Journal of Molecular Catalysis, 48 (1988) 69 - 79 69

MECHANISTIC STUDIES ON PALLADIUM-CATALYZED DOUBLE CARBONYLATION OF ARYL IODIDES AFFORDING o-KETO ESTERS

HIROSHI YAMASHITA, TOSHIYASU SAKAKURA, TOSHI-AK1 KOBAYASHI and MASATO TANAKA*

National Chemical Laboratory for Industry, Tsukuba, Zbaraki 305 (Japan)

(Received June 5,1987; accepted May 17,1988)

Summary

In relation to the mechanism of palladium-catalyzed carbonylation of aryl iodides to give a-keto esters, the carbonylation reactivity of some palladium complexes such as RPdILz (I: R = C6H5, L = P(C,H,)s; II: R = &,H,CO, L = P(C,Hs)s) and C6HsCOPd[P(C&15)3]2(C104)~acetone (III) was investigated. In the carbonylation reaction in the presence of alcohols and t-amines, both complexes I and II exhibited the same reactivities. Complex II gave higher selectivities for a-keto esters when solvents of lower dielectric constant and lower donor number were used. The perchlorate complex III, which underwent double carbonylation with a high selectivity when treated with diethylamine and carbon monoxide, mainly gave simple esters in reactions with alcohols under carbon monoxide. The use of an alcohol in conjunction with a t-amine in the reaction of complex II could afford an a-keto ester, while the use of alkoxide resulted in exclusive forma- tion of a simple ester. Heating of complex II with iodobenzene under carbon monoxide gave benzoyl iodide. These results are discussed in relation to the mechanism of catalytic double carbonylation.

Introduction

Recently, interest in the effective use of carbon monoxide has been directed toward not only large scale processes such as 0x0 reactions and CO reductions, but also the synthesis of fine chemicals. We [ 1 - 41 and other groups [5 - 81 previously reported new double carbonylation reactions using palladium catalysts, via which aryl halides were converted into various (Y- keto acid derivatives in one step (eqn. (1)).

PdCl,L2 cat ArX + 2C0 + HNu - ArCOCONu (+ ArCONu) (1)

-base. HX (Nu = NR?, NHR, OR, OH)

*Author to whom correspondence should be addressed.

0304-5102/88/$3.50 0 Elsevier Sequoia/Printed in The Netherlands

70

HX (e) (d)

Schemel.

The catalytic cycle of palladium complex-catalyzed carbonylation of aryl halides to give double and/or mono carbonylated products is assumed to consist of several elemental processes, as shown in Scheme 1 [6, 9 - 111. In the a-keto amide synthesis, simple amides or a-keto amides are proposed to be formed respectively via path (b) or (c) + (e) [ 61. In a preliminary communication on the a-keto ester synthesis, we have pointed out the importance of steric factors of the ligands and alcohols which affected selec- tivity for the double carbonylation [ 31. Further studies have revealed that the steric factor of t-amines used for hydrogen halide trapping and the nature of the solvents also play major roles in determining the selectivity. The effects of these factors are not necessarily the same as those in cx-keto amide synthesis, and the mechanism of a-keto ester formation remains unexplained [12]. The aim of the present paper is to give a mechanistic perspective to this reaction by examining the reactivities of the palladium complexes which are relevant to the catalysis.*

Results and discussion

Comparison of the reactivities of C,HsPdI[P(C6H,)3]2 (I) and C6H5COPdI- [P(GH,), 12 (II)

With the purpose of examining the possibility of path (b) (Scheme l), the reactivity of I was compared with that of II in reactions with methanol or 2-propanol in the presence of t-amines under carbon monoxide.

As shown in Table 1, complexes I and II exhibited almost the same selectivity of the a-keto ester for each alcohol-amine system. In addition, investigation of the time dependence of the reaction of complex I with methanol revealed that selectivity for the a-keto ester remained nearly

*Preliminary results havebeen published [13].

