Preparation of 1,3-diketones by the reaction of bis(iodozincio)methene with acyl cyanides or palladium-catalyzed reaction with acyl chlorides

Article abstract of DOI:10.1055/s-1998-1647

Bis(iodozincio)methane, prepared from lead-catalyzed reaction of zinc with diiodomethane, afforded 1,3-diketones either by the reaction with acyl cyanides or by palladium catalyzed reaction with acyl chlorides. Reaction with adipoyl dichloride gave cyclic enol ester by intramolecular reaction.

Full text of DOI:10.1055/s-1998-1647

March 1998
SYNLETT
267
Preparation of 1,3-Diketones by the Reaction of Bis(iodozincio)methene with Acyl Cyanides
or Palladium-Catalyzed Reaction with Acyl Chlorides
Seijiro Matsubara, Kazunari Kawamoto, and Kiitiro Utimoto*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Yoshida, Sakyo, Kyoto 606-8501, Japan
FAX +81 (0)75 7534863; e-mail utimoto@orgrx2.kuic.kyoto-u.ac.jp
Received 18 December 1997
Abstract: Bis(iodozincio)methane, prepared from lead-catalyzed
reaction of zinc with diiodomethane, afforded 1,3-diketones either by
the reaction with acyl cyanides or by palladium catalyzed reaction with
acyl chlorides. Reaction with adipoyl dichloride gave cyclic enol ester
by intramolecular reaction.
gem-Dimetallic reagents have been used as versatile reagents in organic
1
synthesis. Recent preparation of bis(iodozincio)methane (1) in high
purity has opened novel strategies of C-C bond formation including
carbonyl-olefination and three component coupling by stepwise reaction
2–4
of two different electrophiles. It is conceivable that double acylation
of 1 provides a new entry to 1,3-diketones, but double acylation of
dimetallic reagents containing Cu and Zn gave enol ester by O-acylation
5
at the second step.
Reaction of 1 with benzoyl chloride (6; R = Ph) gave 4-chlorobutyl
benzoate (7; n = 1) as a major product; zinc salt-catalyzed reaction of
Scheme 1
acyl chlorides 6 with THF proceeded mainly. Coupling reaction under
As we have found that 1 reacted with various electrophiles under Pd
Pd catalysis proceeded smoothly yielding 1,3-diketone. Ligand tuning
2
catalysis, reaction of 1 with two acyl groups was examined. This paper
was necessary to obtain satisfactory results, although PPh gave the
3
describes two procedures of double acylation on 1 affording 1,3-
diketones 3; reaction with acyl cyanides 2 in THF and reaction with acyl
chlorides 6 in THF-DMI under Pd catalysis.
expected 1,3-diketone 3 in good yield. As can be seen from the results
shown in Table 2, P(C H -OMe-p) gave better results. Use of 1:1
6
4
3
mixture of THF-DMI depressed the formation of by-product 7 and
9
Reaction of benzoyl cyanide (2, R = Ph; 2 mmol) with 1 (1 mmol)
afforded 1,3-diphenyl-1,3-propanedione (3, R = Ph) in 44% yield. Yield
of the diketone 3 was improved to 90% by the reaction of 1 with 2 in a
molar ratio of 1 : 1, but reaction of 1 with 2 in a molar ratio of 1.5 : 2
afforded 3 exclusively in 89% yield. Reaction using a bulky phosphine
as a ligand proceeded sluggishly affording 7 mainly. Bidentate ligand
also afforded an unsatisfactory result.
6,7
gave 3 in 59% yield. Combination of reagents ratio and the yield of 3
can be explained by equation 2; reaction of
1 2
with gave
zinciomethylated product 4, which reacted with 2 affording 1,3-
diketone 3. Intermediary produced 3 reacted with dimetallic reagent 1 to
produce stable zinc enolate
5
and methylzinc iodide. As any
considerable formation of acetophenone could not be detected from the
reaction mixture, reactivity of acyl cyanides 2 towards intermediary 4 is
much higher than that towards any other nucleophiles in the reaction
mixture; relative order of reactivity towards 2 is 4 >> 1 > methylzinc
iodide. Other acyl cyanides 2 afforded the corresponding 1,3-diketones
Scheme 3
In contrast to the reaction with benzoyl chloride (6; R = Ph), nonanoyl
chloride (6; R = C H ) gave a mixture of 1,3-diketone (3; R = n-
8
3. Results are summarized in Table 1.
8
17
C H ), 4-chlorobutyl ester 7, and O-acylated product 8. The best yield
8
17
of 1,3-diketone 3 was recorded using P(C H -OMe-p) as a ligand and a
6
4
3
mixture of THF-DMI (1:1) as solvent at –15 °C.
Contrary to the above intermolecular reaction, reaction of 1 with adipoyl
dichloride (9) under Pd catalysis in THF-DMI gave cyclic enol ester 10
3,10
in 75% yield by intramolecular O-acylation of intermediary 11.
Mechanistic studies on selective O-acylation in intramolecular reaction
are underway.
Thus symmetrical 1,3-diketones can be produced from dimetallic
reagent 1 and acylating agents, acyl cyanides 2 or acyl chlorides 6, by
single operation.
Scheme 2

