J. Org. Chem. 1980,45, 4720-4725
4720
Registry No. 1, 41757-95-3; 2, 67722-63-8; 3, 74965-98-3; 4, 68817-65-2; 5, 68817-66-3; 6a, 67722-68-3; 6b, 67722-67-2; 7, 7496624-8; 8,74966-25-9; 9, 74966-26-0; 10,74966-27-1; 11,74966-28-2; 12a, 67722-80-9; 12b, 67722-79-6; 13, 68817-64-1; 14, 74966-29-3; 15, 74966-30-6; 16, 74966-15-7; 17a, 67722-76-3; 17b, 67722-75-2; 18, 74966-16-8; 19, 74966-17-9; 20, 74966-18-0; 21a, 67722-84-3; 21b, 67722-83-2; 22, 74966-19-1; 23, 74966-20-4; 24, 41757-96-4; 25, 67722-85-4; 26, 74965-99-4; 27a, 67722-87-6; 27b, 67722-86-5; 28, 74966-21-5; 29, 74966-22-6; 30, 74966-23-7; 31, 74978-11-3; 32, 74966-02-2; 33, 74966-03-3; 34, 74966-05-5; 35a, 67722-89-8; 35b, 67722-88-7; 36, 74966-04-4; 37a, 67722-91-2; 37b, 67722-90-1; 38, 74966-06-6; 40, 70936-91-3; 41, 74966-07-7; 42, 74966-08-8; 43a,
74670-66-9; 43b, 52755-95-0; 44, 74966-09-9; 45, 74966-10-2; 46, 74966-11-3; 47, 74966-12-4; 48a, 74966-00-0; 48b, 74966-01-1; 49, 71035-28-4; 50, 74966-13-5; 52, 74966-14-6; benzo-15-crown-5, 14098-44-3; dibenzo-18-crown-6, 14187-32-7; dibenzo-24-crown-8, 14174-09-5; acetic acid, 64-19-7; heptanoic acid, 111-14-8; tetradecanoic acid, 544-63-8; propanoic acid, 79-09-4; butyric acid, 107-92-6; isobutyric acid, 79-31-2; valeric acid, 109-52-4; isovaleric acid, 50374-2; pivalic acid, 75-98-9; hexanoic acid, 142-62-1; benzoic acid, 65-85-0; nonanoic acid, 112-05-0; decanoic acid, 334-48-5; dodecanoic acid, 143-07-7; octadecanoic acid, 57-11-4; acetyl chloride, 75-36-5; decanoyl chloride, 112-13-0; 4-methylcatechol, 452-86-8; 4-tert-butylcatechol, 98-29-3.
Synthesis of 2,2’-Diacyl-l,l’-biaryls.Regiocontrolled Protection of Ketones in Unsymmetrically Substituted 9,lO-Phenanthrenequinones Miljenko MerviE and Eugene Ghera* Department of Organic Chemistry, The Weizmann Institute of Science, Rehouot, Israel
Received March 26, 1980
A regiocontrolled monoketalization of unsymmetrically substituted phenanthrenequinones by use of 2,2-dimethyl-1,3-propanediol as the ketalizing reagent has been effected with the help of bromo substitution in one of the aromatic rings at the C-1 or C-8 position. The effect of bromo substitution is of a steric nature and the ketalization enabled the regioselective elaboration of 9,lM.etrasubstituted phenanthrenediols which on subsequent oxidative cleavage afforded the required biaryls with nonidentical (2 and 2’) acyl groups.
A recent synthetic approach leading to bis(benzocyc1ooctadiene) lignans, members of the schizandrin group, has been based on zinc-induced cyclization reactions of 2,2‘bis(a-bromoacyl)derivatives of l,l’-biaryls.l In connection with our continuing interest in the synthesis of biologically active lignans with the bis(benzocyc1ooctadiene)structural framework, it was necessary to develop a synthetic route to unsymmetrical biaryls of structure A (where X and Y represent various substituents), possessing nonidentical 2,2’-acyl groups (R1-R4 = H, alkyl, alkenyl, or oxygencontaining carbon groups). Introduction of an a-bromo substituent at each acyl group would then provide the substrates needed for the zinc-induced cyclization leading to the tricyclic diketones B, potential intermediates for the
B
A R
R’
L !
