Boronic acids mediation

Two short syntheses of P-lapachone from readily available naphthols and 3-methylbut-2-enal via a mild phenyl-boronic acid mediated cyclization to 2//-chromenes have been reported. Catalytic hydrogenation of 2H-chromenes with H /Pd-C in ethyl acetate afforded the corresponding naturally occurring chromanes (72) and (73). Oxidation of the adequate chromane with an excess of cerium ammonium nitrate (CAN) furnished P-lapachone in 62% yield [153]. 

Other organometaloids also undergo similar reactions. Analogous Cu(OAc)2 mediated reaction of aryltins, arylsiloxanes, arylbismuth compounds, and arylleads with various amines lead to arylated products in good yields. An interesting modification of amine or amide arylation by aryl boronic acids mediated... 

Furuya T, Ritter T (2009) Fluorination of boronic acids mediated by silver (I) triflate. Org Lett ll(13) 2860-2863... 

The same authors have reported a new fluorination of boronic acids mediated by silver(i) triflate. ° The process and a range of examples are shown in Scheme 15.68. 

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... 

Although there are several reports in the literature on boron-mediated amide formations, the boron reagents had to be used in stoichiometric amounts.1-4-5-6-7-8-9 Recently, Yamamoto et al. presented the first truly catalytic method allowing for a direct amide formation from free carboxylic acids and amines as the reaction partners.10-1112 Best results were obtained by using phenylboronic acids bearing electron withdrawing substituents in the meta- and/or para-positions such as 3,4,5-trifluorophenylboronic acid or 3,5-bis(trifluoromethyl)boronic acid as the catalysts. 

Allyl tetrafluoroborates are also useful allylboration reagents. They can be made from allylic boronic acids and are stable solids.63 The reaction with aldehydes is mediated by BF3, which is believed to provide the difluoroborane by removing a fluoride. The addition reactions occur with high stereoselectivity, indicating a cyclic TS. 

Using Pd-mediated cross-coupling reactions, such as Suzuki, Heck, and Sonoga-shira- Hagihara reaction, researchers efficiently constructed a library of 151 coumarin derivatives from eight 3-bromocoumarins cross-coupled with ten aryl/heteroaryl boronic acids, ten alkenes, and ten alkynes (Fig. 4). 

Recently, interest in copper-catalyzed carbon-heteroatom bond-forming reactions has shifted to the use of boronic acids as reactive coupling partners [133], One example of carbon-sulfur bond formation is displayed in Scheme 6.65. Lengar and Kappe have reported that, in contrast to the palladium(0)/copper(l)-mediated process described in Scheme 6.55, which leads to carbon-carbon bond formation, reaction of the same starting materials in the presence of 1 equivalent of copper(II) acetate and 2 equivalents of phenanthroline ligand furnishes the corresponding carbon-sulfur cross-coupled product [113]. Whereas the reaction at room temperature needed 4 days to reach completion, microwave irradiation at 85 °C for 45 min in 1,2-dichloroethane provided a 72% isolated yield of the product. 

The electron-rich thiophene ring system can be elaborated into complex, fused thiophenes by acid-mediated intramolecular annelation reactions. For example, treatment of alcohol 96 with trimethylsilyl triflate promoted a Friedel-Crafts acylation and subsequent dehydration giving benzo[b]thiophene 97, a potential analgesic <00JMC765>. Treatment of ketone 98 with p-toluenesulfonic acid resulted in the formation of fused benzo[b]thiophene 99 <00T8153>. Another variant involved the cyclization of epoxide 100 to fused benzo[f>]thiophene 101 mediated by boron trifluoride-etherate . 

In this method, Furstner converts N-BOC protected pyrrole to the 2,5-dibromo compound (122) with NBS and this is followed by metalation and carbomethoxylation with t-butyl lithium in THF and subsequent trapping of the metalated species with methyl chloroformate to yield a pyrrole diester (123). Bromination of this diester at positions 3 and 4 with bromine in water followed by Suzuki cross-coupling with 3,4,5-trimethoxyphenyl boronic acid yields the symmetrical tetrasubstituted pyrrole (125). Base-mediated N-alkylation of this pyrrole with 4-methoxyphenethyl bromide produces the key Boger diester (126) and thereby constitutes a relay synthesis of permethyl storniamide A (120). 

TABLE 9.7. Lewis Acid Mediated Aldol Condensations of Boron Enolate 100b... 

Boronic acid hnkers (Tab. 3.6) are useful for the attachment of diols, the protection of glycosides [105] or as precursors for the metal-mediated cleavage [106]. The boronates formed are sensitive to water and simple hydrolysis is sufficient for cleavage. Recently, Carreaux and Carboni developed a new boronate-based strategy for traceless sohd-phase synthesis of aromatic compounds [107]. 

A Pd(0)-catalyzed/Cu(l)-mediated carbon-carbon cross-coupling of 3,4-dihydropyrimidine-2-thiones 520 and boronic acids occurs under microwave-assisted conditions to give 2-aryl-l,4-dihydropyrimidines 521 in moderate to high yield <20040L771>. In contrast, Gu(ll)-mediated reaction of the same substrates leads to carbon-sulfur cross-coupling. 

Chlorodifluoromethylketones underwent aldol reactions (Eq. 124) via zinc enolates, to afford good yields of a,a-difluoro-/ -hydroxy ketones, in a study by the Kyoto group [327]. Copper(I) or silver salt catalysis was essential and boron-trifluoride additive appeared to exert a key role in the conversion to the enolate. Earlier [328], chlorodifluoromethyl ketones had been converted to the di-fluoroenoxy silanes by the action of zinc in the presence of chlorotrimethyl silane. A difluoroenoxy silane was used by McCarthy and co-workers [329] to synthesise a kynureninase inhibitor (Eq. 125) Lewis acid-mediated reaction with a chloroglycinate installed the key carbon-carbon bond. 

A highly stereoselective synthesis of retinol via a Cm + C6 route was depicted by De Lera et al. [52]. A Suzuki reaction of a C14 alkenyliodide with a Cg alkenylboronic acid afforded retinol in 83% yield, with retention of the geometries of the coupling partners. The alkenyliodide was obtained by a zirconium-mediated methylalumination and a subsequent Al/I exchange by slow addition of ICN. Coupling with the C6 boronic acid (12 hrs to reach completion), afforded retinol in 83% yield [53], Fig. (21). 

Oxindole 89 was cleanly demethylated upon treatment with boron tribromide. The resulting oxindole 90 was subjected to the prenylation conditions, and the desired alkylated product 91 was obtained in 52% yield. The epoxidation/Lewis acid-mediated cyclization proved to be successful on this substrate. The epoxide product was directly treated with SnCl4 in THF to provided the desired 92. When oxindole 92 was treated with NaBHt (1.6 equivjand BF3 OEt2 (3.5 equiv) in THF, the desired 93 was obtained. The indole 93 was treated with TBDMSC1 and imidazole in DMF, to provide the required O-silylated indole, which was easily converted to the gramine 94 through the well known Mannich procedure. 

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