We report the regioselective and enantioselective formal hydroamination of unsymmetrical internal alkenes catalyzed by a copper catalyst ligated by DTBM-SEGPHOS. The regioselectivity of the reaction is controlled by the electronic effects of ether, ester, and sulfonamide groups in the homoallylic position. The observed selectivity underscores the influence of inductive effects of remote substituents on the selectivity of catalytic processes occurring at hydrocarbyl groups, and the method provides direct access to various 1,3-aminoalcohol derivatives with high enantioselectivity.

Regioselective copper-catalyzed boracarboxylation of vinyl arenes with bis(pinacolato)diboron and carbon dioxide has been achieved. New boron-functionalized α-aryl carboxylic acids, including nonsteroidal anti-inflammatory drugs (NSAIDs), are obtained in moderate to excellent yields. The synthetic utility of the transformation was shown through subsequent derivatization of the carbon-boron bond yielding formal hydroxy- and fluorocarboxylation products as well as anionic difluoroboralactones.

We report the palladium-catalyzed gem-difluoroallylation of aryl halides and pseudo halides with 3,3-difluoroallyl boronates in high yield with high regioselectivity, and we report the preparation of the 3,3-difluoroallyl boronate reactants by a copper-catalyzed defluorinative borylation of inexpensive gaseous 3,3,3-trifluoropropene with bis(pinacolato)diboron. The gem-difluoroallylation of aryl and heteroaryl bromides proceeds with low catalyst loading (0.1 mol % [Pd]) and tolerates a wide range of functional groups, including primary alcohols, secondary amines, ethers, ketones, esters, amides, aldehydes, nitriles, halides, and nitro groups. This protocol extends to aryl iodides, chlorides, and triflates, as well as substituted difluoroallyl boronates, providing a versatile synthesis of gem-difluoroallyl arenes that we show to be valuable intermediates to a series of fluorinated building blocks.The difluoromethylene (CF 2 ) unit can be used to fine-tune the physical, chemical, and biological properties of pharmaceuticals, agrochemicals, and materials. [1] This unit can serve as a bioisostere for an ether linkage or a keto group in pharmaceuticals, [2] and, when positioned at a benzylic site, it can block metabolic oxidation at otherwise labile benzylic CÀH bonds. [2] Difluoromethylene groups also have been used to alter the lipophilicity and ground-state conformation of organic molecules. [2] Compounds containing difluoromethylene groups even serve as valuable reactants, for example undergoing CÀF bond activation during reactions that form alkyl fluorides. [3] However, the installation of a difluoromethylene group poses synthetic challenges. Classical approaches to access 1,1difluoroalkanes, such as the deoxyfluorination of ketones with DAST or Deoxo-Fluor , [4] the fluorodesulfurzation of dithianes, [5] and the hydrofluorination of alkynes, [6,7] typically proceed in low yield and exhibit poor functional group tolerance. Recently, difluoroalkylations catalyzed by transition-metal complexes have provided an alternative, convergent route to access compounds containing the difluoro-methylene group. [8] Among these, difluoroallylations are notable for their ability to simultaneously install a difluoromethylene group and a versatile alkene functional group. In 2014, Zhang et al. reported the palladium-catalyzed coupling of arylboron reagents 1 and 3-bromo-3,3-difluoropropene (2) to provide synthetically versatile gem-difluoroallyl arenes 3 (Scheme 1 a). [9] Similarly, Feng et al. demonstrated that aryl boronic acids 4 undergo cross-coupling with 2-aryl difluoroallyl quaternary ammonium salts 5 to provide 2-aryl difluoroallyl arenes 6 (Scheme 1 b). [10] However, the arylboron reagents used in these reactions as the source of the aryl group are much less available than aryl halides and the 3bromo-3,3-difluoropropene reagent used as the source of the difluoroallyl group in one protocol is expensive; [11] it is prepared from dibromodifluoromethane and ethylene by Scheme 1. Background on the difluoroallylation of a...

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Thiophene-containing cycloparaphenylenes (CPPs) bearing 8, 10, and 16 aromatic and heteroaromatic units in the macrocyclic ring structures were synthesized. Specifically, two and four thiophene-2,5-diyl units were incorporated into functionalized [6]- and [12]CPP macrocyclic carbon frameworks, respectively. In addition, two 2,2'-bithiophene-5,5'-diyl units were inserted into a functionalized [6]CPP carbon framework. The cyclic and differential pulse voltammetry and the UV-vis and fluorescence spectra of the fully aromatized macrocycles and their precursors exhibited interesting electrochemical and optical properties.

Few allylic electrophiles containing two different substituents at a single allyl terminus and none in which one of the two substituents is a heteroatom, have been shown previously to react with iridium catalysts to form substitution products. We report that iridium-catalysts are uniquely suited to form tertiary allylic fluorides enantioselectively by the addition of a diverse range of carbon-centered nucleophiles at the fluorine-containing terminus of 3-fluoro-substituted allylic esters. The products contain tertiary stereogenic centers bearing a single fluorine, which are isosteric with common tertiary stereocenters containing a single hydrogen. Computational studies reveal the principal steric interactions influencing the stability of endo and exo π-allyl intermediates formed from 3,3-disubstituted allylic electrophiles.

We report the silylation of primary C–H bonds located β to secondary and tertiary alcohols by exploiting perfluorinated esters as traceless directing groups. The conversion of a secondary or tertiary alcohol to a perfluoroalkyl ester and conversion of the ester to the corresponding silyl acetals by hydrosilylation allows for selective β-C(sp3)–H silylation catalyzed by the combination of [Ir(cod)OMe]2 and Me4Phen (3,4,7,8-tetramethyl-1,10-phenanthroline) to form 6-membered dioxasilinane. Tamao-Fleming oxidation of these dioxasilinane leads to 1,2 diols. The developed sequence was applied to a series of natural products containing hydroxyl groups.

Alkyl fluorides modulate the conformation, lipophilicity, metabolic stability, and pKa of compounds containing aliphatic motifs and, therefore, have been valuable for medicinal chemistry. Despite significant research in organofluorine chemistry, the synthesis of alkyl fluorides, especially chiral alkyl fluorides, remains a challenge. Most commonly, alkyl fluorides are prepared by the formation of C−F bonds (fluorination), and numerous strategies for nucleophilic, electrophilic, and radical fluorination have been reported in recent years. Although strategies to access alkyl fluorides by C−C bond formation (monofluoroalkylation) are inherently convergent and complexity‐generating, they have been studied less than methods based on fluorination. This Review provides an overview of recent developments in the synthesis of chiral (enantioenriched or racemic) secondary and tertiary alkyl fluorides by monofluoroalkylation catalyzed by transition‐metal complexes. We expect this contribution will illuminate the potential of monofluoroalkylations to simplify the synthesis of complex alkyl fluorides and suggest further research directions in this growing field.