Carbonyl compounds 2+2 cycloadditions, furan

The Patemo-Btichi photocycloaddition reaction - of various carbonyl compounds to furans was initially investigated by Sakurai in 1963 and was found to afford only the head-to-head photoproducts with high exo relative face selectivity. An NMR study by Whipple and Evanega later confirmed the exo mode of cycloaddition. Since the time of the origin report the photoreaction has been systematically studied by several groups and the 2,7-dioxabicyclo[3.2.0]hept-3-ene ring system has been exploited in several facets of synthesis. 

Important studies by Sakurai have highlighted the use of Paterno-Buchi cycloaddition reactions of carbonyl compounds and furans to give fused ox-etanes with high regio- and diastereocontrol [143]. An elegant synthetic application was reported by Schreiber, who used the conversion of furan into cycloadduct 228 as the only observed isomer (>99%, Scheme 18.37) [144, 145]. This cycloaddition could readily be conducted on a 50 g scale and formed the cornerstone in the total synthesis of the antifungal metabolite avenaciolide (229) [145]. 

A-Substituted pyrroles, furans and dialkylthiophenes undergo photosensitized [2 + 2] cycloaddition reactions with carbonyl compounds to give oxetanes. This is illustrated by the addition of furan and benzophenone to give the oxetane (138). The photochemical reaction of pyrroles with aliphatic aldehydes and ketones results in the regiospecific formation of 3-(l-hydroxyalkyl)pyrroles (e.g. 139). The intermediate oxetane undergoes rearrangement under the reaction conditions (79JOC2949). 

Friedrichsen and co-workers (135), along with Padwa, has utilized the carbonyl ylide cycloaddition to generate reactive furan moieties that can be further used in inter- or intramolecular Diels-Alder reactions to prepare aza- and carbocyclic compounds. Friedrichsen conducted a number of synthetic and theoretical studies on the reactivity, regioselectivity, and stereoselectivity of substituted furan formation and subsequent Diels-Alder reaction (Scheme 4.69). 

Anhydro-4-hydroxyoxazoIium hydroxides, such as compound (231), behave as carbonyl ylides (232) in cycloaddition reactions, yielding bicyclic adducts with alkenes and carbonyl compounds (Scheme 24). The adducts produced by combination with alkynes fragment spontaneously in a retro-Diels-Alder reaction, giving furans (equation 57). The formation of a furan by the action of DMAD on the 4(5//)-oxazolone (233) shows that the latter exists in equilibrium with the mesoionic tautomer (234 equation 58) (79JOC626). 

Silyl enolates of a,a-dialkoxy ketones react with furans to form [3 4- 4] cycloaddition products in the presence of SbCls (Eq. 6) [17], Cycloaddition also occurs when 2,2-dialkoxycyclopropanecarboxylic esters and carbonyl compounds are treated with SbCls [18]. 

An example is illustrated in Scheme 67. The sequence can be performed directly on amino-modified resin without a special linker unit. a-Diazo carbonyl compounds of type 140 were reacted wifh an Rh(II) catalyst to form highly reactive Rh(II) carbenoids, which yielded isomiinchnones 141. These underwent [2-1-3] cycloadditions wifh alkynes to form bicyclic intermediates 142. Thermolytic cycloreversion led to fhe desired furans 143 in high purity [163, 164]. 

Furan has been found to form oxetanes with a variety of carbonyl compounds, e.g., ketones,202-205 aldehydes,206 and ethyl cyanofor-mate.207 In most reactions the (2 + 2)-cycloaddition occurred specifically to give a 2,7 dioxabicyclo[3.2.0]hept-3-ene (175) rather than the 2,6-isomer (176). Only the addition of ethyl cyanoformate yielded mixtures of 175 and 176 (R = OEt and R2 = CN), in a ratio of 2 l.207 Two subsequent (2 + 2)-cycloadditions of benzophenone and furans have been reported to give two isomeric products, 177 and 178.205 Substituted furans yielded similar oxetanes.203 Benzo[ >]furans, furo-coumarins, and furochromones also proved to undergo (2 + 2)-cyclo-addition reactions with carbonyl compounds such as ketones, aldehydes, and quinones. Invariably one type of oxetane was formed (179).,37,u3 ,44 200-202 208,20, In the case of 2-methoxycarbonylbenzo[6)-furan, evidence has been provided that the oxetane was produced by addition of the excited triplet state of the olefinic reactant to the ground state of the ketone.208... 

Topics reviewed during the year include the photochemistry of indoles, sulfoxides, pyrazoles and isothiazoles, (S-hetero)cyclic unsaturated carbonyl compounds, photoinduced single electron transfer (SET) reactions of amines and of azo compounds, SET reactions of organosilanes and organostannanes with Qo and ketones, photochromic polypeptides and di(hetero)arylethenes, processes in chromophore sequences on a-helical polypeptides,aryl-aryl coupling in furans, thiophenes and pyrroles," [3+2]cycloaddition of aromatic nitriles (and esters) with alkenes, and reactions of benzylsilane derivatives. ... 

Rh-catalyzed [3 + 2] dipolar cycloaddition. Generally, this transformation is performed at elevated temperatures and affords furans directly in a single step without isolation or even observation of possible cyclopropene intermediate (Section 8.2.1.1). It was first demonstrated by D yakonov that the Cu(II)-catalyzed reaction between a-diazoesters and internal alkynes provided the corresponding 2-alkoxyfurans in moderate yields [201-205]. Consequently, several research groups further elaborated on this transformation in the presence of different transition metal catalytic systems for a variety of differently substituted a-diazo-carbonyl compounds and alkynes. 

Cycloaddition Reactions as an Ene. It has been well established that carbonyl compounds can be added to furan in a highly regioselective [2 + 2] fashion under photochemical conditions, providing relatively unstable 2,7-dioxabicyclo[3.2.0]hept-3-ene compounds (eq 12). These bicyclic oxetanes can be isomerized smoothly by acid treatment to 3-substituted furans (eq 12). ... 

Hydroxy-THISs react with electron-deficient alkynes to give nonisol-able adducts that extrude carbonyl sulfide, affording pyrroles (23). Compound 16 (X = 0) seems particularly reactive (Scheme 16) (25). The cycloaddition to benzyne yields isoindoles in low- yield. Further cyclo-addition between isoindole and benzyne leads to an iminoanthracene as the main product (Scheme 17). The cycloadducts derived from electron-deficient alkenes are stable (23, 25) unless highly strained. Thus the two adducts, 18a (R = H, R = COOMe) and 18b (R = COOMe, R = H), formed from 7, both extrude furan and COS under the reaction conditions producing the pyrroles (19. R = H or COOMe) (Scheme 18). Similarly, the cycloadduct formed between 16 (X = 0) and dimethylfumarate... 

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