LETTER

617

Preparation of (±)-1-Allyl-4-deoxy Mannose Derivatives Twana Saleh, Gérard Rousseau* Laboratoire des Carbocycles (Associé au CNRS), Institut de Chimie Moléculaire d'Orsay Bât. 420, Université de Paris-Sud, 91405 ORSAY, France Fax 33 1 69 156278; E-mail: [email protected] Received 18 January 1999

Abstract: Preparation of 4-deoxy mannose intermediates, useful for the synthesis of hemibrevetoxin is reported by a short reaction pathway. Key words: hemibrevetoxin, hetero Diels-Alder, allylation, iodoetherification, 4-deoxy mannose

Hemibrevetoxin B1 is a natural marine product, 1 of the brevetoxin family of which brevetoxin A 2,3 and brevetoxin B 4 are representative examples. This 6,6,7,7-tetracyclic ether, isolated from Gymnodinium breve contains 10 stereogenic centres (Figure). The interest in this family of products is due to its very high neurotoxic activity.1 HO

H

A

O

O

B

O

H

H

CH3 H

C H O

H

O

tion of aldehydes with 1-methoxy-2-(trimethylsilyloxy)1,3-butadiene. Besides, asymmetric cycloadditions have been well studied.12 Following the Danishefsky procedure the racemic enone 1 was prepared and stereospecifically reduced to the allylic alcohol 2 (Scheme 2). Reaction of the latter with m-chloroperbenzoic acid in the presence of methanol gave diol 3a. After benzylation, subsequent allylation using allyltrimethylsilane in acetonitrile at 0 °C (2 days) led to a diastereoisomeric mixture (96:4) of the two allylic tetrahydropyrans 5, 6 (overall yield 80%). The low reactivity of 4a in the allylation reaction led us to prepare and examine the behavior of the 2-methoxyethoxy derivative 4b. This compound was obtained as reported above for 4a by reaction of allylic alcohol 2 with m-chloroperbenzoic acid in the presence of 2-methoxyethanol, followed by benzylation and allylation. In this case, completion of the allylation reaction was achieved in 12 h, but

H

D CH3 OH

O

OCH3 O

Figure BnO

ZnCl2/ C6H6 +

0 °C to rt, 36 h OSi(CH3)3

H

5

A variety of synthetic approaches has been explored. The total synthesis of hemibrevetoxin B1 has been accomplished by the groups of Nicolaou,6 Yamamoto,7 Nakata 8 and Mori.9 Except for the Nakata strategy, which consists of the construction of the A cycle in the final steps of the synthesis, the other approaches implied the construction of the A ring first. This ring was obtained 6 in twelve steps from D-mannose (Scheme 1).

BnO

1 (92%) OH

OH

OH

mCPBA/ROH

DIBAL-H Toluene -78 °C BnO

0 °C, 2 h

BnO

2 (100 %)

3b R = CH3OCH2CH2 (83%)

HO

O

OH

BnO

SiMe3 OBn

BF3.Et2O/CH3CN

BnBr / NaH/THF

OTBS

OH

OR

3a R = CH3 (95%)

OBn HO

O

O

OBn

OH

O

0 °C to rt, 12h BnO

O

0 °C to rt, 48 h

OR

O 4a R = CH3 (89%)

D-mannose

4b R = CH3OCH2CH2 (96%)

Scheme 1 OBn

OBn OBn

We recently reported a new method to obtain bicyclic ethers 10 and we decided to apply this strategy to the synthesis of hemibrevetoxin B. However, we were interested first to look for a shorter preparation of the A ring of this compound. Our approach was based on the pioneer work of Danishefsky 11 concerning the hetero Diels-Alder reac-

