Bifunctional‐Thiourea‐Catalyzed Diastereo‐ and Enantioselective Aza‐Henry Reaction

Bifunctional thiourea 1 a catalyzes aza‐Henry reaction of nitroalkanes with N‐Boc‐imines to give syn‐β‐nitroamines with good to high diastereo‐ and enantioselectivity. Apart from the catalyst, the reaction requires no additional reagents such as a Lewis acid or a Lewis base. The N‐protecting groups of the imines have a determining effect on the chirality of the products, that is, the reaction of N‐Boc‐imines gives R adducts as major products, whereas the same reaction of N‐phosphonoylimines furnishes the corresponding S adducts. Various types of nitroalkanes bearing aryl, alcohol, ether, and ester groups can be used as nucleophiles, providing access to a wide range of useful chiral building blocks in good yield and high enantiomeric excess. Synthetic versatility of the addition products is demonstrated by the transformation to chiral piperidine derivatives such as CP‐99,994.     

Pyridine‐Enhanced Head‐to‐Tail Dimerization of Terminal Alkynes by a Rhodium–N‐Heterocyclic‐Carbene Catalyst

A general regioselective rhodium‐catalyzed head‐to‐tail dimerization of terminal alkynes is presented. The presence of a pyridine ligand (py) in a Rh–N‐heterocyclic‐carbene (NHC) catalytic system not only dramatically switches the chemoselectivity from alkyne cyclotrimerization to dimerization but also enhances the catalytic activity. Several intermediates have been detected in the catalytic process, including the π‐alkyne‐coordinated Rh^I species [RhCl(NHC)(η²‐HC?CCH₂Ph)(py)] ( 3 ) and [RhCl(NHC){η²‐C(tBu)?C(E)CH?CHtBu}(py)] ( 4 ) and the Rh^III–hydride–alkynyl species [RhClH{? C?CSi(Me)₃}(IPr)(py)₂] ( 5 ). Computational DFT studies reveal an operational mechanism consisting of sequential alkyne C? H oxidative addition, alkyne insertion, and reductive elimination. A 2,1‐hydrometalation of the alkyne is the more favorable pathway in accordance with a head‐to‐tail selectivity.     

The Absolute Configuration of (+)‐Ethyl cis‐1‐Benzyl‐3‐hydroxypiperidine‐4‐carboxylate and (+)‐4‐Ethyl 1‐Methyl cis‐3‐Hydroxypiperidine‐1,4‐dicarboxylate; a Revision

Discrepancies between chiroptical data from the literature and our determination of the structure of the title compounds (+)‐ 5 and (+)‐ 9a were resolved by an unambiguous assignment of their absolute configuration. Accordingly, the dextrorotatory cis‐3‐hydroxy esters have (3R,4R)‐ and the laevorotatory enantiomers (3S,4S)‐configuration. The final evidences were demonstrated on both enantiomers (+)‐ and (?)‐ 5 by biological reduction of 4 by bakers' yeast and stereoselective [Ru^II(binap)]‐catalyzed hydrogenations of 4 (Scheme 2), by the application of the NMR Mosher method on (+)‐ and (?)‐ 5 (Scheme 3), as well as by the transformation of (+)‐ 5 into a common derivative and chiroptical correlation (Scheme 4).     

1‐Thiacyclooct‐4‐yne (=5,6‐Didehydro‐3,4,7,8‐tetrahydro‐2H‐thiocin), and Its Sulfoxide and Its Sulfone

1‐Thiacyclooct‐4‐yne (=5,6‐didehydro‐3,4,7,8‐tetrahydro‐2H‐thiocin; 9 ) can be prepared from thiocan‐5‐one ( 6 ) in three steps by applying the so‐called selenadiazole method. The heterocyclic alkyne can be oxidized to the corresponding sulfoxide 16 and sulfone 17 . Due to their geometrical strain, all three cyclic alkynes show high reactivities in Diels? Alder and 1,3‐dipolar cycloadditions. Moreover, tetrathiafulvalenes can be prepared from 9 and 16 by the reaction with CS₂.     

Transition‐Metal‐Catalyzed Laboratory‐Scale Carbon–Carbon Bond‐Forming Reactions of Ethylene

Ethylene, the simplest alkene, is the most abundantly synthesized organic molecule by volume. It is readily incorporated into transition‐metal‐catalyzed carbon–carbon bond‐forming reactions through migratory insertions into alkylmetal intermediates. Because of its D_2h symmetry, only one insertion outcome is possible. This limits byproduct formation and greatly simplifies analysis. As described within this Minireview, many carbon–carbon bond‐forming reactions incorporate a molecule (or more) of ethylene at ambient pressure and temperature. In many cases, a useful substituted alkene is incorporated into the product.     

