Desymmetrization of Diboron(4) by a Trifluorination B-Masking Strategy: Practical Synthesis of Unsymmetrical Diboron Species.

Herein, we report a straightforward practical and simple method for efficiently synthesizing a BF-containing unsymmetrical diboron salt. This method involves the direct desymmetrization of commercially available diboron(4). This desymmetrization is based on a selective B-masking strategy via nucleophilic trifluorination, providing the elusive diborons bearing a trifluoroborate group.

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 alkene molecular frameworks could involve the sequential selective activation and cross-coupling of strong bonds instead of conventional C-C bond formation.

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.

Synthesis and Functionalization of Thiophosphonium Salts: A Divergent Approach to Access Thioether, Thioester, and Dithioester Derivatives.

Herein, we report a straightforward practical method for efficiently obtaining a diverse range of thiophosphonium salts. This method involves the direct coupling of commercially available thiols and aldehydes with PhP and TfOH. The setup is simple and carried out in a metal-free manner.

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.

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

A new method to access β-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 PPh . 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 β-keto-gem-diborylalkane product.

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,BF 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.

Sequential Selective C-H and C(sp )- P Bond Functionalizations: An Entry to Bioactive Arylated Scaffolds.

Organophosphonium salts containing C(sp )- P bonds are among the most utilized reagents in organic synthesis for constructing C-C double bonds. However, their use as C-selective electrophilic groups is rare. Here, we explore an efficient and general transition-metal-free method for sequential chemo- and regioselective C-H and C(sp )- P bond functionalizations.

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

Although -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) -diborylalkenes. These reactions provide a general and efficient method for the stereoselective conversion of -diborylalkenes to rapidly access 1,1-bisborylcyclohexenes.

Long-term ovarian reserve and fertility outcomes in female survivors of childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, yet data regarding long-term ovarian reserve of female survivors are limited. The aim of this study was to investigate whether there is a differential pattern of anti-Mullerian hormone (AMH) levels in female childhood ALL survivors compared with the normal age-matched population. In a cohort of 56 female childhood ALL survivors (median age 29 years; median follow-up 20.

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.

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 1,1bis(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.

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.

Stereoselective Desymmetrization of gem-Diborylalkanes by "Trifluorination".

An efficient and general method for the chemoselective synthesis of unsymmetrical gem-diborylalkanes is reported. This method is based on a late-stage desymmetrization through nucleophilic "trifluorination", providing chiral gem-diborylalkanes bearing a trifluoroborate group. The reaction offers a highly modular and diastereoselective approach towards the synthesis of gem-diborylcyclopropanes.

Zirconocene-Mediated Selective C-C Bond Cleavage of Strained Carbocycles: Scope and Mechanism.

Several approaches using organozirconocene species for the remote cleavage of strained three-membered ring carbocycles are described. ω-Ene polysubstituted cyclopropanes, alkylidenecyclopropanes, ω-ene spiro[2.2]pentanes, and ω-ene cyclopropyl methyl ethers were successfully transformed into stereodefined organometallic intermediates, allowing an easy access to highly stereoenriched acyclic scaffolds in good yields and, in most cases, excellent selectivities.

gem-Diborylalkanes: recent advances in their preparation, transformation and application.

Recently, gem-diborylalkanes have attracted much attention as versatile building blocks and fundamental intermediates in organic synthesis, because they enable multiple C-C bond construction and further transformation at C-B bonds. Importantly, gem-diborylalkanes can be utilised as bisnucleophilic partners in a variety of chemo-selective C-C bond-forming reactions. This review describes recent developments in synthesising gem-diborylalkanes in complex molecules along with their chemical transformation.

Construction of Enantiopure Taxoid and Natural Product-like Scaffolds Using a C-C Bond Cleavage/Arylation Reaction.

An approach to construct enantiopure complex natural product-like frameworks, including the first reported synthesis of a C17 oxygenated taxoid scaffold, is presented. A palladium-catalyzed C-C activation/cross-coupling is utilized to access these structures in a short sequence from (+)-carvone; the scope of this reaction is explored.

Synthesis and Stereochemical Assignment of Crypto-Optically Active (2) H6 -Neopentane.

