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1.1.2 Intramolecular Nozaki–Hiyama–Kishi Coupling Reactions

DOI: 10.1055/sos-SD-221-00001

Gao, S.; Wang, D.Science of Synthesis: Metal-Catalyzed Cyclization Reactions, (2016131.

The development and application of organochromium(III) species in organic synthesis started in the 1970s. Nozaki, Hiyama, and co-workers demonstrated that by reacting allyl and vinyl halides with chromium(II) chloride under aprotic and oxygen-free conditions organochromium(III) reagents could be generated, which react as nucleophiles with aldehydes to give allylic and homoallylic alcohols (Nozaki–Hiyama reaction).[‌75‌,‌76‌] Kishi[‌77‌] and Nozaki[‌78‌] independently discovered that nickel(II) catalyzes the formation of C—Cr(III) bonds. This chromium(II)/nickel(II)-mediated “Barbier type” reaction is known as the Nozaki–Hiyama–Kishi (NHK) reaction (Scheme 19), and has been one of the most powerful tools for constructing carbon–carbon bonds both inter- and intramolecularly in organic synthesis, especially in natural product synthesis. The nucleophilic addition of organochromium(III) reagents to a carbonyl compound produces stable chromium alkoxide [O—Cr(III)] species, therefore NHK reactions normally require stoichiometric chromium(II) [>2 equiv of Cr(II) per 1 equiv of organic halide). Fürstner and co-workers developed a chromium-catalyzed process by adding a chlorosilane to release the metal salt from the chromium alkoxide, and manganese powder to reduce the released chromium(III) and regenerate chromium(II).[‌79‌‌81‌]

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