Synthesis of highly hindered 1,2-diaryl diketones and of cis- and trans-1,2-diacetoxy-1,2-bis(aryl)ethenes

Article abstract of DOI:10.1039/a809045i

Highly hindered 1,2-diaryl diketones can be synthesized in good yields by the reaction of 1-aryllithium with CO in THF solution at atmospheric pressure; preparation of cis- and trans-1,2-diacetoxy-1,2-bis(Mes)ethene can be also afforded by a similar procedure and further quenching with Ac₂O.

Full text of DOI:10.1039/a809045i

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422 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
1999, 422^423y
Synthesis of Highly Hindered 1,2-Diaryl
Diketones and of cis- and
trans-1,2-Diacetoxy-1,2-bis(aryl)ethenesy
Norma Nudelman* and Hernan Schulz
Departamento de Qu|mica Organica, Facultad de Ciencias Exactas y Naturales, Universidad de
Buenos Aires, Pab. II, P. 3, C. Universitaria, 1428 Buenos Aires, Argentina
Highly hindered 1,2-diaryl diketones can be synthesized in good yields by the reaction of 1-aryllithium with CO
in THF solution at atmospheric pressure; preparation of cis- and trans-1,2-diacetoxy-1,2-bis(Mes)ethene can
be also afforded by a similar procedure and further quenching with Ac2O.
Table 1 Carbonylation of MesLi 1a in THF quenching with
50 lL of aqueous NH4Cl
Symmetrical
a-diketones,
RCOCOR,
are
useful
intermediates for the synthesis of oxygenated ¢ne
chemicals,1 and several methods have been recently
attempted for their preparation. Most of the reported
methods for the synthesis of aromatic a-diketones are based
on the coupling of carbonyl compounds, promoted by dif-
ferent means.2;3 Novel routes to aryl 1,2-diketones utilise
treatment of benzotriazole derivatives with butyllithium
and subsequent reaction with esters; no diaryl compounds
were reported.4 Since coupling of ortho-substituted
derivatives is unfavourable because of steric hindrance, a
strategy based on the formation of an oxycarbene that
would favor coupling is proposed here, as a procedure
for the synthesis of highly hindered aromatic a-diketones
under mild reaction conditions.
Products(%)a
1a/mmol
VolumeCO/mL
T/ 8C
2a
4a
0.8
0.3
1.2
0.4
10
5
14
8
50
0
25
35
67
54
52
44
27
42
36
56
aDetermined by GC, against decalin as internal standard.
Table 2 Carbonylation of MesLi 1a quenching with 50lL of
acetic anhydride
Products(%)
The reaction of 1-aryllithium 1 with CO at atmospheric
pressure allowed the synthesis of hindered 1,2-diaryl
diketones 2 in good yields; giving in some cases also the
diarylketone 3 as a side product [eqn. (1)]. A careful search
of conditions was carried out for the reactions of
2,4,6-trimethylphenyllithium, (MesLi) 1a, which was pre-
pared from mesityl bromide and n-butyllithium.
1a/mmol
VolumeCO/mL T/ 8C
4a
8a
8b
0.8a
1.2a
0.4a
0.6b
4.5c
4.5c
4.5c
35
17
8
20
18
27
39
78
35
25
30
60
36
39
64
30
43
46
20
41
25
6
8
10
0
2
11
38
5
15
14
45
80
100
130
ArLi
+
CO
ArCOCOAr
+
ArCOAr
(1)
a[1a]=0.4M in THF. b[1a]=0.3M in THF. cMesLi (solid phase
reaction).
1
2
3
In this case, only the 1,2-diaryl diketone 2a is produced in
yields > 50%; to the best of our knowledge, 2a was pre-
viously obtained in only 8% yield.5 The reaction mixture
contains also variable amounts of the corresponding
hydrocarbon 4a [eqn. (2)] plus some other trace products
(Table 1).
In the present study, the ¢nding of mesitylene in the
reaction mixture could, in principle, be explained in analogy
to a transmetallation reaction, which was reported to yield
the p-stabilised benzyl anion at temperatures higher than
10 8C.8 Nevertheless, formation of 4a can be better
‡
explained by a partial escape of (MesLi) from the cage,
5 ꢀAr ˆ Mes†, and subsequent H abstraction from THF
by the mesityl radical formed.
MesLi
+
CO
MesCOCOMes
+
MesH
(2)
Treatment of the reaction mixture with acetic anhydride
before quenching produces cis- and trans-1,2-diacetoxy-
1,2-bis(2,4,6-trimethylphenyl)ethene 8 [eqn. (4)]. This is a
further proof for the reaction mechanism mentioned above
and indicates that the intermediate is the 1,2-dilithium-
diolate 7 formed by dimerization of 6a ꢀAr ˆ Mes†.9
1a
2a
4a
In a previously reported mechanistic study of the reaction
of phenyllithium with CO,6 the reaction is shown to be
initiated by electron transfer from PhLi to CO, giving
the radical cation^radical anion pair 5 (Ar ˆ Ph); further
reaction within the cage gives the transient acyl anion inter-
mediate 6,7 which is in equilibrium with an oxycarbene
species [eqn. (3)].
Ac2O
2 [6a]
Mes(LiO)C=C(OLi)Mes
Mes(AcO)C=C(OAc)Mes (4)
7
8
It can be seen from Table 2 that the production of
isomers 8a (cis) and 8b (trans) is strongly dependent on
the temperature. At relatively high temperature the yield
of 8b is slightly higher than those of the cis isomer 8a, while
at lower temperatures the cis/trans ratio increases, and
reaction at 78 8C yields only the cis-isomer (Table 2).
These isomers were characterized by analogy with the cis,
trans isomers of 1,2-diacetoxy-1,2-bis(phenyl)ethene.10
The cisoid con¢guration of the transition state in which
(3)
ArLi
+
CO
(ArLi)•+, (CO)•–
ArC(O)Li
ArCOLi
5
6
* To receive any correspondence.
y This is a Short Paper as de¢ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1999, Issue 1]; there is
therefore no corresponding material in J. Chem. Research (M).

