1,2-Bis(dialkylphosphino)ethanes are readily prepared from the parent phosphine oxides,viaa novel sodium aluminium hydride/sodium hydride reduction protocol of intermediate chlorophosphonium chlorides. This approach is amenable to multi-gram syntheses, utilises readily available and inexpensive reagents, and benefits from a facile non-aqueous work-up in the final reductive step.
From a series of gold complexes of the type t-BuXPhosAu(MeCN)]X (X=anion), the best results in intermolecular gold(I)-catalyzed reactions are obtained with the complex with the bulky and soft anion BAr4F?BAr4F?=3,5-bis(trifluoromethyl)phenylborate] improving the original protocols by 10–30% yield. A kinetic study on the 2+2] cycloaddition reaction of alkynes with alkenes is consistent with an scenario in which the rate-determining step is the ligand exchange to generate the (η2-phenylacetylene)gold(I) complex. We have studied in detail the subtle differences that can be attributed to the anion in this formation, which result in a substantial decrease in the formation of unproductive σ,π-(alkyne)digold(I) complexes by destabilizing the conjugated acid formed.
Dynamic systems based on consecutive thia-Michael and Henry reactions were generated and transformed using lipase-catalyzed asymmetric transformation. Substituted thiolane structures with three contiguous stereocenters were resolved in the process in high yields and high enantiomeric excesses.
Isonitriles are delicately poised chemical entities capable of being coaxed to react as nucleophiles or electrophiles. Directing this tunable reactivity with metal and non-metal catalysts provides rapid access to a large array of complex nitrogenous structures ideally functionalized for medicinal applications. Isonitrile insertion into transition metal complexes has featured in numerous synthetic and mechanistic studies, leading to rapid deployment of isonitriles in numerous catalytic processes, including multicomponent reactions (MCR). Covering the literature from 1990–2014, the present review collates reaction types to highlight reactivity trends and allow catalyst comparison.
The combination of benzyl bromide, sodium hydroxide and 15-crown-5 in tetrahydrofuran is shown to be an efficient method for installing benzyl groups at both the 4- and 6-positions regioselectively directly from peracetylatedN-trichloroacetyl-protected glucosamine and galactosamine. Application of this benzylation strategy proved to significantly shorten the synthetic route to hyaluronic acid tetra- and hexamers.
The arylation of sp3-hybridized C–H’s bonds is a powerful strategy to build molecular complexity and diversity. A novel and efficient palladium-catalyzed direct sp3C–H arylation of aryl and alkyl benzyl thioether derivatives with aryl bromides is reported. The reaction involves reversible deprotonation of the benzylic C–H’s of the thioether with either LiN(SiMe3)2or NaN(SiMe3)2and subsequent cross-coupling to provide the functionalized products in up to 97% yield.
Bridged bicyclic rings containing nitrogen heterocycles are important motifs in bioactive small organic molecules. An enantioselective copper-catalyzed alkene carboamination reaction that creates bridged heterocycles is reported herein. Two new rings are formed in this alkene carboamination reaction whereN-sulfonyl-2-aryl-4-pentenamines are converted to 6-azabicyclo3.2.1]octanes using Ph-Box-Cu](OTf)2or related catalysts in the presence of MnO2as stoichiometric oxidant in moderate to good yields and generally excellent enantioselectivities. Two new stereocenters are formed in the reaction, and the C-C bond-forming arene addition is a net C-H functionalization.
Substitution of one of the phenyl groups of triphenylphosphine with a 2-benzyloxy-, 2-benzyloxymethyl- or 2-benzyloxyethyl-phenyl moiety results in a set of simple ligands, which exhibit strikingly different behaviour in various nickel(II)-catalyzed olefin dimerization reactions. Complexes of ligands with 2-benzyloxyphenyl-, 2-benzyloxymethylphenyl-diphenylphosphine (L5andL6respectively) are most active for hydrovinylation (HV) of vinylarenes, with the former leading to extensive isomerization of the primary 3-aryl-1-butenes into the conjugated 2-aryl-2-butenes even at ?55 °C. However, 2-benzyloxymethyl-substituted ligandL6is slightly less active, leading up to quantitative yields of the primary products of HV at ambient temperature with no trace of isomerization, thus providing the best option for a practical synthesis of these compounds. In sharp contrast, hydrovinylation of a variety of 1,3-dienes is best catalyzed by nickel(II)-complexes of 2-benzyloxyphenyldiphenylphosphine,L5. The other two ligands, 2-benzyloxymethyl-(L6) and 2-benzyloxyethyl-diphenylphosphine (L7) are much less effective in the HV of 1,3-dienes. Nickel(II)-catalyzed cycloisomerization of 1,6-dienes into methylenecyclopentanes, a reaction mechanistically related to the other hydrovinylation reactions, is also uniquely effected by nickel(II)-complexes ofL5, but not ofL6orL7. In an attempt to prepare authentic samples of the methylencyclohexane products, nickel(II)-complexes ofN-heterocyclic carbene-ligands were examined. In sharp contrast to the phosphines, which give the methylenecyclopentanes, methylenecyclohexanes are the major products in the (N-heterocyclic carbene)nickel(II)-mediated reactions.
