Design of an Organocatalyst for the Enantioselective Diels−Alder Reaction with α-Acyloxyacroleins

Abstract

We have realized the first enantioselective organocatalytic Diels-Alder reaction between alpha-substituted acroleins, such as alpha-acyloxyacroleins, and not only cyclic but also acyclic dienes. alpha-Acyloxyacroleins are useful as synthetic equivalents of alpha-haloacroleins. The present catalyst could be prepared in situ from pentafluorobenzenesulfonic acid (2.5-3.0 equiv) and chiral triamine (1 equiv) derived from H-l-Phe-l-Leu-N(CH2CH2)2. The enantioselective Diels-Alder reaction of 5-(benzyloxymethyl)cyclopentadiene, cyclopentadiene, cyclohexadiene, 2,3-dimethylbutadiene, and isoprene with alpha-(p-methoxybenzoyloxy)acrolein catalyzed by the above chiral ammonium salt (2.5-20 mol %) at -20-22 degrees C gave the corresponding adducts with 83, 83, 91, 92, and 88% ee, respectively.

Enantioselective Diels–Alder Reaction of α‐Acyloxyacroleins Catalyzed by Chiral 1,1′‐Binaphthyl‐2,2′‐diammonium Salts

“…Diamines 2c, [16] 2d, [17] 2e, [18] 3a [19] were prepared according to the reported procedure. a-(p-Methoxybenzoyloxy)-acrolein (Table 3), [9,11] a-(cyclohexanecarbonyloxy)acrolein (Tables 3-5), [9] a-(cyclopentanecarbonyloxy)acrolein (Tables 3 and 5), [11] (Tables 1 and 2), [9,11] (Table 3), [9,11] …”

“…[9,11] (Tables 3 and 5) This compound was prepared according to the reported procedure. [9,11] Representative Procedure for the Enantioselective Diels-Alder Reaction: [11] To a solution of (S)-2a (5.7 mg, 0.02 mmol) and trifluoromethanesulfonimide (10.7 mg, 0.038 mmol) in propionitrile or nitroethane (0.8 mL) was added a-acyloxyacrolein (0.4 mmol). After cooling to À75 8C, diene (1.6 mmol) was added to the solution, and the reaction mixture was stirred at À75 8C for several hours.…”

“…The ee and the absolute configuration of major enantiomer were established according to the reported procedure [9,11] by HPLC analysis (Daicel Chiralcel OJ-H column, hexane-i-PrOH = 40:1, flow rate = 1 mLmin…”

“…The ee and the absolute configuration of major enantiomer were established by the same procedure as described above for (À)-(1S,2S,4S)-2-formylbicyclo- + : 349.1804. The ee was determined, according to the reported procedure [9,11] by chiral HPLC (Daicel OD-H, hexane-i-PrOH = 40:1, flow rate 0.5 mL min…”

“…Recently, we reported the enantioselective organocatalytic Diels-Alder reaction with a-acyloxyacrolein. [9] Our catalyst is the chiral ammonium salt of the chiral triamine 1 bearing a primary aliphatic amino group with pentafluorobenzenesulfonic acid (C 6 F 5 SO 3 H). [10] The Diels-Alder reactions of acyclic dienes and cyclohexadiene with a-(p-methoxybenzoyloxy)acrolein give the adducts with high enantioselectivities.…”