Astruc D. - Modern arene chemistry (2002)(en)

14.4 Other Reagents for the Oxidative Coupling Reaction 503

Tab. 22. Oxidative cyclization of benzil derivatives mediated by several oxidants.

99	R	Reagent/solvent	Yield 100 (%)
a	OCH3	VOF3/CH2Cl2	23
a	OCH3	VOF3/(Cl2CH)2	88
b	O-iC5H11	VOF3/CH2Cl2	82
c	OC6H13	VOF3/CH2Cl2	86
d	OC10H21	VOF3/CH2Cl2	91
d	OC10H21	Tl2O3/CH2Cl2	36
d	OC10H21	Pd(OAc)2/AcOH	0

Scheme 24. The synthesis of tylophorine by vanadium(V)-mediated oxidative cyclization of septicine.

Scheme 25. Oxidative coupling of a protected tyrosine substrate promoted by vanadium(V) reagents.

A/B (206a/b, Scheme 51) and alkaloids such as murrastifoline F (108), the results of Bringmann and co-workers emphasize the fact that the various oxidants are not interchangeable [77]. Thus, an interesting Pb(IV)-mediated homocoupling of the O-protected alkaloid murrayafoline A (107) provided murrastifoline F (108) in 60 % yield. Other oxidants (PIFA, VOF3) failed in this reaction (Scheme 26).

Feldman and co-workers used lead tetraacetate to generate the biaryl products 110a,b in a preparative study of the coupling reaction of methyl gallates 109a,b, respectively, for the synthesis of members of the ellagitannin family (Scheme 27) [78]. The outcome of this reaction is strongly influenced by the substitution pattern on the ring. In the case of the sim-

504 14 Oxidative Aryl-Coupling Reactions in Synthesis

Scheme 26. The synthesis of murrastifoline by lead(IV)-mediated oxidative dimerization of murrayafoline.

Scheme 27. Lead(IV)-mediated oxidative dimerization of gallic acid derivatives.

ple methyl ether-protected gallate derivative 109c, the product of the reaction is a quinone ketal 111 (Scheme 28). The bulkier protecting groups in 109a,b favor nucleophilic attack on a putative ‘‘phenoxonium ion’’ intermediate from another aryl unit rather than acetate trapping.

Scheme 28. Lead(IV)-mediated oxidation (Wessely reaction) of a simple gallic acid derivative without biaryl formation.

14.4.3

Copper(II)

Copper/amine complex-mediated oxidative coupling has received a lot of attention, especially in the binaphthol field after the work of Brussee [79, 80] and Feringa [81]. This reagent combination permits high yielding, clean, and regioselective oxidative homocoupling of many 2-naphthol derivatives. Cross-coupling reactions can also be performed.

Few examples of cross-coupling between di erently substituted 2-naphthols were known when Hovorka and co-workers investigated this reaction in more detail. Anaerobic condi-

14.4 Other Reagents for the Oxidative Coupling Reaction 505

Tab. 23. Copper(II)/amine-mediated cross-coupling of variously substituted 2-naphthol derivatives.

Substrates

T ( C)

t (min.)

Yield (%)

Selectivity 69 (%)

68a/68f	50	30	97	f-f (5)
68f/68j	41	120	93	f-f (12)
68f/68i	50	110	95	f-f (5)
68f/68g	23	5	85	f-f (5)
68f/68h	23	120	80	f-f (5)
68a/68i	23	1440	80	a-a (25)

f-a (91) f-j (88) f-i (92) f-g (89) f-h (81) a-i (48)

a-a (4) j-j (0) i-i (3) g-g (6) h-h (14) i-i (27)

tions and the use of tert-butylamine or ethylamine in methanol allowed good selectivities for the unsymmetrical compounds (Table 23) [82].

These authors speculated that this high selectivity in favor of the cross-coupling product stemmed from the preferential formation of an intermediate radical from the electron-rich component [83, 84]. This radical would then react with the anion derived from the more electron-deficient species. Coupling between partners having similar electron density (e.g. 68a and 68i) resulted only in a statistical ratio of products. These authors also showed that the amine base could be substituted by NaOMe without a ecting the reactivity or the regioselectivity. A significant observation from this work was that either the conditions are suitable and the reaction is fast and gives mainly the cross-coupling product, or the reaction is slow and gives mixtures of homoand hetero-coupling products.

