4897
J. Am. Chem. SOC.1990,112,4897-4905 spectrum, m / z 258.1 (MH').
GN500 N M R spectrometer.
Acknowledgment. This work was supported by an unrestricted grant from Eli Lilly and Company. Grants N I H 1531957 and N S F C H E 85-14500 provided funds for the General Electric
Supplementary Material Available: IH and 13CN M R spectral data recorded for (CD,)$O solutions (3 pages). Ordering information is given on any current masthead page.
Mechanism of the Asymmetric Isomerization of Allylamines to Enamines Catalyzed by 2,2'-Bis( dipheny1phosphino)-1,l '-binaphthyl-Rhodium Complexes Shin-ichi Inoue,t*tHidemasa Takaya,*sl Kazuhide Tani,l Sei Otsuka,ll Tsuneo Sate,+ and Ryoji Noyori*.t Contribution from the Department of Chemistry, Nagoya University, Chikusa, Nagoya 464, Japan, the Chemical Materials Center, Institute for Molecular Science, Myodaiji, Okazaki 444, Japan, and the Department of Chemistry, Faculty of Engineering Science, Osaka University, Toyonaka, Osaka 560, Japan. Received September 18, 1989
Abstract: Cationic Rh complexes containing the 2,2'-bis(diphenylphophino)-l,l'-binaphthyl (BINAP) ligand catalyze a highly enantioselective isomerization of diethylgeranylamine or -nerylamine to give (R)-or (S)-citronellal (E)-diethylenamine in >95% ee. A new, nitrogen-triggered mechanism is postulated for the double-bond-migration reaction on the basis of IH and 31PNMR studies, kinetic measurements, and deuterium-labelingexperiments. The initial nitrogen-coordinatedallylamineRh+ complex causes a four-centered hydride elimination from C( 1) via dissociative mechanism to generate a transient iminium-RhH complex. Delivery of the hydrogen from Rh to C(3) gives the enamine q3-complex. The latter, having an aza-allyl structure, serves as the chain carrier in the catalytic cycle. The BINAP-Rh+ complexes differentiate efficiently the enantiotopic C( 1) hydrogens of the allylamines through interaction with the adjacent nitrogen atoms. The overall 1,3-hydrogen shift occurs in a suprafacial manner from an s-trans-type conformer of the flexible substrates. The origin of the chiral recognition has been interpreted in terms of the chiral environments of the BINAP-based Rh+ complexes.
The successful design of the 2,2'-bis(dipheny1phosphino)1,l'-binaphthyl (BINAP) ligand (l),l characterized by C2chirality, a fully arylated structure, and molecular pliancy, has allowed innovative asymmetric catalyses with transition-metal complexes.2 The cationic Rh complexes possessing this unique diphosphine ligand cause asymmetric isomerization of diethylgeranylamine (2) or -nerylamine to give citronellal (E)-diethylenamine (3) in >95% ee., This highly enantioselective cSH5)2
' '
0
(R)-1
Scheme I
8 '
P(CdtJz
'
2
(C6H5)2
0 (s)-1
reaction now serves as a key step in the industrial production of (-)-menthol (4)4 (Scheme I), providing an example of the most effective applications of transition-metal-catalyzed asymmetric reactions in homogeneous phase which have been developed during the past two decadess We describe herein the mechanism and steric course of the isomerization, elucidated by using 'H and 31PN M R techniques, kinetic study, and deuterium-labeled experiments. For transition-metal-catalyzed double bond migration, two mechanisms have Nagoya University. *Visiting scientist at Nagoya University from the Department of Applied Chemistry, Aichi Institute of Technology, Toyota 470-03, Japan. 4 Institute for Molecular Science. Present address: Department of Industrial Chemistry, Faculty of Engineering, Kyoto University, Kyoto 606, Japan. Osaka University.
A 4
been recognized.6 One is the metal hydride addition-elimination mechanism (eq 1)' and the other is the *-allyl mechanism resulting ( I ) (a) Miyashita, A.; Yasuda, A.; Takaya, H.;Toriumi, K.; Ito, T.; Souchi, T.; Noyori, R. J . Am. Chem. Soc. 1980, 102, 7932. (b) Miyashita, A.; Takaya, H.;Souchi, T.; Noyori, R. Tetruhedron 1984. 40, 1245. (c) Noyori, R.; Takaya, H.Chemicu Scriptu 1985, 83, 25. (d) Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumobayashi, H.; Taketomi, T.; Akutagawa, S.; Noyori, R. J . Org. Chem. 1986, 51, 629.
0002-7863/90/ 15 12-4897$02.50/0 0 1990 American Chemical Society
4898 J. Am. Chem. SOC.,Vol. 112, No. 12, 1990 Scheme I1
-7-i L S
vpYL Rh*
v p R h * /L
7 - ST L P-P
BINAP
5, L = acetone, THF, N(CzH,),, etc.
in an intramolecular 1,3-hydrogen shift (eq 2).* However, many lines of evidence indicate that the Rh-catalyzed isomerization of allylamines proceeds via a new, nitrogen-triggered mechanism (eq
3).