Carbohydrate‐2‐deoxy‐2‐phosphonates: Simple Synthesis and Horner–Emmons Reaction

Phosphorus meets carbohydrates : Dimethyl phosphite reacts with ceric(IV) ammonium nitrate (CAN) to give phosphonyl radicals that add to glycals 1 . The derivatives 2 were isolated in high yields and during a subsequent Horner–Emmons reaction underwent an interesting elimination to give 3,6‐dihydro‐2H‐pyrans 3 . The short sequence with simple precursors is applicable to the transformation of hexoses, pentoses, and disaccharides. Bn=benzyl.

     

Unexpected Ritter Reaction During Acid‐Promoted 1,3‐Dithiol‐2‐one Formation

A series of aryl‐substituted 1,3‐dithiol‐2‐ones was prepared by the Bhattacharya? Hortmann cyclization method. Unexpectedly, a Ritter reaction occurred during the acid‐catalyzed cyclization at the cyano group of the aryl substituents and 1,3‐dithiol‐2‐ones bearing a carboxy or a carboxamide group could be selectively obtained (see 1 and 2a in Scheme 1). The formation of the acid or the amide functionality was temperature‐dependent so that the one or the other group could be introduced selectively by modifying the reaction temperature.     

Orthogonal Dual‐Triggered Shape‐Memory DNA‐Based Hydrogels

DNA‐based shape‐memory hydrogels revealing switchable shape recovery in the presence of two orthogonal triggers are described. In one system, a shaped DNA/acrylamide hydrogel is stabilized by duplex nucleic acids and pH‐responsive cytosine‐rich, i‐motif, bridges. Separation of the i‐motif bridges at pH 7.4 transforms the hydrogel into a quasi‐liquid, shapeless state, that includes the duplex bridges as permanent shape‐memory elements. Subjecting the quasi‐liquid state to pH 5.0 or Ag⁺ ions recovers the hydrogel shape, due to the stabilization of the hydrogel by i‐motif or C‐Ag⁺‐C bridged i‐motif. The cysteamine‐induced transformation of the duplex/C‐Ag⁺‐C bridged i‐motif hydrogel into a quasi‐liquid shapeless state results in the recovery of the shaped hydrogel in the presence of H⁺ or Ag⁺ ions as triggers. In a second system, a shaped DNA/acrylamide hydrogel is generated by DNA duplexes and bridging Pb²⁺ or Sr²⁺ ions‐stabilized G‐quadruplex subunits. Subjecting the shaped hydrogel to the DOTA or KP ligands eliminates the Pb²⁺ or Sr²⁺ ions from the respective hydrogels, leading to shapeless, memory‐containing, quasi‐liquid states that restore the original shapes with Pb²⁺ or Sr²⁺ ions.     

Scope and Limitations of the Base‐Free Copper(I) Oxide Catalyzed N‐Heteroarylation of 1H‐(Benz)imidazoles with B‐Heteroarylboronic Acids or 2‐Heteroaryl‐4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolanes

The known, very efficient base‐free copper(I) oxide catalyzed N‐arylation reaction performed in MeOH at room temperature for the synthesis of N‐substituted azoles and amines was extended to the heterocyclic series, i.e., we report herein the base‐free copper(I) oxide catalyzed N‐heteroarylation of 1H‐(benz)imidazole, by means of electron‐rich or electron‐deficient B‐heteroarylboronic acids or 2‐heteroaryl‐4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolanes (Schemes 1 and 2). Under these conditions, N‐heteroarylated 1H‐(benz)imidazoles were obtained in good to excellent yields (Tables 1 and 2). This is the first time that 2‐heteroaryl‐4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolanes were used in this type of reaction.     

Mechanism of the Reaction of Amines with 5‐[(Aryl‐ or Alkylamino)hydroxymethylene]‐2,2‐dimethyl‐1,3‐dioxane‐4,6‐diones in the Presence of Chlorotrimethylsilane (Me3SiCl)

Addition of chlorotrimethylsilane (Me₃SiCl) to the mixture of a carbamoyl‐substituted Meldrum's acid, i.e., a 5‐[(arylamino)hydroxymethylene]‐2,2‐dimethyl‐1,3‐dioxane‐4,6‐dione of type 1 and a secondary amine as nucleophile strongly accelerated the rate of their reaction. The reason for this phenomenon observed, during our previous research, remained, however, unclear. To elucidate the mechanism of this reaction, we assumed and verified three possible pathways for the action of Me₃SiCl (cf. Scheme 2): The acceleration of the reaction is caused i) by formation of a O‐trimethylsilylated Meldrum's acid of type 2 , ii) by the silylated amine 3 , or iii) by the presence of HCl liberated from Me₃SiCl. The performed experiments revealed that the faster course of reaction is caused by the formation of N‐trimethylsilylated amines of type 3 .