Desymmetrization of N‐Sulfonated Aziridines by Alkyllithium Reagents in the Presence of Chiral Ligands

The stereochemical course of the rearrangement of the N‐sulfonylaziridines 5, 15 , and 25 in the presence of s‐BuLi/(?)‐sparteine to the bicyclic sulfonamides 4, 16 , and 17 , respectively, has been investigated chemically and by X‐ray structure analysis. The absolute configurations of the products were, in all cases, opposite to those of the alcohols formed upon rearrangement of the corresponding epoxides. Similarily, the allylic sulfonamide 10 , resulting from rearrangement of 7‐[(4‐methylphenyl)sulfonyl]‐7‐azabicyclo[4.1.0]heptane ( 7 ) under the same reaction conditions, had the (R)‐configuration, while cyclohexen‐3‐ol, obtained upon rearrangement of cyclohexene oxide, is known to be (S)‐configured. Deuterium labelling showed that the rearrangement of 7 proceeds via enantioselective α‐elimination to a carbene, which undergoes a 1,2‐H shift.     

An Unusual Rearrangement and its Dependence on Configuration

In the course of a synthetic study, we encountered an unusual rearrangement that we now report, one that involves a 5‐nitronorbornenyl system having 7‐endo‐ and 7‐exo‐pyridin‐2‐yl groups being treated under Nef‐reaction conditions. The stereoisomers differ in their Nef‐reaction behavior: the isomer with the pyridin‐2‐yl group exo to the NO₂ moiety primarily affords the Nef reaction, however, with formation of a rather unusual rearrangement side‐product. The endo‐pyridyl stereoisomer proceeded exclusively with rearrangement.     

Kinetic and thermodynamic control in the cyclization via thiiranium ions. Stereoselective synthesis of a 2,3,5‐trisubstituted tetrahydropyran ring

The stereoselective rearrangement of tetrahydrofuran or tetrahydropyran rings having a phenylsulfanyl group in an exo position, via the intermediate thiiranium ions, is reported. The 5‐ or 6‐exo‐tet cyclization of hydroxy sulfides gave the kinetic products while the 6‐endo‐tet or 5‐endo‐tet gave the thermodynamic products. The rearrangement of the 5‐exo product to the 6‐endo‐ one is an interesting way for the stereoselective synthesis of substituted tetrahydropyrans.     

Thermally induced intramolecular oxygen migration of N‐oxides in atmospheric pressure chemical ionization mass spectrometry

N‐Oxides are known to undergo three main thermal degradation reactions, namely deoxygenation, Cope elimination (for N‐oxides containing a β‐hydrogen) and Meisenheimer rearrangement, in atmospheric pressure chemical ionization mass spectrometry (APCI‐MS). The ions corresponding to these thermal degradants observed in the ensuing APCI mass spectra have been used to identify N‐oxides as well as to determine the N‐oxidation site when the analyte contains multiple tertiary amine groups. In this paper, we report a thermally induced oxygen migration from one N‐oxide amine to another tert‐amine group present in the same molecule through a six‐membered ring transition state during APCI‐MS analysis. The observed intramolecular oxygen migration resulted in the formation of a new isomeric N‐oxide, rendering the results of the APCI‐MS analysis more difficult to interpret and potentially misleading. In addition, we observed novel degradation behavior that happened after the Meisenheimer rearrangement of the newly formed N‐oxide: a homolytic cleavage of the N? O bond instead of elimination of an aldehyde or a ketone that usually follows the rearrangement. Understanding of these unusual degradation pathways, which have not been reported previously, should facilitate structural elucidation of N‐oxides using APCI‐MS analysis. Copyright © 2010 John Wiley & Sons, Ltd.     

A Complete Active Space Self‐Consistent Field (CASSCF) Study of the Reaction Mechanism of the α‐Alkynone Rearrangement

The pyrolytic rearrangement of α‐alkynones has been discovered by Karpf and Dreiding [1] in 1979. The mechanism of this reaction, which involves an acetylene‐vinylidene rearrangement followed by cyclization of the intermediate vinylidene carbene by insertion into a β‐C−H bond, has been debated in a couple of theoretical investigations. Restricted Hartree‐Fock (RHF) and single‐point Møller‐Plesset 2 (MP2) calculations at the RHF geometries apparently indicate the carbene cyclization to be the rate‐determining step, contrary to chemical intuition. However, larger‐scale correlated calculations with completely optimized molecular geometries ((8,8) CASSCF/6‐311G**), augmented with a perturbative account for the dynamic correlation contribution to the electronic energy, show vanishing energy barriers to the cyclization step and large activation energies for the acetylene‐vinylidene rearrangement, which is thus confirmed as the rate‐determining step of the title reaction.     

