Kumada cross-coupling method

The first synthesis of HT rr-P3AT (Scheme 9.1), known as the McCullough method was reported in 1992 (Scheme 9.1, Table 9.1, entry 1) [25,26]. The key to this method is the regiospecific generation of 2-bromo-5-bromomagnesio-3-alkylthiophene 3 from 2-bromo-3-alkylthiophene, which is then polymerized by Kumada and coworkers [27-29] cross-coupling methods using catalytic amounts of... 

In Chapter 1, the authors present a general overview of the classical cross-coupling methods, such as Heck-Mizoroki, Suzuki-Miyaura, Sonogashira, Kumada, Negishi, Ullmann coupling, and modern methods for biaryl unit synthesis, with metals such as Fe and Co. This is a very extensive chapter. 

Early preparations of polythiophene employed both electrochemical and chemical methods [1,21-23]. Chemical preparations via oxidative coupling of thiophene or Kumada cross-coupling of Grignard reagents... 

Negishi or Kumada cross-couplings to incorporate one alkenyl substituent (9 or 12) twice, and also, in the former case, the related stepwise, stereoselective Stille couplings to form unsymmetrically substituted, chiral [3] dendralenes 16 (Scheme 1.2). An application of this stepwise approach en route to the natural product triptolide [14] highlighted that when using two different metalloalkene cross-coupling partners, complete control of the stereochemistry of the resulting alkene is sometimes unattainable. Thus, most successful applications of this method incorporate two identical alkenes, so no issues of stereochemistry arise. 

Divinylallene (153) is a dendralene prone to decomposition, but it could be isolated and characterized through a cautious approach [88]. The extreme sensitivity of this compound to dimerization and decomposition dictated that a mild elimination method be used to reveal the last alkene, after the C3-C3 bond was established by Kumada cross-coupling (Scheme 1.22). The isolation of this compound (with a half-life of 43 h at 0.02 M) via this method suggests that similar strategies could be used to obtain and characterize highly reactive dendralenes. 

Since the discovery of transistion metal-catalyzed cross-coupling reactions by the groups of Kochi, Kumada and Corriu in the early 1970s, impressive progress has been achieved in the development of these methods into a synthetically indispensable... 

As was observed with the Kumada and Negishi reactions, the reactions conditions required to conduct the cross-coupling reaction may not be compatible with a wide variety of functional groups. The mild nature of the Suzuki reaction has been demonstrated by the types of functional groups that can be retained unprotected or via methods to modulate the reaction [65]. The coupling of 184 and 185 to generate 186 provided evidence that carboxylic acids and aldehydes are compatible with the Suzuki reaction. 

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