вход по аккаунту


Asymmetric Elimination with High Induction Synthesis of 1-Alkenylsulfoximides with Axial and Central Chirality.

код для вставкиСкачать
Fig. 3. Reaction mechanism of autocatalytic template production. Open arrows indicate reversible reactions, the closed arrow represents an irreversible
o m e n should be in equilibrium with respect to complex
fFrmation. Then, the equilibrium concentration of
A : B :T can be expressed in terms of the equilibrium concentration of T :T. With
: B :TI
K ’ = ___ and
the rate o,f template-directed condensation, which is first
order in A : B :T, is given by
d [ T : T ] - k * [ A : B : T ] = k * K , KFI/2[A][B][T :TI’/’
Accordingly, the reaction order for T :T formation in
terms of T :T is expected to be 1/2. Since the equilibrium
concentration, [T :Tj, is supposed to be only slightly different from half of the total template concentration c(T),
the equation gives an approximate solution for k, in the
autocatalytic term of the empirical rate law.
The rationale of this work is to demonstrate that, in fact,
self-replication occurs without the help of any enzyme[”I
in a chemical model system composed of simple oligonucleotides. Although the system chosen is not very efficient
in terms of its autocatalytic rate, autocatalysis is clearly
evident. Further experiments must show whether autocatalysis also occurs when using other oligonucleotides, and
whether autocatalysis can be enhanced’employing appropriate “environmental conditions” and “energy sources.”
If so, it can be expected that, under certain conditions,
some interesting self-organization phenomena might show
up, similar to natural selection processes in biological systems.“*‘
Received: June 20, 1986;
revised: July 21, 1986 [Z 1825 IE]
German version: Angew. Chem. 98 (1986) 932
[ I ] R. Naylor, P. T. Gilham, Biochemrstry 5 (1966) 2723.
[2] L. E. Orgel, R. Lohrmann, Acc. Chem. Res. 7 (1974) 368; R. Lohrmann,
L. E. Orgel, J . Mol. Biol. 142 (1980) 5 5 5 ; T. Inoue, L. E. Orgel, Science
219 (1983) 859; C. B. Chen, T. Inoue, L. E. Orgel, J. Mol. Biol. 181
(1985) 271.
131 T. Inoue, G. F. Joyce, K. Grzeskowiak, L. E. Orgel, J. M. Brown, C. B.
Reese, J . Mol. Biol. 178 (1984) 669.
[4] N. H. Horowitz, S. L. Miller, Fortschr. Chem. Org. Naturst. 20 (1962)
423; S L. Miller, L. E. Orgel: The Origins of Life on the Earth, Prentice
Hall, Englewood Cliffs, NJ, USA 1974.
[5l M. Eigen, P. Schuster: The Hypercycle, Springer, Berlin 1979.
Angew. Chem. Int. Ed. Engl. 25 (1986) No. 10
IS] H. Kuhn, J. Wasser, Angew. Chem. 93 (1981) 495; Angew. Chem. Int. Ed.
Engl. 20 (198 I)500.
[7] W. A. Denny, W. Leupin, D. R. Kearns, Helu. Chim. Acta 65 (1982) 2372,
and references cited therein.
(81 Triethylammonium salts: ‘H-NMR (360 MHz, DzO, 0.1 M NaCI, 0.1 pvl
NaD2P04/Na2DP04,pD=7.5): A : 6=8.04(s; 8-H, Gua), 7.65, 7.59 (d:
6-H, Cyt), 6.24, 6.16, 6.06 (t; 1‘-H), 5.96, 5.91 (d; 5-H, Cyt), 3.36 (s; 5‘OCH3); B : 6=8.00, 7.81 (s: 8-H, Gua), 7.46 (d; 6-H, Cyt), 7.31, 6.98,
7.18, 7.22 (ABCD: o-chlorophenyl), 6.17, 6.01, 5.87 (t; I’-H), 5.90 (d;
5-H, Cyt); T : 6=7.98, 7.86, 7.86 (s; 8-H, Gua), 7.67, 7 58, 7.47 (d: 6-H,
Cyt), 7.10-7.42 (m; o-chlorophenyl), 3.39 (s; 5’-OCH,).
[9] Z. A. Shabarova, N. C. Dolinnaya, V. L. Drutsa, N. P. Melinkova, A. A.
