Diversity-oriented synthesis of indole-fused scaffolds and bis(indolyl)methane from tosyl-protected tryptamine.

An efficient, diversity-oriented synthesis of indole-1,2-fused 1,4-benzodiazepines, tetrahydro-ß-carbolines, and 2,2'-bis(indolyl)methanes was established starting from tosyl-protected tryptamine. These diverse privileged skeletons were controllably constructed by adjusting different hydride donors and Brønsted acids. A variety of indole-1,2-fused 1,4-benzodiazepines were facilely accessed using benzaldehydes bearing cyclic amines as hydride donors via a cascade N-alkylation/dehydration/[1,5]-hydride transfer/Friedel-Crafts alkylation sequence. The reaction site could be switched when benzaldehydes bearing an alkoxy moiety as hydride donors were used for the generation of tetrahydro-ß-carbolines. On the other hand, the switchable synthesis of 2,2'-bis(indolyl)methanes could be achieved as well by applying p-TsOH·H2O as a catalyst. The reactions feature mild conditions, simple and practical operation, excellent efficiency and the use of EtOH as a green solvent. Using the concept of diversity-oriented, reagent-based synthesis, the inexpensive feedstock tryptamine was efficiently converted to three different types of privileged scaffolds, which facilitates rapid compound library synthesis for accelerating drug discovery.

Dearomatization of 3-Aminophenols for Synthesis of Spiro[chromane-3,1'-cyclohexane]-2',4'-dien-6'-ones via Hydride Transfer Strategy-Enabled [5+1] Annulations.

The Sc(OTf)3-catalyzed dearomative [5+1] annulations between readily available 3-aminophenols and O-alkyl ortho-oxybenzaldehydes were developed for synthesis of spiro[chromane-3,1'-cyclohexane]-2',4'-dien-6'-ones. The "two-birds-with-one-stone" strategy was disclosed by the dearomatization of phenols and direct α-C(sp3)-H bond functionalization of oxygen through cascade condensation/[1,5]-hydride transfer/dearomative-cyclization process. In addition, the antifungal activity assay and derivatizations of products were conducted to further enrich the utility of the structure.

Alkyl amines and ethers as traceless hydride donors in [1,5]-hydride transfer cascade reactions.

The use of alkyl amines and ethers as traceless hydride donors in [1,5]-hydride transfer cascade reactions represents a promising strategy that greatly enriches redox-neutral hydride transfer chemistry. This review summarizes the remarkable progress made in this field, and focuses on (1) alkyl amines as traceless hydride donors in cascade [1,5]-hydride transfer/elimination reactions and (2) alkyl ethers as traceless hydride donors in [1,5]-hydride transfer cascade reactions. The reaction mechanisms, features, scope, limitations, and synthetic applications are included, where appropriate. Importantly, its powerful ability in allene synthesis and the combination with [Re]-vinylidene and carbocation chemistries render this strategy attractive enough to inspire chemists to develop colorful reactions for building molecular complexity.

Chemoselective and diastereoselective construction of 4-alkylidene-tetrahydroquinoline via a redox-neutral vinylogous cascade [1,7]-hydride transfer/6-endo-trig cyclization strategy.

Herein, we disclose a chemoselective and diastereoselective synthesis of the medicinally significant 4-alkylidene-tetrahydroquinoline via a redox-neutral vinylogous cascade condensation/[1,7]-hydride transfer/6-endo-trig cyclization strategy, which features a novel product skeleton, high chemoselectivity and diastereoselectivity, facile introduction of 4-alkylidenyl motifs, employment of α,ß,γ,δ-unsaturated dicyanoalkenes as novel hydride acceptors, and green and metal-free conditions with water as the only by-product. Additionally, the versatility of α,α-dicyanoalkenes has been fully exploited as hydride acceptors and γ-exclusive nucleophiles consecutively for accessing novel heterocyclic skeletons.

Responses of greenhouse gas emissions to residue returning in China's croplands and influential factors: A meta-analysis.

Climate change is a global issue threatening agricultural production and human survival. However, agriculture sector is a major source of global greenhouse gases (GHGs), especially CH4 and N2O. Crop residue returning (RR) is an efficient practice to sequestrate soil carbon and increase crop yields. However, the efficiency of RR to mitigate climate change and maintain food security will be affected by the response of GHG emissions at both per area-scale and per yield-scale. Therefore, a national meta-analysis was conducted using 309 comparisons from 44 publications to assess the responses of GHG emissions to RR in China's croplands. The results indicated that little response of GWP to RR was observed with conditions under lower nitrogen fertilizer input rates (0-120 kg ha-1), mulch retention, returning one time in double cropping systems, returning with half residue, weakly acidic soil (pH 5.5-6.5), initial SOC contents >20 g kg-1, or mean annual precipitation <1000 mm. In order to mitigate climate change and sustain food security, RR combined with paddy-upland rotation, nitrogen fertilizer input rates of 240-360 kg ha-1, and neutral soil (pH 6.5-7.5) could decrease GWP at per unit of crop yield, which ultimately leads to a lower effect on GHGI and a higher crop production efficiency. In-depth studies should be conducted in the future to explore the interactions between various factors influencing GHG emissions under RR conditions. Overall, optimizing the interactions with management and site-specific conditions, potential for regulating GHGs emissions of RR can be enhanced.

