2376 J . Org. Chem., Vol. 35, No. 7 , 1970
TABUSHI, FUJITA, AND ODA
2.5 hr. The removal of morpholine under reduced pressure gave white crystals and 5.4 g of red oils. The crystals were filtered, and recrystallization from ethanol gave 6.1 g (91%) of morpholine hydrobromide, mp 202', lit.9 mp 202'. The filtrate was stirred with 2 N potassium hydroxide solution for 1 hr at room temperature. The solution was then acidified with hydrochloric acid and extracted with chloroform. After drying, the chloroform was evaporated to dryness and the residue was recrystallized from water to yield 1.1g (49%) of 1, mp 104105.5'. Reaction of 2,5-Dibromocyclopentaone (9) with Morpholine. -To a stirred solution of 21.7 g (0.25 mol) of morpholine in 100 ml of dry ether, 12.1 g (0.05 mol) of 9 was added dropwise with an ice-water bath cooling. The mixture was stirred for several hours at room temperature. The precipitated morpholine hydrobromide was filtered and the removal of ether and surplus morpholine under reduced pressure gave 8.1 g of viscous oils. The oils were crystallized after standing for a few days at -70". The crystals that formed were recrystallized from a small amount of methanol, affording 4.8 g (57.5%) of 2-morpholino-2-cyclopentenone (10): mp 63'; uv max (n-hexane) 285 mp ( E 20,000); ir (KBr) 1690 (C=O), 1613 (C=C), 1110 cm-I (C-0-C); nmr (CDCla) 6 6.42 (broad s , l), 3.81 (m, 4), 3.09 (m, 4), 2.47 (almost s, 1). Anal. Calcd for CgHlaOZN: C, 64.65; H , 7.84. Found: C, 64.61; H , 8.02. Reaction of 2,6-Dibromocyclohexanone(11)with Morpholine. -To a solution containing 28.0 g (0.11 mol) of 11 in 100 ml of (9) J. Gilbert and H. Gault, Bull. S O C Chim. . Fr., 2975 (1965).
absolute ether, 47.6 g (0.55 mol) of morpholine was added a t room temperature, dropwise and with stirring. After standing overnight, the deposited morpholine hydrobromide was filtered off, and the resulting oil was distilled to yield 5.1 g (25.5%) of 1cyclopentene-1-carboxymorpholide (12) : bp 113-1 14' (0.07 mol); nZoD1.5254; dZo4 1.1326; uv max (EtOH) 213 mp ( E 10,000); ir (film) 1620 (C=O), 1120 cm-I (C-0-C); nmr (CCla) 6 5.80 (broads, l ) , 3.57 (sharp s, 8), 2.48 (m, 4), 1.86 (m, 2). Anal. Calcd for CloHlfiOzN: C, 66.27; H, 7.73. Found: C, 66.04; H, 7.58. A solution of 1.4 g (0.0077 mol) of 12 in 12 ml of 2 N hydrogen chloride was stirred at 80" for 2 hr. The reaction mixture was then cooled and filtered, affording 0.4 g (80%) of l-cyclopentene1-carboxylic acid, mp 124', lit.lo mp 120-121'. Reaction of 2-Bromocyclohexanone with Morpho1ine.-To a solution of 9.8 g (0.055 mol) of 2-bromocyclohexanone in 50 ml of dry ether, 14.7 g (0.17 mol) of morpholine was added with an ice-water bath cooling. After standing overnight at room temperature, the reaction mixture was then filtered and the resulting oil was distilled to yield 5.1 g (50.5%) of 2-morpholinocyclohexanone, bp 114-115' (3 mm), lit." bp 148" (20 mm). Anal. Calcd for CloH1702N: C, 65.54; H , 9.39; N, 7.64. Found: C, 65.40; H , 9.49; N, 7.53.
Registry No.-1, 80-71-7; 6, 24454-32-8; 10, 2445433-9; 12,24454-34-0. (10) H.Sletter and K . Kiehs, Ber., 98,2099 (1965). (11) M.Mousseron, J. Jullien, and Y. Jolchine, Bull. SOC.Chim. Fr., 767 (1952).
