T H E J O U R N A L OF
Organic Chemistry 0 Copyright 1987 by the American Chemical Society
VOLUME52, NUMBER20
OCTOBER2, 1987
Carbon-Skeletal [ 1,2] Anionic and Radical Sigmatropic Rearrangements: Group Migratory Aptitudes as a Probe of Charge Type in the 1,2-Shifts of P-Phenyl-P-(2-pyridyl)-and P-Phenyl-@-(4-pyridyl)ethylSystems1 John J. Eisch,* Csaba A. Kovacs,2 Prabodh C h ~ b eand , ~ Marek P. Boleslawski Department of Chemistry, State University of New York at Binghamton, Blnghamton, New York, 13901, and Department of Chemistry, The Catholic University of America, Washington, DC 2001 7 Received December 15, 1986
In order to probe the occurrence and relative ease of carbon-skeletal [1,2] sigmatropic rearrangements of the free-radical, anionic, or radical-anionic type, derivatives of the P,P-diphenyl-P-(2-pyridyl)and the P,P-diphenyl-P-(4-pyridyl)ethanesystems, PyPh2CCH2E (A), were treated with reagents expected to generate radical or anionic sites. The ensuing, competitive [1,2]-shifts of the phenyl and/or pyridyl groups were then used as a diagnostic sign of the mechanism of rearrangement. Both the treatment of A (E = p-tolyl) with MeLi or K H and the reaction of A (E = C1) with sodium or lithium in donor solvents caused an exclusive [1,2]-pyridylshift. Gas chromatographic and mass spectral analyses were able to place the limit of any [1,2]-phenyl shift as under 0.5%. In such alkali metal reactions, persistent aromatic radical-anions were detected by ESR spectroscopy until the completion of the reaction. Such signals and the significant amounts of carbon-carbon bond cleavage products support the formation of pyridyl radical-anions as precursors for such cleavages and [ 1,2]-pyridyl rearrangements. That such radical-anions could lead to spiro intermediates that promote the [ 1,2]-pyridyl migrations wins corroboration from the finding that the methiodide of l-chloro-2-methyl-2-(4-pyridyl)propane can be reduced with lithium in T H F to yield the isolable 1,1,6-trimethyl-6-azaspiro[2.5]octa-4,7-diene. The same two chlorides of A responded differently under other rearrangement conditions: (1)in preparing such chlorides from the corresponding alcohols, PyPh2CCH20H,with thionyl chloride, the 4-pyridyl isomer underwent a Wagner-Meerwein rearrangement with exclusive [ 1,2]-phenyl migration; the 2-isomer underwent normal displacement of OH by C1; (2) toward the free-radical reducing agent, (n-Bu)$hH, the 2-chloro isomer underwent both [ 1,2]-phenyl and -pyridyl shifts, while the 4-chloro isomer underwent neither reduction nor rearrangement; it simply induced the formation of hexa-n-butylditin. A similar reducing action was observed with bis(l,5cyc1ooctadiene)nickel. These observations are analyzed with the aid of Hiickel molecular orbital theory and the rearrangements observed with reducing agents are assessed in terms of three types of mechanisms: (1)authentic [ 1,2]-anionic shifts; (2) authentic [ 1,2]-free-radical shifts; and (3) competing electron transfer from the metal to the chloride center or from the metal to the pyridyl ring, which permits anionic rearrangements to compete with rearrangements mediated by radical-anion or dianions, which latter processes form the crucial spiro intermediate by intramolecular nucleophilic displacement on the CH2C1group.
Carbon-skeletal [1,2] sigmatropic shifts are one of the most commonly encountered rearrangements in organic chemistry, possibly because they can proceed by a variety of mechanisms (eq 1). In Wagner-Meerwein 1,2-shifts R
I I
I t
-Cq-C2"1
- I7;I -cq-c2-
2
I I
-C1"-C2-
P t
(1)
cationic carbon appears to foster the shift (1, n = +l);4 in Grovenstein-Zimmerman rearrangements anionic carbon is involved (1, n = -1),5 and even radical carbon centers can undergo skeletal reorganization (1,n = Oh6 Molecular orbital calculations offer some useful insights into the relative ease with which such rearrangements might be expected to take place.' Formation of the intermediate or transition state 2 for such [1,2]-shifts (1 3, eq 1)
-
3
(1) Part 23 of the series 'Rearrangements of Organometallic Compounds". Previous part: J . Org. Chem. 1984,49, 4631. (2) Present address: Eastman Kodak Company, Rochester, New York
14692. (3)Present address: Sudarshan Chemical Company, Pune, India.
