508
J . Org. Chem. 1986, 51, 508-512
[ 1,4] Addition of (Methy1thio)methyl p -Tolyl Sulfone to a$-Unsaturated
Carbonyl Compounds Katsuyuki Ogura,* Nobuhiro Yahata, Masanori Minoguchi, Kazuo Ohtsuki, Kazumasa Takahashi, and Hirotada Iida Department of Synthetic Chemistry, Faculty of Engineering, Chiba Uniuersity, Yayoicho 1-33, Chiba 260, Japan
Received June 14, 1985 The lithio derivative of (methy1thio)methyl p-tolyl sulfone (1) reacted with various a,@-unsaturatedcarbonyl compounds to afford [ 1,4]adducts in good to high yields. The introduced (methylthio)(p-tolylsulfony1)methyl group was easily converted to a (methy1thio)carbonyl group or a formyl group. When the reaction of 1 with methyl acrylate using sodium hydride as a base was performed in DMF at an ambient temperature, 2-(methoxycarbonyl)-4-(methylthio)-4-~-tolylsulfonyl)cyclohexanone (8)was obtained in 81% yield. Furthermore, 8 was shown to be an important intermediate for preparing 2-substituted 2-(methoxycarbonyl)-1,4-cyclohexanediones.
To date, much attention has been paid to the [1,4] addition of the carbanions of dithioacetals and their S-oxides to a$-unsaturated carbonyl compounds mainly because the [1,4] adducts are useful for the preparation of synthetically important lP-dicarbonyl compounds. The ratio of the [1,4] and [1,2] adducts has proven to depend on the carbanion nature, the counterion, and the reaction conditions (temperature and In the reaction of a,p-unsaturated carbonyl compounds with highly delocalized or well-stabilized carbanions, reversible additions are normally observed: The [1,2] and [1,4] adducts are usually the results of kinetic and thermodynamic control, respectively. For example, 2-lithio-1,3-dithianes generally react with a,p-unsaturated carbonyl compounds to give only the [ 1,2] adducts,14 whereas 2-lithio-2-phenyl-l,3dithiane affords the [1,4] adduct with 2-cyclohexenone in a thermodynamically controlled manner (at 25 OC)? It was also reported that the reaction of [bis(methylthio)(stannyl or silyl)methyl]lithium and [tris(phenylthio)methyl]lithium with a,b-unsaturated ketones resulted in the exclusive formation of [ 1,4] adduct^.^^^^^ These reports prompted us to investigate the base-induced addition of (methylthio)methyl p-tolyl sulfone ( l ) I 5 to a,p-unsaturated carbonyl compounds, where the production of [ 1,4] adducts
Scheme I
n-BuLi
/SCH3
CH
-
%OZT0l
‘SOpTol
1
2
Hi
RCHCHZCOY
1
CH
0022-3263/86/1951-0508$01.50/0
(TOl=p-tolyl)
hv(254 nm)
I \
RCHCH2COY
-
(H20)
1
C H 3 S ‘S02Tol
CHO
5
41 RCHCHzCOY
H*
I
CH
RCHCHZCOY 1 COSCH1
-
7
C H 3 S 6 ‘S02Tol
6
Scheme I1 1 + 2CH2=CHCOOCH3
_ i )
2NaH DMF
TcH3sQ0 olS02
3e
COOCH3
8 RX
9
(1) (a) Mukaiyama, T.; Narasaka, K.; Furusato, M. J. Am. Chem. SOC. 1972,94,8641. (b) Cohen, T.; Herman, G.; Falck, J. R.; Mura, A. J., Jr.; J. Org. Chem. 1975, 40, 812. (2) Herrmann, J. L.; Richman, J. E.; Schlessinger, R. H. Tetrahedron Lett. 1973. 2599. (3) Herimann, J. L.; Richman, J. E.; Schlessinger, R. H. Tetrahedron Lett. 1973, 3271, 3275. (4) Seebach, D.; Burstinghaus, R. Angew. Chem., Int. Ed. Engl. 1975, 14, 57. (5) Manas, A. R. B.; Smith, R. A. J. J . Chem. Soc., Chem. Commun. 1975, 216. (6) Ziegler, F. E.; Schwartz, J. A. Tetrahedron Lett. 1975, 4643. (7) Ostrowski, P. C.; Kane, V. V. Tetrahedron Lett. 1977, 3549. (8) Ogura, K.; Yamashita, M.; Tsuchihashi, G.Tetrahedron Lett. 1978, 1303. (9) (a) Cohen, T.; Nolan, S. M. Tetrahedron Lett. 1978, 3533. (b) Cohen, T.; Yu, L.-C. J . Org. Chem. 1985,50, 3266. (10) Brown, C. A,; Yamaichi, A. J . Chem. SOC., Chem. Commun. 1979, 100. (11) Lucchetti, J.; Dumont, W.; Krief, A. Tetrahedron Lett. 1979, 2695. (12) Colombo, L.; Gennari, C.; Resnati, G.; Scolastico, C. J . Chem. SOC.,Perkin Trans. 1 1981, 1284. (13) Chung, S. K.; Dunn, L. B., Jr. J . Org. Chem. 1984, 49, 935. (14) Corey, E. J.; Crouse, D. J . Org. Chem. 1968, 33, 298. (15) This reagent (1) can be conveniently synthesized by the reaction of acetoxymethyl methyl sulfide with sodium p-toluenesulfinate.’2 By our investigations, 1 has proven to be a useful reagent for making various organic compounds such as S-methyl a-ketocarbothioate, carboxylic esters, cycloalkanones, a-methoxy-a-arylacetic esters, and aldehyde^.'^.'^ (16) Ogura, K.; Yahata, N.; Watanabe, J.; Takahashi, K.; Iida, H. Bull. Chem. SOC.J p n . 1983, 56, 3543.
