A novel and convenient synthetic route toward (+/-)-beta-cuparenone and many other sesquiterpene natural product precursors has been developed via palladium-catalyzed tandem Heck cyclization of 1-bromo-5-methyl-1-aryl-hexa-1,5-dien-3-ols. [reaction: see text].
Direct coupling between N-tosylhydrazones and various coupling partners such as 1,3-azoles, alkynes, and heteroatoms in the presence of Cu catalysts has turned out to be an extremely attractive route for carbon-carbon and carbonheteroatom bond formation. Recently, both intra-and intermolecular versions, along with cascade reactions involving sequential inter-and intramolecular coupling, have made a significant impact in synthetic chemistry. Emphasis has been placed on
Efficient Pd-catalyzed cyclization of homoallylated bbromo-vinylalcohols via a domino process to carbocycle derivatives in presence of different bases is reported. An unexpected and novel palladium-mediated Heck-type intramolecular oxidative cyclization of 1-bromohexa-1-ene-5-yn-3-ol derivatives is also described.The formation of carbon-carbon bonds using in situ generated organometallic reagents is of fundamental importance in organic synthesis. 1 Palladium catalysts have emerged as extremely powerful tools for the construction of carbon-carbon bonds. 2 Their popularity stems in part from their capability to oxidize, 3a,b reduce, 3c,d isomerize 3e,f as well as to form new bonds. Substituted carbocycles represent a common structural component of naturally occurring and biologically active molecules. 4 The cyclization of unsaturated substrates using an intramolecular Heck reaction promoted by organopalladium complexes is of fundamental importance for the construction of a vast array of mono-and polycarbocyclic and also polyheterocyclic systems 5 and is therefore a highly attractive feature in the synthesis of cyclic natural products. 5e In this context, we have recently reported 6 a new palladium-promoted domino C-C cyclopalladation sequence allowing the facile one-pot synthesis to cyclopentenones with promising synthetic value. The 1-bromohexa-1,5-diene-3-ol derivatives underwent Pd-catalyzed oxidative cyclization to functionalized cyclopentenones in very good yields. In this communication we wish to report the reactivity of new sensitive substrates towards palladium-catalyzed intramolecular Heck reaction, which provides an efficient route to cyclopentenones and cyclohexenones.The starting materials were synthesized by addition of the Grignard reagents derived from 4-bromo-1-butene and Mg to bromoaldehydes (Scheme 1) in tetrahydrofuran (THF) to afford bromo alcohols (1a-6a, Table 1) in good yield.Applying Heck reaction to the compounds 1a-6a under standard conditions, 7 produced substituted cyclohexenones (Scheme 2) exclusively through 6-exo-trig cyclization pathways.
Scheme 2In our previous communication, we opted for HCOONa as the base, but later, we performed the reaction with other bases (Na 2 CO 3 , K 2 CO 3 , NaOAc, Et 3 N) and acetonitrile as solvent. In all these cases we successfully isolated the cyclized products. To improve the yield further, we incorporated tetrabutyl ammonium chloride as additive, which was found to be effective in all cases ( Table 2).The structure of 6b was unambiguously determined by Xray crystallographic analysis (Figure 1). Figure 1 ORTEP view of the structure 6bAs we could not isolate any intermediate for this reaction, we speculate that the mechanism follows the sequence in Scheme 3. During the search for an intermediate, we synthesized compound I by O-alkylation of 1-(2-bromoBr H OH Pd(OAc) 2 / PPh 3 DMF or MeCN O TBAC bases Scheme 1 Br CHO THF, -78 °C to 0 °C Br H OH Mg, 4-bromo-1-butene Downloaded by: UC Santa Barbara. Copyrighted material. 2136 D. Ray et al. LETTER Synlett...
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