close

Вход

Забыли?

вход по аккаунту

?

Anthracyclinone Ring C Synthesis via Chelate Carbene Complexes.

код для вставкиСкачать
Experimental Procedure
The generation of I and their reactions with acid chlorides were performed
in one flask as typified in the following example (reaction 3 in Table I).
A mixture of Zn-Cu couple [I71 ( I 10 mg, 1.7 mmol) and 3-iodopropyl phenyl
ketone (356 mg, 1.3 mmol) in dry benzene (4 mL) and HMPA (0.5 mL) was
stirred at room temperature for 1 h and then at 40 "C for 1 h under nitrogen.
Then, solutions of [Pd(PPh,),] (46 mg, 0.04 mmol) in benzene ( I mL) and octanoyl chloride (163 mg, 1.0 mmol) in benzene (1 mL) were successively added at 40 "C and the mixture was stirred at the same temperature for 2 h.
After dilution with ether, successive washing with I N HCI and aqueous
N a H C 0 3 , and drying over MgSO,, followed by evaporation o f the solvents,
the residue was purified by column chromatography over silica gel (hexanein 80% yield.
ethyl acetate gradient) to provide I-phenyl-1,5-dodecanedione
Received: April 21, 1987;
revised: July 27, 1987 [ Z 2208 IE]
German version: Angew. Chem. 99 (1987) 1193.
CAS Registry numbers:
4 (n=2, X = E t , R'=Ph), 4437-46.1; 4 (n=2, X = E t , R'=C7H15), 11074358-3; 4 ( n = 3 , X = P h , R'=C,H15), 110719-02-3; 4 ( n = 3 , X = P h ,
R'=p-MeOC6H,), 110719-03-4; 4 ( n = 3 , X = M e , R'=H,C=CH), 5129743-9; 4 (n=4, X, R = P h ) , 3375-38-0; 4 ( n = 4 , X = P h , R'=C,H,), 11074359-4; 4 ( n = 4 , X = E t , R'=C,), 103260-26-0; 4 ( n = 5 , X = P h , R'=C2HS),
110719-04-5; 4 ( n = 6 , X = P h , R'=C2HI), 110719-05-6; PhCO(CH,),Ph,
5407-9 1-0; PhCO(CH2),C(CH2)C4H9, 110719-06-7; PhCO(CH2)&(CH2)C.,H9,
110719-07-8;
(E)-PhCO(CH2)3CH=CHC4HP1
110719-08-9;
(9PhCO(CH2)3CH=CHC4H9, 110719-I 1-4; PhCO(CHZ)SCH=CH2, 11071909-0; PhCO(CH2),SnnBu,,
1107 19-10-3; EtCO(CH2)21, 72357-44-9;
PhCO(CH2),I, 65488-05-3; MeCO(CH2),1, 3695-29-2; PhCO(CH,),I, 6686064-8; EtCO(CH,),I, 110719-00-1; PhCO(CH2)51, 71919-91-0; PhCO(CH,),I,
I10719-01.2; PhCOCI, 98-88-4; C,H,,COCI, I 1 1-64-8; p-MeOC6H,COCl,
100-07-2; H,C=CHCOCI, 814-68-6; C~HSCOCI,79-03-8; CHiCOCI, 75-365; PhI, 591-50-4; H2C=C(OTf)C4H9, 37555-23-0; (E)-ICH=CHCsH9, 1664498-7; (Z)-ICH=CHC4H, 16538-47-9; CICH2CH=CH2, 107-05-1; nBu3SnCI,
146 1-22-9; Pd(P(o-Tol),)2C12, 40691 -33-6; Pd(PPh,), 14221-01-3 ; CuCN, 54492-3.
[ I ] Leading reviews on synthetic equivalents of B-metallocarbonyls; a) N.
H. Westiuk, Tetrahedron 39 (1983) 205; b) D. Hoppe, Angew. Chem. 96
(1984) 930; Angew. Chem. Int. Ed. Engl. 23 (1984) 932; c) I Ryu, N.
Sonoda, Yuki Gosei Kagaku Kyokaishi 43 (1985) 112.
