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Catalytic Hydrogenationof Chiral 2-(2-Furyl)-3,4-dimethyl-5-phenyloxazolidineFelix Polyak a b , Tatiana Dorofeeva a & GunarZelchan aa Latvian Institute of Organic Synthesis , LV-1006,Riga, LATVIAb Department of Chemistry , Technion–IsraelInstitute of Technology , Haifa, 32000, IsraelPublished online: 16 Feb 2007.

To cite this article: Felix Polyak , Tatiana Dorofeeva & Gunar Zelchan (1995) CatalyticHydrogenation of Chiral 2-(2-Furyl)-3,4-dimethyl-5-phenyloxazolidine, SyntheticCommunications: An International Journal for Rapid Communication of SyntheticOrganic Chemistry, 25:19, 2895-2900, DOI: 10.1080/00397919508011419

To link to this article: http://dx.doi.org/10.1080/00397919508011419

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SYNTHETIC COMMUNICATIONS, 25(19), 2895-2900 (1995)

CATALYTIC HYDROGENATION OF CHIRAZ, 2- (2-FURYL)-3,4-DIMETHYL-5-PHENYLOXAZOLIDINE

Felix Polyak*#, Tatiana Dorofeeva, Gunar Zelchan

Latvian Institute of Organic Synthesis, LV-1006 Riga, LATVIA

Abstract. Reduction of chiral 2-(2-furyl)-3,4-dimethyl-5-phenyloxazo- lidines-1,3 by H2/Raney nickel proceeds simultaneously as hydrogenation of the furan ring and opening of the oxazolidine ring on C2-0 bond. Diastere- oselectivity in the first reaction was established as ca 40% and 80% depending on the configuration of the oxazolidine 1 and 2.

The optically active 2-substituted 1,3-oxazolidines are known as the

effective semi-products of the asymmetric reactions of "chiral auxiliary"

Such intermediates may be obtained by the reaction of the aldehyde

possessed a prochiral group with optically active P-aminoalcohols. As a rule

the asymmetric reactions of chiral 1,3-oxazolidines with a prochiral group in

position 2 proceed with high stereoselectivity. In the present work an attempt

to carry out the asymmetric catalytic hydrogenation of the furan ring under

chiral control of the oxazolidine ring has been undertaken.

* To whom correspondence should be addressed # Present address - Department of Chemistry, Technion - Israel Institute of Technology, Haifa, 32000, Israel.

2895

Copyright 0 1995 by Marcel Defier, Inc.

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2896 POLYAK, DOROFEEVA, AND ZELCHAN

Chiral 2-furyloxazolidines were obtained by the reactions either of

(1R,2S)-ephedrine or (lS,2S)-pseudoephedrine with furfural in the presence

of molecular sieves5. The optically pure (2S,4S,jR)-l and (2S,4S,5S)-2 are: hy-

drogenated by hydrogen in ethanol at ambient temperature in the presence of

Raney nickel. All attempts to carry out the hydrogenation of 1 and 2 under

platinum, palladium or palladium on coal have failed. Unfortunately, instead

of the desired single hydrogenated product - 2-tetrahydrofuryloxaolidine,

we observed the gradual formation of three substances - 3 , 5 , 7 from 1 and 4,

6, 8 from 2. After the complete disapperance of 1 and 2 the ratio of 3 5 7 was

1.5 : 1 : 1 and of 4:6:8 - 6.8 : 3.3 : 1. During further hydrogenation the amount

of 3 and 5 (or 4 and 6 correspondingly) decreased in the reaction mixture

while the amount of 7 and 8 increased, and the latter remained as the only re-

action product. Using the preparative GC we succeeded to isolate all the com-

pounds in both reaction mixtures and to determine their structures by means

of 'H NMR and chromato-mass-spectra. Thus, in 'H NMR spectrum of 4 we

observed the typical multiplets of the protons of the tetrahydrofuran ring

CH,-CH2- (1.78-2.11 pprn) and -CH2-O-CH- (3.73-4.18 ppm) and the signals

of the protons of the oxazolidine ring. In the 'H NMR spectrum of 6 there are

signals of the furan ring protons (6.13-6.38 pprn (Hp and q) and 7.49 ppm

(Ha)). At the same time the typical proton signals H2, H4 and H5 of the oxa-

zolidine ring are absent; the AB-quartet at 3.64 ppm and the broad signal of

the OH group at 4.49 ppm are observed instead of them. In the 'H NMR

spectrum of 8, the signals of both groups of protons of the tetrahydrofuran

ring (1.78-2.09 ppm for -CH-CH- and 3.88-4.07 ppm for -CH-O-CH-) and

Al3-quartet at 3.82 ppm and the broad proton signal of OH group at 4.38 ppm

are observed (Table 1). According to these data we suppose that 4 is 2-(2-te-

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CATALYTIC HYDROGENATION 2897

