1,721,044 research outputs found
Nickel/Bis(oxazoline)-Catalyzed Asymmetric Kumada Reactions of Alkyl Electrophiles: Cross-Couplings of Racemic α-Bromoketones
No full textThe first asymmetric Kumada reactions of alkyl electrophiles are described, specifically, cross-couplings of racemic α-bromoketones with aryl Grignard reagents. Several features of this investigation are of interest. First, the couplings proceed at remarkably low temperature (−40 or −60 °C), which enables the asymmetric synthesis of racemization-prone alpha-arylketones. Second, dialkyl ketones undergo enantioselective coupling in good ee and yield. Third, readily available bis(oxazolines) are shown for the first time to be effective ligands for cross-couplings of alkyl electrophiles, thereby opening the door to new opportunities in asymmetric catalysis.National Institute of General Medical Sciences (U.S.) (Grant R01-GM62871)Merck Research LaboratoriesNovartis (Firm
Enantioselective Alkenylation via Nickel-Catalyzed Cross-Coupling with Organozirconium Reagents
No full textA new family of organometallic compounds, organozirconium reagents, are shown to serve as suitable partners in cross-coupling reactions of (activated) secondary alkyl electrophiles. Thus, the first catalytic method for coupling secondary α-bromoketones with alkenylmetal reagents has been developed, specifically, a mild, versatile, and stereoconvergent carbon−carbon bond-forming process that generates potentially labile β,γ-unsaturated ketones with good enantioselectivity.National Institute of General Medical Sciences (U.S.) (grant R01-GM62871)Novartis (Firm)Merck Research Laboratorie
Nickel-Catalyzed Asymmetric Negishi Cross-Couplings of Racemic Secondary Allylic Chlorides with Alkylzincs
No full textThe transition metal-catalyzed enantioselective coupling of allylic electrophiles with carbon nucleophiles has been the focus of intense investigation.5 Salient examples include palladium-catalyzed couplings with enolates, nickel-catalyzed couplings with Grignard reagents, and copper-catalyzed couplings with Grignard and diorganozinc reagents.6 Despite impressive progress, the development of methods that have broader scope with respect to the nucleophile, as well as improved functional-group compatibility, persist as important challenges
Palladium-Catalyzed Alkyl-Alkyl Suzuki Cross-Couplings of Primary Alkyl Bromides at Room Temperature: (13-Chlorotridecyloxy)triethylsilane [Silane, [(13-chlorotridecyl)oxy]triethyl-]
No full textA. 1-Bromo-8-chlorooctane (1). An oven-dried, 200-mL, two-necked,
round-bottomed flask equipped with an argon inlet and a magnetic stirbar
(octagonal, molded pivot ring, 25 mm length and 6 mm diameter) is purged
with argon for 5 min and then charged through the open neck with CH2Cl2
(50 mL via syringe) (Note 1), imidazole (2.19 g, 32.1 mmol, 1.10 equiv)
(Note 2), and dichlorotriphenylphosphorane (10.4 g, 31.2 mmol, 1.07 equiv)
(Note 3). The open neck is capped with a rubber septum, and the stirred
solution is cooled in an ice bath for 5 min. A solution of 8-bromo-1-octanol
(5.0 mL, 6.11 g, 29.2 mmol, 1.00 equiv) (Note 4) in CH2Cl2 (10 mL) (Note 1)
is added via syringe over 5 min. The reaction mixture is allowed to warm to rt, and the resulting heterogeneous solution (a white precipitate formed) is
stirred for 4 h. The progress of the reaction is followed by TLC analysis on
SiO2 (10% EtOAc/hexanes as the eluent; visualization with a KMnO4 stain;
the alcohol starting material has an Rf = 0.2, and the chloride product has an
Rf = 0.9) (Note 5). After the alcohol is consumed, the reaction is diluted with
pentane (200 mL), and the mixture is filtered through a pad of SiO2 (7 cm
diameter 6 cm height) in a sintered glass funnel. The SiO2 is washed with
additional pentane (400 mL). The filtrate is concentrated by rotary
evaporation (20 mmHg, 30 °C), which furnishes the desired product as a
colorless oil (6.23–6.44 g, 94–97 % yield) (Note 6). The product is used in
the next step without further purification
Nickel-Catalyzed Coupling Reactions of Alkyl Electrophiles, Including Unactivated Tertiary Halides, To Generate Carbon–Boron Bonds
Full text linkThrough the use of a catalyst formed in situ from NiBr[subscript 2]·diglyme and a pybox ligand (both of which are commercially available), we have achieved our first examples of coupling reactions of unactivated tertiary alkyl electrophiles, as well as our first success with nickel-catalyzed couplings that generate bonds other than C–C bonds. Specifically, we have determined that this catalyst accomplishes Miyaura-type borylations of unactivated tertiary, secondary, and primary alkyl halides with diboron reagents to furnish alkylboronates, a family of compounds with substantial (and expanding) utility, under mild conditions; indeed, the umpolung borylation of a tertiary alkyl bromide can be achieved at a temperature as low as −10 °C. The method exhibits good functional-group compatibility and is regiospecific, both of which can be issues with traditional approaches to the synthesis of alkylboronates. In contrast to seemingly related nickel-catalyzed C–C bond-forming processes, tertiary halides are more reactive than secondary or primary halides in this nickel-catalyzed C–B bond-forming reaction; this divergence is particularly noteworthy in view of the likelihood that both transformations follow an inner-sphere electron-transfer pathway for oxidative addition.National Institute of General Medical Sciences (U.S.) (Grant R01-GM62871