BnO

OBn + BnO

O

5

96: 4

O

6

total yield: 80 % from 4a, 74 % from 4b

Scheme 2 Synlett 1999, No. 5, 617–619

ISSN 0936-5214

© Thieme Stuttgart · New York

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LETTER

T. Saleh, G. Rousseau

5, 6 were obtained with the same 96:4 ratio. The structures of the two diastereomers 5, 6 were established from their 1 H and 13C NMR spectra.13 Their relative configuration was determined in 1H NMR by 2D NOESY experiments. Besides, confirmation of the α configuration of the allyl substituent for the main isomer was established by preparing an intermediate reported by Nicolaou (vide infra). Allylation of 4b, with allyltrimethylsilane followed by workup of the reaction mixture with acetic anhydride 14 led to 7 (Scheme 3). Selective cleavage of the 2-O-benzyl ether was then accomplished by reaction with iodine in acetonitrile. A mixture of tetrahydrofuran 8a (2 diastereoisomers) and tetrahydropyran 8b (1 diastereoisomer) was obtained in a good overall yield. Subsequent reaction with zinc in acetic acid afforded the 1-allyl derivative 9.13 The mixture of iodo ethers was also treated with potassium carbonate, and the free alcohol function was protected as a t-butyldiphenylsilyl ether to give the mixture 10a-10b. Reaction with zinc with this mixture led to the 1-allyltetrahydropyran 11 whose 1H NMR spectrum was identical to the one previously reported.6

OBn OBn

CH3COOH / H2SO4 4a 75 °C, 3 h

BnO

O

OH

12 88 % OBn OBn

PCC / CH2Cl2 rt, 30 min

BnO

O

O

13 78 % OBn OBn

MgCl /THF -78 °C to 0 °C, 6 h

BnO

O

OH

14

HSiEt3/BF3.Et2O - 50 °C to - 20 °C, 30 min

5 (20) + 6 (80) 52 % (from 13)

Scheme 4 OBn

SiMe3 4b

OBn

In conclusion we have developed an efficient procedure to obtain α-1-allyl tetrahydropyran derivatives 5, 9 and 11 which can be useful synthons for the preparation of brevetoxin derivatives. Work is in progress to apply these results in the optically pure series.

BF3.Et2O then Ac2O AcO

0 °C to rt, 48h

O

7 (80%) OBn I2 / CH3CN 0 °C to rt, 12h

OBn O

O +

RO

1) K2CO3/MeOH 2) TPSCl/imidazole rt, 36h

O

I

References and Notes RO

O

8a R = Ac (52 %)

8b R = Ac(19 %)

10a R = TPS

10b R = TPS

I

OBn OH Zn/CH3COOH rt, 12h

RO

TPS = tBuPh2Si

O 9 R = Ac (78 %) 11 R = TPS (80 % (from 8a-8b))

Scheme 3

We were also interested to find conditions in which 6 could be obtained in good yield. This problem was solved by a four step procedure using the Kishi’s methodology.15 Compound 4a was deprotected under acidic conditions into hemiacetal 12, and then oxidised to lactone 13. Addition of allylmagnesium chloride on the carbonyl group led to the tertiary alcohol 14 which was reduced in the presence of triethylsilane in methylene chloride (1-1 v/v mixture) to the two diastereoisomers 5, 6 in a 20:80 ratio. We were unable to avoid the formation of 5 during the reduction step (Scheme 4).

Synlett 1999, No. 5, 617–619

ISSN 0936-5214

(1) Prasad, A.V.K.; Shimizu, Y. J. Am. Chem. Soc. 1989, 111, 6476-6477. (2) Shimizu, Y.; Chou, H.-N.; Bando, H.; Van Duyne, G.; Clardy, J. J. Am. Chem. Soc. 1986, 108, 514-515. (3) Pawlak, J.; Tempesta, M.S.; Golik, J.; Zagorski, M.G.; Lee, M.S.; Nakanishi, K.; Iwashita, T.; Gross, M.L.; Tomer, K.B. J. Am. Chem. Soc. 1987, 109, 1144-1150. (4) Lin, Y.Y.; Risk, M.; Ray, S.M.; Van Enge, D.; Clardy, J.; Golik, J.; James, J.C.; Nakanishi, K. J. Am. Chem. Soc. 1981, 103, 6773-6775. (5) a) Kadota, I.; Matsukawa, Y.; Yamamoto, Y. J. Chem. Soc., Chem. Commun. 1993, 1638-1641. b) Feng, F.; Murai, A. Chem. Lett. 1992, 1587-1590. c) Feng, F.; Murai, A. Chem. Lett. 1995, 23-24. d) Feng, F.; Murai, A. Synlett 1995, 863865. e) Ishihara, J.; Murai, A. Synlett 1996, 363-365; f) Nakata, T.; Nomura, S.; Matsukura, H.; Morimoto, M. Tetrahedron Lett. 1996, 37, 217-220. g) Matsukura, H.; Morimoto, M.; Nakata, T. Chem. Lett. 1996, 487-488. h) Gleason, M. M.; Mc Donald, F. E. J. Org. Chem. 1997, 62, 6432-6435. (6) a) Nicolaou, K.C.; Reddy, K.R.; Skokotas, G.; Sato, F.; Xiao, X.-Y. J. Am. Chem. Soc. 1992, 114, 7935-7936. b) Nicolaou, K.C.; Reddy, K.R.; Skokotas, G.; Sato, F.; Xiao, X.-Y.; Hwang, C.-K. J. Am. Chem. Soc. 1993, 115, 3558-3575. (7) Kadota, I.; Yamamoto, Y. J. Org. Chem. 1998, 63, 6597-6606. (8) Morimoto, M.; Matsukura, H.; Nakata, T. Tetrahedron Lett. 1996, 37, 6365-6368. (9) Mori, Y.; Yaegashi, K.; Furukawa, H. J. Am. Chem. Soc. 1997, 119, 4557-4558.

