J . Org. Chem., Vol. 43, No. 9, 1978
Asymmetric Hydrogenation of Piperitenone 30 min. To the cooled m i x t u r e was added dropwise enough 5% sodium hydroxide t o discharge the gray color. T h e m i x t u r e was filtered a n d dried, a n d t h e ether was removed by r o t a r y evaporation t o give 1.31 g (74%) of 2,5-dimethyl. 4-hexen-2-01. T h e spectral data was identical w i t h t h a t reported by Chandall.32 2,5-Dimethyl-2-acetoxyhexane(7). U s i n g the procedure described for t h e synthesis of l, 1.0 g (0.0077 mol) of 2,5-dimethyl-2hexanol, 0.87 g (0.0085 mol) of acetic anhydride, and 30 mL of pyridine gave 1.2 g (89%) of 7: IR (neat) 1735,1462,1381,1255,1220,1160,1140, 1118, 1085, 1020, 945 cm-'; NMR (CCld) 6 0.90 (6 H,d, J = 6 Hz), 1.1-1.8 (5 H,m ) , 1.40 ((3 H,s), 1.91 (3 H,s).
Acknowledgment. We would like to thank the National Science Foundation (NSF-URP), the California State University, Los Angeles Foundation, and the National Institutes of Health, Research Grant RR08104, Minority Student Training for Biomedical Research (MBS), for support of this research. Registry No.-1, 34106-07-5; 2, 65149-96-4; 3, 65149-97-5; 4, 142-30-3; 56323-20-7; 7, 65149-98-6; 2,5-dimethylhex-3-yne-2,5-diol, trans-2,5-dimethyl-3-hexene-2,5-diol, 927-81-1; 2,5-dimethylhexane-2,5-diol, 110-03-2; 2,5-dimethyl-2-hexanol, 3730-60-7.
References and Notes (1) (a) Portions of this work were presented at the 10th Western Regional Meeting of the American Chemical Society, San Francisco, Calif., Oct 16-18. 1974.(b) National Science Foundation Undergraduate Research Participant, Summer 1975.(c) MBS Trainee. (2)P. N. Rylander, "Catalytic Hydrogenation over Platinum Metals", Academic Press, New York, N.Y., 1967,pp 59-80:M.Friefelder, "Practical Catalytic Hydrogenation", Wiley-lnterscience, New York, N.Y., 1971,pp 96-109; E. N. Marvel and T. Li, Synthesis, 457 (1973). (3)H. Lindlar, Helv. Chin,. Acta, 35,446 (1952). (4)N. Anand, J. S. Bindra, and S.Raganathan, "Art in Organic Synthesis", Holden-Day, San Francisco, Calif., 1970. (5) D.Papa, F. J. Viliani, and H. F. Ginsberg, J. Am. Chem. SOC.,76,4446 (1954); J. Martel, E. Toromanoff, and C. Huynh, J. Org. Chem., 30, 1752 (1965);E. B. Hershberg, E. P. Oliveto, C. Gerald, and L. Johnson, J. Am. Chem. Soc., 73,5073 (1951);L. Ruzicka and P. Muller, Helv. Chim. Acta,
22,755 (1939). (6)E. 5.Maxted and A. G. Walker, J. Chem. Soc., 1093 (1948).For reviews, see E. B. Maxted, Adv Catal., 3, 129 (1951), and R. Baltzly, Ann. N.t: Acad. Sci., 145,31 (1967). (7)A . S.AI-Ammar, S. .J. Thomson, and G. Welch, J. Chem. SOC.,Chem. Commun., 323 (1977). (8) M. Freifelder, Adv. C,?ta/. 13. 203 (1963).