Research by Vyskocil and co-workers extended the naphthol cross-coupling reaction to mixtures of 2-naphthols and naphthylamines (Scheme 29) [85, 86]. In general, good selectivity in favor of cross-coupling over homo-coupling was observed.

Scheme 29. Selective cross-coupling of 2-naphthol (68a) and 2- naphthylamine (70a) mediated by copper(II) and an amine base.

In a comprehensive study of these cross-coupling reactions with 2-naphthol derivatives, and as a response to Ding’s advances on the same transformation using iron reagents [57], Vyskocil and co-workers presented a rational explanation for the outcomes of the di erent

50614 Oxidative Aryl-Coupling Reactions in Synthesis

reactions [58, 59]. The ease of oxidation of each molecule is the deciding factor. In general, 68f, which is least prone to generate a radical cation by one-electron oxidation, acts as an acceptor towards the intermediate radical cation formed from either 68a, 70a, 70b, or 70c. Similarly, simple 2-naphthol (68a) most probably participates as the radical cation component when it is combined with 70a because 68a is now the most easily oxidized species present. These considerations are related to the energy levels of the SOMO, HOMO, and LUMOs of these compounds. Examining the system from this MO perspective allows rationalization of the outcome of the reaction.

In a very recent paper, Vyskocil and co-workers focused on the homocoupling of aryl amines (Scheme 30) [87]. Although these electron-rich units were expected to follow the same reactivity patterns as their oxygenated counterparts, notable di erences in the product distributions were seen. For example, formation of carbazoles 113a–c, 116, 121, 123, 125 was observed from oxidative coupling of naphthylamines 70a–c, 114, 119, 122, and 124, respectively (Scheme 30 and Table 24).

Scheme 30. Survey of copper(II)/amine-mediated oxidative dimerizations of various aryl amines.

14.4 Other Reagents for the Oxidative Coupling Reaction 507

Tab. 24. Product distributions from the copper(II)/amine-mediated oxidative dimerizations of the aryl amines indicated above.

Substrate	Diamine (%)	Carbazole (%)	Other (%)
70a	112a (58)	113a (@1)	–
70b	112b (26)	113b (21)	–
70c	112c (45)	113c (3)	–
114	115 (43)	116 (39)	–
117	–	–	118 (87)
119	120 (2)	121 (78)	–
122	–	123 (25)	–
124	–	125 (85)	–

The results seem to indicate that arylamines do not follow the same mechanism that presumably underlies the coupling of oxygen-substituted aryls. According to the authors, NaN dimerization (70 ! 126) is a competitive pathway that is favored with hindered substrates. This NaN coupling can eventually lead to both the CaC coupled product (path a) and the carbazole product (path b). The ratio depends upon the structure of the starting material (Scheme 31).

Scheme 31. Proposed mechanism for both carbazole and binaphthyl formation upon exposure of naphthylamine derivatives to copper(II) and an amine base.

The use of only catalytic amounts of copper reagent in this oxidative coupling has also been described. Smrcina and co-workers showed that a catalytic cycle could be sustained by using AgCl as a stoichiometric oxidant for copper (see Section 14.6.4) [88]. Nakajima and Koga have improved the turnover of the reaction by using the complex CuCl(OH) tetramethylethylenediamine (TMEDA) (1 mol %) and dioxygen as the oxidant [89]. This procedure provides a simpler and more e cient coupling reaction and a ords the binaph-

50814 Oxidative Aryl-Coupling Reactions in Synthesis

Tab. 25. Copper(II)-catalyzed oxidative dimerizations of substituted 2-naphthol derivatives.