[2] a) E. Nakamura, 1. Kuwajima, J . Am. Chem. SOC.99 (1977) 7360; b) 106
(1984) 3368; c) H. Oshino, E. Nakamura, 1. Kuwajima, J. Org. Chenr. 50
(1985) 2802; d ) E. Nakamura, J. Shimada, I. Kuwajima, Organometallics
4 (1985) 641 ; e) E. Nakamura, H. Oshino, I. Kuwajima, J . Am. Chem.
SOC.108 (1986) 3745; see also 9 H.-U. Reissig, Tetrahedron Lett. 22
(1981) 2981.
[3] a) Y. Tamaru, H. Ochiai, T. Nakamura, K. Tsubaki, 2. Yoshida, Tetrahedron Leu. 26 (1985) 5559; b) Y. Tamaru, H. Ochiai, T. Nakamura, Z.
Yoshida, ibid. 27 (1986) 955.
141 For 8-lithiated amides, see: a) P. Beak, J. E. Hunter, Y. M. Jun, J. Am.
Chem. SOC.10s (1983) 6350; b) P. E. Eaton, G. Castaldi, ibid. 107 (1985)
724.
151 a) D. P. G . Hamon, R. W. Sinclair, Chem. Commun. 1968, 890; b) A. A.
Ponaras. Tetrahedron Lett. 1976. 3105.
161 Neither tri-n-butyl-3-benzoylpropylstannane
nor tri-n-butyl-2-ethoxycarbonylethylstannane, prepared according to reaction (0, reacted with
benzoyl chloride under the conditions shown in the text.
[7] a) R. E. Hutton, J. W. Burley, J. Organomet. Chem. 156 (1978) 369; b) R.
A. Howie, E. S. Paterson, J. L. Wardell, J . W. Burley, ibid. 259 (1983) 71.
[8] a) A. DeBoer, C. H. DePuy, J . Am. Chem. SOC.92 (1970) 4008; b) I. Ryu,
K. Matsumoto, M. Ando, S. Murai, N. Sonoda, Tetrahedron Lett. 21
(1980) 4283.
[9] a) M. A. Bennet, G . B. Robertson, R. Watt, P. 0. Whimp, Chem. Commun. 1981. 752; b) B. L. Booth, S. Casey, R. P. Critchley, R. N. Haszeldine, J . Organornet. Chem. 226 (1982) 301; see also c) P. DeShong, G. A.
Slough, Organometallics 3 (1984) 636.
[lo] For the addition reaction of a P-keto radical, generated from the corresponding mercuric compounds, to olefins, see: a) 9. Giese, G . Kretzschmar, Angew. Chem. 93 (1981) 1015; Angew. Chem. Int. Ed. Engl. 20
(1981) 965; b) B. Giese, H. Horler, W. Zwick, Tetrahedron Lett. 23 (1982)
931.
1111 a) S. Brewis, P. R. Hughes, Chem. Commun. 1965. 489; ibid. 1966, 6 ;
rbid. 1967. 71; b) Y. Tamaru, Z . Yoshida, J. Org. Chem. 44 (1979) 1188;
c) T.-W. Lai, A. Sen, OrganometaNics 3 (1984) 866.
[I21 1. Ryu, 1. Rhee, M. Ryang, H. Omura, S. Murai, N. Sonoda, Synth. Commun. 14 (1984) 1175.
1131 I. Ryu, M. Ando, A. Ogawa, S. Murai, N. Sonoda, J . Am. Chem. SOC.
I05 (1983) 7192.
[I41 The reaction of 1 (n=4, X = Ph) with 2.3 molar equivalents of Me,SiCI
gave I-phenylcyclopentene in 51% yield. This result indicates that
M e S C I assists the cyclization of 1 to zinc cycloalkanolates 3.
1 158
0 VCH Verlagsgesellschaji mbH, 0-6940 Weinherm, 1987
[IS] During 'H-NMR measurement in CDCl?/benzene/DMA, gradual decomposition of 1 ( n = 3 , X = P h ) was detected by the weakening and
broadening of the signal for the methylene protons attached to zinc
(6=0.29 ppm (t), J=7.3 Hz). Nosuch behavior was observed in CDCI,/
benzene/H M PA.
