Feb. 20, 1961
COMMUNICrlTIONS TO
a n incomplete reaction with triethylamine in heavy water, it contains no deuterium; (ii) the product (IV: Et in place of Me) from the reaction of Nethyl-5-phenylisoxazoliumfluoroborate with sodium acetate in heavy water contains only a small and variable amount of deuterium bound t o carbon; (iii) t h e rate of the reaction of acetic acid with the a-ketoketenimine (X: R = CGHS,R ' = H, R" = Et) in methylene chloride is depressed by addition of triethylamine. The reactions of many other nucleophiles with isoxazolium salts2 all receive ready rationalization in terms of the initial production of cr-ketoketenimines. The great facility of the reactions is dramatically illustrated by the rapid combination of (I) with azide ion in aqueous solution to give (XII) (Found: C, 59.30; H, 5.06; N, 28.18)
THE
1009
EDITOR
for a general approach to the synthesis of these compounds and wish to report the successful conversion of 6-hydroxy-Z-@-tosyloxyethyl) - 1,2,3,4-tetrahydronaphthalene (11) to the compound in the title.
I
I1
IV
Winstein and Bairdza first observed the conversion of $-(w-tosyloxybuty1)-phenol (111) to spiro(4,5)-deca-lJ4-diene-3-one through so-called Arl 5 participation. Since then only a few examples of this type of reaction have been recordedzb and the application has been limited to simple p-substituted Me phenols. Refluxing a dilute (0.01 M) solution of I1 in NMe N ' -N // tert-butyl dcohol with a slight excess of potassium C6HsCOCH2C CsH2COCH2-c t-butoxide for six hours afforded in approximately \ Q 90% yield a colorless l i q ~ i d nZ% , ~ 1.5738 (found: N-N Ns 246 mp ( E 1.57 X lo4) C, 82.75, H , 8.17) "::A: XI1 XI11 6.02 p, 6.17, 6.22 (shoulder) ; semicarbazone, [infrared spectrum (CHzC1z)-4.69 p , 5.90, 6.17; ultraviolet spectrum (Et0H)-348 mp (6,000), m.p. 222-224' (found: C, 67.71, H, 7.52). In 285(1,500), 245 (12,500)]. This substance is the view of the elementary analyses and spectral evionly known simple iminoazide8; in hydroxylic dence, this liquid is represented by formula IV. solutions it cyclizes readily [tlI2 100 min. in The yield appeared to be the highest ever reported MeOH/H20: 1/1 a t 27'1 to the isomeric tetrazole for this type of reaction. Undoubtedly this smooth (XIII)s [infrared spectrum (CH2CI2)-5.90 p ; cyclization was effected by an advantageous orienultraviolet spectrum (Et0H)-285 mp (1,600), tation of the carbon atom carrying the tosylate 245(14,200)], which is hydrolyzed by hot 2 N group. Side reactions are suppressed by the tertiary sodium hydroxide to benzoic acid and 1,5-dimethyl- c g atom, a structural feature not present in 111. Preparation of 11.-The Reformatsky reaction of tetrazole, identical with an authentic sample.'O T h e reaction of the N-methyl-5-phenylisoxazo- 6-methoxy-P-tetralone4 with ethyl bromoacetate lium cation (I) with acetate ion to give the enol produced a P-hydroxy ester (V), b.p. 174-175' ester (IV) exemplifies a process for converting a (0.75 mm.) (found: C, 66.73, H , 7.75). The ester carboxylate group into a reactive ester group by a (V) was dehydrated with thionyl chloride and very rapid and smooth reaction, occurring under pyridine to an unsaturated ester (VI), b.p. 135conditions of exceptional mildness. The adaptation 137' (0.09 mm.) (found: C, 72.90, H, 7.60). of the reaction for use