Purmal, Nucleic Acid Res. 9 (1981) 5747; Z. A. Shabarova, M. G. Ivanovskaya, M. G. Isaguliants, FEES Lett. 154 (1983) 288.
[lo] N G. Dolinnaya, E. S. Gromova, Usp. Khim. 52 (1983) 138; S. M.
Freier, D. D. Albergo, D. H. Turner, Biopolymers 22 (1983) 1107.
[II] Enzymatic replication of RNA in vitro has been studied extensively using QP-RNA/Qp-replicase: see C. K. Biebricher, Euol. Biol. 16 (1983)
1121 According to Eigen and Schusrer. systems composed of self-replicating
molecules that compete for their constituents under the constraint of
constant organization should show Darwinian selection behavior if the
reaction order of autocatalysis is larger than zero and smaller than or
equal to one I S ] , p. 12.
Asymmetric Elimination with High Induction :
Synthesis of 1-Alkenylsulfoximides
with Axial and Central Chirality**
By Irene Erdelrneier, Hans-Joachim Gais,* and
Hans J . Lindner
Asymmetric eliminations with high induction to give chiral alkenes are rarely observed;“’ the few known examples
are characterized by removal of a chiral group with loss of
chirality”“.’] and/or transfer of chirality.“” We report here
the synthesis of the axially chiral alkenylsulfoximides
Sa, b and 17 from the /3-hydroxysulfoximides 3a, 617,and
15a, respectively, which involves an asymmetric elimination that takes place with high diastereotopic differentiation and without loss of chirality. The stereoselective carbonylolefination of the ketone 9 to give either the (Q- or
the (0-alkenylsulfoximide 12 or 13, respectively, exemplifies the application of this reaction. Asymmetric carbonylolefinations with high and moderate selectivity to give
axially chirai alkenes have been achieved previously by
Homer-Emmons”“’ and Wittig reactions,l*’I respectively.
Selective ex0 addition [ - 78 “C, tetrahydrofuran (THF)]
of the lithiosulfoximide 2L3.41
to the ketone lI5]gave the
/3-hydroxysulfoximide 3a[6s1in 96% yield and with 298%
diastereoselectivity (ds). The surprisingly smooth silylation
(-7SoC-25”C, THF) of the lithium alkoxide 3b with
Me,SiCI afforded the /3-siloxysulfoximide 3c in > 95Yo
yield. When this compound was treated with n-butyllithium (nBuLi) at -78°C (molar ratio 1 : 1) in THF, asymmetric elimination of LiOSiMe3 took place with high induction to give the (S.aR)-alkenylsulfoximide 5a,’‘’.’l
which could be isolated in 91% yield and with 298% ds.
From 1 and rac-2, rac-5a (90%) was also obtained with
[+I, DipLlng. I. Erdelrneier
Prof. Dr. H. J. Lindner
Institut fur Organische Chemie und Biochemie
der Technischen Hochschule
Petersenstrasse 22, D-6100 Darmstadt (FRG)
[*] Prof. Dr. H.-J. Gais
Present address:
lnstitut fur Organische Chemie und Biochemie der Universitat
Albertstrasse 21, D-7800 Freiburg (FRG)
This work was supported by the Fonds der Chemischen Industrie and
by Schering AG, Berlin. I . E. thanks the Stiftung Stipendien-Fonds des
Verbandes der Chernischen Industrie for a fellowship. We thank Prof.
Dr. H . Gdnther. Siegen, for NOE data and Dr. S. Braun for the 2 D ‘ H NMR spectra.
0 VCH Verlagsgesellschaji mbH, 0-6940 Weinheim. 1986
0570-0833/86/1010-0935 $ 02.50/0
3a: R = H
3b: R = Li
3 d : R = Me
R = SiMe3
6: R' = Me, R2 = H
8a: R = H ( t 50)
7: R' = H, R, = Me
8 b : R = Me(
+ 5b)
2 98% ds.''' Interestingly, the extent and direction of the
asymmetric induction observed in the elimination reaction
of 3a did not change when the dilithium compound 4a,
obtained by metalation of 3a (2 nBuLi, -3O"C, THF), was
allowed to react with Me3SiC1 ( - 70°C); 5a was isolated
in 69% yield and with 2 9 8 % ds. This was also true for the
diastereomeric methyl derivatives 6L6cJ
and 7,[6d' which
were obtained in 89% yield in a ratio of 3 : 1 by methylation
(MeI, O'C, THF, HMPA) of 4a. The mixture of the two
stereoisomers underwent metalation (2 nBuLi, O'C, THF)
to give the dilithium compound 4b and subsequent reaction with Me,SiCI ( - 30°C) to give the alkenylsulfoximide
5bL6']in 73% yield and with 298% ds. In contrast, we obtained mixtures of the diastereomers 5a/8a (70%, 4 : 1) and
5b/8b (75%, 1 : 1) when 4a and 4b, respectively, underwent
titanation ( - 3 0 T , THF) with C12Ti(OiPr)2.
