Notes
3416 J . Org. Chem., V d 44, No. 19, 1979
3-(p-Toluenesulfonyl)butanal(6). Glacial acetic acid (6.0 g, 5.8 mL, 0.10 mol) was added dropwise to a solution of sodium p-toluenesulfinate monohydrate (21.4 g, 0.1 mol) in water (100 mL) plus tetrahydrofuran (50 mL) stirred at 0 "C under nitrogen. Freshly distilled crotonal 16.0 g, 8.25 mL, 0.1 mol) in T H F (25 mL) was added, and the mixture was stirred for 21 h at room temperature. Water (250 mL) was then added, and the mixture was extracted with methylene chloride, which was dried and stripped to yield an oil. NMR analysis showed the material to be pure sulfone aldehyde 6, which was used directly in the next step: NMR 6 9.78 (1 H, s), 7.78 (2 H, d, J = 8 Hz), 7.38 (2 H, d, J = 8 Hz),3.64 (1€I, m), 3.17 (1H, d of d, J = 19,4 Hz), 2.60 (1H, d of d, J = 19, 8 Hz), 2.44 (3 H, s), 1.28 (3 H, d, J = 8 Hz). 2-[ 24p-Tol uenesulfonyl)propyl]-1,3-dioxolane(7). Crude aldehyde 6 (0.LO mol) was dissolved in dry benzene (200 mL) plus ethylene glycol (6.2 g, 5.6 mL, 0.10 mol) and p-toluenesulfonic acid (100 mg) was added as a catalyst. The mixture was refluxed under nitrogen through a Dean-Stark trap for 5 h, then the solution was cooled and washed with aqueous NaHC03, and the organic phase was dried and stripped. The oil was crystallized by taking it up in hexanelethyl acetate, cooling in a dry ice/ ethanol bath, and scratching briskly with a glass rod. The resulting white crystals were filtered and dried to yield 22.8 g (84%): mp 31--33 "C; NMR d 7.74 (2 H, d, J = 8 Hz),7.32 (2 H, d, J = 8 Hz), 4.96 (1H, t,, J = 5 Hz), 3.85 (4 H, m), 3.3 (1H, m), 2.45 (3 H, s), 2.2 (1 H, m), 1.8 ( I H, m), 1.32 (3 H, d, J = 8 Hz). 2 4 (p-Tolnenesulfonyl)-2-(carboxyethyl)propyl]-1,3-dioxolane (8). Sulfone acetal 7 (19.8 g, 73 mmol) was dissolved in dry T H F (200 mL) under nitrogen, to which triphenylmethane (100 mg) had been added as an indicator. Then, a solution of n-butyllithiuni in hexane (43 mL of 1.7 M solution, 73 mmol) was added dropwise and the mixture was stirred for 15 min at room temperature. The temperature was maintained with a water bath as ethyl chloroformate (11.9 g, 9.6 mL, 110 mol) was added over the period of h min. The solution was stirred for 21 h, then water was added and the product was extracted with methylene chloride, which was dried and stripped to yield 8 (25 g, 99%) as an oil: NMR Is 7.72 12 H, d, J = 8 Hz), 7.34 (2 H, d, J = 8 Hz), 5.00 (1 H. d of d, J = 6 , 4 Hzj, 4.16 (2 H, q, J = 7 Hz), 3.8 (4 H, m), 2.58 (1H , d of d , *I = 14, 6 Hz), 2.45 (3 H, s), 2.20 (1 H, d of d, J = 14, 4 Hz), 1.67 (3 H, s), 1.21 (3 H, t, J = 7 Hz). 3 4 p-Toluenesulfonyl)-3-(carboxyethyl)butanal(9).Ester 8 (3.42 g, 10 nimol) was dissolved in dioxane (50 mL) and water (8 mL) and cooled to O "C under nitrogen as 60% aqueous perchloric acid (42 mL,) was added dropwise over 15 min. The mixture stirrc:d at 0 "C for 2 h, then water (200 mL) was added and the product was extracted with methylene chloride. The organic phase was washed with water, dried, and stripped to yield sulfone aldehyde 9, which was used immediately in the next step: NMR 6 9.74 (1 H, s), 7.72 (2 H, d, J = 8 Hz), 7.32 (2 H, d, J = 8 Hz), 4.12 (2 H, q, J = 7 Hz), 3.54 (1 H, d, J = 18 Hz), 2.94 (1 H , d, J = 18 H z ) , 2.4!5 (3 H, SI, 1.84 (3 H, s), 1.17 (3 H, t, J = 7 Hz). E t h y l B-Formylmethacrylate (10). Aldehyde 9 (10 mmol) was dissolved in ether (50 mL) and trimethylamine gas was bubbled thro;igh while cooling in a water bath. An oil formed and precipitated, and the ether solution was decanted. The precipitate was shown by NMR to be trimethylammonium ptohenesulfinate. The ether solution was washed with brine, and the ether was carefully removed under a nitrogen stream. The crude yellow oil was purified by molecular distillation a t 100 "C (0.2 mmHg), yielding pure unsaturated ester 10 of undetermined stereochemistxy, but with greater than 90% selectivity (presumably the E isomer). The yield was 785 mg (56% from 8): NMR 6 10.28 ( 1 H, d: J = 8 Hz), 6.84 (1 H. d of q, J = 8, 1 Hz), 4.30 (2 H, q, ,I = 7 Hz), 2.34 (3 H, d, J = 1 Hz), 1.34 (3 H, t, J = 7 Hz). 3-Methyl-5-hydroxy-2(5H)-furanone (2-Methyl-4hydroxybut-2-enolide) (1). Unsaturated ester 10 (785 mg, 5.6 mmol) was heated at 100 "C for 2 h under nitrogen in 10% aqueous sulfuric acid 110 mL). The mixture was then cooled to room temperature, saturated with NaC1, and extracted three times with methylene chloride. The organic phase was dried and carefully stripped to yield the crystalline hydroxy lactone. The material could be purified by sublimation at 100 OC (0.25 mmHg), but was best purified by recrystallization from cyclohexane plus 0022-326317911944-3416$01.00/0
a few drops of ether to give a total of 420 mg (72%) from two crystal crops: mp 69-71 " C (lit.5 69-71 "C); NMR b 6.90 (1 H, m), 6.10 (1 H, q, J = 1 Hz), 3.7 (1 H, s br), 1.90 (3 H, d, J = 1
Hz). Registry No. 1,931-23-7;2,616-02-4;3, 40834-42-2;4, 4170-30-3; 5, 824-79-3;6,71041-35-5;7, 70451-38-6;8, 71041-36-6; 9, 71041-37-7; 10, 71041-38-8; ethyl chloroformate, 541-41-3.
