Coupling Of Boronic Acids Research Articles

Process Research and Development for an Efficient Synthesis of the HIV Protease Inhibitor BMS-232632

Development of an efficient and scalable process for the human immunodeficiency virus (HIV) protease inhibitor BMS-232632 1-[4-(pyridin-2-yl)phenyl]-5(S)-2,5-bis{[N-(methoxycarbonyl)-l-tert-leucinyl]-amino}-4(S)-hydroxy-6-phenyl-2-azahexane, is described. The key step in the synthesis of the intermediate N-1-(tert-butyloxycarbonyl)-N-2-[4-(pyridin-2-yl)benzylidene]hydrazone (11) was the Pd-mediated coupling of boronic acid 9 with 2-bromopyridine. An efficient procedure was developed for the chemoselective reduction of hydrazone 11 to hydrazine carbamate 4. The key intermediate N-(tert-butyloxycarbonyl)-2(S)-amino-1-phenyl-3(R)-3,4-epoxy-butane (6) was prepared stereoselectively from chiral diol 10. The subsequent union of 4 and 6 followed by coupling with N-methoxycarbonyl-l-tert-leucine provided the free base BMS-232632 in high yield. Evaluation of a variety of salts and identification of bisulfate salt 19 with enhanced bioavailability are also described.

Expanding the diversity of purine libraries

In recent years, there has been a resurgence of interest in the synthesis of purine derivatives due to the discovery of purine-derived ligands for a variety of nucleotide dependent enzymes. The majority of chemistry has focused on substitution of the purine core structure by alkylation at N9 and nucleophilic–aromatic substitution reactions at C2 and C6. Here we report the syntheses of aryl, N-aryl, O-aryl substituted purine libraries by the palladium-mediated coupling of boronic acids, anilines or phenols at the C2 position, and copper(II)-mediated N-arylation with boronic acids at the N9 position. The chemistry described here greatly expands our ability to introduce different functionality and create new purine scaffolds.

Chelating Monoborane Phosphines: Rational and High-Yield Synthesis of [(COD)Rh{(η2-BH3)Ph2PCH2PPh2}][PF6] (COD = 1,5-cyclooctadiene)

The rational and high-yield synthesis of [(COD)Rh{(η2-BH3)Ph2PCH2PPh2}][PF6] (1), which bears a chelating monoborane phosphine, is reported; the solid-state structure shows that the borane coordinates to the metal via two 2e−3c B−H−Rh bonds, which in solution at room temperature are fluxional between all three B−H bonds. Complex 1 is isolated as an air-stable crystalline salt, and its applicability as a catalyst in organic synthesis has been demonstrated in the coupling of boronic acids with enones.

Synthesis of novel retinoid X receptor-selective retinoids.

Retinoids 1-5 have been identified as potent RXR agonists for evaluation in the treatment of non-insulin-dependent (type II) diabetes mellitus (NIDDM). Highly convergent syntheses of 1-5 have been developed. The core tetrahydronaphthalene 7, employed in the synthesis of 1 and 2, was prepared in 98% yield using an AlCl(3)-catalyzed (0.03 equiv) Friedel-Crafts alkylation of toluene with 2,5-dichloro-2,5-dimethylhexane 6. A nitromethane-mediated Fridel-Crafts acylation of 7 with chloromethylnicotinate 9 was developed to prepare ketone 10 in 68% yield. Chelate-controlled addition of MeMgCl to 10 followed by dehydration afforded olefin 11 in 65% yield. Cyclopropanation of 11 with trimethylsulfoxonium ylide, followed by saponification, completed a five-step synthesis of 1 in 33% yield. FeCl(3)-catalyzed (0.05 equiv) Friedel-Crafts acylation of 7 with chloromethylterephthalate 14 afforded ketone 15 in 81% yield. Saponification of 15 and reaction with 50% aqueous NH(2)OH in AcOH afforded a 9:1 mixture of cis and trans oximes, from which the desired cis-oxime 2 was isolated in 43% yield. The core bromo-dihydronaphthalene 29 required for the synthesis of 3-5 was prepared by a Shapiro reaction. Transmetalation of 29 and reaction with Weinreb amides 30b or 36 afforded ketones 32 and 37, which were converted into 3-5 using chemistry comparable to the tetrahydronaphthylene series. Suzuki coupling of boronic acids 41 and 42 with vinyl triflate 43 provided an alternative approach to the synthesis of this class of compounds.

