-2-ones 879 (Scheme 243, Table 38). A slight improvement in yield can be observed by using keto alcohols masked as their 1,3-acetals <1998T2161>. 

Acylation of the thiol moiety of thiosalicylic acid is the starting point for a synthesis of 2-substituted thiochromones in which the key step is an intramolecular Wittig reaction (Scheme 203) <2001T9755>. 

Very likely the ammonium fluorides are the proton sources and therefore the reason for incomplete conversions, since potassium fluoride in acetonitrile gives high yields in a very elegant [3 + 2]-annuIation process 87). It combines a Michael addition to a vinyl phosphonium salt with an intramolecular Wittig reaction and proceeds only in the presence of 18-crown-6 with satisfying yield. This cyclopentene synthesis has been executed in a repetitive manner to prepare linear triquinanes as illustrated in Scheme 6. Unfortunately, the sequence is non-stereoselective with regard to the ethoxycarbonyl functions. 

The ring closure involving an intramolecular Wittig reaction is exemplified by Scheme 50 . 

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