Unusual Palladium-Catalyzed Cascade Arylation ofα,β-Unsaturated Phenyl Sulfones under Heck Reaction Conditions

Abstract

Over the last two decades the Heck reaction has emerged as one of the most versatile tools for the synthesis of carbonsubstituted alkenes. [1] The mechanism of this reaction is generally accepted to proceed through an oxidative addition/ syn-carbopalladation/syn-b-hydrogen elimination sequence. The Heck reaction is also the origin of a fascinating variety of cascade reactions in which the key common feature is the formation, after the carbopalladation step, of a s-alkylpalladium(ii) intermediate lacking a suitable b-hydrogen syn with respect to the palladium center. [1,2] A particularly interesting case is that in which the s-alkylpalladium(ii) complex undergoes an intramolecular CÀH activation process to give a palladacycle intermediate. [3] In our research into the use of substituted vinyl sulfones in stereoselective synthesis, [4] we envisaged that acyclic b,b'disubstituted-a,b-unsaturated sulfones could be stereoselectively prepared by simple Heck arylation of a,b-unsaturated sulfones through the seemingly evident syn-carbopalladation/ syn-b-hydrogen elimination pathway. [5] However, we describe herein that the palladium-catalyzed reaction of trans-a,bunsaturated phenyl sulfones with excess iodobenzene/Ag 2 CO 3 proceeds by an intermolecular four-component cascade reaction to give 1-phenyl-9-phenylsulfonyl-9,10-dihydrophenanthrenes in which four CÀC bonds are formed in a single step.To test the behavior of vinyl sulfones in intermolecular Heck reactions, [6] we began by treating the model substrate 1 a (see Eq. (1), Table 1, R iPr) [7] with iodobenzene under typical Heck reaction conditions: Pd(OAc) 2 (10 mol %), K 2 CO 3 , N,N-dimethylformamide (DMF), 120 8C. However, only the base-catalyzed isomerization of the vinyl sulfone to form the corresponding allyl sulfone was observed. [8] Therefore, we turned our attention to the use of Ag 2 CO 3 , a milder base that has proved to be very efficient in the Heck reactions of a,b-unsaturated sulfoxides. [9] The reaction of 1 a with iodobenzene (1 equiv) and Ag 2 CO 3 (200 mol %) in DMF at 120 8C for 72 h gave a mixture of four compounds: the starting vinyl sulfone (32 %), the isomerized allyl sulfone (30 %), the expected Heck product 2 a (26 %), and, quite surprisingly, the dihydrophenanthrene 3 a (21 %; Eq. (1)). The yield of 3 a improved progressively in the presence of increasing amounts of iodobenzene since the formation of 3 a requires the participation of three molecules of iodobenzene. The optimal 2 a:3 a ratio was obtained in the presence of ten equivalents of iodobenzene [10] (2 a:3 a 5:95, Table 1, entry 1).In order to determine the versatility of this unprecedented Heck-type cascade process on acyclic alkenes, the arylation of several trans-a,b-unsaturated phenyl sulfones 1 [7] was studied (Table 1, entries 1 ± 5).Remarkably, the cascade product 3 predominated largely over the Heck product 2 (2:3 ratio from 12:88 to 3:97, 82 ± 86 % yields of mixtures of 2 and 3) with both b-alkyl- (Table 1, entries 1 ± 3) and b-aryl-substituted vinyl sulfones (Table 1, ent...

Intermolecular Domino Reaction of Two Aryl Iodides Involving Two CH Functionalizations

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On the Enantioselective Hydrogenation of Isomeric Methyl 3-Acetamidobutenoates with RhI Complexes

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“… Frühe Arylierung von C‐H‐Bindungen unter Beteiligung von Pd 0 /Pd II /Pd IV ‐Katalyse (Carretero et al., 2001 ) 41…”

An Efficient Synthesis of Liquid Crystalline Gigantocycles Combining Banana-Shaped and Rod-Like Mesogenic Units

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