Sulfoxide-controlled SN2′ displacements between cuprates and vinyl and alkynyl epoxy sulfoxides

The S_N2′ displacement of readily available vinyl epoxy sulfoxides with organocopper reagents takes place in good yields with high anti selectivity and a good degree of E/Z stereocontrol to produce enantiopure α-hydroxy vinyl sulfoxides. A second allylic displacement on the related mesyloxy vinyl sulfoxides allows for the asymmetric construction of two adjacent chiral centers. In addition, cuprate mediated S_N2′ addition to alkynyl epoxy sulfoxides affords α-hydroxy allenyl sulfoxides in good yields.     

Highly regio- and stereocontrolled SN2′ reactions of gem-difluorinated vinyloxiranes with monoalkylcopper reagents

Reaction of gem-difluorinated vinyloxiranes with RCu(X)Li allowed us to introduce the R group regioselectively at the fluorine-attached terminal carbon atom in an S_N2′ manner to afford (E)-allylic alcohols exclusively, while homoallylic alcohols with anti stereochemical relationship were found to be obtained selectively from higher-ordered cuprates derived from CuCl and RMgBr in a ratio of 1:3.     

Preparation of N-protected allylic amines and α-methylene-β-amino acids from vinylalumination/Baylis-Hillman products via tandem SN2′ substitution-Overman rearrangement

S_N2′ reaction on the acetates obtained from vinylalumination or Baylis-Hillman products, followed by in situ reduction afforded allylic alcohols. Upon conversion to trichloroacetimidates and [3,3]-sigmatropic rearrangement, the corresponding N-protected β-substituted allylic amines were obtained in good yields. Utilization of hydroxy group as the nucleophile furnished allylic hydroxy esters, which were converted to protected α-methylene-β-amino acids via Overman rearrangement.     

Facile oxygenation of organic sulfides with H2O2 catalyzed by Mn-Me3TACN compounds

Two binuclear Mn-Me₃TACN (Me₃TACN is 1,4,7-N,N′,N″-trimethyl-1,4,7-triazacyclononane) compounds catalyze the oxygenation of organic sulfides utilizing H₂O₂ under ambient conditions. Both phenyl sulfide and ethyl phenyl sulfide were converted to the corresponding sulfones and chloroethyl phenyl sulfide proceeds to its elimination product of phenyl vinyl sulfone.     

Inorganic-Organic Hybrid Materials: Synthesis and X-Ray Structure of N,N′-Dimethylimidazolium Salts [(Me2Im)2][Cd2(SCN)6] and N,N′-Dicyclohexylimidazolium [(Cy2Im)2][Cd2(SCN)6]·C3H6O

Two novel N,N′-dialkylimidazolium thiocyanate-cadmium complexes [(R₂Im)₂][Cd₂(SCN)₆] for R=Me (3), and cyclohexyl (4) have been synthesized and characterized by single-crystal X-ray diffraction. Compound 3 crystallizes in the monoclinic unit cell dimensions of 17.468(3), 7.7273(12), 10.6750(16) Å, 104.833(2)°, and space group C2 with two [(Me₂Im)₂] [Cd₂(SCN)₆] per unit cell. The two cadmium atoms in 3 are octahedrally coordinated in 4N2S and 2N4S coordination environment, and linking into one-dimensional zigzag chains. Compound 4 belongs to the monoclinic space group Cc with unit cell of dimensions 13.3049(12), 17.5550(16), 20.8012(19) Å, 101.494(2)°, and four [(Cy₂Im)₂][Cd₂(SCN)₆]·C₃H₆O per unit cell. The cadmium atoms in 4 are all 3N3S hexa-coordinated with six bridging SCN⁻ ions in an fac configuration and form infinite zigzag polymeric chains. The infinite chains in 3 form an approximate hexagonal array, making triangular channels which are occupied by N,N′-dimethylimidazolium ions, whereas the chains in 4 form layered structure, and the layers are stacked perpendicularly with respect to the orientation of the infinite anionic chains alternatively. N,N′-dicyclohexylimidazolium cations and solvent molecules fill in between layers.     

