Alkylidenes substitution

The thermolysis of bis[(trimethylsilyl)methyl]sulfoxides (27) at 100 °C in hexamethylphosphoramide (HMPA) results in the elimination of hexamethyldisi-loxane, and thiocarbonyl ylides appear as reactive intermediates (53). This protocol allows the generation of the parent species la, as well as monosubstituted and alkylidene-substituted representatives such as lb and Ic, which are difficult to obtain by other methods (Scheme 5.9). 

The synthesis of these derivatives from the appropriate pyridine compound is usually more convenient than by alkylation of an indolizine, and almost any pattern of alkyl or alkylidene substitution can be achieved using the methods of synthesis already described. 

The synthesis of 2-alkylidene-substituted l,3-benzoxathiepan-5-one 267 possessing a 0,V-ketene acetal structure was achieved by heterocyclization of 266 in the presence of BF3 NEt3 (Scheme 82) <2001RCB1255>. The reaction corresponds to a formal type a (0—C—C—C—C—0-C) synthesis. 

When propargyl allyl ethers are subjected to transition metal-catalyzed enyne cyclization reactions, 3-alkylidene-substituted tetrahydrofurans are usually formed. A useful variation of this scheme is the Pd(0)-catalyzed tandem enyne cyclization/Suzuki coupling reaction with various arylboronic acids (Equation 90) <2005JOC1712>. The stereoselectivity of this reaction is explained by invoking a chairlike transition state. 

Cyclopropene can also be used as the aUcene component and affords bicyclo[3.1.0]hexen-2-ones upon reaction with alkyne dicobalt octacarbonyl complexes in the presence of NMO (Scheme 250). Vinyl ethers and vinyl esters serve as ethene equivalents in Pauson-Khand reactions. For example, reaction of vinyl benzoate with complex (169) furnished cyclopentenone (170) (Scheme 251). This reaction was used in a synthesis of (-l-)-taylorine and nortaylorine. Allenes participate in intermolecular Pauson-Khand reactions affording alkylidene-substituted cyclopentenones (Scheme 252). ... 

Diastereofacial differentiation in the photooxygenation of alkylidene-substituted norbornenes has been investigated. For 5-cthylidenebicyclo[2.2.1]hept-2-cne, the principal products are exo-and enclo-10, which are formed in a 74 26 ratio (47%), and the regioisomeric norbornadiene 11 (23%)51. 

Bowers GE, Macielag MJ, Xu X, Paget S, Weidner W (2005) Preparation of 7-(alkylidene-substituted-heterocyclic amino) quinolones and naphthyridones as bactericides. WO Patent 33108, 14 Apr 2005... 

Yoshida and coworkers used an ozonolysis of aniline derivative 81 to produce y-aminoester derivative 82 (2005H(65)1481 Scheme 9). Subsequent hydrolysis of trifluoroacetamide 82 led to the alkylidene-substituted 3-pyrrolin-2-one 83. 

Chatzimpaloglou and colleagues employed this approach for a total synthesis ofphaeosphaeride A, a natural antitumor compound (2012JOC9659). They stirred 5-alkylidene-substituted furan-2-one with methoxyamine hydrochloide and LiHMDS in dry THF at —78 °C for 2 h to give the resulting 3-pyrrolin-2-one. 

Buehrdel has demonstrated that a rearrangement is possible from 2-imi-nolactone to form 5-alkylidene-substituted 3-pyrrolin-2-ones upon treatment with TFA (2008JHC845). 

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