Copper-Catalyzed Regio- and Stereoselective Formal Hydro(borylmethylsilyl)ation of Internal Alkynes via Alkenyl-to-Alkyl 1,4-Copper Migration.

Catalytic reactions involving 1,n-metal migration from carbon to carbon enable a nonclassical way of constructing organic molecular skeletons, rapidly providing complex molecules from relatively simple precursors. By utilization of this attractive feature, a new and efficient synthesis of alkenylsilylmethylboronates has been developed by formal hydro(borylmethylsilyl)ation of unsymmetric internal alkynes with silylboronates under copper catalysis. The reaction proceeds regioselectively and involves an unprecedented alkenyl-to-alkyl 1,4-copper migration. The reaction mechanism has been investigated by a series of kinetic, NMR, and deuterium-labeling experiments.

Chiral Phosphoric Acid-Palladium(II) Complex Catalyzed Asymmetric Desymmetrization of Biaryl Compounds by C(sp3)-H Activation.

Desymmetrization is an essential method for the synthesis of chiral compounds, particularly chiral biaryls. We have developed an enantioselective synthesis of axially chiral biaryls by desymmetrization using C(sp3)-H activation catalyzed by chiral palladium phosphate. Mechanistic studies show that C-H activation is the rate- and enantiomer-determining step. To the best of our knowledge, this is the first report of asymmetric desymmetrization of axially chiral compounds by C(sp3)-H activation.

Palladium-Catalyzed Siloxycyclopropanation of Alkenes Using Acylsilanes.

Currently, catalytically transferable carbenes are limited to electron-deficient and neutral derivatives, and electron-rich carbenes bearing an alkoxy group (i.e., Fischer-type carbenes) cannot be used in catalytic cyclopropanation because of the lack of appropriate carbene precursors. We report herein that acylsilanes can serve as a source of electron-rich carbenes under palladium catalysis, enabling cyclopropanation of a range of alkenes. This reactivity profile is in sharp contrast to that of metal-free siloxycarbenes, which are unreactive toward normal alkenes. The resulting siloxycyclopropanes serve as valuable homoenolate equivalents, allowing rapid access to elaborate ß-functionalized ketones.

Catalytic Enantioselective Construction of Decalin Derivatives by Dynamic Kinetic Desymmetrization of C2-Symmetric Derivatives through Aldol-Aldol Annulation.

We have developed and investigated a catalytic desymmetrization reaction strategy that affords functionalized decalin derivatives with high enantioselectivities from C2-symmetric derivatives through aldol-aldol annulation. We identified the structural moieties of the catalyst necessary for the formation of the decalin derivative with high enantioselectivity. We elucidated the mechanisms of the catalyzed reactions: the first aldol reaction step was reversible, and the second aldol step was rate-limiting and stereochemistry-determining and was enantioselective. Using theoretical calculations guided by the experimental results, we identified the interactions between the catalyst and the transition state that led to the major enantiomer. The information obtained in this study will be useful for the development of catalysts and chemical transformations.

On the origin and evolution of the asteroid Ryugu: A comprehensive geochemical perspective.

Presented here are the observations and interpretations from a comprehensive analysis of 16 representative particles returned from the C-type asteroid Ryugu by the Hayabusa2 mission. On average Ryugu particles consist of 50% phyllosilicate matrix, 41% porosity and 9% minor phases, including organic matter. The abundances of 70 elements from the particles are in close agreement with those of CI chondrites. Bulk Ryugu particles show higher δ18O, Δ17O, and ε54Cr values than CI chondrites. As such, Ryugu sampled the most primitive and least-thermally processed protosolar nebula reservoirs. Such a finding is consistent with multi-scale H-C-N isotopic compositions that are compatible with an origin for Ryugu organic matter within both the protosolar nebula and the interstellar medium. The analytical data obtained here, suggests that complex soluble organic matter formed during aqueous alteration on the Ryugu progenitor planetesimal (several 10's of km), <2.6 Myr after CAI formation. Subsequently, the Ryugu progenitor planetesimal was fragmented and evolved into the current asteroid Ryugu through sublimation.

Palladium-Catalyzed Silylacylation of Allenes Using Acylsilanes.

We have developed a palladium-catalyzed addition of a C-Si bond of acylsilanes across a range of unactivated allenes. The reaction proceeds with complete regioselectivity, in which a silyl group binds to the central carbon of the allene, allowing for the straightforward access to functionalized alkenylsilane derivatives.

Phosphine-Catalyzed Intermolecular Acylfluorination of Alkynes via a P(V) Intermediate.

We report the phosphine-catalyzed intermolecular carbofluorination of alkynes using acyl fluorides as fluorinating reagents. This reaction promises to be a useful method for the synthesis of highly substituted monofluoroalkene derivatives since acyl fluorides can be easily prepared from the corresponding carboxylic acid derivatives and the reaction proceeds under ambient conditions without the need for a transition-metal catalyst. Experimental and computational studies indicate that a five-coordinate fluorophosphorane is involved as the key intermediate in the fluorination step.