Synthesis of Cryptolepine and Cryptoteckieine from a Common Intermediate

Both cryptolepine 1 and cryptotackieine 3 have been synthesized from 1,3‐bis(2‐nitrophenyl)propan‐2‐one. The approach to 1 involved reduction of the NO₂ groups, oxidative cyclization with PhI(OAc)₂, and N‐methylation, whereas 3 was obtained via bromination, Favorskii rearrangement, reduction (in situ cyclization), and N‐methylation.     

Sulfonamide bond cleavage in benzenesulfonamides and rearrangement of the resulting p‐aminophenylsulfonyl cations: application to a 2‐pyrimidinyloxybenzylaminobenzenesulfonamide herbicide

The gas‐phase fragmentation/rearrangement reactions of compound 1, [2‐(4,6‐dimethoxypyrimidin‐2‐yloxy)‐benzyl]‐[4‐(piperidine‐1‐sulfonyl)phenyl]amine, have been examined by Fourier transform ion cyclotron resonance mass spectrometry (FTICR‐MS). The analyses reveal that under sustained off‐resonance irradiation collision‐induced dissociation (SORI‐CID) conditions in the FTICR cell, protonated 1 undergoes two competitive pathways initiated by different protonation positions. The first pathway is initiated by protonation on the amino group and yields only one fragment ion due to loss of the entire benzenesulfonamide moiety. In the second pathway, protonation of the sulfonamide group leads to cleavage of a sulfonamide bond with loss of the neutral piperidine, followed by loss of SO via a sulfonyl cation rearrangement. An intramolecular S_NAr mechanism is proposed to rationalize the rearrangement of the p‐aminophenylsulfonyl cation and the resulting SO loss. To test the generality of this process, SORI‐CID spectra of protonated sulfamethoxazole and of the p‐aminophenylsulfonyl cation (SBN) were obtained. For the SBN ion, SORI‐CID experiments as well as density functional theory (B3LYP) calculations show that rearrangement, assigned as a S_NAr reaction of the sulfonyl cation group, can account for the observed SO loss process. Candidate transition state structures were optimized at the B3LYP/6‐31+G (d, p) level of theory using the Gaussian98 molecular modeling package. The computational results show that the barrier for SO loss from SBN is much lower than that for SO₂ loss, which satisfactorily rationalizes the SORI‐CID experimental results for SBN. Moreover, it is proposed that a fragment ion at m/z 196 in the MS/MS spectrum of protonated 1 is formed via the ion resulting from SO loss via a second intramolecular S_NAr mechanism. Copyright © 2005 John Wiley & Sons, Ltd.     

Competitive Gold‐Promoted Meyer–Schuster and oxy‐Cope Rearrangements of 3‐Acyloxy‐1,5‐enynes: Selective Catalysis for the Synthesis of (+)‐(S)‐γ‐Ionone and (−)‐(2S,6 R)‐cis‐γ‐Irone

We report a simple, highly stereoselective synthesis of (+)‐(S)‐γ‐ionone and (‐)‐(2S,6R)‐cis‐γ‐irone, two characteristic and precious odorants; the latter compound is a constituent of the essential oil obtained from iris rhizomes. Of general interest in this approach are the photoisomerization of an endo trisubstituted cyclohexene double bond to an exo vinyl group and the installation of the enone side chain through a [(NHC)Au^I]‐catalyzed Meyer–Schuster‐like rearrangement. This required a careful investigation of the mechanism of the gold‐catalyzed reaction and a judicious selection of reaction conditions. In fact, it was found that the Meyer–Schuster reaction may compete with the oxy‐Cope rearrangement. Gold‐based catalytic systems can promote either reaction selectively. In the present system, the mononuclear gold complex [Au(IPr)Cl], in combination with the silver salt AgSbF₆ in 100:1 butan‐2‐one/H₂O, proved to efficiently promote the Meyer–Schuster rearrangement of propargylic benzoates, whereas the digold catalyst [{Au(IPr)}₂(μ‐OH)][BF₄] in anhydrous dichloromethane selectively promoted the oxy‐Cope rearrangement of propargylic alcohols.     

Synthesis of Highly Substituted Cyclobutane Fused‐Ring Systems from N‐Vinyl β‐Lactams through a One‐Pot Domino Process

In this contribution, aminocyclobutanes, as well as eight‐membered enamide rings, have been made from N‐vinyl β‐lactams. The eight‐membered products have been formed by a [3,3]‐sigmatropic rearrangement, whereas the aminocyclobutanes have been derived from a domino [3,3]‐rearrangement/6π‐electrocyclisation process. The aminocyclobutanes have been obtained in a highly diastereoselective fashion. The cyclobutane ring system tolerates fusion even if adjacent quaternary centres are present. Systems containing up to four fused rings are readily accessible. The reaction profile has been investigated by using Gaussian 03. This study suggests that two reaction pathways for aminocyclobutane formation are possible. In one pathway the [3,3]‐sigmatropic rearrangement is the rate‐limiting step and in the second pathway the electrocyclisation is rate limiting. Taken together, these reactions should facilitate the construction of fused heterocycles.     