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(9)K. Kindler, H.-G. Helling, and E. Sussner, Justus Liebigs Ann. Chem., 605, 200 (1957). IO) G. F. Henion, W. A. Schroeder, R. P. Lu, and B. Scanlon, J. Org. Chem., 21, 1142 (1956);R. A. Raphael and F. Sondheimer, J. Chem. Soc., 2693
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S. H. Harper and R. J. D. Smith, J. Chem. Soc., 1512 (1955);E. B. Hershberg, E. P. Oliveto. C. Gerald, and L. Johnson, J. Am. Chem. Soc., 73,5073 (1951);D. J. Cram and N. L. Allinger, ibid., 78,2518 (1956). 12) T. FukuQ and T. Kusama. Bull. Chem. Soc. J m . 31. 339 (1958):T. Fukuda. /bid., 32,420 (1959). (13)R. J. Tedeschi and G. Clark, Jr., J. Org. Chem., 27, 4323 (1962);R . J. Tedeschi, H. C. McMahon, and M. S. Pawlak, Ann. N. Y. Acad. Sci., 145, 11)
91 (1967). (14)R. C. Cookson, D. P. G. Hamon, and R. E. Parker, J. Chem. SOC., 5014 (1962);G. C. Bond and J. S. Rank, Roc. Int. Congr. Catal., 3rd, 1964,2, 1225(1965);J. D. Bream, D. C. Eaton, and H. B. Henbest, J. Chem. SOC., 1974 (1957);J. F. Sauvage, R. H. Baker, and A. S. Husseg, J. Am. Chem. Soc., 83,3874 (1961). (15) R. J. D. Evans, S. R. Landor, andR. T. Smith, J. Chem. SOC.,1506 (1963); I. Nagaideli, Zh. Obshch. Khim., 33,379 (1963);A. Giger, M. Fetizon, J. Henniker, and L. Jacque, C. R. Hebd. Seances Acad. Sci., 251,2194(1960); W. G. Dauben, W. K. Hayes, J. S. P. Schwarz. and J. W, McFarland, J. Am. Chem. Soc., 82,2232 (1960). (16)R. J. Tedeschi. J. Org. Chem., 27, 2398 (1962). (17)K. Alder, H. V. Brachel. and K. Kaiser, Justus Liebigs Ann. Chem., 608, 195 (1957). (18)S. H. Harper and R. J. D.Smith, J. Chem. Soc., 1512 (1955). (19)S. Siegel and J. R. Cozort, J. Org. Chem., 40,3594(1975).and references contained therein; A. Steenhoek, 8. H. van Wisngaarden. and H. J. J. Pabon, Red. Trav. Chem. Pays-Bas, 90,961 (1971). (20)S. Siegel. Adv. Catal. 16, 123 (1966);R. L. Burwell and J. B. Peri, Annu. Rev. Phys. Chem., 15, 131 (1964). (21)E. W. Garbisch, Jr., L. Schreader, and J J. Frankei, J. Am. Chem. Soc.,
89,4233 (1967). I. V. Gostunskaya, N. B. Dobruserdova, and B. A. Kazanskii, Zh. Obshch. Khim., 27, 2396 (1957). W. G. Dauben, J-S. Paul Schwarz, W. K. Hayes, and P. D. Hance. J. Am. Chem. Soc., 62,2239 (1960). A. P. G. Kieboom, J. F. de Kreuk. and H. van Bekkum, J. Catal., 20, 58 (1971);S. Mitsui, Y. Kudo, and M. Kobayashi, Tetrahedron. 25, 1921
(1969). R. Baltzly, J. Org. Chem., 41,928 (1976). K . Wiberg, "Laboratory Technique in Organic Chemistry", McGraw-Hill, New York, N.Y., 1960,p 228. J. E. H. Hancock and D. R. Schenchenpflug, J. Am. Chem. Soc., 80,3621
(1958). K. Griesbaum, A. A. Oswald, and W. Naegele. J. Org. Chem., 29, 1887
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(29)R. Ya. Levina and Yu. S. Shabaroo, Vestn. Mosk. Univ., Ser. Fiz. Mat. Estestv. Nauk, No. 4,61 (1956);Chem. Abstr., 51, 7299b (1957). (30)U. Schollkopf, Angew. Chem., 71,260 (1959). (31)R. S. Bly and R. T. Swindell. J. Org. Chem., 30, 10 (1965). (32)J. K. Crandall. D.B. Banks, R. A. Colyer, R. J. Watkins, and J. P. Arrington, J. Org. Chem., 33,423 (1968).
