Cobalt-Catalyzed, Directed C-H Functionalization/Annulation of Phenylglycinol Derivatives with Alkynes.

A new method for cobalt-catalyzed C(sp2)-H functionalization of phenylglycinol derivatives with terminal and internal alkynes directed by picolinamide auxiliary has been developed. This method offers an efficient and highly regioselective route for the synthesis of 1-hydroxymethyltetrahydroisoquinolines. The reaction employs commercially available Co(II) catalyst in the presence of Mn(III) cooxidant and oxygen as a terminal oxidant and proceeds with full preservation of original stereochemistry.

Cobalt-catalyzed carbonylation of the C-H bond.

Direct carbonylation of the C-H bond is a great tool for installing a carbonyl group in a wide variety of substrates. This review summarizes the C-H bond carbonylation methodologies using the cobalt-catalyzed C-H bond functionalization approach. Despite the fact that cobalt-catalyzed carbonylation methodologies have been known since Murahashi's report in 1955, this area is still underdeveloped, particularly carbonylation of the C(sp3)-H bond.

Cobalt-Catalyzed Coupling of Benzoic Acid C-H Bonds with Alkynes, Styrenes, and 1,3-Dienes.

A method for cobalt-catalyzed, carboxylate-directed functionalization of arene C-H bonds is reported. Alkynes, styrenes, and 1,3-dienes can be coupled with benzoic acids to provide cyclic products in good yields. The reactions proceed in the presence of a cobalt(II) hexafluoroacetylacetonate catalyst, (TMS)2 NH base, Ce(SO4 )2 cooxidant, and oxygen oxidant.

Unsaturated syn- and anti-1,2-amino alcohols by cyclization of allylic bis-trichloroacetimidates. stereoselectivity dependence on substrate configuration.

Disubstituted allylic bis-imidates undergo Lewis acid catalyzed or spontaneous cyclization to oxazolines, which are precursors of unsaturated amino alcohols. Stereoselectivity of the cyclization is mainly determined by the substrate configuration. Highly selective cis-oxazoline formation is achieved starting from anti-E-bis-imidates while trans-oxazoline predominantly forms from anti-Z-bis-imidates. On the basis of DFT calculations, the stereoselectivity trends can be explained by the formation of the energetically most stable carbenium ion conformation, followed by the cyclization via most favorable bond rotations.

Semisynthesis of libiguin A and its analogues by trans-lactonization of phragmalin.

Libiguins are limonoids with highly potent sexual activity enhancing effects, originally isolated from the Madagascarian Meliaceae species Neobeguea mahafalensis, where they exist in only minute quantities. Their low natural abundance has hampered mapping of their biological effects. Here we describe an approach to the semisynthesis of libiguin A and its close analogues 1-3 starting from phragmalin, which is a limonoid present in high amounts in a commercially cultivated Meliaceae species, Chukrasia tabularis, allowing the preparation of libiguins in appreciable quantities.

Cobalt-catalyzed, aminoquinoline-directed C(sp²)-H bond alkenylation by alkynes.

A method for cobalt-catalyzed, aminoquinoline- and picolinamide-directed C(sp(2))-H bond alkenylation by alkynes was developed. The method shows excellent functional-group tolerance and both internal and terminal alkynes are competent substrates for the coupling. The reaction employs a Co(OAc)2⋅4 H2O catalyst, Mn(OAc)2 co-catalyst, and oxygen (from air) as a terminal oxidant.

Cobalt-catalyzed C(sp2)-H bond imination of phenylalanine derivatives.

Herein we report the cobalt-catalyzed, picolinamide-directed C-H bond imination protocol of phenylalanine derivatives using isocyanides and a Co(dpm)2 catalyst. A wide range of functional groups were tolerated under the reaction conditions, yielding imines in high yields. The obtained imine products can easily be transformed to 1-aminoisoquinoline derivatives under reductive conditions, providing an attractive alternative to already existing methodologies. The control experiments indicated that C-H activation might occur via an electrophilic pathway.

C-H bond functionalization by high-valent cobalt catalysis: current progress, challenges and future perspectives.

Over the last decade, high-valent cobalt catalysis has earned a place in the spotlight as a valuable tool for C-H activation and functionalization. Since the discovery of its unique reactivity, more and more attention has been directed towards the utilization of cobalt as an alternative to noble metal catalysts. In particular, Cp*Co(III) complexes, as well as simple Co(II) and Co(III) salts in combination with bidentate chelation assistance, have been extensively used for the development of novel transformations. In this review, we have demonstrated the existing trends in the C-H functionalization methodology using high-valent cobalt catalysis and highlighted the main challenges to overcome, as well as perspective directions, which need to be further developed in the future.

Cobalt-Catalyzed C(sp2)-H Carbonylation of Amino Acids Using Picolinamide as a Traceless Directing Group.

