Mechanistic insights into the rearrangement of azetidine N-oxides to isoxazolidines

Various functionalized azetidines were oxidized with mCPBA or hydrogen peroxide, to produce the corresponding N-oxide and study its fate in the [1,2] Meisenheimer rearrangement. This ring expansion leading to isoxazolidines occurs readily, without trapping of the transient N-oxide. Starting with azetidines bearing a nitrile or an ester group at C-2, the rearrangement is regioselective. However, a varying amount of epimerization on the migrating radical is observed, which can also be observed with the related [1,2] Stevens rearrangement.     

Sigmatropic Rearrangements of Hypervalent‐Iodine‐Tethered Intermediates for the Synthesis of Biaryls

Metal‐free dehydrogenative couplings of aryliodanes with phenols to afford 2‐hydroxy‐2′‐iodobiaryls have been developed. This reaction proceeds through ligand exchange on the hypervalent iodine atom followed by a [3,3] sigmatropic rearrangement and with complete regioselectivity. This coupling, in combination with in situ oxidation by mCPBA, enables the convenient conversion of iodoarenes into desirable biaryls. The obtained biaryls have convertible iodo and hydroxy groups in close proximity, and are thus synthetically useful, as exemplified by the controlled syntheses of π‐extended furans and a substituted [5]helicene. DFT calculations clearly revealed that the rearrangement is sigmatropic, with C?C bond formation and I?O bond cleavage proceeding in a concerted manner. Acetic acid, which was found to be the best solvent for this protocol, renders the iodine atom more cationic and thus accelerates the sigmatropic rearrangement.     

Regioselective electrophilic addition vs epoxidation of mCPBA towards anti-Bredt olefin of fulleroid

The mCPBA oxidation of methano-bridged [5,6] open fulleroid 1 anomalously resulted in the selective electrophilic addition at the bridgehead anti-Bredt double bond rather than the usual epoxidation. The mechanistic preference for the unprecedented stepwise addition of mCPBA vs the concerted epoxidation was explained in terms of the notable π-orbital misalignment (>30°) based on the B3LYP/6-31G(d) level calculation.     

Synthesis and reactions of the optically active selenols derived from monoterpenes

A convenient methodology for the synthesis of optically active selenols, derived from p-menthane, carane, and pinane, is described. The selenols were oxidized with air to give the optically active diselenides, and were also converted into the corresponding allylic selenides via reaction with Z- and E-cinnamyl, geranyl, and neryl chlorides. Oxidation of the allylic selenides with mCPBA gave the optically active alcohols via [2,3]-sigmatropic rearrangement of the in situ generated allylic selenoxides.     

Lewis acid-catalyzed oxidative rearrangement of tertiary allylic alcohols mediated by TEMPO

Two methods for the oxidative rearrangement of tertiary allylic alcohols have been developed. Most of tertiary allylic alcohols studied were oxidized to their corresponding transposed carbonyl derivatives in excellent to fair yields by reaction with TEMPO in combination with PhIO and Bi(OTf)₃ or copper (II) chloride in the presence or not of oxygen. Other primary oxidants of TEMPO such as PhI(OAc)₂, mCPBA, and Oxone^® were unsatisfactory giving the enone in modest to low yields.     

PhI- and polymer-supported PhI-catalyzed oxidative conversion of ketones and alcohols to α-tosyloxyketones with m-chloroperbenzoic acid and p-toluenesulfonic acid

Various ketones were converted to the corresponding α-tosyloxyketones with mCPBA and p-toluenesulfonic acid in the presence of a catalytic amount of iodobenzene. Moreover, secondary alcohols were directly converted to the corresponding α-tosyloxyketones using mCPBA and catalytic amounts of iodobenzene and potassium bromide, followed by treatment with p-toluenesulfonic acid in a one-pot manner. Poly(4-iodostyrene) could be also used as a recyclable catalyst for the same α-tosyloxylation of ketone     

Stereoselective synthesis and transformations of pinane-based 1,3-diaminoalcohols

A library of pinane-based 1,3-diaminoalcohols and 5-aminomethyloxazolidin-2-ones was developed from commercially available (1R)-(?)-myrtenol which was transformed to N-trichloroacetyl protected allyl amine via Overmann rearrangement followed by stereoselective epoxidation with mCPBA resulting in key intermedier epoxy-amine. In order to obtain the diaminoalcohol moiety, aminolysis and azidolysis of the oxirane ring was performed. The cleavage of the oxirane ring proceeded regioselectively, affording N-trichloroacetyl protected 1,3-diaminoalcohols and oxazolidin-2-ones, which were obtained also via a thermal cyclisation. Since N deprotection of diaminoalcohols was unsuccessful under varied conditions, the protecting group was changed and Boc-protected analogues were synthesised. In this case, removal of the Boc protecting group was successful resulting in the planned diamino alcohols. An unexpected extreme δ Me_α-9 value (0.11 ppm) was measured for the dibenzylaminomethyl-substituted oxazolidine-2-one, and the stereostructure was refined by means of DFT geometry optimization. The obtained potential catalysts were applied in the test reaction of benzaldehyde and diethylzinc with low to moderate enantioselectivities (up to 74% ee).     