Mechanism of the Cationic Addition-n,n-Transannular Cyclization of Disubstituted Methanes with 1,5-Cyclooctadiene IWAO TABUSHI, KAHEEFUJITA, AND RYOHEI ODA Department of Synthetic Chemistry, Kyoto University, Sakyo-Ku Kyoto, Japan Received September 8, 1969 The reaction of 1,5-cyclooctadiene with methoxymethyl acetate, dimethoxymethane, or chloromethyl methyl ether (Lewis acid catalysis) afforded mainly addition-a,a-transannular cyclization products, cis-bicyclo [3.3.0]octane derivatives which exclusively consisted of endo-2-methoxymethyl isomers, and bicyclo[3.2.l]octane derivatives. The stereochemistry of the products and the high tendency of cyclization showed that attack of methoxymethyl cation was from the outside of the boat l,5-cyclooctadiene with a simultaneous nucleophilic attack of the A3 double bond on the transient carbonium ion, which was followed by a partially concerted attack of an anion moiety (Scheme VII).
The well-documented double-bond participation in carbonium ion solvolyses1 suggests that unconjugated dienes of appropriate configuration and conformation should form cyclized products upon reaction with cationic species.2 A suitable system for investigating this cationic addition-r,r-transannularcyclization is cis,cis-l,5cycIooctadiene [1,5-COD]. A model indicates that its boat form, shown to be the stable conformer by dipole measurement^,^ affords the close proximity necessary for orbit'al overlap. In addition, double-bond participation has previously been shown to be important in the solvolysis of the related compounds, A4-cyclooctenyltosylate and b r o ~ y l a t e . ~ , ~ I n the present paper, reactions of several disubstituted methane-Lewis acid combinations and 1,5(1) P. D.Bartlett, "Nonclassical Ions," W.A. Benjamin, Inc., New York, N. Y.,1965. (2) Cationic addition cyclizations are also known in some instances [e.g., H. F. Tiemann and F. W. Seemler, Chem. Ber., 26, 2708 (1893); L. Ruzicka, Helu. Chim. Acta, 6 , 483 (1923)],but detailed mechanistic investigations are rather scarce [ e . g . , W. 6 . Jonnson, A. van der Gen, and J. J. Swoboda, J. Amer. Chem. Soc., 89, 171 (1967)l. (3) J. D.Roberts, ibid., 72, 3300 (1950). (4) W. D.Closson and G. T. Kwiatkowski, Tetrahedron Lett., 6435 (1966). (5) A. C. Cope, J. M. Crisar, and P. E. Peterson, J. Amer. Chem. Soc., 82, 4299 (1960).
COD are described which afford predominately cyclic products.6 This high proportion of cyclic productJs agrees with the previously reported results from the reaction of 1,5-COD with formic acid7 and acetyl chloride.8 However, the stereochemistry of the product reported from the latter reaction is quite contrary to our findings. Results more similar to ours were reported for the reaction of cis,cis-1,6-cyclodecadiene with Brz in methanolg although even these results differ in a significant manner. The folIowing paper describes the reaction of 1,5COD with methoxymethylacetate, dimethoxymethane, and chloromethyl methyl ether (Lewis acid catalysis). From careful analysis of the stereochemistry of the products, a mechanism for the cationic addition-cyclization reaction is presented, The discussion of this mechanism includes a comparison with results on similar (6) Preliminary reports have been presented on the subject: I. Tabushi, K . Fujita, and R. Oda, Tetrahedron Lett., 3815, 3755 (1967). (7) A. C. Cope and P. E. Peterson, J. Amer. Chem. Soc., 81, 1643 (1959). (8) T. S. Cantrell, J. Org. Chem., 92, 1669 (1967); only formation of the cyclized product was described. (9) F. M. Gipson, H. W. Guin, 8. H. Simonsen, C. G. Skinner, and W. Shive, J . Amer. Chem. Soc., 8 8 , 5366 (1966).
J. Org. Chem., Vol. 36, No. 7, 1970 2377
ADDITION-CYCLIZATION OF DISUBSTITUTED METHANES systems and an interpretation of the correlations and discrepancies.