Fragmentation of oxime and silyl oxime ether odd‐electron positive ions by the McLafferty rearrangement: new insights on structural factors that promote α,β fragmentation

The McLafferty rearrangement is an extensively studied fragmentation reaction for the odd‐electron positive ions from a diverse range of functional groups and molecules. Here, we present experimental and theoretical results of 12 model compounds that were synthesized and investigated by GC‐TOF MS and density functional theory calculations. These compounds consisted of three main groups: carbonyls, oximes and silyl oxime ethers. In all electron ionization mass spectra, the fragment ions that could be attributed to the occurrence of a McLafferty rearrangement were observed. For t‐butyldimethylsilyl oxime ethers with oxygen in a β‐position, the McLafferty rearrangement was accompanied by loss of the t‐butyl radical. The various mass spectra showed that the McLafferty rearrangement is relatively enhanced compared with other primary fragmentation reactions by the following factors: oxime versus carbonyl, oxygen versus methylene at the β‐position and ketone versus aldehyde. Calculations predict that the stepwise mechanism is favored over the concerted mechanism for all but one compound. For carbonyl compounds, C–C bond breaking was the rate‐determining step. However, for both the oximes and t‐butyldimethylsilyl oxime ethers with oxygen at the β‐position, the hydrogen transfer step was rate limiting, whereas with a CH₂ group at the β‐position, the C–C bond breaking was again rate determining. n‐Propoxy‐acetaldehyde, bearing an oxygen atom at the β‐position, is the only case that was predicted to proceed through a concerted mechanism. The synthesized oximes exist as both the (E)‐ and (Z)‐isomers, and these were separable by GC. In the mass spectra of the two isomers, fragment ions that were generated by the McLafferty rearrangement were observed. Finally, fragment ions corresponding to the McLafferty reverse charge rearrangement were observed for all compounds at varying relative ion intensities compared with the conventional McLafferty rearrangement. Copyright © 2012 John Wiley & Sons, Ltd.     

Studies on Sequential Claisen Rearrangement: Charge‐Accelerated [3,3]‐Sigmatropic Rearrangement Leading to Polyheterocycles

A number of quinolone‐annulated pentacycles have been regioselectively synthesized in 90–95% yields by sequential Claisen rearrangements. The second synthesis is anhydrous AlCl₃‐catalyzed charge‐accelerated aromatic Claisen rearrangement of 1‐aryloxymethyl‐6‐alkyl‐3H‐pyrano[2,3‐c]quinolin‐5(6H)‐ones in dichloromethane at rt for 5–10 min. The precursors were synthesized by the thermal [3,3]‐sigmatropic rearrangement of the corresponding ethers.     

Asymmetric Catalytic Formal 1,4‐Allylation of β,γ‐Unsaturated α‐Ketoesters: Allylboration/Oxy‐Cope Rearrangement

A highly enantioselective formal conjugate allyl addition of allylboronic acids to β,γ‐unsaturated α‐ketoesters has been realized by employing a chiral Ni^II/N,N′‐dioxide complex as the catalyst. This transformation proceeds by an allylboration/oxy‐Cope rearrangement sequence, providing a facile and rapid route to γ‐allyl‐α‐ketoesters with moderate to good yields (65–92 %) and excellent ee values (90–99 % ee). The isolation of 1,2‐allylboration products provided insight into the mechanism of the subsequent oxy‐Cope rearrangement reaction: substrate‐induced chiral transfer and a chiral Lewis acid accelerated process. Based on the experimental investigations and DFT calculations, a rare boatlike transition‐state model is proposed as the origin of high chirality transfer during the oxy‐Cope rearrangement.     

Pressure‐Induced Bond Rearrangement and Reversible Phase Transformation in a Metal–Organic Framework

Pressure‐induced phase transformations (PIPTs) occur in a wide range of materials. In general, the bonding characteristics, before and after the PIPT, remain invariant in most materials, and the bond rearrangement is usually irreversible due to the strain induced under pressure. A reversible PIPT associated with a substantial bond rearrangement has been found in a metal–organic framework material, namely [tmenH₂][Er(HCOO)₄]₂ (tmenH₂²⁺=N,N,N′,N′‐tetramethylethylenediammonium). The transition is first‐order and is accompanied by a unit cell volume change of about 10 %. High‐pressure single‐crystal X‐ray diffraction studies reveal the complex bond rearrangement through the transition. The reversible nature of the transition is confirmed by means of independent nanoindentation measurements on single crystals.     