Reactivity of TEMPO anion as a nucleophile and its applications for selective transformations of haloalkanes or acyl halides to aldehydes

Sodium 2,2,6,6-tetramethylpiperidine-N-oxide (TEMPO⁻Na⁺), generated by reduction of TEMPO· with sodium naphthalenide in THF, reacted with alkyl halides or acyl halides to produce O-alkylated or acylated TEMPOs, which were in turn oxidized with mCPBA or reduced with DIBAL-H to afford the corresponding aldehydes, thus accomplishing a new protocol for the halides-carbonyls conversion.     

Desulfonyloxyiodination of arenesulfonic acids with mCPBA and molecular iodine

Treatment of p-alkylbenzenesulfonic acids with mCPBA and molecular iodine gave p-alkyliodobenzenes in good to moderate yields via electrophilic ipso-substitution by the iodonium species (I⁺) formed. This desulfonyloxyiodination was promoted by the addition of a catalytic amount of iodoarenes, such as o-iodobenzoic acid. The same treatment of dimethylbenzenesulfonic acids and trimethylbenzenesulfonic acids with mCPBA and molecular iodine proceeded smoothly both in the absence and in the presence of o-iodobenzoic acid to provide the corresponding monoiodo-dimethylbenzene and diiodo-dimethylbenzene, and diiodo-trimethylbenzene and triiodo-trimethylbenzene, in good to moderate yields, respectively. On the other hand, the same desulfonyloxyiodination of benzenesulfonic acid and p-chlorobenzenesulfonic acid with mCPBA and molecular iodine proceeded only in the presence of o-iodobenzoic acid to generate iodobenzene and p-chloroiodobenzene, respectively, in moderate yields.     

A novel preparation of chlorophospholenium chlorides and their application in the synthesis of phospholene boranes

A novel preparation of 1-chloro-3-methyl-3-phospholenium chlorides was developed by reacting 1-substituted-3-methyl-3-phospholene 1-oxides with oxalyl chloride. The obtained cyclic chlorophosphonium salts were reacted with LiBH₄ to afford the corresponding 1-substituted-3-methyl-3-phospholene boranes. The latter protocol involves a silane-free deoxygenation, and borane complex formation. In one instance, a 2-phospholene borane and the corresponding P-oxide were synthesized via rearrangement of the double bond in the cyclic chlorophosphonium salt. This double bond migration was investigated by quantum chemical calculations.     

Hypervalent Iodine Catalyzed Cyclization of Aryl‐Substituted Alkanoic Acids

A novel and efficient procedure was developed for direct preparation of aryl‐substituted lactones from corresponding aryl‐substituted alkanoic acids, catalyzed by the in situ generated hypervalent iodine intermediate from iodobenzene (PhI). In this protocol, aryl‐substituted alkanoic acids were treated with m‐chloroperbenzoic acid (mCPBA) and KBr in the presence of a catalytic amount of PhI in 2,2,2‐trifluoroethanol at room temperature for 24 h, resulting in corresponding aryl lactones in moderate‐to‐good yields.     

A convenient separation of ursolic and oleanolic acid

A convenient route has been developed to separate regioisomeric ursolic and oleanolic acid by treating the mixture with mCPBA or formic acid/hydrogen peroxide.     

Deconstructive Oxygenation of Unstrained Cycloalkanamines

A deconstructive oxygenation of unstrained primary cycloalkanamines has been developed for the first time using an auto‐oxidative aromatization promoted C(sp³)?C(sp³) bond cleavage strategy. This metal‐free method involves the substitution reaction of cycloalkanamines with hydrazonyl chlorides and subsequent auto‐oxidative annulation to in situ generate pre‐aromatics, followed by N‐radical‐promoted ring‐opening and further oxygenation by 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) and m‐cholorperoxybenzoic acid (mCPBA). Consequently, a series of 1,2,4‐triazole‐containing acyclic carbonyl compounds were efficiently produced. This protocol features a one‐pot operation, mild reaction conditions, high regioselectivity and ring‐opening efficiency, broad substrate scope, and is compatible with alkaloids, osamines, and peptides, as well as steroids.     

