Continuous copper catalyzed reactions

Scheme 4 Continuous copper catalyzed reactions. Batch conditions NaNs, DMF-H2O, 100 °C, copper wire, 2 h.

The main features of the copper catalyzed autoxidation of ascorbic acid were summarized in detail in Section III. Recently, Strizhak and coworkers demonstrated that in a continuously stirred tank reactor (CSTR) as well as in a batch reactor, the reaction shows various non-linear phenomena, such as bi-stability, oscillations and stochastic resonance (161). The results from the batch experiments can be suitably illustrated with a two-dimensional parameter diagram shown in Pig. 5. 

Subsequently copper-catalyzed ATRA reactions were developed continuously and the progress was reviewed thoroughly (reviews [281-286]). Therefore, only selected recent examples are highlighted here. A number of ligands (Fig. 55), such as TMEDA, aliphatic tri- and tetramines 214, 215, or 216, PyBOX derivatives 5, bipyridines 26, terpyridines 8, bis- or tris(2-pyridylmethyl)amines 217 and 218, picolinaldehyde imines 219, tris(pyrazolyl)borates 220, or thionophosphates 221 [287], were applied successfully. Phenanthrolines or the bis(TPMA) ligand (cf. Part 2, Fig. 13) also proved valuable to perform ATRA under mild conditions at... 

Kobayashi and coworkers reported addition of enol silanes (72) to aldehydes (71) catalyzed by Cu(OTf)2/(52) (Scheme 17.14) [19]. Moderate to good enantioselectivities could be obtained with low syn/antiselectivity. The reduced enantioselectivity relative to bidentate acceptors employed may be attributed to single-point coordination to the Lewis acid. This point is noteworthy, as acceptors restricted to single-point coordination continue to be challenging substrates in copper-catalyzed aldol reactions. 

Enantioselective Mannich-type addition of enolate equivalents to imines continues to be an attractive strategy for the preparation of chiral p-amino carbonyl compounds. In the area of copper-catalyzed enantioselective Mannich reactions, a number of outstanding examples have appeared in this decade. In particular, work from Kobayashi s laboratories has led this field in recent years. Kobayashi and coworkers have developed a Cu(OTf) 2/diamine catalyst (121) for highly enantioselective addition of enolate equivalents to N-acylimino esters [36]. This methodology... 

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