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Doubly Deprotonated Allylacetophenone. First Example of a УDirectФ E5 Synthon

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Ca. 40h (TLC check), in anhydrous benzene after rinsing with pure
nitrogen, stationary N2 atmosphere, Philips mercury high-pressure lamp
HPK 125 W (quartzg1ass)at 20"C,0.005mol in 1 liter. After concentration
in a vacuum (Rotavapor) at 35 to 40°C water-bath temperature the
residue is chromatographed on 200g silica gel (6 0.15 to 0.30mm):
elution of ( 2 ) with 3 liters of light petroleum (b.p. 30 to 70°C) and
finally of ( 3 ) with 3 liters of light petroleum (b.p. 30 to 70"C)/acetone
(10: 1).
Prepared in 18 % yield according to [l]. Colorless crystals from light
petroleum (b.p. 30 to 70"C)/ether, m.p. 151 to 153"C, I R (CHCI,):
vc=o= 1680 cm-'; exact mass determination of MS molecular signal
(C13HloCINOSe,intensity: 3 %): calc. 310.9616, obs. 310.9652 amu,
referred to the isotope '"Se.
appear bold in the formulas) which could be obtained pure
in yields between 25 and 80 % by chromatography on silica
gel (see Table 1). The configuration of these P,y-unsaturated
ketones is determined by the nature of the electrophile: pro-
f
Doubly Deprotonated Allylacetophenone.
First Example of a "Direct" E5 Synthon[**]
(4)
(3)
By Manat Pohmakotr and Dieter Seebach"]
Doubly unsaturated conjugated carbonyl compounds such
as the ketone (I) react at the terminal C-5 atom with nucleophiles (N5 attack)[']. We have now found that this reactivity
is reversed-as with N' and N 3 attack[']-on
use of the
dianion derivative (2). We obtained this derivative by double
deprotonation of the allylacetophenone (3) containing two
hydrogen atoms more. An a-carbonyl proton was first
abstracted with potassium hydride (THF/45 min/O°C) to give
(4)13], which was treated with sec-butyllithium (2 equiv.
TMEDA/4 h/-78 to O°C)-a deep violet-red solution of (2)
was obtained. Addition of an equimolar mixture of electrophile and hexamethylphosphoric triamide in a little T H F (3
to 5 h/-78"C to room temperature) permitted, after aqueous
workup, isolation of product ( 5 ) or (6) (newly formed bonds
See-BuLi
tonation, alkylation with halides and epoxide, and a-hydroxyalkylation with aliphatic aldehyde and ketone gave exclusively the cis compound (5)C41, whereas the reaction of (2)
with aromatic carbonyl derivatives (benzaldehyde, allylacetophenone, benzophenone) furnished only trans adducts (6)
(see Table 1, NMR coupling constants). In no case did we
observe mixtures of configurational isomers ( 5 ) / ( 6 ) ; structural isomers resulting from attack of the electrophile on
an atom other than C-5 in (2) were not detected either on
Table I . Products (S), (61, and ( 7 ) from the dianion ( 2 ) and electrophiles. All IR and 'H-NMR spectral data are compatible with the structures given.
The cis and trans coupling constants in (5) and (6) were determined in decoupling experiments. All compounds gave elemental analyses correct to within
0.3 %. ( 7 f ) , (791, (7i), and ( 7 j ) are obtained as mixtures of two diastereoisomers (according to I3C-NMR analysis).
Electrophile
treated
with ( 2 )
No.
E
Products (5) and (6)
Yield Phys. data
["/.I
J,i,( 5 ) or
Jtrans
No.
R
Product (7)
R'
Yield
[
(6)
x] [a]
[HZ1
Phys.
data
nb2:m.p.
