Comptes Rendus de l'Académie des Sciences - Series IIC - Chemistry最新文献

This communication describes our preliminary results on the radical cyclization of homopropargylic bromomethyldimethylsilyl ethers, an unknown reaction. With precursor 5a, only the very rare 7-endo-dig process was observed. The reduction of the resulting vinyl radical is not stereoselective and gives a cis/trans, 1.35:1 mixture of silaoxepan derivatives, as determined after a methyllithium treatment yielding olefins 11 and 12. This represents a new example of formation of a trans heterocyclic cycloheptene. With disubstituted precursor 5b, the system is less reactive and still no 6-exo-dig radical cyclization has been observed.

The 3-methyl-substituted analog (±)-3 of the angiotensin converting enzyme inhibitor A58365A (1) was synthesized from lactone 4 and amino acid ester 16, via key intermediates 18, 19 and 21a,b. Compound (±)-3 was found to possess powerful ACE inhibitory activity (IC₅₀ = ca 500 nM), as judged by in vitro tests against porcine kidney ACE, under conditions in which the commercial drug captopril has IC₅₀ = 280 nM.

Radical cyclization of N-(α-methyl)benzyl substituted trichloroacetamides upon α,β-unsaturated nitriles has been studied. Tributyltin hydride treatment of trichloroacetamides 5a and 5b gives morphan derivatives (1 and 2), through a 6-exo-trig radical cyclization, and unexpectedly normorphans 6 and 7 as a result of a stereoespecific process in which the stereogenic benzylic carbon undergoes a configurational inversion.

The dimethyl methylmalonyl radical was generated upon photolysis of dimethyl bromomethylmalonate or treatment of dimethyl methylmalonate with Mn(OAc)₃·2 H₂O. This radical was added to an exocyclic olefin appended to 1-acyl or 3-acyl indoles, with subsequent cyclization to generate 1,2- or 2,3- fused indole derivatives, respectively.

A set of allenic derivatives 1 bearing a C=N bond in β position and diversely substituted in R³ and Z was prepared. The behaviour of compounds 1 towards the Bu₃Sn^• radical was then studied. Depending on the nature of R³ and Z, products 2, 3, and 4 were obtained in diverse ratios. When the steric hindrance on the C-atom of the C=N bond was low (R³ = H), the product ‘normally’ obtained was 2. When the steric hindrance of R³ was higher, the formation of 3 and 4 became competitive. In this case, the ratio between 2, 3, and 4 can be explained on the basis of the polarity of R³ and Z. The higher the electroattractive effect of R³ and Z, the higher the quantity of 2 and 4 in comparison with 3.

This review describes the free radical cyclisation of enamides using tributyltin hydride, manganese(III) acetate, copper(I) complexes or dichlorotris(triphenylphosphine)ruthenium(II). These cyclisations can proceed via either 4-exo or 5-endo pathways, to produce β- or γ-lactam products, respectively. In general, the reactions produce γ-lactams derived from an unusual (disfavoured) 5-endo-trig radical cyclisation. These results can be explained on the basis of a reversible cyclisation mechanism; the 4-exo cyclisation produces the kinetically favoured β-lactam while the 5-endo cyclisation produces the thermodynamically more stable γ-lactam.

Combining atom transfer carbonylations of bifunctional amines with an appropriate choice of cyclization conditions enables the preparation of nitrogen-containing heterocycles via the incorporation of carbon monoxide.

Polysubstituted 1,6-dienes 1 and 6, derived from 6-iodo-d-manno- and d-glucopyranosides through Boord fragmentation and subsequent olefination, undergo cyclization upon addition of TsSePh under radical conditions. Functionalized cyclopentitols result from tributyltin hydride mediated reduction of the adducts. A tentative rationalization of steroinduction is given, and a comparison is made with related data in the literature.

An approximate rate constant for the intermolecular addition of a primary alkyl radical onto bis-methanesulfonyl oxime ether 2 has been measured to be k_a = 1.7·10⁶ M^–1·s^–1 at 80 ^oC, which is in reasonably good agreement with the data obtained from competition experiments.