~
(2) (a) Noyori, R.;Ohta. M.; Hsiao, Yi; Kitamura, M.; Ohta, T.; Takaya, H. J. Am. Chem. Soc. 1986,108,7117. (b) Takaya, H.; Ohta, T.; Sayo, N.; Kumobayashi, H.; Akutagawa, S.;Inoue, S.; Kasahara, I.; Noyori, R.1. Am. Chem.Soc. 1987,109,1596. (c) Ohta, T.; Takaya. H.; Kitamura, M.; Nagai, K.; Noyori, R.J . Org. Chem. 1987,52, 3174. (d) Noyori, R.;Ohkuma, T.; Kitamura, M.; Takaya, H.; Sayo, N.; Kumobayashi, H.; Akutagawa, S. J . Am. Chem. Soc. 1987, 109, 5856. (e) Kitamura, M.; Manabe, K.; Noyori, R.;Takaya, H. Tetrahedron Lett. 1987,28,4719. (f) Kitamura, M.; Hsiao, Yi; Noyori, R.;Takaya, H. Tetrahedron Lett. 1987,28,4829. (8) Ohta, T.; Takaya, H.; Noyori, R. Inorg. Chem. 1988, 27, 566. (h) Kitamura, M.; Ohkuma, T.; Inoue, S.; Sayo, N.; Kumobayashi, H.; Akutagawa, S.;Ohta, T.; Takaya, H.; Noyori, R.J. Am. Chem. Soc. 1988,110,629. (i) Kitamura, M.; Kasahara, 1.; Manabe, K.; Noyori, R.;Takaya. H. J . Org. Chem. 1988, 53,708. (i)Kitamura, M.; Ohkuma, T.; Takaya, H.; Noyoti, R.Tetrahedron Lett. 1988.29, 1555. (k) Nishi, T.; Kitamura, M.; Ohkuma, T.; Noyori, R. Tetrahedron Lett. 1988, 29, 6327. (1) Noyori, R.;Ikeda, T.; Ohkuma, T.; Widhalm, M.; Kitamura, M.; Takaya, H.; Akutagawa, S.;Sayo, N.; Saito, T.; Taketomi, T.; Kumobayashi, H. J. Am. Chem. Soc. 1989, Ill, 9134. (m) Noyori, R. Chem. Soc. Rev. 1989, 18, 187. (3) (a) Tani, K.; Yamagata, T.; Otsuka, S.; Akutagawa, S.;Kumobayashi, H.; Taketomi, T.; Takaya, H.; Miyashita, A.; Noyori, R.J. Chem. Soc., Chem. Commun. 1982,600. (b) Tani, K.; Yamagata, T.; Akutagawa, S.;Kumabayashi, H.; Taketomi, T.; Takaya, H.; Miyashita, A.; Noyori, R.;Otsuka, S . J. Am. Chem.Soc. 1984,106,5208. (c) Tani, K.; Yamagata, T.; Tatsumo, Y.; Yamagata, Y.; Tomita, K.; Akutagawa, S.;Kumobayashi, H.; Otsuka, S. Angew. Chem., Int. Ed. Engl. 1985, 24, 217. (4) The catalytic process is working on up to a 74011 scale at Takasago International Co. Ltd., Japan. ( 5 ) To our best knowledge, the first example was given in 1966 Nozaki, H.; Moriuti, S.; Takaya, H.; Noyori, R. Tetrahedron Lett. 1966,5239. For a pertinent review, see: Kagan, H. B. Comprehensive Organometallic Chemistry;W i b n , G., Stone, F. G. A., Abel, E. W., Eds.; Pergamon h: Oxford, 1982; Vol. 8 , p 463. Asymmetric Synthesis; Morrison, J. D., Ed.; Academic Press, Inc.: Orlando, FL, 1985; Vol. 5. Noyori, R.;Kitamura, M. Modern Synthetic Methods;Scheffold. R.,Ed.; Springer Verlag: Berlin, 1989; p 115. (6) For review, see: Parshall, G. W. Homogeneous Catalysis; Wiley: New York, 1980; Chapter 3. Orchin, M. Advances in Catalysis, Eley, D. D., Pines, H., Weisz, P. B., Eds.; Academic Press: New York, 1966; Vol. 16, pp 1-47. Chaloner, P. A. Handbook of coordination Catalysis in Organic Chemistry; Butterworths: London, 1986; Chapter 5. (7) (a) Tolman. C. A. J . Am. Chem. Soc. 1972,91, 2994. (b) Hendrix, W. T.; Von Rosenberg, J. L.J. Am. Chem. Soc. 1976,98,4850. (c) Cramer, R. J. Am. Chem. Soc. 196688.2272. (d) Clark, H. C.; Kurosawa, H.Inorg, Chem. 1973,12, 1566. ( 8 ) (a) Hendrix, W.T.; Cowherd, F. G.; Von Rosenberg, J. L. J. Chem. Soc., Chem. Commun. 1968.97. (b) Cowherd, F. G.; Von Rosenberg, J. L. J. Am. Chem. Soc. 1%9,91,2157. (c) Casey, C. P.; Cry, C. R.J. Am. Chem. Soc. 1973,95,2248. (d) Bingham, D.; Hundson, B.; Webster, D. E.; Wells, P. B. J. Chem. Soc., Dalton Tram. 1974, 1512.
Inoue et al.
