Bromo Alcohol Research Articles

Regioselective Epoxide Ring Opening for the Stereospecific Scale-Up Synthesis of BMS-960, A Potent and Selective Isoxazole-Containing S1P1 Receptor Agonist

This article presents a stereospecific scale-up synthesis of (S)-1-((S)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylic acid (BMS-960), a potent and selective isoxazole-containing S1P1 receptor agonist. The process highlights an enzymatic reduction of α-bromoketone toward the preparation of (S)-bromo alcohol, a key precursor of (S)-4-(oxiran-2-yl)benzonitrile. A regioselective and stereospecific epoxide ring-opening reaction was also optimized along with improvements to 1,2,4-oxadiazole formation, hydrolysis, and crystallization. The improved process was utilized to synthesize batches of BMS-960 for Ames testing and other toxicological studies.

Synthesis of ceramides NS and NP with perdeuterated and specifically ω deuterated N-acyl residues.

The synthesis of 12 deuterated ceramides with either a deuteration at the last carbon atom of the amide bound fatty acid or a perdeuterated fatty acid chain is described. The ceramides were prepared starting from sphingosine or phytosphingosine and ω deuterated or perdeuterated fatty acids with PyBOP® as activating agent in high yields. For the synthesis of the specifically deuterated fatty acids, dicarboxylic acids were transformed into ω deuterated alkyl bromide, which was chain elongated with blocked ω bromo alcohols by copper catalyzed Grignard coupling. Oxidation of regenerated alcohol function yields the ω deuterated fatty acids.

Synthesis of the spiroacetal fragments of spirofungins A and B, antibiotics isolated from Streptomyces violaceusniger Tü 4113

Abstract The spiroacetal [C(9)–C(20)] fragments of spirofungins A and B, antibiotics isolated from Streptomyces violaceusniger Tü 4113, were prepared from a known bromo alcohol derived from (S)-citronellal, using thermodynamically controlled iodolactonization and spiroacetalization as the key steps.

Catalytic, Enantioselective Synthesis of Taranabant, a Novel, Acyclic Cannabinoid-1 Receptor Inverse Agonist for the Treatment of Obesity

Chiral amide 1 (MK-0364, taranabant) is a potent, selective, and orally bioavailable cannabinoid-1 receptor (CB-1R) inverse agonist indicated for the treatment of obesity. An asymmetric synthesis featuring a dynamic kinetic resolution via hydrogenation for the preparation of the bromo alcohol 5 is disclosed. Conversion of the alcohol intermediate to the chiral amide 1 is accomplished in good overall yield.

O‐Phenylenediamine as a New Catalyst in the Highly Regioselective Conversion of Epoxides to Halohydrins with Elemental Halogens.

AbstractFor Abstract see ChemInform Abstract in Full Text.

O-Phenylenediamine as a New Catalyst in the Highly Regioselective Conversion of Epoxides to Halohydrins with Elemental Halogens

The regioselective ring opening of epoxides using elemental iodine and bromine in the presence of o-phenylenediamine as a new catalyst affords vicinal iodo alcohols and bromo alcohols in high yields. The major advantages of this method are versatility, high regioselectivity, a cheap and commercially available catalyst, mild and neutral reaction conditions, and short reaction times. Fourier transform Raman spectroscopy was used to study the reaction of iodine with o-phenylenediamine. The results indicate that the complex [(Diamine)I]+·I5− is formed, and we suggest that the major nucleophile is the pentaiodide ion. This bulky nucleophile has a fundamental role in the high regioselectivity observed attacking the less sterically hindered epoxide carbon.

Halogenated Cleavage of Epoxides into Halohydrins in the Presence of a Series of Diamine Podands as Catalyst with Elemental Iodine and Bromine.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Cleavage of Epoxides into Halohydrins with Elemental Iodine and Bromine in the Presence of 2,6‐Bis[2‐(o‐aminophenoxy)methyl]‐4‐bromo‐1‐methoxybenzene (BABMB) as Catalyst.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Cleavage of epoxides into halohydrins with elemental iodine and bromine in the presence of 2,6-bis[2-( o-aminophenoxy)methyl]-4-bromo-1-methoxybenzene (BABMB) as catalyst

The ring opening of epoxides with elemental iodine and bromine in the presence of 2,6-bis[2-( o-aminophenoxy)methyl]-4-bromo-1-methoxybenzene as a new catalyst affords vicinal iodo alcohols and bromo alcohols in high yields. This new procedure occurs regioselectively under neutral and mild conditions in various aprotic solvents even when sensitive functional groups are present.