The determination of the absolute configuration of chiral molecules is at the heart of asymmetric synthesis. Here we probe the spectroscopic limits for chiral discrimination with NMR spectroscopy in chiral aligned media and with vibrational circular dichroism spectroscopy of the sixfold-deuterated chiral neopentane. The study of this compound presents formidable challenges since its stereogenicity is only due to small mass differences.

Selective C-C and C-H bond activation/cleavage of pinene derivatives: synthesis of enantiopure cyclohexenone scaffolds and mechanistic insights.

The continued development of transition-metal-mediated C-C bond activation/cleavage methods would provide even more opportunities to implement novel synthetic strategies. We have explored the Rh(I)-catalyzed C-C activation of cyclobutanols resident in hydroxylated derivatives of pinene, which proceed in a complementary manner to the C-C bond cleavage that we have observed with many traditional electrophilic reagents. Mechanistic and computational studies have provided insight into the role of C-H bond activation in the stereochemical outcome of the Rh-catalyzed C-C bond activation process.

Quinazoline-based tricyclic compounds that regulate programmed cell death, induce neuronal differentiation, and are curative in animal models for excitotoxicity and hereditary brain disease.

Expanding on a quinazoline scaffold, we developed tricyclic compounds with biological activity. These compounds bind to the 18 kDa translocator protein (TSPO) and protect U118MG (glioblastoma cell line of glial origin) cells from glutamate-induced cell death. Fascinating, they can induce neuronal differentiation of PC12 cells (cell line of pheochromocytoma origin with neuronal characteristics) known to display neuronal characteristics, including outgrowth of neurites, tubulin expression, and NeuN (antigen known as 'neuronal nuclei', also known as Rbfox3) expression.

Selective carbon-carbon bond cleavage for the stereoselective synthesis of acyclic systems.

Most of the efforts of organic chemists have been directed to the development of creative strategies to build carbon-carbon and carbon-heteroatom bonds in a predictable and efficient manner. In this Review, we show an alternative approach where challenging molecular skeletons could be prepared through selective cleavage of carbon-carbon bonds. We demonstrate that it has the potential to be a general principle in organic synthesis for the regio-, diastereo-, and even enantioselective preparation of adducts despite the fact that C-C single bonds are among the least reactive functional groups.

Merging allylic carbon-hydrogen and selective carbon-carbon bond activation.

Since the nineteenth century, many synthetic organic chemists have focused on developing new strategies to regio-, diastereo- and enantioselectively build carbon-carbon and carbon-heteroatom bonds in a predictable and efficient manner. Ideal syntheses should use the least number of synthetic steps, with few or no functional group transformations and by-products, and maximum atom efficiency. One potentially attractive method for the synthesis of molecular skeletons that are difficult to prepare would be through the selective activation of C-H and C-C bonds, instead of the conventional construction of new C-C bonds.

The Cu(I) catalyzed Meerwein reaction in aqueous solutions proceeds via a radical mechanism. The effect of several ligands.

The effect of the ligands 2,5,8,11-tetramethyl-2,5,8,11-tetraaza-dodecane and fumarate on the mechanism and kinetics of the Cu(I) catalyzed Meerwein reaction was studied. The results point out that initially the Cu(I) ion binds to the aromatic ring with the diazo substituent. This reaction is followed by a redox process involving N2 loss and the formation of an aryl radical, R˙.

The effect of pyrophosphate, tripolyphosphate and ATP on the rate of the Fenton reaction.

It has been recently reported that pyrophosphate, tri-polyphosphate, ATP and analogous ligands considerably decrease the yield of hydroxyl radicals by the Fenton reaction under conditions where [H(2)O(2)]>>[Fe(II)L(n)]. It was suggested that this effect is due to the slowing down of the Fenton reaction by these ligands. This suggestion seemed surprising as polyphosphate ligands stabilize Fe(III).

Selectivity in metal-catalyzed carbon-carbon bond cleavage of alkylidenecyclopropanes.

When more complex system leads to simpler reactivity profile; the ring-opening of strained three-membered rings such as methylene- and alkylidenecyclopropanes generally lead to several products. If one starts with more functionalized carbon skeletons, selective reactions are now observed and rationalization as well as synthetic applications are described in this concept article. This methodology could be used to the preparation of challenging structural motifs possessing quaternary carbon stereocenters in acyclic systems.