Substrates	R1	R2	Oxidant	Time (h)	Temp.	Product	Yield (%)
68a	H	H	O2	8.5	0 C	69a	90
68h	H	CH3	O2	1	r.t.	69h	92
68i	CH3O	H	O2	1.5	r.t.	69i	96
68f	H	CO2CH3	O2	96	reflux	69f	99a
129	9-phenanthrol		O2	0.5	r.t.	130	79
68a	H	H	Air	20	0 C	69a	96
68h	H	CH3	Air	1	r.t.	69h	96
68i	CH3O	H	Air	2	r.t.	69i	95
68f	H	CO2CH3	Air	144	reflux	69f	99a
129	9-phenanthrol		Air	1.5	r.t.	130	77

a Reaction was performed in CH3OH.

thol compound in very high yield (Table 25). This protocol was later modified by removing the solvent and performing the reaction in the solid state (Table 26) [90]. Compared to oxidative coupling involving iron (Section 14.4.1) or vanadium (Section 14.4.2), this procedure o ers some advantages. The catalytic character is clearly an improvement over the iron

Tab. 26. Copper(II)-catalyzed, solid-state oxidative dimerizations of substituted 2-naphthol derivatives.

Substrates	R1	R2	R3	R4	Yield (%)
68a	H	H	H	H	92
68h	CH3	H	H	H	88
68f	CO2CH3	H	H	H	93
68b	H	H	Br	H	92
68i	H	H	H	OCH3	92
129	aCHbCHaCHbCHa		H	H	89

14.4 Other Reagents for the Oxidative Coupling Reaction 509

methods that require an excess of the reagent to drive the reaction to completion. Copperbased reagents are also less toxic than their vanadium analogues. Furthermore, the yields are more consistently high for the oxidative coupling of phenol derivatives. Nakajima et al.’s aerobic conditions (Table 26) are a simple and e cient way of creating the binaphthol unit.

14.4.4

Electrochemical Methods

In principle, electrochemistry should be an e ective method for initiating oxidative arylic coupling. It is easy to set the electrode to the right oxidation potential. However, this approach has not received a great deal of attention because of problems such as the formation of films around the electrodes that suppress the electrochemical reduction step. In 1993, Osa and co-workers published an electrocatalytic version of oxidative aromatic coupling. By using a 2,2,6,6-tetramethyl-1-piperidinyloxy- (TEMPO-) modified graphite felt, they succeeded in coupling naphthols and methyl quinolines with high conversions and high current e ciencies (Table 27) [91, 92].

Tab. 27. Electrocatalytic oxidative coupling of naphthalene and quinoline derivatives.

Substrates	Coupling	Current	Isolated yield of
		E ciency (%)	biaryl (%)
	2-20		11
87a	2-40	92	36
	4-40		44

----------------------------------------------------------------------------------------------------------------

68a 4-40 96 99

----------------------------------------------------------------------------------------------------------------

	2-20		7
87b	2-40	93	38
	4-40		50

----------------------------------------------------------------------------------------------------------------

87c	4-40	94	97
131	2-20	92	95
132	4-40	91	94

51014 Oxidative Aryl-Coupling Reactions in Synthesis

Tab. 28. Survey of oxidants for the intramolecular cyclization of stegane precursors.

Oxidant	Eq.	Time	Yield 134 (%)
RuO2 2H2O	2	18 h	98
Tl2O3	0.52	30 min	73
Mn(OAc)3 2HO2O	1.9	15 min	84
Ce(OH)4	4.8	3 h	72
V2O5	4.8	5 d	87
Re2O7	1.9	3 h	98
Fe(OH)(OAc)2	3.8	5 h	62
Co3O4	9.5	3 da	78
CF3CO2Ag	14	1 d	86
CrO3	3.8	6 d	71
Rh2O3 5H2O	4.8	14 d	39
IrO2	4.8	16 d	77
Pr2O11	11.6b	64 h	74
SeO2	5	8 h	70
TeO2	10	2 d	80
Cu(OAc)2 H2O	3.8	1 d	22

a ultrasound;

b 11.6 eq. of PrO2.

