Nozaki-Hiyama-Kishi reaction enantioselectivity

Bandini, M., Cozzi, P. G., Umani-Ronchi, A. The first catalytic enantioselective Nozaki-Hiyama-Kishi reaction. Polyhedron 2000, 19, 537-539. 

Berkessel, A., Menche, D., Sklorz, C. A., Schroder, M., Paterson, I. A highly enantioselective catalyst for the asymmetric Nozaki-Hiyama-Kishi reaction of allylic and vinylic halides. Arrgew. Chem., Int, Ed, Engl, 2003,42,1032-1035. 

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]. 

The unique features of the Nozaki-Hiyama Kishi reaction make this an attractive methodology in the application to natural products synthesis, particularly the pronounced chemoselectivity and remarkable compatability with an array of functional groups. However, there are very few reports published of the application of enantioselective NHK reactions in the total synthesis of natural products. This section is divided into three parts 1) preparation of fragments with the NHK reaction in the synthesis of a portion of a natural product 2) the NHK reaction in the final or second last step of a natural product 3) the NHK reaction utilized anywhere in the total synthesis of a natural product. The next several pages show natural products where the NHK reaction have been employed in the syntheses of natural products since Fiirstner s review published in 1999. ... 

This chapter will review the literature up to the end of 2011 on the stereoselective Nozaki-Hiyama-Kishi reaction and applications in natural product synthesis. The transformation of the NHK reaction from using stoichiometric to catalytic amounts of chromium will be addressed initially then the diastereoselective NHK, followed by the enantioselective version (with an emphasis on the different classes of chiral ligands that have been employed in a wide variety of carbon-carbon bond forming processes), and finally, selected examples of the application of the NHK reaction to natural product synthesis will be described. 

Considering the unique features that the Nozaki-Hiyama-Kishi reaction possesses and its undoubted potential in the synthesis of complex natural products, the development of an efficient enantioselective version to control the absolute stereochemical outcome for a range of processes was highly desirable. However, because of the difficulties such as ligand coordination and specificity combined with the tendency of chromium(II) to form dimers or clusters with polydentate ligands, considerable effort has been devoted to the development of enantioselective variants. These studies have resulted in the expansion of the NHK to now include an impressive array of carbon-carbon, bond-forming processes (Scheme 12.6). 

Ligands containing a chiral oxazoline ring have been widely applied to a range of catalytic asymmetric pro-cesses, including with considerable success, the catalytic enantioselective 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]... 

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