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Isoquinolines and Naphthalenes from -Polyketones Model Reactions for an Extraordinary Alkaloid Biosynthesis.

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+ H2
c.u / T H k
R = H, alkyl
Isoquinolines and Naphthalenes from p-Polyketones:
Model Reactions for an Extraordinary Alkaloid
By Gerhard Bringrnann*
The catalysts for the preparation of MgH2 (Mg-anthracene-CrCI, or -TiC1,)[9’are also suitable for the addition of
MgH, to ethylene or propene to give, respectively, diethylor dipropylmagnesium.
Zirconium tetrahalides and magnesium hydride (MgH,ZrX,; X = C1, Br, I) are considerably more active catalysts
for the addition step (4). By this means MgH2 can also be
added smoothly to higher I-alkenes. The following modification to the procedure has proved useful: Mg is initially
hydrogenated to the highly reactive MgHz in the presence
of the chromium catalyst at room temperature; addition of
1 mol% zirconium tetrahalide at 70-90°C in the presence
of 1 -alkenes leads to dialkylmagnesium compounds. The
“hydromagnesation” of higher boiling I-alkenes (b.p.
>70°C) can be carried out at atmospheric pressure by refluxing (Fig. 1)[12]. The best results are obtained using catalysts containing ZrX,, particularly Z1-14 (80-85% conversion after 1-2 h).
Until now it has been assumed that in nature isoquinoline alkaloids are formed, without exception, via the Mannich reaction of phenylethylamines with aldehydes or a0x0 acids. Because of its unusual substitution pattern, ancistrocladeine 1, obtained from the spasmolytically active
3HJ , -q0H
tropical liana“] Ancistrocladus heyneanus, appears to necessitate a different biosynthetic route. We report the synthetic approach to both molecular moieties (9 and 11) of 1
by successive cyclization of b-polyketones, which can be
viewed as a model reaction for the formation of a n isoquinoline alkaloid from acetate units.
R’, R2 =
3 R’ = H, RZ = OCH,
OH f?
Fig. I. Course of the MgHl addition to I-octene with time using different catalysts in boiling media; MgHz prepared in siru at 25°C in presence
of the Cr catalyst. MgH?: I-octene:cat. = 100:230: I : [cat.]=O.O12mol/L:
ZrL: (-0-), ZrCI,: (-D-),
ZrBr4: (-V-),
TiCI4; ( - 0 - ) ,
-), without catalyst.
HfCI,: (-O-), (C5H,),TiCI2: (-
Reaction of the dialkylmagnesium compounds with
electrophiles indicates that the catalytic “hydromagnesation” of I-alkenes proceeds practically regiospecifically
(>99.7%) in the sense of M-C1 addition. Addition of
MgH2 to 1,l- and 1,2-dialkylalkenes is, in comparison,
very slow.
The dialkylmagnesium compounds can be isolated pure
and catalyst-free. They can be used in situ in syntheses instead of Grignard reagents. For example, tetrabutyltin
(83%) could be isolated from a solution containing catalyst, tin tetrachloride, and dibutylmagnesium, or nonanoic
acid (78%) could be obtained from dioctylmagnesium with
C 0 2 / H 2 0 . Trioctylphosphane (84%) and tetraoctyltin
(95%) could be prepared, respectively, from pure isolated
dioctylmagnesium and phosphorus trichloride and tin
tetrachloride, respectively.
Received: September I I , 1981 [Z 1 1 IE]
German version: Angew. Chem. 94 (1982) 206
The complete manuscript of this communication appears in:
Angew. Chem. SuppI. 1982, 457-460
191 B. Bogdanovii S. Liao, M. Schwickardi, P. Sikorsky, B. Spliethoff, Angew. Chem. 92 (1980) 845: Angew. Chem. Inr. Ed. Engl. 19 (1980) 818.
[I21 4.0 mL of the suspension was removed at specific intervals, centrifuged,
and the Mg content of the clear solution determined acidometrically.
