Cycloaddition of carbonyl compounds

The [ 2 + 4]-cycloaddition reaction of aldehydes and ketones with 1,3-dienes is a well-established synthetic procedure for the preparation of dihydropyrans which are attractive substrates for the synthesis of carbohydrates and other natural products [2]. Carbonyl compounds are usually of limited reactivity in cycloaddition reactions with dienes, because only electron-deficient carbonyl groups, as in glyoxy-lates, chloral, ketomalonate, 1,2,3-triketones, and related compounds, react with dienes which have electron-donating groups. The use of Lewis acids as catalysts for cycloaddition reactions of carbonyl compounds has, however, led to a new era for this class of reactions in synthetic organic chemistry. In particular, the application of chiral Lewis acid catalysts has provided new opportunities for enantioselec-tive cycloadditions of carbonyl compounds. 

Scheme 6 Mechanistic spectrum of [2+2] cycloaddition of carbonyl compounds with alkenes and atkynes...

Increasing use is being made of pyran syntheses based upon [4 + 2] cycloadditions of carbonyl compounds. The appropriate unsaturated aldehyde with ethyl vinyl ether yields 53 with peracids this affords an epoxide that undergoes ring contraction to the aldehyde 54 (Scheme 23) and rhodium catalyzed decarbonylation affords the required 3-alkylfuran with the optical center intact.116 Acetoxybutadiene derivatives add active carbonyl compounds giving pyrans that contract under the influence of acids to give... 

Barriocanal, J. A. and Doren, D. J. Cycloaddition of carbonyl compounds on Si(100) New mechanisms and approaches to selectivity for surface cycloaddition reactions. Journal of the American Chemical Society 123, 7340-7346 (2001). 

G. )ones, in A. Padwa (ed.). Organic Photochemistry, vol. 5, Dekker (1981). This is a review of synthetic applications of the photochemical cycloaddition of carbonyl compounds. 

PATERNO-BUCHI REACTION. Formation of oxetanes by photochemical cycloaddition of carbonyl compounds to olefins. 

Another synthesis based on the combination of these fragments is the 1,3-dipolar cycloaddition of carbonyl compounds to nitrile ylides. The latter are generated by photolysis of 1-azirines when the irradiation is carried out in the presence of an acyl chloride and triethylamine, oxazoles are formed in moderate yields (equation 121). 

Diels-Alder cycloadditions of carbonyl compounds with aldehydes and ketones provide a powerful method for synthesis of 5,6-dihydropyrans, which are useful synthons for a variety of purposes. This methodology was slow to develop since early work indicated that simple carbonyl compounds react poorly with most alkyl and aryl substituted 1,3-dienes. However, with the understanding that [4 + 2] cycloadditions are facilitated by Lewis acid catalysts and high pressure, along with the recent availability of highly reactive oxygenated dienes, this chemistry has been increasingly exploited in total synthesis. 

Cycloadditions of carbonyl compounds to olefins generally involve exci-plexes and biradicals. (Cf. Section 7.4.4.) While normal olefins frequently yield a number of products, photoinduced electron transfer may be utilized in the case of electron-rich olefins to influence the regioselectivity. Thus, irradiation of the ketene acetal 165 and biacetyl (164) yields exclusively the oxetane 167. Since the radical cation 166 could be trapped, electron transfer... 

Early applications of chiral Lewis acid catalyzed stereoselective Diels Alder reactions used either boron- or aluminum-derived systems in carbocyclic ring formation18 1Q, or studied the effect of chiral shift reagents, such as Eu(hfc)3, in hetero-Diels-Alder cycloadditions of carbonyl compounds to dienes20 23,77, 78. The latter type of transition metal catalyzed addition is classified as heterocarboration and is described in Section 1.5.8.4. 

Four-membered P.O-heterocycles 31 were obtained from [2 + 2]-cycloaddition of carbonyl compounds to phosphorylated carbenes generated from a-diazabenzyl-phosphine oxide under thermal- or photoinitiation (Scheme 16) [32-34], 2-Oxo-l,2-... 

The formation of oxetanes by photochemical (2 + 2)-cycloaddition of carbonyl compounds, such as aldehydes, ketones, and quinones, with carbon-carbon double bonds has been reported for various heterocyclic compounds. Maleic anhydride,142 isocoumarin (and its derivatives),143,144 benzol 61 thiophene 1,1-dioxide,144 l,3-dihydroimidazol-2-ones,131,132... 

Two papers describe cycloaddition reactions leading to P-C(sp ) systems. Pudovik et al. have continued their work on the cycloaddition of carbonyl compounds to... 

Noteworthy, very few reports can be found on UV light-initiated cycloaddition of carbonyl compounds to tetrafluoroethylene (TFE). " The yields of oxetanes in these processes are generally low due to facile polymerization of TFE under the reaction conditions. 

Fluorinated oxetanes can be obtained in decent yield through an electrophilic [2 + 2] cycloaddition of carbonyl compounds and fluoroolefins. The formation of oxetane 2 was first reported by Weinmayr in 1963. The reaction of TFE with paraformaldehyde... 

The cycloadditions of carbonyl compounds with dienes lead to 5,6-dihydro-2//-pyrans. Electron-deficient aldehydes have to be employed in combination with butadienes bearing electron-donating groups. However, using non-activated dienes rate acceleration can be achieved by applying high temperatures, high pressure or Lewis acids. 

The application of Lewis acids, such as the europium salt Eu(fod)3, in [4+2] cycloadditions of carbonyl compounds (e.g. glyoxylates and aldehydes) with 1-methoxy-3-trimethylsilyloxy-l,3-butadiene (Danishefsky s diene) has been intensively examined by Danishefsky et al. and employed in natural product synthesis. ... 

Describe intramolecular cycloaddition of carbonyl compounds in dimerization and oxetane formation. 

Gotthardt, H., Steinmetz, R., and Hammond, G.S., Mechanisms of photochemical reactions. Llll. Cycloaddition of carbonyl compounds to allenes, /. Org. Chem., 33, 277-2780, 1968 Gotthardt, H., Steinmetz, R., and Hammond, G.S., Photocyclic addition of carbonyl compounds to allenes,. Chem. Soc. Chem. Commun., 480—482, 1967 Arnold, D.R. and Glick, A.H., The photocycloaddition of carbonyl compounds to allenes,/. Chem. Soc., Chem. Commun., 813-814,1966 ... 

Gotthardt, H., Steinmetz, R., and Hammond, G.S., Mechanisms of photochemical reactions in solution. LIII. Cycloaddition of carbonyl compounds to aUenes,/. Org. Chem., 33, 2774, 1968. 

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