71

TABLE 1

Reactions of RPdI[P(CeHs)3]2 (I: R = C&s; II: R = C&I&O) with alcohols in the pres- ence of tertiary amines under carbon monoxidea

Run Alcohol

(ROH)

Amine Complex Time Yieldb Selectivity for (min) (%) C$IsCOC02RC (%)

1 methanol 2 methanol 3 2-propanol 4 2-propanol 5 2-propanol 6 2-propanol 7 2-propanol 8 2-propanol 9* 2-propanol

lo* 2-propanol

triethylamine I II

triethylamine I II

N-methylpyrrolidine I II

tripropylamine I II

triethylamine I II

30 49 49 30 49 51 75 29 92 75 28 94 40 27 90 40 23 91

120 14 92 120 14 93

30 32 34 30 31 35

aReaction condition: complex 0.03 mmol, alcohol 2 mmol, amine 2 mmol, benzene 2 ml, CO 40 atm, 60 “C. bYield of CsHsCOC02R + C&COzR. =Selectivity = C&COC0~R/(C&sCOCO~R + C&IsCOzR) x 100. *DMF was used as solvent in place of benzene.

Time (h)

Fig. 1. Time dependence of the reaction of C&IsPdI[P(C&)& (I) with methanol ~~~ the in presence of triethylamine under 55 atm of carbon monoxide. 0: yield of C&COCO&Hs; A: yield of C&IsCOzCHs; 0: selectivity for C.&C!OC02CH~.

constant from the beginning (Fig. 1). Furthermore, the yield of the ester continued to increase long after the very initial period during which starting complex I would have been transformed into the benzoyl complex.

In the cy-keto amide synthesis, the formation of a simple amide as a side product is ascribed to the intervention of the path (b) to some extent [6]. However, the results shown in Table 1 and Fig. 1 indicate that the path (b) is not responsible for the formation of a simple ester under the condi- tions of double carbonylation. Similar conclusions have also been drawn through a different approach by Milstein [14]. It may be safely concluded that both ester and a-keto ester must come from a benzoyl-palladium species like complex II.

12

TABLE 2

Reactions of C&15COPdI[P(C&5),]2 (II) with alcohols in the presence of additional triphenylphosphine under carbon monoxidea

Alcohol (ROH)

Additional Time Yield (%) Selectivity for P(C6l-G (h)

CdI5CO2R C&5COCO2R C&15COC0,Rb (%)

(mmol)

methanol 0 3 44 30 41 methanol 0.03 3 9 23 72 2-propanol 0 6 6 42 88 2-propanol 0.03 6 1 13 93

aReaction conditions: complex 0.015 mmol, alcohol 1 mmol, triethylamine 1 mmol, benzene 1 ml, CO 30 atm, 60 “C. bSee footnote c, Table 1.

Effect of phosphine addition on the reaction of C6H,COPdI[P(C,H,),], (II) In the catalytic double carbonylation of iodobenzene, the presence of

phosphines in excess, i.e., phosphine/Pd > 2, favored a higher selectivity [ 121. Similarly, addition of triphenylphosphine to the carbonylation reaction of complex II with methanol or 2-propanol enhanced the selectivity (Table 2). Interestingly, formation of both ester and the o-keto ester was suppressed by the addition of phosphine; the former was more strongly suppressed than the latter. Although still speculative, the results are compatible with the prerequisite dissociation of a phosphine molecule during formation of the ester (eqn. (2)).

C,HSCOPdILZ + ROH

C,H,COPdIL NR, - C6H,C0,R (2) 3

Effect of solvents on the reactions of C6H,COPdI[P(C6H,),], (II) with alcohols under carbon monoxide

The nature of the solvent is one of the important factors in controlling the selectivity in o-keto ester synthesis [ 7, 121. In the catalytic reactions of iodobenzene with 2-propanol, the selectivity for the double carbonylation decreased with increasing the donor number (DN) of the solvents, which has been proposed by Gutman [15] as a measure of the capability of solvents to stabilize cationic species. As illustrated in Fig. 2, the same trend was also proved true in the reaction of complex II under nearly the same conditions as those in the catalytic reactions.

