J . Org. Chem., Vol. 43. N o . 6, 1978 1259
Notes H, unresolved multiplets, aryl H's and vinyl H), 4.91 (2 H, d, J = 2 Hz, CHzO), 4.20-(2 H, q, COOCHz), 1.30 (3 H, t, COOCH2CH3);HRMS 204.0771 (34, M+ calcd for C12H12O3: 204.0788), 175 (loo), 131 (89), 77 (28).Anal. Calcd for C12H1203: C, 70.58; H, 5.92. Found: C, 70.26; H, 5.94. 9-Ethoxycarbonyl-7-oxabicyclo[4.3.0]-1(9)-nonene (14). To a suspension of 144 mg (3.00 mmol) of a 50% oil dispersion of NaH, washed free of oil with dry pentane, in 5 mL of dry THF at 0 "C is added 432 mg (3.78 mmol) of freshly distilled 2-hydroxycyclohexanone dropwise over a 3-rr~inperiod. After 1h, 709 mg (3.00 mmol) of compound 1 is added dropwise over a 20-min period by means of a syringe pump. The reaction solution is refluxed for 24 NH4C1,diluted with water, and extracted and dried over Na2S04, evaporated, and chromatographed on silica gel, eluting with ethyl acetatehexane (2:6, v/v), to afford 230 mg (39%)of 14 ( R f 0.40 eluting with 40% EtOAc/ hexane) as a clear liquid: IR (thin film) 1710 cm-l; 'H-NMR (CC14) 6 4.63 ( 2 H, broad, CHzO), 4.13 (2 H, q, COOCHz),3.7-3.3 (1H, unresolved multiplet, CHO), 2.4-1.0 (8 H, unresolved multiplets, cyclohexyl H's), 1.38 (3 H, t, COOCH2CH3);HRMS 196.1057 (35, M+ caicd for CllH1603: 196.1099),194 (41),151 (531,150(71), 123 (loo), 122 141). Anal. Calcd for (21lH1603:C, 67.32; H, 8.22. Found: C, 66.83; H, 8.17.
Acknowledgments. Support for this research was provided by funds from t h e National Science Foundation (Grant No. GP-31321X) and the National Institutes of Health (Grant No. CA-12617). We thank Professor Martin Semmelhack for informing us of his similar research with compound 1 prior to publication [see accompanying note]. Registry No.-1, 20345-61-3; 2, 64739-80-6; 3, 64739-81-7; 8, 64739-82-8;9, 64739-83-9;13, 57543-58-5;14, 64739-84-0;ethyl 2diethylphosphonopropeionate, 3699-66-9; phenylselenyl bromide, 34837-55-3; cyclohexanone, 108-94-1; salicylaldehyde, 90-02-8; 2hydroxycyclohexanone,533-60-8;i, 64739-85-1.
References and Notes (a)E. E. Schweizer,L. D Smucker, and R. J. Votral, J. Org. Chem., 31, 467 (1966);(b) E. E. Schweizer and G. J. O'Neill, /bid., 30, 2082 (1965);(c)E. E. Schweizer and K. K . Light, /bid., 31, 870 (1966);(d) E. E. Schweizer and J. G. Liehr, /bid., 33, 583 (1968);(e) E. E. Schweizer, J. Liehr, and D. J. Monaco, ibid., 33, 2416 (1968);(f) I. Kawamoto, S. Muramatsu,and Y. Yura, Tetrahedron Lett., 4223 (1974), and referecces cited therein. (a)G. M. Kosolopoff, J. Am. Chem. Soc., 70, 1971 (1948);(b) A. N. Pudovik,
G. E. Yastrebova, and V . I. Nikitiva, Zh. Obshch. Khim., 37, 2790 (1967). H. J. Reich. J M. Renga, and I. L. Reich. J. Am. Chem. SOC.,97, 5434 (1975). D. Seebach and E. J. Corey, J. Org. Chem., 40, 231 (1975). (a)C. Pascual,J. Meier. and W. Simon, Helv. Chim. Acta, 49, 164 (1966): (b) L. M. Jackman and S. Sternhell, "Applications of Nuclear Magnetic Resonance Spectroscopy in Organic Chemistry", 2nd ed, Pergamon Press, New York, N.Y., 1969, pp 184-187. (a)S. C. Watson and d. F. Eastham, J. Organomet. Chem., 9, 165 (1967): (b) W. G. Kofron and L. M. Baclawski, J. Org. Chem., 41, 1879 (1976). The unknown compound was not distinguishable by TLC from 12 and was not detectable by GLC From the fact that the 'H-NMR spectrum of the
product after Kugelrohr distillation contained an additional aromatic singlet and absorptions characteristicof the methylene protons of a diethylphosphonate functional groJp. and that the IR spectrum showed a weak OH stretching abjorption. the unknown compound was postulated to have structure i
c%ph E t . W 1
Preparation of 2-(Alkylthiomethy1)acrylates M. F. Semmelhack,' J. C. Tomesch, M. Czarny, and S. Boettger Department of ChemistrS),Cornell Uniuersity, li-haca, N e u York 14853 H~ceiuedAugust 23, 1977
T h e synthesis of trisubstituted alkenes has been a n active area of study in recent years; many general strategies are now avai1able.l We are pursuing a plan for synthesis of t h e
0022-3263/78/1943-1259$01.00/0
sesquiterpene a-methylene-y-lactones which utilizes intramolecular Reformatsky-type reaction2 and necessitates t h e preparation of t h e 2-substituted acrylate unit as in 1. P r e viously developed stereospecific methods were applied to simple systems related t o 1 with some success b u t required
