COMMUNICATIONS TO THE EDITOR
July 20, 1962
TABLE I Run No.
1 2 3 4
5
6
Base-
c
Solvent
Nature
(CH3)aCOH n-CdHgOH CzHbOH CHaOH HOCHzCHzOH HzO
(CH3)aCOK TZ-C~HBOK CzHsOK CH30K HOCHzCHzOK HOK
7 8 9 10 11 12 Solutions 0.32 M in water.
Concn., N
0.30 0.30 0.37 0.30 0.085-1.00 0.30-1.1-9.7
(CH3)xCOK 0.16 (CH3)rN'OH0.16 HOCHzCHzOK 0.34 (CHa)dN+OH0.34 HOCHzCHzOK 0.088 (CH3)rN'OH0.11 Solutions 0.68 M in H2O.
T;
Yield,
100 100
83 72 58 73 21-48 27-58
c.
100 100 100 100
53 53 25 25 53 53
%
78 59 52 50 51 42
Ket steric course
80% Ret. 68% Ret. 60% Ret. 44y0 Ret. 15-3770 Ret. 2 % Inv.-lOyo I n ~ . - 7 0 7Ret. ~ 92% Ret. 60% Ret. 48% Ret. 46% Ret. 37'% Ret. 3470 Ret.
of a proton donor a t the front of the carbanion in amide (+)-I, m.p. 112-112.2', rQ1Iz5546 +32.6' (c 9, dioxane), was prepared from (-t)-II, [ C ~ ] ~ ~ 6 4 6the base-catalyzed reaction of RN,H provides for +12.8' ( I = 1 dm., neat), by the usual method. the retention mechanism, whereas a nitrogen Repeated recrystallization of grossly optically molecule as a shield a t the front of the carbanion impure (-)-I from ether-pentane gave optically provides for the inversion mechanism.' (4) In relatively non-polar solvents the homolytic cleavage [a!Iz5646 -35.4' pure (-)-I, m.p. 112.5-113', (c 9, dioxane). These data relate the configura- of RNzH can be eliminated, but not in water or tions and maximum rotations of starting materials ethylene glycol. (5) In water, different intermediates are involved in the anionic cleavage and products in reactions ( l ) , (2) and (3). Cleavage of sulfonamide (+)-I without base a t depending on whether I or I1 are starting materials. 100' in water, t-butyl alcohol or dimethyl (7) Compare nitrogen as leaving group with carbon and hydrogen. sulfoxide gave completely racemic 111. Results (a) D. J. Cram, J. L. Mateos, F. Hauck, A. Langemann, K. R. Kopecky, obtained in the presence of base are summarized W. D. Nielsen and J. Allinger, ibid., 81,5774 (1959); (b) D. J. Cram, A. Kingsbury and B. Rickborn, ibid., 83,3688 (1961). in Table I. Except in ethylene glycol and water, C. (8) Eastman Kodak Fellow, 1961-1962. base concentrations were reached where an inDEPARTMENT OF CHEMISTRY DONALD J. CRAM crease in base did not change stereospecificity. JERALD S. BRADSHAW~ In ethylene glycol, retention increased regularly UNIVERSITY OF CALIFORNIA AT WALTERLWOWSKI as base was increased (run 5 ) . I n water, as base Los ANGELES, GRAHAM R. KNOX 24, CALIFORNIA concentration increased, the reaction occurred Los ANGELES RECEIVED JUNE 4, 1962 first with increasing net inversion and then with increasing net retention (run 6). Oxidation of I1 with potassium periodate under EVIDENCE FOR PARALLEL CONTROL OF REACTION conditions of runs 1, 3 and 4 gave results within RATE AND STEREOCHEMISTRY via THE experimental error of the corresponding cleavages ELECTROSTATIC INFLUENCE OF REMOTE SUBSTITUENT DIPOLES of I. In water, oxidation of I1 without base a t 100' gave 1 0 0 ~ oracemization, whereas a t 0.012 Sir : We wish to report evidence we have obtained in to 0.30 ill base, 30-32y0 inversion was observed studies of sodium borohydride reduction of 4(compare with run 6). Treatment of (-)-2-phenyl-2-butylamine p - substituted cyclohexanones indicating that, in toluenesulfonate ( 9 5 O , 3 M solution of sodium systems where rate variations are strongly governed hydroxide in 90yo water-l OyOethanol) with hy- by remote substituent effects, parallel control of droxyl~imiiie-0-sulionicacid6 gave I11 (10%) with product stereochemistry also is exercised. Fur32% net retention. Cleavage of I under the thermore, the existence of a field effect of this nature average conditions of the above reaction gave I11 appears to be unexpected in view of assumptions (83Oj,) with 37y0 net retention. Oxidation of I1 to the contrary applied in various interpretatioiis under the same average conditions gave I11 (10%) of rate and stereochemical effects.1-6 The rates of reduction