Results and Discussion Behavior of the BINAP-Rh+ Complexes in the Presence of Donor Molecules. As outlined in Scheme 11, the square-planar d8 Rh+ complexes of type [Rh(binap)S2]+ (S = solvent or other coordinative molecule) undergo ligand exchange reaction with other donor ligands (L). The reaction proceeds with retention of configuration via an associative mechanism probably involving transient trigonal-bipyramidal intermediates? Occurrence of such ligand exchange was conveniently monitored by 31P NMR spectroscopy (162 MHz, 85% H3P04as external standard).*O The complexes of type [Rh(binap)S2]+ or [Rh(binap)L,]+ have two homotopic phosphorus atoms, exhibiting a doublet split by Rh-P coupling. The phosphorus nuclei of the mixed-ligand complex, [Rh(binap)SL]+,however, are diastereotopic and hence the mutual coupling gives two sets of doublets of doublets (eight-line signals). Thus when [Rh((S)-binap)(CH30H)2]C104 was dissolved in acetone-d6 at -80 "C and the temperature was raised to 0 "C, the 31PNMR spectrum showed only one doublet centered at 6 53.52 (JRh-p = 199.6 Hz) due to [Rh((S)-binap)(a~etone-d~)~]C104. Addition of 5 equiv of triethylamine, an inactive analogue of 2, to this solution at -40 OC produced [Rh((S)-binap)(acetone-d6)(triethylamine)]C104 exhibiting two doublets of doublets at 6 43.53 (JRtP= 191.8 Hz, Jpp = 47.0 Hz) and 53.90 ( J u - p = 21 7.1 Hz), and then [ Rh((S)-binap)(triethylamine)2]C104 which showed a single doublet at 6 51.60 (JRh-p = 195.7 Hz). The ligand-exchange reaction with the tertiary amine took place only above -60 "C. At -80 "C, no change was observed in the ,IP NMR spectrum. The IH NMR spectrum showed line broadening and a -0.1 ppm downfield shift of the methylene signal of triethylamine, ascribable to rapid, reversible formation of a donoracceptor complex between [Rh((S)-binap)(acet~ned~)~]+and triethylamine. No signals due to intermediary pentacoordinated complexes were detected at -80 OC. Addition of 10 equiv of 2-methyl-2-butene (a trisubstituted olefin related to 2) did not cause any spectral change in the temperature range -80-25 O C . I o The bis-BINAP complex, [Rh((S)-binap),]C104 is rather inert to the ligand exchange, but a 31P NMR study confirmed that ligand displacement between this complex (31Pdoublet at 6 27.24) and triethylamine (20 equiv) could occur at 90" C, giving some free BINAP (6 -13.97) and [Rh((S)-binap)(triethylamine)2]C104. Mechanism of the Rh-Catalyzed Isomerization of Mylamines. The simplest mechanism of the BINAP-Rh complex-promoted isomerization of diethylgeranylamine (2) and other related allylic amines is outlined in Scheme 111, where structures of the allylic amines are simplified. The reaction starts from the simple nitrogen-coordinated Rh+ complex 6 generated by ligand exchange between the bis-solvent complex 5 and the substrate 2. The square planar complex 6 undergoes ,&elimination via liberation of the solvent molecule" to form a transient iminium-RhH T complex 7.'*J3 This complex is converted to the q3 enamine complex 8 by delivery of the hydrogen atom from Rh to C(3). The aza-allyl type structure 8 acts as catalyst in the real catalytic cycle involving 9 in place of 6. Liberation of the enamine product from the mixed (9) Basolo, F.; Pearson, R. G. Mechanism oflnorganic Reactions; Wiley: New York, 1967; Chapter 5 . Cattalini, L.; Ugo, R.;Orio, A. J. Am. Chem. Soc. 1968,90,4800. (IO) Chemical shift of 3'P signals of BINAP-Rh+ complexes is highly dependent on the nature of the trans ligands. Phosphorus atoms trans to oxygen or nitrogen ligands give signals at low field, 4Q5-4 ppm, while signals due to the nuclei trans to olefinic ligands (norbomadiene, I,S-cyclooctadiene, etc.) appear at rather high field, 25-26 ppm. See also ref lb. (1 1) The reaction has bcen conceived to occur directly from 16-electron complex 6 or 9." We deeply appreciate a referee pointing out the significance of the dissociative mechanism. See: Thorn, D. L.; Hoffmann, R. J. Am. Chem. Soc. 1978, 100, 2079. For stable 14-electron, T-shaped tricoordinatc Rh(1) complexes, see: Yoshida, T.; Okano, T.; Thorn, D. L.; Tulip, T. H.; Otsuka,S.;Ibers, J. A. J . Organomet. Chem. 1979, 181, 183. (12) Murahashi, S.;Watanabe, T. J . Am. Chem. Soc. 1979, 101, 7429. Shvo, Y.; Laine, R. M. J. Chem. Soc., Chem. Commun. 1980,753. Laine, R. M.; Thomas, D. W.; Cary, L. W.; Buttrill, S.E. J . Am. Chem. Soc. 1978, 100, 6527. Shvo, Y.; Thomas, D. W.; Laine, R. M. Ibid. 1981, 103, 2461. Gamage, N. S.;Morris, R. H.; Rettig, S. J.; Thackray, D. C.; Thorburn, I. S.; James, B. R.J. Chem. Soc., Chem. Commun. 1987, 894. (13) For q2-iminium-metal complexes, see: Fong, C. W.; Wilkinson, G. J . Chem. Soc., Dalton Trans. 1975, 1100.
