Stereoselective C-B and C-H Bonds Functionalization of PolyBorylated Alkenes.

Alkenes are fundamental functional groups which feature in various materials and bioactive molecules; however, efficient divergent strategies for their stereodefined synthesis are difficult. In this regard, numerous synthetic methodologies have been developed to construct carbon-carbon bonds with regio- and stereoselectivity, enabling the predictable and efficient synthesis of stereodefined alkenes. In fact, an appealing alternative approach for accessing challenging stereodefined alkenes molecular frameworks could involve the sequential selective activation and cross-coupling of strong bonds instead of conventional C-C bond formation. In this study, we introduce a series of programmed site- and stereoselective strategies that capitalizes on the versatile reactivity of readily accessible polymetalloid alkenes (i.e. polyborylated alkenes), through a tandem cross-coupling reaction, which is catalyzed by an organometallic Rh-complex to produce complex molecular scaffolds. By merging selective C-B and remote C-H bond functionalization, we achieve the in-situ generation of polyfunctional C(sp2)-nucleophilic intermediates. These species can be further modified by selective coupling reactions with various C-based electrophiles, enabling the formation of C(sp2)-C(sp3) bond for the generation of even more complex molecular architectures using the readily available starting polyborylated-alkenes. Mechanistic and computational studies have provided insight into the origins of the stereoselectivities and C-H activation via a 1,4-Rh migration process.

PolyBorylated Alkenes as Energy-Transfer Reactive Groups: Access to Multi-Borylated Cyclobutanes Combined with Hydrogen Atom Transfer Event.

While polyborylated alkenes are being recognized for their elevated status as highly valuable reagents in modern organic synthesis, allowing efficient access to a diverse array of transformations, including the formation of C-C and C-heteroatom bonds, their potential as energy-transfer reactive groups has remained unexplored. Yet, this potential holds the key to generating elusive polyborylated biradical species, which can be captured by olefins, thereby leading to the construction of new highly-borylated scaffolds. Herein, we report a designed energy-transfer strategy for photosensitized [2+2]-cycloadditions of poly-borylated alkenes with various olefins enabling the regioselective synthesis of diverse poly-borylated cyclobutane motifs, including the 1,1-di-, 1,1,2-tri-, and 1,1,2,2-tetra-borylated cyclobutanes. In fact, these compounds belong to a family that presently lacks efficient synthetic pathways. Interestingly, when α-methylstyrene was used, the reaction involves an interesting 1,5-hydrogen atom transfer (HAT). Mechanistic deuterium-labeling studies have provided insight into the outcome of 1,5-hydrogen atom transfer process. In addition, the polyborylated cyclobutanes are then demonstrated to be useful in selective oxidation processes resulting in the formation of cyclobutanones and γ-lactones.

Stereodefined polymetalloid alkenes synthesis via stereoselective boron-masking of polyborylated alkenes.

Polyborylated-alkenes are valuable polymetalloid reagents in modern organic synthesis, providing access to a wide array of transformations, including the construction of multiple C-C and C-heteroatom bonds. However, because they contain similar boryl groups, many times their transformation faces the main challenge in controlling the chemo-, regio- and stereoselectivity. One way to overcome these limitations is by installing different boron groups that can provide an opportunity to tune their reactivity toward better chemo-, regio- and stereoselectivity. Yet, the preparation of polyborylated-alkenes containing different boryl groups has been rare. Herein we report concise, highly site-selective, and stereoselective boron-masking strategies of polyborylated alkenes. This is achieved by designed stereoselective trifluorination and MIDA-ation reactions of readily available starting polyborylated alkenes. Additionally, the trifluoroborylated-alkenes undergo a stereospecific interconversion to Bdan-alkenes. These transition-metal free reactions provide a general and efficient method for the conversion of polyborylated alkenes to access 1,1-di-, 1,2-di-, 1,1,2-tris-(borylated) alkenes containing BF3M, Bdan, and BMIDA, a family of compounds that currently lack efficient synthetic access. Moreover, tetraborylethene undergoes the metal-free MIDA-ation reaction to provide the mono BMIDA tetraboryl alkene selectively. The mixed polyborylalkenes are then demonstrated to be useful in selective C-C and C-heteroatom bond-forming reactions. Given its simplicity and versatility, these stereoselective boron-masking approaches hold great promise for organoboron synthesis and will result in more transformations.

Photoredox-Mediated Deoxygenative Radical Additions of Aromatic Acids to Vinyl Boronic Esters and gem-Diborylalkenes.

A new method to access ß-keto-gem-diborylalkanes, by direct deoxygenative radical addition of aromatic carboxylic acids to gem-dibortlalkenes, is described. The reaction proceeds under mild photoredox catalysis and involves the photochemical C-O bond activation of aromatic carboxylic acids in the presence of PPh3 . It generates an acyl radical, which further undergoes an additional reaction with gem-diborylalkenes to form an α-gem-diboryl alkyl radical intermediate, which then reduces to the corresponding anion, which after protonation, affords the ß-keto-gem-diborylalkane product. Moreover, the same scenario has been extended to the vinyl boronic esters, for example, gem-(Ar, Bpin)-alkenes, and gem-(Alkyl, Bpin)-alkenes. Importantly, this protocol provides a general platform for the late-stage functionalization of bio-active and drug molecules containing a carboxylic acid group.