Halogenated Cleavage of Epoxides into Halohydrins in the Presence of a Series of Diamine Podands as Catalyst with Elemental Idoine and Bromine

The ring opening of epoxides with elemental iodine and bromine in the presence of three diamine podands 7-9 as new catalysts affords vicinal iodo alcohols and bromo alcohols in high yields. This new procedure occurs regioselectively under neutral and mild conditions in various aprotic solvents even when sensitive functional groups are presented.

An enantioselective strategy to macrocyclic bisindolylmaleimides. An efficient formal synthesis of LY 333531.

[reaction: see text]. The ability to employ a bromo alcohol as a nucleophile in a palladium-catalyzed dynamic kinetic asymmetric transformation leads to an efficient synthesis of a selective PKC inhibitor under clinical development.

The halogen-mediated opening of epoxides in the presence of pyridine-containing macrocycles

The ring opening of epoxides with elemental iodine and bromine in the presence of three pyridine-containing macrocyclic diamides as new catalysts affords vicinal iodo alcohols and bromo alcohols in high yields. This new procedure occurs regioselectively under mild conditions in various aprotic solvents. The catalysts are easily recovered and can be reused several times.

Absolute Orientation of Molecules of Amphiphilic Alcohols in Crystalline Monolayers at the Air−Water Interface

The absolute orientations of the amphiphilic molecules α-hydroxy ω-bromo alcohols BrCnH2n OH, n = 21, 22, and the alkyl hydroxy esters CmH2m+1COO(CH2)nOH, m = 14, 15, n = 10, in crystalline monolayer forms on water have been determined, the former by grazing incidence X-ray diffraction (GIXD) and the latter by sum frequency generation (SFG). The assignment was made for the alkyl hydroxy esters by establishing the polar angle between the terminal CH3−C bond and the normal to the plane of the monolayer; for the bromo alcohols the assignment was made by a determination of the two-dimensional crystal structure via X-ray structure factor calculations. The SFG results are in agreement with reported GIXD and lattice energy analyses of the alkyl hydroxy esters m = 19, n = 9, 10. These studies have further revealed the absolute orientation of the alcohol C−OH bonds at the water surface, which in turn can be correlated with the ice-nucleating behavior of the monolayers on supercooled water drops in terms of the odd and even values of n.

Schiff-Base Complexes of Metal(II) as New Catalysts in the High-Regioselective Conversion of Epoxides to Halo Alcohols by Means of Elemental Halogen

Abstract The ring opening of epoxides with elemental iodine and bromine in the presence of some Schiff-base complexes of the first-row transition metal(II) as new catalysts affords vicinal iodo alcohols and bromo alcohols in high yields. This new procedure occurs regioselectively under mild conditions in various aprotic solvents. The catalysts are easily recovered and can be reused several times.

ChemInform Abstract: Sodium Bis(2‐methoxyethoxy)aluminium Hydride in Petroleum Ether; a Reagent for the Selective Reduction of Brominated Fatty Esters to Bromo Alcohols.

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.

On the mechanism of the stereo- and regioselective ether-ring opening of 1,2,3,4-tetrahydro-1β,4β-epoxy-2α,3α-carbonyldioxy arene systems with boron tribromide

Stereo- and regioselective formation of bay-region bromo alcohols observed during etherbridge opening of the titled systems with boron tribromide has been rationalized, on the basis of AM1 calculations, by the intramolecular same-face delivery of the bromide ion from the intermediate borate group and the relative stability of the bay-region versus non-bay-region benzylic cations, respectively.

