Catalyst-controlled doubly enantioconvergent coupling of racemic alkyl nucleophiles and electrophiles

Stereochemical control in the construction of carbon-carbon bonds between an alkyl electrophile and an alkyl nucleophile is a persistent challenge in organic synthesis. Classical substitution reactions via SN1 and SN2 pathways are limited in their ability to generate carbon-carbon bonds (inadequate scope, due to side reactions such as rearrangements and eliminations) and to control stereochemistry when beginning with readily available racemic starting materials (racemic products). Here, we report a chiral nickel catalyst that couples racemic electrophiles (propargylic halides) with racemic nucleophiles (β-zincated amides) to form carbon-carbon bonds in doubly stereoconvergent processes, affording a single stereoisomer of the product from two stereochemical mixtures of reactants.

Synthesis of Spirocyclic Amines by 1,3-Dipolar Cycloaddition of Azomethine Ylides and Azomethine Imines

Simple ketone starting materials with a halide leaving group and an alkene were prepared in one step and heated with glycine or glycine esters to promote a tandem imine formation, cyclization, and dipolar cycloaddition cascade. The chemistry was also feasible with acetylhydrazide. In each case a single stereoisomer of the tricyclic amine or pyrazolidine product was formed and the stereochemistry was verified by single crystal X-ray diffraction. When the reaction with glycine, which occurs with loss of CO2, was unsuccessful, the cascade process could be promoted by cross metathesis to give the vinyl sulfone starting material that provides a more reactive dipolarophile. Reductive cleavage of the pyrazolidine gave a spirocyclic diamine product.

Synthesis of a [6]rotaxane with singly threaded γ-cyclodextrins as a single stereoisomer

A series of hetero [4]-, [5]- and [6]rotaxanes containing both cucurbit[6]uril (CB[6]) and γ-cyclodextrin (γ-CD) as the macrocyclic components have been synthesized via a threading-followed-by-stoppering approach. Due to the orthogonal binding of CB[6] to ammonium and γ-CD to biphenylene/tetra(ethylene glycol), the [n]rotaxanes display a specific sequence of the interlocked macrocycles. In addition, despite of the asymmetry of γ-CD with respect to the orthogonal plane of the axle, only one stereoisomer of the [6]rotaxane was obtained.

Synthesis of a Chiral Auxiliary Family from Levoglucosenone and Evaluation in the Diels–Alder Reaction

A new family of chiral auxiliaries has been developed based on the lignocellulosic biomass pyrolysis product levoglucosenone. A promising single stereoisomer with an alcohol and π-stacking phenyl substituents was prepared in excellent yield in two steps from di­hydrolevoglucosenone without chromatography on >50 g scale. Acrylate esters prepared from the auxiliaries underwent diastereoselective Lewis acid promoted Diels–Alder reactions with cyclopentadiene (­endo/exo 98:2, endo d.r. up to 98:2), dimethylbutadiene (d.r. 93:7), and isoprene (d.r. > 98:2)

Racemic hemiacetals as oxygen-centered pronucleophiles triggering cascade 1,4-addition/Michael reaction through dynamic kinetic resolution under iminium catalysis. Development and mechanistic insights

Racemic 2-hydroxydihydropyran-5-ones react as unconventional O-pronucleophiles in a conjugate addition/Michael reaction cascade process under DKR, leading to the formation of a single stereoisomer out of 16 possible ones.

Stereoselective Separation and Acute Toxicity of Tau-Fluvalinate to Zebrafish

Tau-fluvalinate (TFLV) is one of the most potent chiral synthetic pyrethroids to control a wide range of pests in agricultural fields, especially in apiary. In this study, two stereoisomers of TFLV were fully separated by high-performance liquid chromatography (HPLC) with a semipreparative chiral column using cellulose-tris(3,5-dimethylphenylcarbamate) as chiral stationary phase andn-hexane and 2-propanol (96/4, v/v) as mobile phase at a flow rate of 2.5 mL min−1. The (+)-stereoisomer was first eluted by detecting with an optical rotation detector. After obtaining pure single stereoisomer of TFLV, acute toxicities of each isomer and TFLV standard to zebrafish were evaluated. The results showed that the (+)-stereoisomer exhibited 273.4 times higher toxicity than the (−)-stereoisomer and 6.7 times higher than TFLV standard, according to their LC50values at 96 h after exposure. This indicates that the toxicity of TFLV mainly originates from (+)-stereoisomer. These results are very helpful to prepare single stereoisomer of chiral pesticides and evaluate their different toxicological effects to aquatic organisms.

Alternating stereoselective self-assembly of SSSS/RRRR or RSSR isomers of tetrakisphosphines in the row of 14-, 16-, 18- and 20-membered macrocycles

Covalent self-assembly of novel 18- and 20-membered P,N-corands as single stereoisomer is described.

Synthesis of the Leu - Trp Component of the Celogentin Family of Cyclic Peptides Through a C - H Activation - Cross-Coupling Strategy

A bioinspired approach to the central leucine(C3)–tryptophan(C6) cross-linked moiety present in the celogentin family of cyclic peptide natural products was achieved. The key transformation was enabled through a palladium-catalyzed C–H activation–cross-coupling of leucine quinoline amide and 6-iodotryptophan derivatives. X-Ray crystallographic analysis of a β-(indol-6-yl)-leucine derivative confirms the stereochemistry of the cross-linked adduct matches that of the natural products. The method enables the preparation of the Leu–Trp adduct as a single stereoisomer from l-leucine and l-tryptophan.