In reactions of the analogous benzoyl-palladium complex with diethyl- amine, solvents of higher dielectric constant are reported to favor the cx-keto amide formation [6, lo]. This solvent effect has been reasonably explained by considering cationic species such as [CJ!IsCOPd(CO)(PR,),]’ as the key intermediate for double carbonylation. However, one can easily recognize exactly the opposite trend when the solvent effect on the a-keto ester

73

20. 0 10 20 30

Donicity number

Fig. 2. Solvent effect on the reactions of C&COPdI[P(C&)& (II) with alcohols in the presence of triethylamine under 35 atm of carbon monoxide. 0: 2-propanol; 0: methanol.

TABLE 3

Reactions of C&&OPdI[P(C,&)& (II) with alcohols in the presence of triethylamine under carbon monoxidea

Alcohol (ROW

Solvent E Yield (%) Selectivity for

CeHsCOzR C&COC02R C&COC02Rb (%)

2-propanol dichloromethane 8.9 4 45 93 2-propanol acetone 20.7 18 40 69 2-propanol DMF 36.7 38 28 43 2-propanol DMSO 46.7 53 19 27 methanol dichloromethane 8.9 21 58 73 methanol acetone 20.7 35 54 61

aReaction condition: complex 0.015 mmol, alcohol 6.0 mmol, triethylamine 3.5 mmol, solvent 1 ml, CO 35 atm, 60 “C, 30 min. bSee footnote c, Table 1.

synthesis is reconsidered in terms of dielectric constant. Table 3 summarizes the reactions of complex II with alcohols. Solvents with higher dielectric constants gave more ester and less cx-keto ester. As a result, the selectivity decreased with increasing dielectric constant.

Reactions of C6H,COPd [P(C,H,),] ,(ClO,)-acetone (III) Solvents of high dielectric constant are considered to facilitate the dis-

sociation of the iodine atom from the benzoyl-palladium complex, and solvents of high DN stabilize the resulting cation through solvation. There- fore, the observed solvent effect (uide supra) appears to indicate the undesirable intermediacy of solvent-separated cationic palladium species for the cr-keto ester formation, The following experiments are consistent with this explanation.

As shown in Fig. 3, the benzoyl-palladium perchlorate complex (III), when treated with 20 atm carbon monoxide in dichloromethane, was con- verted into the cationic complex, [C6H5COPd(CO){P(C,H,)}~]+ as deter-

I-

O I

2000 -1 1 cm

50 IO

Fig. 3. IR spectrum of C&IH,COPd[P(C&IH,)s]~(CIO ) 4 *acetone (III) under 20 atm of carbon monoxide in dichloromethane at 25 “C.

mined from the appearance of a new IR band at about 2135 cm-’ due to the coordinated CO*. To this high pressure system, we injected the nucleophile, diethylamine or alcohols in conjunction with triethylamine, through a high pressure injection pump. The results (Table 4) are strikingly different, depending on the nucleophile. Injection of diethylamine gave mainly the cr-keto amide with a small amount of amide. On the other hand, when the alcohol-triethylamine couples were injected, the main products were the esters, the monocarbonylation products. The selectivity for the double carbonylation was as low as 9%, which was much lower than 93% (for 2-propanol) and 73% (for methanol) observed when starting with the neutral benzoyl-palladium iodide complex (Table 3).

TABLE 4

Reactions of C&IsCOPd[P(C&)s]~(ClO ) 4 -acetone (III) with diethylamine or alcohols in the presence of triethylamine under carbon monoxidea

Nucleophile (NuH)

Yield (%)

C&CONu CJ-IsCOCONu

Selectivity for C&COCONub (%)

diethylamine 3 61 95 2-propanol 48 5 9 methanol 81 8 9

aReaction conditions were same as those shown in Table 3. bSee footnote c, Table 1.

