Arylboronic functionalization

Arylboronic acids have traditionally been prepared via the addition of an organomagnesium or organolithium intermediate to a trialkyl borate. Subsequent acidic hydrolysis produces the free arylboronic acid. This limits the type of arylboronic acids one can access via this method, as many functional groups are not compatible with the conditions necessary to generate the required organometallic species, or these species may not be stable intermediates. 

As first described by Krizan and Martin,6 the in situ trapping protocol, i.e., having the base and electrophile present in solution simultaneously, makes it possible to lithiate substrates that are not applicable in classical ortho-lithiation reactions.7 Later, Caron and Hawkins utilized the compatibility of lithium diisopropylamide and triisopropyl borate to synthesize arylboronic acid derivatives of bulky, electron deficient neopentyl benzoic acid esters.8 As this preparation illustrates, the use of lithium tetramethylpiperidide instead of lithium diisopropylamide broadens the scope of the reaction, and makes it possible to functionalize a simple alkyl benzoate.2... 

The palladium-catalyzed coupling of boronic acids with aryl and alkenyl halides, the Suzuki reaction, is one of the most efficient C-C cross-coupling processes used in reactions on polymeric supports. These coupling reactions requires only gentle heating to 60-80 °C and the boronic acids used are nontoxic and stable towards air and water. The mild reaction conditions have made this reaction a powerful and widely used tool in the organic synthesis. When the Suzuki reaction is transferred to a solid support, the boronic add can be immobilized or used as a liquid reactant Carboni and Carreaux recently reported the preparation of the macroporous support that can be employed to efficiently immobilize and transform functionalized arylboronic adds (Scheme 3.12) [107, 246, 247]. 

Complementary to the use of zinc reagents for the introduction of (functionalized) alkyl groups is the rhodium-catalyzed conjugate addition of aryl- and alkenylboron reagents. This method rapidly became popular, also because arylboron reagents are air and moisture stable and a large variety of them is commercially available . 

A rhodium-chiral phosphine complex catalyzes the enantioselective addition of phenylboronic acid to 1-naphthaldehyde to give a chiral diaryl carbinol but with moderate ee (Scheme 13) [39]. When considering the introduction of functionalized aryl groups, arylboronic acid is a promising alternative arylating reagent to diarylzinc compounds. 

Synthesis of arylboronates via the palladium(0)-catalyzed cross-coupling reaction of tetra(alkoxy)diboranes with aryl triflates has been reported.114 The cross-coupling reaction of (RO)2B-B(OR)2 (OR = methoxy and pinacolato) with aryl triflates to give arylboronates 178-189 was carried out at 80 °C in the presence of PdCl2(dppf) (3 mol%), and KOAc (three equivalents) in dioxane. The reaction was generalized to various functional groups such as nitro, cyano, ester, and carbonyl groups (Scheme 30). 

The first synthesis of arylboronic esters 209-215 via the coupling of bis(pinacolato)diborane(4) with easily prepared aryldiazonium tetra-fluoroborate salts was reported. The palladium-catalyzed borylation reaction proceeds efficiently under mild reaction conditions in the absence of a base to afford various functionalized arylboronic esters in moderate to high yields (Scheme 34).121... 

Figure 5.39 shows the preparation of an arylboronic acid as an example of the ortho-selective functionalization of an aromatic compound containing an O-bonded DMG. The LTArBlOMefj complex is generated and then hydrolyzed during workup. 

Fig. 5.39. Electrophilic functionalization ortho to an 0-bonded DMG preparation of an arylboronic acid.

Iron-catalyzed Suzuki-Miyaura coupling reactions were also reported by Nakamura and colleagues (entry 27) [67]. Alkyl halides 1 and mixed pinacol aryl(butyl)borates, generated in situ from arylboronates and butyllithium, were used as the reagents and 10 mol% of the iron complexes 16a or 16b as the catalysts. The addition of 20 mol% of MgBr2 was essential for the success of the reaction. Products 3 were isolated in 65-99% yield. The methodology tolerates ester and nitrile functions. The reaction starts probably by initial boron-iron transmetalation to generate a diaryliron(II) complex. 

The carbamate substituted DHP derivative 647 has been deprotonated with f-BuLi in THF at — 78 °C to give the vinyllithium 648950 (Scheme 169). This reagent has been functionalized with a variety of electrophiles in good yields. The iodinated derivative 649 (X = I) underwent Suzuki-Miyaura couplings with arylboronic acids to afford the corresponding a-arylated DHPs. 

Bromo- and iodoimidazoles are useful intermediates for further functionalization. 4(5)-Aryl- I //-imidazoles 57 can be efficiently and selectively prepared by palladium-catalyzed Suzuki-Miyaura reaction of commercially available 4(5)-bromo-l//-imidazole 56 with arylboronic acids under phase-transfer conditions, which then underwent highly selective palladium-catalyzed and copper(I) iodide mediated direct C-2-arylation with a variety of aryl bromides and iodides under base-free and ligandless conditions to produce 2,4(5)-diaryl-l//-imidazoles 58 in modest to good yields <07JOC8543>. A new procedure for the synthesis of a series of substituted 2-phenylhistamines 60 utilizing a microwave-promoted Suzuki... 

The triethoxysilyl endgroup is a popular functional group to bind the catalyst to a polymeric support [238]. Polymeric supports include silica gel, MCM-41 (mesoporous silica gel) and ITQ-2 (delaminated zeolite) [247]. Corma et al. used this approach to synthesise gold(I) and palladium(II) NHC complexes for Suzuki cross-coupling reactions between iodobenzene and various arylboronic acids (see Figure 4.78) [247]. The results were very modest at 35-80% dependent upon the substitution pattern of the arylboronic acid. Yields with gold(I) catalysts were marginally better than those for palladium(II) complexes. 

Various arylboronic acids having o-, m-, and p-substituents smoothly underwent the addition to benzyl crotonate (7e) with high yields and high %ee (entries 5-11). There is no appreciable difference in yields and %ee between m- and p-functionalized arylboronic acids. The presence of o-substituent slightly retarded the addition due to its steric hindrance (entries 10 and 11) and the methoxy group again diminished the %ee (entry 11). The addition of 4-methylphenylboronic acid and 1-naphthylboronic acid to 7g resulted in 48 and 1 l%ee, respectively (entries 12 and 13). 

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