Results and Discussion Reaction of 1,5-COD with Methoxymethyl Acetate.The reaction gave the products shown in Scheme I. SCHEMEI
Zax-cx a (12.3%)
Zan-cn a (9.0%)
/CHzOMe
y\
f
I
4a-c a (4.2%)
3a-c a (13.4%)
5
6x
(26.0%)
(3.5%)
6n
(1.4%)
7 (trace) a, Y=OAc
b, Y = c,
c1
n, Y ' = e n d o x,
Y
bicyclo [3.3.0]oct-2-yl alcohols, lo the absorption in 8n at T 5.95 (broader) was assigned to the exo proton, a to the hydroxyl, and the absorption in 8x at r 6.40 to the endo proton. The assignment of the structure for 3a was based mainly on spectroscopic evidence. The infrared spectrum of 3a showed the presence of methoxyl (1100 cm-l) and acetoxyl (1700 and 1245 cm-l). The nmr spectrum showed a singlet for the a proton to the acetoxy1 group, very similar to the absorption reported in the spectrum of anti-bicyclo [3.2.l]oct-8-yl acetates, 7.e Hydrolysis of 3a produced the alcohol 13. Oxidation of alcohol 13 to the corresponding ketone was much slower than oxidation of alcohol 8, a fact consistent with the assigned structure for 13." The acetates 6x, 6n, and 7 were not soluble in aqueous silver nitrate and were unreactive toward Br2-CH2C12. These saturated acetates were identified by comparison of their vapor phase chromatographs and infrared spectra with those of authentic samples. The olefin 5 was soluble in aqueous silver nitrate and reacted readily with Br2-CH2C12. Hydrogenation on Pt02 converted the olefin to 10n, identical with the authentic sample from Scheme 111. Contrary to the previous report of a single product 17b,12 dehydration of cyanohydrin 16 produced two cyanides 17a and 17b in a ratio of 55:45 as determined by analysis of either the nmr spectrum or the vapor phase chromatograph. This mixture of products is more reasonable since simple trans elimination should lead to both isomers. The mixture of cyanides was hydrolyzed to a mixture of isomeric carboxylic acids 18a and 18b present in a ratio of 56 : 44; hydrogenation of this mixture quantitatively produced a single saturated carboxylic acid 19n. Completion of the reaction scheme produced a mixture of saturated ethers 10n and lox, the latter compound also being synthesized by another reaction sequence shown in Scheme IV. Reaction of 1,5-COD with Chloromethyl Methyl Ether or Din1ethoxymethane.-The reactions gave the products shown in Scheme I. Comparison of the product composition for these two reactions and the previously discussed reaction with methoxymethylacetate are shown in Table I. Product
=ex0
Y=OMe
The skeletal structure, endo-2-methoxymethyl-cisbicyclo [3.3.0]octane, was determined for 2ax and 2an by the chemical conversion shown in Scheme 11. Saponification of the isomeric acetates 2ax and 2an gave the alcohols &axand 8an which were converted to the tosylates, 9x and 9n, and reduced with lithium aluminum hydride. The main product 10n was identified by comparison with an authentic sample prepared as shown in Scheme 111. Further, the brosylates l l x and l l n from the mixture of alcohols 8x and 8n were treated with trifluoroacetic acid and then hydrogenated on PtOz to give 1011 as the major product. Oxidation of the mixture of alcohols 8n and 8x with the chromic oxide-pyridine complex gave a single ketone, 12, indicating that the acetates 2ax and 2an were stereoisomers. The two were distinguished by comparison of nrnr spectra of the alcohols. By analogy to the nmr absorptions of the known exo- and endo-cis-
TABLE I PRODUCT COMPOSITION (PERCENT) Product
ax
an
8
4
a b
31.6 22.6 15.2
23.9 26.4 24.2
34.4 12.2 17.9
10.8 38.8 42.7
C
determinations were made by chemical conversions to appropriate derivatives and by nmr measurements. (10) E. W. C . Wong and C. C. Lee, Can. J . Chem., 43, 1245 (1964); the a proton to the hydroxyl group in ezo-cis-hicyclo[3.3.O]oot-2-yl alcohol absorbs at T 6.27; the absorption for the corresponding proton in the endo isomer is broader and is at 7 5.91. (11) The hydroxyl function on the highly strained bridge of the bicyclic compound (e.g., bicyclo[3.2.1 loot-8-yl alcohol) is reasonably expected to be oxidized more sloivly than that of relatively less strained compounds (e.g. cis-bicyclo[3.3.0loct-2-ylalcohol), because oxidation to ketone increases bond angle strain. sun-Bicyclo [3.2.l]oct-8-yl alcohol is oxidized 16.1 times faster than the anti isomer (ref 5). Therefore, it is reasonable that 18 was recovered under the reaction condition where 2ax and %ax were completely oxidized. (12) A. C. Cope and M. Brown, J . Amer. Chem. Soc., 80, 2859 (1958).