3-Ethylidenecyclohexyl Acetates from Acetic Acid Treatment of 1-(l-Hydroxyethyl)bicyclo[3.l.0]hexanes N. G. Steinberg,* G. H. Rasmusson, G. F. Reynolds, J. P. Springer, and B. H. Arison Merck Sharp & Dohme Research Laboratories, Rahway, N e w Jersey 07065 Received April 6, 1979
In the course of studies directed toward the partial synthesis of vitamin D analogues, it became of interest to prepare 3-ethylidenecyclohexanolsin which the geometry of the exocyclic double bond could be controlled by the choice of an appropriate synthetic method. Surprisingly, the parent system has not yet been reported, and a general, stereoselective synthesis of such a ?,&disubstituted homoallylic system apparently has not been studied. Of the methods available for the preparation of homoallylic alcohols,' we chose to investigate the rearrangement of the cyclopropylcarbinyl system generated from 1-(1hydroxyethd) bicyclo[3.1.0]hexane (1 This system, which
la c e g
R=H R = a-naphthNHCO R = 3,5-(NO,),C,H,CO R = CH,CO
2a
lb d f
h
2b
is present in the rigid framework of 6a- and 6 f l - h ~ droxy-3a,5a-cyclosteroids,has been found to rearrange selectively and in high yield on acid treatment to give the corresponding steroidal 5-en-3P-01system.* Solvolysis of the closely related bicyclo[3.l.0]hex-l-ylmethylp-nitrobenzoate affords >BO % yield of 3-methylenecyclohexan0l.~ Recent studies on the solvolysis of 3,5-cyclovitamin D (1) (a). B. Belleau and T. F. Gallagher, J . Am. Chem. Soc., 73, 4458 (1951); (b) M. F. Lipton and R. H. Shapiro, J. Org. Chem., 43,1409 (1978), and references therein; (c) M. Naruse, K. Ultimoto, and H. Nozaki, Tetrahedron Lett., 2741 (1973); (d) R. S.Lenox and J. A. Katzenellenbogen, J. Am. Chem. Soc., 95,957 (1973); (e) E. J. Corey, N. M. Weinshenker, T. K. Schaaf, and W. Huber, ibid., 91,5675 (1969); (0 W. G. Salmond, M. A. Barta, and J. L. Havens, J. Org. Chem.,43,790 (1978); (g) E. Femholz and W. L. Ruigh, J . Am. Chem. SOC.,62, 3346 (1940). (2) S. Winstein and E. M. Kosower, J. Am. Chem. SOC.,81,4399 (1959). (3) W. D. Cloason and G. T. Kwiatkowski, Tetrahedron, 21,2779 (1955).
0 1979 American Chemical Society
Notes
J . Org. Chem., Vol. 44, N o . 19, 1979 3417
+
-\022
16
Figure 1. Perspective drawing of the 3,5-dinitrobenzoate le. For clarity, hydrogens have not been included.
derivatives have shown that 3@hydroxyvitamins of 5E and 52 geometry are formed, with the natural 52 isomer being present in higher amounts than would have been predicted with only steric consideration^.^ We thus anticipated that the rearrangement of 1 would likewise be selective to give 3-ethylidenecyclohexanol and that any variation in the geometry of the product olefin would be dependent on the relative orientation of the hydroxyl group to the cyclopropane ring in the two diastereoisomers of 1. Racemic 1 was prepared in two steps from l-acetylcyclopentene" by reaction with dimethylsulfoxonium methylide followed by sodium borohydride reduction. The diastereoisomeric alcohols were formed in a ratio of about 2:l as analyzed by NMR and high-pressure LC. These could be separated by preparative high pressure LC utilizing a recycle feature to give the major, more mobile isomer (la) and a less mobile isomer (lb). Each isomer could be distinguished from the other by the NMR shift of the methine hydrogen of the hydroxyl-bearing carbon, the quartet of la being centered at 3.64 ppm and that of l b a t 3.48 ppm. Crystalline derivatives lc,e and ld,f of each isomer were prepared by reaction with a-naphthyl isocyanate and with 3,li-dinitrobenzoyl chloride, respectively. The structure of the 3,5-dinitrobenzoate (le) of la was determined by X-ray analysis and is depicted in the ORTEP drawing of Figure 1. Acetates (lg and lh) of each alcohol were also prepared. The alcohols la and lb proved to be quite stable to glacial acetic acid at room temperature, remaining unaltered after 8 h. Exposure to hot (110 "C) glacial acetic acid resulted in rapid conversion to a mixture of olefinic acetates. Both la and lb on heating at 110 "C in this solvent for 210 min gave the same major product along with a second component whose relative yield was dependent upon the configuration of the starting alcohol. A third, minor (
