Efficient Regio- and Stereoselective Formation of Azocan-2-ones via 8-Endo Cyclization of α-Carbamoyl Radicals

被引:40
作者
Fang, Xinqiang [1 ]
Liu, Kun [1 ]
Li, Chaozhong [1 ]
机构
[1] Chinese Acad Sci, Key Lab Synth Chem Nat Subst, Shanghai Inst Organ Chem, Shanghai 200032, Peoples R China
基金
中国国家自然科学基金;
关键词
ATOM-TRANSFER CYCLIZATION; MEDIUM-SIZED LACTONES; RING-CLOSING METATHESIS; MOLECULAR BUILDING KIT; LEWIS-ACID; ADDITION-REACTIONS; (ALKOXYCARBONYL)METHYL RADICALS; CONJUGATE ADDITIONS; MANZAMINE ALKALOIDS; UNSATURATED AMIDES;
D O I
10.1021/ja9082649
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The iodine-atom-transfer 8-endo cyclization of alpha-carbamoyl radicals was investigated experimentally and theoretically. With the aid of Mg(ClO4)(2) and a bis(oxazoline) ligand, N-ethoxycarbonyl-substituted N-(pent-4-enyl)-2-iodoalkanamides underwent 8-endo cyclization leading to the formation of only the corresponding 3,5-trans-substituted azocan-2-ones in excellent yields Similarly, the BF3 center dot OEt2/H2O-promoted reactions of N-ethoxycarbonyl-N-(2-allylaryl)-2-iodoalkanamides afforded exclusively the benzazocanone products with a 3,5-cis configuration in high yields The bidentate chelation of substrate radicals not only significantly improved the efficiency of cyclization but also resulted in the change of stereochemistry of azocanone products from 3,8-trans to 3,8-cis Theoretical calculations at the UB3LYP/6-31G* level revealed that the cyclization of N-carbonyl-substituted alpha-carbamoyl radicals occurs via the E-conformational transition states without the presence of a Lewis acid. On the other hand, the cyclization proceeds via the Z-conformational transition states when the substrates form the bidentate chelation with a Lewis acid In both cases, the 8-endocyclization is always fundamentally preferred over the corresponding 7-exo cyclization The complexed radicals having the more rigid conformations also allow the better stereochemical control in the iodine-atom-abstraction step To further understand the reactivity of alpha-carbamoyl radicals, the competition between the 8-endo and 5-exo cyclization was also studied The results demonstrated that the 8-endo cyclization is of comparable rate to the corresponding 5-exo cyclization for alpha-carbamoyl radicals with fixed Z-conformational transition states As a comparison, the 8-endo mode is fundamentally preferred over the 5-exo mode in the cyclization of INIH-amide substrates because the latter requires the Z-conformational transition states, whereas the former proceeds via the more stable E-conformational transition states.
引用
收藏
页码:2274 / 2283
页数:10
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