Development of Safe and Scalable Continuous-Flow Methods for Palladium-Catalyzed Aerobic Oxidation Reactions.
The synthetic scope and utility of Pd-catalyzed aerobic oxidation reactions has advanced significantly over the past decade, and these reactions have potential to address important green-chemistry challenges in the pharmaceutical industry. This potential has been unrealized, however, because safety concerns and process constraints hinder large-scale applications of this chemistry. These limitations are addressed by the development of a continuous-flow tube reactor, which has been demonstrated on several scales in the aerobic oxidation of alcohols. Use of a dilute oxygen gas source (8% O(2) in N(2)) ensures that the oxygen/organic mixture never enters the explosive regime, and efficient gas-liquid mixing in the reactor minimizes decomposition of the homogeneous catalyst into inactive Pd metal. These results provide the basis for large-scale implementation of palladium-catalyzed (and other) aerobic oxidation reactions for pharmaceutical synthesis.
Ye
Xuan
X
Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706. USA; ; Tel: (+1) 608-265-6288.
Johnson
Martin D
MD
Diao
Tianning
T
Yates
Matthew H
MH
Stahl
Shannon S
SS