Aldehydes Nozaki-Hiyama-Kishi reaction

The multi-component procedure is also effective for the chromium-catalyzed addition of organic halides to aldehydes (the Nozaki-Hiyama-Kishi reaction) [73]. The active Cr(II) species is recycled by redox interaction with Mn powder as the stoichiometric co-reductant in the presence of MesSiCl (Scheme 34), which mainly liberates the chromium catalyst from the alkoxide adduct. The chemo- and diastereo-selective addition reaction is performed with a variety of organic halides and alkenyl triflates. In the case of crotyl bromide, the addition is highly stereoconvergent, i.e., the respective anti-... 

The Nozaki-Hiyama Kishi reaction has been successfully utilized in the total synthesis of palytoxin (355) [170] brefeldin (356) [172], halichondrin B [173], brevetoxin [174], pinnatoxin A [174a] and others. The coupling of alkynyl iodides with aldehydes can be carried out smoothly using CrCl2 and 0.01% of NiCk... 

Many catalytic reactions are not sensitive to the presence of a sulfur atom on the substrate. Two examples can be quoted the Nozaki-Hiyama-Kishi reaction where a chlorosilane-mediated Cr-Mn-catalyzed C-C coupling occurs between a halogenoalkene and an aldehyde [63], and the [IrCl(CO)3]-catalyzed intramolecular allyl transfer in functionalized 1,3-thiozanes [64]. 

The total synthesis of the marine toxin polycavemoside A was achieved by J.D. White and co-workers. In order to couple the central pyran moiety in a Nozaki-Hiyama-Kishi reaction, the aldehyde side chain had to be first homologated to the corresponding terminal alkyne and subsequently transformed into a vinyl bromide. The aldehyde substrate was treated under the Ohira-Bestmann protocol, and the desired alkyne product was obtained in high yield. 

Durandetti, M., Nedelec, J.-Y., Perichon, J. An electrochemical coupling of organic halide with aldehydes, catalytic in chromium and nickel salts. The Nozaki-Hiyama-Kishi reaction. Org. Lett. 2001, 3, 2073-2076. 

Alkylations. Using Cp2Cr as catalyst together with Mn and MejSiCl to induce the reaction of iodoarenes, iodoalkynes, allyl bromides, and enol triflates to aldehydes, secondary alcohols are formed. This process is a catalytic version of the Nozaki-Hiyama-Kishi reaction. Active Cr(II) catalyst can also be generated by Mn reduction of CpCrClj or CrClj. 

A catalytic variant of the Nozaki-Hiyama-Kishi reaction was recently introduced by Fiirstner [140]. The stoichiometric reaction generally requires at least three equivalents of chromium for the transformation to be complete. The large excess of CrCl2 and the toxicity of the chromium salts precludes the application of this reaction in industrial processes. The reaction developed by Fiirstner employs manganese powder and chlorotrimethylsilane to produce a catalytic cycle illustrated in Fig. 10-8 for the addition of vinyl iodides to aldehydes. The stereo-... 

These ligands were initially tested in the nickel(ll)-catalyzed enantioselec-tive fluorination of oxindoles and P-ketoesters, yielding the corresponding products with enantioselectivities of up to >99% ee and high yields. Application of the chiral pincer ligands in the chromium-catalyzed enantioselective Nozaki-Hiyama-Kishi reaction of aldehydes gave the corresponding alcohols with a maximum enantioselectivity of 93% [34]. 

One of the attractive features of the Nozaki-Hiyama-Kishi reaction is that crotyl bromide and other -Y-monosubstituted allylic hahdes usually react with aldehydes to form homoal-lylic alcohols with a high degree of a/jfr-selectivity (Scheme 12.4). This preference for the a fr-product is independent of the double-bond configuration of the starting halide. 

Pilli and Victor reported on a concise synthesis of (—)-decarestrictine D 32, which uses an intramolecular Nozaki-Hiyama-Kishi reaction as the penultimate step. Aldehyde 33 was prepared via a Dess-Martin oxidation and immediately submitted to NHK conditions of CrCl2-0.5% NiCl2 (15 equiv) in DMF to afford the tert-butyldimethyl-silyl-protected (—)-decarestrictine D 34 (Scheme 12.31). 5-(Z)-7-Oxozeaenol, also known as LL-Z1640-2 35, was isolated in 1978 by McGahren et al. from an unidentified fungus Lederle culture 121640 and has attracted interest as a potent kinase inhibitor (Figure 12.4). ... 

Solandelactones A, B, E, and F have been synthesized by White et al., in which the diene side chain was installed using a Nozaki-Hiyama-Kishi reaction. Aldehydes 48 and 49 were prepared by tetrapropylammonium perruthenate oxidation of the corresponding alcohols and were immediately treated with CrCla and NiCl2 to afford the natural products solandelactone A, B, E, and F (Scheme 12.36). ... 

Berkessel et al. have used an asymmetric Nozaki-Hiyama-Kishi reaction for the synthesis of several laulilamide analogs. (/ ,/ )-DlANANE ligand 14 was used for the key NHK coupling of the macrocyclic aldehyde 61 and iodide 62. Ten mol% of the chromium(ll) complex of 14 overcame the substrate selectivity and afforded the desired configuration in a dr of 78 22 and yield of 43% (Scheme 12.40). 

Grigg R, Putnikovic B, Urch CJ. Electrochemically driven catalytic Pd(0)/Cr(II) mediated coupling of organic halides with aldehydes. The Nozaki-Hiyama-Kishi reaction. Tetrahedron Lett. 1997 38 6307-6308. 

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. 

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]... 

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. 

The one-pot Barbier-type addition of alkenyl, aryl, allyl, vinyl, propargyl, alkynyl, or allenylchromium compounds to aldehydes or ketones is known as the Nozaki-Hiyama-Kishi (NHK) reaction. An excellent review by Furstner published in 1999 detailed the exhaustive literature on the carbon-carbon bond formations involving organochromium(III) reagents. This chapter will present major developments and examples of recent carbon-carbon bond formation methodology and improvements as well as their use in natural products synthesis since 1999. 

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