Isomerization Catalyzed by BINAP- Rhodium Complexes
J . Am. Chem. SOC.,Vol. 11 2, No. 12, 1990 4899
Scheme I11
5 allylamlna
9
ligand complex 9, giving a 14-electron species, is followed by immediate hydride elimination to form 7, which goes back to 8. Thus the catalytic cycle is completed. To test the validity of this mechanism, reactions of geranylamine 2 and BINAP-Rh+ complexes were examined by N M R at temperatures ranging from -80 O C to room temperature, and the presence of several species given in this scheme was proven. As has been observed with triethylamine model, the substrate 2 has only a weak interaction with [Rh((s)-binap)(a~etone-d,)~]+ a t -80 OC; the 'H N M R spectrum of the equimolar mixture of 2 and [Rh((S)-binap)(acet~ne-d~)~]ClO~ in acetone-d6 (each 0.01 M) displayed merely line broadening and slight downfield shift of the NCH2CH3signal. The 31PN M R spectrum showed a single doublet at 6 53.25 and no signal change was observed, suggesting maintenance of the original tetracoordinate Rh structure. However, when the mixture was warmed up to -60 OC, the intensity of the doublet decreased with concomitant appearance of a pair of four-line signal, centered at 6 30.42 (Jbp = 193.7 Hz, Jp-p = 58.7 Hz) and 49.87 (JRh-p= 193.7 Hz). The signal pattern indicates the presence of two diastereotopic phosphorus nuclei and we assigned this complex to the $-enamine complex 8 possessing an aza-allyl structure. These new signals developed substantially at -40 OC, but still a considerable amount of the starting bisacetone-Rh complex remained unchanged. Above 0 OC, this same reaction proceeded smoothly, and toward the end of the reaction a new doublet emerged at 6 50.99 (JWp= 199.5 Hz), assignable to the nitrogen-coordinated bis-enamineRh-BINAP complex of type 11. The 9l ligand in 11 dissolved in CDCl, was not affected by addition of acetone or THF. These mono- and bis-enamine complexes, 8 and 11, respectively, were also formed by addition of (R)-enamine 3 to [Rh((S)-binap)(acetone-d6),]Cl0, in acetone-d, at -40 OC.14
8IR 10,R
= i.
(CH&hCHCH&Hz CHs
The enamine complex 8 was isolated as deep-red powder by evaporation of solvent followed by washing with cold pentane. This compound (>95% pure), giving consistent NMR spectra in CD2C12 (see Experimental Section), was extremely air-sensitive and thermally unstable, and decomposed easily above -30 OC in the solid state. The instability and difficulty in purification were somewhat mitigated by using a simple model substrate. Thus reaction of [Rh((S)-binap)(acet~ne)~]ClO~and diethyl(3methyl-2-buteny1)amine in acetone at -80 OC for 7 days afforded 10, which showed eight-line 31PN M R signals centered at 6 29.4 and 49.8 in CD2C12. The 'H NMR spectrum in CD2C12was fully consistent: 6 0.03 (m, CH(CH3),), 0.21 (d, J = 6.4 Hz, CH(CH3)2), 0.45 (t, J = 7.0 Hz, NCH,CH3), 0.67 (d, J = 6.4 Hz, CH(CH,),), 0.73 (t, J = 6.7 Hz, NCH2CH3), 1.50-1.52 and 1.90-2.05 (two multiplets coupled with protons at 6 0.45, NCH2CH3),3.10-3.23 and 3.23-3.35 (two multiplets coupled with protons at 6 0.73, NCH2CH3),4.92 (broad t-like, Jc(I)H-P:(~ = 14.0 Hz, Jc(z)H-P(~)H = 7.3 Hz, C(2)H), and 5.06 (broad c(1)H). The enantiotopic isopropyl methyls and N-ethyls of the enamine become diastereotopic in the Rh complex 10. In addition, on going from the free enamine to the Rh-bound enamine, line broadening of the olefinic proton signals is seen owing to the coupling with Rh," and the C(1) proton causes upfield shift ( A 0.81 ppm), while C(2) proton exhibits downfield shift (A 0.83 ppm). Integration of the signals established the 1:l stoichiometry of BINAP and the enamine and no incorporation of acetone molecules. No substantial solvent effect (acetone-d, vs CD2C12) was observed on the N M R spectra. Similar changes in the 31PN M R signal patterns of the BINAP-Rh complexes were observed with a higher (8:l) substrate/complex ratio. Other short-lived complexes could not be detected by the present NMR techniques. Although spectroscopic evidence for the formation of the key mixed-ligand complex 6, has not been obtained, judging from the model exchange reaction using 5 and triethylamine, it must form during the isomerization reaction. The induction process, 5 to 8, has thus been substantiated by stoichiometric reaction of the Rh complex 5 and substrate 2. In the actual catalytic reaction, the aza-allyl Rh complex 8 is the only detectable intermediate and is acting as the chain-carrying species. Isolated 8 indeed catalyzed the isomerization of 2. In this overall scheme, conversion of 8 to 9 by the interaction with the substrate would be the rate-determining step. Reaction of 8 and enamine product 3, giving 11, terminates or retards the catalytic reaction.
d,
Inoue et al.
4900 J . Am. Chem. SOC.,Vol. 11 2, No. 12, 1990 Scheme IV
7 -
6 -
[R h(( R)-blnap)]'
5 -
-
N
52
4 R'
3 -
E
R
0
F v
2.-
R
5
l/[A],
10
= (CH,),C=CHCH,CH,,
simple alkyl, C,H,, elc.
15
(mol'' L )
Scheme V
Figure 1. Plots of the reciprocal of the initial rate of the isomerization versus the reciprocal of the initial substrate concentration for the isomerization of diethylgeranylamine (2) with [Rh((S)-binap)(CH30H)2]C10, in acetone-d6at 15 OC.