Studied Directed toward the Synthesis of Phomenoic Acid. Part 2. Stereocontrolled Synthesis of the C(7)‐to‐C(14) Segment

AbstractStarting from the esters (2E,4S)‐6 and (2E,4R)‐6, bromo aldehydes (S)‐9 and (R)‐9 as well as bromo alcohols (S)‐10 and (R)‐10, respectively, were prepared. Bromo alcohol (R)‐8 was converted to the diol (2E,4R)‐16. Ozonolysis of the latter led to aldehyde (R)‐17, which was transformed, by a Wittig reaction, to (2R,4E,6R)‐18, corresponding to the C(7)‐to‐C(14) segment of phomenoic acid (1). Attempts to improve the yields by applying a Julia coupling of (R)‐23, which was prepared from (2E,4R)‐7, with (R)‐24 were unsuccessful. Finally, the coupling of the iodo derivative (2E,4S)‐28 with the lithiated derivative of 1,3‐dithiane 30 by the Corey‐Seebach ‘Umpolung’ led to (3S,4E)‐32 which is a derivative of the C(7)‐to‐C(14) segment of 1, suitable for further transformations.

Diastereo‐ and enantioselective synthesis of the 18‐membered lichen macrolide (+)‐aspicilin

AbstractThe asymmetric synthesis of the lichen macrolide (+)‐aspicilin (1) was realised in 19 steps and with high stereoselectivity (de ≥ 91 %, ee ≥ 96%). Three of the four stereogenic centres were generated by employing the SAMP/RAMP hydrazone method. Key steps of the synthesis are the α,α′‐double alkylation of RAMP hydrazone (R)‐10 of 2,2‐dimethyl‐1,3‐dioxan‐5‐one B and the enantioselective synthesis of the bromo alcohol (S)‐9 (subunit A) by a combination of SAMP hydrazone α‐alkylation with subsequent Baeyer‐Villiger oxidation.

Synthesis of 3‐alkyl‐8‐substituted‐ and 4‐hydroxy‐8‐substituted‐2,3,4,5‐tetrahydro‐1H‐2‐benzazepines

AbstractBased on the Schmidt reaction and an iodolactone ring expansion reaction, two different synthetic routes to substituted 2,3,4,5‐tetrahydro‐1H‐2‐benzazepines were developed. The Schmidt reaction on 2,3‐dihydro‐2H‐1‐naphthalenone (1) gave 3, the product resulting from the alkyl group migration, as the major product instead of the tetrazole 2. This prompted the investigation of the Schmidt reaction on aromatic ketones 8 and 12. The product 9 due to alkyl group migration was the major product of the Schmidt reaction on 2‐methyl‐3,4‐dihydro‐2H‐1‐naphthalenone (8). The β‐keto diester 12 gave a mixture of decarb‐oxylated lactams after the Schmidt reaction. In this case, the lactam 13 resulting from the migration of the aromatic ring dominated over the other lactam 14. When lactam 14 was subjected to nitration, a single regioisomer was produced and transformed to the bromo alcohol 19. The other approach was based on the single pot ring expansion of the iodolactone 22 to the lactam 23 in the presence of methanolic ammonia. The iodolactone 22 was readily prepared from 2‐allylbenzoic acid.

Cyclodextrin-induced fluid solution room-temperature phosphorescence from acenaphthene in the presence of 2-bromoethanol

A 1:1 stoichiometric ratio and a formation constant of 130 1 mol −1 were obtained for the binary inclusion complex between acenaphthene and β-cyclodextrin (CD). On addition of 2-bromoethanol, effective quenching of the fluorescence emission and enhancement of the room-temperature phosphorescence (RTP) of acenaphthene is observed. The use of 2-bromoethanol as an external “heavy atom” to obtain room-temperature phosphorescence in fluid solutions is discussed. The RTP emission from acenaphthene included in β-CD was optimized and characterized. The apparent formation constant of the ternary associate was determined to be 880 1 mol −1 by the use of RTP enhancement in the presence of 1% 2-bromoethanol. The data indicate a ternary association between acenaphthene, β-CD and the bromo alcohol. The use of sodium sulfite, for chemical deoxygenation, to obtain RTP emission from a non-heavy atom-containing luminophor is shown to be feasible. The kinetics of the deoxygenation reaction were established and a photochemical catalytic effect on the reaction was demonstrated.