Enantioselective Pd‐Catalyzed Allylic Alkylation Reactions of Dihydropyrido[1,2‐a]indolone Substrates: Efficient Syntheses of (−)‐Goniomitine, (+)‐Aspidospermidine,and (−)‐Quebrachamine

The successful application of dihydropyrido[1,2‐a]indolone (DHPI) substrates in Pd‐catalyzed asymmetric allylic alkylation chemistry facilitates rapid access to multiple alkaloid frameworks in an enantioselective fashion. Strategic bromination at the indole C3 position greatly improved the allylic alkylation chemistry and enabled a highly efficient Negishi cross‐coupling downstream. The first catalytic enantioselective total synthesis of (?)‐goniomitine, along with divergent formal syntheses of (+)‐aspidospermidine and (?)‐quebrachamine, are reported herein.     

Synergistic Ir/Cu Catalysis for Asymmetric Allylic Alkylation of Oxindoles: Enantio- and Diastereoselective Construction of Quaternary and Tertiary Stereocenters

3,3-Disubstituted oxindoles bearing quaternary and tertiary stereogenic centers are privileged structural motifs, which widely exist in pharmaceutical and natural products. Herein, a highly regio-, enantio-, and diastereoselective allylic alkylation of 3-alkyl oxindoles through synergistic iridium and copper catalysis is described, which provides a series of 3,3-disubstituted oxindole derivatives containing adjacent quaternary and tertiary stereogenic centers in excellent yields, enantiomeric excess, and diastereomeric ratio (for 30 examples, up to 97 % yield, >99 % ee, and >20 : 1 dr). This method provides exclusive branched selectivity, excellent enantio- and diastereoselectivities, and good functional compatibility. Control experiments suggested that the chiral copper catalyst is required for achieving high reactivities and diastereoselectivities under mild reaction conditions.     

Vanadium‐Catalyzed Solvent‐Free Synthesis of Quaternary α‐Trifluoromethyl Nitriles by Electrophilic Trifluoromethylation

The direct electrophilic trifluoromethylation of silyl ketene imines (SKIs) with hypervalent iodine reagents leads to the formation of quaternary α‐trifluoromethyl nitriles in good yields. This new reaction has been carried out with a variety of substituted SKIs under solvent‐free conditions using a vanadium(IV) catalyst (5 mol %). The corresponding products may be transformed into useful organofluorine building blocks.     

An Effective Preparation of Sulfonyl‐ or Sulfinyl‐Substituted Fluorinated Alkenes and their Stereoselective Addition–Elimination Reactions with Organocuprates

Treatment of trifluorovinyl‐ or pentafluoropropen‐1‐yl sulfone or sulfoxide, which are easily prepared from commercially available 1,2‐dibromofluoroalkanes, with various organocuprates affords substitution or β‐reduction products in good to excellent yields through an addition–elimination reaction sequence.     

Alkylation of Pyridines at Their 4‐Positions with Styrenes plus Yttrium Reagent or Benzyl Grignard Reagents

A new regioselective alkylation of pyridines at their 4‐position was achieved with styrenes in the presence of yttrium trichloride, BuLi, and diisobutylaluminium hydride (DIBAL‐H) in THF. Alternatively, similar products were more simply prepared from pyridines and benzyl Grignard reagents. These reactions are not only a useful preparation of 4‐substituted pyridines but are also complementary to other relevant reactions usually giving 2‐substituted pyridines.     

Iridium‐Catalyzed Stereoselective Allylic Alkylation Reactions with Crotyl Chloride

The development of the first enantio‐, diastereo‐, and regioselective iridium‐catalyzed allylic alkylation reaction of prochiral enolates to form an all‐carbon quaternary stereogenic center with an aliphatic‐substituted allylic electrophile is disclosed. The reaction proceeds with good to excellent selectivity with a range of substituted tetralone‐derived nucleophiles furnishing products bearing a newly formed vicinal tertiary and all‐carbon quaternary stereodyad. The utility of this protocol is further demonstrated via a number of synthetically diverse product transformations.     

