Aryl boronic acids synthesis

D. O., Micro-reactor synthesis synthesis of cyanobiphenyls using a modified Suzuki coupling of an aryl halide and aryl boronic acid, in Ehefeld, W. (Ed.), Microreaction Technology 3rd International Conference on Microreaction Technology, Proc. of... 

Recently, Larock and coworkers used a domino Heck/Suzuki process for the synthesis of a multitude of tamoxifen analogues [48] (Scheme 6/1.20). In their approach, these authors used a three-component coupling reaction of readily available aryl iodides, internal alkynes and aryl boronic acids to give the expected tetrasubsti-tuted olefins in good yields. As an example, treatment of a mixture of phenyliodide, the alkyne 6/1-78 and phenylboronic acid with catalytic amounts of PdCl2(PhCN)2 gave 6/1-79 in 90% yield. In this process, substituted aryl iodides and heteroaromatic boronic acids may also be employed. It can be assumed that, after Pd°-cata-lyzed oxidative addition of the aryl iodide, a ds-carbopalladation of the internal alkyne takes place to form a vinylic palladium intermediate. This then reacts with the ate complex of the aryl boronic acid in a transmetalation, followed by a reductive elimination. 

Several microwave-assisted protocols for soluble polymer-supported syntheses have been described. Among the first examples of so-called liquid-phase synthesis were aqueous Suzuki couplings. Schotten and coworkers presented the use of polyethylene glycol (PEG)-bound aryl halides and sulfonates in these palladium-catalyzed cross-couplings [70]. The authors demonstrated that no additional phase-transfer catalyst (PTC) is needed when the PEG-bound electrophiles are coupled with appropriate aryl boronic acids. The polymer-bound substrates were coupled with 1.2 equivalents of the boronic acids in water under short-term microwave irradiation in sealed vessels in a domestic microwave oven (Scheme 7.62). Work-up involved precipitation of the polymer-bound biaryl from a suitable organic solvent with diethyl ether. Water and insoluble impurities need to be removed prior to precipitation in order to achieve high recoveries of the products. 

Scheme 26 Synthesis P-lactam and arylation by using Suzuki coupling with aryl boronic acid...

Trisphaeridine, [8]. The synthesis [9] of trisphaeridine (17) (Scheme 4) involved the known aryl boronic acid 18 and the sterically unencumbered o-bromophenylcaibamate 19 as coupling partners in the Suzuki reaction. The biaryl 20, thus obtained in customary good yield, underwent a Bischler-Napieralsky cyclisation with phosphorus oxychloride to afford the chlorophenanthridine 21. The latter on catalytic dechlorination furnished 17. 

An interesting polymer-assisted variant of the Suzuki-reaction was recently disclosed by Vaultier and coworkers (Scheme 17) [43]. Aryl boronic acids can be immobilized on an ion exchange resin. Under Suzuki-Miyaura coupling conditions bisaryl species are released into solution and isolated with minimum purification. The authors also demonstrated that this strategy can be employed for the synthesis of macroheterocycles. 

Petasis, N. A., Goodman, A., Zavialov, I. A. A new synthesis of a-arylglycines from aryl boronic acids. Tetrahedron 1997, 53,16463-16470. 

This method was used by Hudlicky in a synthesis of the alkaloid narciclasine. The diol 90 was trapped as the usual acetal and reacted as a diene with the nitroso ester Me02C-N0 in a hetero-Diels-Alder reaction to give 91. Suzuki coupling of the vinylic bromide with the right aryl boronic acid gave 92 and the N-0 bond was reduced with Mo(CO)6 to give the advanced intermediate 93 on the way to narciclasine28 94. 

Enantiopure diaryl methanols (1) are important intermediates for the synthesis of biologically active compounds.[1] Here, a synthetic approach which employs aromatic aldehydes and readily accessible and commercially available aryl boronic acids is reported.[2,3] The catalysis with planar chiral ferrocene (2)[4] yields a broad range of optically active diaryl methanols with excellent enantioselectivities. Upon addition of DiMPEG (dimethoxy polyethyleneglycol) to the reaction mixture the enantioselectivity is increased. 

The allylic carbamate 193 formed as shown in Scheme 17 can be exploited in the synthesis of a pancratistatin analogue. Thus, Suzuki-Miyaura cross-coupling of this carbamate with aryl boronic acid 61 (Scheme 18) afforded the expected arylated cyclohexene 200 (87%) that upon sequential treatment with diborane, alkaline hydrogen peroxide, aqueous acid then acetic anhydride gave the triacetate 201 (42%). Subjecting this last compound to the Bischler-Napieralski reaction... 

A simple modification of the reaction sequence shown above has allowed for the synthesis of e f-narciclasine (cnt-188). Thus, as shown in Scheme 20, Suzuki-Miyaura cross-coupling of the previously prepared 2-bromocyclohex-2-enamine 209 with the readily synthesised aryl boronic acid 212 afforded the expected lactam 213 (63%). Once again, treatment of the last compound with TMS-Br resulted in exhaustive cleavage of the MOM ether residues and, this time, the formation of the target compound cnt-188 (48%). 

Readily available functionalized aryl siloxanes are also viable cross-coupling partners for Pd(dba)2-catalyzed allylic arylations. A mixture of 5% Pd(dba)2, allylic halide, and in situ-generated aryl zinc reagent produces allylated arenes in high yield. Aryl boronic acids have been converted to allylated arenes as well. Diastereoselective intramolecular Stille-type coupling of two allylic moieties (aUylic acetate and allylic stannane) has been performed in high yield to produce the key intermediate in the synthesis of racemic 10-ep/-elemol (eq 19). ... 

Romagnoli et al. have reported a convergent synthesis of a class of microtubule targeting agents where they aj lied the Suzuki-Miyaura reaction to highly substituted 5-bromothiazoles. With various aryl boronic acid, highly substituted thiazole derivatives were prepared and evaluated for their anti-proliferative activity against a panel of human tumor cell lines. 

Mukheijee N, Ahammed S, Bhadraa S, Ranu BC. Solvent-free one-pot synthesis of 1,2,3-triazole derivatives by the Click reaction of alkyl halides or aryl boronic acids, sodium azide and terminal aUcynes over a C11/AI2O3 surface under ball-milling. Green Chem 2013 15 389-97. 

Abstract A synthesis of an aryl boronic acid and the subsequent Suzuki coupling to an aryl indole has been developed and successfully scaled up to pilot plant scale. The Suzuki coupling was optimized by design of experiments and run with a catalyst loading of 0.1 mol%. The article describes the strategic approach for the optimization of the reaction and the most critical issues, such as the cryogenic synthesis of the boronic acid, the catalyst optimization, and the palladium removal, are discussed in detail. 

Keywords Aryl boronic acid Indole synthesis Palladium Suzuki coupling Contents... 

A number of aryUead triacetates were synthesised in this section of the PhD project to be utilised in the C-arylation of p-keto aUyl esters. In total, 11 aryUead triacetates were prepared according to the synthetic methods described in Sect. 4.7.1. AU of the aryllead reagents were prepared using Pb(OAc)4, either by direct plumbalion or by transmetallation from the corresponding aryl stannane or aryl boronic acid. The synthesis of all of the aryllead triacetates used in this project has been previously reported, many for the first time by this research group [53, 80, 81, 99]. 

Catellani and coworkers [31] observed dramatic effects of added olefins on the product selectivity in Pd-catalyzed/norbornene-mediated reactions of aryl iodides, aryl bromides, and aryl boronic acids in the synthesis of o-teraryls 91 (Scheme 3.23). 

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