obtained by use of the with net retention. The stereochemical results vary enough with concentrations of kinetic method devised by Brown and c o - w ~ r k e r s ~ hydroxylamine, base and sodium sulfate to make are presented in the accompanying data table. the three results within experimental error of one The existence of a linear free energy relationship another. (1) W. G. Dauben, G. J. Fonken and D. S.Noyce, J. A m . Chem. These data suggest several conclusions : (1) Soc., 78,2579 (1956). (2) W. G. Dauben and R. E Bozak, J. Org. Chem., 24, 1596 (1959). The same intermediate, probably RN2H, is pro(3) A. H. Beckett, N. J. Harper, A. D. J. Balon and T. H. E. duced in all three of the reactions employed. (2) Watts, Tetrahedron, 6 , 319 (1959). This intermediate partitions between a base(4) W. M. Jones and H. E. Wise, Jr., J . Am. Chem. SOL, 84, 997 catalyzed anionic elimination reaction t o give 111 (1962). (5) S. Winstein and N. J. Holness, ibid., 7 7 , 5562 (1955). somewhat stereospecifically, and a homolytic (6) E. L. Eliel, J . Chem. Educ., 37,126 (1960). elimination to give racemic 111. (3) Generation ( 6 ) A Nickon and A. Sinz, J. Am. Chcm. Sac., 82,753 (1960).
(7) H. C. Brown, 0. H. Wheeler and K. Ichikawa, Tetrahedron, Vol. 1, 214 (1957).
2834
Vol. 84
COMMUNICATIONS TO THE EDITOR
TABLE I RATEAND PRODUCT DATA 4 -Substituted cyclohexanone
NaBHr Reductionb
I"
S a B H I ProductC 70 (cis)
102 ( k ) (1. mole-' sec. - 1 )
Al(oipr)s % cis
-H 0 1.62 (1.61)' ... ... 26.1 -CHa +0.03 1.90 22.4 (1512, 253) -di-CHa +0.09 2.40 ... t-Bu + O . 016 2.47 24.1 (21)6 -0CHS +0.25 5.72 41.4 49.1 -COOC2H' $0.30 7.42 73.8 -OCOC6H5 + O . 469 19.9 67.0 49.2 - Cl +0.47 21.9 66.0 (S3)I2 48.1 a M o s t of these values were obtained from R . W. Taft, J . A m . Chem. Soc., 79, 1045 (1957). The positive UI values of alkyl groups were inferred from the data given in ref. 8. Rates were measured a t 0" in isopropyl alcohol solution according to the procedure of ref. 7. Determination of the cis-trans composition of the product was carried out by vapor phase chromatography on the quantitatively acetylated product mixture.
is established by the plot of log k us. U I from which PI = +2.78 was computed. For comparison purposes the corresponding rates of reduction of a series of para substituted acetophenones were measured, yielding a value PH = +2.6. Once agains we note that the somewhat greater value of PI vs. PH correlates with the smaller distance of separation from the reaction center and the magnitude and orientation of the substituent dipole. The question as to whether the polar substituent effect is transmitted predominantly through the carbon chain or through the dielectric medium surrounding these bonds is clearly answered by the stereochemistry of the cyclohexanol products (also listed in the table). Thus, although the number and types of bonds between the substituent and reaction centers are identical for the alternative transition states leading (respectively) to cis and trans product, it is quite apparent that the degree of preference for formation of the cis product is directly proportional to the electron withdrawing capacity of the substituent. Furthermore, when the ~1 values of the substituents are plotted against the log of the cis product fraction, the resulting linear relationship suggests that the identical electrostatic effects are a t work deciding both rate and stereochemistry. The preference for cis product formation induced by electronegative substituents is obviously the consequence of the shorter distance and (thereby) increased electrostatic interaction in the cis transition state. By means of a simple graphical computation9it is possible to dissect the stereop1 (as distinct from the ve1oc.-pI) into two components: pcis= 3.78 and ptvans = +1.96. This affords a quantitative measure of the greater probability of the cis transition state developing in the field of a remote electronegative center.