2378
J. Org. Chem., Vol. 56, No. 7, 1970
TABUSHI, FUJITA, AND ODA SCHEME I1
H
H qH20Me
-@
H CHzOMe
@
NaOH
OAc 2ax, OAc ( e x o ) n, OAc (endo)
:+ T
@
LiAIH,
__t
OH
OTs
8x, OH (exo) n, OH (endo)
9x, OTs ( e x o ) n, OTs (endo)
9 I H
CHzOMe
CH,OMe
HrPt
ion
4
llx, OBs ( e x o ) n, OBs (endo)
12
-
ACO
NaOH
&H
+ s T
CH20Me
-
T %
LiAIH,
CHzOMe
+H20Me
CHzOMe
14
13
3a
SCHEME I11
SCHEME IF'
16
6- 6-
15
6 6 OT +
H
17b
LiAlH,
1. NaH 2. Me1
H 19x
H 2lx
17a
+
Pd on C
18b
H
H lox
18a
2In
The chemical conversions and interconversions are summarized in Scheme V. Mechanism of the Reaction.-The formation of the methoxymethyl cation from methoxymethyl acetat,e and a Lewis acid and its attack on a double bond have been previously reported. la After the attack of methoxymethyl cation on one double bond, the resultant carbonium ion was attacked competitively by an anion to give the noncyclized product or by A5 double bond to give the cyclized product. Therefore, the amount of the cyclized product formed in the reactions of 1,s-COD with CHsOCHeY depends on the nucleophilicity of the anions: BFsAcOCH20CHa, 89.8%; ZnClz-CICHzOCHa, 61.2%; and BFa-(CHs0)2CHz, 57.3%. As the nucleophilicity
&+&
21x
H
H
10n
lox
(13) R. Oda, K. Fujita, and I. Tabushi, J . Chsm. SOC.Jap., Pure Chem. Bect., 87, 756 (1966).
J . Org. Chem., Vol. 56, No. 7, 1970 2379
ADDITION-CYCLIZATION OF DISUBSTITUTED METHANES SCHEME V
H vH20Me 1,6-COD
+
H
+
MdXHzOMe
SH20Me
@
+
' H
OMe
/
1. NaH
t)Me
2cx
M%
Me0
4c
3c
I
H vHzOMe
6
+ CH20Me
2cn
2. Me1
CHzOMe
I J?
MeI-Ag,O
MeI-Ag,O
HO 8x
CHzOMe
13
4.
&
-
CHzOMe
2bx
3b
2bn
I
/
\
YMe7
4b
Na-MeOH
4 CHzOMe
14
10n
of Y- increases, OAc- < C1- < OMe-, the cyclization tendency (cyclizability) of 1,5-COD decreases. This is consistent with the idea that the stronger nucleophile competes more effectively with the As double bond, resulting in decreased cyclizability. I n the attack of methoxymethyl cation on one double bond of 1,5-COD, exclusive formahion of the endo-methoxymethyl isomer results despite its expected thermodynamic instability'd relative to the m o isomer. Thus, the product is kinetically controlled, and attack by the methoxymethyl cation is from the outside of the preferred boat form of 1,5-COD with a simultaneous nucleophilic attack of the A5 double bond on the transient carbonium ion (step b), leading to new bond formation between C1 and Cg as shown in Bcheme VI. SCHEME VI
The stereochemistry of the acetoxyl group shows that step c, the attachment of the acetate ion, is not completely concerted with steps a and b. If step c were concerted with a and b, the acetate ion should attack the endo position of CS (as shown in step c of Scheme VI) ; if step c is nonconcerted, the thermodynamically favored exo product should predominate. The observed exolendo ratio of 1.37 to 1.00 indicates that step c is only partially concerted with a and b. Also supporting this contention by indicating the formation of free endo-6-methoxymethyl-cis-bicyclo[3.3.0]oct-2-yl cation, (22) is the isolation of 3a and 5. The latter, a bicyclic olefin, is the result of loss of a proton from this carbonium ion 22. The former, a bicyclo[3.2.1] derivative, results from the breaking of the C g c l bond of the carbonium ion 15 with subsequent formation of a bond from C8-C2 and concerted attack of acetate ion at the C1 position (see Scheme VII). SCHEME VI1
H CH20Me (14) endo-cis-Bicyclo [3.3.0loct-2-yl alcohol gave a mixture of 61 % ezo alcohol and 39% endo alcohol upon refluxing with aluminum isopropoxide in isopropyl alcohol. Also, endo-cis-bicyclo [3.3.0loctane-2-carboxylicacid was readily converted to the ezo isomer on treatment with hot alcoholic base: A. C. Cope, M. Brown, and H. E. Petree, J. Amer. Chem. SOC.,80, 2852 (1958).