X
my C
elaboration of the natural compounds. From a search of previous work in this area we were not aware of an effective route leading to systems A. The Ullman reaction does not usually provide an effective answer for the coupling of nonidentical aryl moieties, whereas the recently reported (1) (a) E. Ghera, Y. Ben David, and D. Becker, Tetrahedron Lett., 463 (1977); (b) M. MerviE:and E. Ghera, J. Am. Chem. Soc., 99,7673 (1977); (c) E. Ghera and Y. Ben David, J . Chem. Soc., Chem. Commun., 480 (1978). 0022-32631801 I945-472O$OI.O0/0
coupling of a-haloarylimines2 and of other haloaryl derivative~~ did not involve compounds with (latent) ketone groups in both moieties. Moreover, the selective halogenation required by the above-mentioned methods at coupling sites in both moieties is sometimes difficult to bring about in the presence of other substituents in the rings. A different approach leading to biaryls A can be envisaged via the oxidative cleavage of the 9,lO-substituted bond of unsymmetrical phenanthrenes. However, in spite of a large variety of methods for the synthesis of phenanthrenes: no effective route leading to phenanthrenes of structure C with nonidentical C-9 and C-10 carbon groups (R, R1) and unsymmetrical substitution in the peripheral rings is a ~ a i l a b l e . ~ The present investigation was therefore intended to approach the synthesis of biaryls A by developing a general route for the regiocontrolled substitution of the 9,lO-bond of unsymmetrical phenanthrenes. We now describe how this objective can be achieved by a selective ketalization, when a bromine substituent is adjacent to one of the carbonyl functions of the corresponding phenanthrenequinones. (2) F. E. Ziegler, K. W. Fowler, and S. Kanfer, J. Am. Chem. Soc., 98, 8282 (1976);F. E. Ziegler, K. W. Fowler, and N. D. Sinha, Tetrahedron Lett., 2767 (1978);A. S. Kende and D. P. Curran, J . Am. Chem. Soc., 101, 1857 (1979). (3) E. Negishi, A. 0. King, and W. Okukado, J. Org. Chem., 42,1821 (1977); E. R. Larson and R. A. Raphael, Tetrahedron Lett., 5041 (1979). (4) A. J. Floyd, S. F. Dyke, and S. E. Ward, Chem. Reu., 76,509 (1976); see also A. J. Liepa and R. E. Summons, J. Chem. Soc., Chem. Commun., 826 (1977). (5) For a synthesis of some phenanthrenes of this structure via acid-
catalysed cyclodehydration which requires, however, a preliminary preparation of biaryls, aee C. K. Bradsher and L. S. Wissow, J.Am. Chem. Soc., 68,2149 (1946); C. K. Bradsher and W. J. Jackson, ibid., 76,4140 (1954). The Perkin-Pschorr sequence to 9-carboxylates,Bfollowed by other steps for C-10 substitution, may also possibly provide a route for the regioselective preparation of systems C although no literature examples of such syntheses were found. (6) D. F. DeTar, Org. React., 9, 409 (1957).
0 1980 American Chemical Society
J. Org, Chem., Vol. 45, No. 23,1980 4721
Synthesis of 2,2’-DiacyLl,l’-biaryls Scheme Ia CHO
CH2PPP3Br
R’
R+4
+
Table I. Characterization of Phenanthrenequinonesaib
R8
yield,
-
p+7
4
3
lbd
74
mp, C 195-197
IC
77
154
7a
71
159-161
7b
75
112-113
7d’
77
203-204
7e
75
163-165
7f’
73
206-208
7g
72
291-292
7h
71
185-187
%c
5
6a b c d d‘ e f f‘ g h
R’
6 R2
H H H H Br H H Br Br H
OMe OMe OMe OMe OMe Me OMe OMe H Me
7
R4
R3
OMe OMe OMe OMe OMe OMe OMe OMe OMe OMe H Me OMe OMe OMe OMe OCH,O H Me
R5
R6
H OMe OMe H H H H H H H
H H OMe OMe CCH,O OCH,O OCH,O H H Br H CN H Br H Br H
R’
R* H Br Br H H Br H H H H
a Substituents R1-R* in compounds 3, 4,and 5 are the same as those in phenanthrenes 6, except for 6b (R* = H in the precursors), 6d’ (see 6d for substitution) and 6f’ (see 6f).
