EQUILENXHYDROARO~IATIC WITH AKGULAR L~ETHYLGROUPS
May 20, 1950:
[ COSTRIBUTIOS FROM
LABORATORY, THE
THE AICPHERSOS CHEMIC.4L
2331
OHIO STATE UNIVERSITY]
Synthesis of Hydroaromatic Compounds Containing Angular Methyl Groups. Equilenin Series B Y GEOFFREY EGLINTON,' J.
c. NEVENZEL,'
A. I.
SCOTT3 A S D L f E L V I N
V.
s. N E W N A N 4
RECEIVED SOVEMBER 18, 1955 The sl-ntheses of cis- ( V I ) and trii~zs-3-1netlioxy-ll-ketocquilenane ( I S ) and of S-methos)--ll-keto-l.2,l~-deh?.droequilenane (17111) are described.
In this paper the application of methods previously developed for the synthesis of hydroaromatic compounds containing angular methyl groups and ketonic functionsb to the synthesis of cis- and trans-3-methoxy-ll-ketoequilenane, VI and IX, is described. The synthetic scheme is illustrated in the chart.
to IX under conditions which led to ready ring closure in the cis series (V to VI). However, this difficulty was overcome by cyclization of the unsaturated acid VI1 to VIII, followed by hydrogenation. The structures of the final products VI and IX were established by reduction to the corresponding CHB
R '01C \,I\ CHB
CHB R'02 "\:Al RLi
4-
o/i-l
I
+
I
SI
@ '
CH,/W
I1
I
'
'
x1.1
1, H30' 2, OH-
IS
In general the yields were satisfactory although not precisely determined in every case. An interesting feature of these syntheses is the stereospecificity of reduction. Route A (on the right) led mainly to the cis isomer, reduction being effected before homologation. Route B led mainly to the trans isomer, reduction being effected after homologation and cyclization. This reversal of stereochemical specificity would not have been predicted by any current theory regarding catalytic hydrogenation and the explanation is not apparent from study of molecular models. A noteworthy feature of route B is that the saturated trans-acid X did not cyclize (1) Post-doctoral Fellow, U. ( 2 ) Post-doctoral Fellow, U.
1,OH+ 2, H i -
R is the 6-methoxy-2-naphthyl radical
1-111
O\\-IA,
S . Public Health Service, 1951-1952, S. Public Health Service, 1949-1951.
( 3 ) Post-doctoral Fellow, U. S. Public Health Service, 1952-1953. (4) T o whom inquiries should be sent. is) fa) hf. S . Newman and A l . 12. Farhman, T H I S J O U R I I A L , 66, I.5.X (1944); (hj M. S . Newman and K. D . Closson. i b i d . , 66, 15.53 ( In I 4 I , ( c ) A I . S. N e a m a n , C.. Eglinton and €i. (:rotta, zbzii , 75, 31!4 ll%%): ( d ) G. Rglintnn, J . C . Nevenzel, R1. S. Newman and A . I. : i c o t t , ( ' k e r n i s f r y b I i l d i r i t i y , 685 (19;3)
X~.III-cis SIX-trans
\'I
cis-and truns-3-xricthoxyequilenanesXVII I and X I X and direct comparison of these with authentic samp l e ~ . The ~ structure of VI11 was also confirmed by Huang-Minlon reduction to 3-methoxy-13,l%dehydroequilenarie (XVII). The trans compound IX was demethylated to the corresponding trans-3hydroxy- 1I-ketoequilenane, but the corresponding cis-3-hydroxy-1 1-ketoequilenane was not obtained pure. *is in previous cases,jc if the hydroxy ester were hydrolyzed with alkali, an open chain keto acid XI (R = H) was obtained. MThen the isopropyl ester of XI was heated to 200" with boric acid, a compound was obtained which is believed to be the diketone XI1 on the basis of its analysis, infrared spectrum and chemical behavior. The same diketone XI1 was obtained in small yield from alkaline hydrolysis of the isopropyl ester of 11, presumably by way (fi)A . 1,. Wilds, J . A . Johnson, .Ir , and I
