Stereoselective Disposition of the Geminal Dimethyl Group in the Cyclization of Geranyl Acetate under Zeolite Confinement Conditions

Abstract

The stereochemistry in the acid-catalysed biomimetic cyclization of [8,8,8-D 3 ]geranyl acetate was examined in solution and under conditions of zeolite Y confinement. In the intrazeolite reaction the gem-allylic methyl group adopts a diastereoselective disposition in the cyclization product (64 % dr). In contrast, the gem-dimethyl disposition in a homogeneous medium (ClSO 3 H/2-nitropropane) proceeds

Acid‐Catalyzed Cyclization of Terpenes Under Homogeneous and Heterogeneous Conditions as Probed Through Stereoisotopic Studies: A Concerted Process with Competing Preorganized Chair and Boat Transition States

“…Identical results were found by performing the ClSO 3 H-catalyzed reaction in the less polar CH 2 Cl 2 (À78 8C). The results presented in Scheme 5 resemble substantially the stereochemical outcome in the cyclization of [D 3 ]-1 [24] (Scheme 3). A further mechanistic approach regarding the cyclization of geranyl acetate was performed by measuring the intermolecular kinetic b-secondary isotope effects upon competition …”

“…We decided to compare the value of k H /k D % 1.3 to the kinetic b-secondary isotope effect during the FeCl 3 -catalyzed [27] cyclization of 6,7-epoxy geraniol ([D 0 ]-14) and its labeled counterpart [D 6 ]-14 [26] (Scheme 6) because the acidcatalyzed cyclization of epoxy polyene terpenes is a well-established concerted process. In the presence of FeCl 3 (1.0 equiv, CH 2 Cl 2 , 208C), 6,7-epoxygeraniol yields a mixture of the carbocyclization product 15 [14] and the bicyclic ether 16, [14] [24] or under homogeneous conditions without detectable isomerization of the noncyclized starting material. This implies that the low diastereoselection under homogeneous conditions (products 3 and 4), or the higher diastereoselection under heterogeneous conditions (products 11 and 12) does not result from any isomerization on the terminal double bond, C6=C7, of [D 3 ]-1 prior to cyclization.…”

“…(E)-6-(tert-Butyldiphenylsilyloxy)-4-methylhex-4-enoic acid (6): A solution of NaClO 2 (13.6 g, 150.3 mmol) and NaH 2 PO 4 (17.9 g, 114.6 mmol) in water (90 mL) was added over 20 min to a stirred solution of 5 [24] (6.0 g, 16.4 mmol) and 2-methyl-2-butene (45 mL) in tert-butanol (240 mL). The mixture was stirred at ambient temperature for 12 h and then diluted with water (200 mL).…”

“…]-1) a significant difference was found regarding the stereochemical disposition of the gem-dimethyl group in the cyclized a-or g-cyclogeranyl acetate on going from homogeneous (ClSO 3 H, 2-nitropropane, À78 8C) to heterogeneous (zeolite NaY) conditions (Scheme 3). [24] Under homogeneous conditions the diastereomeric products 3 and 4 are formed in almost equimolar amounts, with 3 slightly prevailing, whereas under heterogeneous conditions 3 substantially predominates over 4. Although we postulated that within the zeolite cavities an initially formed tertiary carbocation possibly undergoes cyclization at a faster rate than the rotation around the terminal Me 2 C + À C bond, we also considered the possibility of cyclization through competing chair and boat transition states.…”

“…The synthesis of [D]-1 was accomplished with > 97 % deuterium incorporation on C-6 by following the procedure shown in Scheme 4. The known aldehyde 5 produced by the oxidative cleavage of the TBDPS-protected 6,7-epoxygeraniol [24] (TBDPS = tert-butyldiphenylsilyl) was oxidized with NaClO 2 to the corresponding carboxylic acid 6. The acid 6 was reduced with LiAlD 4 to form the labeled [D 2 ]-alcohol 7, which was oxidized with pyridinium chlorochromate (PCC) to yield the deuterated aldehyde 8.…”