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Iron-Mediated Diastereoselective Spiroannelation to the Spiro[1 2 3 4-tetrahydroquinoline-4 1-cyclohexane] System and a Novel Rearrangement to 2 3-Dihydroindole Derivatives.

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[9] K. Moock, K. Seppelt, 2. Anorg. A&. Chem. 561 (1988) 132.
[lo] G. M. Anderson, J. Iqbal, D. W. A. Sharp, J. M. Winfield, J. H. Cameron,
A. G. McLeod, J. Fluorine Chem. 24 (1984) 303; G. A. Heath, K. H.
Moock, D. W. A. Sharp, L. J. Yellowless, unpublished.
[ l l ] J. M. Winfield, .
I
Fluorine Chem. 25 (1984) 91.
[I21 H. Ahrens, J. Inorg. Nucl. Chem. 2 (1956) 290; Geochrm. Cosmorhim. Acta
2 (1952) 155; ibrd. 3 (1953) 1.
[13] B. Jaselskis, Science (Washmgron D C ) 146 (1964) 263.
[14] An accurate estimation of the redox potential Cse/Cs3@was not possible.
True, the ionization potentials and the salvation energy of&@ are known,
but Cs3' is presumably not spherical-shaped but disk-shaped with a radius
ratio of 1 :2. The solvation energy of a charged particle depends approximately on r - '. All desired redox potentials can be predicted when 60 5 T I .
ri 5 120 pm.
[15] S . H. Strauss, K . D. Abney, 0. P. Anderson, Inorg. Chem. 25 (1986) 2806;
F. Sladky, H. Kropshofer, 0. Leitzke, P. Peiger, J Inorg. Nucl. Chem.
Herbert H . Hyman Mem. Vol. 1976, 69.
The iron-complex 2 is readily accessible in four steps from
p-methoxyphenylacetic acid l.[61
Compound 2 is converted
by 0-functionalization (3) and hydride abstraction into the
complex salts 4. The spiroannelation with p-anisidine 5 leads
diastereoselectively to the spiro[l,2,3,4-tetrahydroquinoline4,1'-cyclohexaneJ derivative 6 a (Schema 1 ) . Cyclization to
OH
OH
1
2
OCH,
OCH,
I\,FelCOl,
Iron-Mediated Diastereoselective Spiroannelation
to the Spiro(l,2,3,4-tetrahydroquinoline-4,l'-cyclohexane] System and a Novel Rearrangement
to 2,3-Dihydroindole Derivatives **
By Hans-Joachim Knolker,* Rolaod Boese,
and Konrad Hartmann
The use of iron-diene complexes in the synthesis of heterocycles recently opened up a versatile entry to carbazole
derivatives."] We have now extended this concept to the
synthesis of other nitrogen-heterocycles. Cyclization, instead
of being carried out oxidatively, as hitherto, was now
achieved via nucleophilic substitution. This permitted closure of the C-C bond and the C-N bond in a one-pot reaction and thus the stereoselective synthesis of spirocycles.
The discorhabdins ['I and prianosins [31 recently isolated
from marine sources are distinguished by their high cytotoxic and antimicrobial activity. The discorhabdin D
described only recently[41also exhibits a strong antitumor
activity in vivo. A common feature of these compounds
'-cyclohexane] subis a spiro[ 1,2,3,4-tetrahydroquinoline-4,1
structure. We report here on an iron-mediated diastereoselective entry to this ring system.
The addition of nucleophiles to tricarbonyl(q5-l-aIkyl4-methoxycyclohexadienylium)iron cations enables the stereocontrolled synthesis of quaternary centers.I5' We have recently been able to show that iron-complexed cyclohexadienylium cations are very effective as mild electrophiles for
the reaction with highly substituted electron-rich and thus
oxidation-sensitive arylamines.[ll With the iron-complex
salts 4 we have now succeeded for the first time in using this
electrophilic substitution of aromatic systems for the
diastereoselective generation of quaternary carbon atoms.
Combination of this reaction with the subsequent in situ
nucleophilic substitution of the leaving group in the side
chain of 4 affords a new method for spiroannelation.