0022-3263/87/1952-4427$01.50/0
(4) (a) Wagner, G. Zh. Russ. Fir.-Khim. 0-ua. 1899, 31, 680. (b) Meerwein, H.; van Emster, K. Chem. Ber. 1920,53, 1815. (5) (a) Grovenstein, E. Angew. Chem., Int. Ed. Engl. 1978,17,313.(b) Zimmerman, H.A.;Zweig, A. J . Am. Chem. SOC.1961,83,1196. (6)Kaplan, L. J. Am. Chem. SOC.1966,88,4531. (7) Zimmerman, H. A,; Zweig, A. J. Am. Chem. SOC. 1961,83,1196.
0 1987 American Chemical Society
4428 J . Org. Chem., Vol. 52, No. 20, 1987
Eisch et al.
involves putting zero, one, or two electrons into a moderately antibonding orbital, depending upon whether the rearrangement is of the carbenium, free-radical or carbanionic charge type ( n = +1, 0, or -1 in eq 1). Consequently, all factors being comparable, the ease of attaining 2 and thus a 1,2-sigmatropic rearrangement should decrease in the order7 carbenium ion > free radical > carbanion. These theoretical considerations are of especial interest for those situations where rearrangements of different charge type might compete with each other. In the present study we have sought to test the utility and validity of these HMO predictions for [1,2]-sigmatropic shifts that could involve either free-radical or carbanionic intermediates. In the well-known GrovensteinZimmerman rearrangement, P,P,P-triarylethyl halides undergo a skeletal rearrangement to (a,a,P-triarylethyl)metallics upon treatment with alkali metals in donor so1vents.j Although such processes have generally been interpreted as proceeding via carbanions, the possible role of free-radical intermediates in certain instances has remained in question.8 We hoped to make a distinction between these two shifts of different charge type by observing differing migratory aptitudes of the carbon groups (R in eq 1) undergoing rearrangement. As our test substrates we chose the @,P-diphenyl-P-(2-pyridyl)-and P,Pdiphenyl-@-(4-pyridyl)ethylsystems 4 and 5, which were treated under conditions favoring free-radical or anionic reactions. The competition thereupon observed between
Scheme I Ph
Ph
Ph
Ph
6
r-
8
0
Ph
4a Ph
Ph
Ph Sa
Ph
10
N
D
I
l
H
Ph
N>T-T-E
I
C H, P h
CI
5c Ph
Ph
Ph
4c
6 Ph
C H 1C I
H
I
S c h e m e I1 Ph
Ph
H
4a: E = C I 4b: E 4-tofyt 4C: E = I
Ph
H
5a: E = C I
5b: E = 4 - t o l y f
the phenyl and pyridyl groups in the ensuing 1,2-skeletal shift has then served as a probe of the charge type in eq 1. In addition, by the use of model reactions, an attempt was made to decide whether structures of type 2 were intermediates or transition states in such 1,2-shifts and what charge type n might favor the formation of 2.
Results Preparation of the B,P-Diphenyl-@-(2-pyridyl)-and B,B-Diphenyl-B-(4-pyridyl)ethylSubstrates for Rearrangement. It was hoped that both the 2- and 4-(2chloro-1,l-diphenylethy1)pyridines(4a and 5a) could be prepared in a similar manner, namely, the reaction of the corresponding benzhydrylpyridine with formaldehyde under basic conditions to generate the 2-substituted ethanols 8 and 10 and then the reaction of these alcohols with thionyl chloride to form the desired chlorides (e.g., Scheme I for 4a). This approach did in fact yield 4a according to plan, but with alcohol 10, treatment with thionyl chloride led to a skeletal rearrangement, in a Wagner-Meerwein fashion, and provided instead the product of a [1,2]-phenyl shift, 5c. However, both chlorides could be obtained from their corresponding benzhydrylpyridines by generating the anions from 6 and 7 and adding methylene chloride (Scheme I). In a similar manner, the requisite iodide, 4c, could also be obtained without skeletal rearrangement. (8) Eisch, J.; Kovacs, C.A. J. Organomet. Chem. 1970,25, C33. In that publication, what we consider to be 4-(2-chloro-l,l-diphenylethyl)pyridine has now been idcntified aa 4-(l-chloro-l,2-diphenylethyl)ppidine. In this article we show how this isomer was formed in the attempted formation of 5a from alcohol 10. Because of this erroneous assumption (Le., that 5c was 5a) we had concluded that free radicals might be involved.
