An efficient route to 4-substituted coumarins, 2(5H)-furanones, and pyrones via palladium-catalyzed couplings of alkenyl tosylates with organoindium reagents

Highly efficient palladium-catalyzed couplings of alkenyl tosylates with organoindium reagents under mild conditions are described, which give rise to 4-substituted coumarins, 2(5H)-furanones, and pyrones in good to excellent yields.     

Oxidative Difunctionalization of Alkenyl MIDA Boronates: A Versatile Platform for Halogenated and Trifluoromethylated α‐Boryl Ketones

The synthesis of halogenated and trifluoromethylated α‐boryl ketones via a one‐pot oxidative difunctionalization of alkenyl MIDA boronates is reported. These novel densely functionalized organoborons bearing synthetically and functionally valuable carbonyl, halogen/CF₃ and boronate moieties within the same molecule are synthetically challenging for the chemist, but have great synthetic potential, as demonstrated by their applications in a straightforward synthesis of borylated furans. The generality of this reaction was extensively investigated. This reaction is attractive since the starting materials, alkenyl MIDA boronates, are easily accessible.     

PhI(OAc)2-mediated iminobromination for synthesis of bromomethyl cyclic imines starting from alkenyl carbonitriles and Grignard reagents

PhI(OAc)₂-mediated iminobromination was developed starting from alkenyl carbonitriles and Grignard reagents. The present transformation is carried out by a sequence of nucleophilic addition of Grignard reagents to alkenyl carbonitriles to form N-H imines and their iminohalogenation by subsequent treatment with PhI(OAc)₂.     

(Z)-(2-bromovinyl)-MIDA boronate: a readily accessible and highly versatile building block for small molecule synthesis

Iterative cross-coupling represents a potentially general approach for the simple, efficient, and flexible construction of a wide range of functional small molecules. In this context, (Z)-(2-bromovinyl)-N-methyliminodiacetic acid (MIDA) boronate is a very useful building block for small molecule synthesis. This compound can serve as a starting material for the preparation of a wide range of cis-alkene-containing MIDA boronates. This compound can also be used for the iterative cross-coupling-based synthesis of various cis-olefin-containing targets. Collectively, these results contribute to the expanding generality of the MIDA boronate platform.     

Stereoselective Direct Chlorination of Alkenyl MIDA Boronates: Divergent Synthesis of E and Z α‐Chloroalkenyl Boronates

The individual molecules of α‐chloroalkenyl boronates include both an electrophilic C−Cl bond and a nucleophilic C−B bond, which makes them intriguing organic synthons. Reported herein is a stereodivergent synthesis of both E and Z α‐chloroalkenyl N ‐methyliminodiacetyl (MIDA) boronates through the direct chlorination of alkenyl MIDA boronates using t BuOCl and PhSeCl reagents, respectively. Both reaction processes are stereospecific and the use of sp³‐B MIDA boronate is the key contributor to the reactivity. The synthetic value of the boronate products was also demonstrated.     

Preparation of α,β-unsaturated esters and amides via external-CO-free palladium-catalyzed carbonylation of alkenyl tosylates

Palladium-catalyzed carbonylation of tosylates with phenyl formate is described. This procedure needs neither external carbon monoxide nor any pressure-resistant apparatus. A variety of cyclic and acyclic alkenyl tosylates can be converted into the corresponding phenyl esters in good yields. Furthermore, this method is effective for the one-pot synthesis of α,β-unsaturated amides.     

Direct Access to MIDA Acylboronates through Mild Oxidation of MIDA Vinylboronates

Acylboronate esters/trifluoroborates represent an elusive class of boronates that are of increasing interest for both fundamental study as well as applications at the interface of chemistry and biology. Their preparation has been limited by the use of strongly basic anions, often introduced in multistep reactions. Herein, we demonstrate the facile preparation of acylboronate N‐methyliminodiacetyl (MIDA) esters from alkenyl‐2‐boronate esters through mild dihydroxylation and meta ‐periodate cleavage. Given the well‐known functional‐group tolerance of this mild reaction sequence and the availability of alkenyl‐2‐boronates, this method should greatly increase access to acylboronate MIDA esters.     