22
3a
2380 J . Org. Chem., Vol. 36,No. 7 , 1970
TABIJSHI, FUJITA, AND ODA
The remaining products isolated, 6x, 6n,and 7, arise from a secondary reaction in which the elements of acetic acid are added to 1,5-COD. The best rationalization of this is that it involves proton transfer from carbonium ion 22 to 1,5-COD, resulting in olefin 5 and a new carbonium ion, bicyclo [3.3.0]oct-2-yl cation (23), which reacts with acetic acid to give 6x, 6n, and 7 (see Scheme VIII).6
SCHEME IX
y # R
??,
RX
SCHEME VI11
H
substituted cis-bicyclo [3.3.0]octanes indicates that the radical attacked the boat form of 1,5-COD from the inside of the double bonds, just the opposite of cationic attack (Scheme IX). I n the cationic addition, the
---b
CH,OMe
@ -
+
R
X
1.5-COD
MeOCH,OAc and/or
23
24
H
22
+
6
or
+CH,OMe
H
5
23
I
OAc and/or MeOCH,OAc
I
6x n
The exolendo ratio of the bicyclic esters 2a also depends on the nucleophilicity of the anion in the system. Thus, the addition of methoxymethyl acetate (BF3OEtz catalyzed) gives the acetates 2a with an exolendo ratio of 1.37. For acetic acid addition (BF3-OEt2 catalyzed), this ratio is 1.67,6 while for formic acid addition (perchloric acid catalyzed) it is 2.26. This increasing exolendo ratio reflects a decreasing amount of concerted character of step c. The outside cationic attack on a cyclic diene system (step a) with concerted cyclization (step b) is similar to that reported recently for the addition of Brz in methanol to cis,cis-1,6-cyclodecadiene. The isolation of only endo-2-bromo-endo-7-methoxymethyl-cis-bicyclo[4.4.0]decane, indicating a concerted step c, is contrary to expectation based on our results; it is quite possible that only the major product was isolated and reported. A more serious discrepancy exists in the finding of Cantrells that exo-2-acetyl-6-chloro-cis-bicyclo[3.3.0]octane was formed in the reaction of 1,5COD with acetyl chloride under AIC13 catalysis. Two possibilities may explain this contradiction : (1) heterogeneity of the reaction or (2) isomerization from endo to ezo isomer in his procedure for the replacement of chlorine with hydrogen using sodium in t-butyl alcohol. An interesting difference exists in the free-radical 0 0
ll
I/
addition of CHCl3, HCNMe,, and CHICH to 1,5-COD as reported by Dowbenko.16 The isolation of ex0-2(15) R. Dowbenko, Tetrahedron, 20, 1843 (1964).
outside attack of the cation with concerted intramolecular participation of the double bond seems to decrease remarkably the energy of the transition state relative to that of the nonconcerted process. I n the radical reaction, on the other hand, the energy decrease of the transition state in the concerted addition is less important; instead, the free-radical intermediate is best stabilized when it is on the n-electron cloud. I n contrast to the high cyclizability of 1,5-COD in reaction with methoxymethyl acetate, l,&hexadiene shows little cyclization (