[*] Dr. H.-J. Knolker, DipLChem. K. Hartmann
[**I
Institut fur Organische Chemie der Universitat
Schneiderberg 1 B, D-3000 Hannover 1 (FRG)
Dr. R. Boese
Institut fur Anorganische Chemie der Universit5t-Gesamthochschule
Universitatsstrasse 5-7, D-4300 Essen 1 (FRG)
Transition-metal Diene Complexes in Organic Synthesis, Part 3. This work
was supported by the Volkswagen foundation and the Deutsche Forschungsgemeinschaft. We thank Dr. K Wruy, Gesellschaft fur Biotechnologische Forschung, Braunschweig-Stockheim fur the 13C and 2D-NMR
spectra and Dr. K.-H. Geiss, BASF AG, Ludwigshafen, for a supply of
pentacarbony1iron.-Part 2: [l b].
1618
0 VCH
krlagsgesellschafi mbH. 0-6940 Weinheim, 1989
4
6a
Scheme 1. DIBAH
= diisobutylaluminum
hydride, B = base
6a still takes place even with the methoxy derivative 4a. A
systematic optimization of the spiroannelation could be
achieved by varying the leaving group in the side-chain
(Table 1). In some cases (4a,c,d), owing to the stability of
Table 1. Variation of the leaving group R in the complex salt 4, and results of
the spirocyclization to 6a.
R
3, Yield
[%I
4, Yield [%]
~
CH3
CH,SO,
4-CH3(C6H,)S02
CH,CO
CF,CO
4-N02(C6H4)C0
~
4a, 69 (PF;) (61
4b, 77
4c, 27 (PF;)
4d, 74 (PF;) [6]
4e, 80
4f, 92
3a, 96 [6]
3b, 94
3c, 87
3d, 98 [6]
3e, 80
3f, 98
6a, Yield [%]
~~~~
20
53
54
68
53
80
the salt, the hexafluorophosphate had to be used. The route
via the p-nitrobenzoate derivatives 3f and 4f proved to be
the best over a11 three steps (2 3 --t 4 -+ 6 4 .
The structure of 6a follows from spectroscopic data ('H-,
I3C- and COSY-NMR spectra) and an X-ray structure analysis (Fig. l).['' The latter revealed that the aryl ring is anti to
the Fe(CO), group referred to the cyclohexadiene ring plane.
This can be explained by the stereodirecting effect of the
Fe(CO), group (anti selectivity). With the amines 5b-5e the
same diastereoselectivity is observed in the spiroannelation
as with 5a (Scheme 2, Table 2). The stereochemistry was established by comparison of the 'H- and 13C-NMR spectra of
6b-6e with those of 6a. In addition, the synthesis of 6d
clearly demonstrates that the reaction with 3,4-disubstituted
anilines is regiospecific.
0570-0833/89j1212-1678$02.50/0
--f
Angew. Chem. Int. Ed. Engl. 28 (1989) No. 12
free ligand 7 a (nonacarbonyldiiron, THF, 67 "C) leads exclusively to the anti-configurated complex 6 a again.
During the demetalation of 6a a novel rearrangement occurs with ring contraction and aromatization to the dihydroindole derivative 8 (Scheme 3 , Table 2). This reaction
P
7
I
CH3
3
6e
Fig. 1. Structure of 6a in the crystal [7]. Selected bond lengths [A]: Fe-Cll
2.096(3), Fe-C12 2.054(4), Fe-C13 2.099(3), Fe-C14 2.116(4), C4-Cll 1.529(5),
C I l - C I 2 1.432(6), C12-Cl3 1.412(6), C13-CI4 1.437(6), C14-Cl5 1.516(6), C4C15 1.561(6).
OCH,
L
J
"3
I
n
FelCOl,
BF,O
CH&N
+
Rz+
Scheme 3
824:
R'
/NH
5
OCH,
proceeds via the free ligand 7 e which is oxidized to 8 during
chromatography on silica gel. The structure of 8 was derived
from spectroscopic data ('H-, I3C-, COLOC- and inverse
'H-' 3C-correlated NMR spectra). The driving force behind
this rearrangement is undoubtedly aromatization of the cyclohexadiene ring. The influence of the substitution pattern
of the arylamine component and the mechanism of this rearrangement are currently under investigation.
R'
R'
6
Received: June 30, 1989 [Z 3418 IEI
German version: Angew. Chem. 101 (1989) 1745
7
Scheme 2.
