Boronic or Boronate, transition metals, coupling reactions

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Several of the transition metals, Cu, Ni, Rh, especially Pd are very important for organic synthesis. In the contrast to the reactions involving main-group metals, like lithium and magnesium, transition metals play a role as catalysts in the reactions. The studies of transition metals in organic synthesis started from 1960s, and since 1990, boronic acids and the corresponding esters, boronates became more and more popular in organic synthesis. Reactions like Suzuki coupling, Buchwald coupling, Hartwig coupling, Heck reaction, Stille coupling, Negishi coupling and Kumada coupling etc provide a variety of synthetic methodology for C-C bond, C-N bond, C-O bond, C-B bond formation and CO insertion. I hope following figure could summarize the general name reactions related with transition metals. Pd is broadly used in heterocycle synthesis recently.

Transition metal reactions:

Copper (Cu)

Lithium dimethylcuprate: Corey and Posner discovered (CH₃)₂CuLi could replace iodine and bromide with methyl in alkyl, alkenyl and aryl derivatives.
Ullman Coupling: Aryl halides form biaryl compounds catalyzed by copper alloy or Cu (I) salt, like CuSO₃CF₃.
Normant reagent: Mixed copper-magnesium reagents, RCuMgBr₂, undergoes addition to terminal acetylenes to afford alkenylcopper reagents, which could work as good nucleophiles.

Nickel (Ni)

Ni(CO)₄ is the most useful nickel catalyst that reacts with allylic halides to yield pi-allyl complexes. Allyl complexes could couple with a variety of halides.
Kumada coupling reaction: Nickel (II) salts, especially (Ph₂PCH₂CH₂PPh₂)₂Cl₂, could catalyze the coupling reaction between aryl or alkenyl halide with Grignard reagents.

Rhodium (Rh)

Wilkinson Rh catalyst: Rh(PPh₃)₃Cl It is made from the refluxing of RhCl₃ and PPh₃in EtOH. It catalyzes carbonylation, decarbonylation, oxygenation, and homogeneous hydrogenation.
Fisher-Tropsch process is the reductive conversion of carbon monoxide to alkane.
Hydroformation is that Rhodium catalyst, like Rh₂O₃, could catalyze the reaction of alkenes with hydrogen and carbon monoxide to give aldehydes. This reaction is different from another hydroformation, Vilsmeier-Haack reaction, in which formaldehyde reacts with POCl₃ to form Vilsmeier-Haack reagent that hydroformylates alkenes or aromatic rings.

Palladium (Pd)

The Tsuji-Trost reaction is the palladium catalyzed allylation of nucleophiles. Basically, Pd catalyst forms a complex with allyl group. The complex is electronically deficient, could be subjected to a nucleophlic attack.
The Wacker reaction is that Pd catalyst forms a Pd-Alkene complex subjected to water attack as a nucleophilic addition. The addition intermediate undergoes beta-elimination affords enol that tautomerized to methyl ketone or aldehyde.
The Heck reaction is the palladium catalyzed coupling reaction between aryl halide or triflate with olefin. This reaction is used in making aryl substituted with olefin, biaryl compounds, and heterocycles.
The Stille coupling is the Palladium catalyzed cross coupling between an organotin and alkenyl or aryl halide or triflate.
The Kumada coupling is the Pd catalyzed cross coupling reaction between a Grignard and alkenyl or aryl halide or triflate.
The Negishi coupling is the cross coupling reaction between organozinc with alkenyl or aryl halide or triflate by Pd catalyst.
The Buchwald-Hartwig is the cross coupling reaction to make C-O bond or C-N bond catalyzed by Pd catalyst. The yield of this type of reaction is highly depended on the substrates, and notoriously unpredictable. Many year experience of doing it, still have no control.
The Hiyama coupling is that an organosilicon activated by a strong nucleophile such as -F (very strong Si-F bond) or -OH reacts with aryl halide or triflate.
The Sonogashira reaction is the coupling reaction between copper (I) arylacetylenes with aryl halide or bromide.
The Suzuki coupling is not need to be introduced any more. It is very iiiiiiiiiiiiiiiiiiiiimportant, and chemists would live miserable without it.
More coming latter, like Dr. MacMillan using trimethyl ammonium of aniline to do coupling reaction. The First Suzuki Cross-Couplings of Aryltrimethylammonium Salts, J. AM. CHEM. SOC. 9 VOL. 125, NO. 20, 2003, 6047.