*The conversion of C&IsCOPd[P(CHs)(C&I&]~(ClO~) into [C&&OPd(CO)- {P(CHa)(C&)&r has been well established [6, lo].

75

Effect of alcohol acidity and comparison of the reactivity of alcohols with that of alkoxide toward C6H5COPdI[P(C6H5)3]2 (II)

A second possibility which can be deduced from the solvent effect is that formation and participation of an alkoxide under the catalytic condi- tions may also be undesirable for the cy-keto ester formation. The following experiments, the results of which are summarized in Table 5, rationalize this possibility*.

TABLE 5

Reactions of C&I&OPdI[P(CeH&]~ (II) with alcohols or alkoxide under carbon mon- oxidea

Run Alcohol (ROH) or CO Temp. Yield (%) Selectivity for alkoxide (atm) (“C) C&COzR C&,COC02R

C&COC02Rb (%)

1C ethanol 10 40 75 16 18 2c 2,2,2-trifluoroethanol 10 40 95 0 0 3d 2-propsnol 30 70 12 7 37 4e sodium 2-propoxide 30 70 60 0 0

Womplex used was 0.03 mmol. bSee Table 1 c. CAlcohol 6 mmol, triethylamine 3 mmol, acetonitrile 1.5 ml, 1 h. d2-Propanol 1 ml, trietbylamine 0.05 mmol, 55 h. e2-Propanol 1 ml, sodium 2-propoxide 0.05 mmol, 1 b.

In the first set of experiments, we compared the performance of ethanol and 2,2,2-trifluoroethanol in the carbonylation reaction with complex II in the presence of triethylamine. The former gave us the cx-keto ester, although in a low yield. However, the latter, which is more acidic and more readily forms the alkoxide anion, afforded only the ester; double carbonylation did not take place at all. Consistent with these observations is the comparison of the performance of 2-propanol in the presence of triethyl- amine with that of sodium 2-propoxide in analogous reactions. The car- bonylation of complex II in the presence of 2-propanol and triethylamine gave some double carbonylation product, while very fast and exclusive formation of the ester took place when the complex was carbonylated with sodium 2-propoxide.

Formation of C6H,COI from C6H,COPdI[P(C,H,),], (II) An entirely different path for the formation of esters could exist via

the intermediacy of benzoyl iodide. To verify this possibility, we treated complex II with carbon monoxide (100 atm) and excess iodobenzene in benzene solvent at 120 “C without adding any base. The resulting solution,

*Participation of alkoxide anions in ester formation in the palladium complex- catalyzed carbonylation has been suggested [16].

76

obtained after heating for 24 h, exhibited an IR band at -1760 cm-’ which was assigned to benzoyl iodide (eqn. (3)).

C,H,COPdI[P(C6H5)3]2 + C,H,I + CO 3 C,H,COI

(excess) 100 atm 1760 cm-’

1) Degas > C6H5COOC2H,

2) OH-N(CzHs)3 - 200%/Pd (3)

Carbon monoxide was carefully expelled and ethanol-triethylamine mixture added to the system. After these procedures, the amount of ethyl benzoate (therefore, of benzoyl iodide) was estimated by gas chromatography at -200% based on complex II. Even though the turnover is low, the result clearly shows that benzoyl iodide formation from complex II can actually take place. The low turnover under the present conditions is presumably due to the higher reactivity of the product (benzoyl iodide) than of iodobenzene toward the resulting palladium(O) complex, In our view, this process can occur more readily under catalytic conditions where a t-amine and an alcohol are available for converting the benzoyl iodide product into the corresponding ester, which is not reactive toward the palladium catalyst molecule.