0 Verlag Chemie GmbH. 6940 Weinheim, 1982
H O,
8 , R = CHzCHzOH
9 , R = H
10, R = H
11, R = CH,
Scheme I. a) 0,. - 78 “ C (see Procedure). b) S O 2 , Et20, 25 “C. c) Me2SOJ,
K2CO?,acetone, 25°C. d) Conc. NH,, CH,OH, 25°C. e) KH, tetrahydrofuran, 25°C. f) KOH, CH,OH, 25°C. g) Me2S04, 10% aqueous KOH, CHIOH,
12 h reflux.
The synthesis of 9 and 11 is shown in Scheme 1. The ketalized pentaketone 4 [‘H-NMR (CDCl3): 6 = 5.42, s, olefin. C H of the enol form] is liberated as an oil from 2 by
mild ozonolysis in the absence of oxygen. This method of
who did not succeed
obtaining 4 stems from Birch el
in cyclizing 4 to afford phenols. We found that the ring
closure of 4 to 6 (m.p.= 139°C) can, nevertheless, be realized smoothly by filtering the ozonolysis product through a
[*] Dr. G. Bringmann
Organisch-chemisches lnstitut der Universitst
Orleans-Ring 23, D-4400 Miinster (Germany)
[**I This work was supported by the Deutsche Forschungsgemeinschaft.
0570-0833/82/0303-0200 $ 02.50/0
Angew. Chem. Int. Ed. Engl. 21 (1982) No. 3
short silica gel column. After methylation of 6, the second
ring closure proceeds smoothly to give the isoquinoline 8
(m.p.= 187"C), from which 9 (m.p.=229-231 "C) can be
obtained by selective cleavage of the hydroxyethyl group.
11, which also occurs in the free state in tropical eboniesL3],is synthesized from 3, which like 2 can readily be
prepared from 5,6-dimethyl-2-indanone.Mild ozonolysis
affords 5 , which immediately cyclizes to 7 (m. p. = 125 "C)
on silica gel. The latter compound condenses regiospecifically to the oxidation-sensitive 10, which also occurs in
the anthelmintically active berries of Diospyros rn011is[~~
(m.p. = 141 "C). Methylation leads to the naphthalene derivative 11 (m.p.=87"C).
This synthesis of both molecular moieties of 1, which is
orientated towards biogenetic considerations, also opens
up an effective route to otherwise difficultly accessible 8hydroxyisoquinolines.
The X-ray structure determination of 4 (space group:
P2,/c, a = 1633.9(3), b = 1953.5(4), c=2172.9(4) pm,
= 106.56(3)", Z = 4 , four-circle diffractometer data,
R 1=0.060)
[ F ~ & ( S C H ~ C ~ H S ions
) ~ ] ~in- the crystal (Fig. 1).
In the anion of 4 the six Fe atoms have an approximately planar arrangement (mean deviation from the best
plane: 5.8 pm). The Fe, core consists of two nearly equilateral coplanar triangles of Fe atoms ( < Fe-Fe-Fe:
59.28(5) to 60.77(5)", d(Fe-Fe): 269.4(2) to 273.5(2) pm)
separated from each other by short Fe-Fe
(280.4(2) and 274.8(2) pm) to form a square central Fe,
A further novel structural principle is the quadruply
bridging S1 atom which is located below the center of the
Fe4 square and defines the vertex of an approximately regular square-pyramidal [(p4-S)Fe4J unit (mean Fe-S distance: 233.3 pm). In addition, the anion contains inorganic
S atoms acting as triply- and doubly-bridging substituents.
The arrangement leads to a distorted tetrahedral coordination of the four central Fe atoms by inorganic S ligands
( Q S-Fe-S:
100.32(9) to 124.95(9)"), whereas Fel and
Fe6 are additionally bonded to one S atom of a benzylthiolate ligand (mean Fe-S distance: 228.4 pm, < S-Fe-S:
101.49(9) to 116.36(9)").
The mean oxidation state of Fe is formally +2.67. Due
to the short Fe-Fe distances, which indicate direct metalmetal interactions, assignment of discrete oxidation levels
to the central and outer Fe atoms would result in an unsatisfactory description of the true electronic situation. According to the Mossbauer spectrum the two outer Fe atoms
are presumably in a higher oxidation state.
