Nozaki reaction intramolecular

Nozaki reaction (12, 137 14, 96 15, 95). An intramolecular version of this reaction can effect cyclization even to a strained nine-membered ring. Thus 1 on treatment with CrCl2 at a low temperature cyclizes mainly to 2, a mixture of epimers in which a cyclononadiyne ring is fused to a cyclopentene ring. After acetylation of the secondary hydroxyl group, the mixture is dehydrated to 3, with a nine-membered enediyne ring. 

Intramolecular Nozaki reaction. The addition of a vinyl-chromium compound to an aldehyde (12, 137 14, 96) is useful for macrocyclization, particularly if the CrCl2 reagent is activated by a catalytic amount of Ni(acac)2. Under these conditions, the vinyl iodide with a w-formyl group (1) cyclizes to (+ )-brefeldin C 12) and the 4-epimer as a 1 4 mixture in 60% yield.1... 

Lubineau A, Billault I (1998) New access to unsaturated keto carba sugars (ga-bosines) using an intramolecular Nozaki-Kishi reaction as the key step. J Org Chem 63 5668... 

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]. 

Danishefsky s total synthesis of avermectin (3a) was accomplished via an aldol reaction to join the northern and southern segments, intramolecular Nozaki aldol cyclization [138] to construct the southern ring system, Mukaiyama macro-lactonization, deconjugation to the C3-C4 double bond, and NIS-mediated gly-cosidation (Fig. 7). 

Example 3, Intramolecular Nozaki-Hiyama-Kishi reaction ... 

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. 

Scheme 3.13 Protecting-group directed stereoselective intramolecular Nozaki-Hiyama-Kishi reaction. A concise and efficient total synthesis of amophidinolactone A.

Scheme 3.14 Stereoselectivity in the intramolecular Nozaki-Hiyama-Kishi reaction influence of the substitution pattern and protecting groups in the construction of 10-membered lactones.

Nicolaou and coworkers have reported an expeditious IBX (2-iodo3gr-benzoic acid, l-hydro q -l, 2-benziodoxol-3(l//)-one 1-oxide) mediated synthesis of Z-vancosamine " starting from vinyl iodide and protected aldehyde via an intramolecular Kishi-Nozaki coupling reaction. The coupling product, as a mixture of alcohols, was immediately oxidized with DMP (Dess-Martin periodinane). The oxidation was followed by a sodium borohydride/cerium chloride reduction to produce a protected alcohol intermediate. In the next step, the required alcohol was reacted... 

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). ... 

Mohapatra DK, Das PP, Pattanayak R, Gayatri G, Sastry GN, Yadav, JS. Protecting-group directed stereoselective intramolecular Nozaki-Hiyama-Kishi reactions a concise and efficient synthesis of Amphidinolactone A. Eur. J. Org. Chem. 2010 4775 784. 

Pilli RA, Victor MM. Total synthesis of (—)-Decarestrictine D through a stereoselective intramolecular Nozaki-Hiyama-Kishi reaction. Tetrahedron Lett. 1998 39 4421 1424. 

---