Cyclization zirconium-mediated

Scheme 12 Low-valent zirconium-mediated cyclization of eneynes.45...

A small number of stable compounds have been produced with substituents at both peri and end positions. The first such system was the product of repeated application of a zirconium-mediated cyclization to phthalate ester 35, leading to the heavily substituted pentacene 36 in 11 steps (Scheme 3.8) [51]. Little discussion of the properties of this pentacene derivative was presented, but it was soluble and stable enough for complete characterization. This unusual approach to the synthesis of pentacene is one of the few to yield such high substitution. 

Similarly, the regio- and diastereoselective formation of azetidines can be accomplished through olefin insertion into the Zr-C bond of zirconaaziridines (Eq. 14). Cleavage of the Zr-C bond with I2 introduces an alkyl iodide functionality, which alkylates at nitrogen to result in intramolecular cyclization and the diastereoselective formation of azetidines, the products of the formal zirconium-mediated [2+2] reaction of an imine and an olefin. Hindered cyclic alkenes can also insert into the Zr-C bonds of zirconaaziridines to yield bi-cyclic products [55], albeit with low diastereoselectivity (2 1 for norbornene). 

Electrophilic cyclization of a wide variety of (Z)-enynols affords substituted (Z)-5-(l-iodoylidene)-2,5-dihydrofur-ans with high regio- and stereoselectivity under mild reaction conditions. To access the cyclization precursors 27, a zirconium-mediated cross-coupling reaction of three different components involving an alkyne, a ketone, an alkynyl bromide in a one-pot procedure has been developed (Scheme 34) <2005JOC6999>. 

Carbohalogenation of double and triple bonds can be achieved in various ways one method is a two-step version via carbometalation, followed by oxidative cleavage of the newly formed metal carbon bond (see Section 1.5.8.4.4.). Several examples using this methodology in stereoselective organic synthesis have employed catalytic (see Section I.5.8.4.4.) or stoichiometric use of transition metals. An example of the latter case is the zirconium-mediated cyclization of 1,6-hep-tadienes which leads to tram- or (is-1,2-bis(haIomethyI)cydopentane (1), depending on the metal reagent1. 

Makabe M, Sato Y, Mori M (2004) Zirconium-mediated intramolecular cyclization of yne-imine. Synthesis 1369-1374... 

The concept of their homologation method is outlined in Scheme 11.34. Starting from the 3,4,5,6-tetraalkylphthalates 6, reduction and bromination of two ester groups, alkynylation of the resulting dibromides 87, zirconium-mediated cyclization of diynes 88 with dimethyl acetylenedicarboxylate and subsequent aromatization by DDQ (2,3-dichloro-5,6-dicyano-l,4-benzoquinone) afforded the anthracene derivatives 91 in six steps. Tricyclic compounds 91 thus formed are also substituted phtha-late derivatives, which are the same as 86. The tricyclic skeleton of 91 can again be extended to pentacyclic compounds 92 by the same combination of procedures as for 86 [35],... 

Another example of elaboration of tetrasubstituted double bonds by RCM was disclosed by Kotora et al. in a formal total synthesis of estrone (Scheme 1.17). Starting from 110, two zirconium-mediated cyclizations enabled the preparation of compound 112 whose RCM catalyzed by [Ru]-II (20mol%) (toluene, 90 °C) provided estrone precursor 113 in 82% yield [21]. 

The reductive cyclization of non-conjugated diynes is readily accomplished by treatment of the acetylenic substrate with stoichiometric amounts of low-valent titanium52 523 and zirconium complexes.53 533 Hence, it is interesting to note that while early transition metal complexes figure prominently as mediators of diyne reductive cyclization, to date, all catalyzed variants of this transformation employ late transition metal complexes based on nickel, palladium, platinum, and rhodium. Nevertheless, catalytic diyne reductive cyclization has received considerable attention and is a topic featured in several review articles. ... 

Chemistry of low-valent titanium and zirconium has produced a number of powerful methods for the transformation of carbohydrates to carbocyclic compounds. The Ti(III)-mediated generation of a radical from epoxides and its subsequent cyclization [32] was discussed earlier under free radical methods (see Scheme 9). As shown in Scheme 12,... 

Zinc The cychzation of 2-homoallylphenols to chromanols is mediated by zinc chloride (1.5 equiv) in the ionic liquid (BuPy)2SnCl4 at 70°C [59]. Zirconium zirconium tetrachloride brings about the cyclization of 2-aUylphenols to 2-methyl-diyhdrobenzofurans (0°C, CH2CI2, 10-12 h), but the substrate range appears to be limited to phenols with 71-acceptor substituents [60]. 

This reagent can participate in a variety of reactions, involving different reaction mechanisms. For the Schwartz reagent-mediated radical cyclization, it is proposed that the key step is the homolytic cleavage of the zirconium-hydrogen bond, as illustrated here. 

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