Coupling Negishi

Compared to these phosphinimine-derived nickel pincer complexes, the PNS- and PNO-pincer complexes 20-24 show much higher activity, as Negishi coupHng 

Bis(oxazoline)pyridine (Pybox) and terpyridine (terpy) belong to the family of tridentate ligands that are often excluded from the discussions on pincer chemistry. However, recent studies have shown that in some cases they are redox-active [52, 53] and exhibit properties closely resembling those of pincer ligands. Thus, cross-coupling reactions catalyzed by nickel complexes containing these ligands are also discussed in this chapter. 

Since 2003, the Fu group has published a series of papers involving Negishi coupling of various organic halides with a special interest in forming C 3 -C, 

This radical mechanism can be exploited for cascade catalysis if the rate of radical cychzation (or other rearrangement reactions) for R is significantly faster than the rate of R attack on nickel. Cardenas and coworkers [53] have proved this concept 

Vidal and co-workers used 2-oxazolylzinc chloride to enhance an SAR study of orally efficacious A2B adenosine receptor antagonists. The oxazole was also appended through the C4 position by utilizing a Stille reaction of the C4 stannane.  

Vedejs utilized a Negishi reaction in synthesizing the core of aziridinomitosene A. The C5 position of a C2-substituted oxazole was lithiated and transmetalated with ZnCh. The 5-oxazolylzinc chloride was utilized in an intermolecular Negishi reaction with a vinyl triflate in 70% yield with no reported intramolecular reaction at the alkyl iodide.  

Hodgetts has shown that C2 chlorides and C4 and C5 bromides all participate in Negishi coupling with 2-pyridylzinc bromide in approximately 70% yield. Stambuli did not attempt Negishi coupling of the halooxazoles, probably due to the lability of the thioether under Negishi-like conditions.  

---

Heck, Suzuki, Stille, and Negishi coupling reactions... 

Scheme 6.21 First successful Pd-NHC mediated Negishi coupling by Organ et al.

Scheme 6.23 Nickel-catalysed Negishi coupling between unactivated aryl chlorides and oiganozinc reagents...

The consistent observation of the arylated products with 92% ee confirms that the enantioselectivity of the asymmetric deprotonation was preserved during the transmetalation with ZnCl2 and retained during the Pd-catalyzed coupling. In fact, the Negishi coupling with 3-bromopyridine (entry 16) was performed at 60 °C, and still provided 26m in 92% ee, which constitutes a formal total synthesis of (R)-nicotine [27]. 

Negishi coupling of 2-furylzinc chloride with vinyl telluride provided 2-substituted furan with (Z)-double bond in a stereoselective manner, which was used in the total synthesis of l-(Z)-atractylodinol, a biologically active natural product as depicted in the following scheme <06TL8183>... 

Another example with the same substrate was a highly C-4-selective Negishi coupling (ArZnCl/ Pd) <06T2380>. 

Furstner has extended this strategy to the halitulin core by using Negishi coupling conditions and this is presented in Scheme 28. 

Dihydropyrrole triflate 55 is smoothly converted to the 2-phenyl derivative 56 under Negishi conditions [53]. This sequence represents a useful alternative to conventional pyrrole Negishi couplings. 

The Negishi coupling of halogenated porphyrins has also been described [54,55]. 

In continuation of his extraordinarily versatile and efficient directed-metalation technology, Snieckus employed indole 87 to selectively lithiate C-4 and to effect a Negishi coupling with 3-bromopyridine to give 88 in 90% yield [110]. In contrast, a Suzuki protocol gave 88 in only 19% yield (with loss of the TBS group). 

Dilithio-fS-carboline (89), which was generated from 1-bromo-P-carboline, undergoes the Negishi coupling with 2-chloroquinoline to form the alkaloid nitramarine (90) [111]. 

---