Ring-expansion of tertiary cyclic alpha-vinylamines by tandem conjugate addition to (p-toluenesulfonyl)ethyne and formal 3-aza-Cope rearrangement

A novel ring-expansion protocol is based on the conjugate additions of cyclic alpha-vinylamines to (p-toluenesulfonyl)ethyne, followed by aza-Cope rearrangements of the resulting zwitterions, to afford medium and large-ring cyclic amines under remarkably mild conditions.     

Stereospecific rearrangements during the synthesis of pyrrolidines and related heterocycles from cyclizations of amino alcohols with vinyl Sulfones

Conjugate additions of amino alcohols derived from alpha-amino acids to vinyl sulfones, followed by N-benzylation, chlorination, and intramolecular alkylation, provide a convenient route to substituted pyrrolidines. The process is accompanied by the stereospecific rearrangement of substituents from the alpha-position of the amine to the beta-position of the product and takes place via the corresponding aziridinium ion intermediates. Another type of rearrangement was observed during the reaction of (2-piperidine)methanol or 2-(2-piperidine)ethanol with phenyl trans-1-propenyl sulfone, in which the methyl group appears to migrate from the beta- to the alpha-position of the sulfone moiety. This process involves the isomerization of phenyl trans-1-propenyl sulfone to phenyl 2-propenyl sulfone by the addition-elimination of catalytic benzenesulfinate anion to the former vinyl sulfone, followed by conjugate addition of the amino group to the latter sulfone. Chlorination and intramolecular alkylation then afford the corresponding rearranged indolizidine and quinolizidine derivatives, respectively.     

An atom efficient route to N-aryl and N-alkyl pyrrolines by transition metal catalysis

The synthesis of N-aryl, N-tosyl, and N-alkyl pyrrolines from allyl alcohols and amines has been developed. The reaction sequence includes a palladium-catalyzed allylation step in which non-manipulated allyl alcohol is used to generate the diallylated amine in good to excellent yield. An excess of allyl alcohol was necessary for efficient diallylation of the amine, where the excess alcohol could be recycled three times. For aryl and tosyl amines, Pd[P(OPh)(3)](4) was used and for benzyl and alkyl amines a catalytic system comprising Pd(OAc)(2), P(n)Bu(3), and BEt(3) was used. Both the electronic properties and the steric influence of the amine affected the efficiency of the allylation. The isolated diallylated amines were transformed into their corresponding pyrrolines by ring-closing metathesis catalyzed by (H(2)IMes)(PCy(3))Cl(2)RuCHPh in good to excellent yield. A one-pot reaction was developed in which aniline was transformed into the corresponding pyrroline without isolating the diallylated intermediate. This one-pot reaction was successfully scaled-up to 1 mL of aniline in which the N-phenyl pyrroline was isolated in 95% yield. The versatility of the reaction in which 3-methyl-1-phenyl pyrroline was prepared in two-steps was demonstrated.     

Copper‐Catalyzed Cyclization/aza‐Claisen Rearrangement Cascade Initiated by Ketenimine Formation: An Efficient Stereocontrolled Synthesis of α‐Allyl Cyclic Amidines

An efficient and convenient synthesis of α‐allyl cyclic amidines has been achieved by applying a novel cascade reaction. Copper(I)‐mediated in situ N‐sulfonyl ketenimine formation from the reaction of a terminal alkyne with sulfonyl azide is followed by an intramolecular nucleophilic attack on the central carbon atom by an allylic tertiary amine, and then an aza‐Claisen rearrangement takes place through a chair transition state to furnish the titled amidines with complete stereocontrol.     

Chemical reaction kinetics measurements for single and blended amines for CO2 postcombustion capture applications