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J. CHEM. RESEARCH (S), 1999 423
Table 3 Carbonylation of 1-aryllithium 1 in THF quenching with
50lL of saturated NH4Cla
1,2-Dimesityldiketone 2a was isolated by column chromatography,
mp 118^120 8C (lit.5 122 8C).
Bis(2,6-dimethylphenyl)glyoxal 2b was obtained from the reaction
of CO with 1b in THF at 78 8C and was crystallised from hexane,
giving yellow plates, mp 151±153 8C (lit.14 153±154 8C).
Bis(2-methylphenyl)glyoxal 2c was independently prepared by the
method described by Shacklett and Smieth15 and crystallised from
ethanol, mp 90^92 8C (lit. 92±94 8C).
Mesityllithium 1a Xylyllithium 1b
o-Tolyllithium 1c
T/ 8C
2a
3a
2b
3b
2c
3c
78
0
25
94
96
90
0
0
0
96
96
98
< 1
0
0
67
32
30
30
67
70
2,20-Dimethylbenzophenone 3c was prepared by reaction of
1.5 mmol of o-tolyllithium with 180 mg (1.5 mmol) of o-tolualdehyde
in THF at 0 8C. The resulting alcohol was isolated by column
chromatography. The alcohol was converted to the benzophenone by
reaction with Jones solution; 3c was isolated by chromatography and
crystallised from ethanol, mp 64^66 8C (lit.16 64±67 8C).
1,2-Diacetoxy-1,2-bis(2,4,6-trimethylphenyl)ethene 8 was charac-
aThe yields represent % conversion. Variable amounts of the
respective hydrocarbon were also found.
both oxygens are coordinated to both lithium atoms
requires less energy and thus formation of the cis isomer
7a is favoured at low temperatures.
1
terised as follows: FT IR(KBr)/cm 3025, 3001, 2946, 2920, 2850,
2721, 1630, 1605, 1461, 1370, 876, 615, 600. 1H dH(CDCl3) 6.66
(s, 4H), 2.13 (s, 18H), 2.07 (s, 6H). MS: m/z, (rel. int.) 380 (21),
338 (50), 296 (100), 235 (10), 220 (12), 176 (21), 158 (8), 148 (55),
147 (73), 133 (31), 105 (15), 103 (13), 79 (10), 77 (20), 65 (9), 43 (50).
mp 8a 155 8C (lit.17 164±165 8C).
Recently, increasing interest has focused on reactions car-
ried out in the solid state,11 and we have reported earlier
that performing the reaction of PhLi with CO in the absence
of solvent could be an e¤cient method for the synthesis of
a; a-diphenylacetophenone in yields > 90%.12 The carbony-
lation of 1a was therefore tested in the solid phase, at sev-
eral temperatures, and results are shown in Table 2 (see
footnote c). In this case, no improvement in the yields
of 8 was found, and a major production of 4a and
by-products was observed at T ꢁ 80 8C.
General Procedure for Reactions with Carbon Monoxide in the Solid
State.öA septum-capped reaction £ask containing 1a as a powder
was immersed in a silicone-oil bath at the working temperature
and was exposed to CO at atmospheric pressure. When the absorption
was complete the reaction mixture was worked-up by adding THF
and subsequently Ac2O. The product composition was determined
by GC.
Received, 19th November 1998; Accepted, 26th March 1999
Paper E/8/09045I
In order to expand the scope of this work, the
carbonylation of other hindered aryllithiums, namely
(2,6-dimethyphenyl)lithium 1b and (2-methyphenyl)lithium
