Phenyl Boronic Acid Synthesis Scheme

This concept has been applied in the phenyl boronic acid synthesis (Scheme 3.1) [177]. 

Phenyl Boronic Acid Synthesis (Scheme 6.1) (Clariant/Frankfiirt + IMM)... 

Temperature profile of the phenyl boronic acid synthesis along the major steps of the process flow scheme. The difference in the temperatures of the conventional batch and the microreactor processes stand for the reduction in energy consumption and respective heat-transfer equipment when using the latter [10]... 

The Baccatin III synthesis by K. C. Nicolaou and co-workers is summarized in Scheme 13.54. Diels-Alder reactions are prominent in forming the early intermediates. In Step A the pyrone ring served as the diene. This reaction was facilitated by phenyl-boronic acid, which brings the diene and dienophile together as a boronate, permitting an intramolecular reaction. 

Krische and coworkers [44] developed a Rh-catalyzed asymmetric domino Michael/aldol reaction for the synthesis of substituted cyclopentanols and cyclohex-anols. In this process, three contiguous stereogenic centers, including a quaternary center, are formed with excellent diastereo- and enantioselectivity. Thus, using an enantiopure Rh-BINAP catalyst system and phenyl boronic acid, substrates 2-108 are converted into the correspondding cyclized products 2-109 in 69-88% yield and with 94 and 95% ee, respectively (Scheme 2.24). 

Wulff and his collaborators reported, in 1989, the preparation of imprinted polymers able to perform enantioselective synthesis [11, 12]. The imprinting complex was prepared by reacting 3,4-di-hydroxy-phenyl-alanine methyl-ester (l-DOPA methyl ester) (16) with the 4-vinyl-salicylaldehyde (17) to form the corresponding Schiff s base (18), which was further reacted with the 4-vinyl-phenyl-boronic acid (19) to afford to the corresponding ester (20) (Scheme 4). The imprinting complex obtained was then polymerised and the template removed. The resulting polymers were incubated with sodium glycinate to allow formation... 

Tschierske developed a variety of molecules containing a p-terphenyl unit as backbone equipped with two terminal decyloxy chains and laterally attached crown ethers of different sizes [51-53]. The synthesis was straightforward starting from methyl-2,5-dibromobenzoate 30 that was coupled with [4-(decyloxy)phenyl]boronic acid 31 in a subsequent Pd°-catalyzed Suzuki reaction. The 2-hydroxymethyl crown ethers 32 were attached in the last step (Scheme 18) to yield mesogenic 33. 

Typical industrial process for the synthesis of phenyl boronic acid from phenylmag-nesium bromide and boronic acid trimethoxy ester requires strict temperature control (—25 to —55 °C) to minimize the formation of side products. Recently, Hessel and coworkers reported that a micromixer (width 40 pm and depth 300 pm)/ tubular reactor system gave the phenyl boronic acid at high yield (>80%) even at higher temperatures (22 or 50 °C) with minimum amounts of the side products (Scheme 4.48) [66]. They also achieved a pilot-scale production by employing a caterpillar minimixer (width range 600-1700 pm and depth range 1200-2400 pm). 

Suh et al.65 have reported a formal total synthesis of Mansonone F and this is described in Scheme 12. 5-Methoxy-a-tetralone (127) was converted to 1-methyl-5-hydroxy-naphthalene (128) by the standard organic reactions. Treatment of (128) with phenyl boronic acid, paraformaldehyde and propionic acid followed by catalytic hydrogenation yielded compound (129). This on alkylation gave the compound (130) which on alkaline hydrolysis was converted to acid. The acid halide underwent intramolecular Friedal-Crafts acylation affording an intermediate (131) whose transformation to Mansonone F has been accomplished by Best and Wege.59... 

Boronic esters (3) can be homologated to a-chloroboronic esters (4) (Scheme 2) replacement of the chlorine atom by carbon nucleophiles, such as Grignard reagents, and oxidation of the carbon-boron bond gives a new route to alcohols/ If the sequence is performed with (+)- or (-)-pinanediol boronic esters it can be made into a directed chiral synthesis of alcohols, as illustrated in Scheme 3 from phenyl boronic acid the homologation steps were found to occur with diastereoselectivities in excess of 90%, the chlorine replacement proceeds with inversion, and the oxidative step with retention of configuration. 

Palladium-mediated catalysis has only been exploited relatively recently in the synthesis of substituted PPV derivatives. The use of aryl dibromides as monomers is particularly useful as it allows the synthesis of PPVs substituted with alkyl rather than alkoxy sidechains. The Suzuki [53, 54], Heck [55], and Stille [56] reactions have been used in the synthesis of new PPV derivatives, but attaining high molecular weight PPV derivatives by these methodologies has proved problematic. A phenyl-subslilutcd PPV material PPPV 31 was synthesized by a Suzuki coupling (Scheme 1-10) of dibromoethene and fo/.v-boronic acid 30. Its absorption (2ni ix=385 nm) and emission (2max=475 nm) maxima were strongly... 

The use of expensive and unstable ZnPli2 in the preparation of chiral di-arylmethanol derivatives, with electronically and sterically similar aryl rings, made this approach less attractive for the enantioselective synthesis. In order to avoid this inconvenience, other alternative preparations of arylzinc reagents were evaluated.As a first choice, Yus et al. proposed the use of arylboronic adds as a viable source of phenyl (Scheme 4.19). Thus, the reaction of various boronic acids with an excess of ZnEt2 at 70 °C gave the corresponding arylzinc intermediates (probably aryl(ethyl)zincs), which were trapped by reaction with dif-... 

Carbon-11 labeled BPA, 4, was synthesized from the corresponding aldehyde, 4-boronophenylacetaldehyde, 9. This boronated aldehyde was prepared from commercially available 4-bromophenylacetic acid, 10, in five synthetic steps (Scheme 1). The synthesis was initiated by the borane reduction8 of acid 10 to the 2-(4-boronophenyl)ethyl alcohol, 11. Alcohol 11 was then carefully oxidized9 to aldehyde 12. In the next step, 4-bromophenylacetaldehyde, 12, was refluxed with ethylene glycol in the presence of a catalytic amount ofp-toluenesulfonic acid to obtain the corresponding acetal 13.10 The boronic acid moiety was introduced at the para position of the phenyl ring by the reaction with butyllithium followed by triisopropyl borate" to obtain the 4-bronophenylacetaldehyde ethylene acetal, 14. In the final step of the synthesis, acetal 14 was treated with concentrated hydrochloric acid in methanol as solvent to obtain the desired precursor, 4-boronophenylacetaldehyde, 9, for the synthesis of carbon-11 labeled BPA, 4, Scheme 2. 

Optically active allylboronates bearing chiral auxiliary located at the boron atom found widespread applications in asymmetric synthesis. Enantiomerically enriched a-alkylidene-y-lactones and lactams can also be synthesized following such a synthetic approach. VUlieras et al. (41, 45] demonstrated the potential of chiral allylboronates derived from 2-phenyl-2,3-bomanediol, ephedrine, or norephedrine for this purpose. Chiral allylboronates 46a,b were obtained in a sequence of reactions involving transformation of achiral precursors 32 into the corresponding boronic acids 44 followed by their esterification with enantiomerically pure diol or 1,2-aminoalcohol 45 (Scheme 4.10). In the case of methyl-substituted derivatives 32b (R = Me), initial composition of E- and Z-isomers was transferred to the target allylboronates 46b. Importantly, the isomeric mixture was separated by means of the column chromatography. 

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