Abstract
The reactions of 1-(2-haloethyl)pyrrole-2-carbaldehydes with
(1S )-1-phenylglycinol or (1S )-valinol gave the corresponding fused
tricyclic oxazolidines as single diastereomers from which 1,2-disubstituted
1,2,3,4-tetrahydropyrrole[1,2-a ]pyrazines
were obtained by addition of organometallic reagents. The diastereoselectivity
was dependent on the nature of both the chiral auxiliary and the
organometallic reagent. The best diastereoselectivity (dr ≤ 98:2) was
obtained by using Grignard reagents with the oxazolidine derived
from (1S )-phenylglycinol. (+)-1-Methyl-
and (+)-1-ethyl-1,2,3,4-tetrahydropyrrole[1,2-a ]pyrazines were obtained by
reductive removal of the N2-substituent.
Key words
asymmetric synthesis - diastereoselectivity - Grignard reagents - heterocycles - oxazolidines - tetrahydropyrrolopyrazines
References
1 Peresada VP.
Medvedev OS.
Likhosherstov AM.
Skoldinov AP.
Khim.-Farm.
Zh.
1987,
21:
1054 ; Chem. Abstr. 1988 , 108 , 68298g
2 Seredenin SB, Voronina TA, Likhosherstov AM, Peresada YP, Molodavkin GM, and Halikas JA. inventors; US 5378846.
; Chem. Abstr. 1995 , 123 , 83350w
3 Seredenin SB, Voronina TA, Beshimov A, Peresada VP, and Likhosherstov AM. inventors; RU 2099055.
; Chem. Abstr. 1998 , 128 , 290245j
4 Varlamov AV.
Borisova TN.
Voskressensky LG.
Synthesis
2002,
155
5 Negoro T.
Murata M.
Ueda S.
Fujitani B.
Ono Y.
Kuromiya A.
Komiya M.
Suzuki K.
Matsumoto J.-i.
6 Skoldinov AP, Likhosherstov AM, and Peresada VP. inventors; SU 798104.
; Chem. Abstr. 1981 , 95 , 7337k
7 Skoldinov AP, Likhosherstov AM, and Peresada VP. inventors; DE 2832488.
; Chem. Abstr. 1980 , 93 , 46720h
8 Skoldinov AP, Likhosherstov AM, and Peresada VP. inventors; GB 2025936.
; Chem. Abstr. 1981 , 93 , 186406k
9 Likhosherstov AM.
Peresada VP.
Vinokurov VG.
Skoldinov AP.
Zh.
Org. Khim.
1986,
22:
2610 ; Chem. Abstr. 1987 , 107 , 236660u
10 Flament I.
Sonnay P.
Ohloff G.
Helv.
Chim. Acta
1977,
60:
1872
11 Peresada VP.
Tsorin IB.
Kirsanova GYu.
Likhosherstov AM.
Chichkanov GG.
Skoldinov AP.
Pharm. Chem. J.
1988,
22:
755
12 Peresada VP.
Medvedev OS.
Likhosherstov AM.
Skoldinov AP.
Pharm.
Chem. J.
1988,
22:
619
13 Jirkovsky IL.
Baudy R.
Synthesis
1980,
481
14 Jirkovsky IL. inventors; US 4188389.
; Chem. Abstr. 1980 , 92 , 198428m
15a Abou-Gharbia M.
Moyer JA.
Patel U.
Webb M.
Schieser G.
Andree T.
Haskins JT.
J. Med. Chem.
1989,
32:
1024
15b Likhosherstov AM.
Filippova OV.
Peresada VP.
Kryzhanovskii SA.
Vititnova MB.
Kaverina NV.
Reznikov KM.
Pharm. Chem. J.
2003,
37:
6
16 Katritzky AR.
Jain R.
Xu Y.-J.
Steel PJ.
J. Org. Chem.
2002,
67:
8220
17 Henrik M, Weil T, Müller S, Nagel J, Kauss V, Zemribo R, and Erdmare E. inventors; WO 2009095254.
; Chem. Abstr . 2009 , 151 , 245654
18 Zhu B.
Marinelli BA.
Goldschmidt R.
Foleno BD.
Hilliard JJ.
Bush K.
Macielag M.
Bioorg. Med. Chem. Lett.
2009,
19:
4933
19a Alvaro G.
Di Fabio R.
Gualandi A.
Savoia D.
Eur.
J. Org. Chem.
2007,
5573
19b Albano G.