+ MeO-M-X
1, X = Br, OH, SR
M
=
metal
several steps, some involving vigorous reaction conditions.2 Here we report a method for preparation of t h e desired acrylate unit under mild conditions and with high efficiency. T h e method is based on Wittig reagents of t h e sort represented by 2 a n d 3. A general technique for preparation of phosphorus reagents such as 2b is due to Corey3 a n d to S c h l o ~ s e rb, u~t we have failed in our attempts t o apply that method in preparation of 2a (X = OH) or 3a (X = OH). Apparently. reaction of \
(:=pphd A 2a, R = C0,Me; X = OH b, R = alkyl; X = OH
3a, R = C0,Me; X = OH b, R = alkyl; X = OH
2a or 3a with an aldehyde is slower than elimination of Ph3PO (from 2a) and HOP(O)(OMe)2 (from 3a). With other heteroatom units X in 2a a n d 3a (e.g., X = acetate), elimination of X- is invariably too rapid. Nevertheless, we expected that t h e elimination of X- could be reversible, still providing useful concentrations of 2a a n d 3a. After a series of unsuccessful experiments with oxygen anions (in eq l), t h e thiolate anion (X = S) was found t o lead
0
0
f
4
3a
4a, R" = Me b, R" = Et
( 21-5
( E)-5
to t h e desired conversion. T h e requisite methyl 2-(diethylphosphon0)acrylate 4 was prepared according t o t h e procedure of P ~ d o v i kwhich ,~ is presented in detail in t h e Experimental Section. T h e yield of 4 was only moderate, b u t t h e procedure is direct, a n d t h e reagent can be prepared on large scale, distilled, and stored for later use. T h e n addition of 4 t o a suspension of sodium hydride a n d t h e thiol in tetrahydrofuran, followed by a n aldehyde (stirring for 2.0 h at 25 "C), affords t h e 2-(alkylthiomethy1)acrylate( 5 ) in high yield. Table I displays the results of experiments designed to test t h e effects of solvent polarity, cation type, a n d structure of the organic unit in the thiolate anion on the efficiency and t h e stereochemical outcome of t h e reaction. In this case n-heptanal, phosphonoacrylate 4b, a n d a thiolate anion were allowed to react under a variety of conditions. T h e yield of combined E a n d 2 isomers was high in every case.6 T h e d a t a in Table I demonstrate t h a t t h e ratio of isomers depends upon counterion, solvent, a n d t h e nature of t h e thiolate anion, although no useful correlation is evident. T h e 1978 American Chemical Society
Notes
1260 J . Org. Chern.. Vol. 43, No. 6 , 1978 Table I. Effects of Reaction Conditions on Isomer Distribution n
t
(a Sa>,
RSH
SR
CO Et
Thiol R
Solvent
Base
E /z
Isopropyl Isopropyl Isopropyl Isopropyl Isopropyl Isopropyl tert-Butyl tert-Butyl Benzyl Phenyl
THF T!IF THF THF THF DMF TEIF DMF THF 'THF
n -BuLia n-BuLib NaHc KHc Triton BC NaHc NaHa NaHa NaHc NaHa
46/54 10/90 45/55 10/90 30170 10/90 45/55 10/90 36/64 18/82
a The reaction time was 1 h . b T h e reaction time was 1 4 4 h. c T h e reaction time was 1 2 h .
ratio of isomers also depends upon whether equilibrium between the isomers is established; addition of 0.1 mol equiv of -6 sodium isopropylthiolat e effected rearrangement of pure (E) into an 18:80mixture of ( E ) - 6 / ( 2 ) - 6in less t h a n 5 rnin a t 25 "C in DMF.6 A parallel experiment in THF gave the same result, but only after 24 h. Presumably, equilibration of t h e E and Z isomers occurs, by conjugate additiodelimination of the thiolate. Under conditions designed t o minimize the rate of equilibration (nonpolar solvent, deficiency of RS-), the ratio of isomers is generally about 1:l.After equilibration, the Z isomer usually predominates by a factor of 8:1 or 9:l. Chromatographic separation provides samples of the pure isomers with good efficiency. A number of difunctional aldehydes have been converted t o 2-(alkylthiomethy1)acrylates; examples such as 7 and 8 are obtained in high yields. A more demanding example is the preparation of the 4-chlorocrotonate derivatives, 9, from chloroacetaldehyde under the usual conditions. T h e yield of (E)-9and (Z)-9is 980/0,with an isomer ratio of 1:2.8.
RCH&HO
i-PrSH, NaH +
RCHKH-C
4'03 E -
C0,Me /
Ls
