Abstract
Until now, 2,6-dialkyltropones have not been described. 2,6-Dimethyltropone
(5 ) represents an appropriate material
for synthesis of naturally occurring antiviral compounds. A new,
convenient method for synthesis of 2,6-dimethyltropone (5 ) from 2,6-dimethylcyclohexanone in five
optimized steps and 52% overall yield has been developed.
Trimethylsilyl enol ether 1, prepared from
2,6-dimethylcyclohexan-1-one, was treated with dichlorocarbene,
to give 7,7-dichloro-2,6-dimethyl-1-trimethylsilyloxybicy-clo[4.1.0]heptanes
(2 ). Acid promoted ring opening of 2 at room temperature gave 2-chloro-3,7-dimethylcyclohept-2-ene-1-one (3a ). At higher temperatures (150-300 °C)
a mixture of 3a and 2-chloro-3,7-dimethyl-1-trimethylsilyloxycyclohepta-1,3-diene
(3b ) was obtained in the ratio 2.1:1.0,
respectively. Gamma bromination of 3a by
NBS/AIBN gave diastereoisomers 4a and 4b in the ratio 5:1, which were converted
to 2,6-dimethyltropone (5 ) by Li2 CO3 in DMF
at 120 °C. All new compounds were characterized
by their NMR and HRMS spectra. The relative configuration and the
structure of the preferred conformer of 3a and 4a were determined by HMQC, COSY and NOE
NMR measurements.
Key words
tropone - cycloheptanes - conjugation - ketones - ring expansion - diastereoselectivity - shielding
effect in NMR
References 1 Monoalkyltropones: 2-Me;
[2a-k 2u 2a b 2l-n 2u n -Pr;
[2b o i -Pr;
[2b g m n 2p-s n -Bu;
[2b 2r 2t-v i -Bu;
[2g t -Bu;
[2w n -octyl;
[2b 2x y i -Pr;
[2q-s 2y 3a b n -Bu
[3c d 2i j x 3d-k i -Pr(Nezukon);
[2h q r o 3d 3k-s n -Bu.
[3l 2l 3t u 2j 3v 2b j 3t w x 2r 3u y 3a-e 4g 2y 4c i -Pr-5-Me;
[2b 3v x i -Pr-2-Me;
[4f i -Pr-2-Me;
[2l 3v i -Pr-7-i -Pr;
[2r 4h n -Bu-2-Me;
[4f n -Bu-2-Et;
[4f t -Bu-7-t -Bu.
[4e 2l 4i 2r 4h j k i -Pr-7-i -Pr-4-Me;
[2r 4h t -Bu-7-t -Bu-4-Me;
[4j m t -Bu-4-t -Bu-6-t -Bu.
[4l 2r 4h i -Pr-7-i -Pr-4-Me-5-Me.
[2r 4h 4n-p
2a Mukai T.
Nippon Kagaku Zasshi
1958,
79:
1547 ; Chem. Abstr . 1960 , 23846
2b Brady WT.
Hieble JP.
J.
Am. Chem. Soc.
1972,
94:
4278
2c Schuster DI.
Wang L.
van der Veen JM.
J. Am. Chem. Soc.
1985,
107:
7045
2d Gavrilova GV.
Nikanorov VA.
Shiryaevskaya IA.
Galakhov MV.
Rozenberg VI.
Reutov OA.
Russ. Chem. Bull.
1987,
36:
2676
2e Wang L.
Schuster DI.
van der Veen JM.
Tetrahedron Lett.
1983,
24:
2627
2f Shono T.
Nozoe T.
Maekawa H.
Kashimura S.
Masuda H.
Okada T.
Kashimura S.
Tetrahedron
Lett.
1988,
29:
555
2g Shono T.
Nozoe T.
Maekawa H.
Yamaguchi Y.
Kanetaka S.
Masuda H.
Okada T.
Kashimura S.
Tetrahedron
1991,
47:
593
2h Asao T.
Yagihara M.
Kitahara Y.
Heterocycles
1981,
15:
985
2i Rosenblum M.
Watkins JC.
J. Am. Chem. Soc.
1990,
112:
6316
2j Zbiral E.
Jaz J.
Wessely F.
Monatsh
Chem.
1961,
92:
1155
2k Morita N.
Kurita M.
Ito S.
Asao T.
Sotokawa H.
Tajiri A.
Tetrahedron: Asymmetry
1995,
6:
35
2l Zbiral E.
Takacs F.
Wessely F.
Monatsh.
Chem.
1964,
95:
402
2m Maatschappij NV. inventors; Shell International Res., French
Patent 1342142.
; Chem. Abstr. 1964 , 60 , 13199
2n ter Borg AP.
van Helden R.
Bickel AF.
Recl. Trav. Chim. Pays-Bas
1962,
81:
591
2o Jones G.
J. Chem.
Soc. C
1970,
1230:
1232
2p Childs RF.
Varadarajan A.
Can.
J. Chem.
1981,
59:
3252
2q Noyori R.