1
The bis-BINAP complex, [Rh(binap),]C104, also serves as excellent catalyst precursor for the enantioselective isomerization. Although a rather high temperature (80-100 "C) is required to gain a reasonable reaction rate,% a distinct practical advantage is secured by its high stability and crystallinity. Since triethylamine is capable of displacing the BINAP ligand at 90 OC, even in this case, the dissociated mono-BINAP-Rh complexes are considered to effect the isomerization. Indeed, addition of free BINAP ligand to the reaction system caused a marked retardation of the isomerization. Further, when the reaction of 2 with 10 mol % of the bis-BINAP complex in acetone at 90 O C was monitored by 31P NMR, a very small singlet (90%) reduction of geranial-1-d (15) to (S)-geraniol-1-d [(S)-16]. The Mitsunobu aminationZ0of (S)-16 with phthalimide as nucleophile occurred with clean inversion of configuration, and hydrazinolysis of crystalline (R)-17 afforded (R)-geranylamine-1-d [(R)-18] in 93% ee (98.6% deuterium content). The enantiomeric excess was determined by 400-MHz IH N M R analysis of the (R)-MTPA amid$' by using a triple resonance technique. Synthesis of the desired tertiary amine substrate, (R)-19, was completed by reductive condensation with acetaldehyde.22 When (R)-19 was treated with 2.5-5 mol % of the chiral catalyst precursor, [Rh((S)-binap)(CH30H)2]C104, in T H F at 40 O C for 24 h, a clean intramolecular migration of C(1) protium took place to give (R,E)-enamine, (R)-20. Exposure of (R)-19 to the corresponding (R)-BINAP-Rh+ catalyst caused a 1,3deuterium shift, affording (S,E)-enamine, (S)-21. The enantiomeric purity, determined by 400-MHz 'H and 61-MHz ZH N M R analyses, was greater than 97%. No isotope effect on the selectivity was observed. Scheme VI illustrates the formal stereorelationship of the geranylamine substrate 19 (drawn by hypothetical canonical conformations) and the enamine 20 or 21 possessing E configuration. If one assumes an s-trans-type conformation for the geranylamine (with respect to the C(2)-C(3) double bond and the diethylamino function), the 1,3-hydrogen shift is seen to be occurring in a suprafacial manner.23 Alternatively, the stereochemical outcome may be envisaged as antarafacial shift from the s-cis conformer which involves bond rotation around C(2)-C(3) a t some stage of the multistep conversion. Mechanism and Origin of the Cbiral Recognition. Now with the stereochemical outcome in hand, we would hope to analyze how the two enantiotopic hydrogens a t C( 1) are discriminated by the action of the BINAP-based Rh catalysts. Any postulated mechanisms should be reasonable from the viewpoints of both organic and coordination chemistry. In Scheme 111, a nitrogen-triggered pathway has been described for the 1,3-hydrogen migration. The stereo-determining step, we postulate, is the hydride abstraction in the tricoordinate species, (17) Katsuki, T.; Sharpless, K. B. J . Am. Chem. Soc. 1980. 102, 5974. (18) Nishizawa, M.; Noyori, R. TetrahedronLett. 1980,21,2821. Noyori, R.; Tomino, 1.; Yamada, M.; Nishizawa, M. J . Am. Chem. Soc. 1984.106, 67 17. . . (19) Midland, M. M.; Greer, S.;Tramontano, A.; Meric, S.A. J. Am. Chem. Soc. 199, 101, 2352. (20) Mitsunobu, 0.;Wads, M.; Sano, T. J. Am. Chem. Soc. 1972,94,679. (21) Dale, J. A.; Dull, D. L.; Mosher, H. S.J . Om, Chem. 1W. 31.2543. See also: Yamaguchi, S.Asymmetric Synthesis: M99.8%) were dried over freshly baked molecular vacuum distilled, and stored over molecular sieves (3 A) in sieves (3 a calibrated Schlenk tube equipped with a J. Young Teflon screwcock. For NMR measurements these solvents were vacuum-transferred into the NMR tubes prior to sealing. Active manganese oxide, silver carbonate on Celite,)' and (R)-(+)-a-methoxy-a-(trifluoromethyl)phenylacetyl chloride (MTPACI) were prepared according to published procedures?1 Other commercial solvents and chemicals were used without further purification. All air-sensitive compounds were handled in an argon atmosphere by standard Schlenk techniques. Chromatography. Thin-layer chromatography (TLC) were carried out with Kieselgel 60 FZ5,(E. Merck, Art. 5715, 0.25 mm thick) and spots were recorded by R, values. For column chromatography Kieselgel60 (E. Merck, Art. 7734,70-230 mesh) was used. High-performance liquid chromatography (HPLC) was done on a Waters 6000A instrument equipped with JASCO UVIDEC-100 (254 nm). For analytical purpose a YMC Si100 (3 pm, 4.6 X 300 mm) column was used, while for isolation and purification of the samples a YMC Si70 (15 pm, 22 X 300 mm) column was used. Peak positions were described by retention volumes (VR).Gas chromatography (GLC) was performed on a Hitachi 163 instrument equipped with flame-ionization detector using nitrogen as carrier gas. A stainless steel column (3 X 3000 mm) packed with 5% Carbowax 20M on Chromosorb WAW was used unless otherwise stated.
A),
(32) Fetizon, M.; Golfier, M. C. R.Acad. Sci. C 1968, 267, 900.
J . Am. Chem. SOC.,Vol. 1 1 2, No. 12, 1990 4903
isomerization Catalyzed by BINAP- Rhodium Complexes
28
side view Figure 2. Side and top views of the square planar structure of (S)-BINAP-Rh+ complex 28.
