3356 J. Org. Chem., Vol. 36, No. 22, I971
SHROFF,STEWART, UHM,AND WHEELER
Synthesis of cis-2-Aza-3-oxo-4-oxabicyclo[4.2.0]octaneand cis-2-Aza-3-oxo-4-oxabicyclo[4.l.0]heptane C. C. SHROFF,~ W.S. STEW ART,^ S. J. U H M ,AND ~ J. W. WHEELER* Department of Chemistry, Howard University, Washington, D . C. 20001 Received December 26, 1070 Internal urethanes, cis-2-aza-3-oxo-4-oxabicyclo [4.2.O]octane (17)and cis-2-aza-3-oxo-4-oxabicyclo [4.1.0] heptane (7), have been synthesized. Reactions of these compounds and of their trans counterparts are discussed. The difference in reactivities of several comparable intermediates in the cyclopropane and cyclobutane systems is marked.
Although cyclopropanes2 and cyclobutanes3 containmolecules (3.56 us. 4.20) and an observation noted in ing functional groups on C1 and Ce have been studied the reduction of acid esters 4 and 12 indicates that relextensively, disubstituted molecules containing differative solubilities of the intermediate boron compounds ent functional groups have received scant n ~ t i c e . ~ are ~ ~ important. While turbidity disappears upon furWe have investigated a series of 1,2-disubstituted threether introduction of diborane with the cyclobutyl comand four-membered rings with known stereochemistry. pound, a viscous gum precipitates on the sides of the Our starting point for each synthesis was the 1,2flask and does not redissolve with the cyclopropyl diacid l6or 10.' The cis series was prepared from the analog. anhydride 2 (or 11) as outlined in Schemes I and 11. This difference in the behavior of cyclopropane and Reduction of acid chloride ester 13 gave cyclobutane cyclobutane systems was amplified in conversion of alcohol ester 14.* Although the cyclopropane alcohol hydrazides 6 and 16 to cyclic urethanes 7 and 17. ester 4 spontaneously closed to lactone 5,4d,ecycloTreatment of cyclobutane alcohol hydrazide 16 with butane alcohol ester 14 was somewhat more stable. nitrous acid gave 2-aza-3-oxo-4-oxabicyclo [4.2.O]ocAlaier and SayracI4dand IGrmse and Dietrich4e have tane (17) in good yield under a variety of conditions. prepared lactone 5 by two alternate routes, both proI n contrast, treatment of cyclopropane alcohol hydracedures involve separation from other products. zide 6 with nitrous acid gave large amounts of lactone While reduction of cyclobutane acid ester 12 to al5 as well as 2-aza-3-oxo-4-oxabicyclo [4.1,O]heptane cohol ester 14 by diborane was accomplished cleanly (7). Urethane 7 could be prepared in satisfactory yield with formation of little diol as a by-product, reduction only by rigorous control of both the acidity of the soluof cyclopropane acid ester 3 to alcohol ester 4 was tion and temperature. Formation of lactone 5 was grossly incomplete. Further reduction of the mixture greatly facilitated by addition of ferric chloride, a Lewis gave 5 1 0 % of diol as well as 4. acid used to convert azides to isocyanates.'l The two Since reduction of carboxylic acids with diborane insubstituents (hydroxymethyl and azide) which are ~ volves formation of a t r i a ~ y l b o r a t e ,intramolecular necessarily eclipsed in the cyclopropane case must be hydrogen bonding might account for the difference in ideally situated so that the hydroxyl group can particia , ~determined the reduction of 4 and 12. I l l ~ C o y l ~has pate. Lewis acid complexation of the carbonyl oxygen facilitates nucleophilic attack at the carbonyl carpK1 of l b and Bodelo" has determined the pK1 of lob. bon by the hydroxyl group. Loss of hydrazine from The small difference in acid strength between these two the protonated hydrazide and loss of azide ion from (1) Abstracted from the Ph.D. Dissert,ations