The soft nucleophilicity of organotellurolates driving the SN2-type lactone ring-opening reaction

Lithium and magnesium organotellurolates were reacted with lactones producing the corresponding tellurocarboxylic acids. Treatment of the reaction mixture with lithium aluminum hydride allowed the isolation of the corresponding hydroxytellurides in a one-pot operation.     

Lewis acid mediated nucleophilic ring opening followed by cycloaddition of 2-aryl-N-tosylaziridines with carbonyl compounds: further support towards an SN2-type mechanism

A highly regioselective S_N2-type ring opening of 2-aryl-N-tosylaziridines with carbonyl compounds in the presence of a Lewis acid to afford various 1,3-oxazolidines and 1,2-amino alcohols in excellent yields and moderate to high enantioselectivity is described. The formation of non-racemic products provides convincing evidence for the S_N2-type ring opening mechanism.     

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.     

The reaction of biphenyl radical anion and dianion with alkyl fluorides. From ET to SN2 reaction pathways and synthetic applications

The reaction of dilithium biphenyl (Li₂C₁₂H₁₀) with alkyl fluorides has been studied from the point of view of the distribution of products. Two main reaction pathways, the nucleophilic substitution (S_N2) and the electron transfer (ET), can compete to yield the same alkylation products in what is known as the S_N2-ET dichotomy. S_N2 seems to be the main mechanism operating with primary alkyl fluorides (n-RF). Alkylation proceeds in good yields, and the resulting alkylated dihydrobiphenyl anion (n-RC₁₂H₁₀Li) can be trapped with a second conventional electrophile (E⁺) affording synthetically interesting dearomatized biphenyl derivatives (n-RC₁₂H₁₀E). The reaction gives a higher amount of ET products as we move to secondary (s-RF) and to tertiary alkyl fluorides (t-RF), in which case the mechanism seems to be dominated by ET. In this case, alkylation by radical coupling is still feasible, giving access to the synthesis of t-RC₁₂H₁₀E, although in lower yields. A rational interpretation of this S_N2-ET dichotomy is given on the basis of the full distribution of products observed when 5-hexenyl fluoride and 1,1-dimethyl-5-hexenyl fluoride were are used as radical probes in their reaction with Li₂C₁₂H₁₀ and LiC₁₂H₁₀.     

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.     

Lewis acid mediated SN2-type nucleophilic ring opening followed by [4+2] cycloaddition of N-tosylazetidines with aldehydes and ketones: synthesis of chiral 1,3-oxazinanes and 1,3-amino alcohols

A highly efficient strategy for Cu(OTf)₂ mediated S_N2-type nucleophilic ring opening followed by [4+2] cycloaddition reactions of enantiopure 2-phenyl-N-tosylazetidines with various aldehydes and ketones afforded a variety of substituted 1,3-oxazinanes and 1,3-amino alcohols in excellent yields, excellent de and good to excellent ee. The proposed S_N2-type mechanism of the cycloaddition reaction is supported by experimental evidence.     

Reaction of indium ate complexes with allylic compounds. Controlling SN2/SN2′ selectivity by solvents

Vinyl and methylindium ate complexes (indates) were prepared and both the tendency of immigration and regioselectivity toward cinnamyl bromide were investigated. The vinyl group was more preferably transferred than the Me group, giving a regioisomeric mixture of S_N2 and S_N2′ products. The ratio of S_N2/S_N2′ selectivity can be controlled by solvents; in the presence of polar solvents, such as N-butylpyrrolidone (NBP) and THF, the S_N2′ product was mainly obtained, whereas the S_N2 product was selectively prepared in solutions containing hexane. The vinylindium compound, generated by the reaction of allylic-type diindium reagents with imine, was also converted to the corresponding vinyl indate, which was allowed to react with allyl chloride to give a three-component coupling product.     

Benzyne-induced ring opening reaction of thiiranes. Efficient synthesis of phenyl vinyl sulfides

A series of thiiranes react with benzyne to provide an efficient synthesis of phenyl vinyl sulfides. The reaction is stereospecific, thus producing cis-(phenylthio)-stilbene from cis-2,3-diphenylthiirane and trans-(phenylthio)stilbene from trans-2,3-diphenylthiirane.     