These relationships are illustrated in Scheme I. Finally, the preparation of both 2-(4-methylphenyl)l,l-diphenyl-l-(2-pyridyl)ethane(4b) and 2-(4-methyl)l,l-diphenyl-l-(4-pyridyl)ethane (5b)was carried out by simply coupling the metal salts (Li or K) of the (diphenylmethy1)pyridines 6 and 7 with 4-methylbenzyl chloride (eq 2). Ph
I
I Py-C-H
I Ph
:'8;.; ME
Ph
-
I
I Py-C-M
p.TolCHgCI
I Ph Ph
I
PY-C-CH,-P-TOI
I Ph
(2)
Preparation of the Potential Rearrangement Products. The unambiguous syntheses of the possible diphenyl(2-pyridy1)ethanesthat could result from these rearrangement reactions, namely 2-(l,l-diphenylethyl)pyridine (1l), 2-(2,2-diphenylethyl)pyridine(12), and 2(1,2-diphenylethyl)pyridine (13), were achieved by lithiating the appropriate 2-methylpyridine (either 2-(diphenylmethyl)pyridine, 2-methylpyridine itself, or 2benzylpyridine) with n-butyllithium and then quenching the 2-(1ithiomethyl)pyridinederivative with the necessary halide (methyl iodide, diphenylmethyl bromide, or benzyl chloride). The synthesis of the illustrative 2-(1,1-diphenylethy1)pyridine (11 ) is depicted in Scheme 11. In order to gain assurance that the starting 2- and 4(2-halo-1,l-diphenylethy1)pyridines did not themselves undergo a cationic rearrangement in the reaction medium
J. Org. Chem., Vol. 52, No. 20, 1987 4429
Carbon-Skeletal 1,2] Sigmatropic Rearrangements Scheme I11
Table I. Composition of the Hydrolysis Products from t h e Reaction of 2-(2-Chloro-l,l-diphenylethyl)pyridine(4a) with Lithium i n Tetrahydrofuran at -65 OC as a Function of
0-H
I I
Time
H-C-H Hac-C-
+&0-
H3C-C-CH3
H-C-H
I
time, min4 60 75 90 180 195 210 24OC
SOCI)
20
18 CI
%
C H3
CI
I
I
H3C-C-CH3
Ph2CHCHZPy (12) 6.0 7.2 7.5 62.0 63.0 61.0 70.0
PyPhZCCH3 (11) 3.5* 3.3 5.0 7.0
1.4 9.0 12.0
Aliquots were withdrawn with a gas-tight syringe after the stated time and hydrolyzed with DzO. The organic products were examined by GLPC and 'H NMR analyses. bAt no time did the proportion attain a maximum and then decrease (such a buildup would have betokened that 11 was derived from a rapidly formed rearrangement precursor, which then rearranged at a slower rate). CTheend composition of a reaction conducted at 25 "C for 24 h (500 mg of 4a, 2.2 equiv of lithium, and 10 mL of THF) was the following: 18% of 4a, 69.4% of 12, and 14.2% of 11; in addition, there was 0.97% of 2-benzhydrylpyridine and 1.4% of 1,l-diphenyl-2-(2-pyridyl)ethene.For a comparable run conducted at 25 "C in diethyl ether for 72 h, the end composition was: 0% of 4a, 55.5% of 12, 39.1% of 11, and 3.83% of 2-benzhydrylpyridine. All gas chromatographic analyses were conducted with a HewlettPackard instrument, Model 5880, and fractions identified by a H-P mass spectrometer, Model 5992. (I
I
22
PyPhZCCH2Cl (4a) 90.5 89.5 87.5 31.0 29.6 30.0 18.0
CH3
23
I
CH3
(2.78)
24 ('H NMR s i g n a l s )
of THF, these compounds were individually dissolved in anhydrous T H F and allowed to stand for 24 h. In a blank workup, such solutions were then treated with HzO, and the T H F layer was then separated and dried. Removal of the solvent yielded only the unhydrolyzed and unrearranged starting 4a and 5a. In like manner, the syntheses of the possible diphenyl(4-pyridy1)ethanes were conducted in straightforward steps. Again, 4-(l,l-diphenylethyl)pyridine(14), 4-(2,2-diphenylethyl)pyridine(15), and 4-(1,2-diphenylethy1)pyridine (16) proved to be readily discernible from each other by their spectral and chromatographic properties. Preparation of the B,&Dimethyl-8-(2-pyridyl)-and 8,D-Dimethyl-8-(4-pyridy1)ethyl Chlorides and the