Fanyang Mo

Silver-mediated trifluoromethylation of aryldiazonium salts: conversion of amino group into trifluoromethyl group.

A novel strategy for aromatic trifluoromethylation by converting aromatic amino group into CF3 group is reported herein. This method, which can be considered as trifluoromethylation variation of the classic Sandmeyer reaction, uses readily available aromatic amines as starting materials and is performed under mild conditions.

Direct Conversion of Arylamines to Pinacol Boronates: A Metal-Free Borylation Process

Arylboronic acids or arylboronates have found widespread applications in transition-metal-catalyzed C C bond forming reactions, as represented by the Suzuki–Miyaura crosscoupling reaction. These applications have created an increasing demand for various boronic acids and esters. The most commonly utilized method to prepare these boron compounds is the reaction of aryl Grignard reagents or aryllithium reagents with trialkyl borates followed by hydrolytic workup. This traditional approach, although still widely used, suffers some obvious drawbacks such as rigorous anhydrous conditions and narrow functional group compatibility. In 1995, Miyaura and co-workers reported a Pdcatalyzed cross coupling of arylbromides or iodides with a diboron pinacol (pin). The favorable tolerance of this method to a variety of functional groups means that it is now well-established as a complementary route to arylboronates. In addition to these two important methods, it should be mentioned that great efforts have been made in transition-metal-catalyzed direct borylation of aromatic C H bonds. 10] Arylamines are cheap and abundant starting materials, which are easily available from arenes through nitration and subsequent reduction. The aromatic amino group can be converted into various functional groups by the Sandmeyer reaction. The standard procedure for converting arylamines to arylboronic acids or boronates would need two steps, namely a Sandmeyer reaction to convert the amino group into a halogen group, followed by use of a Grignard reagent or a Pd-catalyzed borylation. Although the two-step procedure is highly reliable and widely used in organic synthesis, the combination of these reactions in the conversion of arylamines to arylboronates is usually not very efficient because of the generally low-yielding and tedious separation procedures required. Moreover, metals that might contaminate the final boron products and cause environmental problems in large-scale production are inevitably involved in these steps. In this context, the direct borylation of arylamines to arylboronates would be highly desirable. Herein, we describe a novel method for the synthesis of arylboronates by the reaction of the diboron pinacol ester B2pin2 with arylamines in the presence of tert-butyl nitrite. The reaction is metal-free and can be carried out under air at room temperature. The Sandmeyer reaction is a classic reaction in which an aromatic amino group is replaced with a halogen, as well as with other groups such as hydrogen, hydroxy, cyano, and azido groups. Diazonium ions are the common intermediates in these synthetically very useful transformations. In view of the diversity of transformations that occur via diazonium ions, we hypothesized that it might be possible to replace an aromatic amino group with a boron group under Sandmeyer reaction conditions. To the best of our knowledge, this type of transformation has not been reported to date. After some initial attempts, it was concluded that tert-butyl nitrite (tBuONO, 3) was a suitable diazotization agent for this transformation. Thus, a solution of aniline 1 a, B2pin2 2, and tBuONO 3 in acetonitrile was heated at 60 8C for 1 h. To our delight, phenylboronate 4a was formed in 40% yield as shown by GC–MS analysis (Table 1, entry 1). Encouraged by this initial result, we further proceeded to optimize the reaction conditions. Initially, we explored the use of additives that could promote this transformation. Possible additives include KOAc (Table 1, entry 2), which may accelerate trans-borylation of B2pin2, [4] and metal salts (Table 1, entries 3–6), which may speed up the decomposition of the phenyldiazonium ion. However, the reaction was not significantly improved by these additives. Notably, Cu and Cu salts, which are commonly used in the classic Sandmeyer reaction, afforded 4a in only 8% and 7% yields, respectively (Table 1, entries 3,4). In both cases, diphenylamine was the major product. It was noted that use of Fe(OAc)2 significantly improved the yield (Table 1, entry 6). As it is suggested that the Sandmeyer reaction proceeds by a radical mechanism, 18] the radical initiators 2,2’-azobisisobutyronitrile (AIBN) and benzoyl peroxide (BPO) were introduced into the reaction mixture in subsequent experiments. It was indeed observed that higher yields could be obtained in the presence of these radical initiators (Table 1, entries 7–13). Furthermore, when BPO was used as an additive, the reaction could be carried out at room temperature with improved yields, although the reaction time was extended from 1 to 3 hours [*] F. Mo, D. Qiu, Dr. Y. Zhang, Prof. Dr. J. Wang Beijing National Laboratory of Molecular Sciences (BNLMS) and Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry, Peking University Beijing 100871 (China) Fax: (+ 86)10-6275-1708 E-mail: wangjb@pku.edu.cn Homepage: http://www.chem.pku.edu.cn/physicalorganic/ home.htm

Catalytic Functionalization of Unactivated sp3 C–H Bonds via exo-Directing Groups: Synthesis of Chemically Differentiated 1,2-Diols

We describe a Pd-catalyzed site-selective functionalization of unactivated aliphatic C-H bonds, providing chemically differentiated 1,2-diols from monoalcohol derivatives. The oxime was employed as both a directing group (DG) and an alcohol surrogate for this transformation. As demonstrated in a range of substrates, the C-H bonds β to the oxime group are selectively oxidized. Besides activation of the methyl groups, methylene groups (CH(2)) in cyclic substrates and methine groups (CH) at bridge-head positions can also be functionalized. In addition, an intriguing oxidative skeleton rearrangement was observed using the menthol-derived substrate. The use of exo-directing groups in C-H activation, as illustrated in this work, would potentially open doors for the discovery of new transformations and new cleavable DGs.