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Preparation of (±)-1-Allyl-4-deoxy Mannose Derivatives

(10) Simart, F.; Brunel, Y.; Robin S.; Rousseau, G. Tetrahedron 1998, 54, 13557-13566. (11) Danishefshy, S.; Kerwin, J.F.; Kobayashi, S. J. Am. Chem. Soc. 1982, 104, 358-360. (12) Schaus, S.E.; Brånalt, J.; Jacobsen, E.N. J. Org. Chem. 1998, 63, 403-405 and references cited therein. (13) Selected data:5 1H NMR (400 MHz, CDCl3): δ 1.78 (dt, J = 13 and 3 Hz, 1H); 2.00 (m, 1H); 2.32 (m, 2H); 3.46 (t, J = 5 Hz, 1H); 3.53 (dd, J = 5 and 10 Hz, 2H); 3.75 (dd, J = 7 and 10 Hz, 1H); 3.70 (m, 1H); 3.93 (m, 1H); 4.08 (d, J = 4 Hz, 1H); 7.31 (m, 15H). 13C NMR: δ 28.79; 34.32; 69.3; 69.6; 70.8; 71.3; 71.6; 72.41; 72.74; 74.3; 116.5; 126.1-127.7 (15 C); 133.8; 137.8 (3 C). 6 1H NMR (200 MHz, CDCl3): δ 1.90 (m, 2H); 2.35 (m, 2H); 3.28 (t, J £ 0.5 Hz, 1H); 3.50 (m, 4H); 3.68 (d, J = 2 Hz, 1H); 4.60 (m, 6H); 5.13 (m, 2H); 5.69 (m, 1H); 7.30 (m, 15H). 13C NMR δ 29.3; 35.9; 70.0; 72.9; 73.3; 73.9; 75.6; 75.6; 78.5; 79.2; 117.0; 127.1-128.7 (15 C); 134.6; 138.2; 138.4; 138.8.

619

9 1H NMR (250 MHz, CDCl3): δ 1.83 (m, 2H); 2.08(s, 3H); 2.36 (m, 2H); 3.67 (m, 1H); 3.80 (m, 1H), 3.89 (m, 1H); 3.95 (m, 1H); 4.09 (dd, J = 3 and 11 Hz, 1H); 4.33 (dd, J = 8 and 12 Hz, 1H); 4.59 (AB system, J = 12 Hz, 2H); 5.08 (m, 2H); 5.82 (m, 1H); 7.35 (bs, 5H). 11 13C NMR: δ 19.22; 26.84; 28.41; 34.56; 65.84; 68.20; 70.28; 70.35; 73.40; 74.89; 117.01; 127.63; 127.74; 127.90; 128.53; 129.62; 133.56; 134.41; 135.59; 137.75. (14) Hung, S.-C.; Lin; C.-C.; Wong, C.-H. Tetrahedron Lett. 1997, 38, 5419-5422. (15) Lewis, M.D.; Cha, J. K.; Kishi, Y. J. Am. Chem. Soc. 1982, 104, 4976-4979.

Article Identifier: 1437-2096,E;1999,0,05,0617,0619,ftx,en;G02099ST.pdf

Synlett 1999, No. 5, 617–619

ISSN 0936-5214

© Thieme Stuttgart · New York