+
(8) H. K w a r t and L. J. Miller, J . .4m.Chem. Soc., 83, 4552 (1961). (9) From various plots of t h e product composition d a t a os. PI these equations can be deduced
+ log (k, + kt) 2.78 + 0.18 2 + log (re-) k + kc 1.0 1.35 2 4- log "-) k, 0.82 + 1.94
(a) 2 (b) (c)
=
UI
=
UI+
=
UI
t
(kt
+
B y simple transfnrmations and substitutions we obtain
( d ) log k, = 3.78 (e)
UI
log kt = 1.96 UI
- 2.47 - 1.88
where ko and kt are the calculated r a t e cun,tants corresponding t o L L S and tvaus alcohol formation.
Since the transition state for borohydride reduction of ketones is known to resemble the structure of the products we have deduced that (I) and (11) depict the (respective) cis and trans chargedipole interactions.10 It will be seen that a single 06-
I
I1 Et0
I11
point, that of the carbethoxyl group, stands above the stereo-pI line, though the corresponding group value accords very well with the veloc. PI line. The greater extent of cis product formation, than is predictable from the U I value, suggests the operation of a factor previously identified for the -COOEt group in our earlier studies on addition to cyclohexenes. Here the propensity for neighboring group participation by the -COOEt group can result in the reaction passing through the boat conformation in the transition state depicted by (111). This would effect a somewhat exalted amount of cis product without necessarily causing significant departure of the log k value predicted by the ve1oc.-PI line. Clearly the additional energy expended in achieving the unfavorable boat is regained in the form of the resulting increased interaction energy. I t may be predicted, too, that a change in the character of the reducing agent from borohydride to aluminum isopropylate will alter the extent of electrostatic interaction and thereby stereochemical control by the remote substituent. This follows from the coordinating capacity of the aluminum tending to diminish the charge developing on oxygen in the transition state represented by IV. The limited number of data we have obtained thus far appear to bear out this conclusion since the plot of log 70cis vs. UI is clearly non-linear, im(10) See also h l . G. Combe and H G. Henbest, Telvahedvon L e f l e v s . 404 (1961), where t h e authors have suggested entirely similar rrprrsentations of these transition states.
July 20, 1962
~ O l t I l t l U N I C 4 T I O N STO THE EDITOR
2s33
Hydrogenation’O of (11) yielded the alkyl derivative (111). Anal. Calcd. for C35H4003hr4: C, 74.44; H, 7.14; N, 9.92. Found: C, 73.86; H, 7.17; N, 9.94. Oxidative degradation of (111) yielded only methylethylmaleimide in the neutral fraction. Oxidation of (I) by oxygen in alkaline dimethylformamide yielded a dicarbonyl derivative (IV) . IV Anal. Calcd. for C35H3806N4:C , 70.68; H, 6.44; plying that product formation is controlled by K, 9.42. Found: C, 70.31; H, 6.32; K, 9.46. other factors than the field effect of the remote Under the same conditions mesopyropheophorbide substituent. a (V) yielded the C9-Clo ring diketone.” (111) was likewise oxidized to its dicarbonyl derivative DEPARTMENT OF CHEMISTRY UNIVERSITYOF DELAWARE HAROLD KWART (VI). Further oxidation of (VI) by HzOz in alkaNEWARK, DELAWARE T. TAKESHITA line dimethylformamide yielded a tricarboxylic RECEIVED MAY24,1962 acid (VII). A portion was methylated and converted to its zinc complex. Anal. Calcd. for ZnC35H3cO3N4(OCH3),: OCH,, 13.0. Found: OCH,, STUDIES OF CHLOROBIUM CHLOROPHYLLS. V. 12.9. The remainder was dried a t 100’ to yield CHLOROBIUM CHLOROPHYLLS (660)’ a product (VIII) whose visible absorption spectrum Sir: resembled that of purpurin 18.12 It was methylThe evidence presented below suggests that ated and converted to its zinc complex. Anal. Chlorobium chlorophylls (660) are derivatives of Calcd. for ZnCa5Ha504N4(0CH3) : OCH3, 4.62. 