Ethylcyclopentane ring opening reaction over PtGe/Al2O3 catalysts prepared by controlled surface reaction

Platinum-germanium catalysts supported on a non-acidic Al₂O₃ have been prepared by adding Ge in amounts corresponding nominally to 1/8 (PtGe1/8/Al₂O₃); 1/2 (PtGe1/2/Al₂O₃); 1 (PtGe1/Al₂O₃) and 2 (PtGe2/Al₂O₃) monolayers by controlled surface reaction of Ge(n-C₄H₉)₄ to Pt/Al₂O₃. These catalysts were characterized by electron microscopy (TEM), FTIR of CO adsorption and H₂ chemisorption. The ring opening of ethylcyclopentane (ECP) was studied as a test reaction between 543 and 633 K. PtGe1/8/Al₂O₃ catalyst produced the most ring opening products (ROP) in the whole temperature range. A good agreement with statistical values of ROP was observed at low temperature, but at higher temperature, the opening became selective, producing mostly heptane. Bimetallic catalysts PtGe1/Al₂O₃ and PtGe2/Al₂O₃ led to a nonselective hydrogenolysis, similar to the monometallic platinum catalyst Pt/Al₂O₃. The catalysts PtGe1/Al₂O₃ and PtGe2/Al₂O₃ produced ROP with the lowest selectivity; instead, much aromatics and fragments were formed, in increasing amounts above 600 K.     

Photo-SRN1 reactions of phenyl telluride anion with haloarenes

Phenyl telluride anion was prepared in liquid ammonia by reaction of dipheyyl ditelluride with two equivalents of sodium metal under nitrogen. This anion reacts with haloarenes under irradiation to form aryl phenyl tellurides, probably by the photo-S_RN1 mechanism of aromatic substitution.     

Regio- and stereoselective ring opening of vinyl epoxides with MgBr2

The regio- and stereoselective ring opening of vinyl epoxides has been achieved by the use of Lewis acid, MgBr₂, affording bromohydrins in excellent yield, which are readily transformed to azidoalcohol, a key intermediate of several classes of pyrrolizidine and indolizidine alkaloids. The scope and limitations of the reaction are discussed.     

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%).     

First enantioselective synthesis of 4-aminoalcohol quinoline derivatives through a regioselective SN2 epoxide opening mechanism

Mefloquine derivatives, contrary to chloroquine derivatives have not been widely studied to date. Consequently, mefloquine and its derivatives still remain very attractive synthetic targets. Although mefloquine is usually used clinically as a racemic mixture, some studies have shown that its (+)-enantiomer is more potent than the (−)-enantiomer. Moreover, the (−)-enantiomer is responsible for side effects due to reaction with the central nervous system adenosine receptors, while the (+)-enantiomer does no bind at this binding site. Recently, different libraries of racemic 4-aminoalcohol quinolines showed interesting antimalarial activities. Herein, we describe an enantiopure synthetic and straightforward route to prepare pure enantiomer 4-aminoalcohol quinoline derivatives through a 4-oxirane key-intermediate. A regioselective S_N2 ring opening of this epoxide, by diverse amines, allows us to obtain the corresponding (R) or (S) 4-aminoquinolines with good yields and enantiomeric excesses generally superior to 92%. The reported methodology appears suitable for the synthesis of a large number of pure enantiomer 4-aminoalcohol quinoline derivatives.     

Facile preparation of alkoxybenzoxazoles via direct SNAr on the benzoxazole ring

The synthesis of alkoxybenzoxazoles is in general quite challenging. During our investigation, we discovered that C-4 and C-7 fluoro precursors undergo S_NAr with alkoxides affording moderate to excellent yields of substituted product.     

Synthesis of gamma-methylene oxacycles and alpha- and beta-alkylidene lactones via silicon-assisted ring opening of cyclopropyl carbinols

Cyclopropyl carbinols bearing a (tert-butyldiphenylsilyl)methyl substituent undergo silicon-assisted regioselective ring cleavage and the resulting beta-silyl carbocation is intramolecularly trapped with hydroxy and ester functions to generate gamma-methylene oxacycles and alpha- and beta-alkylidene lactones without the cleavage of the silicon function.     

An ab initio molecular orbital study of the SN2 reaction of H− with HF

Ab initio SCF MO calculations have been performed for the reactants, products and reaction complex in the title reaction. The influence of diffuse and polarization basis functions in determining the presence of a reaction barrier was investigated. No barrier to the forward or reverse reactions was found.     

Nitrile anion cyclization with epoxysilanes followed by brook rearrangement/ring opening of cyclopropane nitriles/alkylation

The reaction of delta-silyl-gamma,delta-epoxypentanenitrile derivatives with a base and an alkylating agent affords delta-siloxy-gamma,delta-unsaturated pentanenitrile derivatives via a tandem process that involves the formation of the cyclopropane derivative by epoxy nitrile cyclization followed by Brook rearrangement and an anion-induced cleavage of the cyclopropane ring.