Cobalt-Catalyzed Intramolecular Hydroacylation Involving Cyclopropane Cleavage.

A simple cobalt-diphosphine catalyst has been found to efficiently promote intramolecular cyclization of ortho-cyclopropylvinyl- and cyclopropylidenemethyl-substituted benzaldehydes into benzocyclooctadienone and benzocycloheptadienone derivatives, respectively. This ring-opening hydroacylation likely involves aldehyde C-H oxidative addition, olefin insertion, cyclopropane cleavage by ß-carbon elimination, and C-C bond-forming reductive elimination, as was supported by mechanistic experiments and DFT calculations.

Mechanism and Origin of Stereoselectivity in Chiral Phosphoric Acid-Catalyzed Aldol-Type Reactions of Azlactones with Vinyl Ethers.

The precise mechanism of the chiral phosphoric acid-catalyzed aldol-type reaction of azlactones with vinyl ethers was investigated. DFT calculations suggested that the reaction proceeds through a Conia-ene-type transition state consisting of the vinyl ether and the enol tautomer of the azlactone, in which the catalyst protonates the nitrogen atom of the azlactone to promote enol tautomerization. In addition, the phosphoryl oxygen of the catalyst interacts with the vinyl proton of the vinyl ether. The favorable transition structure features dicoordinating hydrogen bonds. However, these hydrogen bonds are not involved in the bond recombination sequence and hence the catalyst functions as a template for binding substrates. From the results of theoretical studies and experimental supports, the high enantioselectivity is induced by the steric repulsion between the azlactone substituent and the binaphthyl backbone of the catalyst under the catalyst template effect.

Enantioselective Epoxidation of 2,3-Disubstituted Naphthoquinones by a Side Chain Truncated Guanidine-Urea Bifunctional Organocatalyst.

An organocatalytic enantioselective epoxidation of 2,3-disubstituted naphthoquinones with tert-butyl hydroperoxide as an oxidant was developed using a guanidine-urea bifunctional catalyst lacking C2 symmetry, which was designed based upon the insights obtained from the DFT calculation model for our previous C2 symmetric catalyst. The present organocatalytic reaction provides access to a variety of optically active naphthoquinone epoxides bearing aryl and methyl substituents at C2 and C3 in high yields with high enantioselectivities (up to 97:3 er).

Chiral bifunctional sulfide-catalyzed asymmetric bromoaminocyclizations.

A BINOL-derived chiral bifunctional sulfide catalyst bearing a phenylurea moiety was applied to enantioselective bromoaminocyclization reactions of 2-allylaniline derivatives, which provide optically active 2-substituted indoline products as important motifs for biologically active compounds. A protecting group on the nitrogen of the 2-allylaniline substrate was carefully optimized, and highly enantioselective reactions were achieved by employing the p-biphenylsulfonyl-protected substrates. The origin of the good level of enantioselectivity for the present bromoaminocyclization was also investigated on the basis of DFT calculations. The resultant optically active 2-(bromomethyl)indoline products could be transformed to various 2-substituted indolines with no loss of the optical purity.

Catalytic Asymmetric Iodoesterification of Simple Alkenes.

Catalytic asymmetric iodoesterification of simple alkenes was achieved using a dinuclear zinc-3,3'-(R,S,S)-bis(aminoimino)binaphthoxide (di-Zn) complex. For iodoesterification using p-methoxybenzoic acid, the N-iodonaphthalenimide (NIN)-I2 system was effective for producing iodoesters in a highly enantioselective manner. The synthetic utility of chiral iodo-p-methoxybenzoates was also demonstrated. The quartet of metal ionic bond, hydrogen bond, halogen bond, and π-π stacking is harmonized on the single reaction sphere of di-Zn catalyst for enabling the highly enantioselective catalytic asymmetric iodoesterification of simple alkenes for the first time.

Stereoselective Synthesis of Four Calcitriol Lactone Diastereomers at C23 and C25.

(23 S,25 R)-Calcitriol lactone is a major metabolite of vitamin D3, but its synthesis has been far less well investigated than that of 1α,25(OH)2 vitamin D3, the active form of vitamin D3, even though the lactone is present at a significant level in serum. This paper describes stereoselective syntheses of natural calcitriol lactone and its diastereomers at C23 and C25. This work features (i) the diastereoselective Reformatsky-type crotylation of aldehyde 25 in the presence of chiral ligand L2 to construct the stereochemistry at C23 and (ii) the diastereoselective epoxidation of homoallylic-allylic alcohol 31 to control the stereochemistry at C25. These key reactions allowed us to synthesize CD-ring synthon 30 with all four stereoisomers, and these were further converted into calcitriol lactones 3a-3d by reaction with ene-yne-type A-rings 33 in the presence of a palladium (0) catalyst.

BINOL-derived bifunctional sulfide catalysts for asymmetric synthesis of 3,3-disubstituted phthalides via bromolactonization.

An efficient enantioselective synthesis of 3,3-disubstituted phthalides possessing a chiral quaternary carbon center was achieved via catalytic asymmetric bromolactonization that utilized BINOL-derived bifunctional sulfide catalysts. Transformations of the bromo group in optically active phthalide products were also performed to demonstrate the utility of this novel synthetic protocol.