Regio- and Diastereoselective Synthesis of Cyclohexadienylborons via an Intermolecular Diels–Alder Reaction of Alkenyl MIDA Boronates with 2-Pyrones

An efficient synthesis of highly functionalized cyclohexadienylborons via an inverse electron-demand Diels–Alder reaction/CO₂ extrusion of alkenyl MIDA boronates with 2-pyrones is outlined. By controlling the reaction temperature, the corresponding C(sp³)-rich bicyclolactones could also be readily formed. The exo-selective reactions feature good functional-group tolerance, broad substrate scope, and excellent regio- and diastereoselectivity. Oxidation of the cyclohexadienylborons in a one-pot procedure led to the construction of aromatic boronates bearing valuable functional groups. Synthetic transformations of the C−B bond were demonstrated.     

Rh(I)-catalyzed cross-coupling reactions of alkenyl tosylates with potassium aryltrifluoroborates

RhCl(PPh₃)₃/DPPF was successfully employed as an efficient catalyst in the Suzuki-Miyaura cross-coupling reactions of potassium aryltrifluoroborates with alkenyl tosylates, affording the corresponding products in good to excellent yields.     

Synthesis of Acylborons by Ozonolysis of Alkenylboronates: Preparation of an Enantioenriched Amino Acid Acylboronate

A concise synthesis of acylborons was achieved by ozonolysis of alkenyl MIDA (N ‐methyliminodiacetic acid) boronates. This reaction exhibits excellent functional‐group tolerance and is applicable to various acyl MIDA boronates and potassium acyltrifluroborates (KATs) which could not be synthesized by previous methods. In addition, α‐amino acylborons, which would be essential for peptide ligations, were prepared for the first time. The acylboron of l ‐alanine was obtained in high enantiopurity and found to be configurationally stable. Oligopeptide synthesis between the α‐amino KATs and amino acid in dilute aqueous media was studied.     

Tandem cycloisomerization/Suzuki coupling of arylethynyl MIDA boronates

A tandem gold-catalyzed cycloisomerization/Suzuki cross-coupling sequence involving arylethynyl-N-methyliminodiacetic acid boronates is described. Combining the mildness of homogeneous gold catalysis with the versatility of N-methyliminodiacetic acid (MIDA) boronates, this tandem two-step method enables the rapid assembly of various aryl-substituted heterocycles without having to isolate or purify any heterocyclic MIDA boronate intermediates. Another major advantage of this method is that a wide range of heterocycles bearing different aryl groups may be made from a single MIDA boronate alkyne precursor.     

Visible-light-promoted alkylation of unsaturated MIDA boronates using Ru(bpy)3Cl2 as the photoredox catalyst

The development of a visible light-mediated atom transfer radical addition (ATRA) of perfluoroalkyl iodides to ethynyl-, vinyl- and allyl-MIDA boronates using the reductive and oxidative quenching of [Ru(bpy)₃]Cl₂ is described. Using an operationally simple and mild protocol, the corresponding MIDA boronates containing perfluoroalkyl groups were obtained in moderate to high yields. The structures of three products were confirmed by single crystal X-ray diffraction studies.     

Copper-catalyzed radical oxytrifluoromethylation of alkenyl oximes at ambient temperature

A mild and efficient copper-catalyzed radical oxytrifluoromethylation reaction of alkenyl oximes was successfully developed. The method provides a straightforward access to a wide range of CF₃-containing isoxazolines in good to excellent yields.     

Mild and efficient Sonogashira couplings of 8-oxa- and 8-thiabicyclo[3.2.1]octanone derived alkenyl nonaflates

We demonstrate in this report that bicyclic alkenyl nonaflates (nonafluorobutanesulfonates) generated from 8-heterobicyclo[3.2.1]octan-3-one derivatives are excellent substrates for Sonogashira couplings with alkynes. Employing CuI, Pd(OAc)₂, PPh₃ in DMF/i-Pr₂NH as standard reagents structurally diverse bicyclic nonaflates were coupled with phenyl acetylene in generally high yields. Particularly efficient are transformations of precursors 16, 18, and 20 bearing methyl groups at the bridgehead carbons, which furnished the expected enynes 17, 19, and 21 in approximately 90% yield. With respect to the alkyne component the scope of this palladium-catalyzed reaction seems also to be fairly broad. Thus, trimethylsilyl acetylene and propargyl alcohol could also be used, affording coupling products 22, 23, and 25 with high efficacy. The protocol of Grieco was applied to induce a domino coupling of tricyclic alkenyl nonaflate 14 with trimethylsilyl acetylene affording product 26 in moderate yield and as 1:1 mixture of the expected two diastereomers.     