Asymmetric and Regioselective Hydrogenation of Piperitenone by Homogeneous Rhodium Complexes John Solodar Corporate Research Department, Monsanto Co., S t . Louis, Missouri 63166 Receiued J u l y 19, 1977 Piperitenone (1) has been hydrogenated w i t h homogeneous r h o d i u m catalysts containing c h i r a l phosphine ligands. T h e major product, pulegone (2), has been obtained in up t o 38% o p t i c a l purity. Piperitone (3), menthone ( 5 ) , a n d ieomenthone (6) were t h e predominant m i n o r products.
Following the initial report of Knowles and Sabacky,la the use of homogeneous transition metal catalysts for asymmetric synthesis has grown tremendously.' In addition, the ability of homogeneous transition metal catalysts to effect selective transformation of functional groups2 has led to a recognition of the potential for such catalysts to operate on organic molecules in a highly specific manner. Piperitenone ( I ) offers a unique challenge in selective hydrogenation due to the presence of two different olefinic bonds and one ketonic bond. Hydrogenation of either one or more of these unsaturated sites leads to the structures 2-10, whereas
complete reduction leads to the four diasteromeric alcohols of the menthol series 11-14. In addition, piperitenone is prochiral and thus offers the possibility for asymmetric synthesis of pulegone (2) and piperitone (3).Achievement of chirality at C1 of 2 is particularly advantageous because the hydrogen atom a t C1 is not labile. Thus, whatever degree of chirality is attained in conducting an asymmetric hydrogenation of 1 to 2 is locked in on further reduction. Pulegone of high optical purity is thus the c o r nerstone of a direct synthesis of optically active menthol (11) since the configuration and enantiomeric excess obtained a t
0022-3263/78/1943-1787$C~1.00/0 0 1978 American Chemical Society
1788 J . Org. Chem., Vol. 43, No. 9, 1978
Table 1. Hydrogenation of Piperitenone
__ Run No.
Solodar
Temp,
"C
Ligand" Solcent
Press, psig
Conversion,%
Time, Pulegone, h %
1 2 3 4 5 6 7
(+)-15 (+)-15 (+)-15 (+)-15 (+)-15 (+)-15 (+)-15
DMFd DMF DMF DMF DMF DMF DMAd
80 60 40 80 60 60 60
180 180 180 120 120 325 180
96 94 74
8 9 10
(+)-15 (+)-15 (+)-15 (+)-15 (+)-15 (+)-15 (+)-15 (+)-15
MeOH MeOH MeOH MeOH MeOH MeOH MeOH MeOH
80 60 40 80 60 40 80 60
180 180 180 120 120 120 60 60
86 84 50 72 48 37 NA' 62
2.5 3.0 4.0 3.0 4.0 6.5
(-)-16 (-)-21 (-)-21 (+)-17 (+)-17 (+)-18 19g 20g (-)-21 (+)-22
DMF DMF DMF DMF DMF DMF DMF DMF MeOH MeOH MeOH
60 100 80 60 60 60 60 60 80 40 60
180 180 180 180 120 180 180 180 180 180 120
45 32 44 55 42 18 8 28 76
22 20 20 22 21 22 22 20 18 6.5 3.0
11 12
13 14 15 16 17 18 19 20 21 22 23 24 25 26
(+)-23
82 88
53 62
-
52
74 88 92 85 89 76 51
18 22 20 6 19 20 21
59 68 78 61 71
74 64 68
6.0
73 47 62 75 67 51 48 77 19
Product selectivity* PiperMenMinor peaks, itone, % thones,c % % 4 3 3 8
4 10
18
