Secondary Alkyl Chlorides Research Articles

ChemInform Abstract: Cobalt‐Catalyzed Directed Alkylation of Olefinic C—H Bond with Primary and Secondary Alkyl Chlorides.

AbstractThe reaction succeeds using a 2‐pyridyl group as the directing group, but is delivered with low or no yield when switching to a pyrazole or imine group.

Cobalt-Catalyzed Directed Alkylation of Olefinic C–H Bond with Primary and Secondary Alkyl Chlorides

Cobalt-Catalyzed Directed Alkylation of Olefinic C–H Bond with Primary and Secondary Alkyl Chlorides

Carbon–Carbon Bond Formation Reactivity of a Four-Coordinate NHC-Supported Iron(II) Phenyl Compound

The preparation and characterization of a NHC-coordinated (NHC = N-heterocyclic carbene) ferrous phenyl complex [(IPr2Me2)2FePh2] (1; IPr2Me2 = 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene) as well as its C–C bond formation reactivity have been studied. The four-coordinate iron(II) phenyl complex was prepared from the reaction of ferrous chloride with PhMgBr and IPr2Me2. It reacts with nonactivated primary and secondary alkyl bromides and chlorides to furnish cross-coupling products and the iron(II) monophenyl species (IPr2Me2)2FePhX (X = Br (2), Cl). When it is treated with cyclooctatetraene (cot) or [Cp2Fe][BArF4] in the presence of PMe3, it undergoes coordination or one-electron oxidation induced reductive elimination of biphenyl to form the corresponding iron(0) or iron(I) species [(IPr2Me2)2Fe(η4-cot)] (3) or [(IPr2Me2)2Fe(PMe3)2][BArF4] (4). All of these iron-containing products have been fully characterized by various spectroscopic methods. Complex 1 and (IPr2Me2)2FeCl2 catalyze the reaction of n...

Cobalt-Catalyzed Directed Alkylation of Olefinic C–H Bond with Primary and Secondary Alkyl Chlorides

A cobalt–N-heterocyclic carbene catalytic system promotes pyridine-directed olefinic C–H alkylation reactions using a variety of primary and secondary alkyl chlorides under mild conditions. Radical clock experiments suggest that the reaction involves single-electron transfer from the cobalt intermediate to the alkyl chloride.

Progress toward the total synthesis of N-methylwelwitindolinone B isothiocyanate.

Progress toward the welwitindolinone alkaloid N-methylwelwitindolinone B isothiocyanate is reported. A key reaction to synthesize the [4.3.1] bicycle embedded in the core of the molecule is a furan type 2 intramolecular Diels-Alder reaction with a tetrasubstituted dienophile, which sets the two vicinal quaternary centers present in the natural product. The sterically encumbered cycloaddition precursor was synthesized using a Horner-Wadsworth-Emmons reaction followed by a Suzuki cross-coupling reaction. Finally, introduction of the secondary alkyl chloride was achieved by a regio- and diastereoselective opening of a [2.2.1] oxobicycloheptane functionality.

Cobalt-Catalyzed Chelation-Assisted Alkylation of Arenes with Primary and Secondary Alkyl Halides

Cobalt–N-heterocyclic carbene catalytic systems have been developed for chelation-assisted ortho-alkylation of aromatic compounds with alkyl halides. Aryl imines can be selectively monoalkylated at room temperature by various primary or secondary alkyl chlorides or bromides. The catalytic system can also be applied to 2-arylpyridine derivatives, which in the absence of steric hindrance are amenable to dialkylation by an excess of the alkyl halide. Mechanistic experiments, including reactions of stereochemical probes and radical clocks, indicate that the reaction involves single-electron transfer from the cobalt center to the alkyl halide to form the corresponding alkyl radical, which has a finite lifetime before it undergoes C–C bond formation.

Expedient Iron‐Catalyzed Coupling of Alkyl, Benzyl and Allyl Halides with Arylboronic Esters

While attractive, the iron-catalyzed coupling of arylboron reagents with alkyl halides typically requires expensive or synthetically challenging diphosphine ligands. Herein, we show that primary and secondary alkyl bromides and chlorides, as well as benzyl and allyl halides, can be coupled with arylboronic esters, activated with alkyllithium reagents, by using very simple iron-based catalysts. The catalysts used were either adducts of inexpensive and widely available diphosphines or, in a large number of cases, simply [Fe(acac)3] with no added co-ligands. In the former case, preliminary mechanistic studies highlight the likely involvement of iron(I)-phosphine intermediates.

Nickel‐Catalyzed CH Alkylations: Direct Secondary Alkylations and Trifluoroethylations of Arenes

A versatile nickel catalyst allowed for C-H alkylations of unactivated arenes with challenging secondary alkyl bromides and chlorides. The high catalytic efficacy also set the stage for direct secondary alkylations of indoles as well as C-H trifluoroethylations with ample substrate scope.

Cobalt-catalyzed directed alkylation of arenes with primary and secondary alkyl halides

Abstract A cobalt–N-heterocyclic carbene catalyst allows ortho-alkylation of aromatic imines with unactivated primary and secondary alkyl chlorides and bromides under room-temperature conditions. The scope of the reaction encompasses or complements that of cobalt-catalyzed ortho-alkylation reactions with olefins as alkylating agents that we developed previously. Stereochemical outcomes of secondary alkylation reactions suggest that the reaction involves single-electron transfer from a cobalt species to the alkyl halide to generate the corresponding alkyl radical. A cycloalkylated product obtained by this method can be transformed into unique spirocycles through manipulation of the directing group and the cycloalkyl groups.

