Titanocene(III)-Catalyzed Precision Deuteration of Epoxides

被引:23
作者
Henriques, Dina Schwarz G. [1 ]
Rojo-Wiechel, Elena [1 ]
Klare, Sven [1 ]
Mika, Regine [1 ]
Hoethker, Sebastian [1 ]
Schacht, Jonathan H. [1 ]
Schmickler, Niklas [1 ]
Gansauer, Andreas [1 ]
机构
[1] Univ Bonn, Kekule Inst Organ Chem & Biochem, Gerhard Domagk Str 1, D-53121 Bonn, Germany
关键词
catalysis; deuteration; mechanism; radicals; titanium; ANTI-MARKOVNIKOV ALCOHOLS; H BOND ACTIVATION; ASYMMETRIC EPOXIDATION; BENZYLIC HYDROXYLATION; H/D EXCHANGE; METABOLISM; COMPLEXES; DEUTERIUM; CATALYSIS; HYDROGEN;
D O I
10.1002/anie.202114198
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
We describe a titanocene(III)-catalyzed deuterosilylation of epoxides that provides beta-deuterated anti-Markovnikov alcohols with excellent D-incorporation, in high yield, and often excellent diastereoselectivity after desilylation. The key to the success of the reaction is a novel activation method of Cp2TiCl2 and (tBuC(5)H(4))(2)TiCl2 with BnMgBr and PhSiD3 to provide [(RC5H4)(2)Ti(III)D] without isotope scrambling. It was developed after discovering an off-cycle scrambling with the previously described method. Our precision deuteration can be applied to the synthesis of drug precursors and highlights the power of combining radical chemistry with organometallic catalysis.
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页数:7
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