Mechanism of double carbonylation of aryl iodides affording esters and a-keto esters

The results obtained in the present paper and in the catalytic reactions [ 121 are consistent with the equations for the formation of esters and a-keto esters outlined in Scheme 2. Since monocarbonylation was promoted in the system which facilitates the formation of alkoxy anion, it is plausible that alkoxy anions participate in path (a). With regard to the a-keto ester forma- tion (path (c)), although aroylcarbonyl-palladium species is considered

(IV)

Scheme 2.

77

the precursor of IV, neither the coordination states of phosphine, CO and iodine atom nor their geometries are definite at present. But cationic aroyl- carbonyl-palladium species generated from III, which was certainly of solvent-separated form, was very unfavorable for cr-keto ester formation. In our view, the key intermediate for the formation of IV must have the iodine atom in close proximity to the palladium center, The formation of cx-keto esters would be associated with a non-ionic or contact ion-paired cationic aroylcarbonyl-palladium intermediate.

Experimental

Infrared spectra were recorded on a Jasco A-302 or a Shimadzu IR-408 spectrometer. Mass spectral determinations were made using a Shimadzu QP-1000 (70 eV) GC-MS spectrometer. Microanalyses were performed by the Institute of Physical and Chemical Research, Japan.

Solvents, alcohols and amines were dried by standard methods and distilled under nitrogen. C6H,PdI[P(C6H5)3]2 (I) [ 171 and CJI,COPdI-

P(WU,I, (11) WI were prepared by the literature methods. C,H&OPd- [P(C&15)3]2(C104).acetone (III) was prepared by the method similar to that reported previously [lo]: m.p. 110 - 118 “C (dec.); Anal. Calcd for C&H4,C106P,Pd: C, 61.83; H, 4.62%. Found: C, 61.77; H, 4.52%.

All the reaction products were identified by comparison of GC reten- tion times with those of authentic samples and/or by analysis of mass frag- mentation patterns of the products. The amount of the products was esti- mated by GC using internal standards.

Reaction of RPdI[P(C6H5)3]2 (I: R = C,H,; II: R = C6H,CO) with alcohols in the presence of tertiary amine under carbon monoxide (Table 1)

A small glass vessel containing complex I or II (0.03 mmol) was placed in an autoclave. The alcohol (2 mmol), tertiary amine (2 mmol) and solvent (2 ml) were carefully charged into the autoclave under nitrogen so as not to let them touch the complex. The autoclave was set in an oil bath adjusted to 60 “C. After 15 min, 40 atm of carbon monoxide was introduced, and the contents were vigorously mixed to start the reaction. The mixture was stirred for the period specified in Table 1. Then the autoclave was im- mediately cooled in an ice bath. Carbon monoxide was discharged and the products were analyzed by GC.

Time dependence of the reaction of C6H5PdI[P(C6H5)3]2 (I) with methanol in the presence of triethylamine under carbon monoxide (Fig. 1)

To complex I (0.15 mmol) placed in an autoclave equipped with a sampling outlet, benzene (8 ml), methanol (10 mmol) and triethylamine (10 mmol) were added under nitrogen. The mixture was stirred at 60 “C for 15 min, and 55 atm of carbon monoxide was introduced. A small portion

78

of the solution was periodically taken out through the sampling outlet for product analysis.

Reactions of C6H,COPdI[P(C6H,),], (II) with nucleophiles under carbon monoxide (Tables 2 and 5)

To complex II (0.015 mmol) with or without additional triphenyl- phosphine (0.03 mmol) placed in an autoclave, benzene (1 ml), alcohol (1 mmol) and triethylamine (1 mmol) were added at room temperature under nitrogen, and 30 atm of carbon monoxide was introduced. The reac- tions were conducted under the conditions specified in Table 2. For the reac- tions in Table 5, reactants were mixed at -20 “C under carbon monoxide and stirred under the specified conditions.