[I61 R. D. Miller, D. R. McKean, Tetrahedron Left. (1979) 2305.
[I71 R. D. Smith, H. E. Simmons in H. E. Baumgarten (Ed.): Organic Synfheses. Col. Vol. V. Wiley, Newy York 1973, p. 855.
[IS] J. K. Stille, Angew. Chem. 98 (1986) 504; Angew. Chem. Int. Ed. Engl. 25
(1986) 508.
1191 Before the addition of ally1 chloride, the zinc ketone was filtered under
nitrogen to remove unreacted zinc metal.
[20] For these experiments, the factor y is 1.05, and the yields in the equations refer to the isolated ones, based on the electrophiles. All the products presented here were properly characterized by spectral data (IR,
'H-NMR, "C-NMR, high-resolution MS) and elemental analyses.
1211 A. Alexaxis, G. Cahiez, J. F. Normant, Org. Syn/h. 62 (1984) I.
1221 G. Zweifel, C. C. Whitney, J. Am. Chem. SOC.89 (1967) 2753.
1231 Chelation generally causes the absorption of the C O stretching to shift
by 40-80 cm ' to lower wavenumbers: [2d, 71.
Anthracyclinone Ring C Synthesis via
Chelate Carbene Complexes**
By Karl Heinz Dotz* and Michael Popall
Dedicated to Professor Ulrich ScholIkopf on the occasion
of his 60th birthday
Anthracyclinones, the aglycone components of the antitumor-active anthracyclines,"] usually feature neighboring
central quinone and hydroquinone structures in their linear tetracyclic skeleton and are therefore potential targets
of syntheses involving annelation of chromium carbonyl
carbene complexes.[31The most important anthracyclinone
is daunomycinone 1 , whose B and C rings should be accessible in principle by a variety of routes-each starting
from an unsaturated carbene ligand, a carbonyl ligand,
and an alkyne (Scheme I).
After the B ring had been constructed via routes (a) and
(b),[4-61
we directed our attentions to the synthesis of the C
ring.
The starting point was the carbene complex 2 [route (c)],
which underwent decarbonylation in refluxing tert-butyl
methyl ether to give quantitatively the chelate carbene
complex 3.I7l Crucial for the annelation of the carbene to
the alkyne to afford the hydroquinone skeleton is the long
chromium-oxygen bond,"] which can be opened under
mild conditions (ca. 40 "C). In the presence of the alkynes
4a or 4b, regiospecific annelation of the carbene ligand
occurs to give the coordinated naphthols 5a or Sb, respectively. The metal carbonyl fragment is conveniently
cleaved off under CO atmosphere, affording hexacarbonylchromium in practically quantitative yield. The latter,
in turn, can be used again to generate the carbene complex
3.
Functionalization of the ketone 6 to give the carboxylic
acid 7 is necessary for the formation of ring B. It is
achieved, following 0-methylation, with isocyanomethyl@-tolyl)sulfone."O1 Finally, the carboxylic acid is cyclized to the diketone 8 in acid (trifluoroacetic acid(TFA)/
trifluoroacetic anhydride (TFAA)). This reaction was used
earlier by Sih et al.["I and by Rao et a1.1'21as part of a
longer route leading to intermediates in the synthesis of
[*I Prof. Dr. K. H.
I**]
Dotz, Dr. M. Popall
Fachbereich Chemie der Universitat
Hans-Meerwein-Strasse, D-3550 Marburg (FRG)
Carbene Ligands as Anthracyclinone Synthons, Part 5. This work was
supported by the Deutsche Forschungsgemeinschaft and the Fonds der
Chemischen 1ndustrie.-Part 4: [I].
0570-0833/87/1111-1158 $ 02.50/0
Angew. Chem. In,. Ed. Engl. 26 (1987) No. I 1
OMe
I
R
!
?H
I1
0
dH
R
OH
1, R = OMe
Scheme I . Synthesis of daunomycinone 1, R=OMe, via carbene complexes.