trahydro-furyl)-1,3-oxazolidine - the product resulting from the hydrogena-

tion of the furan ring 2 and 6 is 2-(P-hydroxyethylamino)-methylfuran derived

as a result of the opening of the oxazolidine cycle 2 via the C2-0 bond and 2-

@-hydroyethylamino)-methyltetrahydrofuran 8 appears to be the terminal

product of the hydrogenation of 2 (Scheme 1). The data of mass-spectra of the

compounds 4, 6 and 8 confirm the structures mentioned above. We suggest

that the most characteristic peaks (4 - m/z 176 and 71,6 - m/z 138 and 81,s

- m/z 142 and the peak of the molecular ion) correspond to the fragments of

the molecules as shown on the Scheme 1. Compounds 3,s and 7 - products

of the hydrogenation of 1 have an analogous structures as 4,6 and 8. Spectra

'H NMR of 3 and 4 present a double set of signals of the protons of the oxa-

zolidine ringe. This duplication is due to the existence of the pair of diastereo-

mers which appear in nonequal ratio as a result of the asymmetric

hydrogenation of the furan ring. The ratio of diastereomers 343b - 7:3 and

4a/4b - 9:l shows that diastereoselectivity of hydrogenation of 2 (oxazolidine

derived from pseudoephedrine) is higher than that of 1 (oxazolidine derived

from ephedrine). Thus, the catalytic hydrogenation of 2-(2-furyl)oxazolidines

1 and 2 proceeds simultaneously via hydrogenation of the furan ring and the

opening of the oxazolidine cycle as well, the rate of the first process being

considerably higher. The semiproducts obtained undergo the same transfor-

mations affording 7 or 8. The reductive cleavage of C2-0 bond of oxazolidines

by action of hydrogen under Raney Ni seems to be of the common character.

So we propose this reaction as a new method of the synthesis of the

N-methylene substituted derivatives of the P-hydroxyamines via intermediate

oxazolidines.

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2898 POLYAK, DOROFEEVA, AND ZELCHAN

Ph

Me \ Me

192 1- 2s, 4s, 5R 2- 2s, 4s, 5s

Raney Ni

Ph OH

Me 138 I N * \ 81

Ph 176: 71 ,I \ Me Me

Me

5, 6 394

Me

Scheme 1

EXPERIMENTAL

'H NMR spectra were obtained on a Bruker WH-90/DS (90 MHz) spec-

trometer for solutions in CDC1, with tetramethylsilane as an internal stand-

ard. GC analysis was carried out on a Chrom-5 instrument equipped with a

flame-ionization detector using a glass column (1.2 m x 3 mm) packed with

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CATALYTIC HYDROGENATION 2899

Table 1. 'H NMR spectra of the compounds 3-8 (6, ppm, J, Hz)

3 0.89 (3H, d, C-Me, J=7); 1.82-2.11 (4H, m, CH2-CH2); 2.42 (3H, s, N-Me); 2.84 (lH, m, 4-H); 3.84-4.09 (3H, m, CH-0-CH2); 4.89 (lH, d,

4 1.11 (3H, s, C-Me, J =6); 1.78-2.11 (4H, m, CH2-CH2); 2.38 and 2.42 (3H, 2s, N-Me); 2.84 (lH, m, 4-H); 3.73-4.18 (3H, m, CH-0-CH2); 4.16 and 4.22(1H,2~,2-H);4.44and4.50 (lH,2d,SH,J=9);7.31(5H,s,Ph).