14.4.5

Other Metals

Robin and Planchenault have studied oxidation procedures for non-phenolic biaryl coupling in extensive research directed toward stegane synthesis [93, 94]. This comprehensive study explored commonly used oxidizing reagents such as thallium and vanadium, as well as other metals ranging from ruthenium to tellurium (Table 28). The authors concluded that the intramolecular oxidative coupling of stegane precursor 133 was best accomplished with either ruthenium or rhenium reagents. However, changing the substitution pattern on the aryl rings led to di erent results: methylenedioxy-protected compounds gave better results with thallium, manganese, and cerium.

Titaniumand cerium-based reagents have been used to prepare binaphthol structures [95, 96]. Jiang showed that treatment of 2-naphthol (68a) with cerium(IV) ammonium nitrate (CAN) leads to the biaryl product 69a in yields of around 90 % (Scheme 32). Crosscoupling of di erently substituted naphthols can be accomplished using the same reagents, albeit in lower yields.

14.4 Other Reagents for the Oxidative Coupling Reaction 511

Scheme 32. Cerium(IV)-mediated oxidative dimerization of 2-naphthol.

Doussot was the first to use TiCl4 to generate binaphthalene structures from naphthalene precursors. For a large number of substrates, the reaction a orded the desired compounds in good to high yields (Table 29). These last two methods feature two new reagents for performing oxidative aryl couplings. Both use a stoichiometric (or greater) amount of oxidant, although it is worth noting that the titanium method is applicable to non-oxygenated substrates (135a,b).

Methods involving palladium-mediated oxidative coupling have been explored for the combination of non-phenolic aromatic units and for benzene itself. Mukhopadhyay and coworkers have shown that in the presence of a co-catalyst, a catalytic amount of PdCl2 promotes the coupling between two benzene molecules in the presence of oxygen (air or dioxygen pressure) (Table 30) [97]. The co-catalysts and the presence of oxygen in solution prevent the formation of palladium black and aid in the regeneration of Pd2þ. Although the mechanism of this reaction is extremely complex due to the number of components employed, the authors suggest that the m-peroxocobalt(III) species 139 is formed initially, which then reacts

Tab. 29. Titanium(IV)-mediated oxidative dimerization of naphthol and naphthalene derivatives.

Substrate	TiCl4 (eq.)	Temp. ( C)	Time (h)	Product	Yield (%)
87d	2	50	0.8	88d	70
87c	2	50	1	88c	60
87e	1	20	18	88e	40
68a	1	40	4.5	69a	60
135a	1	20	48	136a	33
87f	2	20	1	88f	85
87b	1	20	18	88b	45
87a	1	20	18	–	–
135b	1	20	48	136b	30

51214 Oxidative Aryl-Coupling Reactions in Synthesis

Tab. 30. Palladium(II)-mediated dimerization of benzene in the presence of various co-catalysts.

Zr(OAc)4 (mol %)	Co(OAc)2 (mol %)	Mn(OAc)2 (mol %)	Acac (mol %)	Yield (%)
0	1.8	1.8	3.1	83
2.0	0	1.8	3.1	76
2.0	1.8	0	3.1	79
2.0	1.8	1.8	0	82
2.0	1.8	1.8	3.1	89

with palladium(0) to lead to the palladium(II)-peroxo complex 141 (Scheme 33). This complex inserts into a CaH bond of the benzene ring to furnish intermediate 142, which, after insertion into another benzene CaH to yield 143, undergoes reductive elimination to a ord the biphenyl product 138.

Scheme 33. Possible mechanistic course of the Pd(II)/Co(III)-mediated dimerization of benzene.

Reaction of methyl benzoate (144) with a palladium acetate/heteropolyacid mixture has been studied by Lee and coworkers [98]. They showed that aryl–aryl coupling occurs mainly at the 2-20 positions in the presence of various heteropolyacids (HPA; e.g. H3PMo12O40, H5PMo9V3O40, H5PMo10V2O40, etc.) (Scheme 34). The selectivity in favor of the 2-20 coupling product is between 53 and 84 %, but the conversions are low (0.48 to 6.93) due to deactivation of the catalyst. The observed selectivity can be rationalized in terms of formation of the s-palladium complex 146 with stabilization by the carbonyl group (Figure 3).

Scheme 34. Regioselective palladium(II)-mediated dimerization of methyl benzoate.