Hayakawa Y.
Tetrahedron
1985,
41:
5879
2r Takaya H.
Hayakawa Y.
Makino S.
Noyori R.
J. Am. Chem. Soc.
1978,
100:
1778
2s Noyori R.
Makino S.
Okita T.
Hayakawa Y.
J. Org. Chem.
1975,
40:
806
2t Doering H.
J.
Am. Chem. Soc.
1952,
74:
5688
2u Brady WT.
Hieble JP.
Tetrahedron
Lett.
1970,
3205
2v Cavazza P.
J.
Chem. Soc., Chem. Commun.
1974,
501
2w Berger C.
Dietrich S.
Dilger U.
Geuenich D.
Helios H.
Herges R.
Kirchmer P.
Rottele H.
Schroder G.
Angew.
Chem. Int. Ed.
1998,
37:
1854
2x Sendelbach S.
Schwetzler-Raschke R.
Radi A.
Kaiser R.
Henie GH.
Korfant H.
Reiner S.
Foehlisch B.
J. Org. Chem.
1999,
64:
3398
2y Lee CJ.
Cho SY.
Cha JK.
Tetrahedron
Lett.
1999,
40:
7675
3a Shono T.
Nozoe T.
Yamaguchi Y.
Ishifune M.
Sakaguchi M.
Masuda H.
Kashimura S.
Tetrahedron Lett.
1991,
32:
1051
3b Franck-Neumann M.
Brion F.
Martina D.
Tetrahedron Lett.
1978,
5033
3c Cavazza M.
Pietra F.
J. Chem. Soc., Perkin Trans.
1
1985,
2283
3d Cavazza M.
Guerriero A.
Pietra F.
J.
Chem. Soc., Perkin Trans. 1
1986,
2005
3e Akroyd P.
Haworth RD.
Jefferies PR.
J. Chem. Soc.
1954,
286
3f Akroyd P.
Haworth RD.
Jefferies PR.
J. Chem. Soc.
1951,
3427
3g Schreiber J.
Pesaro M.
Leimgruber W.
Eschenmoser A.
Helv. Chim. Acta
1958,
41:
2103
3h Nikanorov VA.
Gavrilova GV.
Rozenberg VI.
Reutov OA.
Russ. Chem.
Bull.
1987,
36:
2174
3i Miller J.
Ponte CD.
J. Chem. Res. Miniprint
1988,
3:
914
3j Nikanorov VA.
Gavrilova GV.
Yur"ev AV.
Rozenberg VI.
Reutov OA.
Russ. Chem. Bull
1995,
44:
1767
3k Itoh A.
Saito T.
Oshima K.
Nozaki H.
Bull. Chem. Soc. Jpn.
1981,
54:
1456
3l Shono T.
Naekawa H.
Nozoe T.
Kashimura S.
Tetrahedron Lett.
1990,
31:
895
3m Wenkert E.
Greenberg RS.
Kim H.-S.
Helv.
Chim. Acta
1987,
70:
2159
3n Davies HML.
Clark TJ.
Kimmer GF.
J. Org. Chem.
1991,
56:
6440
3o Banwell MG.
Cowden CJ.
Gravatt GL.
Rickard CEF.
Aust.
J. Chem.
1993,
46:
1941
3p Banwell MG.
Gravatt GL.
Rickard CEF.
J. Chem. Soc., Chem. Commun.
1985,
514
3q Birch AJ.
Keeton R.
J. Chem.
Soc. C
1968,
109
3r Hatakawa Y.
Sakai M.
Noyori R.
Chem.
Lett.
1975,
509
3s Froehlisch B.
Korfant H.
Meining H.
Frey W.
Eur. J. Org. Chem.
2000,
7:
1335
3t Sato T.
Nippon
Kagaku Zasshi
1959,
80:
1347 ; Chem. Abstr. 1961 ,
4525
3u Trahanovsky WS.
Emeis SL.
Lee AS.
J. Org. Chem.
1976,
41:
4043
3v Kato M.
Yamamoto S.
Nomura S.
Miwa T.
Bull. Chem. Soc. Jpn.
1990,
63:
64
3w Feldman KS.
Wu M.-J.
Rotella DP.
J. Am. Chem. Soc.
1989,
111:
6457
3x Brady WT.
Synthesis
1971,
415
3y Muehlstaedt M.
Naturwissenschaft
1958,
45:
240 . (z) Muehlstaedt, M. Chem.
Ber. 1960 , 93 ,
2638
4a Mayor C.
Jones WM.
J.
Org. Chem.
1978,
43:
4498
4b Stohrer I.
Hoffmann HMR.
Tetrahedron
1992,
48:
6021
4c Foehlisch B.
Sendelbach S.
Bauer H.
Liebigs Ann.
Chem.
1987,
1
4d Noyori R.
Baba Y.
Makino S.
Takaya H.
Tetrahedron Lett.
1973,
1741
4e Closs C.