Finally, I salute to Japanese chemists for their contribution in transition metal coupling reactions, and to inorganic chemists who have contributed to organic synthesis.

Mechanism

The catalytic cycle generally includes five or four separate steps, oxidative addition, metathetic exchange, transmetalation, cis or trans isomerization if needed, and reductive elimination.

Suzuki (Akira Suzuki 1930 - ) Coupling Mechanism	Heck (Richard Fred Heck 1931 - )Coupling Mechanism

Stille (John Kenneth Stille 1930 - 1989) Coupling Mechanism	Kumada Coupling Mechanism

Negishi Coupling Mechanism	Miyamura Reaction Mechanism

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Reaction Examples

Boronic Acid Synthesis: Hydrolysis of boronate gives boronic acid.

One general way to make boronic acid is to make lithiate first, then nucleophilic substitution happens, followed by hydrolysis.	J. Chem. Soc, Perkin Trans 1; 1990, 715. also see J. Org. Chem.; 1988, 53, 5484
Grignard reagent also works as nucleophile.	J. Org. Chem. 1984, 49 (26), 5237. also see J. Organomet. Chem. 1983, 259, 269.
Borane could works as electrophile too.	J. Organomet. Chem. 1983, 259, 269
Base also is used in the hydrolysis.	Tetrahedron 2002, 58 (22), 4369-4373

Boronate Synthesis: Nucleophilic substitution, Coupling, and from boronic acid.

Nucleophilic substitution.	Synth. Commun. 1996, 26 (19), 3543-3547; Tetrahedron Letters 2000, 41, 3705-3708
Miyaura Boration reaction. Coupling reaction using palladium catalyst.	Tetrahedron 2001, 57 (49), 981-9816; Chem. Lett. 2002, 8, 780; Chem. Lett. 2002, 8, 780
Coupling reaction using Ir catalyst.	Angew. Chem., Int. Ed. 2002, 41 (16), 3056-3058
Coupling reaction with diazo.	Tetrahedron Lett. 2000, 41 (45), 8683.

Borane Synthesis:

Hydroboration.	J. Am. Chem. Soc. 1993, 115 (14), 6065.
Nucleophilic substitution.	Synth. Commun. 2001, 31 (19), 2939; also J. Org. Chem. 1986, 51, 427.
Nucleophilic substitution.	J. Organomet. Chem. 1991, 409, 103; also J. Org. Chem. 1984, 49 (21), 4089
Reduction and boranhydration.	J. Am. Chem. Soc. 1989, 111 (5), 1754.

Coupling reaction examples

Sonogashira reaction.	J. Org. Chem. 1998, 63, 8551
Boronic acid reacts with aldehyde to afford secondary alcohol.	Organic Letters, 2005, 7, 4153-4155
Boronic acid 1,4-addition to unsaturated ester.	Organic Letters, 2005, 7, 3821-3824
Alper carbonylation.	Tetrahedron Lett. 1987, 28, 3237
One pot Suzuki reaction	L. Zhu, J. Org. Chem. 2003, 68, 3729.

Lab Rat's Procedures: For most transition metals catalyzed reactions, degas is a very important step. By the way, if my procedure does not work for you, I am sorry, you have to find better way to COOK your staff.