in a new method of peptide The unsaturated ester was reduced catalytically to synthesis is described in an accompanying com- afford ethyl 6-methoxy- lJ2,3,4-tetrahydronaphthalene-%acetate (VII) ,5 b.p. 127-128' (0.06 mm.), munication.7 We wish to express our appreciation of support which was reduced with lithium aluminum hydride by the National Science Foundation and the to the corresponding alcohol (VIII), b.p. 132-133' (0.07 mm.) (found: C, 75.81, H, 9.00). Pyrolysis National Institutes of Health. of the methylmagnesium iodide complex of VI11 a t ( 8 ) Cf.J. H. Boyer and E. J. Miller, Jr., J . A m . Chem. SOL,81, 4671 175' effected demethylation,'j affording a hydroxy (1959). phenol (IX), m.p. 88-90' (found: C, 75.12, H, (9) This substance was isolated, but described as having a different structure, by W. Stlilcken, ref. 2. 8.21). The phenol (IX) was converted t o II' (10) Cf.Chcm. Abs., 36, 2199 (1932). through the benzyl ether (X), m.p. 61-62' (found: CONVERSEMEMORIAL LABORATORY C, 81.17, H, 7.82) and the benzyl ether tosyl ester R. R. WOODWARD(XI) m.p. 76-78' HARVARD UNIVERSITY (found: C, 71.52, H, 6.50). CAMBRIDGE 38, MASSACHUSETTS R. A. OLOFSON Catalytic hydrogenolysis of XI with palladium on RECEIVED JANUARY 13, 1961 carbon proceeded without difficulty.
'I
-
SYNTHESIS OF 4a,6-ETHANO-5.6 7,s-TETRAHYDRO2(4a)-NAPHTHALENONE
Sir:
Recent investigations' have shown that the bicycle [3,2,l]octane system is a structural unit common t o a number of diterpene alkaloids and diterpenes, e.g., phyllocladene (I). We have searched (1) For instance. see: K. Wiesnet and 2. Valenta, Forfschr. Chem. or#. Nolursioffe, 16, 26 (1958); L. H.Briggs, B. F. Cain,B. R. Davis and J. K. Wllmshurst, Tetrahedron L c t t m , No. 8, 8 (1959).
(2) (a) S. Winstein and R . Baird, J. A m . Chem. Soc., 79, 756 (1957). (b) S. Doring and J. Harley-Mason, Chem. and Ind., 1551 (1959),and references cited therein. (3) This liquid was purified by silicic acid chromatography, then
evaporative distillation at 60' (0.1 mm.). (4) N. A. Nelson, R. S.P. Hsi, J. M. Shuck and L. D. Kahn, J . A m . Chem. SOC.,83, 2573 (1960). (5) The corresponding acid melts at 91-92O (found: C ,71.02, H,
7.13). (6) W.S. Johnson, E. R. Rogier and J. Ackerman, ibid., 78, 6322 (1956). (7) 11 was sensitive t o air oxidation and resisted crystallization.
Purification was achieved by silicic acid chromatography.
1010
COMMUNICATIONS TO THE EDITOR
The cyclization described in this Communication is of interest in gaining further understanding of Arl participation. Moreover, IV is quite suitable for the further construction of ring A of many natural products. The introduction of a ketone group a t Clo2band the construction of ring As are now in progress.g.I0
Vol. 83
form dimers slowly on ~ t a n d i n g ' , ~we , ~ Jhave considered this possibility in our case. Therefore, the structures considered for the interpretation of the spectrum are the monomer I, the chain dimer 11, and the cyclic dimers IT1 and IV.
(8) As an example of a conventional method for this purpose, see: G. Stork, H. J. E. Loewenthal and P. C. Mukharji, i b i d . , 78, 501 (1950). (9) The author is grateful to Mr. John Carmody for his helpful technical assistance. (10) This investigation was supported by a grant (RG-664G) from the National Institutes of Health, Public Health Service.
