Boronic acid, ethyl

OSg, cyc/o-Octasulfur monoxide, 21 172 O2BC2H, Boronic acid, ethyl-, 24 83 02BF4FeCiiHig, Iron(l-t-), dicarbonyl(t) -cyclopentadienyl)(-n -2-methyl-l-pro-penyl)-, tetrafluoroborate(l -), 24 166 O2BNC4H12, Borane, carboxy-compd. with trimethylamine (1 1), 25 81... 

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-... 

In a similar way, Carreaux and coworkers [53] used 1-oxa-l,3-butadienes 4-155 carrying a boronic acid ester moiety as heterodienes [54], enol ethers and saturated as well as aromatic aldehydes. Thus, reaction of 4-155 and ethyl vinyl ether was carried out for 24 h in the presence of catalytic amounts of the Lewis acid Yb(fod)3 (Scheme 4.33). Without work-up, the mixture was treated with an excess of an aldehyde 4-156 to give the desired a-hydroxyalkyl dihydropyran 4-157. Although this is not a domino reaction, it is nonetheless a simple and useful one-pot procedure. 

The closest organic specie to the inorganic boric acid are the boronic acids generally described as R-B(OH)2. Boronic acids have been shown to act as inhibitors of the subtilisins. X-ray crystallographic studies of phenylboronic acid and phenyl-ethyl-boronic acid adducts with Subtilisin Novo have shown that they contain a covalent bond between the oxygen atom of the catalytic serine of the enzyme and the inhibitor boron atom (Matthews et al, 1975 and Lindquist Terry, 1974). The boron atom is co-ordinated tetrahedrally in the enzyme inhibitor complex. It is likely that boric acid itself interacts with the active site of the subtilisins in the same manner. 

With this idea in mind, Deslongchamps treated the cw-decalin-2,7-dione (12) with a mixture of acetic anhydride-acetic acid in the presence of boron trifluoride ethyl etherate, at room temperature, and the twistanone 20 was isolated in 75% yield. The whole synthetic sequence is outlined in Scheme 13.1.7. 

Commercial boron trifluoride ethyl etherate (from Mathe-son Coleman and Bell) is distilled in an all glass apparatus at 46° (10 mm.) from a few pieces of granular calcium hydride. The latter serves to remove small quantities of volatile acids and greatly reduces bumping during distillation. 

A synthetic procedure 33 has been developed for the preparation of boronic acids with a protected aldehyde side chain, 2-(l,3-dioxolan-2-yl)ethyl, which is readily converted into boroOrn peptides similar to 30. Peptides containing boroLys were prepared by a series of reactions analogous to those used for the preparation of 30 except 4-bromobut-l-ene was used as starting material in place of 3-bromoprop-l -ene 36 ... 

Grigg et al. [61] have recently reported a one-pot reaction involving the initial three-component condensation with a 2-halo-benzylamine 112, ethyl glyoxylate 113 and an aryl boronic acid 114, followed by Pd cyclization in the presence of carbon monoxide to give 116, or in the presence of allene to form dihydroisoquinoline amino acid derivatives 117 (Scheme 7.15). 

Milkiewicz and coworkers [16] prepared a series of novel tetra-substituted furo[3,2-b Ipyrroles from the methyl or ethyl 3-bromo-2-phcnyllliro 3,2-/ pyrrole-5-carboxylate 40, which was prepared from 3-bromo-2-phenylfuran-2-carbaldehyde 39. The compounds 40 were subjected to a Suzuki coupling with 4-chlorophenyl boronic acid to form 41, which was treated with a variety of alkylating agents to afford the corresponding esters 42. The esters were then saponified to acids 43 (Scheme 6). 

Enantiomerically enriched a-hydroxy acetals are interesting synthons and can be transformed to a variety of chiral building blocks such as 1,2-diols, a-hydroxy acids, or 1,2-amino alcohols (Scheme 18.4). Whereas the oxidation to (f )-ethyl lactate was rather difficult and required the protection of the OH group, the reduction could be easily accomplished after hydrolysis of the acetal. No significant racemization was observed. With a boronic acid derivative and a secondary amine as described by Petasis and Zavialov,24 it was also possible to synthesize an amino alcohol with high diastereoselectivity. 

A second peptide coupling employing 2-pyrazine carboxylic acid (24) and TBTU affords 25. Finally the boronic ester moiety is removed under acidic conditions using isobutyl boronic acid. This regenerates pinanediol boronic ester 16, which can be used in another batch run of the process. Crystallization from ethyl acetate gives bortezomib in its anhydride (boroxine) form 26. The overall yield for the route is 35% with a typical purity of > 99% w/w. 

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]. 

There are many kinds of capsules but few have the capacity to position co-guests in predictable orientations. We used the ability of 1.24.1 to do so, and applied it to evaluate hydrogen-bonding interactions between boronic acids, carboxylic acids, and primary amides [52], The phenyl boronic acids are useful as components of covalently self-assembled systems [53], and we found that the p-methyl, methoxy, ethyl, and isopropyl derivatives all fit as symmetrical dimers inside I.24.I. The structure of the boronic acid dimer has been debated but a recent theoretical study found the doubly hydrogen-bonded exo/endo conformer (Fig. 10) to be lowest in... 

Fig. 10 The structures of the exo-endo and anti-syn isomers of the H-B(OH)2 hydrogen-bonded dimer. The energy-minimized structure (HF/6-31 g ) of the exo-endo isomer of p-ethyl-phenyl boronic acid dimer in 1.24.1...

We compared combinations of encapsulated carboxylic acids, boronic acids, and carboxamides to determine the strongest interactions - at least in the context of the capsule [55], Direct competition experiments between guests of the same size (the p-ethyl derivatives) were used to eliminate the effects of fit . 

Fig. 11 The downfield region of 1H NMR spectra (600 MHz, mesitylene-dJ2) of 1.24.1 with equimolar mixture of (a) p-ethyl benzamide and p-ethyl benzoic acid, (b) p-ethyl phenyl boronic acid and p-ethyl benzoic acid, (c) p-ethyl phenyl boronic acid and p-ethyl benzamide, and (d) p-ethyl phenyl boronic acid, p-ethyl benzoic acid and p-ethyl benzamide...

Ethylenediammonium diacetate (38734-69-9), 69, 32 Ethyl ether, compd. with boron fluoride (BF3) (1 1), 65, 17 Ethyl formate Formic acid, ethyl ester (109-94-4), 67, 52 (l-Ethyl)heptanyl 3-ketobutanoate, 68, 210... 

Libraries targeted towards proteolytic enzymes, nonproteolytic enzymes, G-protein coupled receptors (GPCRs) and ion-channels have been very successful in lead identification. Libraries of hydroxamates (4), hydroxy ethyl-enes (5), boronic acids (6) and aketo sulfon-... 

Straightforward 5-lithiation results using -BuLi with ethyl 3-mcthoxy-l -methyl-17/-pyrazol-4-earboxy late and halides, zincates, or boronic acids can thus be produced <2002SL769>. A neat device allows 3-lithiation of indazole silylation at N(2) allows the desired 3-metallation (Scheme 60) <2006EJ02417>. 

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