Toward Customized Tetrahydropyran Derivatives through Regioselective α-Lithiation and Functionalization of 2-Phenyltetrahydropyran

被引：10

作者：

Cicco, Luciana ^{[1
]}

Addante, Valeria ^{[1
]}

Temperini, Andrea ^{[2
]}

Donau, Carsten Adam ^{[3
]}

Karaghiosoff, Konstantin ^{[3
]}

Perna, Filippo Maria ^{[1
]}

Capriati, Vito ^{[1
]}

机构：

[1] Univ Bari Aldo Moro, Dipartimento Farm Sci Farmaco, Consorzio CINMPIS, Via E Orabona 4, I-70125 Bari, Italy

[2] Univ Perugia, Dipartimento Sci Farmaceut, Via Liceo 1, I-06123 Perugia, Italy

[3] Univ Munich, Dept Chem, Butenandtstr 5-13,Haus F, D-81377 Munich, Germany

来源：

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY | 2016年 / 2016卷 / 19期

关键词：

Synthetic methods; Carbanions; Lithium; Oxygen heterocycles; Regioselectivity; 6-MEMBERED OXYGENATED HETEROCYCLES; C-H FUNCTIONALIZATION; NATURAL-PRODUCTS; LITHIUM HEXAMETHYLDISILAZIDE; STEREOSELECTIVE-SYNTHESIS; ASYMMETRIC-SYNTHESIS; RELATIVE SOLVATION; AGGREGATION STATE; METAL COMPOUNDS; CYCLIC ETHERS;

D O I：

10.1002/ejoc.201600365

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

In this contribution, the first direct and efficient functionalization of the preformed 2-phenyltetrahydropyran (2-PhTHP) nucleus by electrophilic interception of the corresponding alpha-lithiated derivative by employing sBuLi as the base and THF as the solvent at -78 degrees C was explored. The presence of N,N,N',N'-tetramethylethylenediamine (TMEDA) proved to be critical to governing reaction feasibility both in polar and apolar solvents and for improving the yield of the reaction. Both carbon-and heteroatom-based halides were found to be competent electrophiles for this transformation, as well as aliphatic and aromatic aldehydes and ketones, isocyanates, and carboxylic acid derivatives. The combination of hexane/TMEDA lowered the rate of racemization of a-lithiated optically active 2-PhTHP, which thereby enabled calculation of its barrier to inversion at -78 degrees C.

引用

页码：3157 / 3161

页数：5

共 64 条

[1] Palladium-Catalyzed Directed C(sp3)-H Arylation of Saturated Heterocycles at C-3 Using a Concise Optimization Approach [J].