J.C.S. Perkin I Stereochemistry of the Oxymercuration of Substituted Methylenecyclo- hexanes and Methylenecyclopentanes By Yasuhisa Senda.rsquo; Shin-ichi Kamiyama, and Shin Imaizumi, Department of Applied Science, Tohoku University, Sendai 980, Japan The oxymercuration-reduction of methylenecyclohexanes and methylenecyclopentanes in 50aqueous tetrahydro- furan was studied. With unhindered methylenecyclohexanes attack of hydroxide ion occurs from the axial side of the molecule ; the steric effect of the substituent is dominant in the reaction of hindered compounds. In the case of 2-substituted methylenecyclopentanes, the hydroxide ion attacks from the same side as the substituent. The stereochemistry of this reaction is discussed. 1~ the reduction of ketones by complex metal hydrides, additions have been discussed on the basis of lsquo; product the addition of nucleophiles to unhindered cyclo-development control rsquo; and lsquo; steric approach control.rsquo; hexanones yields predominantly the more stable equa- Explanations of the stereochemistry of these reactions torial alcohols, whereas the axial isomers are obtained w.G. Dauben, G. J. Fonken, and D. s. Noyce, J. Amer.in the reaction of hindered cyclohexanones. These Chew. SOC., 1956, 78, 2579. based on pure steric approach considerations or on eclipsing effects have also been advanced. Kinetic work has shown that hydride reductions yielding the more stable equatorial alcohol predominantly, the outcome of which was previously assumed to be deter- mined by the stability of the products, are in fact kinetically con t rolled.4 To determine the nature of steric effects in addition reactions, we studied the stereochemical course of the oxymercuration-reduction of a series of substituted methylenecyclohexanes and methylenecyclopentanes which have structures similar to the corresponding cycloalkanones.We accept the premise that the oxymercuration of olefins involves rapid pre-equilibrium formation of a mercurium ion as an unstable intermediate, followed by rate-and product-determining attack of solventa5 OH Within this context, the stereochemistry of oxymercur- ation-reduction is determined by the direction of the attack of the hydroxide ion to the unstable mercurium ion. RESULTS AND DISCUSSION The kinetically controlled oxymercuration-reduction of 4-methyl-1-methylenecyclohexane (6) and 1-methyl-ene-4-t-butylcyclohexane (7) in 60 aqueous tetra-hydrofuran at 0 "C produced predominantly the axial alcohols.The amounts of axial cyclohexanols were less in the reaction of 3-substituted methylenecyclohexanes. On introduction of a methyl group at the C-2 axial position of (7), the extent of attack of hydroxide ion from the opposite side to the methyl group was 79, but with a C-2 equatorial methyl group the extent of attack from the axial side was only 44. 23-Di-methyl-1-met hylene-4- t-bu t ylc yclo hexane (9) shows al- most the same product distribution as (7). The extent of attack of hydroxide ion on the mercurium ion of 2-methyl- -methylenecyclohexane (1) is estimated on the basis of the results with cis- and trans-2-methyl- l-methylene-4-t-butylcyclohexanecis-and trans-(S) to be 56-790/,.The oxymercuration product of (1) was 67 cis-isomer, obtained by the attack of hydroxide ion from the same side as the methyl group. This shows that steric hindrance by the methyl group determines the product distribution. The fact that the isomer distribution of the product from mobile (1) is between those of cis-and trans-(8) indicates that the axial methyl conformer, appreciable amounts of which are J. C. Richer, J. Org. Chem., 1965, 30, 324. M. Che'rest and H. Felkin Tetrahedron Le!ters, 1968, 2205. J. Klein, E. Dunkelblum, E. L. Eliel, and Y. Senda, Tetra-hedron Letters, 1968, 6127.W. Kitching, Organometallic Chem. Rev., 1968, 1,61; W. L. Waters and E. F. Kiefer, J. Amer. Chem. Soc., 1967, 89, 6261; W. L. Waters, W. S. Linn, andM. C. Caserio, ibid., 1968, 90, 6741. S. K. Malhotra and F. Johnson, Chem. Comm., 1968, 1149. 531 expected in (1) as a result of At193J methyl-hydrogen interaction,6 as well as the equatorial one, may contribute to the stereochemical results. With increase of the steric bulk of the 2-substituent, the amount of axial attack decreased and exclusive equatorial attack occurred in the reaction of 1-methylene-Z-t-butylcyclo-hexane (3). Oxymercuration-reduction of substituted methylene- cyclohexanes and methylenecyclopentanes Reaction conditions Substrate 0 "C, 15 min 20 "C, 15 mi; Meth y lenecyclohexanes Product 94 (axial attack) 2-Methyl-(1) 33 37 2-Isopropyl-(2) 30 34 2-t-Butyl- (3) 3 4 3-Methyl-(4) 54 54 3-t-Butyl- (5) 58 58 4-Methyl- (6) 68 69 Pt-Butyl- (7) 71 69 ci~-2-Methyl-Pt-butyl-cis-(8) 44 trans-2-Methyl-4-t -bu tyl- Irans-(8) 79 2,2-Dimethyl-4-t-butyl- (9) 73 71 3,3,5-Trimethyl- (10) 71 70 trans-2-Isopropyl-5-methyl-(11) 24 25 Methylenecyclopentanes Product (cis attack) 2-Methyl- (12) 90 79 2-Cyclopentyl- (13) 72 71 2-t-Butyl- (14) No reaction The stereochemical results with unhindered methylene- cyclohexanes are explained by the molecular-orbital distortion suggested by Klein.' Many structures have been suggested for mercurium ions.Which ever is used, it is agreed that the primary interaction involves overlap of the mercury 6s orbital with the x-electrons of an olefin.8 Bach and Henneike suggested that the mer-curium ion more closely resembles a x complex than a three-membered ring struct~re.