Heck reaction. Bromobezene derivative (1 equiv.), methyl acrylate (5 equiv.), TEA (1.5 equiv.), catalyst Pd(OAc)2 (0.1 equiv.), and P(o-Tolyl)3 (0.1 equiv.) were mixed in acetonitrile (depends on the scale). The mixture was degassed and heated to reflux for 5 hours and cooled to room temperature. The resulting mixture was concentrated under vacuum. The residue was purified by silica gel column.
Stille coupling 1. Halo-aromatic ring ( 0.8 equiv.), tributyl (1-ethoxyvinyl) tin (1 equiv.), Pd(PPh3)4 (0.05 equiv.), and K2CO3 (1 equiv.) were mixed in toluene (X mL). The mixture was degassed and heated to 100^oC for 2 hours with N2 inlet. The mixture was concentrated and the residue was mixed with 2N HCl. The mixture was stirred for 2 hours. Ethyl acetate was used to extract the product ( acetyl aromatic ring) from aqueous solution. Organic layer was dried, concentrated, and the residue was separated by silica gel column.
Stille coupling 2. The mixture of bromo-aromatic compound (1 equiv.), Me4Sn (10 equiv.), Pd(OAc)2 (0.05 equiv.), and PPh3 in DMF was heated to 120oC for 30 min. TLC showed the reaction was finished. The resulting mixture was diluted with ethyl acetate, and washed with brine. The organic layer was dried and concentrated. The resulting residue was purified by silica gel column. Check J. Org. Chem. 2005, 70, 841-846 for interesting development in Stille coupling by only using catalytic amounts of tin.
Buchwald-Hartwig reaction. Bromo-aromatic ring (1 equiv.), aniline (1.5 equiv.), Cs2CO3 (10 equiv.), Pd(OAc)2 (0.05 equiv.), and BINAP (0.08 equiv.) were mixed in toluene (X mL). The mixture was degassed, and stirred at 110^oC for 8 hours with N2 inlet. The resulting mixture was filtered with celite, the filtrate was concentrated. The resulting residue was purified by silica gel column.
Suzuki reaction 1 (two phases condition); Halo-aromatic ring (1 equiv.), phenyl boronic acid (1.2 equiv.), PdCl₂(dppf) (0.1 equiv.), and 2 M Na₂CO₃ (X mL) were mixed with toluene/dioxane (4/1, Y mL). The mixture was degassed, and stirred for 4 hours at 85^oC with N2 inlet. The resulting mixture was filtered with celite, and the filtrate was separated. The organic layer was concentrated. The resulting residue was separated by silica gel column. If you want to put an alkyle group that have beta hydrogen by Suzuki coupling, you got to use alkyl borane (R-9-BBN or tri-R borane) rather than alkyl boronate or boronic acid, because of beta elimination is faster than coupling reaction.
Suzuki reaction 2 (room temperature). Bromo-aromatic (1 equiv.), phenyl boronic acid (1.5 equiv.), CTC-Q-PHOS (0.1 equiv.), and tris(dibenzylideneacetone)dipalladium chloroform complex (0.05 equiv.), and CsF (10 equiv.) were mixed into THF. The mixture was stirred at rt. for 12 hours. The resulting mixture was filtered with Celite, and the filtrate was separated by silica gel column to afford 70% desired product.
Suzuki reaction 3 ( Micro wave). The halo-aromatic ring (1 equiv.), boronic acid (1.5 equiv.), PdCl2(dppf) (0.1 equiv.), and 2 M K2CO3 (10 equiv.) were dissolved into N-dimethyl acetate amide. The mixture was reacted on a microwave reactor at 150oC for 20 min. The resulting mixture was filtered, and the filtrate was purified by HPLC. Attention: no solid in micro wave reaction. And chloro substitutent is less active but doable under this condition.
Miyaura boration. The halo-aromatic compound (1 equiv.), Bis(pinacolato)diboron (1.5 equiv.), PdCl2(dppf) (0.05 equiv.), and potassium acetate (10 equiv.) in MDSO, dioxane, or toluene. The mixture was degassed. The resulting mixture was heated to ~95^oC with stirred for 6 hours. The resulting mixture was diluted with ethyl acetate, and the solution was filtered and washed with brine. The resulting organic layer was dried and concentrated. The resulting residue was purified by silica gel column afford boronate 95%. Benzyl boronate could be made using this procedure.
Cyanation of Aromatic ring through coupling reaction from halo-aromatic ring. The mixture of halo-aromatic compound (1equiv.), Zinc cyanide (1.3 equiv.), Pd2(dba)3 (0.05 equiv.), dppf (0.05 equiv.), and Zinc (0.2 equiv.) in N-dimethyl acetate amide was heated to 150oC for 2 hours. The resulting mixture was diluted with ethyl acetate, and washed with brine. The organic layer was dried, and concentrated. The resulting residue was purified by silica gel column. Check Org. Lett., 6 (17), 2837 -2840, 2004 for latest development.
Ullman coupling to build N-C bond. The amine (1 equiv.), iodo-aromatic ring (2 equiv.), potassium phosphate (4 equiv.), N, N'-dimethyl ethylenediamine, and CuI (0.25 equiv.) were suspended in toluene and degassed. The mixture was heated to 100oC for 12 hours with strong stirring. The resulting mixture was filtered. The filtrate was concentrated. The resulting residue was purified by silica gel column.
Chan-Lam coupling to build N-C bond. The amine ( 1equiv.), phenyl boronic acid (2 equiv.), Cu(OAc)2 (1 equiv.), and TEA (5 equiv.) were dissolved into CH2Cl2. The resulting mixture was stirred for 8 hours at room temperature. The resulting mixture was washed with brine, and the organic layer was dried and concentrated. The residue was purified by silica gel column.