A One‐Pot Cross‐Pinacol Coupling/Rearrangement Procedure

A new catalytic retro‐pinacol/cross‐pinacol reaction, followed by subsequent rearrangement or deoxygenation of the intermediately formed vicinal diols, is described. This operationally simple one‐pot protocol allows isolation of geminal α,α‐diphenyl ketones or 1,1‐diphenyl alkenes with high yields and selectivities.     

The unexpected rearrangement of 1,5‐benzodiazepin‐2,4‐dione to a benzimidazol‐2‐one derivative during N,N'‐diglucosylation

Reaction of 1,5‐benzodiazepin‐2,4‐dione with 3‐O‐substituted‐5,6‐anhydro‐1,2‐isopropylidene‐α‐D‐glucofuranose gave the unexpected N,N'‐di‐glucofuranosyl benzimidazol‐2‐one by a novel rearrangement and ring closure reaction. A mechanism is proposed.     

A New Zincate‐Mediated Rearrangement Reaction of 2‐(1‐Hydroxyalkyl)‐1‐alkylcyclopropanol

A novel rearrangement of 2‐(1‐hydroxyalkyl)‐1‐alkylcyclopropanol has been found. It proceeds in the presence of a catalytic amount of organozinc ate complex to give vic‐diols. The rearrangement can be applied to various types of 2‐(1‐hydroxyalkyl)‐1‐alkylcyclopropanol, which can be easily prepared from the corresponding α,β‐epoxyketones and bis(iodozincio)methane. When bicyclo[13.1.0]pentadecane‐1,15‐diol was treated with the organozinc ate complex, the corresponding 14‐membered cyclic vic‐diol was obtained. Thus, this rearrangement is also useful for changing the ring size of cyclic substrates.     

Generation and Rearrangement of N,O‐Dialkenylhydroxylamines for the Synthesis of 2‐Aminotetrahydrofurans

A new diastereoselective route to 2‐aminotetrahydrofurans has been developed from N,O‐dialkenylhydroxylamines. These intermediates undergo a spontaneous C?C bond‐forming [3,3]‐sigmatropic rearrangement followed by a C?O bond‐forming cyclization. A copper‐catalyzed N‐alkenylation of an N‐Boc‐hydroxylamine with alkenyl iodides, and a base‐promoted addition of the resulting N‐hydroxyenamines to an electron‐deficient allene, provide modular access to these novel rearrangement precursors. The scope of this de novo synthesis of simple nucleoside analogues has been explored to reveal trends in diastereoselectivity and reactivity. In addition, a base‐promoted ring‐opening and Mannich reaction has been discovered to covert 2‐aminotetrahydrofurans to cyclopentyl β‐aminoacid derivatives or cyclopentenones.     

Studies toward the Synthesis of (R)‐(+)‐Harmicine

The study toward the total synthesis of (R)‐(+)‐harmicine is reported in this paper. The enantioselective synthesis of pyrrolidinone, the main backbone of of (R)‐(+)‐harmicine, has been completed by the methodology based on photo‐induced Wolff rearrangement of α‐diazo‐β‐carbonyl compounds.     

The Baylis–Hillman Adducts as Valuable Source for One‐Pot Multi‐Step Synthesis: A Facile Synthesis of Substituted Piperidin‐2‐ones

A facile, convenient, and one‐pot multi‐step synthesis of substituted piperidin‐2‐ones from the Baylis–Hillman alcohols derived from various aldehydes and acrylonitrile, involving Johnson–Claisen rearrangement, reduction of an α,β‐unsaturated nitrile moiety into the saturated amine‐skeleton, followed by cyclization, in an operationally simple procedure, is described.     

Pinacol Rearrangement of 3,4‐Dihydro‐3,4‐dihydroxyquinolin‐2(1H)‐ones: An Alternative Pathway to Viridicatin Alkaloids and Their Analogs

3‐Alkyl/aryl‐3‐hydroxyquinoline‐2,4‐diones were reduced with NaBH₄ to give cis‐3‐alkyl/aryl‐3,4‐dihydro‐3,4‐dihydroxyquinolin‐2(1H)‐ones. These compounds were subjected to pinacol rearrangement by treatment with concentrated H₂SO₄, resulting in 4‐alkyl/aryl‐3‐hydroxyquinolin‐2(1H)‐ones. When a benzyl (Bn) group was present in position 3 of the starting compound, its elimination occurred during the rearrangement, and the corresponding 3‐hydroxyquinolin‐2(1H)‐one was formed. The reaction mechanisms are discussed for all transformations. All compounds were characterized by IR, ¹H‐ and ¹³C‐NMR spectroscopy, as well as mass spectrometry.