We have previously reported the first formal hydroamination of enamines for the synthesis of chiral 1,2‐diamines. Here, we describe: (i) the discovery, optimization, and substrate expansion of this ...reaction; (ii) a novel and straightforward protocol for the “click‐type” synthesis of enamines in quantitative yield utilizing sodium sulfate in a dual role as an ancillary and dehydrating agent without the need for workup or purification; (iii) the application of this methodology to the first enantioselective synthesis of orthogonally protected 1,1′‐(1‐(4‐fluorophenyl)ethane‐1,2‐diyl) piperazines, a scaffold for rapid lead optimization in drug discovery; (iv) a computational investigation into the mechanism and rationalization of the enantioselectivities of the reaction.
Chiral 1,2‐diamines are an important structural motif in organic synthesis, and can be prepared by an efficient Cu−H catalyzed asymmetric hydroamination of enamines. The applicability of the hydroamination protocol is demonstrated by an asymmetric synthesis of a MC‐4 receptor antagonist. The origin of the excellent enantioselectivity is investigated using DFT calculations.
Activated sludge (AS) contains highly complex microbial communities. In this study, PCR-based 454 pyrosequencing was applied to investigate the bacterial communities of AS samples from 14 sewage ...treatment plants of Asia (mainland China, Hong Kong, and Singapore), and North America (Canada and the United States). A total of 259 K effective sequences of 16S rRNA gene V4 region were obtained from these AS samples. These sequences revealed huge amount of operational taxonomic units (OTUs) in AS, that is, 1183-3567 OTUs in a sludge sample, at 3% cutoff level and sequencing depth of 16,489 sequences. Clear geographical differences among the AS samples from Asia and North America were revealed by (1) cluster analyses based on abundances of OTUs or the genus/family/order assigned by Ribosomal Database Project (RDP) and (2) the principal coordinate analyses based on OTUs abundances, RDP taxa abundances and UniFrac of OTUs and their distances. In addition to certain unique bacterial populations in each AS sample, some genera were dominant, and core populations shared by multiple samples, including two commonly reported genera of Zoogloea and Dechloromonas, three genera not frequently reported (i.e., Prosthecobacter, Caldilinea and Tricoccus) and three genera not well described so far (i.e., Gp4 and Gp6 in Acidobacteria and Subdivision3 genera incertae sedis of Verrucomicrobia). Pyrosequencing analyses of multiple AS samples in this study also revealed the minority populations that are hard to be explored by traditional molecular methods and showed that a large proportion of sequences could not be assigned to taxonomic affiliations even at the phylum/class levels.
Abstract
Insertion reactions that involve stabilized electrophilic metallocarbenes are of great importance for installing α‐heteroatoms to carbonyl compounds. Nevertheless, the limited availability ...of carbene precursors restricts the introduction of only a single heteroatom. In this report, we describe a new approach based on an I
(III)
/S
(VI)
reagent that promotes the cascade insertion of heteroatoms. This is achieved by sequentially generating two α‐heteroatom‐substituted metal carbenes in one reaction. We found that this mixed I
(III)
/S
(VI)
ylide reacts efficiently with a transition metal catalyst and an X−H bond (where X=O, N). This transformation leads to the sequential formation of a sulfoxonium‐ and an X‐substituted Rh‐carbenes, enabling further reactions with another Y−H bond. Remarkably, a wide range of symmetrical and unsymmetrical α,α‐
O
,
O
‐, α,α‐
O
,
N
‐, and α,α‐
N
,
N
‐subsituted ketones can be prepared under mild ambient conditions. In addition, we successfully demonstrated other cascades, such as CN/CN double amidation, C−H/C−S double insertion, and C−S/Y−H double insertion (where Y=S, N, O, C). Notably, the latter two cascades enabled the simultaneous installation of three functional groups to the α‐carbon of carbonyl compounds in a single step. These reactions demonstrate the versatility of our approach, allowing for the synthesis of ketones and esters with multiple α‐heteroatoms using a common precursor.
A PdII‐catalyzed, domino enantioselective desymmetrizative coupling of 7‐azabenzonorbornadienes with alkynylanilines is disclosed herein. This operationally simple transformation generates three ...covalent bonds and two contiguous stereocenters with excellent enantio‐ and diastereo‐selectivity. The resulting functionalized indole‐dihydronaphthalene‐amine conjugates served as an appealing platform to streamline the diversity‐oriented synthesis (DOS) of other valuable enantioenriched compounds. DFT calculations revealed that the two stabilizing non‐covalent interactions contributed to the observed enantioselectivity.
A palladium‐catalyzed enantioselective desymmetrizative coupling of prochiral 7‐azabenzonorbornadienes with readily available alkynylanilines afforded dihydronaphthalenes via concomitant generation of three covalent bonds. The methods also allows to build two stereocenters and an indole motif in a highly diastereo‐ and enantioselective as well as atom‐economic manner.