A Stereodivergent Approach to the Synthesis of gem-Diborylcyclopropanes.

We report a designed stereodivergent strategy for the synthesis of gem-diborylcyclopropanes. The reaction provides a highly modular approach to prepare cyclopropane ring variants bearing gem-(Bpin,Bpin), gem-(Bpin,Bdan), and gem-(Bpin,BF3 K), with outstanding levels of stereocontrol. This was achieved by diastereoselective Pd-catalyzed cyclopropanation reactions of gem-diborylalkenes with α-diazoarylacetates and α-diazoaryl-trifluoromethyl. The key to the success of this general protocol was the diastereoselective trifluorination reaction of gem-diborylcyclopropanes, followed by the stereospecific interconversion of the trifluoroborate salts into the Bdan group.

Stereoselective Diels-Alder Reactions of gem-Diborylalkenes: Toward the Synthesis of gem-Diboron-Based Polymers.

Although gem-diborylalkenes are known to be among the most valuable reagents in modern organic synthesis, providing a rapid access to a wide array of transformations, including the construction of C-C and C-heteroatom bonds, their use as dienophile-reactive groups has been rare. Herein we report the Diels-Alder (DA) reaction of (unsymmetrical) gem-diborylalkenes. These reactions provide a general and efficient method for the stereoselective conversion of gem-diborylalkenes to rapidly access 1,1-bisborylcyclohexenes. Using the same DA reaction manifold with borylated-dienes and gem-diborylalkenes, we also developed a concise, highly regioselective synthesis of 1,1,2-tris- and 1,1,3,4-tetrakis(boronates)cyclohexenes, a family of compounds that currently lack efficient synthetic access. Furthermore, DFT calculations provided insight into the underlying factors that control the chemo-, regio-, and stereoselectivity of these DA reactions. This method also provides stereodivergent syntheses of gem-diborylnorbornenes. The utility of the gem-diborylnorbornene building blocks was demonstrated by ring-opening metathesis polymerization (ROMP), providing a highly modular approach to the first synthesis of the gem-diboron-based polymers. Additionally, these polymers have been successfully submitted to postpolymerization modification reactions. Given its simplicity and versatility, we believe that this novel DA and ROMP approach holds great promise for organoboron synthesis as well as organoboron-based polymers and that it will result in more novel transformations in both academic and industrial research.

Photoredox-Mediated Reaction of gem-Diborylalkenes: Reactivity Toward Diverse 1,1-Bisborylalkanes.

The use of gem-diborylalkenes as radical-reactive groups is explored for the first time. These reactions provide an efficient and general method for the photochemical conversion of gem-diborylalkenes to rapidly access 1,1-bisborylalkanes. This method exploits a novel photoredox decarboxylative radical addition to gem-diborylalkenes to afford α-gem-diboryl carbon-centered radicals, which benefit from additional stability by virtue of an interaction with the empty p-orbitals on borons. The reaction offers a highly modular and regioselective approach to γ-amino gem-diborylalkanes. Furthermore, EPR spectroscopy and DFT calculations have provided insight into the radical mechanism underlying the photochemistry reaction and the stability of the bis-metalated radicals, respectively.

Unsymmetrical 1,1-Bisboryl Species: Valuable Building Blocks in Synthesis.

Unsymmetrical 1,1-bis(boryl)alkanes and alkenes are organo-bismetallic equivalents, which are synthetically important because they allow for sequential selective transformations of C-B bonds. We reviewed the synthesis and chemical reactivity of 1,1-bis(boryl)alkanes and alkenes to provide information for the synthetic community. In the first part of this review, we disclose the synthesis and chemical reactivity of unsymmetrical 1,1-bisborylalkanes. In the second part, we describe the synthesis and chemical reactivity of unsymmetrical 1,1-bis(boryl)alkenes.

α-Borylalkyl radicals: their distinctive reactivity in modern organic synthesis.

Organoborons are extremely important for synthetic organic chemistry; they can serve as advanced intermediates for a variety of transformations. Such a well-known transformation involves the loss of the boron moiety, creating alkyl radicals. Although these originally developed protocols for alkyl radical generation remain in active use today, in recent years their α-boryl carbon-centred radicals have been joined by a new array of radical generation strategies that offer a unique reactivity to forge a wider diversity of organoborons that often operate under mild and benign conditions. Herein, we will highlight the stability and reactivity of α-borylalkyl radicals and their remarkably recent advances in order to further utilise them for C-C and C-heteroatom bond formation. Their use for this purpose has been reported over the last decade in an attempt to guide the synthetic community. Various transition-metal and metal-free methods for their generation are presented, and more advanced photoredox approaches are discussed, mainly for the period of 2009-2019.