Cyclization Dotz reaction

The formation of the tricarbonylchromium-complexed fulvene 81 from the 3-dimethylamino-3-(2 -trimethylsilyloxy-2 -propyl)propenylidene complex 80 and 1-pentyne also constitutes a formal [3+2] cycloaddition, although the mechanism is still obscure (Scheme 17) [76]. The rf-complex 81 must arise after an initial alkyne insertion, followed by cyclization, 1,2-shift of the dimethylamino group, and subsequent elimination of the trimethylsilyloxy moiety. Particularly conspicuous here are the alkyne insertion with opposite regioselectivity as compared to that in the Dotz reaction, and the migration of the dimethylamino functionality, which must occur by an intra- or intermo-lecular process. The mode of formation of the cyclopenta[Z ]pyran by-product 82 will be discussed in the next section. 

In recent years the group of C. A. Merlic has reported photochemically induced cyclizations of dienyl carbene complexes of type 39 to produce phenol derivatives 40 [19]. In these very intelligently designed reactions, which are related to the Dotz reaction, the primary, photochemically generated intermediates of type 41 undergo a (formal) electrocyclic ring-closure to form linear, conjugated cyclohexadienones 42, which then tautomerize to the phenols (Scheme 12). 

Gordon and Danishefsky [112] used the reaction of a chromium Fischer car-bene complex 164 with a cycloalkine 163 to build the naphthoquinone core 165 (Dotz reaction, review [113]), a procedure often used for synthesis of the linearly condensed anthracyclinones (e.g., [114]). The quinone ketone 165 has nucleophilic and electrophilic centers correctly positioned to furnish a ben-zo[fl]anthraquinone. However, treatment with NaH or Triton B gave the spiro-compounds 166 as a mixture of two stereoisomers. These products evidently arose from Michael addition of the ketone enolate to the naphthoquinone double bond. But the weaker base DBU induced cyclization at ambient temperature to the benzo[a]anthraquinone 167 in 65% yield (Scheme 42). The primary aldol adduct apparently eliminated water and the resulting dihydrobenzo[a]anthraquinone aromatized under basic conditions in the presence of air. This is an instructive example of the influence of the base on the cyclization mode. 

A recent synthesis of this building block has been published by Eastham et al. in 2006 (48). Their key step is a Dotz benzannulation reaction and is shown in Scheme 2.10. The bromohydrin 66 was formed from dihydrofuran (50). Cobalt-mediated cyclization, followed by ozonolysis with reductive work-up yielded 68 after hydrazine formation. Reductive removal of the hydrazine function, followed by chromium-carbonyl formation gave the Dotz reaction precursor 69. This reacted with an alkyne in the Dotz reaction, and was then oxidized and hydrogenated 70). Pyrolysis gave the protected alcohol and the remaining free alcohol was protected as a triflate (—> 71). Reductive removal of the triflate and deprotection of the silyl ether yielded the desired 33 in 1.2% overall yield. 

Alternatively, the arene can be left complexed so that the chemistry of the Ti -arene complex can be exploited (see Section 10.3). " The Dotz reaction between the cyclohexenyl carbene 8.52 and the benzylic alkyne 8.53 in the presence of a silylating agent gave the ti -complex 8.54 (Scheme 8.18). Treatment of this complex with LDA resulted in formation of the anion a- to sulfur 8.55 that cyclized by nucleophilic attack onto the chromium-complexed aromatic ring. Oxidative work-up then gave the tetracycle 8.57. 

Dotz reaction, methylenation of ketones and alkene metathesis (dimerization, cyclization). 

Depending on the types of substituents and the precise reaction conditions (l,3-butadien-l-yl)carbene complexes can undergo direct cyclization to yield cyclo-pentadienes [337,350]. As mentioned in Section 2.2.5.1, cyclopentadiene formation occurs particularly easily with aminocarbene complexes [351]. Alternatively, in particular at higher reaction temperatures, CO-insertion can lead to the formation of a vinylketene complex, which, again depending on the electronic properties of the substituents and the reaction conditions, can cyclize to yield cyclobutenones, furans [91,352], cyclopentenones, furanones [91], or phenols (Dotz benzannulation) [207,251,353]. 

A cyclized product (cyclobutenone) has been observed in the reaction of a nonheteroatom-stabilized complex K. H. DOtz and R. E. Dietz, 7. Organomet. Chem., 1978,157, C55. 

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