-
RCH=CHCOY 3
,SCH3 LiCH
10
(4) is expected because 1 forms a stable carbanion,17 a synthetic equivalent of formyl carbanion, (methy1thio)carbonyl carbanion, or carbonyl dianion.18B20 This paper reports that the lithio derivative (2) of 1 adds to various a$-unsaturated carbonyl compounds (3) to give [1,4] adducts (4), which are synthetic precursors for 3-formyP and (17) Ambident carbanions of allyl sulfones have proven to add to various carbonyl compounds in a [1,4] fassion: (a) Martel, J.; Huynh, C.; Toromanoff, E.; Nomine, G. Bull. SOC. Chim. Fr. 1967,982. (b) Martel, J.;Huynh, C. Bull. Soc. Chim.Fr. 1967, 985. (c) Julia, M.; Guy-Rouault, A. Bull. SOC.Chim. Fr. 1967, 1411. (d) Velluz, L.; Nomine, G.; Martel, J. C. R. Acad. Sci., Paris, Ser. C 1969,268, 2199. (e) Campbell, R. V. M.; Crombie, L.; Pattenden, G. J. Chem. SOC., Chem. Commun. 1971, 218. (f) Crombie, F.; Findley, D. A. R.; Whiting, D. A. J . Chem. SOC.,Chem. Commun. 1972, 1045. (g) Campbell, R. V. M.; Crombie, L.; Findley, D. A. R.; King, R. W.; Pattenden, G.; Whiting, D.(A.J. Chem. Soc., Perkin Trans. 1 1975,897. (h) Kraus, G. A.; Frazier, K. Synth. Commun. 1978, 8 , 483. (i) Hirama, M. Tetrahedron Lett. 1981, 22, 1905. (18) Ogura, K.; Yahata, N.; Hashizume, K.; Tsuyama, K.; Takahashi, K.; Iida, H. Chem. Lett. 1983, 767. (19) Ogura, K.; Yahata, N.; Takahashi, K.; Iida, H. Tetrahedron Lett. 1983, 24, 5761. (20) Ogura, K.; Ohtsuki, K.; Nakamura, M.; Yahata, N.; Takahashi, K.; Iida, H. Tetrahedron Lett. 1985, 26, 2455. (21) Several reports have been published for converting an a,@-unsaturated ketone into a 4-ketoaldehyde by [1,4] addition of a formyl anion equivalent followed by unmasking to an aldehyde.8,9,’2,22,21
0 1986 American Chemical Society
J. Org. Chem., Vol. 51, No. 4,1986
[ 1,4] Addition to a,@-UnsaturatedCarbonyl Compounds
run
Table I. Reaction of 2 (M = Li) with a,P-Unsaturated Carbonyl Compounds (3)" substrate (equiv)b (equiv)b temp, OC/time, h product 4c
1
(1.3)
-7814
(1.3) (1.2) (1.3)
-7813 -2513 -78 14
3a
2 3
4 A PhCH=CHCOCH=CHPh 3c
yield, % d trace
-- -2511 -2011
4Q
011 --c 1513
47 (69) 83 (87)
A
3b
5 6 7
509
trace
MT
(1.3) (1.2) (1.0)
-7813 -2513 -7815
-.-1511 -2511
4b --c
011
40 (62) 70 (83) 71 (81)
4
PhCHCH2COCH=CHPh
I
MT 4c
8
CH2=CHCOCH3
(1.1)
-7815
3d
9 10
11
CH2=CHCOOMe 30
(1.2) (1.5)
-2513 -7815
27 (62)
CH2CH&OCH3
-
I
MT 4d
-1513
29 (39) 44 (50)e
CH2CH&OOMe
I
MT
CH3CH=CHCOOMe 3f
(1.2)
PhCH=CHCOOEt
(1.1)
40 CH3CHCH2COOMe
-7814
67
I
MT 4t
12
-7815
91
PhCHCH2COOEt
I
3P
MT 4P
"In THF. *Molar equiv to 1 are in parentheses. cMT = (methylthio)(p-tolylsulfony1)methyl. dYields based on unrecovered 1 are in parentheses. e2:1 adduct (17, n = 2) of 3e and 1 was also produced in 19% yield (see text).