Herein we report an efficient protocol for the C(sp2)-H carbonylation of amino acid derivatives based on an inexpensive cobalt(II) salt catalyst. Carbonylation was accomplished using picolinamide as a traceless directing group, CO (1 atm) as the carbonyl source, and Co(dpm)2 as the catalyst. A broad range of phenylalanine derivatives bearing diverse functional groups were tolerated. Moreover, the method can be successfully applied for the C(sp2)-H carbonylation of short peptides thereby allowing access for peptide late-stage carbonylation.

Synthesis of 3-Hydroxymethyl Isoindolinones via Cobalt-Catalyzed C(sp2)-H Carbonylation of Phenylglycinol Derivatives.

An efficient method for the synthesis of 3-hydroxymethyl isoindolinones via cobalt-catalyzed C(sp2)-H carbonylation of phenylglycinol derivatives using picolinamide as a traceless directing group is demonstrated. The reaction proceeds in the presence of a commercially available cobalt(II) tetramethylheptanedionate catalyst and employs DIAD as a "CO" surrogate. This synthetic route offers a broad substrate scope, excellent regioselectivity, and full preservation of the original stereochemistry. Besides, the developed method provides a pathway for accessing valuable enantiopure 3-substituted isoindolinone derivatives.

Aminoquinoline-directed, cobalt-catalyzed carbonylation of sulfonamide sp2 C-H bonds.

We report a method for cobalt-catalyzed, aminoquinoline-directed sp2 C-H bond carbonylation of sulfonamides. The reactions proceed in a dichloroethane solvent, and employ diisopropyl azodicarboxylate as a carbon monoxide source, Mn(OAc)2 as a cooxidant and potassium pivalate as a base. Halogen, ester, and amide functionalities are compatible with the reaction conditions. This method allows for a short and efficient synthesis of saccharin derivatives.

Cobalt-Catalyzed, Aminoquinoline-Directed Functionalization of Phosphinic Amide sp2 C-H Bonds.

In this paper, we introduce arylphosphinic acid aminoquinoline amides as competent substrates for cobalt-catalyzed sp2 C-H bond functionalization. Specifically, the feasibility of their coupling with alkynes, alkenes, and allyl pivalate has been demonstrated. Reactions are catalyzed by simple Co(NO3)2 hydrate in ethanol or mixed dioxane/tBuOH solvent in the presence of Mn(OAc)3·2H2O additive, sodium pivalate, or acetate base and use oxygen from the air as an oxidant. Directing group removal affords ortho-functionalized P,P-diarylphosphinic acids.

Cobalt-promoted dimerization of aminoquinoline benzamides.

A method for aminoquinoline-directed, cobalt-promoted dimerization of benzamides has been developed. Reactions proceed in ethanol solvent in the presence of Mn(OAc)2 cocatalyst and Na2CO3 base and use oxygen as a terminal oxidant. Bromo, iodo, nitro, ether, and ester moieties are compatible with the reaction conditions. Cross-coupling of electronically dissimilar aminoquinoline benzamides proceeds with modest yields and selectivities.

Tetrahydro-1,3-oxazepines via Intramolecular Amination of Cyclopropylmethyl Cation.

An efficient synthesis of tetrahydro-1,3-oxazepines was developed involving the regioselective intramolecular amination of cyclopropylmethyl cation. The cation was generated by the abstraction of one imidate group in bis-imidate bearing a carbocation-stabilizing substituent. Using 1,1,2,3-tetrasubstituted cyclopropane substrates, highly diastereoselective intramolecular amination to trans-tetrahydro-1,3-oxazepines was achieved. The resulting tetrahydro-1,3-oxazepines were transformed to the homoallylamine derivatives in high yields.

Cobalt-catalyzed, aminoquinoline-directed coupling of sp(2) C-H bonds with alkenes.

A method for cobalt-catalyzed, aminoquinoline-directed ortho-functionalization of sp(2) C-H bonds with alkenes has been developed. Reactions proceed at room temperature in trifluoroethanol solvent, use oxygen from air as an oxidant, and require Mn(OAc)3 as a cocatalyst. Benzoic, heteroaromatic, and acrylic acid aminoquinoline amides react with ethylene as well as mono- and disubstituted alkenes affording products in good yields. Excellent functional group tolerance is observed; halogen, nitro, ether, and unprotected alcohol functionalities are compatible with the reaction conditions.

Cobalt-catalyzed direct carbonylation of aminoquinoline benzamides.

A method for direct carbonylation of aminoquinoline benzamides has been developed. Reactions proceed at room temperature in trifluoroethanol solvent, use oxygen from air as an oxidant, and require Mn(OAc)3 as a cocatalyst. Benzoic and acrylic acid derivatives can be carbonylated by carbon monoxide affording imides in good yields. Halogen, nitro, ether, cyano, and ester functional groups are tolerated. The directing group can be removed under mild conditions affording phthalimides.