Nozaki-Hiyama-Kishi coupling

A valuable feature of the Nin/Crn-mediated Nozaki-Takai-Hiyama-Kishi coupling of vinyl iodides and aldehydes is that the stereochemistry of the vinyl iodide partner is reflected in the allylic alcohol coupling product, at least when disubstituted or trans tri-substituted vinyl iodides are employed.68 It is, therefore, imperative that the trans vinyl iodide stereochemistry in 159 be rigorously defined. Of the various ways in which this objective could be achieved, a regioselective syn addition of the Zr-H bond of Schwartz s reagent (Cp2ZrHCl) to the alkyne function in 165, followed by exposure of the resulting vinylzirconium species to iodine, seemed to constitute a distinctly direct solution to this important problem. Alkyne 165 could conceivably be derived in short order from compound 166, the projected product of an asymmetric crotylboration of achiral aldehyde 168. 

Nozaki-Takai-Hiyama-Kishi coupling Ni(n)/Cr(n)-mediated 603, 605 f, 620 f. 

Threc-carbon ring expansion was carried out in two stages. First, two-carbon homologation of the exo methylene ketone 8 followed by trapping of the intermediate enolate as the triflate led to 9. Nozaki-Hiyama-Kishi coupling followed by acetylation smoothly converted 9 into 10. 

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

The specific roles of each metal of nickel/chromium catalysts of Nozaki-Hiyama-Kishi coupling of vinyl halides and aldehydes have been studied by UV-visible spectroscopy, electrochemistry, and spectroelectrochemical methods. Chromium(II) chloride does not react with the vinyl halide but converts nickel(II) to nickel(I) species, which does. The unstable nickel-vinyl species can be stabilized in turn by the chromium. ... 

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). 

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. 

Scheme 7.20 Synthesis of LL-Z1540-2 by intramolecular Nozaki-Hiyama-Kishi coupling [82].

Pd cross-coupling ( Nozaki-Hiyama-Kishi coupling Reveromycin B (79)... 

Paterson I, Bergmann H, Menche D, Berkessel A. Synthesis of novel 11-desmethyl analogues of Laulimalide by Nozaki-Hiyama-Kishi coupling. Org. Lett. 2004 6 1293-1295. 

Nozaki-Hiyama-Kishi (NHK) reactions215,216 are well known and often employed as a useful method for the synthesis of natural products by coupling of allyl, alkenyl, alkynyl, and aryl halides or triflates with aldehydes. The organochromium reagents are prepared from the corresponding halides or triflates and chromium(ll) chloride, and are employed in polar aprotic solvents (THF, DMF, DMSO, etc.). Subsequently, it was found that nickel salts exhibited a significant catalytic effect on the formation of the C-Cr bond217,218 (Equation (19)). 

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