1 1-deoxyanthracyclinones. Thus, the chromium-induced
has
via the
carbelle
been integrated into a formal total synthesis of Il-deoxYdaunomycinone 9 ; the synthetic route outlined here is
overall appreciably
than the routes employed so
far.
R
O
Me0
M
e
Cr(CO)5
2
- % z G + e
3
7
0
.
.
OMe
5
75 bar CO
___j
- C w 9 ,
96%
Me6
6Me
6
6
Me0
OMe
59, b: The alkyne 4a or 4b 1131 (7.5 mmol, 1.46 g or 1.13 g, respectively) was
added to a solution of 3 (1.57 g, 5 mmol) 171 in tert-butyl methyl ether
(50 mL). After stirring for I h at 40 "C, an orange-red suspension was ohtained. Removal of the solvent and precipitation by addition of CHzC12/
oentane vielded an oranee-vellow crvstalline uowder. Yields: 2.02 p. 5a (79%)
and 1.86g 5b (80%).--5a: IR (KBr): G(C=O)=1952, 1864.-'H-NMR
(CD,COCD,): 6=7.3-7.9 m, 6.6-7.2 m (3 H, H6-H8); 4.07 (s, 1 H, H3); 3.97
(s, 3 H, 4-OCH,); 3.82 (s, 3 H, 5-OCH,): 3.88 (s, 4 H, OCH2); 3.37 (m. 2 H,
CHI); 1.4-2.9 (m, 7 H, H (cyclohexyl).-5b: IR (KBr): q C = O ) = 1947,
1866.--'H-NMR (CD,COCD,): 6=7.79 (d, I H, H8); 7.35 (m, 1 H, H7); 6.91
(m, I H, H6); 3.89 (5, 3 H, 4-OCH,); 3.83 (s, 3 H, 5-OCH3); 3.37 (m, 2 H,
CHI); 2.1-2.9 (m, 7 H, H (cyclohexyl)).
6 : A solution containing 5a (1.01 g, 2 mmol) in CH2C12(100 mL) was heated
to 70°C in a steel autoclave equipped with a glass insert. CO (75 bar) was
admitted and the solution was allowed to stir for 72 h. After cooling and
careful release of pressure, the solvent was removed and the residue was dissolved in a small amount of ether. The Cr(CO)6 formed was filtered off at
- 50°C. Addition of CH2C12/pentane to the solution afforded a yellow crystalline powder. Yield: 0.82 g (96%).--'H-NMR (CD,COCD,): 6=7.74 (d,
1 H, H8); 7.33 (m, I H, H7); 6.91 (m, I H, H6); 6.63 (s, 1 H, H3); 3.95 (s, 3 H,
4-OCH,); 3.88 (s, 4 H, OCH2): 3.81 (s, 3 H, SOCH,); 3.37 (m,2 H, CHI);
2.1-2.9 (m. 7 H, H (cyclohexyl)).-MS: m / z 372 (M").
8: 6 (0.24 g, 0.65 mmol) was methylated with an excess of a 0.05 M diazomethane solution. The reaction product in T H F was then added at - 10°C to a
T H F solution containing 0.65 mmol of both potassium terr-butoxide and isocyanomethyl@-tolyl)sulfone. The mixture was stirred for 10 min and then
treated with 0.4 g of glacial acetic acid. After removal of the solvent, the residue was dissolved in water and extracted with CH2C12.The crude product
was deesterified with 2 N HCI. Extraction with CH2C12 at pH 1 afforded a
yellow powder, which was treated carefully at 0 "C with 7.5 m L of TFA/
TFAA (1 :2). The red solution was worked up with NaHCO, and water; extraction with chloroform and evaporation of the solvent gave an orange-red
powder, which was purified by preparative thin layer chromatography on
silica gel with CH2C12/THF (2 :1) and whose analytical and spectroscopic
data are in agreement with those reported for the products described in Refs.
[ I l l and [12]. Yield: 0.lOg (45%).-'H-NMR (CDCI,): 6=7.72 (d, 1 H, HI);
7.43 (t. 1 H, H2); 6.83 (d, 1 H, H3); 3.98 (s, 3 H), 3.93 (s, 3 H), 3.89 (s, 3 H)
(4-, 5-, 12-OCH3); 3.6 (m, 2 H, CH2); 2.0-2.9 (m, 8 H, CH2, CH).-MS: m / r
354 (M").