Chemoselective SN2′ reaction of nitroalkanes to dialkyl 2-(bromomethyl)fumarates under cetyltrimethylammonium hydroxide (CTAOH) catalysis

The chemoselective S_N2′ reaction of a variety of primary nitroalkanes to dialkyl 2-(bromomethyl)fumarates can be efficiently performed under cetyltrimethylammonium hydroxide (CTAOH) catalysis. The α,β-unsaturated esters were obtained in satisfactory to good yields with the complete retention of the nitro group.     

Efficient construction of bicyclic systems by an internal SN2′ enolate alkylation/ring-closing metathesis (RCM) strategy: a concise synthesis of the trans-hydrindane nucleus

A concise and efficient synthesis of the trans-hydrindane system has been achieved by a novel intramolecular S_N2′ enolate alkylation/ring-closing metathesis (RCM) strategy with a good degree of stereocontrol.     

Effects of solvent and base on the palladium-catalyzed amination: PdCl2(Ph3P)2/Ph3P-catalyzed selective arylation of primary anilines with aryl bromides

A readily accessible catalytic system, PdCl₂(Ph₃P)₂/Ph₃P, was developed for the selective arylation of primary anilines with aryl bromides. The strong influence of solvents and bases on the catalytic activity was observed. In refluxing o-xylene, triphenylphosphine shows high efficiency for Pd-catalyzed intermolecular amination reactions. By changing the bases, mono- and diarylation of primary amines could be selectively achieved in high yields. Moreover, the catalytic system showed good toleration for the steric hindrance of anilines. A series of N,N,N′,N′-tetraaryl-1,1′-biphenyl-4,4′-diamines, important intermediates of OLED hole transport materials, were synthesized facilely via coupling reactions between 4,4′-diaminobiphenyls and aryl bromides.     

Highly enantioselective copper-catalyzed allylic alkylation with atropos phosphoramidites bearing a D2-symmetric biphenyl backbone

A novel class of atropos dibridged biphenyl phosphoramidites bearing a D₂-symmetric biphenyl backbone was prepared and applied as chiral ligands in the copper-catalyzed allylic alkylation with Grignard reagent. The alkylation products were obtained in quantitative yields with high regioselectivities up to 94:6 of S_N2′/S_N2 ratio and enantiomeric excesses up to 91.1% for S_N2′ products. The unique D₂-symmetric backbone ligands have the advantages of easy preparation and sufficient reusability of their key intermediates from the undesired isomers.     

Convergent synthesis of panclicin-D via intramolecular SN2 displacement approach

A convergent enantioselective synthesis of panclicin-D has been reported from simple octanal using syn aldol reaction via intramolecular S_N2 displacement reaction for the first time towards the construction of anti-β-lactones in panclicin-D. The key steps involved are C-allylation, asymmetric aldolization under Crimmins condition, intramolecular S_N2 displacement, and Mitsunobu esterification reaction.     

On the dichotomy of the SN2/ET reaction pathways: an apparent SN2 reactivity in the reaction of naphthalene dianion with alkyl fluorides

Dilithium naphthalene (Li₂C₁₀H₈) displays a S_N2 reactivity profile in its reaction with alkyl fluorides (n-, s- and t-octyl fluoride). S_N2 seems to be the dominant mechanism operating with primary alkyl fluorides, which presumably turns into competition with ET as we move to secondary and tertiary alkyl fluorides. Significantly, lithium naphthalene (LiC₁₀H₈) seems to have also an important nucleophilic component when reacting with alkyl fluorides, in contrast to the previously proposed general ET process valid for all alkyl halides. These results explain the observed distribution of products and are reinforced by a complete analysis of the products originated by the reaction with 6-halohexenyl radical probes, whose main alkylation products are described here for the first time.     

