C鈥揌 Bond Functionalization via Hydride Transfer: Formation of 伪-Arylated Piperidines and 1,2,3,4-Tetrahydroisoquinolines via Stereoselective Intramolecular Amination of Benzylic C鈥揌 Bonds
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- 作者：Paul A. Vadola ; Ignacio Carrera ; Dalibor Sames
- 刊名：The Journal of Organic Chemistry
- 出版年：2012
- 出版时间：August 17, 2012
- 年：2012
- 卷：77
- 期：16
- 页码：6689-6702
- 全文大小：520K
- 年卷期：v.77,no.16(August 17, 2012)
- ISSN：1520-6904
文摘
We here report a study of the intramolecular amination of sp3 C鈥揌 bonds via the hydride transfer cyclization of N-tosylimines (HT-amination). In this transformation, 5-aryl aldehydes are subjected to N-toluenesulfonamide in the presence of BF3路OEt2 to effect imine formation and HT-cyclization, leading to 2-arylpiperidines and 3-aryl-1,2,3,4-tetrahydroisoquinolines in a one-pot procedure. We examined the reactivity of a range of aldehyde substrates as a function of their conformational flexibility. Substrates of higher conformational rigidity were more reactive, giving higher yields of the desired products. However, a single substituent on the alkyl chain linking the N-tosylimine and the benzylic sp3 C鈥揌 bonds was sufficient for HT-cyclization to occur. In addition, an examination of various arenes revealed that the electronic character of the hydridic C鈥揌 bonds dramatically affects the efficiency of the reaction. We also found that this transformation is highly stereoselective; 2-substituted aldehydes yield cis-2,5-disubstituted piperidines, while 3-substituted aldehydes afford trans-2,4-disubstituted piperidines. The stereoselectivity is a consequence of thermodynamic control. The pseudoallylic strain between the arene and tosyl group on the piperidine ring is proposed to rationalize the greater stability of the isomer with the aryl ring in the axial position. This preferential placement of the arene is proposed to affect the observed stereoselectivity.