ChemInform Abstract: Thiol Ester—Boronic Acid Coupling. A Mechanistically Unprecedented and General Ketone Synthesis.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Thiol Ester−Boronic Acid Coupling. A Mechanistically Unprecedented and General Ketone Synthesis

Thiol Ester−Boronic Acid Coupling. A Mechanistically Unprecedented and General Ketone Synthesis

ChemInform Abstract: Highly Efficient Palladium‐Catalyzed Boronic Acid Coupling Reactions in Water: Scope and Limitations.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Highly Efficient Palladium-Catalyzed Boronic Acid Coupling Reactions in Water: Scope and Limitations.

The "ligandless" palladium acetate-catalyzed Suzuki cross-coupling reaction of ArX with aryl- and vinylboronic acids in water without organic cosolvent in the presence of tetrabutylammonium bromide is reported. Aryl bromides give high yields and considerably accelerate the coupling. A wide variety of functional groups can be tolerated. Aryl iodides, however, give incomplete conversion and aryl triflate coupling shows no improvement over reported conditions.

ChemInform Abstract: Fluoride‐Mediated Boronic Acid Coupling Reactions.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Fluoride-Mediated Boronic Acid Coupling Reactions

Fluoride-Mediated Boronic Acid Coupling Reactions

Convergent Routes to the [1,3]Dioxolo[4,5-j]phenanthridin-6(5H)-one and 2,3,4,4a-Tetrahydro[1,3]dioxolo[4,5-j]phenanthridin-6(5H)-one Nuclei. Application to Syntheses of the Amaryllidaceae Alkaloids Crinasiadine, N-Methylcrinasiadine and Trisphaeridine

Convergent routes to the title nuclei, (1) and (6), have been developed. Thus, Suzuki coupling of boronic acid (8) with aryl bromide (9) gave the biarylylcarbamate (7) which, on treatment with phosphorus oxychloride (POCl3), underwent Bischler-Napieralski cyclization to give, after acid hydrolysis, the Amaryllidaceae alkaloid crinasiadine (1). The cyclization reaction proceeds via an intermediate chlorophenanthridine (11) which can be isolated and N- methylated. Hydrolysis of the resulting iminium species (17) then afforded N- methylcrinasiadine (2). On the other hand, hydrogenolytic dechlorination of compound (II) affords trisphaeridine (14). Related chemistry has been employed in the preparation of 2,3,4,4a-tetrahydro[1,3] dioxolo [4,5-j]phenanthridin-6(5H)-one (6), the tetracyclic skeleton associated with the narcissus alkaloids lycoricidine (3) and narciclasine (4). Thus, treatment of the gem- dibromocyclopropane (20) with silver cyanate resulted in ring opening thereby affording the allylic isocyanate (25) which could be intercepted with added methanol to give carbamate (24). Suzuki coupling of this last compound with boronic acid (8) gave product (18) which was subjected to treatment with and resulted in the formation of (�)-(6). This latter sequence could be adapted to the preparation of both (R)-(6) and (S)-(6).

Polymers tailored for redox‐ and photoactivity

AbstractThe synthesis of polymers tailored for a specific redox‐ and photoactivity is described.The title compounds can generally be depicted as consisting of electrophoric or chromophoric building blocks which are linked by variable bridging groups.Their properties depend on the nature of both units in the polymer chain. The bridging group between the electrophoric units can be saturated or conjugated and can be incorporated directly upon polymer formation. However, in other polymers such bridging groups are already present, which allow one to switch between an unsaturated and saturated linking.With the “reductive polymerization”, a new method to link e.g. anthracene and isopyrene units is proposed. A Heck‐type reaction and the boronic acid coupling according to Suzuki are used for generating conjugated polymers.In the case of polymers containing 2,2′‐distyrylbiphenyl units it is possible to interrupt π‐conjugation via electron‐transfer or UV‐irradiation. With a thermal ring‐opening reaction of cyclobutene units, a method is shown to create conjugation between π‐systems. By hydrogen elimination in a polymethide structure highly conjugated polymers can be created.