~ This implies that the hybridization of the carbons in the mercurium ion moiety is sp2-rather than @-like.Since the stereo- isomer distribution in oxymercuration of substituted methylenecyclohexanes seems to be primarily controlled by steric hindrance, it is supposed that the transition state at the product-determining step is reactant-like, as in the cases of reduction of cyclohexanones 3910 by complex metal hydrides and hydroboration of methy1enecyclohexanes.ll The distortion of the vacant x* bond orbital arising from the bonding C(2)-C(3) x*--b interaction could occur in two stereochemically different transition states at the product-determining step (A) and (B): therefore, the x* bond orbital of the lowest-unoccupied molecular orbital (1.u.m.o.) is distorted to the axial side.The attack of a nucleophile by interaction with the 1.u.m.o. will be easier from the axial direction in (A) than the equatorial side in (B). When a 2-methyl group is introduced, its steric effect ' J. Klein, Tetrahedron Letters, 1973, 4307; Tetrahedron, 1974,30, 3349. G. A. Olah and P. R. Clifford, J. Amer. Chem. SOC.,1973, 95, 6067. R. D. Bach and H. F. Henneike, J. Amer. Chem. Soc., 1970, 92, 5589. lo D. C. Ayres, D. N. Kirk, and R.Sawdaye, J. Chem. SOC.(B),1970, 505. l1 J. Klein and D. Lichtenberg, J. Org. Chem., 1970, 35,2654. 53 becomes a major factor determining the stereochemical results. The hydroxide ion is expected to attack 3,3,5-trimethyl-l -methylenecyclohexane (10) pre-dominantly from the equatorial side, since an axial methyl group at the 3-position has usually shown large -.+ OH-steric liindrance to nucleophilic addition to cyclo-hexanones and electrophilic addition to methylene-cyclohexanes. Unexpectedly, 71yo axial attack was observed in the oxymercuration of (10). This result cannot be explained by the steric hindrance of the axial 3-methyl group. In contrast to six-membered ring compounds, a hydroxide ion attacks methylenecyclopentanes from the same side as the 2-substituent.The oxymercuration of 2-methyl-l-methylenecyclopentane (12) gave 90 cis attack. It seems impossible to explain the prior formation of the cis-alcohol by steric hindrance. This result indicates that, in contrast to six-membered ring compounds, the oxymercuration of (12) reflects the relative stability of the two isomeric products; in other words, the transition state is considered to be product- like in the product-determining step, as in the cases of the reduction of cyc1opentanones,l2 by complex metal liydrides and the catalytic hydrogenation of cyclo-pentanones and methylenecyclopentanes.13 With increase of the steric requirement of the 2-substituent, steric control is also operative.Less l3 Y. Scnda, S. Mitsui, R. Ono, and S. Hosokawa, Hull. Chem. SOG.Jnpax, 1971, 44,2737. l3 S. Illitsui, H. Saito, S. Sckiguchi, Y. Kuniagai, and Y. Senda, Tetvahedvogz, 1972, 28, 4751. J.C.S. Yerkin I stereoselectivity was observed in the reaction of 2-cyclo-pentyl-l-methylenecyclopentane (13). When the t-butyl group is introduced, no product was obtained. This may mean that the I-strain in the product-like transition state is too large to allow the reaction to proceed. EXPERIMENTAL MateriaZs.-Methylenecyclohexanes and methylenecyclo- pentanes were prepared from corresponding cycloalkanones by the procedure of Corey and his co-workers: l4 (l),b.p. 118-120 "C (yield 70); (2), b.p. 111-112 "C (83 mmHg) (66); (3), b.p. 111-114 "C (120 mmHg) (82); (4), b.p.112 "C (75); (5),b.p. 102-103 "C (200 mmHg) (87); (6),b.p. 123-125 "C (60); (7), b.p. 72-73 "C (30mmHg) (70",); (8),b.p. 86-87 "C (30 mniHg) (73y0), as a mixture of cis-and trans-isomers, separated by preparative g.1.c. ; (Y), b.p. 105-106 "C (50 mmHg) (65); (lo), b.p. 89-90 "C (164 mmHg) (50); (II), b.p. 134-135 "C (207 mniHg) (71); (12), b.y. 78-80 "C (70); (13), b.p. 103-104 "C (38 mmHg) (72); and (14), b.p. 132 "C (76). The structure of each substituted methylenecyclo- hexane and niethylenecyclopentane was confirmed by 'H n.rn.r. spectra and analytical g.1.c. Authentic samples of substituted 1-niethylcyclohexanols and 1-methylcyclo-pentanols were prepared by the Grignard reactions of cycloalkanones. Stereoisomeric 1,2-dimethyl-4-t-butyl-cyclohexanols and I-methyl-2- t-butylcyclopentanols were estimated by g.1.c. Oxymercuration-Reduction f'rocedure.'5-T0 a solution of Hg(OAc), (0.324 g, 1 mmol) in 50 aqueous THF (4.0 ml) was added l-methyl-2-methylenecyclohexane (0.110 g, 1 mniol), and the mixture was stirred. It was then reduced by addition of ~N-N~OH in(1.0 ml) and O.~M-N~BH, 3N-NaOH (1.O ml). The solution was extracted three times with ether and the extracts were washed with saturated aqueous NaHCO, and then brine, dried (Na,S04), and concentrated. The residual solution was subjected to g.1.c. 7/1196 Received, 7th July, 19771 l4 l.Greenwald, amp;I. Chaykovsky, and E. J. Corey, J. Ovg. Chetn., 1963, 28, 1188. l5 H. C. Brown and P. Geoghegan, jun., J. Anzer. Chem. Soc., 1967, 89, 1522.
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