One pot conversion of phenols and anilines to aldehydes and ketones exploiting α gem boryl carbanions.

Functional group interconversion is an important asset in organic synthesis. Phenols/anilines being naturally abundant and the carbonyl being the most common in a wide range of bioactive molecules, an efficient conversion is of prime interest. The reported methods require transition metal catalyzed cross coupling which limits its applicability. Here we have described a method for synthesizing various aldehydes and ketones, starting from phenol and protected anilines via Csp2-O/N bond cleavage in a one-pot/stepwise manner. Our synthetic method is found to be compatible with a diverse range of phenols and anilines carrying sensitive functional groups including halides, esters, ketal, hydroxyl, alkenes, and terminal alkynes as well as the substitution on the aryl cores. A short-step synthesis of bioactive molecules and their functionalization have been executed. Starting from BINOL, a photocatalyst has been designed. Here, we have developed a transition metal-free protocol for the conversion of phenols and anilines to aldehydes and ketones.

Reactivity of 1,3-enyne MIDA boronates: exploration of novel 1,2-alkyne shift via gem-difluorination.

The discovery of a new class of heteroatom-rich boron-containing molecules (BCMs) and iterative cross-coupling (ICC) partners created a toolbox for future drug developments using organoboron compounds. Herein, we report the potential utility of 1,3-enyne MIDA boronates to access diverse gem-difluoro MIDA boronates via novel 1,2-alkyne shift. This unique reactivity of 1,3-enyne MIDA boronates offers facile access to previously challenging ß-difluorinated alkyl borons. Furthermore, we demonstrated the synthesis of various novel furan-based BCMs via 5-endo-dig cyclization and iterative coupling partners via copper-catalyzed hydroboration and platinum-catalyzed diboration reaction.

Stereoselective Synthesis of Silylated Vinylboronates by a Boron-Wittig Reaction and Their Application to Tetrasubstituted Olefins.

The highly stereoselective synthesis of a series of tetrasubstituted mono- as well as disilylated vinylboronates is reported by using the boron-Wittig approach. The condensation between acylsilanes and gem-diborylalkanes gave the desired tetrasubstituted olefins in good to excellent yield and high stereoselectivity. Also, a series of trisubstituted silylated vinyl MIDA-boronates was synthesized by using the boron-Wittig reaction followed by a transesterification reaction. This methodology allows direct incorporation of B(pin) and TMS groups in the anti-position of the olefin in a highly stereoselective manner. Further, sequential Suzuki coupling reaction with the silylated vinyl boronic esters generated all-carbon tetrasubstituted alkenes, which have been applied in the total synthesis of the anticancer drug Tamoxifen and aggregation-induced luminogen agent TPE-TF17.

Synthesis of Boronic Esters from Organometallic Reagents and Bis(pinacolato)diboron.

Synthesis of alkyl, aryl, and vinyl boronic esters carrying various chiral and achiral diol-protecting groups were synthesized starting from the corresponding alkyl, aryl, and vinyl lithium or Grignard reagents. Good to excellent yields were obtained for a large range of substrates. The reaction can be conducted in a gram scale to obtain the product over 80 % yield. This approach provides direct access to neopentyl, pinene, and other boronic esters that are difficult to achieve. Using trimethoxyborane or 2-isopropoxy pinacolboronic ester. Detailed mechanistic studies have been conducted to understand the mechanism behind the formation of boronic ester starting from organometallic reagents.

Carbonyl group directed synthesis of 3-boryl-3-substituted alkenyl oxindoles and tetrasubstituted ß-borylenones.

Transition metal-free carbonyl directed boron-Wittig reaction of α-bis(boryl)carbanions with the corresponding isatins or with the α-keto esters/amides was achieved to access alkenyl oxindoles in good yield and high stereoselectivity.

Stereodivergent Zweifel Olefination and its Mechanistic Dichotomy.

