Palladium‐Catalyzed Intramolecular [3C+2C] Cycloaddition of Alkylidenecyclopropanes to Allenes

Abstract

Allenes are useful and versatile twocarbon partners in palladium catalyzed [3C + 2C] intramolecular cycloadditions with alkylidenecyclopropanes enabling the preparation of dienyl bicycloA C H T U N G T R E N N U N G [3.3.0]octane adducts with good yields and high diastereoseletivity. Keywords:alkylidenecyclopropanes; allenes; bicycloA C H T U N G T R E N N U N G [3.3.0]octanes; cycloaddition; palladium Alkylidenecyclopropanes are strained but readily accessible structures which can participate as threecarbon components in metal-catalyzed cycloadditions to afford different types of p-systems.[1] Our group has recently shown that alk-5-ynylidenecyclopropanes undergo a mild [3C + 2C] intramolecular cycloaddition upon treatment with appropriate palladium or ruthenium catalysts to provide a variety of fused bicycloA C H T U N G T R E N N U N G [3.3.0]octenes.[2] More recently we have also demonstrated that it is possible to use alkenes in place of alkynes as two-carbon components in the cycloaddition. Although attaining good efficiencies in these cycloadditions requires a relatively high catalyst loading (6 % of Pd 2 dba 3 , and 20 % of the ligand), the reactions provide a rapid and direct entry to bicyclopentanoid rings equipped with up to three stereogenic centers.[3] The cycloadditions can be performed with either activated (electron-deficient) or non-activated alkenes, but it is less efficient when the terminal position of the alkene is substituted by an alkyl group due to competing b-hydride elimination processes on putative palladacyclic intermediates. Thus, treatment of the cyclopropylideneethylamine 1 with Pd 2 dba 3 (6 mol %) and ligand L1 (20 mol %) in refluxing dioxane provided the cycloadduct 2 in only 57 % yield because of concomitant formation of the dienyl cycloisomerization side product 3 [25 % yield, Eq.(1)].[4] Thereby, while the cycloaddition seems still to be the major reaction pathway, there are competitive processes that result in an important decrease in the efficiency of the transformation. We envisaged that using allenes instead of alkenes might provide a good solution to the above problem and perhaps lead to more efficient [3 + 2] cycloaddition processes owing to the presumably higher reactivity of the allene unit. Allenes are being increasingly used in metal-catalyzed annulation reactions due to their unique reactivity and the special manipulation possibilities that they offer to the resulting products owing to their retaining one double bond of the allene.[5] Despite these potential advantages, we are not aware of studies on the behaviour of this type of p-system in transition metal-catalyzed [3C + 2C] cycloadditions with methylene-or alkylidenecyclopropanes.[6] Herein, we describe the first examples of palladium-catalyzed intramolecular cycloadditions between allenes and alkylidenecyclopropanes, examples that confirm the special utility of allenes as twocarbon partners in this type of annulation.Allene 4a, which can be easily assembled from 1-vinylcyclopropyltosylate and diethyl ...

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Recent Methodologies That Exploit C–C Single-Bond Cleavage of Strained Ring Systems by Transition Metal Complexes

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Recent developments in the reactivity of methylene- and alkylidenecyclopropane derivatives

“…In addition, the authors showed that allenes were also useful two-carbon partners in Pd-catalysed [3þ2] intramolecular cycloadditions with alkylidenecyclopropanes, enabling the preparation of the corresponding dienyl bicyclo[3.3.0]octane adducts with moderate-to-good yields (29e99%) and moderate diastereoselectivity (up to 50% de in favour of the cis-fused bicyclic product). 107 …”