roc1
H2O
D20
CHjI
n-C4HpCI
2-Methylpropanal
Cyclohexanone
Benzaldehyde
Allylacetophenone
Benzophenone
H
D
( 5 ~ ) CH3
( 5 d ) n-CAH9
(50)
(56)
78
76
60-72
59
n6' = 1.5392
nh1=1.5410
nh' = 1.5362
n6' 5=1.5288
8
7.5
8
8
32
20-35
n i 2 = 1.5350
8
8.5
(7e)
m.p. 36-37°C
(7f)
H
C2H5
71
68
1.5196
1.5206
H
(CH3)2CH 72
1.5168
(59)
(CH,),CH-CH(OH)
35
n;"."= 1.5312
8
(79)
(5hi
(CH2)KTOH)
25
m.p. 54-55°C
9
(7h)
(6i)
C6H5CH(OH)
38-53
m.p. 93-95°C
16.5
(7i)
H
CeH5
94
(6j)
CH2=CH-(CH2)2-C(C6H5)(OH)
48
m.p. 64°C
16.0
(7j)
CH2=CH-(CH212
C6Hs
65
(6k)
(CsH5)2C(OH)
40-65
m.p. 111-112°C
16.0
f7k)
C6Hs
C6H5
86
-(CH2)5-
85
1.5342
49-53
1.5573
84-85
[a] Based on (5) or (6).
[*] M. Pohmakotr, M. Sc., Prof. Dr. D. Seehach
['I
Institut fur Organische Chemie der Universitat Giessen
Heinrich-Buff-Ring 58, D-6300 Lahn-Giessen (Germany)
[**I Part ofthe projected Doctoral Thesis by M. P., Universitat Giessen.-M.
P . wishes to thank the DAAD for a stipend. This work was supported
by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen
Industrie.
[ '1 To whom correspondence should be addressed.
Present address: Laboratoriuni fur Organische Chemie der ETH
ETH-Zentrum, Universitltsstrasse 16, CH-8092 Zurich (Switzerland)
320
chromatographic analysis of the products. Apart from (5)
or ( 6 ) , most of the product mixtures were also found to
contain the dimer ( 6 j ) (5-10 %) of the starting ketone (3)
and a mixture (15 to 45 %) of I-phenyl-2-, -3-, and -4-penten-lones. i, e, of ( 3 1 and its isomers.
Treatment oi the adducts of (2) to aldehydes and ketones
or isobutylene oxide in 0.1 M solution [THF :C H 3 0 H
(1 : 1)/6h/room temperature] with 1 equivalent of sodium
Angew. Chem. Int. Ed. Engl. 16 (1977) No. 5
&C
0
H-CH-CH~-$
? R’
H5C 6
2.H,0m
OH
( s f ) - i j h ) . (6il-16k)
mk
1 CHjONa
H5C6
,, 0
R‘
(7fl-(7k)
methoxide followed by workup with aqueous acid gives the
tetrahydrofurans or pyrans (7) in high yields (see Table 1).
The double bond apparently shifts into conjugation with the
carbonyl group, whereupon the HO group undergoes intramolecular addition.
Compound (2) is the first “direct” carbonyl derivative with
reactivity umpolung at (2-5. The only Es building blocks
known hitherto have a protected carbonyl group[51or their
use depends upon a thio-Claisen rearrangementc6].
merically pure form from carbonyl compounds (I ) oia 6-nitro1,3-dicarbonyl compounds (2). Corresponding 5-nitro diketones ( 4 ) should cyclize to five-membered rings ( 5 ) . We
now describe an entry to the derivatives ( 4 ) and the first
examples of their conversion into the products (5), (61, or
( 7 ) , which are formed depending upon the structure of the
precursors and upon the reaction conditions.
