Five- and Seven-Membered Rings from Alkenyl(methoxy)carbene Complexes and Methyl Ketone Enolates

Diastereoselective Synthesis of Cycloheptadienol Derivatives by a Formal [5+2] Carbocyclization Reaction of α,β,γ,δ‐Diunsaturated (Methoxy)carbene Complexes with Methyl Ketone Lithium Enolates

“…Moreover, lithium enolates add to α,β‐unsaturated carbene complexes in a Michael fashion,9 except in the case of (methoxy)carbene complexes and methyl ketone lithium enolates, for which a 1,2‐addition is observed 9a. 10 In this context, we have recently developed the diastereoselective synthesis of five‐membered rings by novel [3+2] and [4+1] carbocyclization reactions,10 as well as the diastereoselective synthesis of seven‐membered rings by a novel [4+3] carbocyclization reaction 10a…”

“…Furthermore, in the reaction of alkenyl ketone lithium enolate 2 g with carbene complexes 1 we observed two competitive reaction patterns. The reaction with carbene complex 1 c afforded a mixture of products 4 i and 5 a , which were separable by flash column chromatography, and were derived from a formal [5+2] and [4+3]10a carbocyclization process, in which the carbene complex acted as a C5 and C3 building block, respectively (Table 1, entry 10). However, the analogous reaction of γ,δ‐substituted carbene complexes 1 e and 1 f afforded exclusively and diastereoselectively the [4+3] carbocyclization products 5 b and 5 c , respectively, in moderate yields (Table 1, entries 11 and 12).…”

“…Accordingly, when the γ,δ positions are substituted, the cyclization is presumably disfavored, and cycloheptadienol derivatives 4 are either formed with difficulty or not at all. Moreover, in the cases of alkenyl methyl ketone lithium enolates, intermediate 7 could also competitively or exclusively evolve by intramolecular Michael addition of the 3‐position of the σ‐dienyl metal fragment to the ketone, giving intermediate 10 , which after hydrolysis, metal decoordination, and double‐bond isomerization, would give rise to cycloheptenone derivatives 5 10a. On the other hand, hydrolysis of intermediate 7 would afford ketone 6 .…”

Three/Four/Five‐Component Diastereoselective Cyclization of Fischer Carbene Complexes, Lithium Enolates, and Allylmagnesium Bromide

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The 1,2-addition reaction of metal enolates to Group 6 Fischer alkoxy carbene complexes produces anionic (1alkoxy-3-oxoalkyl)pentacarbonylmetalate species, which evolve further to give different organic products, depending on the reaction conditions and the structural features of the reaction partners. Alkenyl methoxy carbene complexes also undergo nucleophilic attack at the carbene carbon atom when they are treated with methyl ketone lithium enolates, leading to acyclic unsaturated ketones [2] when the reaction mixture is quenched at low temperature and to five- [4] or seven-membered [4a] carbocycles when the reaction is allowed to reach room temperature. Alkenyl methoxy carbene complexes also undergo nucleophilic attack at the carbene carbon atom when they are treated with methyl ketone lithium enolates, leading to acyclic unsaturated ketones [2] when the reaction mixture is quenched at low temperature and to five- [4] or seven-membered [4a] carbocycles when the reaction is allowed to reach room temperature.

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“…[1] Aryl methoxy carbene complexes react with lithium or potassium enolates of ketones [2] and with lithium enolates of a-haloesters [3] to provide open-chain products after hydrolysis with acid. Alkenyl methoxy carbene complexes also undergo nucleophilic attack at the carbene carbon atom when they are treated with methyl ketone lithium enolates, leading to acyclic unsaturated ketones [2] when the reaction mixture is quenched at low temperature and to five- [4] or seven-membered [4a] carbocycles when the reaction is allowed to reach room temperature. These diastereoselective cyclizations involve intramolecular addition of lithium allylmetalate intermediates, generated in situ, to either the carbonyl group or the b carbon atom of an alkenyl ketone.…”