Cobalt‐Catalyzed CH Bond Functionalizations with Aryl and Alkyl Chlorides

Inexpensive cobalt catalysts derived from N-heterocylic carbenes (NHC) allowed efficient catalytic C-H bond arylations on heteroaryl-substituted arenes with widely available aryl chlorides, which set the stage for the preparation of sterically hindered tri-ortho-substituted biaryls. Likewise, challenging direct alkylations with β-hydrogen-containing primary and even secondary alkyl chlorides proceeded on pyridyl- and pyrimidyl-substituted arenes and heteroarenes. The cobalt-catalyzed C-H bond functionalizations occurred efficiently at ambient reaction temperature with excellent levels of site-selectivities and ample scope. Mechanistic studies highlighted that electron-deficient aryl chlorides reacted preferentially, while the arenes kinetic C-H bond acidity was found to largely govern their reactivity.

ChemInform Abstract: A User‐Friendly Procedure for the Preparation of Secondary Alkyl Chlorides.

AbstractSecondary alkyl sulfonates are converted into the corresponding chlorides upon treatment with Bn‐NBu3+Cl‐.

A User-Friendly Procedure for the Preparation of Secondary Alkyl Chlorides

Secondary alkyl chlorides have been efficiently prepared from secondary alkyl sulfonates under mild and user-friendly conditions. The exchange reaction was generally performed by using benzyltributylammonium chloride in acetone (reflux, 30 min). Yields are excellent from functionalized, base-sensitive and hindered secondary alkyl sulfonates.

Cross-Coupling of Non-activated Chloroalkanes with Aryl Grignard Reagents in the Presence of Iron/N-Heterocyclic Carbene Catalysts

An efficient and high-yielding cross-coupling reaction of various primary, secondary, and tertiary alkyl chlorides with aryl Grignard reagents was achieved by using catalytic amounts of N-heterocyclic carbene ligands and iron salts. This reaction is a simple and efficient arylation method having applicability to a wide range of industrially abundant chloroalkanes, including polychloroalkanes, which are challenging substrates under conventional cross-coupling conditions.

Copper(I)-Catalyzed Boryl Substitution of Unactivated Alkyl Halides

Borylation of alkyl halides with diboron proceeded in the presence of a copper(I)/Xantphos catalyst and a stoichiometric amount of K(O-t-Bu) base. The boryl substitution proceeded with normal and secondary alkyl chlorides, bromides, and iodides, but alkyl sulfonates did not react. Menthyl halides afforded the corresponding borylation product with excellent diastereoselectivity, whereas (R)-2-bromo-5-phenylpentane gave a racemic product. Reaction with cyclopropylmethyl bromide resulted in ring-opening products, suggesting the reaction involves a radical pathway.

Synthesis of (±)-Hapalindoles K, A, and G

Hapalindoles K, A, and G are indole alkaloids produced by the terrestrial blue-green algae. Structurally, they consist of a tetracyclic skeleton and a secondary alkyl chloride stereocenter. Herein, the first total syntheses of (±)-hapalindoles K and A are presented as well as the formal synthesis of (±)-hapalindole G.

ChemInform Abstract: Stereoconvergent Amine‐Directed Alkyl—Alkyl Suzuki Reactions of Unactivated Secondary Alkyl Chlorides.

AbstractThe reaction is a complement of previous reports concerning enantioselective alkyl—alkyl Suzuki couplings directed by carbon‐ and oxygen‐based functional groups.

Tuning Chemoselectivity in Iron‐Catalyzed Sonogashira‐Type Reactions Using a Bisphosphine Ligand with Peripheral Steric Bulk: Selective Alkynylation of Nonactivated Alkyl Halides

The incredible bulk: A highly C-center-selective alkynylation of nonactivated alkyl halides with the corresponding Grignard reagents is achieved by using the iron-phosphine complex 1. Primary and secondary alkyl iodides, bromides, and chlorides take part in the reaction to give the substituted alkynes in good to excellent yields. Sequential cyclization/cross-coupling reactions are also demonstrated.

Amine-Directed Alkyl-Alkyl Suzuki Reactions

This work reports the development of a stereoconvergent aryl amine directed alkyl-alkyl Suzuki coupling. In this protocol, unactivated secondary alkyl chlorides serve as substrates and the desired products are generally obtained with good enantioselectivity using a C 2-symmetric 1,2-diamine ligand.

Stereoconvergent Amine-Directed Alkyl–Alkyl Suzuki Reactions of Unactivated Secondary Alkyl Chlorides

A new family of stereoconvergent cross-couplings of unactivated secondary alkyl electrophiles has been developed, specifically, arylamine-directed alkyl-alkyl Suzuki reactions. This represents the first such investigation to be focused on the use of alkyl chlorides as substrates. Structure-enantioselectivity studies are consistent with the nitrogen, not the aromatic ring, serving as the primary site of coordination of the arylamine to the catalyst. The rate law for this asymmetric cross-coupling is compatible with transmetalation being the turnover-limiting step of the catalytic cycle.

ChemInform Abstract: Alkyl—Alkyl Suzuki Cross‐Coupling of Unactivated Secondary Alkyl Chlorides.

AbstractThe first alkyl—alkyl Suzuki reaction of unactivated secondary chlorides is applicable to both cyclic and acyclic secondary alkyl halides tolerating a variety of functional groups.