of C. C. Shroff and W. S. azide leads not to urethane 7 but to lactone 5. This Stewart, 1969, and the M.S. Thesis of S. J. Uhm, 1970, HowardUniversity. became most apparent when the azide reverted to lac(2) J. K. Hecht, J. J. Flynn, and F. P. Boer, J . Org. Chem., 34, 3645 tone 5 even in a chloroform extract which was free of (1969); F. 1%'. Breitbeil, D. T. Dennerlein, A. E. Fiebig, and R . E. Kuznicki, ibid., SS, 3389 (1968); 9. Sawada, K. Takehana, and Y. Inouye, ihid., 83, acid. I n contrast, the cyclobutane substituents are not 1767 (1968); 0. L. Chapman and R . A. Fugiel, J . Amer. Chem. Soc., 91, eclipsed and formation of lactone 15 presents no serious 216 (1969); T. J. Curphey, C. W. Amelotti, T. P. Layloff, R . L. McCartney, and D. B. Priddy, ibid., 91, 3677 (1969); T. Shono, T. Morikama, A. Oku, problem. and R. Oda, Tetrahedron Lett., 791, 1964; L. L. McCoy, J . Amer. Chem. Sac., Treatment of either urethane 7 or 17 in dioxane with 84,2246 (1962), and references therein. gaseous hydrogen bromide gave bromomethylamine (3) L. I. Peterson, R. B. Hager, 8. F. Vellturo, and G. W. Griffin, J. O w . Chem., 33, 1018 (1968); J. J. Gajemski and C. N. Shih, J . Amer. Chem. hydrobromide 8 or 18. Although cyclobutane 18 is Soc., 91, 5900 (1969); P. Heimbach and W. Brenner, Angem. Chem., 79, stable at room temperature, the cyclopropane analog 8 814 (1967). is unstable even at 5" on prolonged standing. (4) (a) K. B. Wiberg, R. K. Barnes, and J. Albin, J . Amer. Chem. Soc., 79, 4994 (1957); (b) W. G. Dauben and G. W.Shaffer, J . Org. Chem.. 3 4 , Ring expansion of urethanes 7 or 17 might occur on 2301 (1969); (c) 8. J. Rhoads and R . D. Cockroft, J . Amer. Chem. Soc., treatment with hydrogen bromide. However, the spec91, 2815 (1969); (d) G. Maier and T. Sayrac, Ber., 101, 1354 (1968); ( e ) troscopic properties of the products 8 and 18 indicate W. Kirmse and H. Dietrich, ibid., 98, 4028 (1965). (5) (a) R. Gelin, S. Gelin, and C. Boutin, C. E. Acad. Sei., 260, 6393 (1965) ; that cyclopropane and cyclobutane rings are intact. (b) P. G. Gassman and K . T. Mansfield, J. OW. Chem., Sa, 915 (1967). The strong absorptions at 5.0 I* in the infrared spectra ( 6 ) L. L. McCoy, J . Amer. Chem. Soc., 80,6568 (1958). (7) E. C. Coyner and W. S. Hillman, zbid., 71, 324 (1949); subsequently of the two products can be assigned to a CH2-Br wagpurchased from Aldrich Chemical Co. ging vibration.12 (8) Contrary t o expectations considerable amounts of diol were formed Treatment of 8 or 18 with thallium (or sodium) thiowhen diborane was bubbled through tbe solution for a longer period (H. 0. House, "Modern Synthetic Reactions," W.A. Benjamin, New Pork, N. Y., sulfate in either water or methanol gave crude materials 1965, p 43). The original literature indicates t h a t acid chlorides are relatively inert. See ref 9. (9) H. C. Brown and W.Korytnyk, J . Amer. Chem. Sac., 82, 3866 (1960); H. C. Brown and B. C. Subba Rao, ibid., 82, 681 (1960). (10) (a) L. L. McCoy, ibid., 85, 1321 (1963); (b) L. L. McCoy, J . OW. Chem., SO, 3762 (1965); (c) H. Bode, Ber., 67B,332 (1934).
(11) & 8.'I Newman, . J . Amer. Chem. Sac., 70, 317 (1948); R. A. Coleman and M.S. Newman, ibid., 76,4534 (1954). (12) R . M. Silverstein and G. C. Bassler, "Spectrometric Identification of Organic Compounds," Wiley, New York, N . Y., 1968, p 102.
CiS-2-AZA-3-OX~D-4-OXABICYCLOOCTANE AND
J . Org. Chem., Vol. 36, No. 22, 1971 3357
-HEPTANE
SCHEME I
6
C H ~ NH:
I
---6 Tl,Sz08 CHz
9
4
3
~
CH,
NH
8
78% HONO
\0-coI
I Br
SZO,
COzCHs
2
-97% HBr
NH3+Br-
HOHZC
COZH COgCH,
COzH COZH lb
COZH la
NHzNHz c--
CH2 CONHNH2
I OH
7
95%
5
6
SCHEME I1
@.A&&247 2/ COzH
c\/
COzH COzH
COZH COzCH,
*l 0
NaBH, i-PrOH
93%