The complexes 6a-6d can be demetalated with trimethylamine N-oxide[*] to give 7 (Scheme 2, Table 2). The yields of
this reaction are strongly dependent on the reaction condi-
CAS Registry numbers:
2, 75969-38-9; 3a, 75969-40-3; 3b, 123774-94-7; 3c. 123774-95-8; 3d, 7596939-0; 3e, 123774-96-9; 3f, 123774-97-0; 4a, 75978-76-6; 4b, 123751-42-8; 4c,
123751-44-0; 4d, 75969-42-5; 4e, 123751-46-2; 4f, 123774-99-2; Sa. 104-94.9;
Sb, 62-53-3; Sc, 106-49-0; Sd, 95-64-7; Se, 100-61-8; 6a, 123775-00-8; 6b,
123775-01-9; 6c. 123775-02-0; 6d. 123775-03-1; 6e. 123775-04-2; 7a, 12375136-0; 7b, 123751-37-1; 7 c , 123751-38-2; 7 4 123751-39-3; 8, 123751-40-6.
Table 2. Yields of the spirocycles 6 and their demetalation to 7/8.
5
R'
R2
R3
6, Yield
Sa
Sb
H
H
H
H
H
H
CH,
H
OCH,
6a, 80
6b, 55
6c, 58
6d, 53
6e, 48
sc
Sd
H
Se
CH,
H
CH,
CH,
H
[%I
7/8, Yield [%]
7a, 66
7b, 47
7c, 48
7d, 58
8, 68
tions (solvent, temperature, reaction time). Nevertheless, an
optimization of the yields for each individual case was not
carried out, since the metal complex 6 and its free ligand 7
each have the same R, value. Thus all demetalations were
performed under a standard set of conditions (10equiv.
Me,NO, Me,CO, 56"C, 2-5 h).
Acid hydrolysis of the 2-methoxydiene moiety in 7a to the
corresponding enone affords a promising substrate for
stereoselective Michael additions. Recomplexation of the
Angew. Chem. lnt. Ed. Engl. 28 (i989)No. 12
0 VCH
[l] a) H.-J. Knolker, M. Bauermeister, D. BIdser, R. Boese, J.-B. Pdnnek,
Angew. Chem. 101 (1989) 225; Angew. Chem. Inl. Ed. Engl. 28(1989) 223;
b) H.-J. Knolker, M. Bauermeister, J. Chem. Soc. Chem. Commun. 19x9.
1468.
121 N. B. Perry, J. W. Blunt, M. H. G. Munro, Tetrahedron 44 (1988) 1727.
[3] J.-F. Cheng, Y. Ohizumi, M. R. WHlchli, H. Nakamura, Y. Hirata, T. Sasaki,
J. Kobayashi, J. Org. Chem. 53 (1988) 4621.
[4] N. B. Perry, J. W. Blunt, M. H. G. Munro, T. Higa, R. Sakai, J. Org. Chem.
53 (1988) 4127.
[S] A. J. Pearson. Acc. Chem. Res. 13 (1980) 463; A. J. Pearson, in G. Wilkinson, E G. A. Stone, E. W. Abel (Eds): Comprehensive Orgunomerullic
Chemisrry, Vol. 8, Pergamon, Oxford 1982. Chap. 58, p. 939.
[6] A. J. Pearson, M. Chandler, 1 Chem. Sac. Perkin Trans. 1 1980, 2238.
[7] 6a: orthorhombic. Pna2,. n = 14.416(1), b = 12.530(1), c = 9.852(1) A,
a = p = y = 90", V = 1779.5(2) A'. Z = 4. ecalcd= 1.466gcm-'. p =
8.7 cm-'; Mo,, radiation (graphite monochromator); 3" S 2 0 5 50"; 3156
unique reflections, 2999 with Fo 2 4 a ( Q , R = 0.043, R, = 0.056. Further
details of the crystal structure investigation are available on request from
the Fachinformationszentrum Karlsruhe, Gesellschaft fur wissenschaftlichtechnische Information mbH, D-7514 Eggenstein-Leopoldshafen 2 (FRG).
on quoting the depository number CSD-54049, the names of fhe authors,
and the journal citation.
[8] Y. Shvo, E. Hazum, J. Chem. Soc. Chem. Commun. 1974, 336.
Verlagsgesellschaft m b H , 0-6940 Weinheim, 1989
0570-0S33/89/12t2-1679 3 02.50/0
1679
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diastereoselective, rearrangements, iron, cyclohexane, spiro, tetrahydroquinolines, dihydroindole, system, novem, derivatives, mediated, spiroannelation
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