This study establishes the first organocatalytic enantioselective synthesis of axially chiral N,N′‐bisindoles via chiral phosphoric acid‐catalyzed formal (3+2) cycloadditions of indole‐based ...enaminones as novel platform molecules with 2,3‐diketoesters, where de novo indole‐ring formation is involved. Using this new strategy, various axially chiral N,N′‐bisindoles were synthesized in good yields and with excellent enantioselectivities (up to 87 % yield and 96 % ee). More importantly, this class of axially chiral N,N′‐bisindoles exhibited some degree of cytotoxicity toward cancer cells and was derived into axially chiral phosphine ligands with high catalytic activity. This study provides a new strategy for enantioselective synthesis of axially chiral N,N′‐bisindoles using asymmetric organocatalysis and is the first to realize the applications of such scaffolds in medicinal chemistry and asymmetric catalysis.
An organocatalytic enantioselective synthesis of axially chiral N,N′‐bisindoles has been established via chiral phosphoric acid‐catalyzed formal (3+2) cycloaddition of indole‐based enaminones with 2,3‐diketoesters. This study provides a new strategy for the highly selective synthesis of axially chiral N,N′‐bisindoles and shows the successful application of such skeletons in medicinal and synthetic chemistry.
A unique Pd‐catalyzed approach for asymmetric (4+1) annulations via cascade allylation and transient σ‐alkyl‐Pd(II) initiated methylene Csp3−H activation is reported. The enolate fragment derived ...from the decarboxylation of vinyl methylene carbonate is crucial to stabilize the key intermediate. These reactions enable the synthesis of various useful dihydrobenzofurans with excellent enantioselectivity, typically >95 : 5 er, and exclusive (Z)‐stereoselectivity. Compared with the well‐established annulations via Heck‐type C−H activations, this protocol showcases a conceptually new way to generate σ‐alkyl‐Pd(II) species that could initiate challenging asymmetric Csp3−H activations.
A unique catalytic approach for asymmetric (4+1) annulations via cascade allylation and transient σ‐alkyl‐Pd(II) initiated methylene Csp3−H activation is reported. Comparing to the well‐established annulations via Heck‐type C−H activations, this protocol showcases a conceptually new way to generate σ‐alkyl‐Pd(II) species which could initiate challenging asymmetric Csp3−H activations.
A new class of axially chiral styrene‐based thiourea tertiary amine catalysts, which have unique characteristics such as an efficient synthetic route, multiple chiral elements, and multiple ...activating groups, has been rationally designed. These new chiral catalysts have proven to be efficient organocatalysts, enabling the chemo‐, diastereo‐, and enantioselective (2+4) cyclization of 2‐benzothiazolimines with homophthalic anhydrides in good yields (up to 96 %) with excellent stereoselectivities (all >95:5 dr, up to 98 % ee). More importantly, theoretical calculations elucidated the important role of an axially chiral styrene moiety in controlling both the reactivity and enantioselectivity. This work not only represents the first design of styrene‐based chiral thiourea tertiary amine catalysts and the first catalytic asymmetric (2+4) cyclization of 2‐benzothiazolimines, but also gives an in‐depth understanding of axially chiral styrene‐based organocatalysts.
A new class of axially chiral styrene‐based organocatalysts has been rationally designed. They enable the chemo‐, diastereo‐ and enantioselective (2+4) cyclization of 2‐benzothiazolimines. This work represents the first design of styrene‐based chiral thiourea tertiary amine catalysts and the first catalytic asymmetric (2+4) cyclization of 2‐benzothiazolimines, and it gives an in‐depth understanding of axially chiral styrene‐based organocatalysts.
Catalytic asymmetric construction of chiral indole‐fused rings has become an important issue in the chemical community because of the significance of such scaffolds. In this work, we have ...accomplished the first catalytic asymmetric (4+2) and (4+3) cycloadditions of 2,3‐indolyldimethanols by using indoles and 2‐naphthols as suitable reaction partners under the catalysis of chiral phosphoric acids, constructing enantioenriched indole‐fused six‐membered and seven‐membered rings in high yields with excellent enantioselectivities. In addition, this approach is used to realize the first enantioselective construction of challenging tetrahydroindolocarbazole scaffolds, which are found to show promising anticancer activity. More importantly, theoretical calculations of the reaction pathways and activation mode offer an in‐depth understanding of this class of indolylmethanols. This work not only settles the challenges in realizing catalytic asymmetric cycloadditions of indolyldimethanols but also provides a powerful strategy for the construction of enantioenriched indole‐fused rings.
The first catalytic asymmetric (4+2) and (4+3) cycloadditions of 2,3‐indolyldimethanols enable the construction of enantioenriched indole‐fused rings in high yields with excellent enantioselectivities. This approach led to the first enantioselective construction of challenging tetrahydroindolocarbazole scaffolds, which show promising anticancer activity. Theoretical calculations offer an in‐depth understanding of this class of indolylmethanols.
A wearable circular ring slot antenna with electromagnetic bandgap (EBG) structure for wireless body area network application is proposed in this letter. According to the analysis of equivalent ...circuit model, the volume of the EBG element is miniaturized for wearable applications. The measured impedance bandwidth of the proposed antenna is observed to be 2.28-2.64 GHz, which covers the 2.4 GHz Industrial Scientific Medical (ISM) band. The measured half-power beamwidths are 60° and 54° in the H -plane and the E -plane, respectively, and the front-to-back ratios are 17 and 13 dB in the H -plane and the E -plane, respectively. The specific absorption rate calculated values for tissue in 1 g (for the U.S. standard) and 10 g (for Europe standard) are both less than the limitations. In conclusion, it is proper to use the proposed antenna in wearable applications.
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