Regio- and stereoselective access to highly substituted vinylphosphine oxides via metal-free electrophilic phosphonoiodination of alkynes.

In general, the P-centered ring-opening of quaternary phosphirenium salts (QPrS) predominantly leads to hydrophosphorylated products, while the C-centered ring-opening is primarily confined to intramolecular nucleophilic reactions, resulting in the formation of phosphorus-containing cyclization products instead of difunctionalized products generated through intermolecular nucleophilic processes. Here, through the promotion of ring-opening of three-member rings by iodine anions and the quenching of electronegative carbon atoms by iodine cations, we successfully synthesize ß-functionalized vinylphosphine oxides by the P-addition of QPrS intermediates generated in situ. Multiple ß-iodo-substituted vinylphosphine oxides can be obtained with exceptional regio- and stereo-selectivity by reacting secondary phosphine oxides with unactivated alkynes. In addition, a variety of ß-functionalized vinylphosphine oxides converted from C-I bonds, especially the rapid construction of benzo[b]phospholes oxides, demonstrates the significance of this strategy.

Hypervalent iodine-mediated ß-difluoroalkylboron synthesis via an unusual 1,2-hydrogen shift enabled by boron substitution.

ß-Difluoroalkylborons, featuring functionally important CF2 moiety and synthetically valuable boron group, have great synthetic potential while remaining synthetically challenging. Herein we report a hypervalent iodine-mediated oxidative gem-difluorination strategy to realize the construction of gem-difluorinated alkylborons via an unusual 1,2-hydrogen migration event, in which the (N-methyliminodiacetyl) boronate (BMIDA) motif is responsible for the high regio- and chemoselectivity. The protocol provides facile access to a broad range of ß-difluoroalkylborons under rather mild conditions. The value of these products was demonstrated by further transformations of the boryl group into other valuable functional groups, providing a wide range of difluorine-containing molecules.

Assembly of multicyclic isoquinoline scaffolds from pyridines: formal total synthesis of fredericamycin A.

The construction of an isoquinoline skeleton typically starts with benzene derivatives as substrates with the assistance of acids or transition metals. Disclosed here is a concise approach to prepare isoquinoline analogues by starting with pyridines to react with ß-ethoxy α,ß-unsaturated carbonyl compounds under basic conditions. Multiple substitution patterns and a relatively large number of functional groups (including those sensitive to acidic conditions) can be tolerated in our method. In particular, our protocol allows for efficient access to tricyclic isoquinolines found in hundreds of natural products with interesting bioactivities. The efficiency and operational simplicity of introducing structural complexity into the isoquinoline frameworks can likely enable the collective synthesis of a large set of natural products. Here we show that fredericamycin A could be obtained via a short route by using our isoquinoline synthesis as a key step.

Synthesis of fluorinated amphoteric organoborons via iodofluorination of alkynyl and alkenyl MIDA boronates.

The iodofluorination of alkynyl and alkenyl MIDA (N-methyliminodiacetyl) boronates led to the synthesis of two types of fluorinated organoborons bearing a valuable C-I bond. The B(MIDA) moiety confers exclusive regioselectivity to the reaction, and the products were formed in generally good yields. Preliminary utility of the products was demonstrated.

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.

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.

gem-Difluorination of Alkenyl N-methyliminodiacetyl Boronates: Synthesis of α- and ß-Difluorinated Alkylborons.

Organofluorine compounds are widely used in pharmaceutical, agrochemical, and materials sciences. The syntheses and applications of fluorinated organoborons facilitate the rapid and modular assemblies of fluorine-containing molecules because of the versatility of C-B bonds in diverse chemical transformations. Reported herein is a migratory geminal difluorination of aryl-substituted alkenyl N-methyliminodiacetyl (MIDA) boronates using commercially available Py⋅HF as the fluorine source and hyperiodine as the oxidant. The protocol offers facile access to α- and ß-difluorinated alkylboron compounds, both of which have previously been challenging to prepare. Mild reaction conditions, broad substrate scope, good functional-group tolerance, and moderate to good yields were observed. The utility of these products is demonstrated by further transformations of the C-B bond into other valuable functional groups.

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 tBuOCl 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.

Direct Assembly of Prenylated Heteroarenes through a Cascade Minisci Reaction/Dehydration Sequence.

The prenyl group is an important component in bioactive compounds. Herein, we report the assembly of prenylated heteroarenes through a cascade Minisci reaction and acid-promoted dehydration sequence. The use of potassium (3-hydroxy-3-methylbut-1-yl)trifluoroborate as a new coupling reagent allows the direct introduction of prenyl and 3-hydroxy-3-methylbutyl groups to a wide variety of electron-deficient heteroarenes. Synthetic application is also demonstrated.

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.

Mild Mn(OAc)3-Mediated Aerobic Oxidative Decarboxylative Coupling of Arylboronic Acids and Arylpropiolic Acids: Direct Access to Diaryl 1,2-Diketones.

A simple and efficient method for the synthesis of diaryl 1,2-diketones has been developed. The reaction represents the first example of diaryl 1,2-diketones that are synthesized directly from arylboronic acids and arylpropiolic acids by a radical pathway in moderate to good yields. This reaction proceeds under mild reaction conditions and with good tolerance of a variety of functional groups. Preliminary mechanistic studies were conducted.

Mild rhodium(III)-catalyzed C-H allylation with 4-vinyl-1,3-dioxolan-2-ones: direct and stereoselective synthesis of (E)-allylic alcohols.

A rhodium(III)-catalyzed C-H direct allylation reaction with 4-vinyl-1,3-dioxolan-2-ones has been developed. The reaction provides a facile and stereoselective access to substituted-(E)-allylic alcohols under mild and redox-neutral reaction conditions. Olefinic C-H activation is applicable, giving multifunctionalized skipped dienes in good yields. Minimal double-bond migration was observed.