I
Me = CH, P h = C,H,
DEPARTMENT OF CHEMISTRY SATORU MASAMUNE OF WISCONSIN UNIVERSITY MADISON, WISCONSIN RECEIVEDJANUARY 21, 1961
Me" RESTRICTED ROTATION IN AMINOBORANES
I11
Iv
Sir: Structure I1 is ruled out because the two methyl I n a recent publication concerning unsymmetri- groups attached to nitrogen would be non-equivcally substituted aminoboranes of the type R1R2-alent, giving two bands. Structure IV would N B R B R the ~ tentative suggestion was made that have only one kind of methyl group attached to such compounds may exhibit cis-trans isomerism.' boron. An equilibrium between two or more forms This hypothesis was made, in the main, on the basis also is excluded because of the observation of only of the melting points and change of melting points three methyl resonances. Structure I11 is consistof mixtures of constant composition and of their ent with the room-temperature spectrum, but does molecular weights. We are now, on the basis of not afford any explanation of the change of band other observations, in a position to offer definite shape as the temperature is raised. Thus i t is conproof of hindered rotation about a boron-nitrogen cluded that our sample consisted of the monomeric form, I, in the whole temperature interval. bond, leading to cis and trans conformations. We have investigated the proton resonance specOn the basis of the temperature variation, up to trum of (methylphenylamino)-dimethylborane,2 118*,of the separation and shape for the resonances (CH3NCeHs)B(CH&, and find that, a t room tem- associated with methyl groups attached to boron, perature, the two methyl groups attached to boron we make a preliminary estimate of the barrier to are non-equivalent. When the temperature is rotation as 15 f 3 kilocalories per mole; the liferaised above 100' these two groups become magnet- time of the individual molecular states is about ically equivalent as rotation about the N-B bond second a t 100'. evidently becomes more rapid. (4) H. J. Brcher and J. Goubeau, 2. anorg. allgcm. Chcm., 268, 133 The p.m.r. spectrum a t room temperature, ob- (1952). (5) E. Wiberg, A. Botz and P. Buchheit, i b i d . , 868, 285 (1948). tained in a Varian high-resolution n.m.r. spectromOF CHEMISTRY GEORGE E. RYSCHKEWITSCH eter a t 60 mc., shows four distinct peaks: (1) a DEPARTMENT OF FLORIDA WALLACE S. BREY,JR. complex phenyl peak, (2) a single sharp N-methyl UNIVERSITY FLORIDA AKEMI SAJI peak a t 4.15 ppm. to high field of the center of the GAINESVILLE, RECEIVED DECEMBER 12, 1960 phenyl peak, (3) a sharp peak, assigned to one Bmethyl, a t 6.64 ppm. above the phenyl, and (4)a sharp peak, assigned to the other B-methyl, a t A NEW SYNTHESIS OF PEPTIDES 6.92 ppm. above phenyl. No other peaks appear. Sir: Peaks (3) and (4) are seen to be relatively close Carboxylates (RCOO-) react rapidly and together. As the temperature is raised, each of smoothly with 3-unsubstituted isoxazolium salts these peaks broadens and they move closer to- (I), under very mild conditions, to give enol esters gether, finally merging into one a t about 100'; (II).' We now record the application of this reaca t yet higher temperatures this single peak nar- tion as the carboxyl-activating step in a simple and rows. This is the characteristic behavior when the practical new synthesis of peptides. rate of intramolecular rotation varies with temperaR'~OCOR tures. a The molecular weight of (methylpheny1amino)dimethylborane has been determined, presumably H cryoscopically in benzene for a freshly distilled I sample, and indicated a monomeric species.2 However, since some aminoboranes are reported to Clearly the activating reagent (I) may be varied, through specific choices for the groups R', R 2 and (1) K. Niedenzu and J. W. Dawson, J . Am. Chcm. Soc., 82, 4223 (1960). R3,with a view to conferring a special degree of (2) B.P. 6 7 O at 14.0 mm., prepared according to R. Niedenzu and reactivity, or particular physical properties, on the J. W.Dawson, ibid., 81, 6663 (1959). reagent, the activated ester intermediate (11), or (3) J. A. Pople, W. G. Schneider and H. J. Bernstein, "Highresolution Nuclear Magnetic Resonance," McGraw-Hill Book Company, Inc., New York, N. Y.,1959, pp. 218-224.
(1) R. B. Woodward and R. A. Olofson. 1.Am. Chcm. Soc., 88, 1007 (1961).