A green and mild protocol for the dehydrogenative olefination of cyclic enaminones was devised via palladium catalysis at room temperature using oxygen as the terminal oxidant. The synthetic utility of the olefinated cyclic enaminones afforded a series of unique 1,3,5-trisubstituted benzenes via an unanticipated Diels-Alder tandem reaction. The broad substrate scope and good yields achieved with this new protocol provide an alternative pathway for arene functionalization.
A mild, catalytic, atom economical synthesis of imidazo1,2-a]pyridines has been developed: catalytic PicAuCl2in the presence of an acid produces a range imidazo1,2-a]pyridines in good yield. This strategy is mild and forseen to be of particular use for the installation of stereogenic centers adjacent to the imidazo1,2-a]pyridine ring without loss of enantiomeric excess.
Phosphine-catalyzed 3+2] and 4+3]annulation reactions of C,N-cyclic azomethine imines with allenoates have been developed to give a variety of pharmaceutically attractive tetrahydroisoquinoline derivatives in moderate to excellent yields. The two distinct reaction pathways, 3+2] and 4+3]cyclization, depend on the nature of the nucleophilic phosphine and the allenoate. Generally, for α-alkylallenoates, the reactions always proceed with 3 +2]cyclization as the major pathway no matter what phosphine was used; for α-ArCH2-substituted allenoates, the reaction pathway was controlled by the phosphine catalyst used.
A concise thiolation of C(sp3)–H bond of cycloalkaneswith diaryl disulfides in the presence of oxidant ofdi-tert-butylperoxide (DTBP) has been developed. This reactionwithout using any of metal catalyst, tolerates varieties of disulfides andcycloalkanes substrates, giving good to excellent chemical yields, whichprovides a useful approach to cycloalkyl aryl sulfides from unactivatedcycloalkanes.
The water-insoluble and water-soluble Nheterocyclic carbene (NHC)–amine palladium complexes, Ipr-Pd(deba)Cl and SO3-Ipr-Pd(deba)Cl, were synthesized. Both catalysts exhibit excellent activity in the phosphine-free double carbonylation of aryl iodides with amines to produce a-keto amides. Moreover, as the water-soluble catalyst exhibits significant compatibility in the aqueous phase with the activities of different Pd-NHC complexes, we conclude that the intramolecular amine ligand strongly affects the selectivity of the products in double carbonylation reaction and serves as an alternative of phosphine ligands.
A highly efficient palladium-catalyzed decarbonylative dehydration reaction of carboxylic acids is reported. This method transforms abundant and renewable even-numbered natural fatty acids into valuable and expensive odd-numbered alpha olefins. Additionally, the chemistry displays a high functional group tolerance. The process employs low loading of palladium catalyst and proceeds under solvent-free and relatively mild conditions.
We describe the development of efficient benzannulations of siloxy alkynes with pyridinium and isoquinolinium salts. Such reactions are successfully promoted by a stoichiometric amount of silver(I) benzolate under mild reaction conditions. This process proceeds via a formal inverse-electron demand Diels-Alder reaction, followed by fragmentation of the initially produced bicyclic adducts to deliver a range of synthetically useful phenols and naphthols.
Enantioenriched potassiumβ-trifluoroboratoamides have been synthesizedviaan asymmetric, copper-catalyzed 1,4-addition of tetrahydroxydiboron (BBA) and tetrakis(dimethylamino)diboron toα,β-unsaturated amides. These dibora reagents provide access to the desired organotrifluoroborates using effective and atom economical sources of boron. The copper-catalyzedβ-boration is extended toα,β-unsaturated ketones and esters. Desired potassium organotrifluoroborates are synthesized with yields up to 92% and enantiomeric ratios up to 98:2. The enantioenriched potassiumβ-trifluoroboratoamides are successfully cross-coupled with an array of aryl and heteroaryl chlorides in high yield with complete stereochemical fidelity as the transmetalation proceeds through an SE2 mechanismviaan open transition state.