Slow addition of cooled amine-free solutions of the Li enolates of the ketones ( I ) to a stirred T H F solution of an
equimolar amount of P-nitropropionyl chloride[’] at - 80 to
- 100°C furnishes the diketones ( 4 ) in 65 to 90 % yield[31
(see Table 1, above). Cyclization was initially conducted under
the conditions worked out for the reaction (2) -+ (3)[”(variant
A): Pouring of the dilithium salt ( 4 ‘ ) , dissolved in THF,
into a large volume of water and slow neutralization with
Received: January 25, 1977 [Z 656 IE]
German version: Angew. Chem. 89. 333 (1977)
Publication delayed at authors’ request
(3)
CAS Registry numbers:
(1),4734-99-0:(2), 61812-39-3:( 3 ) ,3240-29-7:( 4 ) , 61752-44-1:( 5 0 ) . 61752( j c ) , 61 752-47-4:(5 d ) , 61 752-48-5:(5e), 61 752-49-6;
45-2;(5 h),61752-46-3;
(5f),61752-50-9;
(5y),61752-51-0;
(5h),61787-97-1;(6i),61752-52-1;(6,j),
61752-53-2;(6k), 61752-54-3:( 7 e ) , 10599-29-8:c i s - ( 7 f ) , 61752-55-4:trans(7.f),61752-56-5;cis-(79), 61752-57-6;trans-(7g), 61752-58-7;(7h), 6175259-8;cis-( 7 i ) . 61752-60-1;trans-(7i), 61752-61-2;c i s - ( 7 j ) , 61752-62-3;trans( 7 j ) . 61752-43-4:(7k), 61752-64-5:H 2 0 , 7732-18-5;D 2 0 , 7789-20-0;CH31,
74-88-4:rl-CIHul, 542-69-8:isobutylene oxide, 558-30-5; propanal, 123-38-6:
2-methylpropanal, 78-84-2:cyclohexanone, 108-94-1: benzaldehyde, 100-52-7;
henzophenone, 119-61-9:
potassium hydride, 7693-26-7;
see-butyllithium, 59830-1 : Z-1 -phenyl-2-penten-l-one, 61 752-65-6: E-l-phenyl-2-penten-l-one,
61752-66-7
Examples: G. KBbrich, W E. Breckofl, W Drischel, Justus Liehigs
Ann. Chem. 704, 51 (1967):E. J . Core). et al., J. Am. Chem. Soc. 94,
4395 (1972):Tetrahedron Lett. 1973, 1611; B. Canem, ibid. 1974, 4467;
F . Kido, 7: Fu/ishita, K . Tsutsumi, A. Yoshikoshi, J. Chem. Soc. Chem.
Commun. 1975, 337.
D. Seebuck. N. Meyer. Angew. Chem. 88, 484 (1976); Angew. Chem.
Int. Ed. Engl. 15.438 (1976);K . H . Geiss, D. Srebach, B. Seurrng, Chem.
Ber. I10 11977),in press: and references cited therein.
Hydrolysis at this point regenerates the starting ketone ( 3 ) with unshifted
double bond.
Cf. the dilithium derivative of 1,3,5-hexatriene: R . E . Bates el a/., J.
Am. Chem. Soc. 96, 5640 (1974);97, 6271 (1975);J. Org. Chem. 41,
1620 ( I 976).
[. Fkming, W. E . Long, Synth. Commun. 5, 177 (1975).
H . Yui?rumoto et al., J. Am. Chem. SOC. 95, 2693, 4446, 5803 (1973).
4-Hydroxy-2-cyclopenten-1-ones from Ketones and 3Nitropropionyl Chloride. A Facile Method for the Construction of Five-Membered Rings[**]
By Dieter Seebach, Marvin S. Hoekstra, and Gerd Protschukl*l
We recently reported a cyclization“] yielding highly functionalized and substituted six-membered rings (3) in diastereo-
[‘I, Dr. M. S . Hoekstra, G. Protschuk
Institut fur Organische Chemie der Universitat
Heinrich-Buff-Ring 58. D-6300 Lahn-Giessen (Germany)
We acknowledge support of this work by the Deutsche Forschungsgemeinschaft (Project Se I58/11) and the Fonds der Chemischen Industrie.
[*] Prof. Dr. D. Seebdch
[**I
[ ‘1 Present address: Laboratorium fur Organische Chemie der ETH
ETH-Zentrum, Universitatsstrasse 16, CH-8092 Zurich (Switzerland)
14 ‘I
17)
acetic acid. We have meanwhile discovered a simplified procedure (variant B), according to which a T H F solution of the
nitro diketone (4) is added to a buffer solution (pH=ca.
8.5). After a short reaction time, there result the hydroxycyclopentenones ( 6 ) , which rearrange completely to the isomers
(7) if the reaction is allowed to run over a prolonged period
of timeL4].In only one case could we isolate the nitrocyclopentanone ( 5 ) (see Table I), certainly formed as intermediate
in all the reactions. The derivatives ( 5 ) and ( 6 ) are preferentially formed in one diastereomeric isomer; assignment has
yet to be performed.
The IR, ‘H-, I3C-NMR, and MS spectra, and elemental
analyses of the new compounds ( 4 ) to (7) are in accord
with the given structures. Thus the P-hydroxy ketone structure
of these rearrangement products follows from the “coupled”
I3C-NMR signals of the carbonyl C atoms of ( 7 ) (splitting
321
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