Tributyltin Hydride-Mediated Free-Radical Cyclization of Allene-Tethered Oxime Ethers and Hydrazones

Abstract

In this work, we have shown that the tributyltin hydride-mediated cycloisomerization of allene-tethered oxime ethers or hydrazones is a convenient method for the preparation of (vinylstannyl)cyclopentylamine derivatives in terms of simplicity and chemical yields. As a result, the first and detailed analysis of the tributyltin hydride-mediated free-radical cyclization of alkyl-substituted allene-tethered oxime ethers and hydrazones is reported. The site-directed intermolecular attack of the tributyltin radical at the allene moiety and the final size of the ring after cyclization depends on the type of substitution in the substrate. Some general trends can be observed: (1) In crowded substrates having full substitution at Cβ or at the terminal-trigonal carbon, the steric hindrance favors attack at the digonal carbon. (2) When different positions in the allene are free for attack, the kinetically more favored irreversible mode of cyclizations (5-exo > 6-exo > 6-endo) determines the ratio of isomers or the final size of the ring. Finally, after acid hydrolysis of the vinyltin products, the resulting O-methyl- or O-benzyl(hydroxylamino)cycloalkanes have been obtained in good yield.

Mechanistic Aspects and Synthetic Applications of Radical Additions to Allenes

“…In 1992, the Hatem group described a tandem addition/cyclization of β-allenyl O -methyloximes 428 initiated by a tributyltin radical. The resultant products were cyclopentenes of the form 429 , bearing an amine substituent and a vinyl stannyl functionality. , A HCl-facilitated destannylation transforms 429 to 430 (Scheme ). A limited scope of alkyl-substituted allenes was examined; however, in these cases, the tributyltin radical regioselectively attacks the central allene carbon to form an allylic radical, which then cyclizes onto the oxime carbon to establish the cyclopentene backbone.…”

“…In 1994, the Hatem group described a similar tandem addition/cyclization initiated by a tributyltin radical using N , N -dimethyl β-allenyl hydrazones 431 as radical acceptors , (Scheme a). Hydrostannylation was observed in most cases to give 432 as the major product.…”

3H-Pyrroles, Alkylidene-Pyrrolines and Functionalized Pyrrolidines by Radical Cyclization of β-Allenyliminyl Radicals

“…[1] Recently, we tried to obtain nitrogen heterocycles from the tin hydride-mediated free radical cyclization of allene-tethered benzoyloximes. As already reported, [2] this pathway allowed us to produce highly unsaturated nitrogen heterocycles in fairly good yield but only with strongly hindered allenic precursors.…”

“…-2,3,3-trimethyl-3H-pyrrole (5f):1 H NMR (CDCl 3 , 400 MHz): δ ϭ 1.00 [s, 6 H, (CH 3 ) 2 ], 1.05 [d, J ϭ 6.9 Hz, 6 H, (CH 3 ) 2 CH], 1.98 (s, 3 H, CH 3 ), 2.56 [d sept, J ϭ 6.9 Hz and 1.4 Hz, 1 H, (CH 3 ) 2 CH], 5.48 (d, J ϭ 1.4 Hz, 1 H, CH).Ϫ 13 C NMR (CDCl 3 , 100 MHz): δ ϭ 14.8 (CH 3 ), 21.0 (CH 3 ), 21.8 (CH 3 ), 29.4 (CH), 55.8 [C(CH 3 ) 2 ], 125.3 (CHϭC), 160.1 (CϪN), 187.7 (CϭN). 3,4-Dihydro-2-isopropylidene-4,4,5-trimethyl-2H-pyrrole (6f): 1 H NMR (CDCl 3 , 400 MHz): δ ϭ 1.02 [s, 6 H, (CH 3 ) 2 ], 1.55 (m, 3 H, CH 3 CϭC), 1.85 (m, 3 H, CH 3 CϭC), 1.91 (s, 3 H, CH 3 CϭN), 2.26 (m, 2 H, CH 2 ).…”

Tin-free radical mediated C-C bond formation via the Xanthate transfer

“…). Vinylic radicals are very reactive species and have previously been reported to undergo trapping by the oxime ether 177. Applying this strategy to our current approach would produce the corresponding O-benzyl oxime ether derivatives of methylene lactones.…”