Key words copper catalyst - aryl iodides - disilathiane - carbon–sulfur bond formation - diaryl sulfides
Scheme 1 Catalytic construction of a) dibenzyl sulfides, and b) diaryl sulfides
Sulfides (thioethers), R–S–R, are an important class of structural units in organic chemistry, and a number of research groups have devoted extensive effort to the development of novel and efficient synthetic strategies for the construction of these skeletons.[1 ] Our group has reported the indium-catalyzed reductive construction of thioethers from benzoic acids,[2a ] benzaldehydes,[2a ] and benzyl alcohols[2b ] using a combination of elemental sulfur (S8 ) and hydrosilanes. In these reactions, the in situ generation of a disilathiane ([Si]2 S) from unactivated S8 and a hydrosilane is considered to be a key activation process for the formation of dibenzyl sulfides (Scheme [1, a ]). Sulfides obtained by these procedures, however, have primarily been limited to the dibenzyl variety. Also, the protocol could not undertake the formation of the corresponding diaryl alternatives in principle. To produce diaryl sulfides, the transition-metal-catalyzed double formation of a carbon–sulfur bond between two molecules of an aryl halide and an appropriate S1 source has been a reliable and efficient procedure. Various sulfur sources have been utilized for this type of diaryl sulfide synthesis: S8 ,[3 ] thiourea,[4 ] xanthogenate,[5 ] thioester,[6 ] KSCN,[7 ] Na2 S,[8 ] CS2 ,[9 ] Na2 S2 O3 ,[10 ] and K2 S.[11 ] To the best of our knowledge, the use of a disilathiane ([Si]2 S) as a S1 source for the catalytic construction of diaryl sulfides is unprecedented. Herein, we describe the copper-catalyzed, one-pot synthesis of symmetrical diaryl sulfides using a variety of aryl iodides and hexamethyldisilathiane (Scheme [1, b ]).
Table 1 Optimization of the Reaction Conditionsa
Entry
Ligand
Base
Solvent
Yield (%)b
1
none
none
NMP, 120 °C
0
2
phen
none
NMP, 120 °C
trace
3
none
K2 CO3
NMP, 120 °C
66
4
phen
K2 CO3
NMP, 120 °C
90 (92)c
5
phen
K2 CO3
NMP, 100 °C
63
6
phen
K2 CO3
NMP, 80 °C
trace
7
phen
K2 CO3
DMF, 120 °C
64d
8
phen
K2 CO3
DMSO, 120 °C
40e
9
phen
K2 CO3
toluene, 120 °C
0
a Reaction conditions: 1a (0.5 mmol), (Me3 Si)2 S (0.25 mmol), CuI (0.025 mmol), 1,10-phenanthroline (0.025 mmol), and K2 CO3 (0.5 mmol) in NMP (0.5 mL) at 120 °C for 14 h.
b GC yield.
c Isolated yield, 1 mmol scale.
d The corresponding disulfide was also generated in a 14% GC yield.
e The corresponding disulfide was also generated in a 13% GC yield.
Scheme 2 Substrate scope for aryl iodides 1 . Reagents and conditions : 1 (1 mmol), (Me3 Si)2 S (0.5 mmol), CuI (0.05 mmol), 1,10-phenanthroline (0.05 mmol), and K2 CO3 (1 mmol) in NMP (1 mL) at 120 °C for 14 h. Isolated yields of diaryl sulfides 2 are shown. a NMR yield.
Optimization of the conditions for sulfidation using iodobenzene (1a ) and (Me3 Si)2 S was initially investigated (Table [1 ]). When the reaction was performed with only a catalytic amount of CuI in N -methyl-2-pyrrolidone (NMP) as a solvent at 120 °C for 14 h, the formation of the desired sulfide 2a was not observed, as determined by GC analysis (Table [1 ], entry 1). The addition of 1,10-phenanthroline (phen) as a ligand produced a trace amount of 2a (Table [1 ]
, entry 2). Instead, the addition of a stoichiometric amount of K2 CO3 effectively increased the yield of 2a to 66% (Table [1 ], entry 3). The reaction with both the ligand and the base afforded 2a in a 90% GC yield.[12 ] Under these conditions, 92% of diphenyl sulfide (2a ) was isolated using 1 mmol of 1a (Table [1 ], entry 4). The reaction temperature was investigated to achieve milder reaction conditions, but the higher reaction temperature (120 °C) was essential to complete the conversion (Table [1 ], entries 4–6). Next, the solvents were screened. Reactions in either DMF or DMSO proceeded to form sulfide 2a in moderate yields, but the undesired disulfide, diphenyl disulfide, was simultaneously detected as a byproduct in 14% and 13% GC yields (Table [1 ], entries 7 and 8). The reaction did not proceed when using toluene as a solvent (Table [1 ], entry 9).
Copper-catalyzed production of diaryl sulfides 2 using a disilathiane was then conducted with several iodoarenes 1 (Scheme [2 ]). When the reaction of iodobenzene bearing a 4-methoxy group 1b was performed under the optimal conditions, the corresponding product 2b was obtained in a 72% isolated yield. Sulfur-containing iodoarene 1c was also converted into product 2c , and the reactions with the alkyl-substituted versions 1d –g proceeded to form the corresponding diaryl sulfides 2d –g , regardless of the position of the substituent on their benzene rings. Substrates bearing electron-withdrawing acetyl 1h , trifluoromethyl 1i , cyano 1j , and nitro 1k groups were also suitable for the sulfidation and provided products 2h –k in excellent isolated yields. When using halogen-substituted iodobenzenes such as 1-fluoro-4-iodobenzene (1l ), 1-chloro-4-iodobenzene (1m ), and 1-bromo-4-iodobenzene (1n ), each activation occurred at the carbon–iodine bond selectively over C–F, C–Cl, and C–Br bonds, giving 4-halo-diaryl sulfides 2l –n . The reaction of an iodoarene bearing a 1-naphthyl moiety 1o proceeded to give the corresponding sulfide 2o . Heteroaromatic substrates 3-iodopyridine (1p ) and 2-iodothiophene (1q ) were also applicable to the conversion to afford products 2p and 2q , respectively.
Scheme 3 Proposed mechanism for the preparation of diaryl sulfides
A plausible catalytic cycle for the present reaction is illustrated in Scheme [3 ]. The starting copper(I) inserts to the C–I bond of iodoarene 1 to afford the Ar–Cu–I species, which undergoes a ligand exchange between a disilathiane and a base. The first C–S bond formation occurs by reductive elimination and provides benzenethiol derivative 3 with a regeneration of copper(I). Again, the oxidative addition of 1 to copper(I) occurs to form an Ar–Cu–I species, followed by transmetalation between 3 and the formed Ar–Cu–I to generate an Ar–[Cu]–SAr species. Finally, the second reductive elimination of the species occurs to provide diaryl sulfide 2 .[13 ]
In summary, we described an efficient copper catalytic system for the production of diaryl sulfide using iodoarenes and a disilathiane via a double carbon–sulfur bond formation.[14 ] A variety of iodobenzene derivatives were applied to this protocol with highly functional group tolerance, which yielded the corresponding sulfides.[15 ] The results of a preliminary mechanistic study supported the plausibility of using benzenethiol as an intermediate.[16 ]
Scheme 4
