Dialkyl-, cycloadditions

A large number of pyridazines are synthetically available from [44-2] cycloaddition reactions. In one general method, azo or diazo compounds are used as dienophiles, and a second approach is based on the reaction between 1,2,4,5-tetrazines and various unsaturated compounds. The most useful azo dienophile is a dialkyl azodicarboxylate which reacts with appropriate dienes to give reduced pyridazines and cinnolines (Scheme 89). With highly substituted dienes the normal cycloaddition reaction is prevented, and, if the ethylenic group in styrenes is substituted with aryl groups, indoles are formed preferentially. The cycloadduct with 2,3-pentadienal acetal is a tetrahydropyridazine derivative which has been used for the preparation of 2,5-diamino-2,5-dideoxyribose (80LA1307). 

In the alternative approach.the 1,3-dipolar system can be constructed in several ways. Treatment of a-chloroacylhydrazones of diaryl ketones and certain aralkyl and dialkyl ketones (382) with NaH in anhydrous THF gives l-(disubstituted methylene)-3-oxo-l,2-diazetidinium inner salts (383). Reaction of (383) with DMAD in methylene chloride gave (384), a 2 1 adduct with loss of CO. Double bond migration in (384) occurred on heating to give (385). The intermediate in the cycloaddition was found to be (386), which on heating lost CO to form a new ylide system which in turn underwent reaction with more DMAD <81JA7743). 

Cycloaddition reactions of aziridines with a wide assortment of dipolarophiles have been studied. The reaction of dialkyl azodicarboxylates with the cf5-aziridine (27) is stereospecific... 

Diaziridine, 3-benzyl-1,3-dimethyl-inversion, 7, 7 Diaziridine, 1,2-dialkyl-reaction with iodides, 7, 217 thermal decomposition, 7, 217 Diaziridine, dibenzoyl-rearrangement, 7, 214 Diaziridine, 3,3-dimethyl-Raman spectra, 7, 202 Diaziridine, fluoro-synthesis, 7, 232 Diaziridines acylation, 7, 213 from azomethines, 7, 231 calculations, 7, 198 from chloramine, 7, 230 cycloaddition reactions, 7, 28 electron diffraction, 7, 19 199 c/s-fused NMR, 7, 201 hydrolysis, 7, 216 inversion stability, 7, 200... 

Indolizine, 1 -cyano-2-(methylthio)-synthesis, 4, 465 Indolizine, 3,5-dialkyl-synthesis, 4, 475 Indolizine, dihydrosynthesis, 4, 467, 468 Indolizine, dimethyl-mass spectrometry, 4, 187 Indolizine, 1,2-dimethyl-oxidative dimerization, 4, 458 Indolizine, 2,6-dimethyl-cycloaddition reaction, 4, 460 reduction, 4, 459... 

The above cycloaddition process consists of two separate [3-1-2] cycloaddition steps and represents a 1,3-2,4 addition of a multiple bond system to a hetero-1,3-diene [7S7]. The structure ot the azomethine imine intermediate has been proved unequivocally by X-ray analysis [195] Ethylene [194], acetylene [/iS2] . many alkyl- and aryl- as well sgemmal dialkyl- and diaryl-substituted alkenes [196,197, 198, 199], dienes [200], and alkynes [182, 201], certain cyclic alkenes [198, 199,... 

Highly alkylated l-chloro-2-(trimethylsilyl)cyclopentenes 44, which are of interest as possible cyclopentyne precursors, were prepared by reacting 3-chloro-3-methyl-l-(trimethylsilyl)but-l-yne (45) with 1,1-dialkylated or 1,1,2-trialkylated ethylenes in the presence of titanium tetrachloride35. Because of the low S/v 1 reactivity of 45, the yields of the products were moderate. The stepwise [3 + 2]-cycloaddition mechanism discussed above was proven by the isolation of the intermediate acyclic adduct (in 74% yield) when 45 and isobutene were reacted in the presence of BCI3. Under these conditions, the intermediate 46 could be trapped by Cl since BCI4 is more nucleophilic than TiC.15 (equation 16). 

A diastereoselective synthesis of bis(3,5)pyrazolophanes was accomplished by sequential inter- and intramolecular cycloadditions of homochiral nitrilimine intermediates . A-Alkyl pyrazolidine-3,5-diones were synthesized in a three-step sequence from dialkyl malonates <00JHC1209>. Methyl acetoacetate was employed as the initial substrate to 3-carboxamido-4-pyrazolecatboxylic acid derivatives <00JHC175>. Vilsmeier type reagent 33 reacted with imines 34 to afford enaminoimine hydrochlorides 35, which were transformed to pyrazoles 36 upon addition of hydrazine <0OJHC13O9>. 

The mode of reaction of titanacydobutenes with carbonyl compounds is largely dependent on steric factors (Scheme 14.31) [72]. Ketones and aldehydes tend to insert into the titanium—alkyl bond of 2,3-diphenyltitanacydobutene, and homoallylic alcohols 70 are obtained by hydrolysis of the adducts 71 [65a,73]. On the contrary, when dialkyl-substi-tuted titanacydobutenes are employed, the reaction with aldehydes preferentially proceeds through insertion into the titanium—vinyl bond. Thermal decomposition of the adducts 72 affords conjugated dienes 73 with E-stereoselectivity as a result of a concerted retro [4+2] cycloaddition [72]. 