3-(methy1thio)carbonylderivatives (5 and 7 of Scheme I) of 3. We also describe the optimal conditions for a tandem double [ 1,4] addition-Dieckmann condensation of 1 with methyl acrylate leading to a useful intermediate (8) for synthesizing 2-substituted 2-(methoxycarbonyl)-1,4cyclohexanedione (10) as depicted in Scheme 11. Results and Discussion First we examined the reaction of a typical a,@-unsaturated carbonyl compound, 2-cyclohexenone (3a),with the lithio derivative 2 in THF. After 2 was generated by the action of n-butyllithium on 1 at -78 "C room temperature, 3a was added. The yield of a [1,4] adduct (4a) was found to be crucially dependent on the reaction temperature. A t -78 "C, a trace of 4a was formed. When the temperature was slowly raised from -78 "C to 0 "C,the yield of 4a increased to 47%. An NMR analysis showed that the reaction mixture contained a 2:l adduct of 3 s and 1, which was probably formed due to the presence of a large amount of the unreacted 3a in the reaction system. It seems indispensable for the efficient formation of 4a that 3a is consumed as soon as it is introduced into a solution of 2. Indeed, when 3a was added dropwise to a solution of 2 in T H F a t -25 to -10 "C, 4a was obtained in 83% yield. This is in sharp contrast to the fact that the lithio derivatives of 1,3-dithiane and methyl (methy1thio)methyl sulfoxide react with 3a to give the corresponding [1,2] adducts."J4 Since the corresponding [ 1,2]adduct (11) could not be isolated in spite of many efforts, sufficient data are not available for distinguishing possible mechanisms of the present [ 1,4] addition: thermodynamically and kinetically controlled paths. Similar phenomena were observed in the reaction of 2 with 2-cyclopentenone (3b) (Table I, runs 4-6). Acyclic a,@-unsaturatedketones and a,@-unsaturatedesters gave
-
the best results when the reaction temperature was kept a t -78 "C, as shown in Table I. In the reaction of 2 with an a,@-unsaturatedaldehyde, cinnamaldehyde (12), a [1,2] adduct (14) was exclusively obtained in 85% yield (98% based on the unrecovered 1). In order to obtain the thermodynamically stable [1,4] adduct, the reaction was performed at an elevated temperature (-78 "C -25 "C 0 " C room temperature), but a dehydration product (15) was obtained as the sole product (55%).
- - -
2
PhCH=CHCHO
Lio I
/
-
HO
S C H ~ H+
I
13
.1
/
' S O ,
'S02Tol
12
SCH3
PhCH=CHCHCH
PhCH=CHCHCH
Toi
14
7CH3
PhCH=CHCH=C
---(
'SO,
1)
Toi
15
During the course of our study of the conditions for the base-induced [1,4] addition of 1 with methyl acrylate (3e), we discovered that a tandem double [1,4] addition-Dieckmann condensation efficiently occurred in the presence of sodium hydride. In the addition of 2 to 3e, n:l adducts (17) as well as 4e were formed, indicating that an intermediate carbanion (16, M = Li) derived from 2 and 3e is stable enough to react with another molecule of 3e. The reaction of 1 with 3a (1.5 equiv) in T H F using sodium hydride (1 equiv) as a base (0 "C room temperature) gave 2-(methoxycarbonyl)-4-(methylthio)-4-(p-tolylsulfony1)cyclohexanone(8) in 42% yield together with 4e (11%).The formation of 8 may be rationalized by the path depicted in eq 2. Since the carbanion 16 (M = Na) is less stable, a proton transfer takes place to give a new car-
-
510 J Org rhem., Vol 57, No. 4, I986 I
’1AI
Ctl,?,
--
36
:,HCH,
a-
5- e
3e
\“
l01sc~
L
~
--*
CK