The present study has established the direct pseudo–first‐order reaction kinetics of different aqueous‐based single and blended amines over the temperature range of 298.15‐313.15 K using stopped‐flow techniques. The single amines include one primary amine (monoethanolamine, MEA), two secondary amines (diethanolamine, DEA and 2‐ethyl(amino)ethanol, 2EAE), four tertiary amines (N‐methyldiethanolamine, MDEA, 1‐dimethylamino‐2‐propanol, 1DMA2P, 3‐dimethylamino‐1‐propanol, 3DMA1P, and 2‐dimethylaminoethanol, 2DMAE), one sterically hindered amine (2‐amino‐2‐methyl‐1‐propanol, AMP), and one cyclic diamine (piperazine, PZ). The blend systems used are MEA/PZ, DEA/PZ, MDEA/PZ, AMP/PZ, MEA/AMP, MDEA/2EAE, 1DMA2P/2EAE, 3DMA1P/2EAE, and 2DMAE/2EAE. Different reaction mechanisms for the reaction of CO₂ with aqueous solutions of amines, such as base‐catalysis, zwitterion, termolecular, hybrid of zwitterion, hybrid of base‐catalysis‐zwitterion, and hybrid of base‐catalysis‐termolecular reaction mechanisms, are used to correlate the experimental data. For the single amines, the zwitterion mechanism is well suited to fit the experimental data of primary, secondary, sterically hindered and cyclic amines with an absolute average deviation (AAD%) less than 5%. The base‐catalysis mechanism fits the experimental data of all the tertiary amines well with an AAD less than 5%. For the blends, the hybrid of zwitterion mechanism fits the experimental data of MEA/PZ, DEA/PZ, AMP/PZ, and MEA/AMP well with an AAD less than 5%, whereas the hybrid of base‐catalysis‐zwitterion mechanism fits the experimental data of MDEA/PZ, MDEA/2EAE, 1DMA2P/2EAE, 3DMA1P/2EAE, and 2DMAE/2EAE well with an AAD less than 5%.     

Catalytic N-sulfonyliminium ion-mediated cyclizations to alpha-vinyl-substituted isoquinolines and beta-carbolines and applications in metathesis

[reaction: see text] Catalytic Sn(OTf)2-induced cyclization of linear, aryl-containing allylic N,O-acetals produced vinyl-substituted tetrahydroisoquinolines and tetrahydro-1H-beta-carbolines. The usefulness of the vinyl moiety in the resulting products was demonstrated via the synthesis of various key building blocks for alkaloid structures. The alpha-vinyl moiety was utilized in a [2,3] sigmatropic rearrangement, in ring-closing metathesis and a cross-metathesis-based synthesis of vincantril, an antianoxia agent, and a synthetic member of the vincamine type natural products.     

Palladium-Catalyzed Fluorinative Bifunctionalization of Aziridines and Azetidines with gem-Difluorocyclopropanes

An unprecedented Pd-catalyzed fluorinative bifunctionalization of aziridines and azetidines was successfully developed via regioselective C−C and C−F bond cleavage of gem-difluorocyclopropanes, leading to various β,β′-bisfluorinated amines and β,γ-bisfluorinated amines. This reaction was achieved by incorporating a 2-fluorinated allyl group and a fluorine atom scissored from gem-difluorocyclopropane in 100 % atom economy for the first time. The mechanistic investigations indicated that the reaction underwent amine attacking 2-fluorinated allyl palladium complex to generate η²-coordinated N-allyl aziridine followed by fluoride ligand transfer affording the final β- and γ-fluorinated amines.     

Ruthenium porphyrin catalyzed tandem sulfonium/ammonium ylide formation and [2,3]-sigmatropic rearrangement. A concise synthesis of (+/-)-platynecine

meso-Tetrakis(p-tolyl)porphyrinatoruthenium(II) carbonyl, [Ru(II)(TTP)(CO)], can effect intermolecular sulfonium and ammonium ylide formation by catalytic decomposition of diazo compounds such as ethyl diazoacetate (EDA) in the presence of allyl sulfides and amines. Exclusive formation of [2,3]-sigmatropic rearrangement products (70-80% yields) was observed without [1,2]-rearrangement products being detected. The Ru-catalyzed reaction of EDA with disubstituted allyl sulfides such as crotyl sulfide produced an equimolar mixture of anti- and syn-2-(ethylthio)-3-methyl-4-pentenoic acid ethyl ester. The analogous "EDA + N,N-dimethylcrotylamine" reaction afforded a mixture of anti- and syn-2-(N,N-dimethylamino)-3-methyl-4-pentenoic acid ethyl esters with a diastereoselectivity of 3:1. The observed catalytic activity of [Ru(II)(TTP)(CO)] for the ylide [2,3]-sigmatropic rearrangement is comparable to the reported examples involving [Rh(2)(CH(3)CO(2))(4)] and [Cu(acac)(2)] as catalyst. Similarly, cyclic sulfonium and ammonium ylides can be produced by intramolecular reaction of a diazo group tethered to allyl sulfides and amines under the [Ru(II)(TTP)(CO)]-catalyzed reaction conditions. The subsequent [2,3]-sigmatropic rearrangement of the cyclic ylides furnished 2-allyl-substituted sulfur and nitrogen heterocycles in good yields (>90%). By employing [Ru(II)(TTP)(CO)] as catalyst, the cyclic ammonium ylide [2,3]-sigmatropic rearrangement reaction was successfully applied for the total synthesis of (+/-)-platynecine starting from cis-2-butenediol.     