Model for a Spiro Intermediate. Both 2-isopropyl- and 4-isopropylpyridines (17 and 18) were individually added to formaldehyde and the resulting 2-methyl-2-(2-pyridyl)and 2-methyl-2-(4-pyridyl)-l-propanols (19 and 20) then converted to their chlorides (21 and 22) by means of thionyl chloride. The synthesis of the 4-pyridyl isomer is given in Scheme 111. Compound 22 was then quaternized with methyl iodide, and the methiodide 23 was treated in a T H F suspension a t 0 "C with lithium metal. From this reaction 1,1,6-trimethyl-6-azaspiro[2.5]octa-4,7-diene (24) was isolated as an unstable oil. Its proton NMR spectrum, however, was in excellent accord with its cyclopropylic, enaminic structure (Scheme 111). Rearrangements of 2-(2-Chloro-l,l-diphenylethyl)pyridine (4a) and 4- (2-Chloro-1,l-diphenylethyl)pyridine (5a) with Alkali Metals. The individual reactions of 4a and 5a in diethyl ether or in tetrahydrofuran, either a t low temperatures or 25 "C, led in each case to a single type of [1,2] shift: an exclusive pyridyl shift. By combined gas chromatographic and mass spectral analyses, used in conjunction with authentic samples of the possible rearrangement products, it could be concluded that if any [ 1,2]-phenyl migration product were formed in these reactions, such a component would have to be present in less than 0.5% (cf. Tables I and 11). Workup of such reaction mixtures with D 2 0 yielded deuteriated rearrangement products (12a and 16a, eq 3 and 4). Small to significant proportions of unrearranged reduction products 11 and 14 were formed in each reaction, but it worthy of note that deuteriolytic workup gave these products in their undeu-
Table 11. Compositions of t h e Hydrolysis Products from (5a) t h e Reaction of 4-(2-Chloro-l,l-diphenylethyl)pyridine with Sodium Metal a n d with Lithium Metal i n Donor Solvents at 25 OC after Completion of Reaction Na in Na in Li in Li in products of metal THF, 48 EtzO, 72 THF, 48 Et,O, 72 reacn h h h h 4-PyPh2C-CHZCl 1.4 0.0 0.0 0.0 (54 4-Py-CHZ-CHPhZ 80.8 87.4 73.8 13.3 (16) 4-PyPh2C-CH3 (14) 0.6 0.0 4.5 1.2 4-PyPhZCH 0.9 2.1 2.7 0.2 8.3 6.5 15.5 14.5 PhZCH2 4-PyCH3"-' 8.0 5.0 3.5 10.8 "There were minor components among the reaction products that arose from various solvent-solute-metal interactions; these are neglected in presenting the compositions of these reactions, and the above components are normalized to 100%. bThe values given for the 4-picoline are usually low, since some of this component was lost upon removal of solvent. 'All analyses were conducted with a Hewlett-Packard gas chromatograph, Model 5880, and the identity of each sample was verified by collection and measurement of its mass spectrum, 'H NMR spectrum, and IR spectrum.
teriated form. Therefore, they must have acquired their hydrogen during the reaction proper. The course of rearrangement in the 2-pyridyl system, 4a, was followed both by ESR spectroscopy and by the hydrolytic quenching of samples from the reaction mixture over time. A sample of the reaction mixture, withdrawn at -65 "C and free of suspended lithium, showed an intense ESR signal, 25 G in width, that gradually decreased over 2 h at 0 "C. The analysis of the hydrolyzed samples showed a gradual increase in the amount of 11 and 12 (Table I) and no buildup of 11 early in the reaction. From this hydrolysis study one can conclude that the intermediate required for rearrangement was consumed very rapidly as it was formed. However, the ESR data point to a relatively long-lived paramagnetic intermediate, probably of the aromatic radical-anionic type.