Stereoselective Zweifel olefination using boronate complexes carrying two different reactive π-systems was achieved to synthesize vinyl heteroarenes and conjugated 1,3-dienes in good yield and up to 100 % stereoselectivity, which remains unexplored until now. Most importantly, we report the unprecedented formation of E vs. Z-vinyl heteroarenes for different heteroarenes under identical conditions. Density functional theory (DFT) investigations unveil the mechanistic dichotomy between olefin and heteroarene activation followed by 1,2-migration, leading to E or Z-vinyl heteroarenes respectively. We also report a previously unknown reversal of stereoselectivity by using 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as an electrophile. The Zweifel olefination using a boronate complex that carries two different olefins was previously unexplored due to significant challenges associated with the site-selective activation of olefins. We have solved this problem and reported the site-selective activation of olefins for the stereoselective synthesis of 1,3-dienes.

1,2-Metallate Rearrangement Using Indole Boronate Species to Access 2,3-Diarylindoles and Indolines.

A transition metal-free multicomponent reaction using lithiated indole, boronic ester, pyridine, and ethyl chloroformate was developed to access C2,C3 bis-arylated indoles, which are present in several marketed drugs and bioactive compounds. One-pot access to unsymmetrical C2,C3-diaryl indole from the parent indole remains a huge synthetic challenge. Our group was able to achieve this goal through a transition metal-free 1,2-metalate rearrangement of the indole boronate complex. The reaction of indole boronate species with activated pyridine allows 1,2-migration to access pyridyl-indoleboronate species, which will convert to the corresponding indole upon oxidation and indoline after deborylation. The reaction tolerates substituted pyridines, quinolone, isoquinoline, and more. Both aryl and alkyl boronic esters were accommodated under optimized reaction conditions. Apart from mechanistic studies using 11B-NMR, this methodology has been applied to the gram-scale synthesis of several bioactive compounds.

Recent advances in the synthesis and reactivity of MIDA boronates.

Organoboron compounds have a wide-range of applications in synthetic methodologies, natural products, and bioactive molecule synthesis. The sensitivity of boronic acid toward most synthetic reagents makes it necessary to introduce a protecting group before its utilization. Benchtop stable MIDA boronates have been found compatible with various common synthetic reagents which opens the doors for the synthesis of various small building blocks, natural products, and bioactive compounds. MIDA boronate compounds have been extensively utilized in Suzuki Miyaura coupling and Iterative cross-coupling reactions for the total synthesis of bioactive molecules and polymerization reactions. Different MIDA boronate compounds like vinyl, acyl, formyl, acrylic, and α-carbonyl MIDA boronates also act as novel synthetic building blocks for various synthetic transformations in organic synthesis. This paper summarizes the importance of MIDA boronate compounds in various aspects of organic chemistry.

Iron Catalysis: A New Horizon Towards Organoboron-mediated C-C Cross-coupling.

Transition metal-catalyzed cross-couplings have had a profound impact on chemical synthesis. Among the various transition metals, iron has drawn huge attention due to its cost effectiveness, range of stable oxidation states, Lewis acidic property and releatively less toxicity. Iron complexes have exhibited an efficient catalytic activity towards the cross-coupling reaction using organomagnesium, organolithium and organozinc reagent. Organoboron compounds are also engaged as a coupling partner for Fe catalysed C-C bond forming reactions. Over the last two decades' various iron catalysed C-C bond forming reactions have been developed. This review will summarize the chronological development in this research area along with challenges appearing especially in the past decade.

Mechanistic dichotomy in the solvent dependent access to E vs. Z-allylic amines via decarboxylative vinylation of amino acids.

The solvent plays an important role in the photophysical properties of donor-acceptor based photocatalysts. The solvent-dependent access to E vs. Z-allylic amines was achieved via decarboxylative vinylation of amino acids with vinyl sulfones. Detailed experimental studies have been conducted to understand the role of the solvent in the reactivity and stereoselectivity of the vinylation reactions.

Development of homologous hemizona assay as a potential predictor of fertility in buffalo bulls: A preliminary approach.

