Cryogenics Report of Kumamoto University, 2008, 19, 27-28.
Synthetic Study of Macrocycles
Using Manganese(III)-Based Oxidative Radical Cyclization
Yosuke Ito and Hiroshi Nishino*
Department of Chemistry, Graduate School of Science and Technology, Kumamoto University
Abstract- Manganese(III)-based macrocyclization of alkadienes with bis(3-oxobutanoate)s was investigated and many novel macrodiolides, macrodiamides, cyclophanes, and polycyclic ethers were synthesized in one-pot.
Key words- Macrodiolides; macrocyclization; radical cyclization;
manganese(III) acetate; oxidation
I. INTRODUCTION
ANY naturally occurring macrocyclic compounds, which were isolated from actinomyces soil bacteria [1], marine sponges [2], sea hares [3], senecio plants [4], pathogenic fungi [5], lichens [6], etc., are known and some have significant biological activities. Some macrocyclic compounds reveal supramolecular behavior such as molecular recognition, metal ion transport, enzymatic catalysis, chemical switching, and so on [7]. Therefore, many chemists have been attracted by the total synthesis and physicochemical properties of these macrolides for over four decades [8].
In recent years, our research group has developed various manganese(III)-based oxidation [9]. The characteristics of the oxidation are that the manganese(III) acetate can readily undergo a ligand exchange with 1,3-dicarbonyl compounds in acetic acid to generate the manganese(III)-enolate complex in situ, followed by a one-electron oxidation from the electron- rich carbon-carbon double bond to manganese(III) acetate to give the corresponding carbon radicals [10]. We reported the straightforward access to the functionalized large cyclic compounds which were obtained by the oxidation of oligomethylene di(3-oxobutanoate)s or N,N’-oligomethylene bis(acetoacetamide)s with manganese(III) acetate in the presence of terminal alkadienes [11], [12]. According to the method, we obtained from 11- to 22-membered macrodiolides or macrodiamides, each possessing two-fused dihydrofuran rings, in good yields. It was postulated that the macrocyclization would be caused by the intermolecular cyclization of the one of the terminal alkene part of the alkadienes with the one of the manganese(III)-enolate complex of the bis(3-oxobutanoate)s followed by the intramolecular cyclization of the other carbon-carbon double bond (donor) with the other manganese(III)-enolate complex (acceptor) [10]. Although many ionic macrocyclizations promoted by metal cations are known [13], the oxidative radical macrocyclization is apparently characteristic in the manganese(III)-based oxidation reaction. In connection with the inter- and intramolecular macrocyclic formation, we were interested in the ability of the manganese(III)-based macrocyclization [14].
II. RESULTS AND DISCUSSION
A mixture of terminal alkadienes 1 and oligomethylene bis(3-oxobutanoate)s 2 was allowed to react with manganese(III) acetate in acetic acid at 100 °C or reflux temperature under an argon atmosphere, giving new from 20- to 62-membered macrodiolides 3 in 22-60% yields (Scheme 1).
Since the methylene-tethered terminal alkadienes 1 and the bis(3-oxobutanoate)s 2 seemed to be flexible under the reaction conditions, it was supposed that the macrocyclization should be effective. However, the yield of the macrodiolides 3 was good to moderate.
Mn(OAc)3 AcOH, 100 oC, argon Ph (CH2)x
Ph
Ph Ph 1x (x = 6,8,16,18,28)
2y (y = 6,10,12,20,26)
3x,y O
O (CH2)y Me
O O
Me
O O
(CH2)x
(CH2)y O O
O O
Ph Ph Ph Ph
O O
Me Me
+
Yield: 22-60%, Ring size: 20-62 1x : 2y : Mn(OAc)3 = 1 : 1.3 :7
Scheme 1.
A similar reaction of alkadienes 1 with bis(3- oxobutanoate)s 4 was carried out in the presence of manganese(III) acetate in acetic acid at 100 °C under an argon atmosphere to give new cyclophane-type macrodiolides 5 in 33-60% yields (Scheme 2).
When the reaction of terminal alkadienes 6 using the bis(3- oxobutanoate)s 4 was conducted under similar conditions, new from 32- to 56-membered cyclophane-type macrodiolides 7 were obtained in 21-46% yields (Scheme 3).
The reaction of p-phenylenebis(7,7-diphenyl-6-heptene) 8 with the bis(3-oxobutanoate)s 4 yielded new cyclopeane-type macrodiolides 9 in 57-62% yields (Scheme 4).
In addition, the reaction of p-phenylenebis(7,7-diphenyl-6- heptene) 8 with p-phenylenebis(heptamethylene) bis(3- oxobutanoate) 10 also afforded new 40-membered cyclophane-type macrodiolide 11 in a 49% yield (Scheme 5).
M
Cryogenics Report of Kumamoto University, 2008, 19, 27-28.
Ph (CH2)x Ph
Ph Ph
Mn(OAc)3 AcOH, 100 oC, argon
+
1a: x = 6, 1b: x = 8, 1c: x = 16
X = O
O
(CH2)x
O
X O
O O
Me Ph Ph
Me Ph Ph
O O
y y
4a: y = 1, X = para- 4c: y = 2, X = meta- 4e: y = 3, X = ortho-
y
y X O
O O O
Me O O
Me O O
4b: y = 2, X = ortho- 4d: y = 2, X = para- 4f : y = 3, X = para-
5aa-cfYield: 33-60%, Ring size: 24-46
Scheme 2.
