Vinyl 1,2-disubstituted

Trapping of the Grignard produced in step 3 (see foregoing) with allyl halide proved to be a useful route to allyl-, vinyl-, 1.2-disubstituted arenes [37]. 

Stockman has reported the preparation of alkyl-, aryl-, and vinyl-disubstituted aziridines with good diastereoselectivities and in good yields through treatment of tert-butylsulfmylimines with the ylide 119, derived from S-allyl tetrahydrothio-phenium bromide (Scheme 1.39) [64]. A range of substrates were tolerated, including heterocyclic, aromatic, and aliphatic substrates (Table 1.16). 

Lithiation at C2 can also be the starting point for 2-arylatioii or vinylation. The lithiated indoles can be converted to stannanes or zinc reagents which can undergo Pd-catalysed coupling with aryl, vinyl, benzyl and allyl halides or sulfonates. The mechanism of the coupling reaction involves formation of a disubstituted palladium intermediate by a combination of ligand exchange and oxidative addition. Phosphine catalysts and salts are often important reaction components. 

Whereas the cycloaddition of arylazirines with simple alkenes produces A -pyrrolines, a rearranged isomer can be formed when the alkene and the azirine moieties are suitably arranged in the same molecule. This type of intramolecular photocycloaddition was first detected using 2-vinyl-substituted azirines (75JA4682). Irradiation of azirine (54) in benzene afforded a 2,3-disubstituted pyrrole (55), while thermolysis gave a 2,5-disubstituted pyrrole (56). Photolysis of azirine (57) proceeded similarly and gave 1,2-diphenylimidazole (58) as the exclusive photoproduct. This stands in marked contrast to the thermal reaction of (57) which afforded 1,3-diphenylpyrazole (59) as the only product. 

Thiazole, 4-methyl-5-(2-hydroxyethyl)-in thiamine biosynthesis, 1, 97 Thiazole, 4-methyl-2-methylami nosynthesis, 6, 300 Thiazole, 4-methyl-2-phenyl-alkylation, 6, 256 mercuration, 6, 256 Thiazole, 2-(methylthio)-methylation, 6, 290 thermodynamic values, 6, 291 Thiazole, 2-methylthio-5-phenyl-synthesis, 5, 153 Thiazole, 4-methyl-5-vinyl-occurrence, 6, 327 Thiazole, 2-phenyl-acetylation, 6, 270-271 Conformation, 6, 237 synthesis, 5, 113, 6, 306 Thiazole, 4-phenyl-conformation, 6, 237 2,5-disubstituted synthesis, 6, 304 Thiazole, 5-phenyl-conformation, 6, 237 Thiazole, 2-phenyl-5-triphenylmethyl-synthesis, 6, 265 Thiazole, 2-(2-pyridyl)-metal complexes, 5, 51 6, 253 Thiazole, 4-(2-pyridyl)-metal complexes, S, 51 6, 253 Thiazole, tetrahydro-ring cleavage, 5, 80 Thiazole, 2,4,5-trimethyl-occurrence, 6, 327... 

A valuable feature of the Nin/Crn-mediated Nozaki-Takai-Hiyama-Kishi coupling of vinyl iodides and aldehydes is that the stereochemistry of the vinyl iodide partner is reflected in the allylic alcohol coupling product, at least when disubstituted or trans tri-substituted vinyl iodides are employed.68 It is, therefore, imperative that the trans vinyl iodide stereochemistry in 159 be rigorously defined. Of the various ways in which this objective could be achieved, a regioselective syn addition of the Zr-H bond of Schwartz s reagent (Cp2ZrHCl) to the alkyne function in 165, followed by exposure of the resulting vinylzirconium species to iodine, seemed to constitute a distinctly direct solution to this important problem. Alkyne 165 could conceivably be derived in short order from compound 166, the projected product of an asymmetric crotylboration of achiral aldehyde 168. 