This asymmetric carbonylolefination also allowed us to
selectively synthesize the (9and (E)-alkenylsulfoximides
12 and 13, respectively, which are potential precursors for
the selective synthesis of the (5E) isomers of carbaprostacyclins,'g' from the ketone 9.r'01Selective ex0 addition
(-78"C, THF) of 2 to 9 to give the b-hydroxysulfoximide
10afh'l(93%, 298% ds), silylation (1 nBuLi, -78"C, T H F ;
Me,SiCI, - 70°C-25 "C) to give the b-siloxysulfoximide
l o b , and, finally, elimination (1 nBuLi, -78"C, THF) afforded the (2)-alkenylsulfoximide l2C6g.'' in 96% yield and
was added
with 2 98% ds. On the other hand, when er1t-2~~'
to 9 to give lla[6hJ
(93%, 298% ds) and this compound
was then silylated to give l l b and finally treated with
0 VCH Verlagsgesell.~chafrmhH. 0-6940 Weinheim, 1986
nBuLi ( - 7 8 T , THF), the (E)-alkenylsulfoximide 13[6'J
was obtained, as expected, in 91% yield and likewise with
2 98% ds. Thus, the extent and direction of the asymmetric
induction in the elimination reactions of 10b and l l b are
independent of the chirality center in the 4-position and
only determined by the choice of 2 or ent-2 (reagent control). Unequivocal confirmation of the ( Z ) configuration of
12 (S(O)(NMe)Ph and R 2 0 C H z groups in syn positions)
was achieved by NOE experiments and that of the ( E ) configuration of 13 (anti arrangement of the groups) on the
basis of 2 D 'H-NMR spectra; in each case, the determination of configuration was based on the low-field shift of
the resonance of HI' of the methylene group in the syn position, which is caused by the anisotropy effect of the sulfoximide functionality. Based on these results, the absolute
configuration of the alkenylsulfoximides 5a and 5b was
M e 3 C G 0
150: R = H
16a: R = H
15b: R = SIMe,
16b: R
0570-0833/86/1010-0936 $ 02.50/0
Angew. Chem. Int. Ed. Engl. 25 (1986) No. 10
Interesting differences in selectivity were found in the
elimination reactions of the diastereomeric 0-siloxysulfoximines 15b and 16b, which were obtained by addition[""'
of 2 to the ketone 14 to give the diastereomeric 0-hydroxysulfoximines 15a and 16a" I h l followed by silylation.
Whereas the elimination reaction of the trans diastereomer
15b with nBuLi led to the (S,aS)-alkenylsulfoximide17
(93%)'"' with 2 9 8 % ds, the elimination reaction of the cis
diastereomer 16b gave a mixture (94%) of the chromatographically separable (S.aR)- and (S,aS)-alkenylsulfoximand 17 in a ratio of 2.5 : I.
ides 18'"kJ
The absolute configuration of 17 was determined by Xray structure analysis,"*' in combination with the known
( S ) configuration of 2,'i31to be ( S , a S ) (Fig. 1).
Fig I C r j d structure of 17 . H I O 1121. Selected bond lengths [A] and bond
angles ['I: SI-C2 1.741(7), SI-05 1.427(5), SI-N3 1.534(5), SI-Cl6 1.804(5),
C2-C6 1.353(8), C4-N3 1.504(8); C2-C6-CI 1 126.6(6), C2-C6-C7 I19.4(7);
N3-SI-C'2-C6 - 174(2), SI-C2-C6-C7 173(2), SI-C2-C6-Cll O(2).