A general nickel-catalyzed hydroamination of 1,3-dienes by alkylamines: catalyst selection, scope, and mechanism

A simple colorimetric assay of various transition-metal catalysts showed that the combination of DPPF, Ni(COD)(2), and acid is a highly active catalyst system for the hydroamination of dienes by alkylamines to form allylic amines. The scope of the reaction is broad; various primary and secondary alkylamines react with 1,3-dienes in the presence of these catalysts. Detailed mechanistic studies revealed the individual steps involved in the catalytic process. These studies uncovered unexpected thermodynamics for the addition of amines to pi-allyl nickel complexes: instead of the thermodynamics favoring the reaction of a nickel allyl with an amine to form an allylic amine, the thermodynamics favored reaction of a nickel(0) complex with allylic amine in the presence of acid to form a Ni(II) allyl. The realization of these thermodynamics led us to the discovery that nickel and some palladium complexes in the presence or absence of acid catalyze the exchange of the amino groups of allylic amines with free amines. This exchange process was used to reveal the relative thermodynamic stabilities of various allylic amines. In addition, this exchange reaction leads to racemization of allylic amines. Therefore, the relative rate for C-N bond formation and cleavage influences the enantioselectivity of diene hydroaminations.     

Experimental and theoretical studies on the isomerization of allyl thiocyanate to allyl isothiocyanate

The mechanism of isomerization of allyl thiocyanate to allyl isothiocyanate has been investigated both experimentally and theoretically. The kinetic study indicates that the reaction is unimolecular and is not ionic. The entropy of activation suggests strongly that the mechanism involves a cyclic transition state. The rate of reaction was retarded to a small extent in polar solvents relative to that in nonpolar solvents. Ab initio MO calculations indicate, in agreement with the experimental results, that the reaction proceeds through a cyclic transition state, one in which the SCN moiety is almost linear. Thus, this is a [3,3] sigmatropic rearrangement. The charge separation in the transition state was substantial. The retardation of the reaction in polar solvents was attributed to the difference in solvation in the original state and in the transition state. © 1997 John Wiley & Sons, Inc.     

Cyclic amine initiation of polypivalolactone

Certain monocyclic and polycyclic tertiary amines initiate polymerization of, and copolymerize with, pivalolactone. These comprise three-, four-, and five-membered monocyclic amines and 1-azapolycyclic amines. The polymerization proceeds in three steps: (a) initiation to form a cyclic amine/pivalate betaine, (b) propagation to yield a polylactone zwitterion by an anionic mechanism, and (c) interlinking by a carboxylate end attacking a cyclic amine end to incorporate amine as a comonomer in the chain. When polymerization is carried out at low temperatures, the more stable cyclic amine ring systems yield isolatable step b polymers. These polymeric zwitterions undergo step c by heating, even in the solid state. The mechanism suggests that, for the more labile cyclic amines, a lactone could be the initiator for polyamine formation by a cationic mechanism. Interlinking would lead to incorporation of lactone initiator. In intermediate cases, block copolymers would result. With a proper balance of reactivities, 1:1 alternating copolymers would be possible.     

Further studies on vinamidinium salt amine exchange reactions, borohydride reductions and subsequent transformations

Studies directed at the amine exchange reaction of vinamidinium salts followed by sodium borohydride reduction to secondary and tertiary allylic amines are described. The tertiary allylic amines were alkylated and subjected to base mediated rearrangement to yield a variety of highly functionalized tertiary homoallylic amines.     

Dechalcogenative allylic selenosulfide and disulfide rearrangements: complementary methods for the formation of allylic sulfides in the absence of electrophiles. Scope, limitations, and application to the functionalization of unprotected peptides in aqueous media

Primary allylic selenosulfates (seleno Bunte salts) and selenocyanates transfer the allylic selenide moiety to thiols giving primary allylic selenosulfides, which undergo rearrangement in the presence of PPh3 with the loss of selenium to give allylically rearranged allyl alkyl sulfides. This rearrangement may be conducted with prenyl-type selenosulfides to give isoprenyl alkyl sulfides. Alkyl secondary and tertiary allylic disulfides, formed by sulfide transfer from allylic heteroaryl disulfides to thiols, undergo desulfurative allylic rearrangement on treatment with PPh3 in methanolic acetonitrile at room temperature. With nerolidyl alkyl disulfides this rearrangement provides an electrophile-free method for the introduction of the farnesyl chain onto thiols. Both rearrangements are compatible with the full range of functionality found in the proteinogenic amino acids, and it is demonstrated that the desulfurative rearrangement functions in aqueous media, enabling the derivatization of unprotected peptides. It is also demonstrated that the allylic disulfide rearrangement can be induced in the absence of phosphine at room temperature by treatment with piperidine, or simply by refluxing in methanol. Under these latter conditions the reaction is also applicable to allyl aryl disulfides, providing allylically rearranged allyl aryl sulfides in good yields.     