Synthesis of imidazo[1,2a]pyridines via three-component reaction of 2-aminopyridines, aldehydes and alkynes

A novel three-component reaction towards the synthesis of imidazo[1,2a]pyridines was independently developed based on 2-aminopyridines, aldehydes and alkynes, and thereby imidazo[1,2a]pyridines were obtained in acceptable yields by the CuSO4/TsOH catalyzed three-component reaction.     

Fast and Efficient Synthesis of Sulfinamides by the Oxidation of Sulfenamides Using Potassium Fluoride and m-Chloroperoxybenzoic Acid

A procedure for the synthesis of N-alkyl-, N-cycloalkyl-, N,N-dialkyl-, and N-arylarenesulfinamides from the corresponding sulfenamides using KF/m–chloroperoxybenzoic acid (CPBA) in CH₃CN-H₂O is described. High efficiency (fast reactions, ease of manipulation, and good yields) and absence of overoxidation are the major advantageous features of this protocol.     

Efficient construction of polycyclic chromans through 4-methylbenzenesulfonic acid mediated domino 1,6-addition/oxa-Mannich reaction of ortho-hydroxyphenyl substituted para-quinone methides and cyclic enamides

A practical TsOH promoted novel domino 1,6-addition/oxa-Mannich reaction of cyclic enamides and ortho-hydroxyphenyl substituted para-quinone methides was established smoothly under mild reaction conditions. With this developed protocol, sorts of polycyclic compounds with chroman motifs were obtained in high level of yields and moderate to excellent diastereoselectivities (up to >99% yield, >20:1 dr).     

Application of p-TSA in the one pot synthesis of N-methyl-3-nitro-aryl-benzo[4,5]imidazo[1,2-a]pyrimidin-2-amine

A simple, efficient, eco-friendly, and cost-effective method has been developed for the synthesis of N-methyl-3-nitro-aryl-benzo[4,5]imidazo[1,2-a]pyrimidin-2-amine derivatives using 2-aminobenzimidazole, aldehydes and (E)-N-methyl-1-(methylthio)-2-nitroethenamine, in the presence of catalytic amount of p-toluenesulfonic acid (p-TSA) in ethanol at 80?°C conditions. The advantages of this method are the use of an inexpensive and readily available catalyst, shorter reaction times, a wide range of functional group tolerance, and high yield of products via a simple experimental and work-up procedure.     

Asymmetric synthesis of N,O-diprotected (2S,3S)-N-methyl-δ-hydroxyisoleucine,noncoded amino acid of halipeptin A

The first enantioselective synthesis of N,O-diprotected (2S,3S)-N-methyl-δ-hydroxyisoleucine 4, starting from readily available (tert-butyldimethylsilyl)-2-butyn-1-ol 5, is described. The key steps of this stereochemical flexible synthetic route involve a silyl-assisted [3,3]-sigmatropic rearrangement, for the establishment of the correct stereoisomeric pattern, and a triethylsilane–TFA induced reduction of an oxazolidinone intermediate, to yield the requested N-methylation.     

α-Oxoketene dithioacetal mediated aromatic annulation: highly efficient and concise synthetic routes to potentially carcinogenic polycyclic aromatic hydrocarbons

Highly efficient regiospecific routes to potentially carcinogenic polycyclic aromatic hydrocarbons such as substituted benzo[c]phenanthrenes, benzo[c]fluorenes, 16,17-dihydro-11-methyl-15[H]cyclopenta[a]phenanthrene, 5-methyl-7,8,9,10-tetrahydrochrysene and 1,4-dimethylphenanthrene have been developed. The overall strategy involves our aromatic annulation protocol through base induced conjugate addition-elimination on the cyclic and acyclic α-oxoketene dithioacetals with the appropriate arylacetonitriles followed by acid induced cyclodehydration of the resulting conjugate adducts. Subsequent reductive dethiomethylation (Raney Ni) and dehydrogenation (DDQ) of the cyclized products affords the methyl substituted PAHs in high yields.     

p-TSA-catalyzed facile and efficient one-pot eco-friendly synthesis of novel isoxazolyl amino furo[3,2-c]quinolinone derivatives in aqueous medium

A green and operationally simple approach for the synthesis of novel isoxazolyl amino furo[3,2-c]quinolinone derivatives by a one-pot three-component reaction of 4-amino-3-methyl-5 styrylisoxazoles, aryl glyoxal monohydrates and 4-hydroxy-1-methyl-2-quinolinone using p-TSA as the catalyst in aqueous medium was developed. The protocol proves to be an efficient and an environmentally benign in terms of high yields, operational simplicity, clean reaction profile, compatibility with wide range of substrates, water as a solvent and easy purification.