Gualandi A.
Monari M.
Savoia D.
J. Org. Chem.
2008,
73:
8376
19c Savoia D.
Gualandi A.
Bandini M.
Lett.
Org. Chem.
2009,
434
19d Bandini M.
Eichholzer A.
Gualandi A.
Quinto T.
Savoia D.
ChemCatChem
2010,
2:
661
20 a ]pyrazine and achiral iminium ions
analogous to 9 have been prepared from
1-(2-aminoethyl)pyrrole; see: de Pablo MS.
Gandásegui T.
Vaquero JJ.
García Navío JL.
Alvarez-Builla J.
Tetrahedron
1992,
48:
8793
21 Oi R.
Sharpless KB.
Tetrahedron Lett.
1991,
32:
4853
22 Blaszykowski C.
Aktoudianakis E.
Alberico D.
Bressy C.
Hulcoop DG.
Jafarpour F.
Joushaghani A.
Laleu B.
Lautens M.
J. Org. Chem.
2008,
73:
1888
23 Settambolo R.
Mariani M.
Calazzo A.
J.
Org. Chem.
1998,
63:
10022
24 Other reaction conditions were also
tested by varying the solvent (DMF), the dehydrating agent (molecular
sieves), and the temperature, but less satisfactory results were obtained.
Moreover, mixtures of products 12a and 13a were obtained by carrying out the reactions
in the presence of a base (K2 CO3 or Et3 N).
25 Crystallographic data for compound 14 have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publications CCDC
792774; copies can be obtained free of charge on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44
(1223)336033 or email: deposit@ccdc.cam.ac.uk].
26 It is noteworthy that tricyclic tetrahydrooxazolopyrazolo-pyridine
structures with three carbon stereocenters have been prepared as
single diastereomers from 2-pyrrole-carboxaldehyde, (S )- or (R )-α-amino
acid esters, and (+)- or (-)-norephedrine. The
configuration of the newly formed stereocenter in the oxazolidine
ring depends only on the chirality of the norephedrine. However,
the potential of such compounds as precursors of chiral iminium
ions, which could serve as suitable substrates for the addition
of Grignard reagents, was not considered during the work reported
here.
27a Takahashi H.
Chida Y.
Higashiyama K.
Onishi H.
Chem.
Pharm. Bull.
1985,
33:
4662
27b Yamato M.
Hashigaki K.
Ishikawa S.
Qais N.
Tetrahedron Lett.
1988,
29:
6949
27c Takahashi H.
Hsieh BC.
Higashiyama K.
Chem.
Pharm. Bull.
1990,
38:
2429
27d Yamato M.
Hashigaki K.
Qais N.
Ishikawa S.
Tetrahedron
1990,
46:
5909
27e Hashigaki K.
Kan K.
Qais N.
Takeuchi Y.
Yamato M.
Chem. Pharm.
Bull.
1991,
39:
1126
27f Higashiyama K.
Nakahata K.
Takahashi H.
J.
Chem. Soc., Perkin Trans. 1
1994,
351
27g Higashiyama K.
Nakahata K.
Takahashi H.
Tetrahedron
1994,
50:
1083
27h Higashiyama K.
Inoue H.
Takahashi H.
Tetrahedron
1994,
50:
1083
27i Yamauchi T.
Higashiyama K.
Kubo H.
Ohmiya S.
Tetrahedron: Asymmetry
2000,
11:
3003
27j Amat M.
Elias V.
Llor N.
Subrizi F.
Molins E.
Bosch J.
Eur.
J. Org. Chem.
2010,
4017
28 Demir AS.
Subasi NT.
Sahin E.
Tetrahedron: Asymmetry
2006,
17:
2625
29 SMART & SAINT,
Software Reference Manuals, Version 5.051 (Windows
NT Version )
Bruker Analytical X-ray Instruments
Inc.;
Madison:
1998.
30 Sheldrick GM.
SADABS, Program for Empirical Absorption Correction
University
of Göttingen;
Germany:
1996.
31 Altomare A.
Burla MC.
Camalli M.
Cascarano GL.
Giacovazzo C.
Guagliardi A.
Moliterni AGG.
Polidori G.
Spagna R.
J. Appl. Crystallogr.
1999,
32:
115
32 Sheldrick GM.
SHELXTLplus, Version 5.1 (Windows NT Version):
Structure Determination Package
Bruker Analytical
X-ray Instruments Inc.;
Madison:
1998.