Nair and coworkers have described the [8 + 2] cycloaddition reactions of 2H-cyclohep-ta[fr]furan-2-ones such as 521 in several reports311. The reactions of 521 with alkenes yield azulene derivatives upon extrusion of carbon dioxide. Table 30 summarizes the results of the reactions between 521 and some 6,6-disubstituted fulvenes 522 (equation 151)311b. In the case of 6,6-dialkyl fulvenes 522a-c, the [8 + 2] cycloadducts 523 were the major adducts obtained, the Diels-Alder adducts 524 only being formed in trace amounts. 

TVA -Disulfonylsulfodiimides 244 react exothermically with butadiene to give 1-sulfo-nylimino-2-sulfonyl-3,6-dihydro-l,2-thiazines 245 (equation 130)121,122. IV-Aryl-AT-sul-fonylsulfodiimides 246 are much less reactive as dienophiles. The addition to butadiene to yield 247 takes place in boiling benzene (equation 131)123. No cycloaddition reactions of dialkyl- or diarylsulfodiimides are known. 

Bicyclopropylidene (1) reacts with dimethoxycarbene generated thermally from the diazirine at 25 °C to give a complex mixture of products [116b]. The cycloaddition of several dialkoxycarbenes generated in situ from the corresponding 2,2-dialkoxy-A -l,3,4-oxadiazolines of type 134 with bicyclopropylidene (1) affords the dialkyl acetals of dispiro[2.0.2. l]heptanone 135 (Scheme 29 ) [1251. 

Also in 2009, an elegant combination of two original van Leusen reactions was reported, leading to a MCR toward 4,5-disubstituted oxazoles (19) [136]. The MCR involves the base-induced mono-alkylation of TosMIC (8a) followed by the formal cycloaddition with an aldehyde (Fig. 9). Although dialkylation is a problem often... 

Like the parent compound (1), alkyl- and/or aryl-substituted 1,2,3-trioxolanes can be generated only at low temperatures by the cycloaddition of ozone to alkenes. The concerted nature of the cycloaddition is reflected in the stereochemistry of the products observed aliphatic cis alkenes afford only cis 4,5-dialkyl-1,2,3-trioxolanes, and the analogous trans alkenes yield only trans 4,5-dialkyl-... 

Dialkyl-l,2,4-oxadithiolane-2-5 -oxides (160) have been synthesized from the dihydro thia-diazole (161) via nitrogen extrusion and 1,3-dipolar cycloaddition of the intermediate ylide with sulfur dioxide (Scheme 45) <90BSB265>. The formation and trapping of carbonyl oxides is described... 

Another method used to prepare dialkyl-substituted diazomethanes involves the photolysis of 2-alkoxy-2,5-dihydro-1,3,4-oxadiazoles (209), which can be prepared by the oxidative cyclization of A(-acetyUiydrazones. The diazoalkanes are trapped in situ by cycloaddition with dimethyl acetylenedicarboxylate (54) (Scheme 8.49). The resulting pyrazoles 210 are converted into cyclopropenes 211 by continued irradiation. 

The thermal cycloaddition of 3-acyl-2(3/7)-oxazolones 157 to dialkyl azodicar-boxylates 228 proceeds smoothly under mild conditions (at 80 °C) to give the regiocontrolled cycloadducts 229 exclusively, although two other possible addition modes exist neither diazetidines 230 (1,2-addition) nor isoxazolidines 231 (1,3-addition) are detected. In the case of chiral N-substituents diastereoselectivities of up to 72% de have been obtained. Treatment of the chiral cycloadducts 229 with acidic methanol gives tra i-5-hydrazino-4-methoxy-2-oxazolidmone derivatives 232 that are precursors for a variety of optically active a-amino acids 233 and 2-oxazolidinone auxiliaries 234 (Fig. 5.56 Table 5.10, Fig. 5.57)7 ... 

Oxindol (64) reacts at position 3 to give dialkylation with 2 mol of alkyl halide and a cycloaddition with an a,[Pg.195]

No cycloaddition has been found to occur in the reaction of several indolizines with tetracyanoethylene, substitution occurring instead in the 1- and 3-positions (78JHC1471). Similar products have been formed in the reactions of 2-methylindolizine with nitroethane, yielding (86) (79JPS321), and of indolizines with dialkyl azodicarboxylates, which gave a mixture of (87) and (88) (80TL3673, 79H(12)787>. 

The 1,3-dipolar cycloaddition of allenes with 1,3-dipoles has been reviewed.56 The scope and limitations of palladium-catalysed intramolecular 3 + 2-cycloaddition of diastereomerically pure methylenecyclopropanes (33) yielding methylenecyclopentenes (34) has been investigated (Scheme 12).57 Chiral 2,5-dialkyl-7-phenyl-7-phosphabicy-... 

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