Rhodium‐Catalyzed Asymmetric Arylative Cyclization of meso‐1,6‐Dienynes Leading to Enantioenriched cis‐Hydrobenzofurans

Abstract

Chiral cis-hydrobenzofurans represent a unique motif existing in numerous natural products, for instance, isoambrox, [1] haterumaimide I, [2] rosenonolactone, [3] incarviditone, [4] and millingtonine A [5] (Scheme 1 a). Owing to their diverse biological activities, [1][2][3][4][5] a great deal of attention has been paid to the development of efficient methods toward their enantioselective syntheses. One of the most straightforward and powerful ways to construct such a framework is the catalytic asymmetric desymmetrization of cyclohexadienones (Scheme 1 b). In recent elegant reports, Rovis and co-workers demonstrated the feasibility of using chiral-NHC-catalyzed intramolecular Stetter reactions for the asymmetric desymmetrization of cyclohexadienones to prepare chiral cis-hydrobenzofuranones. [6] Very recently, Sasai and co-workers described the use of bifunctional chiral phosphinothiourea catalysts in a intramolecular Rauhut-Currier reaction for the enantioselective discrimination of cyclohexadienones. [7] Although these protocols [6][7][8] proved to be highly effective, their efforts were mainly focused on the application of chiral organocatalysts in intramolecular reactions with a limited substrate scope. Moreover, transition metal catalyzed asymmetric desymmetrization of cyclohexadienones is quite scarce. [9] During our continuous efforts in exploring rhodium/chiral diene-catalyzed asymmetric arylation, [10] we envisioned that a rhodium-catalyzed tandem arylrhodation/conjugate addition reaction of cyclohexadienone-containing [13,14] 1,6-dienynes, [11,12] which are accessible from dearomatization of corresponding phenols, [15] would provide a novel approach to these enantioenriched cis-hydrobenzofurans (Scheme 1 c). However, two major concerns need to be addressed in this rhodium-catalyzed asymmetric desymmetrization process.One is the competitive reaction between the arylrhodation of the carbon-carbon triple bond and two conjugate addition reactions of the cyclohexadienone with the arylboronic acid. The other is whether the chiral ligand coordinating to rhodium could efficiently discriminate between the mesocyclohexadienones in the cyclization step.With this in mind, several varieties of chiral ligands (Scheme 2) were evaluated for this rhodium-catalyzed asymmetric tandem arylrhodation/conjugate addition of (4-Scheme 1. Catalytic asymmetric desymmetrization of cyclohexadienones for preparing chiral cis-hydrobenzofurans. a) cis-Hydrobenzofurans as structural motifs in natural products. b) Organocatalytic asymmetric desymmetrization of cyclohexadienones. c) Our approach to enantioenriched cis-hydrobenzofurans.

Copper‐Catalyzed Asymmetric Borylative Cyclization of Cyclohexadienone‐Containing 1,6‐Dienes

“…Meantime, the main side product, p ‐cresol was also observed, which was presumably attributed to the direct conjugate borylation to enone and succedent β‐O elimination. Next, several chiral phosphine ligands, including ( S , S p)‐ip‐FOXAP ( L2 ), ( R )‐BINAP ( L3 ), ( R )‐P‐Phos ( L4 ) and ( R , R )‐iPr‐DuPhos ( L5 ) were subjected to this reaction, however, no promising outcomes were gave (Table , entries 2–5). To our delight, the ee value of 3 a dramatically rose up to 74%, albeit in low yield, when ( R , R )‐QuinoxP* ( L6 ) served as ligand (Table , entry 6).…”

Asymmetric transformations of achiral 2,5-cyclohexadienones

“…27 In this case, catalytic [Rh(C 2 H 4 ) 2 Cl] 2 was utilized with ( R )-BINAP as the chiral ligand to provide products 64 from internal alkynes 63 in excellent yields and with high levels of stereocontrol (Scheme 13). Once again, the efficiency and selectivity of the reaction were found to be largely insensitive to both substrate substitution and aryl boronic acid identity.…”

Regioselective β‐Arylation of α‐Angelica Lactone through Isomerization/Addition under Mild Conditions

“…[4g-j, 6] Rhodium-catalyzed 1,4-addition of organoboron reagents to a,b-unsaturated carbonyl compounds offersastraightforward way of constructingC ÀCb onds. [8,9] Various acyclica nd cyclic a,b-unsaturated carbonyl compounds (enones, esters, and amides) have been used for the Rh I -catalyzed 1,4-addition reaction. More recently,t ransition-metal-catalyzed isomerization/ 1,4-addition reactions were developed by Hayashi andc oworkers.…”

“…Lowering the temperature to room temperature increased the yield to 56 %o wing to the reduced dimerizationo fA L( entry 8). Moreover,e xamining the effect of common solvents in Rh I -catalyzed 1,4-addition reactions (i.e.,T HF,C H 3 CN, toluene,a nd 1,2-dichloroethane (DCE), we found that the yields were not improved (entries [9][10][11][12].V arious kindsofrhodiumcatalysts were also tested {i.e.,[Rh(COD)-OH] 2 ,[ Rh(COE) 2 Cl] 2 (COE = cyclooctene), [Rh(C 2 H 4 ) 2 Cl] 2 ,a nd [Rh(CO) 2 Cl] 2 }, and it was found that [Rh(C 2 H 4 ) 2 Cl] 2 was the best catalyst, ascribed to its easy and irreversiblel igand exchange.…”