The possibility of selectively protecting one of the ketone groups was first investigated in phenanthrenequinone itself and in its symmetrically substituted derivatives lb and IC. Cyclic ketals were chosen as suitable protecting groups, the ease of formation of which is known to be influenced by steric and electronic factors.’ Although the possibility of reacting only one of the ketone groups in la has long been known,8 we found that ethylene glycol was unsuitable as a reagent for selective monoketalization: mixtures of mono- and bisketals were obtained along with starting material from compounds la-c by treatment with 1equiv O
w
X
(7) See, e.g., (a) H. J. Dauben, B. Loken, and H. J. Ringold, J. Am. Chem. SOC.,76, 1359 (1954); (b) S. W. Smith and M. S. Newman, ibid., 90, 1249, 1253 (1968); (c) G. Bauduin, and Y. Pietrasanta, Tetrahedron, 29, 4225 (1973); (d) G. Bauduin, Y. Pietrasanta, and B. Pucci, Tetrahedron Lett., 2889 (1975). (8) See, e.g., H. Goldschmidt, Chem. Ber., 16, 2178 (1883); P. V. Laakso, R. Robinson, and H. P. Vandrewala, Tetrahedron, 1,103 (1957); R. Kuhn and H. Trischmann, Chem. Ber., 94, 2258 (1961).
NMR, 6 2.27 (s. 6). 2.38 (s. 6),, . 7.36 (s. 2), ?.’66(s, 2) 3.78(s, 6),3.94 (s, 6),4.01(s, 6),7.35 (s, 2) 3.88(s, 3), 3.96(s, 3),4.03(s, 3), 7.41 (d, J = 8 Hz, l), 7.55(s, l), 7.70 (d, J = 8 Hz, l), 8.11( d , J = 8 Hz, l), 8.80(d, J = 8 Hz, I) 3.75 (s, 3), 3.80(s, 3), 3.94 (s, 6),3.99 (s, 3),4.05(s, 3), 7.28(s, 1) 3.80 (s, 3), 3.92(s, 3),4.06(s, 3), 6.10(s, 2) 7.43(s, l), 8.16 (s, 1) 2.38 (s, 3), 2.63(s, 3), 7.347.68(m, 5) 3.89 (s, 3), 3.96(s, 3),4.10(s, 3), 7.70(d, J = 8 Hz, l), 8.10(d, J = 8 Hz, l), 9.02 \
I
\
,
(s, 1)
6.30(s, 2), 7.21(s, l), 7.61 (d, J = 8 Hz, l), 8.00(d, J = 8 Hz, l), 8.63(s, 1) 2.37 (s, 3), 2.71(s, 3), 7.28(s, l), 7.40-8.05(m, 4)
a For substituents in phenanthrenequinones 7a-h see the corresponding phenanthrenes, Scheme I. For characterization of 7c, see ref 1b. Satisfactory elemental analyses were obtained for all new phenanthrenequinones. Overall yields (from phenanthrenes) include 10-15% recovered starting material, For 2,4,5,7-tetramethylphenanthrene, used for the preparation of l b , see E. V. Blackburn, C. E. Loader, and C. J. Timmons, J. Chem. SOC.C, 1576 (1968).
kinetic control conditions. Use of the bulkier 2,2-dimethyl-l,&propanediol (DMPD) provided, however, under similar conditions, better selectivity: compounds la and IC were converted to monoketals 2a and 2c exclusively, whereas from lb only a small amount of bisketal (