AGRP Neurons Project to the Medial Preoptic Area and Modulate Maternal Nest-Building.

AGRP (agouti-related neuropeptide) expressing inhibitory neurons sense caloric needs of an animal to coordinate homeostatic feeding. Recent evidence suggests that AGRP neurons also suppress competing actions and motivations to mediate adaptive behavioral selection during starvation. Here, in adult mice of both sexes we show that AGRP neurons form inhibitory synapses onto ∼30% neurons in the medial preoptic area (mPOA), a region critical for maternal care. Remarkably, optogenetically stimulating AGRP neurons decreases maternal nest-building while minimally affecting pup retrieval, partly recapitulating suppression of maternal behaviors during food restriction. In parallel, optogenetically stimulating AGRP projections to the mPOA or to the paraventricular nucleus of hypothalamus but not to the LHA (lateral hypothalamus area) similarly decreases maternal nest-building. Chemogenetic inhibition of mPOA neurons that express Vgat (vesicular GABA transporter), the population targeted by AGRP terminals, also decreases maternal nest-building. In comparison, chemogenetic inhibition of neurons in the LHA that express vesicular glutamate transporter 2, another hypothalamic neuronal population critical for feeding and innate drives, is ineffective. Importantly, nest-building during low temperature thermal challenge is not affected by optogenetic stimulation of AGRP→mPOA projections. Finally, via optogenetic activation and inhibition we show that distinctive subsets of mPOA Vgat+ neurons likely underlie pup retrieval and maternal nest-building. Together, these results show that AGRP neurons can modulate maternal nest-building, in part through direct projections to the mPOA. This study corroborates other recent discoveries and underscores the broad functions that AGRP neurons play in antagonizing rivalry motivations to modulate behavioral outputs during hunger.SIGNIFICANCE STATEMENT In order for animals to initiate ethologically appropriate behaviors, they must typically decide between behavioral repertoires driven by multiple and often conflicting internal states. How neural pathways underlying individual behaviors interact to coherently modulate behavioral outputs, in particular to achieve a proper balance between behaviors that serve immediate individual needs versus those that benefit the propagation of the species, remains poorly understood. Here, by investigating projections from a neuronal population known to drive hunger behaviors to a brain region critical for maternal care, we show that activation of AGRP→mPOA projections in females dramatically inhibits maternal nest-building while leaving mostly intact pup retrieval behavior. Our findings shed new light on neural organization of behaviors and neural mechanisms that coordinate behavioral selection.

Hydrogen-bonding-assisted redox-neutral construction of tetrahydroquinolines via hydride transfer.

The hydrogen-bonding-assisted construction of tetrahydroquinolines decorated with structurally diverse 3,3'-difunctional groups has been realized via a hydride transfer-involved three-step cascade reaction in the presence of morpholine. This protocol solves the limitation of acyclic 1,3-dicarbonyl compounds by one-pot synthesis of tetrahydroquinolines, featuring operational simplicity, broadly applicable substrates, and metal- and acid-free conditions with EtOH as a hydrogen-bonding donor.

Fluorinated alcohol mediated N,N'-dialkylation of amino acid derivatives via cascade [1,5]-hydride transfer/cyclization for concise synthesis of tetrahydroquinazoline.

Structurally diverse amino acids and their ester derivatives were conveniently N,N'-dialkylated via a TFE-promoted cascade condensation/[1,5]-hydride transfer/cyclization for straightforward construction of pharmeutically significant tetrahydroquinazolines incorporating various amino acids, which featured broad substrate scope, the use of TFE as a sole solvent, additive-free and mild conditions.

Aromatization-Driven Cascade [1,5]-Hydride Transfer/Spirocyclization Promoted by Fluorinated Alcohols.

The aromatization-driven redox-neutral cascade [1,5]-hydride transfer/spirocyclization and cascade [1,5]-hydride transfer/hydrolysis from para-quinone methide in HFIP were developed. These protocols enabled the synthesis of azaspirocyclohexadienones and ortho-benzylated anilines in good to high yields under mild conditions, featuring room temperature, additive-free, and good functional group tolerance.

Cascade [1,5]-Hydride Transfer/Cyclization for Synthesis of [3,4]-Fused Oxindoles.

The scandium-catalyzed redox-neutral cascade [1,5]-hydride transfer/cyclization between C4-amine-substituted isatins and 1,3-dicarbonyl compounds has been developed. This protocol enabled the synthesis of tricyclic [3,4]-fused oxindoles in good to high yields and excellent diastereoselectivities, featuring high atom- and step economy as well as good functional group tolerance.

Formal [4 + 2] Annulation of Oxindole-Embedded ortho-Quinone Methides with 1,3-Dicarbonyls: Synthesis of Spiro[Chromen-4,3'-Oxindole] Scaffolds.