Cu‐Catalyzed Asymmetric Allylic Alkylation of Phosphonates and Phosphine Oxides with Grignard Reagents

An efficient and highly enantioselective copper‐catalyzed allylic alkylation of phosphonates and phosphine oxides with Grignard reagents and Taniaphos or phosphoramidites as chiral ligands is reported. Transformation of these products leads to a variety of new phosphorus‐containing chiral intermediates.     

Copper‐Free Asymmetric Allylic Alkylation with a Grignard Reagent: Design of the Ligand and Mechanistic Studies

The Cu‐free asymmetric allylic alkylation, catalysed by NHC, with Grignard reagents is reported on allyl bromide derivatives with good results. The enantioselectivity was quite homogeneous (around 85 % ee) on large and various substrates, regardless of the nature of the Grignard reagent. The formation of stereogenic quaternary centres was highly regioselective for both aliphatic and aromatic derivatives with good enantiomeric excess (up to 92 % ee). The methodology developed was found to be complementary with the Cu‐catalysed version. Several new NHCs were tested with improved efficiency. In addition, mechanistic studies, using NMR spectroscopy, led to the discovery of the catalytically active species.     

Liquid Phase Friedel‐Crafts Alkylation over Mixed Metal Oxide Catalyst

Liquid phase Friedel‐Crafts alkylation of benzene with benzyl chloride was carried out over various ferrites viz. CuFe₂O₄, NiFe₂O₄, CoFe₂O₄, ZnFe₂O₄, and MgFe₂O₄. Among the various ferrites ZnFe₂O₄ showed the highest activity. These ferrites were prepared by co‐precipitation technique. The effect of variation of catalyst, speed of agitation and reaction temperature has been studied. Benzylation of other substrates such as toluene, anisole and chlorobenzene was also studied. The catalyst ZnFe₂O₄ was found to be reusable. The acid base properties of the catalyst were studied by cyclohexanol dehydration reaction and the data was correlated with activity.     

Enantioselective Synthesis of Vicinal All‐Carbon Quaternary Centers via Iridium‐Catalyzed Allylic Alkylation

The development of the first enantioselective transition‐metal‐catalyzed allylic alkylation providing access to acyclic products bearing vicinal all‐carbon quaternary centers is disclosed. The iridium‐catalyzed allylic alkylation reaction proceeds with excellent yields and selectivities for a range of malononitrile‐derived nucleophiles and trisubstituted allylic electrophiles. The utility of these sterically congested products is explored through a series of diverse chemo‐ and diastereoselective product transformations to afford a number of highly valuable, densely functionalized building blocks, including those containing vicinal all‐carbon quaternary stereocenters.     

A Convenient Approach to C2‐Chiral 1,1,4,4‐Tetrasubstituted Butanetetraols: Direct Alkylation or Arylation of Enantiomerically Pure Diethyl Tartrates

C₂‐Chiral 1,1,4,4‐tetraaryl‐ or 1,1,4,4‐tetraalkyl‐substituted butanetetraols have been conveniently synthesized via arylation or alkylation of unprotected diethyl (2R,3R)‐ and (2S,3S)‐tartrates with Grignard reagent. The chiral 1,1,4,4‐tetrasubstituted butanetetraols were characterized by IR, ¹H‐ and ¹³C‐NMR, as well as LC/MS.     

Understanding and Practical Use of Ligand and Metal Exchange Reactions in Thiolate‐Protected Metal Clusters to Synthesize Controlled Metal Clusters

It is now possible to accurately synthesize thiolate (SR)‐protected gold clusters (Au_n(SR)_m) with various chemical compositions with atomic precision. The geometric structure, electronic structure, physical properties, and functions of these clusters are well known. In contrast, the ligand or metal atom exchange reactions between these clusters and other substances have not been studied extensively until recently, even though these phenomena were observed during early studies. Understanding the mechanisms of these reactions could allow desired functional metal clusters to be produced via exchange reactions. Therefore, we have studied the exchange reactions between Au_n(SR)_m and analogous clusters and other substances for the past four years. The results have enabled us to gain deep understanding of ligand exchange with respect to preferential exchange sites, acceleration means, effect on electronic structure, and intercluster exchange. We have also synthesized several new metal clusters using ligand and metal exchange reactions. In this account, we summarize our research on ligand and metal exchange reactions.