On the mechanism and origin of the stereoselectivity in iodo-deboronation and chloro-deboronation of hindered alkenyl boronate esters using either ICl-NaOMe or ICl-pyridine

Conversion of hindered alkenyl boronate esters into the corresponding iodoalkene, or alkenyl chloride can be carried out stereoselectively using ICl. In the presence of NaOMe, direct reaction of ICl is favoured yielding the E-iodoalkene, however, the reaction with ICl followed by NaOMe can be used to give different major alkenyl iodide and chloride products, depending upon reaction temperature, ICl source and alkenyl boronate stereoelectronics.     

Diversity‐Oriented Synthesis of α‐Functionalized Acylborons and Borylated Heteroarenes by Nucleophilic Ring Opening of α‐Chloroepoxyboronates

The ring‐opening reactions of N‐methyliminodiacetyl (MIDA) α‐chloroepoxyboronates with different nucleophiles allow the modular synthesis of a diverse array of organoboronates. These include seven types of α‐functionalized acylboronates and seven types of borylated heteroarenes, some of which are difficult‐to‐access products using alternative methods. The common synthons, α‐chloroepoxyboronates, could be viably synthesized by a two‐step procedure from the corresponding alkenyl MIDA boronates. Mild reaction conditions, good functional‐group tolerance, and generally good efficiency were observed. The utility of the products was also demonstrated.     

Vinyl MIDA boronate: a readily accessible and highly versatile building block for small molecule synthesis

Iterative cross-coupling represents a potentially general approach for the simple, efficient, and flexible construction of natural products, pharmaceuticals, and materials. N-Methyliminodiacetic acid (MIDA) boronates represent a promising platform for the development of this type of synthesis strategy. This report describes the discovery that vinyl MIDA boronate (1) is an air- and chromatographically stable compound that can be conveniently prepared on a multigram scale and serve as a versatile starting material for the preparation of a range of new MIDA boronate building blocks. Analogous to tert-butylethylene, 1 is also an excellent substrate for olefin cross-metathesis, providing access to a range of trans-alkenyl MIDA boronates as single stereoisomers. An improved synthesis of the very versatile bifunctional building block trans-(2-bromovinyl) MIDA boronate (2) is also described. Collectively, these results contribute to the expanding generality of the iterative cross-coupling approach.     

Synthesis of 2H-chromenes and 1,2-dihydroquinolines from aryl aldehydes, amines, and alkenylboron compounds

The one-step reaction of salicylaldehydes with amines and alkenyl boronic acids or alkenyl trifluoroborates to form 2H-chromenes (2H-1-benzopyrans) has been investigated in more detail and new suitable conditions have been identified, including the use of tertiary amines and protic solvents including water. This process was applied to a concise synthesis of a tocopherol analog. The analogous condensation reaction between 2-sulfamidobenzaldehydes and alkenyl trifluoroborates provides an efficient synthesis of 1,2-dihydroquinoline derivatives.     

Ruthenium-catalyzed reaction of alkenyl triflates with zinc thiolates

A ruthenium complex coordinated with 3,4,7,8-tetramethyl-1,10-phenanthroline catalyzed the reaction of alkenyl triflates with zinc dithiolates to give alkenyl sulfides.     

Novel stereoselective synthesis of 1-substituted 1,3-dien-2-yl sulfides via Stille coupling reactions of (E)-α-stannylvinyl sulfides with alkenyl iodides

(E)-α-stannylvinyl sulfides are new difunctional reagents which undergo Stille coupling reactions with alkenyl iodides to afford stereoselectively 1-substituted 1,3-dien-2-yl sulfides in good yields.