No abstract

COMMUNICATIONS enantiomeric efficiencies of this method are fully comparable to those of the enzymatic procedure. 4) This method can provide highly vcrsatilc cyclohexenone chiral synthons very efficiently. 5 ) The reaction mechanism has been proven to include a suprafacial 1.3-hydrogen migration pathway. E.uprrinzcntal ProcedureTranzforiiiatioii o i 6 c into 5b. To a stirred solution of 6 c (405 mg. 1.0 mmol) in I,?-dichloroetliane (4.6 mL) was added [Rh:(S)-hinap)(cod)]ClO~ (18.6 mg. 19.9 inniol) i n 1 .Z-dichloroethane (0.5 mL) dropwise at room temperature under argon ;ind the niiytiire w'as relluxed for 17 11. The solvent was evaporated. the residue dissolved 111 T H F ( 5 mL). and the resulting solution stirred with nBu,NF ( I 0 M in 7 IfF, 1 0 inl,) at 0 ' C for 5 min. The solution was diluted with ether and washed succeaiwly with water and brine. dried over MgSO,. and concentrated under reduced pressure. The residue was chromatographed on silica gel (EtOAc: hexanc 1.9) to gi%e 5b a s colorless crystals (276 mg, 94.9%) (96.1 % LT). A single recrystallmition from hexane give the optically pure material (99.5 "/ o ee) as colorless prism\. m p 32 C. [r];' = -27.0 ((, = 1.08 in CHCI,).

COMMUNICATIONSall-E content characteristic of the double elimination process holds for the present case as well: all-E:9Z:[(lIZ) + (13Z)l = 91 :4:5.We compared this new process with those used commerciall~.[~] The Hoffmann-La-Roche process involves a C,, + C, route, and BASF makes use of the Wittig reaction between C,, and C, building blocks. Rh6ne-Poulenc also employs the C,, + C, combination based on the Julia sulfone coupling. Our strategy is novel in that two C , , components are coupled. The C,, skeletons are one of the most common units in terpenoid derivatives and, accordingly, readily available. As a whole, our process has the twofold benefit of ready availability of the starting materials and simple operation.[61 We have shown that the following reactions can be integrated: a) addition of carbanion to carbonyl, b) 0-alkylation of the addition product, and c) successive elimination of the alkoxy and sulfinyl groups. The only modification of the stepwise process is made for the 0-alkylation. This results in not only compaction of the process but increase in the total yield. Although we took up a rather simple case in this study, it has proved that even a slight modification can bring about critical improvements of the chemical process. This suggests the importance and potential of the integrated chemical process for designing a synthesis. Experimental SectionNaI (225 mg. 1.5 mmol), cyclogeranyl sulfone 1 [3c] (362 mg, 1.3 mmol), and T H F (2 mL, dried over sodium benzophenoneketyl) were placed in a flame-dried, twonecked flask. A solution of BuLi in hexane (1.6 M, 0.75 mL, 1.2 mmol) was added, and the mixture stirred at -78 "C (dry ice/MeOH) under argon for 1 h. After thc addition of aldehyde 2 [3c] (211 mg, 1.0 mmol) in T H F (1 mL) followed by MOMCI (0.09 mL, 1.2 mmol), the solution was stirred for 4 h at -78°C and 1 h at room temperature. Cyclohexane (3 mL) and KOMe (701 mg, 10 mmol) were added, and the mixture stirred for 1 h at room temperature and 1 h at 40°C. The reaction was quenched with aqueous NaHCO, solution (10 mL) and ethyl acetate (15 mL). After separation of the organic layer and extraction of the aqueous phase with ethyl acetate (2 x 15 mL), the combined organic fractions were washed with brine (20 mL), dried over MgSO,, and concentrated under reduced pressure (crude, 452 mg). Hexane ( 5 mL), pyridine (0.5 mL), acetic anhydride (2 mL), and DMAP (48 mg, 0.4 mmol) were added to the crude product under argon, and the mixture stirred for 1 h at room temperature. Aqueous NaHCO, solution (20 mL) and ethyl acetate (15 mL) were added at 0"C, and the organic layer separated. The aqueous phase was extracted with ethyl acetate (2 x 15 mL), and the combined organic fractions washed with brine (20 mL), dried over MgSO, and concentrated under reduced pressure (crude, 504 mg). The crude oil was analyzed by HPLC; 76% yield, 248 mg, all-E:9Z:[(llZ) + (13Z)l = 91:4:5 (column: ZORBAX SIL 4.6mmx 25 cm; eluent: terr-butylmethyl ether/hexane 51100; internal standard: 2,6-xylenol).