268
LETTERS
SYNLETT
References and Notes
(1) Marek, I.; Normant, J. F. Chem. Rev. 1996, 96, 3241.
(2) Utimoto, K.; Toda, N.; Mizuno. T.; Kobara, M.; Matsubara, S.
Angew, Chem.1997, 109, 2886.
(3) Takai, K.; Kakiuchi, T.; Kataoka, Y.; Utimoto, K. J. Org. Chem.
1994, 59, 2668.
(4) Eisch, J. J.; Piotuwski, A. Tetrahedron Lett. 1983, 24, 2043.
(5) Knochel, P.; Normant, J. F. Tetrahedron Lett. 1986, 27, 4427.
(6) Typical procedure for the production of bis(iodozincio)methane
(1): A THF solution of bis(iodozincio)methane (1) was prepared
according to the reported procedure with slight modification. A
mixture of acid-washed and dried zinc powder (Wako Pure
Chemical Industries Ltd. Japan, containing 0.04–0.07 mol % of
lead; 12.3 g, 188 mmol) and THF (7.5 mL) was added with CH I
2 2
(2.0 g, 7.5 mmol) and sonicated for 15 min. THF (50 mL) was
added to the mixture, and then the mixture was cooled in a ice-
water bath. To the mixture, a THF (15 mL) solution of CH I
2 2
(20.1 g, 75 mmol) was added over 1 h. The reaction mixture was
stirred for 1 h at 0 °C, then 1 h at room temperature. Yield of
1
bis(iodozincio)methane (1) was determined by H NMR using
2,2,3,3-tetramethylbutane as internal standard. Average yield of
bis(iodozincio)methane (1) was 60%. Bis(iodozincio)methane (1)
was also obtained in 50–60% yield by using a mixture of zinc
powder (Merck Co. or Aldrich Chemical Co.) and 0.5–1 mol % of
PbCl , in place of Wako zinc.
2
(7) Reaction of bis(iodozincio)methane (1) with acyl cyanide 2: To a
THF solution of 1 (3.6 mL of 0.55 M solution containing 2.0
mmol of 1), a THF (7.0 mL) solution of benzoyl cyanide (2, R =
Ph; 262 mg, 2.0 mmol) was added at room temperature. After
being stirred for 2 h at room temperature, the reaction mixture was
added with 20 mL of 1 M aq. HCl. The mixture was extracted
twice with ethyl acetate, then combined organic layer was washed,
dried, concentrated, and purified by column chromatography.
Dibenzoylmethane (3, R = Ph) was obtained in 90% yield.
(8) Reaction of 1 with α,β-unsaturated acyl cyanide (2; R =
PhCH=CH) proceeded both acylation and Michael addition (entry
8 in Table 1). Michael addition (or conjugated addition) of 1 to
α,β-unsaturated carbonyl compounds will be published in a
separate paper.
Scheme 4
(9) To a DMI (10 mL) solution of Pd (dba) •CHCl (0.05 mmol) and
2
3
3
P(C H -OMe-p) (0.4 mmol), a THF solution of 1 (3.6 mL of 0.55
6
4
3
M solution containing 2.0 mmol of 1) was added. A THF solution
(6 mL) of 6 (R = Ph, 263 mg, 2.0 mmol) was added dropwise to
the reaction mixture maintained at –15 °C. After being stirred for
2 h, the reaction mixture was worked up as described above.
(10) A DMI-THF solution containing catalyst and 1 was prepared as
described above. To the solution, a THF solution of adipoyl
dichloride (9, 183 mg, 2.0 mmol in 10 mL THF) was added
dropwise at –10 °C. The reaction mixture was stirred for 1 h, then
quenched by adding 20 mL of ethyl acetate and 1.0 g of NH Cl
4
powder. Product 10 was purified by distillation and
chromatography.
Acknowledgement: This work is supported by the Ministry of
Education, Science, Sports, and Culture (Grant in Aid #09231223,
#09238221).