The oxindole-embedded ortho-quinone methides were employed as reactive intermediates in formal [4 + 2] annulation with 1,3-dicarbonyls, providing an efficient access to spiro[chromen-4,3'-oxindole] scaffolds via a cascade conjugate addition/ketalization/dehydration process. This protocol featured metal-free conditions, wide substrate scope, and excellent yields.

Organocatalytic C(sp3)-H Functionalization of 5-Methyl-2,3-dihydrofuran Derivatives with Trifluoropyruvates via a Sequential exo-Tautomerization/Carbonyl-Ene Process.

An organocatalytic C(sp3)-H functionalization of 5-methyl-2,3-dihydrofuran derivatives with trifluoropyruvates was achieved via a sequential exo-tautomerization/carbonyl-ene process, providing the biologically important CF3-substituted 2,3-dihydrofurans in high yields. This method featured mild metal-free conditions, good chemoselectivity, and easy scalability.

Fluorinated Alcohol-Promoted Reaction of Chlorohydrocarbons with Diverse Nucleophiles for the Synthesis of Triarylmethanes and Tetraarylmethanes.

This article reports an efficient synthesis of triarylmethanes and tetraarylmethanes from chlorohydrocarbons with miscellaneous nucleophiles in fluorinated alcohols, featuring metal-free, wide substrate scope, excellent functional group tolerance, and mild reaction conditions.

Efficient construction of tetrahydroquinolines via fluorinated alcohol mediated cascade [1,5]-hydride transfer/cyclization.

An environmentally benign cascade redox-neutral process was developed for the efficient construction of pharmaceutically significant spirocyclic tetrahydro-quinolines via a 3-step cascade Knoevenagel condensation/[1,5]-hydride transfer/cyclization, which features green and additive-free conditions, wide substrate scope, and high step- and atom-economy.

t-BuOK-Mediated Oxidative Dehydrogenative C(sp3)-H Arylation of 2-Alkylazaarenes with Nitroarenes.

The first transition-metal free and regioselective C(sp3)-H arylation of 2-alkylazaarenes with nitroarenes has been achieved via t-BuOK-mediated dehydrogenative C(sp3)-C(sp2) coupling. This reaction provides an efficient access to the biologically important and synthetically useful 2-benzyl-substituted azaarenes under mild conditions without the need of prefunctionalization of 2-alkylazaarenes or using the specialized arylating agents.

Rhodium-Catalyzed Hydrogen-Releasing ortho-Alkenylation of 7-Azaindoles.

An efficient rhodium-catalyzed dehydrogenative Heck-type reaction between N-aryl-substituted 7-azaindoles and various alkenes through a H2 -releasing process without the need of any oxidizing agent was developed. The novel methodology broadens the scope of metal-catalyzed hydrogen-releasing reactions to include rhodium catalysis.

Rhodium-catalyzed C-C coupling reactions via double C-H activation.

Various rhodium-catalyzed double C-H activations are reviewed. These powerful strategies have been developed to construct C-C bonds, which might be widely embedded in complex aza-fused heterocycles, polycyclic skeletons and heterocyclic scaffolds. In particular, rhodium(iii) catalysis shows good selectivity and reactivity to functionalize the C-H bond, generating reactive organometallic intermediates in most of the coupling reactions. Generally, intermolecular, intramolecular and multi-component coupling reactions via double C-H activations with or without heteroatom-assisted chelation are discussed in this review.

Rhodium(III)-catalyzed C-C coupling of 7-azaindoles with vinyl acetates and allyl acetates.

The behaviour of electron-rich alkenes with 7-azaindoles in rhodium(III)-catalyzed C-H activation is investigated. Various substituted vinyl acetates and allyl acetates as coupling partners reacted smoothly providing a wide variety of 7-azaindole derivatives, and the selectivity of the coupling reaction is alkene-dependent. In addition, the approaches of rhodium(III)-catalyzed dehydrogenative Heck-type reaction (DHR) and carbonylation reaction were quite novel and simple.

One-pot construction of fused polycyclic heteroarenes involving 7-azaindoles and α,ß-unsaturated ketones.

A novel one-pot synthesis of π-conjugated polycyclic compounds, which could undergo further facile transformation to form complex polycyclic heteroarene compounds, has been realized between 7-azaindoles and α,ß-unsaturated ketones. This distinctive cascade process proceeds via a rhodium(iii)-catalyzed alkylation/copper-catalyzed radical annulation-aromatization pathway.

A unique annulation of 7-azaindoles with alkenyl esters to produce π-conjugated 7-azaindole derivatives.

Rhodium(iii)-catalyzed N-directed ortho C-H activation and subsequent roll-over C-H activation represents an important strategy to synthesize fused polycyclic compounds. Herein, the novel methodology broadens the scope of the coupling partner to alkenes, which working smoothly with 7-azaindoles has been proven to be an efficient and atom-economical strategy to access complex π-conjugated 7-azaindole derivatives.