Hypervelocity collision and water-rock interaction in space preserved in the Chelyabinsk ordinary chondrite.

A comprehensive geochemical study of the Chelyabinsk meteorite reveals further details regarding its history of impact-related fragmentation and melting, and later aqueous alteration, during its transit toward Earth. We support an ∼30 Ma age obtained by Ar-Ar method (Beard et al., 2014) for the impact-related melting, based on Rb-Sr isotope analyses of a melt domain. An irregularly shaped olivine with a distinct O isotope composition in a melt domain appears to be a fragment of a silicate-rich impactor. Hydrogen and Li concentrations and isotopic compositions, textures of Fe oxyhydroxides, and the presence of organic materials located in fractures, are together consistent with aqueous alteration, and this alteration could have pre-dated interaction with the Earth's atmosphere. As one model, we suggest that hypervelocity capture of the impact-related debris by a comet nucleus could have led to shock-wave-induced supercritical aqueous fluids dissolving the silicate, metallic, and organic matter, with later ice sublimation yielding a rocky rubble pile sampled by the meteorite.

Catalysis Based on C-I⋠⋠⋠π Halogen Bonds: Electrophilic Activation of 2-Alkenylindoles by Cationic Halogen-Bond Donors for [4+2] Cycloadditions.

Homo- and cross-[4+2] cycloadditions of 2-alkenylindoles, catalyzed by cationic halogen-bond donors, were developed. Under mild reaction conditions, 3-indolyl-substituted tetrahydrocarbazole derivatives were obtained in good to excellent yields. Experimental and quantum calculation studies revealed that the electrophilic activation of 2-alkenylindoles was achieved by C-I⋅⋅⋅π halogen bonds.

Chiral Magnesium Bisphosphate-Catalyzed Asymmetric Double C(sp3)-H Bond Functionalization Based on Sequential Hydride Shift/Cyclization Process.

Described herein is a chiral magnesium bisphosphate-catalyzed asymmetric double C(sp3)-H bond functionalization triggered by a sequential hydride shift/cyclization process. This reaction consists of stereoselective domino C(sp3)-H bond functionalization: (1) a highly enantio- and diastereoselective C(sp3)-H bond functionalization by chiral magnesium bisphosphate (first [1,5]-hydride shift), and (2) a highly diastereoselective C(sp3)-H bond functionalization by an achiral catalyst (Yb(OTf)3, second [1,5]-hydride shift).

Design of Chiral Bifunctional Dialkyl Sulfide Catalysts for Regio-, Diastereo-, and Enantioselective Bromolactonization.

Although a wide variety of chiral organocatalysts have been developed for asymmetric transformations, effective chiral dialkyl sulfide organocatalysts remain relatively rare and under-developed, despite the potential utility of dialkyl sulfide catalysts. Herein, we report the development of chiral bifunctional dialkyl sulfide catalysts possessing a urea moiety for regio-, diastereo-, and enantioselective bromolactonization. The importance of the bifunctional design of chiral sulfide catalysts was clearly demonstrated in the present work. The roles of both the sulfide and urea moieties of the catalyst were clarified based on the results of experimental and theoretical investigation.

Enantioselective Electrophilic Cyanation of Boron Enolates: Scope and Mechanistic Studies.

Chiral ß-ketonitriles bearing a stereogenic carbon center at the α-position are an important class of compounds, many of which serve as useful synthetic intermediates for the preparation of chiral 1,3-aminoalcohols, ß-hydroxy nitriles, and related derivatives. Although the enantioselective electrophilic cyanation of enolate equivalents is one of the most promising approaches for the synthesis of chiral ß-ketonitriles, the available methods are largely limited to reactions of 1,3-dicarbonyl compounds. Herein, we report on enantioselective electrophilic cyanation of boron enolates, which are readily prepared from α,ß-unsaturated ketones and diisopinocampheylborane (Ipc2 BH) to afford chiral ß-ketonitriles with a high level of enantioselectivity. The present method is scalable and provides facile access to both enantiomers of chiral ß-ketonitriles. Analysis of the in situ generated boron enolates by NMR revealed that hydroboration proceeds in a stereospecific manner, providing α,α-disubstituted boron enolates in the form of single isomers. Furthermore, the results of DFT calculations suggest that the cyanation of the boron enolates with p-toluenesulfonyl cyanide (TsCN) proceeds in a highly enantioselective manner through a unique six-membered ring transition state.

Synthesis of 2,6,7-Trisubstituted Prenylated indole.

Prenylated indole alkaloids bearing more than one prenyl or reverse-prenyl group show various biological activities. Among them, synthesis of trisubstituted-type prenylated indoles have not been well explored because of the difficulty in regioselective introduction of multiple prenyl and reverse-prenyl groups due to steric hindrance problems. Herein, we describe a synthesis of 2,6,7-trisubstituted prenylated indole using aza-Claisen rearrangement under mild conditions to introduce a prenyl group at C7 in the presence of the prenyl group at C6.