1c (Ar ˆ Tol†, was examined (Table 3). It can be observed
that with 1c, the least hindered of the three reagents, vari-
able amounts of the diarylketone 3c were also obtained.
The highest formation of 3c was observed at 25 8C, and
can be rationalized by the oxidation of the dilithium
dianion 9c produced from the reaction of the corresponding
transient intermediate 6c with another molecule of 1c, as
observed previously in the case of Ar ˆ Ph,10 [eqn. (5)].
References
1
Comprehensive Organic Synthesis, ed. B. M. Trost and I.
Fleming, Pergamon Press, New York, 1993, ch. 9; T. Wirth,
Angew. Chem., Int. Ed. Engl., 1996, 35, 61.
G. A. Tomaselli, S. Failla and F. P. Ballisteri, J. Org. Chem.,
1988, 53, 830.
2
3
4
R. Karaman and J. Fry, Tetrahedron Lett., 1989, 30, 2757.
A. R. Katritzky, Z. Wang, H. Lang and D. Feng, J. Org.
Chem., 1997, 62, 4125.
5
6
7
E. P. Kohler and R. Baltzly, J. Am. Chem. Soc., 1932, 54,
4015.
N. S. Nudelman and F. Doctorovich, Tetrahedron, 1994, 50,
4651.
These intermediates have been observed previously, and
lithium acyl anions were trapped as silanes (D. Seyferth
and R. Weinstein, J. Am. Chem. Soc., 1982, 104, 5534) or
thioesters (D. Seyferth and R. Hul, Organometallics, 1984,
3, 327).
OLi
–2e
Tol 2C
6c
+ 1c
3c
(5)
CO
Li
9c
The corresponding 1,2-diacetoxy compounds 8 for o-tolyl
and xylyl derivatives could be obtained as described for the
mesityl compounds.
8
9
P. v. R. Schleyer, W. R. Winchester and W. Bauer,
Organometallics, 1987, 6, 2371.
Compound 8 was obtained by adding 50 lL of acetic anhydride
to the reaction mixture. The organic layer was washed with
water, separated and dried with MgSO4.
In conclusion, hindered diaryl diketones
2 can be
obtained in good yields by the reaction of the corresponding
aryllithium with CO in THF at temperatures < 25 8C at
atmospheric pressure. For 1,2-diacetoxy-1,2-bis(aryl)ethenes,
it is possible to tune the selectivity of the reaction by
varying the temperature, in order to obtain the desired
compound in major yield.
10 N. S. Nudelman and A. A. Vitale, J. Organomet. Chem., 1983,
241, 143.
11 F. Toda, Acc. Chem. Res., 1995, 28, 480.
12 N. S. Nudelman and A. A. Vitale, Org. Prep. Proced., 1981,
13, 144.
13 N. S. Nudelman, E. S. Lewcowicz and D. G. Perez, Synthesis,
1990, 917.
14 R. C. Fuson, S. L. Scott, E. C. Horning and C. McKeever, J.
Am. Chem. Soc., 1940, 62, 2091.
15 C. D. Shacklett and H. A. Smieth, J. Am. Chem. Soc., 1953,
75, 2654.
16 J. W. Cook, J. Chem. Soc., 1930, 1087.
17 R. C. Fuson, C. H. McKeever and J. Corse, J. Am. Chem.
Soc., 1940, 72, 600.
Experimental
The reactions of 1 with carbon monoxide were carried out accord-
ing to the general procedure reported previously.13 A stirred solution
of 1 is exposed to CO at ca. 1013 mbar at the working temperature
until absorption is complete. The reaction mixture was treated with
a saturated aqueous solution of NH4Cl (to obtain 2) or with 50 mL
of acetic anhydride (to prepare 8). Quantitative analysis of the com-
pounds was carried out by GC.