I
_
Q@+jR2
Me0
5a
Experimental Procedure
OH
7
Received: July 6, 1987 [Z 2327 IE]
German version: Angew. Chem. 99 (1987) 1220
Me0
OMeO
a: R',
OH OH
OMeO
8
9
R2 = OCH2CH20; b: R', R2 = 0
Angew. Chem.
Int.
Ed. Engl. 26 (1987) No. 11
[ I ] K. H. Dotz, M. Popall, G. Muller, K. Ackermann, Angew. Chem. 98
(1986) 909: Angew. Chem. Int. Ed. Engl. 25 (1986) 911.
121 Recent reviews: a) F. Arcamone: Doxorubicin Anticancer Antibiotics. Academic Press, New York 1981; h) H. S . El Khadem (Ed.): Anthrucycline
0 VCH Verlagsgesellschuft mbH. 0-6940 Weinheim, 1987
0570-0833/87/1111-1159$ 02.50/0
1159.
Antihiolm. Academic Press, New York 1982; c) K. Krohn, Angew.
Cliem. 98 (1986) 788; Angew. Chem. Int. Ed. Engl. 25 (1986) 790.
[ 3 ] Review: K. H. Dotz, Angew. Chem. 86 (1984) 573; Angew. Chem. Int.
Ed Engl. 23 (1984) 587.
141 W. D. Wulff, P. C. Tang, J . Am. Chem. Soc. I06 (1984) 434.
151 K. H. Dotz, M. Popall, J. Organornet. Chern. 291 (1985) C I .
[61 K. H. Dotz, M. Popall, Tetrahedron 41 (1985) 5797.
[ 7 ] K. H. Dotz, W. Sturm, M. Popall, J . Riede, J . Organomet. Chem. 277
(1984) 267.
[8] The C r - 0 bond in 3 (2.!82(2)
[7]) is significantly longer than that in
[(CO),Cr(thf)] (2.123(3) A [9]), which usually serves as a source of coordinatively unsaturated chromium carbonyl fragments.
[9] U. Schubert, P. Friedrich, 0 Orama, J. Organomef. Chem. 144 (1978)
175.
[lo] U. Schollkopf, R. Schroder, Angew. Chem. 84 (1972) 289; Angew. Chem.
Inf. Ed. Engl. 11 (1972) 311.
[I I ] J . Yadav, P. Corey, C.-T. Hsu, K . Perlman, C. J. Sih, Tetahedron Letf. 22
(1981)811.
1121 A. V. Rama Rao, V. H. Deshpande, N. L. Reddy, Tetrahedron Lett. 23
(1982) 775.
[I31 The alkynes 4a and 46 were synthesized from 1,4-cyclohexanedione
1-one ethylene acemonoethylene acetal via 4-pyrrolidino-3-cyclohexental [I41 and propargyl bromide.
1141 P. Nedenskov, W. Taub, D. Ginsburg, Acta Chem. Srand. 7 (1958)
1405.
R=NR3R4, R ' = C N , R'=CO2CH3, are formed with elimination of nitrogen."]
R
A
Methyl (E)-2-( l-Aryl-4,5-dihydrolH-tetrazol-5-ylidene)-2-cyanoacetatefrom
Methyl 3,3-Diazido-2-cyanoacryIate
and Primary Aromatic Amines**
By RoV W. Saalfank, * Michael Fischer, Uwe Wirth, and
Helmuth Zimmermann *
Dedicated to Professor Ulrich Schollkopf on the occasion
of his 60th birthday
Open-chain systems having the general structure 1[***]
can in principle undergo isomerization to give the corresponding cyclic systems 2. Whether formula 1 or 2 represents the more stable structure depends on the substituents
X and R.IZ1For example, acyl azides 1, X =0, exist exclusively in the open-chain f ~ r m , ' ~ whereas
.~]
thioacyl azides
1, X = S, cyclize to give 1,2,3,4-thiatriazolones 2, X = S.[2.41
In the case of imino azides 1, X = N R ' , only electronaccepting substituents R' are capable of stabilizing the
azide form, tetrazoles 2, X = N R ' , being obtained otherWhereas this imino azide-tetrazole isomerizatie#" is documented by numerous examples, there have
been only a few reports on the vinyl azide-4H-triazole
isomerization (1-2 for X=CR'R').".''