We ascribe the similar directions and extents of asymmetric induction in the elimination reactions of 3, 4, 10,
and 15-using 3c and 4a as examples and taking into
consideration the crystal structure of 2 and the configurational stability of lithioalkylsulfoximides at the a-C
atornl"-to the following factors:
1. Initial metalation of 3c to give the lithiosulfoximide
19 (Scheme I), which is also presumably formed upon silyIation of 4a via C/O silyl m i g r a t i ~ n " ~following
2. The establishment of a rapid equilibrium between the
diastereomers 19A and 19B, even at low temperatures, on
account of the low energy barrier for the configurational
change at the anionic C atom in lithioalkyIsulf~ximides.[~~
Received: April 28, 1986:
revised: July 10, 1986 12 1749 IE]
German version: Anqew. Cbem. 98 (1986) 912
CAS Registry numbers:
1, 51716-62-2; 2, 34261-66-0; (en/)-2, 104264-21-3; (ruc)-2, 80374-26-1; 3a,
104264-16.6; 3h, 104172-91-0; 3c, 104172-92-1; 3d, 104173-07-1; 4a, 10417294-3; 4b, 104172-96-5; 5a, 104172-93-2; (rur)-5a, 104264-17-7; 5b, 104172-976 ; 6, 104172-95-4; 7, 104264-18-8; 8a, 104264-19-9; 8b, 104264-20-2; 9,
I041 72-98-7; IOa, I041 72-99-8; lob, 104196-36-3; I la, I041 73-0 1-5: 1 lh,
104173-02-6; 12, 104173-00-4; 13, 104173-03-7; 14,98-53-3; 15a, 104264-22-4;
15b, 104173-04-8: 16a, 104264-23-5: 16b, 104173-05-9; 17, 104173-06-0:
17. H 2 0 , 104264-25-7; 18, 104264-24-6.
[I] a) G. Solladie, R. G. Zimmermann, R. Bartsch, H. M. Walborsky, Sym
rbesis 1985. 662, and ltterature cited therein; G . Solladie, Chem. Scr. 25
(1985) 149; b) S. I. Goldberg, M. S. Sahli, J . Org. Chem. 32 (1967) 2059:
c) A. C . Cope, C. F. Howell, A. Knowles, J . An]. Cbem. Soc. 84 (1962)
3190: d) see also S. I. Goldberg, Sel. Org. Transform. I (1970) 363. J. D.
Morrison, H. S . Mosher: Asymmetric Organrc Reactions, Prentice~Hall,
Englewood Cliffs, NJ (USA) 1976.
121 a ) S. Hanessian, D. Delorme, S. Beaudoin, Y. Leblanc, J . Am. Cbem.
Soc. 106 (1984) 5754; S . Hanessian, Chem. Scr 25 (1985) 5 , b) H. J.
Bestmann, J. Lienert, Angew. Chem. 81 (1969) 751; Angew. Chem. I n / .
Ed. Engl. 8 (1969) 763; H. J. Bestmann, personal communication, Oct
19, 1984.
[3] H . J . Gais, 1. Erdelmeier, H. J. Lindner, J. Vollhardt, Angew. Chem. Y R
(1986) 914; Angew. Chern. In/. Ed. Engl. 25 (1986) 938.
[4] The ( S ) - and (R)-S-methyl-S-phenylsulfoximides
required as starting
materials for the preparation of 2 and enr-2, respectively, are readily
available enantiomerically pure by resolution of the racemate with ( + ) and (-)-10-camphorsulfonic acid (Aldrich): C. R. Johnson, C . W.
Schroeck, J . Am. Chem. Soc. 95 (1973) 7418. The ee values of the sulfoximides were determined by 'H-NMR spectroscopy in the presence of
20 mol-% Eu(tfc)3 in CDC13 on the basis of the resonances of the methyl
groups ( A A 6 ~ 0 . 4ppm) and the o-H atoms of the phenyl groups.
151 R. Lok, J. K. Coward, J. Org. Cbem. 39 (1974) 2377.
[61 a) M.p.= 132-133"C, [a]:'
+36.4 (c= 1.6, acetone); b) [a];: -64.9
( c = 1.5, CH2C12); c) m.p. 142°C. [a];?f78.4 (c=0.8, acetone); d )
m.p.=IlO"C, [a]E +45.3 (c=O.5, acetone); e) [a]??-85.6 (c=0.5,
CHZCIZ):9 m.p.=65-66"C, [a]:? 13.0 (c=0.24, acetone); g) m.p.=4Y
S I T , [a]:' -79.0 (c=0.63, acetone); h) m.p.=67-68"C, Iu]:? -42.0
(c=I.O, acetone); i) [a];;' +59.0 (c=O.38, acetone); j) m.p.=72"C', [a];?
