- Large-Scale Synthesis of 2-Chlorotetrahydroquinoline and 2-Chlorotetrahydroquinolin-8-one
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An efficient large-scale preparation of 2-chlorotetrahydroquinoline with cyclohexanone and benzylamine as starting materials was developed and well optimized, in which benzyl-protected enamide was successfully cyclized and benzyl group was directly removed under Vilsmeier conditions. Azeotropic distillation provided 264 g of 2-chlorotetrahydroquinoline (79%) on a 2 mol scale of reaction without intermediate isolation. The downstream product 2-chlorotetrahydroquinolin-8-one was acquired through Boekelheide rearrangement, hydrolysis of acetate via NaBH 4reduction, and Anelli oxidation. With the developed procedure, the intermediates were not necessary to be isolated and 2-chlorotetrahydroquinolin-8-one was conveniently obtained with solvent slurry in 65% overall isolated yield in a four-step sequence.
- Zong, Zhijian,Wu, Ke,Jin, Liqun,Sun, Nan,Hu, Baoxiang,Shen, Zhenlu,Hu, Xinquan
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p. 3675 - 3683
(2020/09/21)
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- Tin-free visible light photoredox catalysed cyclisation of enamides as a mild procedure for the synthesis of γ-lactams
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The first visible light mediated tin-free cyclisation of α-chloroenamides leading to the synthesis of substituted γ-lactams with excellent stereoselectivity is reported. The protocol employs the single-electron reduction of activated C-Cl bonds, which are typically inert towards reduction.
- Fava, Eleonora,Nakajima, Masaki,Tabak, Martin B.,Rueping, Magnus
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p. 4531 - 4535
(2016/08/19)
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- Bond rotation dynamics of enamides: The effect of the acyl group and potential for chirality transfer during 5-endo trig radical cyclizations
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Barriers to rotation of the N-alkenyl bond in a series of N-cycloalkenyl-N-benzyl acetamide derivatives have been measured in different solvents by variable-temperature NMR experiments. The barriers range from 9.7 to 14.2 kcal/mol, depending on substituents on the acetamide acyl group. Polar solvents such as chloroform and methanol increase the barrier to rotation compared to nonpolar solvents such as toluene. The barrier to rotation of "mimics" for acetamide-based radicals are estimated. The relative order of the values of krot for different acyl groups parallels their reported Taft Es paramaters. For successful chirality transfer in 5-endo trig radical cyclization, it is evident that rotations would need to be significantly slower than those reported here.
- Clark, Andrew J.,Curran, Dennis P.,Geden, Joanna V.,James, Natalie,Wilson, Paul
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p. 4546 - 4551
(2011/07/31)
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- How do analogous α-chloroenamides and α-iodoenamides give different product distributions in 5-Endo radical cyclizations?
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5-Endo cyclizations of N-alkenyl carbamoylmethyl radicals provide γ-lactam radicals, which in turn evolve to reduced or non-reduced (alkene) products depending on reagents and reaction conditions. Several groups have made surprising observations that chlorides are better radical precursors than iodides in such cyclizations. Here is described a detailed study of tin and silicon hydride-mediated radical cyclizations of N-benzyl-2-halo-N-cyclohex-1- enylacetamides. The ratios of directly reduced, cyclized/reduced, and cyclized/non-reduced products depend not only on the reaction conditions and reducing reagent but also on the precursor. Prior explanations for the precursor-dependent product ratios based on amide rotamer effects are ruled out. The precursor-dependent behavior is further dissected into two different effects: (1) the ratio of cyclized/reduced products to cyclized/non-reduced products depends on the ability of the radical precursor to react with the product γ-lactam radical in competition with tin hydride (iodides can compete, chlorides cannot), and (2) the occurrence of large amounts of directly reduced (noncyclized) products in the case of iodides is attributed to a competing ionic chain reaction by which the precursor is reductively deiodinated with HI. This side reaction is not available to chlorides, thereby explaining why the chlorides are better precursors in such reactions. The ability of the iodides to provide cyclized products can be largely restored by adding base. The chlorides and iodides then become complementary precursors, with chlorides giving largely cyclized/reduced products and iodides giving largely cyclized/non-reduced products.
- Curran, Dennis P.,Guthrie, David B.,Geib, Steven J.
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scheme or table
p. 8437 - 8445
(2009/02/02)
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- An aza-wittig/π-furan cyclization approach toward the homoerythrina alkaloid (±)-selaginoidine
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(Chemical Equation Presented) A one-pot procedure was developed to efficiently prepare hexahydroindolinones containing a tethered furan ring. Reaction of a furanyl azide with Bu3P delivered the iminophosphorane, which was allowed to react with
- Cassidy, Michael P.,Oezdemir, Ayse Daut,Padwa, Albert
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p. 1339 - 1342
(2007/10/03)
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- Is an iodine atom almighty as a leaving group for Bu3SnH-mediated radical cyclization? The effect of a halogen atom on the 5-endo-trig radical cyclization of N-vinyl-α-halo amides
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The effect of a halogen atom as a leaving group on Bu3SnH-mediated 5-endo-trig radical cyclization of N-(cyclohex-1-enyl) α-halo amides was examined. The cyclization of α-chloro amides occurred with a high degree of efficiency, whereas the corresponding α-iodo congeners gave only limited quantities of cyclization products. A detailed study revealed that these phenomena could be attributed to the initial conformations of α-halo amides. The cyclizing ability of α-iodo amides can be restored with Bu3SnCl or Bu3SnF as an additive. The cyclization of an α-iodo amide in the presence of Bu3SnF could be applied to a short-step synthesis of lycoranes featuring sequential 5-endo-trig and 6-endo-trig radical cyclizations.
- Tamura, Osamu,Matsukida, Hana,Toyao, Atsushi,Takeda, Yoshifumi,Ishibashi, Hiroyuki
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p. 5537 - 5545
(2007/10/03)
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- The use of an iodine atom as a leaving group for Bu3SnH-mediated 5-endo-trig radical cyclization of α-halo amides is not recommended
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Bu3SnH-mediated 5-endo-trig radical cyclization of N-(cyclohex-1-enyl) α-chloro amides occurred with a high degree of efficiency, whereas the corresponding α-iodo congeners gave only limited quantities of the cyclization products. The cyclizing
- Ishibashi,Matsukida,Toyao,Tamura,Takeda
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p. 1497 - 1499
(2007/10/03)
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- REACTION OF 1-BENZYLIMINO-2-(β-CYANOETHYL)CYCLOHEXANE WITH CARBOXYLIC ACID CHLORIDES
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The acylation of 1-benzylimino-2-(β-cyanoethyl)cyclohexane with carboxylic acid chlorides is regiospecific and leads to the formation of N-acylation products.The latter exist as mixture of two enamine forms with trisubstituted and tetrasubstituted double
- Erzhanov, K. B.,Kayukova, L. A.,Umarova, Z. N.,Yakimovich, S. I.
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p. 2106 - 2111
(2007/10/02)
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