6 - methyl - 2 - desvinyl - 2 - cz - hydroxyethyl- Found: OCH3, 3.03. Dilute methanolic KOH pyropheophorbide converted (VIII) back to (VII). Treatment of Hydrolysis of crude “pheophytin” (660) in dilute the trimethyl ester of (VII) with methanolic KOH hot methanolic KOH and partition chromatography in pyridine did not generate the Molisch phase between aqueous HC1 and ether on Celite columns4 test intermediate as i t does when chlorinee-trigave seven fractions which were designated 1-7. methyl ester is treated 1 i k e ~ i s e . l This ~ result All fractions possessed a conjugated carbonyl excluded the possibility of a cyclohexanone ring group5; all possessed a hydroxyalkyl group which in (I). could be oxidized to a conjugated carbonyl group6 HI in acetic acid converted (I) into a porphyrin or dehydrated t o an alkenyl group?; all gave a containing a conjugated carbonyl group and an negative hlolisch phase test.8 Comparison of ethyl in place of a hydroxyethyl group., .4nal. their visible absorption spectra revealed no sig- Calcd. for C35H3803N4: C, 73.70; H, 6.81; N, nificant differences among them. 9.96. Found: C, 74.32; H, 7.03; X, 10.02. The The neutral imides obtained from the fractions visible absorption spectrum was of the “etio’’ by oxidative degradation were exanlined by gas- type.12 (VII) was heated in HCl (lY0) in a sealed 1 tube at 185’ for three hours. The wave lengths liquid partition c h r o m a t ~ g r a p h y . ~Fractions .~ and 2 yielded an unidentified product; fractions 3 of the absorption maxima of the resulting porphyrin and 4 yielded methyl-n-propylmaleimide; and frac- and of phyll~porphyrin’~ were identical. However, tions 5, 6 and 7 yielded methylethylmaleimide. bands I1 and 111 of the Chlorobium product ab-4fter conversion of the hydroxyalkyl group to an sorbed with equal intensities. alkyl group, fractions 3 and 4 yielded niethylethylThe above result suggested that (I) possessed inaleirnide in addition to tiiethyl-n-propylmaleim- an a l b l group attached to one of the methine ide. Dihydroheinatinic acid imide was shown bridge carbon atonis. I t was shown to be a t earlier to occur iii thc a c i d fractioii l’roni partially Ca by the iollowiIig: (IT)exposed to soinewhat purified pheophorbidc ((KO) .5,g These results in- aged, ctliaiiol-frcc. dry chloroiorii~was converted tlicate ilie nature o f tlic substituents 011 Riitgs I , to a chlorine-containing product (IX) whose visible 1 I and 11.. absorption spectrum was almost superposable F’ractioii 5 ( I ) (..I m I . Calcd. for C:laM40C)4N4: iipon that of (I).’5 . 1 no/. Calcd. for CeaH&C , i 2 . 3 9 ; H, ti.94; N, 9.65. Found: C. 72.45; N I C ~ : C , ti9.40; 13, (i.18: N, 9.81; C1, 6.20. H, 7.43; K,!1.89) was used for the following studies: Foulltl: ‘2, 69.14; 1-1, t-).9i; S , 9.75; C1, 6.10. Dehydration of (1) iii phosphoric acid (lOO:h, Ciso, The same product was obtained using the method 30 min.) yielded the alkenyl derivative (11). described by N’oodward and Skari6.‘6 The proton d n d . Calcd. for C35HaaO&4: C, 74.iO; H, 6.81; magnetic resonance spectra of (111), (V) and (IX) N, 9.96. Found: C, i5.09; H, 6.S3; N , 10.00. were measured in CDCl3. The signal assigned to the C8-protonl6 was absent from the spectra of (1) S . I L ,S>c..,83, IliTC, (10) ( 1I ) (12) (13) (14)
/io,. , I