The cyclic voltammogram of 4 (0.10 M tetraethylammonium perchlorate in acetonitrile) shows a reduction peak at
- 0.6 I V and oxidation peaks at - 0.36 and 0.40 V (relative to Ag/AgCl, scan rate 100 mV/s).
The electronic spectrum of a solution of 4 in acetonitrile
shows two peaks at 296 and 329 nm of approximately
equal intensities, as well as a shoulder at cu. 425 nrn'"'.
4 could serve as a starting point for the synthesis of a
new class of tetrahedrally coordinated Fe-S cluster compounds. The closed parent compound of this class consists
of a completely bonded metal cube defined by eight Fe
atoms, having six p4-S ligands centered above each of its
planes. The tetrahedral coordination of each Fe atom is
achieved by organo-S ligands.
The central [Fe4S9]unit of 4 can be regarded as a fragment of this [Fe,S,,] cage structure.
The [Fe7MOS6] unit, which can formally be derived from
the [FesS,,] cage by substituting one Fe atom of the [Fe&]
core is of particular interest as a model for the active site
of the FeMo-protein of nitrogenase and of the isolated
FeMo cofactor[61.
6:2 (2.82 g, 13.7 mmol) in 1 L of ethanol at - 78 " C was
treated with oxygen-free ozone. After the apparatus had
been flushed with argon, the mixture was hydrogenated
immediately at room temperature and atmospheric pressure in the presence of W/C. The crude 4 was placed on a
short column (silica gel Merck, particle size 0.05-0.2 mm).
After 3 h this was eluted with Et20/MeOH (95 :5). Crystallization from ether yielded 6 (1.65 g, 48%) as small colorless needles.
Received: August 13, 1981 [Z 12 IE]
German version: Angew. Chem. 94 (1982) 205
I l l Review: T. R. Govindachari, P. C . Parthasarathy, He~erocycles 7 (1977)
I21 A. J. Birch, P. Fitton, D. C. C. Smith, D. E. Steere, A. R. Stelfox, J. Chem.
Sot. 1963. 2209.
131 G . S . Sidhu, A. V. B. Sankaram, S. Mahmood Ali, Indian J. Chem. 6
(1968) 681.
141 S . Mongkolsuk, C. Sdarwonvivat, J. Chem. SOC.1965, 1533.
IFe6s,(scH&H&]4- :
A Hexanuclear Iron-Sulfur Cluster Anion
Containing the Square-Pyramidal I(p4-S)Fe41Unit**
By Gerald Henkel, Henry Strasdeit, and Bernt Krebs*
Low molecular weight iron-sulfur complexes with tetrahedral coordination of iron are important as model compounds for the active Fe-S centers of non-heme iron proteins"].
We report the synthesis, properties, and structure of the
novel hexanuclear cluster anion [Fe6S9(SCH2C6H,)2]4-,
obtained by reaction of [Fe(SCH2C6H5)3],with Na2S2and
isolated as
[(CZHs)4Nl,[Fe,S9(SCHZC6HS)zl. H 2 0 4
by precipitation with [(C2Hs)4N]C1.
The Mossbauer spectrum of 4 at 77 K (source: Rh/Co,
zero external magnetic field) exhibits two quadrupole
doublets. Accordingly, 4 contains two types of non-equivalent Fe atoms (Fe": 6=0.30, AEq=0.69 mm/s, Feb:
6=0.1 I , AEq=0.55 mm/s, isomer shifts relative to metallic
1'1 Prof. Dr. B. Krebs, Dr. G. Henkel, Dip1.-Chem. H. Strasdeit
Anorganisch-chemisches Institut der Universitat
Corrensstrasse 36, D-4400 Miinster (Germany)
This work was supported by the Deutsche Forschungsgemeinschaft and
the Fonds der Chemischen Industrie.
Angew. Chem. In[. Ed. Engl. 21 (1982) No. 3
Fig. 1. Structure of [Fe6So(SCH2C6H5)Z]4in crystals of 4; vibration ellipsoids of the Fe and S atoms with 50% probability.
0 Verlag Chemie GmbH, 6940 Weinheim. 1982
0570-0833/82/0303-0201 $ 02.50/0
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mode, extraordinary, naphthalene, isoquinolines, reaction, alkaloid, polyketone, biosynthesis
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