IH and ,lP NMR Studies on the (S)-BINAP-Rh+-Cahlyzed Asymmetric Isomerization of Dlethylgmyhmiae (2) in A~et0ne-d~.In a IO-" diameter NMR tube was placed [Rh((s)-binap)(CH,OH)JCIO, (28.0 mg, 0.0314 mmol) under argon and to this was added dry and degassed acetone-d6(2 mL) by trapto-trap distillation. The mixture was placed in an ice-water mixture and allowed to stand for 30 min with occasional shaking. The resulting orange-red solution was cooled to -90 OC, and into this was transferred carefully a cooled, degassed solution of diethylgeranylamine(6.6 mg, 0.03 14 mmol) in 1 mL of acetone-d6 via Teflon tubing by use of a slight positive pressure of argon. The mixture was frozen under vacuum, and the tube was sealed. This sample was stored in a cold bath, keeping the temperature below -90 "C. The sample thus prepared was quickly loaded in an NMR probe which had been kept at -80 OC. IH and ,IP NMR were recorded alternatively at specified temperature and time intervals. Synthesis of Geranial. The following series of syntheses were done to obtain authentic samples of (&)-16-(*)-19. A mixture of geraniol (7.70 g, 50 mmol), active manganese oxide (60 g), and pentane (300 mL) was stirred at 25 OC for 4 h under argon. Solid material was removed by filtration anathe filtrate was concentrated to give geranial (5.41 g, 77%) as a pale yellow liquid. GLC analysis (180 "C) indicated that this product was a mixture of 90% geranial (tR4.69 min) and 10% neral(4.09 min). 'H NMR spectrum and GLC retention times were identical with those of authentic samples. Synthesis of (*)-Gsmid-J-d. To a stirred suspension of LiAIDl (935 mg, 22.2 mmol) in THF (40 mL) was added dropwise a solution of geranial (6.77 g, 44.5 mmol) in the same solvent (15 mL) at 0 OC under argon. The mixture was stirred at 0 OC for 30 min and added ether (60 mL) followed by 1 N NaOH (3 mL). Insoluble material was removed by filtration, and the filtrate was concentrated to give (A)-geraniol-I-d (6.06 g, 88%) as a colorless oil: IR (neat) 3320 cm-I (OH); IH NMR (CDCI,) 6 1.26 (broads, OH), 1.61 (s, CH,), 1.68 (s, ZCH,), 2.05 (broad s, 2CH2), 4.13 (d, J = 7.0 Hz, CHD), 5.10 (m, = C H ) , 5.41 (d, J = 7.0 Hz, = C H ) ; LRMS m / r 155 (M+). The deuterium content was calculated to be 98.3% by IH NMR. This sample was used for further reaction without purification. Synthesis of N-(Ceranyl-1-d)phthlimide[(*)-IA solution of (*)-geraniol-I-d (6.0 g, 38.7 mmol) in THF (50 mL) was added dropwise to a mixture of triphenylphosphine (15.2 g, 58.1 mmol), diethyl azodicarboxylate (10.1 g, 58.1 mmol), and phthalimide (8.54 g, 58.1 mmol) in THF (250 mL) at 0 OC. The mixture was stirred at the same temperature for 30 min, at 25 OC for 12 h, and then concentrated. The residue was dissolved in CH2C12(200 mL) and the solution was washed with two 50-mL portions of 1 N NaOH, then twicc with each 50 mL of saturated brine, and dried over Na301. Evaporation of the solvent afforded a yellow solid which was purified by column chromatography on silica gel (10% ethyl acetate in hexane) to give N-(geranyl-1-4phthalimide [(*)-I71 (9.78 g, 89%, E / Z = 90:lO). Recrystallization
top view
from hexane at 0 OC afforded a sample with 98% purity contaminated with 2% of N-(neryl-I-d)phthalimide. (*)-17 V, = 12.8 mL (10% ether in hexane); mp 51-52 OC; IR (CHCI,) 1775, 1724,1715 cm-I ( C 4 ) ; IH NMR (CDCI,) 6 1.44 (s, CH,), 1.51 (s, CH,), 1.70 (s, CH,), 1.89 (broads, 2CH2), 4.13 (d, J = 7.5 Hz, CHD), 4.92 (m, = C H ) , 5.15 (d, J = 7.5 Hz, ==CH), 7.65 (m, aromatic protons); LRMS m / r 284 (M+); HRMS calcd for CI8HmNO2D284.1634, found 284.1634. N-(neryl-Id)phthalimide: VR = 11.9 mL (10% ether in hexane); mp 56-57 OC (from hexane at -20 "C); IR (CHCI,) 1775, 1715 cm-I ( C 4 ) ; IH NMR (CDCI,) 6 1.64 (s, CH,), 1.70 (s, 2CH3), 2.22 (m, 2CH2), 4.25 (d, J = 6.4 Hz, CHD), 5.17 (m, =CH), 5.28 (d, J = 6.4 Hz, = C H ) ; LRMS m / r 284 (M'); HRMS calcd for CI8HmNO2D284.1635, found 284.1635. Synthesis of (f)-Ceranylamine-l-d [(*)-18]. A mixture of N((A)-geranyl-I-dphthalimide(10.0 g, 35.2 "01) and hydrazine hydrate (2.56 mL, 52.8 mmol) in methanol (300 mL) was heated at reflux for 1 h and then concentrated in vacuo. The residue was dissolved in 1 N HCI (120 mL) and insoluble compounds were removed by filtration. The filtrate was made basic with 5 N NaOH and extracted with three 150mL portions of ether. The combined ether layer was washed twice with 50 mL of saturated brine and dried over K2C03. Evaporation of the solvent afforded (f)-geranylamine-I-d [(*)-I81 (4.25 g, 79%) as pale yellow liquid. An analytical sample was obtained by short-path distillation, bp 90-140 OC (4 mm): IR (CHCI,) 3360,3200 an-'(NH2); IH NMR (CDCI,) 6 1.20 (s, NH2), 1.62 (s, ZCH,), 1.68 (s, CH,), 2.02 (broad s, 2CH2), 3.25 (d, J = 6.8 Hz, CHD), 5.10 (m, =CH), 5.25 (d, J = 6.8 Hz, =CH); LRMS m / r 154 (M+); HRMS calcd for ClJI18ND 154.1580, found 154.1573. Syatbesis of (*)-aethylper~nylPmine-l-d[(*)-19]. To a mixture of (*)-geranylamine-I-d [(f)-18] (9.89 g, 64.2 mmol) and acetaldehyde (17.9 mL, 321 mmol) in acetonitrile (200 mL) was added sodium cyanoborohydride (6.45 g, 103 mmol) at 0 OC. The mixture was stirred at 25 "C for I5 min and then neutralized with acetic acid. This mixture was further stirred for 2 h in which period the pH of the mixture was occasionally examined and neutralized by addition of acetic acid. The solvent was removed under reduced pressure and the residue was taken up into 2 N NaOH (150 mL). The solution was extracted with three 150-mL portions of ether. The combined ether layer was extracted three times with 50 mL of 1 N HC1 and the aqueous layer was made basic with 5 N NaOH. The liberated (*)-diethylgeranylamine-I-d [(&)-I91 was extracted with three 150-mL portions of ether and the combined ether layer was washed with saturated brine. After being dried over K2C03, the solution was concentrated to give a yellow oil. Distillation in vacuo gave 8.79 g (66%) of (f)-19 as a colorless liquid, bp 86-88 OC (2 mm). GLC (130 "C) analysis showed that this sample was contaminated with 2% of the Z isomer. (f)-19 IR (CHCI,) absorptions due to NH2 group were not observed; IH NMR (CDCI,) 6 1.03 (t. J = 7.03 Hz, ZCH,), 1.59 (s, CH,), 1.63 (s, CH,), 1.67 (s, CH,), 2.04 (broads, 2CH2), 2.50
4904 J . Am. Chem. Soc.. Vol. 112, No. 12, 1990 Scheme VI1
Inoue et al.