Synthesis of chiral β-3-amino-2-hydroxyalkanoates and 3-alkyl-3-hydroxy-β-lactams by double asymmetric induction

Reactions of chiral (2S)-enolates of dioxolan-4-ones, derived from lactic, mandelic, and phenyllactic acids, with aliphatic (S_S)- and (S_R)-tert-butylsulfinyl aldimines afforded conformationally restrained C2-disubstituted N,O-orthogonally protected 3-amino-2-hydroxyalkanoates in the form of N-sulfinyl protected 1′-aminodioxolan-4-ones. The product distribution showed that there is significant kinetic selectivity, due to the presence of ‘matched’ and ‘mismatched’ components, between the (S)- or (R)-tert-butylsulfinyl aldimines and the (2S)-enolates of the 1,3-dioxolan-4-ones. Selective methoxide-induced removal of the acetal group of the N-sulfinyl-1′-aminodioxolanones yielded the corresponding N-sulfinyl protected methyl alkanoates. In addition, the selective acid-induced removal of the sulfinyl group of the N-sulfinyl-1′-aminodioxolanones provided the corresponding N-unprotected 1′-aminodioxolanones, whose base-induced cyclization afforded the corresponding β-lactams.     

Ortho selectivity in SNAr substitutions of 2,4-dihaloaromatic compounds. Reactions with piperidine

A broad survey of aromatic compounds with halogens positioned both ortho and para to activating groups was studied in S_NAr reactions with piperidine. Regioselectivities varied with the substituent group and the polarity of the solvent. Many activating groups exhibited an overall bias toward ortho-substitution, and this led in nonpolar solvents to very high ortho selectivity. More polar solvents uniformly shifted the product ratio toward para substitution. Evidence is presented that argues for coordination via hydrogen bonding as a driver of much of the ortho selectivity observed. The data presented show ample evidence of the generality and synthetic utility of the ortho-directing ability of several common activating groups for this reaction type.     

Metal-organic chains constructed from pre-organized N2S2 donor ligands

Three new N₂S₂ donor ligands 1,1′-((2-(2-(phenylthio)phenylthio)phenyl)methylene)bis(3,5-R-1H-pyrazole), R = H (L^H), R = Me (L^Me), R = i-Pr (L^i-Pr) have been prepared and characterized. These bifunctional ligands incorporate two distinct chelate donor systems, by virtue of the presence of bispyrazole and bisthioether functions. The preferred conformation of these ligands is such that the N₂ and S₂ donor moieties may be oriented in opposite directions, thus favoring the formation of molecular chains when treated with AgBF₄. The X-ray structures of Ag(I) complexes show that, depending on the steric hindrance present on the pyrazole rings, these ligands behave as κ⁴-SSNN-μ bridging tetradentate (when R = H), or κ³-SNN-μ bridging tridentate (when R = Me, i-Pr). Interestingly, [Ag(L^H)]BF₄ crystallizes in the chiral space group P4₁, with the molecular chain that is folded around the 4₁ screw axis.     

Cyclization versus oligomerization of SP- and RP-5′-OH-N-benzoyl-2′-deoxycytidine-3′-O-(2-thio-4,4-pentamethylene-1,3,2-oxathiaphospholane)s

The S_P-isomer of 5′-OH-N⁴-benzoyl-2′-deoxycytidine-3′-O-(2-thio-4,4-pentamethylene-1,3,2-oxathiaphospholane) undergoes DBU-promoted intramolecular cyclization providing as a sole product S_P-deoxycytidine cyclic 3′,5′-O,O-phosphorothioate. Unexpectedly, the R_P-counterpart yields a mixture of products consisting of R_P-deoxycytidine cyclic 3′,5′-O,O-phosphorothioate and macrocyclic oligo(deoxycytidine phosphorothioate)s. The results of molecular modeling indicate that the dychotomy observed for the R_P substrate may result from remarkably higher energy of the corresponding transition states, caused by the presence of bulky ‘spiro’ pentamethylene substituent at the position C4 in the oxathiaphospholane ring.     

Acid-promoted SN1/E1 fragmentation/dimerization of 2-cumylmalonates

Several diethyl 2-cumylmalonates underwent fragmentation and dimerization in PPA at elevated temperatures to give 1,1,3-trimethyl-3-arylindanes in good yields. The same products were obtained from 2-cumylmalonic acid, ethyl 2-cumylcyanoacetate, and 2-cumyl Meldrum’s acid. This represents the first example of an S_N1/E1 ionization with diethyl malonate as the leaving group.     

