Chiral Lewis Base-Assisted Brønsted Acid (LBBA)-Catalyzed Enantioselective Cyclization of 2-Geranylphenols

Abstract

Chiral Lewis base-assisted Brønsted acids (Chiral LBBAs) have been designed as new organocatalysts for biomimetic enantioselective cyclization. A salt of a chiral phosphonous acid diester with FSO(3)H catalyzes the enantioselective cyclization of 2-geranylphenols to give the desired trans-fused cyclized products with high diastereo- and enantioselectivities (up to 98:2 dr and 93% ee).

Selective Bromocyclization of 2‐Geranylphenols Promoted by Phosphite–Urea Cooperative Catalysts

“…We recently reported nucleophilic phosphite–urea cooperative catalysts 1b and 2b (Scheme ), which had high turnover rates for the highly selective bromocyclization of homogeranylarenes . Only 0.5 mol% of 2b successfully catalyzes the bromocyclization of 4‐homogeranyltoluene ( 3 ) to give the corresponding bromocyclization product in 94% yield (Scheme ).…”

Asymmetric Hydroalkoxylation of Non‐Activated Alkenes: Titanium‐Catalyzed Cycloisomerization of Allylphenols at High Temperatures

“…[8] Alternative approaches to catalytic,stereo-or regioselective hydroalkoxylations rely on photocatalysis [9] or oxidation-reduction processes. [10,11] We now report the redox-neutral, asymmetric hydroalkoxylation of an on-activated alkene that is catalyzed by ac hiral titanium-carboxylate complex under thermally forcing conditions (220-240 8 8C). Thec yclization of 2-allylphenols (1)t o2 -methylcoumarans (2-metyl-2,3-dihydrobenzofurans; 2)s erved as the test reaction to screen for hydroalkoxylation catalysts (see Table 1).…”

Construction of Bridged Polycyclic Systems by Polyene Cyclization

“…An umber of meroterpenoids containing ab ridged [7.3.1.0 2,7 ] tricyclics ystem and their derivatives have been isolated and characterized as fungal metabolites since the discovery of neoaustin in 1994 ( Figure 1). [1,2] Although some of these natural products have been reported to display remarkable biological activities (e.g.,i nhibition of caspase-1), studies toward the synthesis of these meroterpenoids have not been reported to date.…”

“…[4] Polyenec yclization is aw ell-known reaction that was first reported in the 1920s [5] and has been extensively studied for 60 years. [6,7] Utilizing this biomimetic reaction, multiple rings can be formedi nasingle operation and stereocenters are installed in as tereoselective manner in many cases. The syntheticu tility of the reaction has been demonstratedb yt he total syntheses of many naturalp roducts containing af used polycyclic ring system.…”

“…With a[ 7.3.1.0 2,7 ]t ricyclic framework successfully constructed, we next undertook an investigation into the extension of the protocolt oc onstruction of at etracyclic system.A se xpected, treatment of vinyl epoxide 22 [33] with Et 2 AlCl in CH 2 Cl 2 at À78 8Cr esulted in the simultaneous creationo ft hree six-membered rings, providing tetracyclo[11.3.1.0 2,11 .0 5,10 ]heptadecane derivative 23 in 37 %y ield (Scheme 4). While there is considerable room for improvement in the chemical yield of 23,t he average yield of approximately 72 %p er ring formed would be acceptable considering the suggestion by Corey and Shenvi that the chemical polycyclizations proceed at best with an efficiency of 70-80% per ring formed.…”