Nozaki-Kishi coupling reaction

Assembly of the subunits began with the Nozaki-Kishi coupling reaction of iodoacetylene 13 and aldehyde 12, in the presence of CrCl2/NiCl2, to provide propargylic alcohol 23, with 3 1 dr at C7 (Scheme 3). The four-step conversion to bromide 24 was followed by the enolate alkylation of methyl ketone 14. 

Usanov and Yamamoto recently found that catalytic amounts of Co(TPP) 367 led to a dramatic rate acceleration of Nozaki-Kishi-Hiyama reactions catalyzed by chromium complex 368 (Fig. 101) [460]. The authors attributed the rate enhancement to initial reduction of 367 to a Co(I) complex. The latter is able to undergo an Sn2 substitution at propargyl bromide 366 giving an allenylCo(ffl) species. It was proposed that its homolysis leads to allenyl radical 366A, which couples to Cr(II) complex 368. The resulting allenyl Cr(III) complex adds in an SN2 process... 

Nozaki-Hiyama Coupling Reaction (Nozaki-Hiyama-Kishi Reaction)... 

Pietruszka used a series of Ru catalysts for RCM of 93 to acquire the desired nine-membered lactone 94. It was found that the Ru complex catalyst-III [84] functions as an efficient catalyst for the reaction, and the highest obtained yield of the lactone 94 was 61% (Scheme 5.34) [85]. Ultimately, the aldehyde derived from 94 was subjected to the Nozaki-Hiyama-Kishi coupling reaction with the corresponding side chains to furnish (—)-6a in 78% yield as a 59 41 separable diastereomeric mixture. 

Coupling of vinyl iodide 82 (a substrate derived from geraniol) with aldehyde 84 was accomplished via a Nozaki-Hiyama-Kishi [56] coupling reaction to give 107 after oxidation (Scheme 24). Three straightforward transformations allowed the authors to isolate thyrsiferol (1) and thyrsiferol 23-acetate (4) in a total of 36 steps and 24 steps for the longest linear sequence. 

We selected the natural product thyrsiferol as an ideal target to test our ideas. Its total synthesis was envisioned to proceed as illustrated in the Scheme 28. The successful coupling between aldehyde 84 and vinyl iodide 82 via a Nozaki-Hiyama-Kishi (NHK) reaction [66] had been demonstrated previously [29]. We therefore sought to model our final steps after precedence presented by Forsyth for the union of these two fragments. The focus of our synthetic strategy centered around the stereoselective synthesis of the ABC framework (84) of thyrsiferol (1) as a scaffold to validate the scope of the Cp2TiCl reaction with epoxides toward the assembly of Q-C-glycosides and cyclic ethers. 

Related reactions Barbier coupling reaction, Kagan-Molander samarium diiodide coupling, Nozaki-Hiyama-Kishi reaction ... 

The Nozaki-Hiyama-Kishi (NHK) reaction involves the mild addition of chro-mium(II) organometallics to aldehydes to give homoallylic alcohols in a regio- and stereo-controlled fashion.111 A very significant achievement in the chromium organometallic chemistry was accomplished by Fiirstner who developed a catalytic version of the NHK reaction based on the coupled use of the redox Mn(0)/Cr(III) couple and trimethylsilyl chloride (TMSC1).[21 Moreover, the integration of the Fiirstner protocol with the addition of the Jacobsen s Salen /V,/V -bis(3,5-di-f-butylsalicylidene)-l,2-cyclohexanediamine] and triethylamine allowed Cozzi, Umani-Ronchi, et al. to develop a catalytic enantioselective route to homoallylic alcohols.[3]... 

Nozaki-Hiyama-Kishi couplings, 253 Nozaki-Hiyama-Kishi reaction, 297, 312 nuclear Overhauser effect, 386 nucleophilic aromatic substitution, 422... 

The first total synthesis of pinnatoxin A (104) was completed by Kishi s group in 1998 [67,68]. Their synthetic strategy is shown in Scheme 13. They planned to make the seven-membered iminium ring at the last stage, and the key macrocyclization was carried out by an intramolecular Diels-Alder reaction. Fragments 138-141 were coupled using the Nozaki-Hiyama-Kishi reaction, Juba coupling reaction etc. 

Pietruszka [75] reported the total synthesis of a series of solandelactones (A-H) by the coupling reaction of the lactone 78, the key intermediate, with side chains 79 and 80 (Scheme 5.27). Lactone 78 was prepared by cyclization of the seco-acid 77 under Yamaguchi conditions in good yield (85%). Finally, the Nozaki-Hiyama-Kishi coupling of the unsaturated lactone aldehyde or its saturated counterpart with the iodide 79 or 80 afforded solandelactones A-H in good yields as separable diastereomeric mixtures (ratio 2 1). 

---