Copper(I) Halide Promoted Diastereoselective Synthesis of Chiral Propargylamines and Chiral Allenes using 2‑Dialkylaminomethylpyrrolidine, Aldehydes, and 1‑Alkynes

Copper bromide promoted reactions of aldehydes, 1-alkynes, and chiral 2-dialkylaminomethylpyrrolidine at 25 °C give the corresponding chiral propargylamine derivatives in up to 96% yield and 99:1 dr that are readily converted to the corresponding disubstitued chiral allenes in up to 81% yield and 99% ee upon reaction with CuI in dioxane at 100 °C

Synthesis of Phenols and Aryl Silyl Ethers via Arylation of Complementary Hydroxide Surrogates

Two transition-metal-free methods to access substituted phenols via the arylation of silanols or hydrogen peroxide with diaryliodonium salts are presented. The complementary reactivity of the two nucleophiles allows synthesis of a broad range of phenols without competing aryne formation, as illustrated by the synthesis of the anesthetic Propofol. Furthermore, silyl-protected phenols can easily be obtained, which are suitable for further transformations

Control of Five Contiguous Stereogenic Centers in an Organocatalytic Kinetic Resolution via Michael/Acetalization Sequence: Synthesis of Fully Substituted Tetrahydropyranols

An organocatalytic kinetic resolution of racemic secondary nitroallylic alcohols via Michael/acetalization sequence to give fully substituted tetrahydropyranols is described. The process affords the products with high to excellent stereoselectivities (up to 19.9:1.5:1 dr and 98% ee). The highly enantioenriched, less reactive (<i>S</i>)-nitroallylic alcohols <b>3</b> were isolated with good to high chemical yields (30–44%). The synthetic application of the resolved substrate is shown toward the synthesis of enantioenriched (+)-(2<i>S</i>,3<i>R</i>)-3-amino-2-hydroxy-4-phenylbutyric acid

Enantioselective Synthesis of Functionalized Polycarbocycles via a Three-Component Organocascade Quadruple Reaction

An efficient organocascade quadruple reaction was conducted to synthesize a functionalized spiropolycyclic scaffold in high chemical yields (43–80%) and excellent levels of stereoselectivity (up to >19:1 dr and 99% ee). The quadruple reaction proceeded smoothly between 1,3-indanedione and aromatic aldehydes with concomitant desymmetrization of prochiral 4-substituted cyclohexanones through the Knoevenagel/Michael/aldol/aldol reaction sequence catalyzed by a bifunctional thiourea catalyst. Two of the formed products were transformed into spirocyclic epoxides containing four contiguous quaternary centers

Doyle–Kirmse Reaction on Alkynyl Hydrazone Carboxylates: Synthesis of 1,4-Allenyne and 1,5-Enyne Thioaryl Carboxylates

The first Doyle–Kirmse reaction on alkynyl diazoacetates using allyl/propargyl sulfides is reported. The development provides diversified 1,5-enyne and 1,4-allenyne thioaryl carboxylates in good yields under ligand-/additive-free AuCl and Rh2(OAc)4 catalysis, respectively (48 examples, up to 96% yield). The study demonstrated the dual role of allyl sulfide as a ligand and substrate. Also, we have exemplified various synthetic modifications of the products to showcase the utility of different functional groups

Highly Enantioselective Synthesis of Chiral Allenes by Sequential Creation of Stereogenic Center and Chirality Transfer in a Single Pot Operation

Chiral allenes are readily accessed in a single pot operation in the reaction of terminal alkynes, aldehydes, chiral secondary amines, and zinc halides in good yields (up to 77% yield) and excellent enantioselectivities (up to 99% ee) in toluene at 120 °C. The reaction proceeds through initial formation of chiral propargylamine intermediates with creation of a new stereogenic center and subsequent chirality transfer via an intramolecular hydride shift to produce chiral allenes with high enantiomeric purities