Conformations diazoketones

The first total synthesis of this natural product was achieved by Chiu and Lam [139]. Key step of the synthesis is a rhodium-catalyzed domino cychza-tion/cycloaddition reaction to form the tricyclic core of the diterpenoid from hnear a-diazoketone 337. Concerning the mechanism of the reaction, it is hkely that the rhodium catalyst, when reacted with 337 at 0 °C, formed a carbenoid species which immediately cyclized to 341 (Scheme 14.53). This 1,3-dipole then underwent an intramolecular cycloaddition with the aUcene to give a mixture of two cycloadducts in 81% yield with 339 as the major product (dr= 1 3.1 338 339). The minor diastereomer 338 was probably formed via a less stable boat conformation of the tether in contrast to the chair conformation shown in 341, leading to the desired product Decreasing the temperature from 0 to —15 °C did not increase the dr but lowered the yield. It is also remarkable that the reaction afforded no more than 0.5 mol% of the rhodium(II)octanoate dimer ([Rh2(Oct)4]). Further transformation of 339 finally furnished (—)-indicol (340) in an overall yield of 10% over 21 steps. 

Most cyclic a-diazoketones are oxidized by peracids to a-diketones in good yield, but low yields were obtained for oxidation of a-diazocyclo-octanone and a-diazo-cyclononanone because of further oxidation to suberic and azelaic anhydrides, respectively. Since the rate of oxidation is only slightly dependent upon ring size, the conformation of the transition state must be similar to that of the ground state a concerted nitrogen extrusion-oxygen addition mechanism has been proposed. 

In general, Kaplan and co-workers found that the syn form is highly preferred in alkyl diazoketones, but that the syn and anti forms are present in approximately equal amounts in the case of diazoacetic esters. " These conformational preferences might be the underlying reason that intermolecular carbene chemistry is much more prevalent in carbene esters than in simple ketocarbenes. ... 

TRUV-VIS studies have also provided evidence to support the role of conformation in the rearrangement reaction. For example, a series of simple diazoketones RCONjH, where R = H, Me, i-Pr, and t-Bu, has been examined by laser flash photolysis methods and also by picosecond transient grating spectroscopy. Within this series, as the steric bulk of R increases, the extent of the anti diazoketone conformer present at equilibrium decreases relative to the syn conformer. Consistent with a direct rearrangement pathway leading to ketene via only the syn conformer, the amount of trappable carbene intermediate decreases as R becomes more bulky. 

Torres, M., Clement, A., and Strausz, O.P., Low-Temperature Photolysis of Diazoketones The Conformational Isomerism of Benzoylphenyhnethylene and the IR Spectrum of Anthronyhdene, Res. Chem. Intermed., 13,1, 1990. 

Kaplan, F. and Mitchell, M.L., Conformational Control of Decomposition Paths of a-Diazoketones, Tetrahedron Lett., 759, 1979. 

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