C46.0 (c=O.S, acetone); k) [a];: -99.0 (c=0.25, acetone). All new compounds gave correct elemental analyses and fitting spectra ( ' H - and "CNMR, MS).
171 Slow ally1 isomerization of 5a and 12 occurs for the substances both in
pure form and on silica.
IS] The silyl group is not crucial for the high ds value, as revealed by the
elimination reaction of fi-methoxysulfoximide 3d (73%), which was synthesized by methylation [Mel, hexamethylphosphoric triamide (HMPA),
THF, O T ] of 3h; after reaction of 3d with nBuLi (-78°C. THF), 5a
was isolated in 82% yield and with 298% ds.
[9] R. C. Nickolson, M. H. Town, H. Vorbriiggen, Med. Res. Reo. 5 (19x5)
[lo] 9 : [a]C -27.5 (c=O.SO, acetone); synthesis by silylation (91%) of 9,
R ' = H instead of SiMe2rBu. W. Skuballa, H. Vorbriiggen, Angew. Chem.
93 (1981) 1080: Angew. Chem. In/. Ed. Engl 20 (1981) 1046. Asymmetric
synthesis of 9 : H:J. Gais, W. Ball, unpublished.
[ I I] a) C. R. Johnson, J. R. Zeller, Terrubedron 40 (1984) 1225; b) (:. R. Johnson, C. W. Schroeck, J. R. Shanklin, J . Am. Chem Soc. 95 (1973) 7424.
1121 17. H20: orthorhombic, space group P2,2,2, u = 17.361(5), h= 17.244(5),
V = 1863
Z = 4 , pC,,,<',=1.107 g/cm'; 4 " 5 @ 5 6 2 . 5 "
( C U K ~I ~=, 154.18 pm, Weissenberg diffractometer), 1660 reflections,
Lorentz and polarization correction, positions of the H atoms calculated
for the ideal geometry, positions of the H atoms of the crystal water
determined by difference Fourier synthesis, anisotropic refinement of
the heavy atoms, R = 0.061 for 1533 unique structure factors IR z 3 oi.
The sulfoximide molecules are linked along the c axis by hydrogen
bonds to the crystal water. Surprisingly, hydrogen bonds are formed beon the
tween the oxygen of the crystal water-and N3 "3.. -012.888
one hand and 0 5 ' [ 0 5 ' . . '01 2.986 A], on the other. Further details of
the crystal structure investigation may be obtained from the Fachlnformationszentrurn Energie, Physik, Mathematik GmbH, D-75 14 Eggenstein-Leopoldshafen 2 (FRG), on quoting the depository number CSD52077, the names of the authors, and the journal citation.
1131 E. V. Johnson, C. R. Johnson, J. Am. Chem. Sor. 93 (1971) 5308, a n d
references cited therein.
[I41 K. Yamamoto, Y. Tomo, S. Suzuki, Tetrahedron Lerr. 21 (1980) 2861.
[IS] The "inverse Peterson olefination" used for the synthesis of 5 , 12, 13,
17, and 18 is particularly successful for readily enolizable carbonyl
compounds. H.d. Gais, 1. Erdelmeier, unpublished; see also 1. Erdelmeier, H.-J. Gais, Te/etrubedron Le!!. 26 (1985) 4359.
Scheme I K = S I M ~ ,X, = -OCH&'H:O-,
L = hgand
3 . The more rapid elimination of LiOSiMe3 in 19A than
in 19B, because the achievement of coplanarity of the p
orbital on the anionic C atom and the d o x y group in 19B
is presumably more strongly hindered by the interaction
between the phenyl and the pro-R methylene group than in
the case of 19A by the interaction between the 0 atom and
the pro-S methylene group.[I5]
A n y m . Chem. In/. Ed. Engl 25 (1986) No. 10
0 VCH VerlugsgesellscbaJi mbH. 0-6940 Weinheim, 1986
0570-0833/86/1010-0937 !$ 02.50/0
Без категории
Размер файла
336 Кб
elimination, axial, central, asymmetric, induction, synthesis, alkenylsulfoximides, high, chirality
Пожаловаться на содержимое документа