Mn(OAc)3 AcOH, 100 oC, argon 6a: x = 1, 6b: x = 2, 6c: x = 3
+
4a: y = 1, 4d: y = 2, 4f: y = 3 O
O Ox O x y y
Ph Ph
Ph Ph
O
O O O
Me O O
Me O O
y O O Me
PhPh
O O
Me PhPh
O O O O
O O O
x xO
y
7aa-cfYield: 21-46%, Ring size: 32-56
Scheme 3.
(CH2)5
(CH2)5 Ph
Ph Ph
Ph +
8
y O O Me
Ph Ph
O O
Me Ph Ph
O O O O
y 4a: y = 1, 4d: y = 2, 4f: y = 3
y Oy
O O O
Me O O
Me O O
9a-f Yield: 57-62%, Ring size: 32-44 Mn(OAc)3
AcOH, 100 oC, argon
Scheme 4.
(CH2) (CH2)
O O
Me Me
O
O O O
O O
O O
O O
Me Ph Ph
Me Ph Ph AcOH, 100 oC, argon
10 (CH2)5
(CH2)5 Ph
Ph Ph
Ph 8
7 7
Mn(OAc)3 +
20 min
11Yield: 49%, Ring size: 40 8 (0.2mmol) : 10 : Mn(OAc)3 = 1 : 1.3 :7
Scheme 5.
Finally, a combination of terminal alkadienes 12 and bis(3- oxobutanoate)s 13 was allowed to react with manganese(III) acetate in acetic acid at 100 °C under an argon atmosphere, producing new crown ether-type macrodiolides 14 in 30-44%
yields (Scheme 6).
O xO Ph
Ph
Ph Ph
Me O O Me
O O
O O
y
Mn(OAc)3
14ba-dd +
O O
O O
O O
Me PhPh
Me PhPh
O O
12b-d: x = 2-4
x
y 13a-d: y = 1-4
argon AcOH 100 oC
Yield: 30-44%, Ring size: 19-34
Scheme 6.
In summary, we have accomplished the unique synthesis of several macrocyclic compounds using the manganese(III)- based oxidative radical cyclization.
III. ACKNOWLEDGMENT
We gratefully acknowledge Professor Teruo Shinmyozu, Institute for Materials Chemistry and Engineering, Kyushu University, Japan, for the measurement of the high resolution FAB mass spectrometry.
IV. REFERENCES [1] Rychnovsky, S. D. Chem. Rev., 1995, 95, 2021-2040.
[2] Kobayashi, J.; Ishibashi, M. Chem. Rev., 1993, 93, 1753-1769.
[3] Spinella, A.; Zubía, E.; MartÎnez,, E.; Ortea, J.; Cimino, G. J. Org.
Chem., 1997, 62, 5471-5475.
[4] Vedejs, E.; Ahmad, S.; Larsen, S. D.; Westwood, S. J. Org. Chem., 1987, 52, 3937-3938.
[5] Schnurrenberger, P.; Hungerbühler, E.; Seebach, D. Tetrahedron Lett., 1984, 25, 2209-2212.
[6] Sinha, S. C.; Keinan, E. J. Org. Chem., 1997,38, 377-386.
[7] (a) Vögtle, F. Supramolecular Chemistry: An Introduction; Wiley:
England, 1989. (b) Gokel, G. W. Crown Ethers and Cryptands; The Royal Society of Chemistry; England, 1994.
[8] (a) Corey, E. J.; Cheng, X.-M. The Logic of Chemical Synthesis; Wiley:
New York, 1989. (b) Nicolaou, K. C.; Sorensen, E. J. Classics in Total Synthesis; VCH: Weiheim, 1996.
[9] (a) Asahi, K.; Nishino, H. Tetrahedron. 2005, 61, 11107-11124. (b) Asahi, K.; Nishino, H. Tetrahedron Lett. 2006, 47, 2759-2762. (c) Asahi, K.; Nishino, H. Eur. J. Org. Chem. 2008, 2404-2416. (d) Asahi, K.;
Nishino, H. Synthesis 2009, 409-423. (e) Tsubusaki, T.; Nishino, H.
Tetrahedron 2009, in press. (f) Cong, Z.-Q.; Miki, T.; Urakawa, O.;
Nishino, H. J. Org. Chem. 2009, 74, in press.
[10] Nishino, H.; Nguyen, V. -H.; Yoshinaga, S.; Kurosawa, K. J. Org. Chem.
1996, 61, 8264-8271.
[11] (a) Ouyang, J.; Nishino, H.; Kurosawa, K. J. Heterocycl. Chem. 1995, 32, 1783-1791. (b) Yoshinaga, T.; Nishino, H.; Kurosawa, K.
Tetrahedron Lett. 1998, 39, 9197-9200.
[12] (a) Chowdhury, F. A.; Nishino, H.; Kurosawa, K. Heterocycl. Commun.
1999, 5, 111-112. (b) Chowdhury, F. A.; Nishino, H. J. Heterocycl.
Chem. 2005, 42, 1337-1343.
[13] (a) Shorthill, B. J.; Granucci, R. G.; Powell, D. R.; Glass, T. E. J. Org.
Chem. 2002, 67, 904-909. (b) Pigge, F. C.; Ghasedi, F.; Rath, N. P. J.
Org. Chem. 2002, 67, 4547-4552.
[14] Itoh, Y.; Nishino, H. Cryogenics Report of Kumamoto University, 2007, 18, 5-9.