5 0.67 (3H, d, C-Me, J=7); 2.29 (3H, s, N-Me); 2.79 (lH, m, Me-CH); 3.74 and 3.87 (2H, AB-q, CH2, J = 8); 4.89 (lH, d, Ph-CH, J = 5); 4.98 (lH, b.s., OH); 6.13 and 6.27 (2H, 2dd,

5-H, J=4); 5.11 (lH, S , 2-H); 7.29 (5H, S , Ph).

and Hy); 7.29 (5H, s, Ph); 7.33 (IH, dd,

6 0.72 (3H, d, C-Me, J=7); 2.28 (3H, s, N-Me); 2.71 (lH, m, Me-CH); 3.56 and 3.73 (2H, ABq, CH2, J = 14); 4.22 (lH, d, Ph-CH, J = 10); 4.49 (IH, b.s., OH); 6.13-6.38 (2H, m, Hp and Hy); 7.27 (SH, s, Ph); 7.49 (lH, dd,

7 0.82 and 0.89 (3H, 2d, C-Me, J = 7); 1.76-2.04 (4H, m, CH2-CH2); 2.31 and 2.38 (3H, 2s, N-Me); 2.84 (lH, m, Me-CH); 3.69 and 3.77 (2H, AB-q, CH2); 3.82-4.16 (3H, m, CH-0-CH2); 4.87 (lH, d, Ph-CH, J =4); 4.91 (lH, b.s., OH); 7.30 (5H, s, Ph).

N-Me); 2.64 (lH, m, Me-CH); 3.76 and 3.89 (2H, AB-q, CH2, J = 8); 3.88-4.07 (3H, m, CH-0-CH); 4.20 (lH, d, Ph-CH, J = lo); 4.38 (lH, b.s., OH); 7.33 (5H, s, Ph).

Hs) .

Hs).

8 0.73 (3H, d, C-Me, J=7); 1.78-2.09 (4H, m, CH2-CH2); 2.36 (3H, s,

Table 2. Mass-spectra of the compounds 3-8 (m/z, rel.abundance,%)

3 176(100); 148(75.8); 133(7.5); 117(15.0); 105(15.1); 91(20.6). 4 176(100); 148(68.8); 133(7.3); 117(15.6); 106(5.2); lOS(7.3); 91(28.1). 5 227(0.8); 176( 17.8); 148( 13.6); 138(33.3); 137(14.2); 106(35.0); lOS(35.0);

6 227(0.1); 176(0.1); 170(0.4); 148(0.1); 138(58.3); 137(9.4); 106( 12.5);

7 231(0.8); 142(53.9); 106(78.7); 105(74.9); 77(78.7); 70(100). 8 231(0.1); 148(0.6); 142( 100); 117(1.1); 106(53.1); 105(54.2); 77(50);

*

8 1 ( 100).

lOS(13.5); 81(100).

70(91.7).

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2900 POLYAK, DOROFEEVA, AND ZELCHAN

5% OV-17 on Chromosorb W-AW (60-80 mesh). Preparative GC was ful-

filled on a Pye-Unicam-105 instrument equipped with a flame-ionization de-

tector using a glass column (1 m x 7 mm) packed with 20% SE-30 on

Chromosorb AW-DMCS. Chromato-mass-spectra were obtained on a Kratos

MS-25 (70 eV) instrument.

Hydrogenation of 2-(2-furyl)-1,3-oxazolidines 1,2.

Raney nickel was added to a solution of 1 or 2 (2.5 g, 10 mmol) in abso-

lute EtOH (50 ml) and hydrogen was passed through the suspension. The re-

action mixture was analyzed every 10 min using GC control until the starting

substance disappeared. The reaction mixture (20 ml) was concentrated to 2, ml

and, using the preparative GC, the compounds were isolated.

REFERENCES

1 Fleming,I. and Kingdom,N. J.Chem.Soc., Chem. Commun., 1987,1177.

2 Berlan,J.; Besace,Y.; Pourcelot,G. and Gresson,P. Tetrahedron, 1986,42,

4754.

3 Colombo,L.; Gennari,C.; Poli,G. and Scolastico,C. Tetrahedron Lett., 1985,

44, 5459.

4 Agami,C.; Meinier,F. and Rizk,T. Synth. Commun., 198?,17, 241.

5 Polyak,F.; Dorofeeva,T.; Zelchan,G. Chern. Heterocycl. Comp. (in Press).

(Received in the UK 15 September 1994)

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