Vinyl azides 1 [ R = NR3R4, X=CCN(CO,CH,)] substituted with donor groups in the 4 position can undergo
both 1,5 and 3,s ring-closure reactions. Depending on the
substituents R and the reaction conditions, either stable
1,2,3-triazoles are formed via the 4H-1,2,3-triazoles 2,
R=NR3R4, X =CCN(CO,CH,),
or 2H-azirines 3,
kX\
N,
4N
N
2
R dN R z
x
=
0,s, NR', C R ' R ~
The thermal transformation of vinyl azides 1
[X=CR'R2], with R, R', R 2 = H , alkyl, aryl, leads exclusively to 2H-azirines 3. As the reaction mechanism, a 3,s
ring closure of 1 with concurrent elimination of nitrogen is
favored over a pathway involving a free nitrene or one involving a 1,5 ring closure to give 4H-1,2,3-triazoles followed by elimination of nitrogen.[2",81
A detailed investigation of the vinyl azides 6[**']
[= 1
with R = NHR', X = CCN(CO,CH,)] revealed that, for
suitable substituents in the 4 position, these compounds
could undergo novel, intermolecular reactions ( 1 3 ring
closure to give 7,'"'' nitrene addition to a C = C bond to
give 9 ) .
Reaction of methyl 3,3-diazido-2-cyanoacrylate4 with
the primary arylamines 5a-c at - 25 "C leads initially to
donor-substituted vinyl azides 6a-c (for experimental
data, see Table 1), which undergo base-catalyzed isomerization in dichloromethane to afford the methyl dihydrotetrazolylidenecyanoacetates 7a-c (Table
"I
R'
0
4
6
3
H
7
['I Prof. Dr. R. W. Saalfrank, DiplLChem.
I**]
[***I
1 160
M. Fischer,
DipLChem. U. Wirth
lnstitut fur Organische Chemie der Universitat Erlangen-Numberg
Henkestrasse 42, D-8520 Erlangen (FRG)
Priv.-Doz. Dr. H. Zimmermann
Institut fur Angewandte Physik (Kristallographie)
der Universitat Erlangen-Niirnberg
Bismarckstrasse 10, D-8520 Erlangen (FRG)
Geminal Vinyl h i d e s , Part 5. This work was supported by the
Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie. We wish to thank Prof. H. Fritz, Ciba-Geigy (Basel), for the
"N-NMR spectrum, and Prof. R . Carrie and Dr. D.Danion. Universiti
Rennes, for stimulating discussions -Part 4: [I].
The (unsystematic) numbering of the compounds 1 , 6 and 7 assists in
discussing the substituent effects and in assigning the spectroscopic
data.
0 VCH Verlagsgesellschafi mbH, 0-6940 Weinheim, 1987
5-7
R'
I
I
a
b
C
d
C,H,
4-H3C-C,H,
4-H3CO-C,H4
6
C"2
Compound 7a dissolves in aqueous potassium hydroxide as the salt 8 (yield 74%, rn.p.=263 "C (from water/
acetone)), which can be converted back into 7a by reaction
with hydrochloric acid.
The constitution of the heterocycIes 7 could not be established unequivocally from the spectroscopic data.
These data would also be in agreement with the methyl Naryl-N-(5-cyano-lN-l,2,3-triazol-4-yl)
carbamidates iso-
0570-0833/87/1111-1160$ 02.50/0
Angew Chem Int. Ed. Engl. 26 (1987) No. 11
Документ
Категория
Без категории
Просмотров
1
Размер файла
335 Кб
Теги
synthesis, carbene, anthracycline, ring, complexes, via, chelate
1/--страниц
Пожаловаться на содержимое документа