4430 J . Org. Chem., Vol. 52, No. 20, 1987
Eisch et al. extraordinarily facile reduction to 1,2-diphenyl-l-(4pyridy1)ethane. Thus, in such a well-documented freeradical reduction p r o c e s ~these , ~ three isomeric chlorides underwent reaction in sharply decreasing ease: 5c > 4a > 5a. It is noteworthy that nickel(0) complexes display a reactivity and pattern parallel to the tin hydride: 5c undergoes very ready reduction to 1,2-diphenyl-l-(4pyridy1)ethane with bis(l,5-cyclooctadiene)nickel;although 4a does not react with (Cod)*Nior (Cod)(bpy)Ni at 25 "C in THF, its iodo counterpart (4c) does react with (Cod)(Bpy)Ni to undergo phenyl vs. pyridyl migration in a 60:40 ratio (12/13). Only a small amount of reduced, unrearranged 11 was found. When workup with D 2 0 was conducted, all three products were found to be free of deuterium. Rearrangements of Anions Formed from 2-(4Methylpheny1)- 1,l-diphenyl-1-(2-pyridyl)ethane (4b) and 2-(4-Methylphenyl)-l,l-diphenyl-l-(4-pyridyl)ethane (5b). Anions could be produced from the 2-pyridyl isomer 4b by methyllithium in T H F and from the 4-pyridyl isomer 5b by potassium hydride in THF, with catalytic potassium piperidide. Both anions underwent a prompt 1,2-shift of exclusively the pyridyl groups (eq 7 and 8).
- Yh ? Ph
H
4a H
Ph
Ph
12a Ph
H
Ph
H
H
11
5a H
Ph
Ph
18a
H
14
In this same connection it is important to note that small but reproducible amounts of the benzhydrylpyridines were formed in these alkali metal reactions, even though starting chlorides 4a and 5a were free of them. In addition, reactions of isomer 5a with these metals produced considerable amounts of diphenylmethane and 4-picoline (Table 11). Such products must have resulted from carbon-carbon bond-cleavage reactions proceeding concurrent with the rearrangements. Rearrangements and Reductions of 2-(2-Halo-l,1diphenylethy1)pyridines 4a and 4c and of 4-(1Chloro-l,2-diphenylethyl)pyridineand 4-(2-Chloro1,l-diphenylethy1)pyridine (5c and 5a) with Tri-n butyltin Hydride and with Nickel(0) Complexes. Isomeric chlorides 4a and 5a differed greatly in their ease of reduction or rearrangement with tri-n-butyltin hydride in toluene. Compound 4a underwent reaction slowly a t 25 "C to give a 65335 ratio of 12/13 but more rapidly a t 110 "C to yield a 58:42 ratio. In both runs, about 8% of the unrearranged reduction product 11 was also formed (eq 5 ) . 2 - Py-c-
Th 7/ I
c-CI
I
Ph
I
-
(n.Bu)aSnH
toluene
Ph
7
I
I
I
I
2-Py-C-C-Ph
H
H
+
Ph
H
D
4b Ph
H
Ph
H
p-Toj
D
Potassium hydride had to be substituted for methyllithium in abstracting a benzylic proton from 5b, since the lithium reagent preferentially added, instead, to the azomethine linkage in 5b. Also, it should be noted that because both benzhydrylic protons in 25 and 26 are quite acidic, the products became dimetalated in the reaction mixture. The proof of structure for 25 and 26 was established in two ways: (1)clean mass spectral fragmentation at 70 eV into the diphenylmethyl and pyridyl(toly1)methyl cations (eq 9), and (2) the cleavage of the central ethane C-C bond o-To1 o-To1
2-Py-C-C-H
I PhI H
+
2-Py-C-C-H
13
I
H
(5)
I I Ph H
Ph
25
11 (1) L i , THF
(2) H20 I
H
,
Ph
26 p-TO1
+
-
Z ( ~ - B U ) ~ S ~ H
Ph
5a (n.Bu)aSnSn(n.Bu)3
+
H2
+
(9!
/
by lithium in THF and the identification of the products (eq
In contrast, isomer 5a could not be reduced or induced to rearrange even after 72 h of heating it with tri-n-butyltin hydride a t reflux in toluene. But a t the end of this reaction, the hydride had been transformed into hexa-n-butylditin (eq 6). However, isomeric chloride 5c underwent N 3 / - C H 2 C l
'>C--Ph
H
H '
H
~k
+
;