The reaction of crotonaldehyde and methyl vinyl ketone with thiophenol in the presence of anhydrous hydrogen chloride effects conjugate addition of thiophenol as well as acetal formation. The resulting j3-phenylthio thioacetals are converted to 1-phenylthio-and 2-phenylthio-1,3-butadiene, respectively, upon reaction with 2 equivalents of copper(I) trifluoromethanesulfonate (Table I). The copper(I)-induced heterolysis of carbon-sulfur bonds has also been used to effect pinacol-type rearrangements of bis(phenyl-thio)methyl carbinols. Thus the addition of bis(phenyl-thio)methyllithium to ketones and aldehydes followed by copper(I)-induced rearrangement results in a one-carbon ring expansion or chain-insertion transformation which gives a-phenylthio ketones. Monothioketals of 1,4-diketones are cyclized to 2,5-disubstituted furans by the action of copper(I) trifluoromethanesulfonate. ... 

Another important click reaction is the cycloaddition of azides. The addition of sodium azide to nitriles to give l//-tetrazoles is shown to proceed readily in water with zinc salts as catalysts (Eq. 11.71).122 The scope of the reaction is quite broad a variety of aromatic nitriles, activated and nonactivated alkyl nitriles, substituted vinyl nitriles, thiocyanates, and cyanamides have all been shown to be viable substrates for this reaction. The reaction of an arylacetylene with an azide in hot water gave 1,4-disubstituted 1,2,3-triazoles in high yields,123 while a similar reaction between a terminal aliphatic alkyne and an azide (except 111 - nitroazidobenzcnc) afforded a mixture of regioisomers with... 

AJC287>. From a complex reaction mixture of BuCH(COCl)2 and 2- 4-[(4-hydroxy-3-carboxyphenyl)hydrazi-no]phenylsulfonylamino pyridine at elevated temperature, tf yr/r >-(3-butyl-2-hydroxy-4-oxo-4//-pyrido[l,2-tf]pyrimi-din-3-ylium)hydroxide was isolated <2001MI53>. Reaction of 2-aminopyridines and diethyl alkylidenemalonates at 175 °C yielded 3-(2,2-disubstituted vinyl)-2-hydroxy-4//-pyrido[l,2-tf]pyrimidin-4-ones from the initially formed... 

Disubstituted furans were synthesized from 1,4-diketones, which were prepared from the reaction of methyl vinyl ketones with arylboronic acids in the presence of CO using rhodium catalyst as illustrated below <06T11740>. 

The synthesis of 4,5-disubstituted triazoles shown in Scheme 208, carried out on a polymer support with microwave assistance, is based on a similar principle. In the first step, sulfinate 1248 is converted to sulfone 1249. Condensation with aldehydes provides vinyl sulfones 1250. Cyclocondensation of sulfones 1250 with sodium azide generates corresponding triazoline intermediates that eliminate sulfinate 1248 to provide triazoles 1251 in moderate to good yield <2006OL3283>. 

The synthesis and properties of heat-resistant polyazomethines containing 2,5-disubstituted oxadiazole fragments, being insulators convertible into semiconductors by doping with iodine, have been described. The radical copolymerization of alkenes with the fluorescent co-monomer 2-/-butyl-5-(4 -vinyl-4-biphenylyl)-l,3,4-oxadiazole has resulted in useful macromolecular scintillators. Anionic polymerization of 2-phenyl-l,3,4-oxadiazolin-5-one has produced a nylon-type product <1996CHEC-II(4)268>. 

An efficient access to 3-carboxy-2,5-disubstituted furans 64 has been developed. p-Keto esters are found to undergo an acid- or a base-catalyzed enolization and a subsequent intramolecular 1,4-addition to afford the desired furans in excellent yields. The carbonyl substituent can be further transformed to a vinylic substituent with a desired substitution pattern <00TL1347>... 

A new entry to exocyclic dienes was reported by Sha who uncovered that a radical cyclization of the vinyl iodide 100 can lead to the formation of an exocyclic dienes fused with a tetrahydrofuran ring. The cyclization is proposed to proceed in a 5-(n-exo)-exo-dig fashion <00OL2011>. 3,4-Disubstituted tetrahydrofurans can also be constructed via the cyclization of O-stannyl ketyls and allylic 0-stannyI ketyls onto electron-rich or electron-poor alkenes <00TL8941>. 

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