Although, myriads of tests are routinely used, no single test can accurately predict fertilization potential of semen. The hemizona assay (HZA) has advantages in two ways: (a) it determines multitude traits of sperm and (b) it is a controlled sperm function test. In the present study, we developed homologous HZA in buffaloes to predict bull fertility. In this experiment, bulls with fertility rate 53.3% and 48.5% were used as control, whereas bulls with fertility rate 32.6% and 32.2% were used as test semen samples. For HZA, matching buffalo hemizonae were co-incubated with processed buffalo sperm for 4 h. The number of sperms bound to the outer surface of hemizona was determined. No significant difference was observed in sperm binding for co-incubation of same bull sperm with matching hemizona (p < .05). Significant difference in sperm binding to matching hemizona was seen, while two halves were incubated with control and test semen, respectively (p < .05). Hemizona assay index (HZAI) of test bull semen has been determined from percentage of test-sperm bound to the matching hemizona in comparison to control-sperm. For finding relation, HZAI was correlated with respective fertility rates of semen samples, and it was found that a significant positive correlation was present with r = 0.83, p < .1. A regression equation of Y = 1.39X - 55.8 (where Y = pregnancy rate of test semen sample and X = HZAI of test semen sample) was presented to predict fertility rates of unknown semen samples. Thus, HZA can be used as a potential predictor of buffalo bull fertility.

Transition-Metal-Free Heterocyclic Carbon-Boron Bond Formation.

Heteroaryl boronic acids and esters are extremely important and valuable intermediates because of their wide application in the synthesis of marketed drugs and bioactive compounds. Over the last couple of decades, the construction of highly important heteroaryl carbon-boron bonds has created huge attention. The transition-metal-free protocols are more green, less sensitive to air and moisture, and also economically advantageous over the transition-metal-based protocols. The transition-metal-free C-H borylation of heteroarenes and C-X (X=halogen) borylation of heteroaryl halides represents an excellent approach for their synthesis. Also, various cyclization and alkyne activation protocols have been recently established for their synthesis. The goal of this review article is to summarize the existing literature and the current state of the art for transition-metal-free synthesis of heteroaryl boronic acid and esters.

Development of Methods to the Synthesis of ß-Boryl Acyls, Imines and Nitriles.

Organoboron compounds are highly important and versatile synthetic intermediates for the preparation of a wide range of organic molecules. Organoboron compounds have drawn significant attention among organic chemists due to their Lewis acidic property, non-toxicity, and commercial availability. Over the last several decades, there has been a substantial development of new organoboron compounds, useful in organic synthesis. Among all other organoboron compounds, ß-boryl carbonyl compounds are the important ones. The ß-boryl compounds have appeared as promising intermediates for various synthetic transformations. The 1,4-conjugate addition of diboron reagents to carbon-carbon double bond in the presence of different transition-metal catalysts has been extensively reported by various research groups across the globe. This mini-review outlines the numerous racemic as well as asymmetric ß-borylation methods developed to date.

Recombinant expression and molecular characterization of buffalo sperm lysozyme-like protein 1.

Several sperm lysozyme-like genes evolved from lysozyme by successive duplications and mutations; however their functional role in the reproduction of farm animals is not well understood. To understand the function and molecular properties of buffalo sperm lysozyme-like protein 1 (buSLLP1), it was expressed in E. coli; however, it partitioned to inclusion bodies. Lowering of temperature and inducer concentration did not help in the recovery of the expressed protein in the biologically active form. Therefore, buSLLP1 was cloned and expressed in Pichiapink system based on auxotrophic Pichia pastoris in a labscale fermenter. The expressed protein was obtained in flow-through by using a 30 kDa ultrafiltration membrane followed by MonoQ anion exchange chromatography, resulting in a homogenous preparation of 40 mg recombinant buSLLP1 per liter of initial spent culture-supernatant. Circular dichroism spectroscopy showed that recombinant buSLLP1 possessed a native-like secondary structure. The recombinant buSLLP1 also showed thermal denaturation profile typical of folded globular proteins; however, the thermal stability was lower than the hen egg white lysozyme. Binding of buSLLP1 to chitin and zona pellucida of buffalo oocytes showed that the recombinant buSLLP1 possessed a competent binding pocket, therefore, the produced protein could be used to study its functional role in the reproduction of farm animals.

Synthesis and reactivity of alkynyl boron compounds.

Over the last century, there have been considerable developments in organoboron chemistry due to the stability, non-toxicity, and easy commercial availability of various boronic esters. Several organoboron reagents have emerged and play an increasingly important role in everyday organic synthesis. Among them, alkynyl boron compounds have attracted significant attention due to their easy synthesis and diverse reactivity. In this review, we summarize the advancement of research on alkynyl boron compounds, highlighting their importance in the synthesis of valuable compounds.