Asymmetric Kumada-Corriu cross-coupling reaction with Pd2(dba)3 and an N-Ar axially chiral mimetic-type ligand catalyst

A catalyst comprised of Pd₂(dba)₃·CHCl₃ and an N-Ar axially chiral mimetic-type ligand, (S)-N-[2-(diphenylphosphanyl)naphthalene-1-yl]-2-(piperidinylmethyl)piperidine, provides good enantioselectivities for the asymmetric Kumada-Corriu cross-coupling reaction of 1-phenylethylmagnesium chloride and E-β-bromostyrene derivatives with which it is more difficult to achieve high enantioselectivity. Furthermore, in the case of styrene derivatives bearing both vinyl and aryl bromide groups, the chemoselective asymmetric cross-coupling reaction of the vinyl bromide group is observed. This N-Ar axially chiral mimetic-type ligand allows easy synthesis of a wide variety of analogues, and starting from the initial ligand, the enantioselectivity of coupling products is improved by modifying the structure in the ligand.     

Characterisation of N-vinyl-2-pyrrolidone-based hydrogels prepared by a Diels-Alder click reaction in water

N-vinyl-2-pyrrolidone-based hydrogels were prepared by the Diels-Alder reaction in water for the first time. Copolymers of N-vinyl-2-pyrrolidone(VP) and furfuryl methacrylate(FM) were synthesised by free radical polymerisation in toluene at 70 °C by using 2,2′-azobisisobutyronltrile as an initiator. Polymeric dienophile (PEG-AMI) was prepared from N-alaninyl maleimide (AMI) and poly(ethylene glycol) (PEG) by using N,N′-dicyclohexylcarbodiimide (DCC) as a dehydrating agent. The prepared dienes and dienophile were then dissolved in water and mixed, leading to gelation via Diels-Alder reaction after some time. The gelation times of different copolymers and PEG-AMI in different solvents and at different temperatures were measured by the vial inversion method, and the swelling behaviour of dried hydrogels was studied using a general gravimetric method. The gelation time was shorter in water than in organic solvents, and the gelation time decreased with the increase of temperature and FM content in copolymers. Conversely, the swelling ratios increased with the decrease of temperature and FM content in the copolymers. Disassembly experiments suggested that N,N-dimethylformamide (DMF) could accelerate the retro-DA reaction.     

Cu(N-N)2Cl2 and Cu(N-N-N)Cl2 and HgCl2 building blocks in the synthesis of coordination compounds—X-ray studies and magnetic properties

A series of complexes containing Cu(N-N)₂Cl₂ (N-N=bis(pyrazol-1-yl)methane (bpzm), bis(3,5dimethylpyrazol-1-yl)methane (bdmpzm), 2,2-dipyridylamine (dpa), 5,6-diphenyl-3-(2-pyridyl)-1,2,4-trazine (dppt) and 2,2′-bipyridine (bipy)), Cu(N-N-N)Cl₂ (N-N-N=2,2′:6′,2″-terpyridine (terpy)) and HgCl₂ building blocks have been synthesized and structurally characterized. Increase in structural dimensionality is observed for [Cu(bpzm)₂][HgCl₄], [Cu(dpa)₂][HgCl₃]₂ and [Cu(terpy)(μ-Cl)HgCl₃] compounds. No coordination polymers have formed in the case of bis(3,5dimethylpyrazol-1-yl)methane, 5,6-diphenyl-3-(2-pyridyl)-1,2,4-trazine and 2,2′-bipyridine. The [Cu(bpzm)₂][HgCl₄] and [Cu(terpy)(μ-Cl)HgCl₃] complexes have been studied by magnetic measurements.     

Efficient entry to 1-benzoxepine ring skeleton via tandem SN2/Wittig reaction. Total synthesis of NADH: ubiquinone oxidoreductase (complex I) antagonist pterulinic acid

Concise synthesis of NADH: ubiquinone oxidoreductase (complex I) antagonist pterulinic acid (1a) is reported. The key architectural framework in the natural product, 1-benzoxepine ring skeleton, was smoothly prepared from known salicylaldehyde 2g and phosphorane 3 via tandem S_N2/Wittig reaction. Pterulinic acid was prepared in 5 steps from 2g with overall yield of 25%. The versatility of tandem S_N2/Wittig reaction was investigated. This tandem reaction tolerated various alkyl, ether, tertiaryamine and nitro substituted salicylaldehyde, and it gave the corresponding 1-benzoxepine ring skeleton in moderated yield (21-72%).