J. Org. Chem. zyxwvut 1982,47, zyxwvu 1329-1334 1329 furan-2(3H)-one (10). Dry triethylamine (107 mg, 0.147 mL, 1.05 “01) was added via a syringe to alcohol zyxwvuts 9 (220 zyxwvut mg, 0.88 mol) in 3.7 mL of CHzClzat -5 “C to -10 “C under Nz with stirring. The reaction mixture was stirred for 5 min and methanesulfonyl chloride (111 mg, 0.075 mL, 0.97 mmol) was added dropwise via a syringe over a 10-min period. The reaction mixture was stirred between 0 and -10 “C for 2.75 h, diluted with 100 mL of CH2C12, and washed with 15 mL of cold HzO, 20 mL of 10% HC1,20 mL of 10% NaHC03, and 15 mL of brine. The organic solution was dried (MgS04)and concentrated in vacuo to afford a quantitative yield of 10 mp 89.5-90 “C; NMR (CDC13) 6 5.30-5.58 (m, 1 H), 4.59-4.92 (m, 1 H, CHOCO, unresolved), 4.42 (d, 2 H), 3.06 (s, 3 H); IR (KBr) 1765, 1340, 1360 cm-’. (3a8,4a(u,5a,9aP)-3a,4a,5,6,7,9,9a-Octahydro-4a,5-di- methyl-3-met hylenenapht ho[2,3- b ]furan-2 (3H) -one (1). DBU (0.191 g, 0.188 mL, 1.26 mmol) was added via a syringe over a 10-min period to sulfonate 10 (330 mg, 1.01 mol) in 4.5 mL of dry benzene under N2 with stirring at room temperature. The reaction mixture was stirred for 3 h and then diluted with 150 mI, of ether. The organic solution was washed with 10 mL of cold HzO, 15 mL of cold 10% HC1, and 10 mL of cold brine, dried (MgS04), and concentrated in vacuo, giving an oil. Chromatography on silica gel G and elution with hexanes and ether-hexane solutions af- forded (183 mg, 78%) of 1: mp 95.5-96.2 “C; NMR (PhD,) 6 6.01 (d, 1 H, J zyxwvu = -1 Hz, H-13), 5.10-5.40 (m, 1 H, H-l), 4.96 (d, 1 H, J = 1 Hz, H-13), 3.70-4.05 (m, 1 H), 2.10-2.60 (m), 1.65-2.0 (m), 0.85-1.60 (m, 5 H), 0.67 (d, J = 6 Hz), 0.63 (s,6 H); irradiation of the C-7 and C-9 hydrogens caused the multiplet at 6 3.70-4.05 to collapse to a singlet at 6 3.93; irradiation of the C-9 hydrogens caused the multiplet at 6 3.70-4.05 to collapse to a doublet at 6 3.93 (J7,* = 4-5 Hz); IR (CH2C12) 1770 cm-’; mass spectrum m/e 232 (M), 217, 190, 145, 119,105,91, 79. Anal. Calcd for CI6HzoO2: C, 77.55; H, 8.68. Found C, 77.79; H, 8.58. Acknowledgment. We thank the Research Adminis- tration Office (SMU) for partial support of this work, Mr. Ashby Johnson, Jr., and Dr. Larry Jaques for recording the 13C NMR spectra, and Mr. John Forehand of the A. H. Robins Co. for mass spectral data. Registry No. (i)-l, 80656-02-6; (&)-2, 20536-80-5; (&)-3, 20536- 77-0; (&)-4, 80594-80-5; (&)-5, 33118-42-2; (&)-6, 80594-81-6; (f)-7, 80594-82-7; (&)-8, 80594-83-8; (&)-S, 80594-84-9; (&)-lo, 80594-85-0. Synthesis of Chiral Dipeptides by means of Asymmetric Hydrogenation of Dehydro Dipeptides Iwao Ojima,* Tetsuo Kogure, Noriko Yoda, Tadashi Suzuki, Momoko Yatabe, and Toshiyuki Tanaka Sagami Chemical Research Center, Nishi-Ohnuma 4-4-1, Sagamihara, Kanagawa zyxw 229, Japan Received October 14, 1981 Asymmetric hydrogenation of various dehydro dipeptides was carried out by using rhodium complex catalysts with a variety of chiral diphosphine ligands. The efficiency of chiral diphosphine ligands as well as the effect of the chiral center in the substrate on the catalytic asymmetric induction was studied. It was found that extremely high stereoselectivities for producing the S,S, R,S, S,R, or R,R isomer were achieved with the proper choice of chiral ligands although a considerably large double asymmetric induction waa observed in some cases. Pyrro- lidinodiphosphines, e.g., Ph-CAPP, p-BrPh-CAPP, BPPM, CBZ-Phe-PPM, and diPAMP, exhibited excellent stereoselectivities, whereas chiraphos, prophos, and BPPFA only gave poor results especially for the reaction of N-acyldehydro dipeptide which had a free carboxylic acid terminus. Stereoselective dideuteration was also successfully performed. It is well-known that the general methods for the for- mation of peptide linkage are based on the coupling of two optically active amino acid components by using, e.g., the acyl chloride method, the acyl azide method, the mixed anhydride method, the carbodiimide method, and the enzyme method. These methods have been developed for the synthesis of naturally occurring polypeptides with minimum racemization. Recently, it has been shown that significant modification of biological activities can be effected through inversion of configuration at one or more chiral centers or through replacement of one or more “natural” amino acid resi- due(s), by “unnatural” amino acid components in a bio- logically active polypeptide such as enkephalin, vaso- pressin, angiotensin 11, gonadoliberin, and other hormones.’ As an approach to the synthesis of chiral olgio- and po- lypeptides with desired structures, it is important to de- velop a facile device which gives a chiral building block for peptide synthesis other than the simple preparation of “unnatural” amino acids. As precursors of modified peptides, dehydro peptides are interesting candidates since catalytic asymmetric hydrogenation, in principle, can convert the dehydro amino acid residue into the amino acid residue with either R or S configuration. In this context, the asymmetric hydrogenation of dehydro dipeptides giving chiral dipeptides is a significant model reaction. We reported the preliminary results on the asymmetric syn- thesis of dipeptides by means of asymmetric hydrogenation catalyzed by chiral rhodium complexes in 1980: and in the same year Kagan et al.,3 and Onuma et al.4 also reported similar results independently. Now, we will describe here a full account of our research on this approach to the synthesis of chiral dipeptides. Results and Discussion As the homogeneous asymmetric hydrogenation of dehydro-a-amino acids catalyzed by rhodium complexes with chiral diphosphine ligands has turned out to be quite effective for the synthesis of chiral a-amino acids: it would (1) For example: Gross, E.; Meienhofer, J. In “The Peptides”; Aca- demic Press: New York, 1979, Vol. 1, Chapter 1. (2) Ojima, I.; Suzuki, T. Tetrahedron Lett. 1980, 1239. (3) Meyer, D.; Poulin, 3.-P.;Kagan, H. B.; Levine-Pinto, H.; Morgat, (4) Onuma, K.; Ito, T.; Nakamura, A. Chem. Lett. 1980, 481. J.-L.;Fromageot, P. J. Org. Chem. 1980, 45, 4680. 0022-3263/82/1947-1329$01.25/0 0 1982 American Chemical Society