Chapter 1
Catalysis In C-Cl Activation

ZHONG-XIA WANG and WANG-JUN GUO

Department of Chemistry, University of Science and Technology of China, Hefei, Anhui, People's Republic of China

1. 1.1 Introduction
2. 1.2 Reductive Dechlorination
   1. 1.2.1 H2 as Reductant
   2. 1.2.2 ROHActivation or ROM as Reductant
   3. 1.2.3 Hydrosilanes as Reductant
   4. 1.2.4 Formic Acid or Its Salts as Reductant
   5. 1.2.5 Borane or Sodium Borohydride as Reductant
   6. 1.2.6 Grignard Reagents as Reductant
   7. 1.2.7 Hydrazine as Reductant
3. 1.3 Formation of C-C Bonds
   1. 1.3.1 Suzuki Reaction
      1. 1.3.1.1 Palladium Catalysts
      2. 1.3.1.2 Nickel Catalysts
      3. 1.3.1.3 Other Metals
   2. 1.3.2 Negishi Reaction
      1. 1.3.2.1 Palladium Catalysts
      2. 1.3.2.2 Nickel Catalysts
      3. 1.3.2.3 Other Metals
   3. 1.3.3 Kumada Reaction
      1. 1.3.3.1 Palladium Catalysts
      2. 1.3.3.2 Nickel Catalysts
      3. 1.3.3.3 Iron Catalysts
      4. 1.3.3.4 Cobalt Catalysts
      5. 1.3.3.5 Copper Catalysts
   4. 1.3.4 Stille Reaction
      1. 1.3.4.1 Palladium-Phosphine Catalysts
      2. 1.3.4.2 Palladium-NHC Catalysts
      3. 1.3.4.3 N,O-Chelate Palladium Catalysts
   5. 1.3.5 Hiyama Reaction
      1. 1.3.5.1 Palladium Catalysts
      2. 1.3.5.2 Nickel Catalysts
   6. 1.3.6 Sonogashira Reaction
      1. 1.3.6.1 Palladium Catalysts
      2. 1.3.6.2 Nickel Catalysts
   7. 1.3.7 Decarboxylative Cross-Coupling
   8. 1.3.8 Heck Reaction
      1. 1.3.8.1 Palladium Catalysts
      2. 1.3.8.2 Nickel and Cobalt Catalysts
   9. 1.3.9 C-H Functionalization with Organic Chlorides
      1. 1.3.9.1 a-Arylation of Carbonyl and Related Compounds
      2. 1.3.9.2 C-H Functionalization of (Hetero)arenes with Organic Chlorides
4. 1.4 Formation of C-N Bonds
   1. 1.4.1 Copper Catalysts
   2. 1.4.2 Palladium Catalysts
      1. 1.4.2.1 The Second-Generation Catalysts
      2. 1.4.2.2 The Third- and Fourth-Generation Catalysts
   3. 1.4.3 Nickel Catalysts
   4. 1.4.4 Iron and Cobalt Catalysts
5. 1.5 Formation of C-O Bonds
   1. 1.5.1 Copper Catalysts
   2. 1.5.2 Palladium Catalysts
6. 1.6 Formation of C-S Bonds
   1. 1.6.1 Copper Catalysts
   2. 1.6.2 Palladium Catalysts
7. 1.7 Formation of C-B Bonds
   1. 1.7.1 Palladium Catalysts
   2. 1.7.2 Nickel Catalysts
8. 1.8 Conclusion and Outlook
9. References

1.1 Introduction

Over the past decades, transition-metal-catalyzed activation and transformation of carbon-halide bonds have achieved great progress. The cross-coupling reactions based on carbon-halide bond activation play an important role in the synthesis of many drugs, natural products, optical devices, and industrially important starting materials [1-3]. Until the late 1990s, the coupling counterparts were predominantly iodides and bromides. Organic chlorides were rarely used due to their low reactivity [4, 5]. However, organic chlorides are cheaper and more widely available compounds. Their use as electrophilic partners would economically benefit a number of industrial processes [5, 6]. On the other hand, organic chlorides such as polychlorobiphenyls and chlorophenols are environmental pollutants. Dechlorination and detoxification of hazardous organic chlorides are also greatly concerned [7, 8]. In view of the above-mentioned reasons, activation and transformation of C-Cl bonds of organic chlorides attracted extensive attention in the past 10-15 years. A range of effective and efficient catalyst systems have been developed. The construction of new C-C and C-heteroatom bonds through catalytic activation of C-Cl bonds has been carried out [9-17]. In this chapter, we summarize the main advances of transition-metal-catalyzed activation and transformation of C-Cl bonds of organic chlorides.