silver carbonate on Celite (22.8 g, 40.0 mmol), and benzene (300 mL) was stirred and gently heated. When refluxing started, about 100 mL of benzene was removed by distillation from the reaction mixture. Heating was continued for 1 h, and then the mixture was cooled to room temperature. Solid material was removed by filtration, and the filtrate was concentrated to give IS (1.62 g, 100%) as a pale yellow oil. This 23A 22A product was subjected to further reaction without purification. The structure of 15 was established by comparison of its 'H NMR spectrum with that of authentic sample.'6 The (E)-15 ( t R 14.2 min) to ( q - 1 5 ( t R 11.5 min) ratio determined by GLC (130 "C) was 98:2. Synthesis of (S)-(+)-Gerpniol-1-d[(S)-16].To a stirred solution of 15 (12.3 g, 80.0 mmol) in dry THF (80 mL) was dropwise added a solution of (R)-Alpine-borane (0.5 M in THF, 192 mL, 96 mmol) at 0 "C. The reaction mixture was stirred at 27 "C for 5 h and cooled to 0 236 228 OC. To this was added acetaldehyde (2.2 mL, 40 mmol), and stirring was continued for 15 min at room temperature. The mixture was concentrated under reduced pressure (0.04 mm), and the residue was diluted with ether (300 mL). 2-Aminoethanol(5.79 mL, 96 mmol) was added carefully at 0 OC, and the precipitated material was removed by filtration. The filtrate was washed with saturated brine and dried over MgS04. Evaporation of the solvent afforded a yellow oil, which was subjected to 23A purification on column chromatography (10% ethyl acetate in hexane) 24 to give 16 (10.6 g, 85%) as a colorless oil. Analytical sample was obtained by short-path distillation, bp 90-150 OC (4 mm). The structure IP.Rh H IP.Rh' of 16 was supported by comparison of its chromatographic properties (TLC and GLC) and 'H NMR spectrum with those of nondeuterated authentic sample, [.]26D +0.44' (c I .23, cyclopentane) (lit.I8 [aIz4D +1.51° (c 1.06, cyclopentane). The deuterium content was calculated 25 26 27 to be 97.7% by comparison of its 'H NMR spectrum with that of authentic sample obtained by the (S)-BINAL-H reduction.18 The absolute R = (CH,kC=CHCHzCHz configuration of 16 was assigned to be S by 'H NMR taken in the iP2 (S)-BINAP presence of Eu(hfbc),. S 8oIvont, substrate, or product Synthesis of N-[(R)-(-)-Gerpnyl-1-dlpbthPlimide [(R)-171. To a stirred mixture of triphenylphosphine (23.7 g, 90.6 mmol), phthalimide (q, J = 7.03 Hz, 2CH2), 3.03 (d, J = 6.4 Hz, CHD), 5.09 (m, = C H ) , (13.3 g, 90.6 mmol), and diethyl azodicarboxylate (15.8 g, 90.6 mmol) 5.25 (d, J = 6.4 Hz, 4 H ) ; LRMS m / z 210 (M+); HRMS calcd for in THF (200 mL) was added dropwise a solution of ( a - 1 6 (9.30 g, 60.4 C14HuND 210.2205, found 210.2204. mmol) in T H F (50 mL) at 0 OC. The reaction mixture was stirred at Synthesis of Ethyl Geranate (13). In a 500-mL three-necked flask 25 "C for 12 h and then concentrated under reduced pressure. The quipped with a dropping funnel, magnetic stirring bar, and thermometer residue was purified on silica gel column chromatography (10% ethyl was placed sodium hydride (60% mineral oil dispersion, 1.56 g, 39.0 acetate in hexane) to give 10.8 g (63%, E / Z = 98:2) of crude (R)-17. mmol) and the contents were washed three times with hexane. To this Recrystallization of this product from hexane at 0 OC afforded almost was added dry THF (30 mL) and the flask was surrounded by an icesalt pure sample ( E / Z = 99.7:0.3) of (R)-17: mp 60-61 Oc; -0.244O mixture. Then a solution of triethyl phosphonoacetate (8.73 g, 39.0 (c 1.34, CHCI,). The structure of (R)-17 was confirmed by comparison mmol) in THF (50 mL) was added with stirring at 0 "C, and the mixture of {R and V, values and 'H NMR spectrum with those of nondeuterated was further stirred at this temperature for 30 min. To this was added authentic samples derived from geraniol and phthalimide. N-[(R)-Nedropwise a solution of 6-methyM-hepten-2-one (3.70 g, 30.0 mmol) in ryl-1-djphthalimide was obtained by concentration of the mother liquor THF (20 mL) at 0 OC. The reaction mixture was stirred at 0 OC for 1 followed by purification on HPLC (5% ether in hexane): mp 56-57 OC h, then at 25 OC for 12 h, and then poured into a mixture of ether (200 (from hexane); [a]%D +0.874O (c 1.17, CHCI,). mL) and saturated aqueous ammonium chloride (50 mL). The ether layer was separated, and the aqueous layer was extracted with ether (100 Synthesis of (R)-(-)-G4Myhmiaej-d[(R)-l8]. A mixture of (R)-17 mL). The combined organic layer was dried over MgS04, and evapo(10.5 g, 37.0 mmol) and hydrazine hydrate (2.78 mL, 55.6 mmol) in ration of the solvent gave a yellow oil. GLC analysis ( 5 % PEG-HT on methanol (300 mL) was heated at reflux with stirring. The mixture was Uniport HP, 3 X 3000 mm) indicated that (E)-13 ( f R 14.0 min) and cooled to room temperature and concentrated. The residue was dissolved ~ min) were formed in 78:22 ratio. This crude product was (2)-13 ( t 10.6 in 1 N HCI (130 mL) and insoluble material was removed by filtration. The filtrate was made basic with 5 N NaOH and extracted with three purified on column chromatography with silica gel (2% ether in hexane) to give 5.29 g (90% yield) of a mixture of (E)-13 and (2)-13. Effective 15@mLportions of ether. The combined organic layer was washed twice with saturated brine (50 mL), dried over KzCO3, and concentrated to separation of (E)-13 and (2)-13 was attained by spinning-band distillation under reduced pressure (1 mm). (E)-13 IR (CHCI,) 1715 (M), give (R)-18 (4.45 g, 78%) as a pale yellow oil. This compound was used 1643 cm-' (C-.C); 'H NMR (CDCI,) 8 1.20 (t, J = 7.0 Hz, CH2CH,), for further reaction without purification. An analytical sample was 1.53 (s, CHI), 1.61 (s, CH,), 2.07 (s, CH,), 2.09 (s, 2CH2), 4.07 (q, prepared by short-path distillation: bp 100-150 OC (3 mm); [a]26D -0.816" (c 1.13, cyclopentane). The structure of (R)-18 was assigned CH2CH3), 5.00 (m, = C H ) , 5.59 (s, = C H ) ; LRMS m / z 196 (M+); HRMS calcd for C12H2002196.1463, found 196.1461. (2)-13IR by comparison of 'H NMR spectrum with that of the nondeuterated (CHCI,) 1715 (M), geranylamine. 1642 an-'(M); 'H NMR (CDCI,) 8 1.27 (t, J 7.0 Hz, CHZCH,), 1.62 (s, CH,), 1.68 (s, CH,), 1.88 (d-like, J = Synthesiis of (R)-(+)-IDiethyly~miaej-d[(R)-l9]. To a stirred 1.3 Hz, CHI). 2.18 (m, CH2), 2.64 (t-like, J = 7.5 Hz, CHI), 4.14 (q, mixture of the amine (R)-18 (2.31 g, 15 mmol), acetaldehyde (4.2 mL, (m, = C H ) , 5.65 (m, = C H ) ; LRMS m / z 196 (M+); C H ~ C H J )5.15 , 75 mmol), and acetonitrile (100 mL) was added sodium cyanoboroHRMS calcd for CI2HmO2196.1463, found 196.1470. hydride (1.51 g, 24 mmol) at 30 OC. After stirring of the mixture for Synthesis of Gernd0I-1,I-d~ (14). To a stirred suspension of LiAlD, 15 min, the mixture was neutralized with acetic acid. Stirring was (1.0 g, 23.8 mmol) in benzene (70 mL) was added dropwise a solution continued for I h, and the solvent was removed under vacuum. To the of (E)-13 (contaminated with 2% of (Z)-13, 4.67 g. 23.8 mmol) in residue was added 2 N NaOH (70 mL), and the mixture was extracted benzene (30 mL) at 0 OC. The mixture was stirred at 26 OC for 5 h and with three SO-mL portions of ether. The combined ether layer was then diluted with ether (100 mL). To this was added carefully 1 N extracted three times with each 50 mL of 1 N HCI. The aqueous layer NaOH (5 mL), and the resulting solid material was removed by filtracombined was made basic with 5 N NaOH and extracted three times tion. Evaporation of the solvent gave 14 (3.90 g, 100%) which was used with 100-mL portion of ether. The combined ether layer was washed for further reaction without purification. The analytical sample of 14 three times with saturated brine and dried over K2C03. Evaporation of (E/Z= 98:2) was obtained by short-path distillation, bp 100-150 OC (4 the solvent left a yellow oil which was subjected to short-path distillation mm): IR (CHCI,) 3610, 3440 cm-' (OH); IH NMR (CDCI,) 8 1.18 to give (R)-19 (1.72 g, 55%): bp 140 OC (3 mm); [aIz6D +2.06O (c 1.47, (broads, OH), 1.61 (s, CHI), 1.67 (s, CH,), 1.69 (s, CH,), 2.05 (broad cyclopentane). This product contained 0.3% of the 2 isomer. Coms, 2CHz), 5.10 (m,