Synthesis of ortho-Acylphenols through the Palladium-Catalyzed Ketone-Directed Hydroxylation of Arenes†

Ketone in charge: a formal ketone-directed palladium-catalyzed ortho-hydroxylation of arenes has been developed as an effective approach to access o-acylphenols from simple arylketones. A Pd-catalyzed oxidative ortho-carbonylation reaction using ketone directing groups to access a ketal-lactone motif is also demonstrated. The ubiquity and versatile nature of ketones make these methods attractive. BTI=PhI(TFA)(2); DCE=1,2-dichloroethane.

Synthesis, Structure, and Reactivity of Anionic sp(2) -sp(3) Diboron Compounds: Readily Accessible Boryl Nucleophiles.

Lewis base adducts of tetra-alkoxy diboron compounds, in particular bis(pinacolato)diboron (B2 pin2 ), have been proposed as the active source of nucleophilic boryl species in metal-free borylation reactions. We report the isolation and detailed structural characterization (by solid-state and solution NMR spectroscopy and X-ray crystallography) of a series of anionic adducts of B2 pin2 with hard Lewis bases, such as alkoxides and fluoride. The study was extended to alternative Lewis bases, such as acetate, and other diboron reagents. The B(sp(2) )-B(sp(3) ) adducts exhibit two distinct boron environments in the solid-state and solution NMR spectra, except for [(4-tBuC6 H4 O)B2 pin2 ](-) , which shows rapid site exchange in solution. DFT calculations were performed to analyze the stability of the adducts with respect to dissociation. Stoichiometric reaction of the isolated adducts with two representative series of organic electrophiles-namely, aryl halides and diazonium salts-demonstrate the relative reactivities of the anionic diboron compounds as nucleophilic boryl anion sources.

Synthesis of Pinacol Arylboronates from Aromatic Amines: A Metal-Free Transformation

A metal-free borylation process based on Sandmeyer-type transformation using arylamines derivatives as the substrates has been developed. Through optimization of the reaction conditions, this novel conversion can be successfully applied to a wide range of aromatic amines, affording borylation products in moderate to good yields. Various functionalized arylboronates, which are difficult to access by other methods, can be easily obtained with this metal-free transformation. Moreover, this transformation can be followed by Suzuki-Miyaura cross-coupling without purification of the borylation products, which enhances the practical usefulness of this method. A possible reaction mechanism involving radical species has been proposed.

Gold(III)-Catalyzed Halogenation of Aromatic Boronates with N-Halosuccinimides

Aromatic boronates bearing halogen substituents in the aromatic ring can be synthesized by AuCl(3)-catalyzed halogenations with N-halosuccinimides.

Synthesis of Aryl Trimethylstannanes from Aryl Amines: A Sandmeyer‐Type Stannylation Reaction

Sandmeyer-type stannylation: Stille coupling is one of the most powerful coupling reactions for CC bond formation, whereas there are only limited methods to access aryl stannane compounds. A mild stannylation process based on a Sandmeyer-type transformation using aromatic amines as the starting materials is described. DCE: 1,2-dichloroethane.

Bifunctional Ligand-Assisted Catalytic Ketone α-Alkenylation with Internal Alkynes: Controlled Synthesis of Enones and Mechanistic Studies.

Here, we describe a detailed study of the rhodium(I)-catalyzed, bifunctional ligand-assisted ketone α-C-H alkenylation using internal alkynes. Through controlling the reaction conditions, conjugated enamines, α,β- or β,γ-unsaturated ketones, can be selectively accessed. Both aromatic and aliphatic alkynes can be employed as coupling partners. The reaction conditions also tolerate a broad range of functional groups, including carboxylic esters, malonates, secondary amides, thioethers, and free alcohols. In addition, excellent E-selectivity was observed for the tetra-substituted alkene when forming the α,β-unsaturated ketone products. The mechanism of this transformation was explored through control experiments, kinetic monitoring, synthesizing the rhodium-hydride intermediates and their reactions with alkynes, deuterium-labeling experiments, and identification of the resting states of the catalyst.

Highly Diastereoselective Addition of the Lithium Enolate of α-Diazoacetoacetate to N-Sulfinyl Imines : Enantioselective Synthesis of 2-Oxo and 3-Oxo Pyrrolidines

The highly enantioselective synthesis of 2-oxo and 3-oxo pyrrolidines has been achieved by diastereoselective addition of the lithium enolate of alpha-diazoacetoacetate to chiral N-sulfinyl imines, followed by photoinduced Wolff rearrangement or Rh(II)-catalyzed intramolecular N-H insertion.