1.2 Reductive Dechlorination

Organic chlorides are manufactured on a large scale and used widely in a variety of chemical industries. Organic chlorides are also often environmental pollutants, such as chlorofluorocarbons (CFCs), 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT), chlorinated dibenzo-p-dioxins (dioxins), polychlorinated biphenyls (PCBs), and chlorophenols. Hence dechlorination of organic chlorides is of great interest in detoxification of hazardous chlorinated organic compounds and in the development of synthetic methodologies.

A range of methods have been developed for dechlorination of organic chlorides, including dechlorinations via photochemical reaction [18], microbial biodegradation [19, 20], oxidative dehalogenation or degradation [21, 22], and reductive dechlorination. In this section, we focus on transition-metal-catalyzed reductive dechlorination of organic chlorides. The cobalamin-mediated reductive dehalogenation is not included. An excellent perspective about this topic has been published recently [23].

1.2.1 H2 as Reductant

The hydrogenolysis of C-Cl bonds of both alkyl and aryl chlorides can be performed in the presence of transition metal catalysts, mainly Ni, Pd, Rh, and Ru. This topic was reviewed previously [7, 24, 25].

Pd/C is a widely employed catalyst for the reductive dechlorination by H2. Sajiki et al. [26] reported a mild and efficient one-pot hydrodechlorination of aromatic chlorides using a Pd/C-Et3N system as the catalyst. When 1 mol% Pd/C (10%) and 1.2 equiv of Et3N are employed, the dechlorination reaction of 4-chlorobiphenyl in MeOH can proceed at room temperature under 1 atm H2 and gives 100% conversion of the chloride. The reaction can be applied to wide aromatic substrates and tolerates a range of functional groups except nitro and furyl groups, which are hydrogenated simultaneously. Studies also show that lipophilic bases such as Me2NH, Me3N, iPr2NEt, iPr3N, DBU, PhNH2, and PhNEt2 greatly enhanced the efficiency of the reaction compared with the less lipophilic NH3 or ethylendiamine, whereas the aromatized heterocyclic bases such as pyridine or quinoline strongly suppressed the hydrodechlorination [27]. In the presence of a quaternary onium salt (Aliquat 336) as the phase-transfer agent, 50% aqueous KOH also leads to a good result in a multiphase system consisting of a hydrocarbon solvent (isooctane). A synergistic activation effect was observed for KOH and the phase-transfer catalyst [28]. A similar multiphase system was used for a Pd/C-, Pt/C-, or Raney-Ni-catalyzed dechlorination of ?-hexachlorocyclohexane (lindane) under normal H2 pressure, generating benzene as the final product. In the presence of KOH and Aliquat 336, the reaction was shown to proceed via the consecutive dehydrochlorination and hydrodechlorination reaction stages, which are also co-promoted by Aliquat 336 and aqueous KOH as mentioned above. In the absence of a base, the reaction proceeds through a removal of a pair of chlorines from lindane at every reaction step by zerovalent metal followed by reduction of metal with hydrogen [29].

H2O or an 80% H2O-EtOH mixture is shown to be a suitable solvent for the Pd/C-catalyzed hydrodechlorination of aryl chlorides. The reaction proceeds at room temperature under normal H2 pressure, leading to complete dechlorination in a short reaction time. The catalyst system tolerates functional groups such as F, CF3, OH, and C(O)Ph [30]. Nan and co-workers [31] carried out the Pd/C-catalyzed regioselective dechlorination of 2,4-dichloropyrimidines at room temperature and normal H2 pressure, forming 2-chloropyrimidines in excellent yields [Eq. (1.1)].

Dehalogenation of aryl or benzyl bromides and chlorides can be performed using Pd/AlO(OH) and a hydrogen balloon under solvent-free conditions. The reaction proceeds at room temperature and gives excellent yields in a short time. The reaction is compatible with a cyano group, but it converts a nitro group into an amino group and converts the carbonyl group of an aldehyde or ketone into a hydroxy group [32]. Complete hydrodechlorination of DDT and its derivatives 1,1-dichloro-2,2-bis(4-chlorophenyl)ethene (DDE) and 1,1-dichloro-2,2-bis(4-chlorophenyl)ethane (DDD) can be achieved using a hydroxyapatite-supported Pd nanoparticle catalyst (Pd0HAP) using H2 (10 atm) as the reducing agent [Eq. (1.2)]. The Pd0HAP catalyst shows good reusability without significant loss of activity [33].

A Pd(PPh3)4-catalyzed selective dechlorination of 2,3-dichloronitrobenzene can be achieved under normal H2 pressure, forming 3-chloronitrobenzene in over 90% selectivity. 3-Chloronitrobenzene can be further transformed into nitrobenzene, 3-chloroaniline, or aniline, depending on the catalyst concentration [34].

Esteruelas and co-workers [35] carried out rhodium-nanoparticle-catalyzed hydrodechlorination of aryl chlorides. The rhodiumnanoparticles are formed from bis(imino)pyridinerhodium(I)...