Reactions of C6H,COPdI[P(C,H,),], (II) or C6H5COPd[P(C,H,)3]2(C104)- acetone (III) with alcohols in the presence of triethylamine under carbon monoxide (Tables 3 and 4)

To complex II or III (0.015 mmol) placed in an autoclave, solvent (1 ml) was added under nitrogen, and 35 atm of carbon monoxide was introduced. After the solution was stirred at room temperature for 30 min, a mixture of alcohol (5 mmol) and triethylamine (3.5 mmol) was injected into the autoclave through a micro high pressure pump, and the resulting mixture stirred at 60 “C for 30 min.

Reaction of iodobenzene with carbon monoxide in the presence of GH, COPdI]P(CsHs Al 2 (14

To complex II (0.03 mmol) placed in an autoclave, benzene (1 ml) and iodobenzene (6 mmol) were added under nitrogen, and 100 atm of carbon monoxide was introduced. After the solution was stirred at 120 “C for 24 h, the autoclave was cooled in an ice bath, and carbon monoxide was discharged. The IR spectra of the reaction mixture showed an absorption at -1760 cm-l assignable to the acyl group of benzoyl iodide. A portion of the mixture (0.3 ml) was degassed by the freeze-thaw technique. Ethanol (0.3 ml) and triethylamine (0.3 ml) were added, and the resulting mixture was stirred overnight. GC analysis showed the formation of ethyl benzoate in a yield of -200% based on II.

References

1 T. Kobayashi and M. Tanaka, J. Organometall. Chem., 233 (1982) C64. 2 Jpn. Pat. Kokai 84185548 (1984) to T. Kobayashi and M. Tanaka; U.S. Pat.

4 503 232 (1985) to the Agency of Industrial Science and Technology, Japan. 3 M. Tanaka, T. Kobayashi, T. Sakakura, I. Itatani, S. Danno and K. Zushi, J. Mol.

Catal., 32 (1985) 115. 4 M. Tanaka, T. Kobayashi and T. Sakakura, J. Chem. SOL, Chem. Commun., (1985)

837. 5 F. Ozawa, H. Soyama, T. Yamamoto and A. Yamamoto, Tetrahedron Lett., 23

(1982) 3383.

79

6 F. Ozawa, H. Soyama, H. Yanagihara, I. Aoyama, H. Takino, K. Izawa, T. Yamamoto and A. Yamamoto, J. Am. Chem. Sot., 107 (1985) 3235.

7 F. Ozawa, N. Kawasaki, T. Yamamoto and A. Yamamoto, Chem. Lett., (1985) 567. 8 B. Morin, A. Hirschauer, F. Hugues, D. Commereuc and Y. Chauvin, J. Mol. Cotal.,

34 (1986) 317. 9 J.-T. Chen and A. Sen, J. Am. Chem. Sot., 106 (1984) 1506.

10 F. Ozawa, T. Sugimoto, Y. Yuasa, M. Santra, T. Yamamoto and A. Yamamoto, Organometallics, 3 (1984) 683.

11 F. Ozawa, T. Sugimoto, T. Yamamoto and A. Yamamoto, Organometollics, 3 (1984) 692.

12 T. Sakakura, H. Yamashita, T. Kobayashi, T. Hayashi and M. Tanaka, J. Org. Chem., 52 (1987) 5733.

13 H. Yamashita, T. Kobayashi, T. Sakakura and M. Tanaka, J. Mol. Catal., 40 (1987) 333.

14 D. Milstein,J. Chem. Sot., Chem. Commun., (1986) 817. 15 V. Gutman, The Donor-Acceptor Approach to Molecular Interaction, Plenum,

New York, 1978. 16 M. Hidai, T. Hikita, Y. Wada, Y. Fujikura and Y. Uchida, Bull. Chem. Sot. Jpn., 48

(1975) 2075. 17 P. Fitton, M. P. Johnson and J. E. Mckeon, J. Chem. Sot., Chem. Commun., (1968) 6. 18 P. E. Garrou and R. F. Heck, J. Am. Chem. Sot., 98 (1976) 4115.