Nozaki cyclization

A very interesting and powerful new cyclization method employing intramolecular attack of a propargylic-allylic anion at a propargylic aldehyde is the Nozaki cyclization [Eq. (10)] even the heavily strained nine-membered ring 37 can be obtained by this procedure [18]. 

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. 

In a more recent synthesis, Lubineau and Billault [44] developed a novel method to access gabosine-related cyclohexene structures by exploiting a Nozaki-Kishi cyclization as the key step (Scheme 31). 

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... 

Cyclic enediynes have been obtained also by elimination of a suitable propargylic alcohol on a preformed cyclic diyne.5 An example is shown in Scheme 19.7, where the cyclization was accomplished through a Nozaki-Hiyama intramolecular allyl bromide addition to an aldehyde.5 This method proved successful for the synthesis of a particular enediyne that, because of conformational biases, could not be obtained by the strategies described above. 

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). 

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). 

Y. Monoguchi, K. Nozaki, T. Maejima, Y. Shimoda, Y. Sawama, Y. Kitamura, Y. Kitade, H. Sajiki, Solvent-free Huisgen cyclization using heterogeneous copper catalysts supported on chelate resins. Green Chem. 15 (2013) 490-495. 

Barrett applied this procedure to the synthesis of sucrose (Scheme 5) [7]. 2,3,4,6-Tetra-O-benzyl-D-glucopyranose was converted into the a-glucopyranosyl ester 25 with excellent selectivity. In this case the methylenation using Tebbe reagent was unsuccessful. However, the Nozaki-Takai protocol gave the desired vinyl ether. After desilylation, the cyclization reaction gave only the P-fructofuranosyl derivative 26 when the reaction was performed in the presence of silica. 

Ikeda M, Teranishi H, Nozaki K, Isibasbi H. Trietbylborane-mediated atom-transfer cyclization of 2-iodo-AL(prop-2-enyljacetamides and related compounds. J. Chem. Soc., Per-kinTrans. 1 1198 (10) 1691-1697. 

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