J. Am.
Chem. Soc.
1961,
83:
599
4f Shono T.
Okada T.
Furuse T.
Kashimura S.
Nozoe T.
Maekawa H.
Tetrahedron Lett.
1992,
33:
4337
4g Yamaga H.
Fujise Y.
Ito S.
Tetrahedron
Lett.
1987,
28:
585
4h Noyori R.
Makino S.
Takaya H.
J.
Am. Chem. Soc.
1971,
93:
1272
4i Baldwin JE.
Broline BM.
J.
Am. Chem. Soc.
1982,
104:
2857
4j Barbier M.
Barton DHR.
Devys M.
Topgi RS.
Tetrahedron
1987,
43:
5031
4k Barbier M.
Barton DHR.
Devys M.
Topgi RS.
J.
Chem. Soc., Chem. Commun.
1984,
743
4l Rieker A.
Renner R.
Mueller E.
Justus
Liebigs Ann. Chem.
1969,
730:
67
4m Hiyama T.
Ozakiano Y.
Nozaki H.
Tetrahedron
1974,
30:
2661
4n Salakhutdinov NF.
Detsina AN.
Koptyug VA.
Russ. J. Org. Chem.
1981,
1312
4o Salakhutdinov NF.
Detsina AN.
Korobeinicheva IK.
Koptyug VA.
Russ.
J. Org. Chem.
1979,
15:
1310
4p Salakhutdinov NF.
Korobeinicheva IK.
Detsina AN.
Koptyug VA.
Bull. Chem. Russ.
1978,
27:
1937
4q Cavazza M.
Morganti G.
Pietra F.
J.
Chem. Soc., Perkin Trans. 1
1984,
4:
727
5 Yoshitake Y.
Nakagawa H.
Eto M.
Harano K.
Tetrahedron Lett.
2000,
41:
4395
6 Saito K.
Ando S.
Kondo Y.
Heterocycles
2000,
53:
2601
7a Nitta M.
Tajima Y.
J.
Chem. Res., Synop.
1999,
6:
372
7b Kumar K.
Kapur A.
Ishar MPS.
Org.
Lett.
2000,
2:
787
8 Kashman Y.
Hirsch S.
Koehn F.
Cross S.
Tetrahedron Lett.
1987,
28:
5461
9 Rosenblum M.
Watkins JC.
J. Am. Chem. Soc.
1990,
112:
6316
10a Hirao T.
Masunaga T.
Hayashi K.
Ohshiro Y.
Agawa T.
Tetrahedron Lett.
1983,
24:
399
10b Amice P.
Blanco L.
Conia JM.
Synthesis
1976,
196
11 Pretsch E.
Clerc T.
Seibl J.
Simon W.
Tables of Spectral Data
for Structure Determination of Organic Compounds
Springer-Verlag;
Berlin:
1983.
p.M90
12a Wenkert E.
Arrhenius TS.
Bookser B.
Gwo M.
Manici P.
J. Org. Chem.
1990,
55:
1185
12b Birch AJ.
Brown JM.
Stansfield F.
J. Chem. Soc.
1964,
5343
12c Patwarden SA.
Dev S.
Tetrahedron
1972,
28:
1075
12d Taylor RT.
Paquette LA.
In Org.
Synth.
Coll. Vol. 7:
John Wiley and Sons;
New
York:
1990.
p.200
13a Birch AJ.
Brown JM.
Stansfield F.
J. Chem. Soc.
1964,
5343
13b Kuroda S.
Sugimori M.
Kawahigashi S.
Matuzaki N.
Nishigama T.
Hiroka S.
Bull. Chem. Soc. Jpn.
1981,
54:
1893
13c Patwardran SA.
Dev S.
Tetrahedron
1972,
28:
1075
13d Sato M.
Tanaka T.
Tsunetsugu J.
Ebine S.
Bull. Chem. Soc. Jpn.
1975,
48:
2395
14a Hudson A.
Bona MAD.
Waterman D.
Alberti A.
Benaglia M.
Macciantelli D.
J.
Chem. Soc., Perkin Trans. 2
1997,
12:
2487
14b Tan Q.
Lou J.
Borhan B.
Karnaukhova E.
Berova N.
Nakanishi K.
Angew. Chem. Int. Ed. Engl.
1997,
36:
2089
15 The superscripts indicate toward which
C-atom (a substituent or H-atom) is assigned hydrogen oriented [for example
HCl -C(6) means the hydrogen at C(6) oriented toward
to Cl].
16 Takaya H.
Hayakawa Y.
Noyori R.
J.
Am. Chem. Soc.
1978,
100:
1778
17 Jones G.
J.
Chem. Soc. C
1970,
1230
18a Almeida WP.
Correia CRD.
Tetrahedron Lett.
1994,
35:
1367 ; (82%, Et3 N, NaI, TMSCl)
18b Duhamel P.
Hennequin L.
Poirier JM.
Tavel G.
Vottero C.
Tetrahedron
1986,
42:
4777
