13-Dipolar cycloaddition 13-Dithiolanes

Scheme 1.64). The Ag(I)-mediated cyclization afforded dipole 306 for 1,3-dipolar cycloaddition with methyl vinyl ketone to yield adducts 307 and the C(2) epimer as a 1 1 mixture (48%). Hydrogenolytic N—O cleavage and simultaneous intramolecular reductive amination of the pendant ketone of the former dipolarophile afforded a mixture of alcohol 308 and the C(6) epimer. Oxidation to a single ketone was followed by carbonyl removal by conversion to the dithiolane and desulfurization with Raney nickel to afford the target compound 305 (299). By this methodology, a seven-membered nitrone (309) was prepared for a dipolar cycloaddition reaction with Al-methyl maleimide or styrene (301). 

The 1,3-dipolar cycloaddition of the carbonyl ylide (31) to the aldimine (32) produces the adduct (33), which has been used to synthesize the taxol C(13) side-chain (34), which is known to be required for the antitumour activity of taxol (Scheme 9).35 The dirhodium tetraacetate-catalysed decomposition of l-diazo-5-phenylpentane-2,5-dione (35) yields the carbonyl ylide (36), which cycloadds to methylenecyclopropanes (37) to produce spirocyclopropanated 8-oxabicyclo[3.2.1]octan-2-ones [(38)-(40)] in 6-75% yields (Scheme 10).36 The 1,3-dipolar cycloadditions of aliphatic or alicyclic thiocarbonyl ylides with thiobenzophenone produce both regioisomeric 1,3-dithiolanes as expected. However, in the case of highly sterically hindered thiocarbonyl ylides, methylene transfer leads to the formation of 4,4,5,5-tetraphenyl-l,3-dithiolane.37,38... 

The 1,3-dipolar cycloaddition of phosphonodithioformate. S -methanides (41) with aromatic thio ketones (42) yields 1,3-dithiolanes (43) and (44). These S-methanides are also trapped by TCNE, maleic anhydride, A-phenylmaleimide, and dimethyl diazenedicarboxylate (Scheme ll).39... 

Thioxanthione and thiobenzophenone 3 -methylide, obtained by the elimination of N2 from 2,5-dihydro-2,2-diphenyl-l,3,4-thiadiazole at —45°, give the spiro[thioxanthene-9,4 -[l,3]dithiolane] 355 through a 1,3-dipolar cycloaddition (Equation 78) <2000EJ01695>. 

A precursor of a thiocarbonyl ylid, a dihydrothiadiazole, was reacted [259] with a sulfine, thiobenzophenone S-oxide, to lead mainly to a dithiolane S-oxide, the formation of which was rationalised through a 1,3-dipolar cycloaddition of the ylid with the C=S bond of the sulfine. It is interesting to note that an opposite regioselectivity was observed for thiofluorenone S-oxide. 

The lower levels of stereocontrol which are often observed in the 1,3-dipolar cycloaddition of acyclic nitrones, as opposed to cyclic nitrones, could be accounted for by the possibility of interconversion of the nitrone geometry. One innovative solution to this problem is Aggarwal s recently reported 1,3-dipolar cycloadditions of the C2-symmetric cyclic alkenyl sulfoxide (l/ ,3/ )-2-methylene-1,4-dithiolane 1,3-dioxide (155) with acyclic nitrones.94 The presence of a C2 symmetry element in 155 means that the exo/endo approaches of 155 to a dipole are symmetry related and therefore identical, thereby reducing the number of possible transition states in the reaction. 1,3-Dipolar cycloaddition of 155 with nitrones 156a-c resulted in single diastereomeric 4,4-disubstituted isoxazolidine products (157a-c) (Scheme 42). Likewise 1,3-dipolar cycloadditions with other acyclic nitrones yielded single diastereomeric products. 

The 1,3-dithiolane 1,3-dioxide 365 was also investigated in the Diels-Alder reaction with a range of simple dienes (cyclopentadiene, 1-methoxybutadiene, l-methoxy-3-trimethylsilyloxybutadiene, furan) <1995JOC4962, 1998J(P1)2771> and 1,3-dipolar cycloadditions with A - /t-butyl-(7-phenyl nitrone <1998JOC3481> or 3-oxidopyr-idinium betaines <20030BC1884>. 

The thiocarbonyl ylide 594 was intercepted by thiobenzophenone via a 1,3-dipolar cycloaddition reaction to afford two isomeric 1,3-dithiolanes 595 and 596 in 52% and 48% yields, respectively (Equation 79) <1999ACS360>. 

High-level quantum-chemical calculations on the 3 + 2-cycloadditions of thioformaldehyde 5 -imides, S -methylide, S-oxide, and 5-sulfide have been reviewed. Theoretical studies on the 1,3-dipolar cycloaddition between thioketene 5-oxide and methyleneimine show that this reaction is concerted but non-synchronous. Adamantanethione 5-methylide reacts with thiocarbonyl compounds to produce 1,3-dithiolanes. A density-functional-theory study of the cycloaddition of the sulfine H2CSO predicts the 2 + 3-mechanism having the lowest pathway, with an activation barrier of 12.3kcalmoP. R The thermal and photochemical reactions of fluorenethione 5-oxide (69) with cyclooctyne (70) involves an initial 1,3-dipolar cycloaddition to produce the adduct (71), followed by an efficient sulfur transfer to cyclooctyne to produce the enone (72) and the dithiin (73) (Scheme 26). ° ... 

Equimolar quantities of acetylenedicarboxylic acid esters (166) and 2-N-substituted l,3-dithiolan-2-imines (169) undergo a 1,3-dipolar cycloaddition, with elimination of ethylene, to yield A -thiazoline-2-thiones (168). The same products result from 2-alkylthio-l,3,4-thiadiazoline-5-thiones (167), with loss of alkyl thiocyanate as shown. They are desulphurized to the corresponding thiazolinones (172) by the action of mercuric acetate in acetone-acetic acid. They react with two further moles of the acetylenic reagent (166) to produce the spiranes (170 e.g. = R = COzMe), which are in turn desulphurized and cleaved by Raney nickel to the AMhiazoline derivatives (171). An analogous series of reactions was carried out using propiolic acid esters. ... 

The dipolar 1,3-cycloaddition reaction of thiocarbonyl ylides to thiones can be a source of 1,3-dithiolanes. Its regioselectivity depends on the nature of substituents in the substrates. Thus, the. J-methylide 589, generated in situ by thermal decomposition of the corresponding l,5-dihydro-l,3,4-thiadiazoles, was reacted with the trithiocarbonate 588 to give a labile 4,4,5,5-tettasubstituted-l,3-dithiolane 590, which easily isomerized to an open-chain compound 591 in the presence of acids in solution (Scheme 84) <2000EJ01695>. 

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