Cycloadditions diazoalkanes with transition metal

Occasionally, the term 1,3-dipolar cycloaddition is also used for the reaction of diazoalkanes with transition metal complexes, e. g., (6-9), investigated by McCrindle and McAlees (1993). This is not, however, a 1,3-dipolar cycloaddition as coined by Huisgen. This term should not, therefore, be used for reactions that involve a dipolar reagent, but only in a cycloaddition with a dipolarophile, as shown in Huisgen s mechanism (Schemes 6-5 and 6-6). They may be called [3 + 1] dipolar cycloadditions, however, in order to underline the difference to the [3 + 2] reactions. 

Diazoalkanes are reactive consequently, cycloaddition occurs without transition metal catalysts. Davies and coworkers reported that aryldiazoacetate 294 underwent the formation of cyclopropanes with styrenes to give trisubstituted cyclopropanes 295 in good yields (Scheme 1.143) [208]. The active carbene was generated under thermal conditions. 

The transition metal-catalyzed reaction of diazoalkanes with acceptor-substituted alkenes is far more intricate than reaction with simple alkenes. With acceptor-substituted alkenes the diazoalkane can undergo (transition metal-catalyzed) 1,3-dipolar cycloaddition to the olefin [651-654]. The resulting 3//-pyrazolines can either be stable or can isomerize to l//-pyrazolines. 3//-Pyrazolines can also eliminate nitrogen and collapse to cyclopropanes, even at low temperatures. Despite these potential side-reactions, several examples of catalyzed cyclopropanations of acceptor-substituted alkenes with diazoalkanes have been reported [648,655]. Substituted 2-cyclohexenones or cinnamates [642,656] have been cyclopropanated in excellent yields by treatment with diazomethane/palladium(II) acetate. Maleates, fumarates, or acrylates [642,657], on the other hand, cannot, however, be cyclopropanated under these conditions. 

Due to their tendency to undergo side reactions and the lack of stereospecificity, free methylene or alkylcarbenes, as generated from diazoalkanes by photolysis or thermal nitrogen extrusion, are of minor synthetic importance for [2 4- 1] cycloadditions. However, transition metal catalysis, most commonly with copper or palladium compounds, offers a convenient solution to this problem (Vol. E19b. p 278)s. Probably the most active catalyst is copper(I) trifluoromcthanesulfonate9. The simple diastereoselectivity of these reactions is often negligible, as demonstrated by the copper(I) chloride or palladium(II) bis(benzonitrilo)dichloride promoted cyclopropanation of phenylethene with diazoethane10. 

Dipolar cycloaddition reactions constitute a powerful and convergent tool for the preparation of various heterocyclic compounds, which have been widely applied in the synthesis of numerous natural products, pharmaceuticals, and functional materials. The chemistry of 1,3-dipolar cycloaddtion reactions has been well documented in a number of reviews [3]. In this section the focus is on transition-metal-mediated 1,3-dipolar cycloaddition reactions with some important 1,3-dipoles, including azides, diazoalkanes, carbonyl ylides, and azomethine ylides, rather than a full review of the reactions of all types of 1,3-dipoles. 

Dipolar cycloaddition reactions of diazoalkanes with dipolarophiles leading to various heterocycles have been well studied in recent decades [13]. In this section we highlight mainly some recent advances in transition-metal-mediated 1,3-dipolar cycloaddition reactions of diazoalkanes for the construction of pyrazoles, where transition metals are usually utilized as promoters to narrow the energy gap between the two reacting components HOMOdipoiarophiie-LUMOdipoie and/or LUMOdipoiarophiie-HOMOdipoie interactions. 

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