Transition metal catalyzed asymmetric multicomponent reactions of unsaturated compounds using organoboron reagents.

Asymmetric multicomponent reactions allow stitching several functional groups in an enantioselective and atom economical manner. The introduction of boron-based reagents as a multicomponent coupling partner has its own merits. In addition to being non-toxic and highly stable, organoboron compounds can be easily converted to other functional groups in a stereoselective manner. In the last decade several transition metal catalyzed asymmetric multicomponent strategies have been evolved using boron based reagents. This review will discuss the merits and scope of multicomponent strategies based on their difference in the reaction mechanism and transition metals involved.

Transition metal-free synthesis of alkyl pinacol boronates.

Alkyl pinacol boronic esters have been routinely used for the synthesis of complex target molecules or high-value chemicals due to their non-toxicity, stability and commercial availability. The synthesis of C-B bonds in the absence of transition metals has gained significant attention due to its added advantages. Numerous methods have been developed for the synthesis of alkyl pinacol boronates without transition metals, which include reactions using organometallic reagents, Lewis acids and bases, photoredox catalysis, and 1,2-metallate rearrangement. Herein, we have analyzed the growing resource of literature related to the transition metal-free synthesis of alkyl pinacol boronic esters based on the differences in their reaction mechanisms.

Functionalization of Heterocycles through 1,2-Metallate Rearrangement of Boronate Complexes.

Over the last decade, 1,2-metallate rearrangement of boronate complex has been dominating the literature of organoboron chemistry for the construction of very important C-C and C-boron bonds. Owing to the coordinative unsaturated nature of the boron atom, a nucleophile can attack on boron center for the formation of a boronate complex, which triggers 1,2-migration under electrophilic activation at the α-carbon. Apart from using stochiometric electrophilic activating reagents, several catalytic methods using transition metals in the presence or absence of light have been reported. The 1,2-migration of boronate complexes allows synthesis of many different classes of racemic and chiral compounds including a wide range of substituted heterocycles. Synthesis of chiral and achiral substituted heterocycles by using 1,2-metallate rearrangement of boronate complexes has been extensively reported by several groups owing to its prevalence in medicinal chemistry. This minireview highlights the methods known to date for the synthesis of heteroaryls by using 1,2-migration of boronate complexes, organized in a chronological manner.

Transition-Metal-Free Synthesis of Heterobiaryls through 1,2-Migration of Boronate Complex.

The synthesis of a diverse range of heterobiaryls has been achieved by a transition-metal-free sp2 -sp2 cross-coupling strategy using lithiated heterocycle, aryl or heteroaryl boronic ester and an electrophilic halogen source. The construction of heterobiaryls was carried out through electrophilic activation of the aryl-heteroaryl boronate complex, which triggered 1,2-migration from boron to the carbon atom. Subsequent oxidation of the intermediate boronic ester afforded heterobiaryls in good yield. A comprehensive 11 B NMR study has been conducted to support the mechanism. The cross coupling between two nucleophilic cross coupling partners without transition metals reveals a reliable manifold to procure heterobiaryls in good yields. Various heterocycles like furan, thiophene, benzofuran, benzothiophene, and indole are well tolerated. Finally, we have successfully demonstrated the gram scale synthesis of the intermediates for an anticancer drug and OLED material using our methodology.

Tandem Allylation/1,2-Boronate Rearrangement for the Asymmetric Synthesis of Indolines with Adjacent Quaternary Stereocenters.

A three-component coupling using lithiated indoles, boronate esters and allylic acetates generates chiral indolines with adjacent quaternary stereocenters. Successful stereocontrol required the use of phosphoramidite ligands not previously described for organopalladium chemistry. Mechanistic studies indicate a monodentate PdL intermediate, and a stepwise allylation-aryl/alkyl migration. A protodeborylation strategy was used to install a C-H bond in place of the C-B bond. A photoredox coupling was used to replace C-B bond with a C-C bond in a highly diastereoselective manner. In the specific case of methyl-vinyl ketone, a novel radical-mediated annulation provides polycyclic products with high enantio- and diastereoselectivity.