Asymmetric Carbon-Carbon Bond Formation gamma to a Carbonyl Group: Phosphine-Catalyzed Addition of Nitromethane to Allenes
Full text linkA chiral phosphine catalyzes the addition of a carbon nucleophile to the γ position of an electron-poor allene (amide-, ester-, or phosphonate-substituted), in preference to isomerization to a 1,3-diene, in good ee and yield. This strategy provides an attractive method for the catalytic asymmetric γ functionalization of carbonyl (and related) compounds.National Institutes of Health (U.S.) (National Institute of General Medical Sciences, Grant R01-GM57034)Merck Research LaboratoriesNovartis (Firm
Palladium/Tris(tert-butyl)phosphine-Catalyzed Suzuki Cross-Couplings in the Presence of Water
No full textDipalladiumtris(dibenzylideneacetone)/tris(tert-butyl)phosphonium tetrafluoroborate/potassium fluoride dihydrate [Pd2(dba)3/[HP(t-Bu)3]BF4/KF⋅2 H2O] serves as a mild, robust, and user-friendly method for the efficient Suzuki cross-coupling of a diverse array of aryl and heteroaryl halides with aryl- and heteroarylboronic acids.National Institutes of Health (U.S.) (National Institute of General Medical Sciences, grant R01-GM62871)Merck Research LaboratoriesNovartis (Firm
Alkyl-Alkyl Suzuki Cross-Coupling of Unactivated Secondary Alkyl Chlorides
Full text linkNo such thing as a problem substrate! In a reaction designed specifically for the title substrates C-C coupling with alkyl boranes occurred in good yield at room temperature with commercially available catalyst components (see scheme). This versatile method is also suitable for Suzuki reactions of secondary and primary alkyl bromides and iodides, as well as primary alkyl chlorides.National Institute of General Medical Sciences (U.S.) (Grant R01-GM62871)Eli Lilly and Company (Fellowship)Martin Family Society of Fellows for Sustainability (Fellowship)Merck Research LaboratoriesNovartis (Firm
Application of a New Chiral Phosphepine to the Catalytic Asymmetric Synthesis of Highly Functionalized Cyclopentenes That Bear an Array of Heteroatom-Substituted Quaternary Stereocenters
No full textThrough the design and synthesis of a new chiral phosphepine, the first catalytic asymmetric method for the [3 + 2] cycloaddition of allenes with olefins has been developed that generates cyclopentenes that bear nitrogen-, phosphorus-, oxygen-, and sulfur-substituted quaternary stereocenters. A wide array of racemic γ-substituted allenes can be employed in this stereoconvergent process, which occurs with good enantioselectivity, diastereoselectivity, regioselectivity, and yield. Mechanistic studies, including a unique observation of a (modest) kinetic resolution of a racemic allene, are consistent with addition of the phosphepine to the allene being the turnover-limiting step of the catalytic cycle.National Institute of General Medical Sciences (U.S.) (grant R01-GM57034)Dainippon Pharmaceutical Co., Ltd. (Fellowship
Nickel-Catalyzed Enantioselective Negishi Cross-Couplings of Racemic Secondary α-Bromo Amides with Alkylzinc Reagents: (S)-N-Benzyl-7-cyano-2-ethyl-N-phenylheptanamide
Full text linkProcedure: A. (5-Cyanopentyl)zinc(II) bromide (1). An oven-dried, 200-mL pear-shaped Schlenk flask equipped with a magnetic stirbar (egg shaped, 25.4 × 12.7 mm) and an argon line connected to the standard taper outer joint is purged with argon for 5 min. Zinc powder (9.80 g, 150 mmol, 1.50 equiv) (Note 1) is added through the open neck, and then the flask is capped with a rubber septum and heated in an oil bath under high vacuum (0.5 mmHg) at 70 °C for 30 min. Then, the flask is refilled with argon, and anhydrous 1,3-dimethyl-2-imidazolidinone (DMI; 100 mL) (Note 2) is added via syringe. Iodine (I2) (634 mg, 2.50 mmol, 0.0250 equiv) (Note 3) is added in one portion through the neck. The neck is re-capped with a rubber septum, and the reaction mixture is stirred at 70 °C in an oil bath until the red color fades (~5 min). 6-Bromohexanenitrile (13.2 mL, 100 mmol, 1.00 equiv) (Note 4) is added via syringe over 4 min, and the reaction mixture is stirred at 70 °C for 12 h. Then, the oil bath is removed, and the mixture is allowed to cool at rt for 1 h without stirring. During this time, the unreacted zinc powder settles at the bottom of the flask. The flask is equipped with a fritted filter tube of medium porosity capped with an oven-dried, 2-necked 250-mL round-bottom flask, and the supernatant solution is filtered under argon by inverting the set-up (Note 5). The resulting clear yellow solution is employed in the next step without further purification. 1H NMR spectroscopy is used to determine that the concentration of the alkylzinc solution is 0.72 M (Note 6). This organozinc solution can be stored under argon at 0-4 °C for up to 3 weeks without deterioration
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