Wittig-type cyclization

Wittig-type cyclization.2 2-Acyloxy- or 2-benzoylbenzoic acids undergo cycli-zation to 3-chloroflavones or 2-chloroindenones, respectively, when treated with excess (C6H5)3P/CCl4 and N(C2H5)3 in CH2C12 in 40-60% yield. This reaction probably involves formation of a chloro ylide (a) via the acid chloride. 

Polycyclic O-Heterocycles - The lactone 132 was prepared from L-xylose-derived lactone 131 by bromoacylation, Wittig-type cyclization and epimeriza-... 

A series of polyoxygenated azepane derivatives 5 were created from azi-dolactol 4 via a Staudinger/aza-Wittig-type cyclization followed by reaction with -alkylmagnesium halides, en route to the synthesis of a library of potent glucosidase inhibitors (140BC8977). 

Intramolecular Wittig-type cyclizations have been used successfully in many ring-synthesis applications, and some further examples reported this year include the preparation of chromones by cyclization of the carbonate (149) and an indole synthesis from O-acyl benzyltriphenylphosphonium salts. The bicyclo[3.3.0]oct-A -en-3-one ring system lacking substituents at C-2 and C-5 is produced by ring closure of the phosphonates (150), although in the case of the parent member of the series (150, R = R = H) a novel dimer is formed... 

Construction of the B Ring. For construction of the penem nucleus the intramolecular Wittig-type cyclization developed by Woodward(38) as modified by Afonso(39) was employed. Compound 18 was N-acylated by treatment with methyl oxalyl chloride in the presence of triethylamine to oxalimide 19.(29) This compound without purification was then heated under reflux in xylene in the presence of triethyl phosphite(40) to yield the tribactam 7. 

A tandem enzymatic aldol-intramolecular Homer-Wadsworth-Emmons reaction has been used in the synthesis of a cyclitol.310 The key steps are illustrated in Scheme 8.33. The phosphonate aldehyde was condensed with dihydroxyacetone phosphate (DHAP) in water with FDP aldolase to give the aldol adduct, which cyclizes with an intramolecular Horner-Wadsworth-Emmons reaction to give the cyclo-pentene product. The one-pot reaction takes place in aqueous solution at slightly acidic (pH 6.1-6.8) conditions. The aqueous Wittig-type reaction has also been investigated in DNA-templated synthesis.311... 

An interesting approach to carbobicyclic polyhydroxylated compounds was proposed by Jarosz.43 It was based on a Lewis acid transformation of sugar allyltins 82 into dieno-aldehydes 83 with the fi-geometry across the internal double bond exclusively. The Wittig-type reaction of 83 afforded a triene, which underwent cyclization under high pressure, providing derivatives of bicyclo[4.3.0]nonane 84. Alternatively, dienoaldehyde 83 was converted into the phosphonate 85, which afforded the bicyclo[4.4.0]-decene derivatives (86) upon reaction with an aldehyde and simultaneous cyclization of the resulting triene.43 (Fig. 29). 

In the total synthesis of filipin III (141) [95], macrocyclization under K2CO3/ 18-crown-6 conditions proceeded (Fig. 4), although the cyclization was unsuccessful under LiCl/DBU conditions, which were useful for roflamycoin (140) [94] and roxaticin [93]. The total synthesis of ulapualide A (142) was accomplished via three Wittig-type couplings [101]. 

Preparation of an HCS by a Wittig-type methodology and subsequent standard transformations into a linear derivative should give the di-olefin ready for the RCM cyclization. 

The retrosynthetic concept of the Nicolaou group is shown in Scheme 22. The target molecule 36 is disconnected via an IMDA cyclization of the diene quinone precursor 138, which would be generated from the tetraline derivative 139 using Wittig chemistry followed by aromatic oxidation. A Claisen-type rearrangement would provide access to 139 whereby the side chain required for the rearrangement of 140 would be introduced by 0-acylation. The core of 141 would be formed via an intermolecular Diels-Alder reaction between diene 142 andp-benzoquinone 130 [42]. 

Benzofuran-2-carbaldehydes readily undergo Wittig reactions in tetra-hydrofuran at room temperature with the resonance-stabilized ylide 2-car-boxy-l-methoxycarbonylethyltriphenylphosphorane, affording high yields of ( )-4-(2-benzofuranyl)-3-methoxycarbonylbut-3-enoic acids. This method is preferable to the Stobbe condensation. The Stobbe-type intermediates undergo quantitative cyclization to methyl l-acetoxydibenzofuran-3-carboxylates on exposure to acetic anhydride at 100 C. Examples are shown in Scheme 27. The intermediate 109 has been used in a synthesis of cannabifuran (110), and the intermediate 111 has been used in a synthesis of the lichen metabolite schizopeltic acid (112). ... 

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