Metal‐Free Reaction of ortho‐Carbonylated Alkynyl‐Substituted Arylaldehydes with Common Amines: Selective Access to Functionalized Isoindolinone and Indenamine Derivatives

Herein we describe a reaction of ortho‐carbonylated alkynyl‐substituted arylaldehydes with common primary amines that can provide functionalized isoindolinone and 3‐hydroxylindenamine products in high yields. Depending on the substituent size of primary amines, two distinct reaction pathways were exploited selectively, that are, an initial aza‐conjugate addition followed by hydrogen transfer to access isoindolinone framework and a unique oxa‐conjugate addition followed by Petasis–Ferrier rearrangement to afford indenamine derivatives. In the presence of Et₃N, the reaction property of small primary amines was changed, proceeding to afford 3‐hydroxylindenamine derivatives efficiently. These products contain interesting substructures that exist in many natural products and bioactive molecules. The reaction features contain the use of transition‐metal‐free catalysts, simple operation, broad substrate scope, and product diversity.     

Stereocontrolled synthesis of cytotoxic anhydrosphingosine pachastrissamine by using [3.3] sigmatropic rearrangement of allyl cyanate

A new route for the synthesis of the cytotoxic anhydrosphingosine pachastrissamine has been developed. [3.3] Sigmatropic rearrangement of an allyl cyanate was employed to construct the allyl amine moiety in 2 from the chiral C-4 unit 3. Oxidative cleavage of the double bond in 2, followed by THF ring formation furnished the target pachastrissamine.     

Synthesis and decrosslinking of networked polymers having zwitterion structure consisted by cyclic amidine and isothiocyanate

We have already found that the polymers, which are obtained by the polymerization of 4‐vinylphenyl isothoiocyanate after the zwitterion formation with cyclic amidines, are networked through the ionic interaction among the zwitterions becoming insoluble to various solvents. We report here on the results of the reaction of nucleophilic reagents such as amines and alcohols with the zwitterionic adduct to investigate about the decrosslinking through the resolution of ionic interactions. In the model reactions of amines and alcohols with the zwitterion compounds, which were consisted of the phenyl isothiocyanate and cyclic amidines, the reaction of nucleophilic reagents and zwitterionic adducts having methyl group at the 2‐position of the amidine proceed quantitatively. Based on the model reaction, such nucleophilic addition was applicable to decrosslinking reaction of the networked polymers containing the zwitterion structure in the side‐chain. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2131–2137     

Kinetics of the reaction of carbon dioxide with blends of amines in aqueous media using the stopped‐flow technique

The effect of mixing 2‐amino‐2‐methyl‐1‐propanol (AMP) with a primary amine, monoethanolamine (MEA), and a secondary amine, diethanolamine (DEA), on the kinetics of the reaction with carbon dioxide in aqueous media has been studied at 298, 303, 308, and 313 K over a range of blend composition and concentration. The direct stopped‐flow conductimetric method has been used to measure the kinetics of these reactions. The proposed model representing the reaction of CO₂ with either of the blends studied is found to be satisfactory in determining the kinetics of the involved reactions. This model is based on the zwitterion mechanism for all the amines involved (AMP, MEA, and DEA). Blending AMP with either of the amines results in observed pseudo‐first‐order reaction rate constant values (k_o) that are greater than the sum of the k_o values of the respective pure amines. This is due to the role played by one amine in the deprotonation of the zwitterion of the other amine. Steric factor and basicity of the formed zwitterion and the deprotonating species have a great bearing in determining the rate of the reactions studied. © 2005 Wiley Periodicals, Inc. Int J Chem Kinet 37: 391–405, 2005     

The Cp2ZrCl2-catalyzed cycloalumination of functionally substituted olefins with triethylaluminum

Reactions of functionally substituted olefins (allylamines, sulfides and ethers, homoallylic alcohols and amines, as well as vinyl ethers) with Et₃Al in the presence of Cp₂ZrCl₂ as a catalyst were studied. Cycloalumination of allylamines occurs with high regioselectivity to furnish after subsequent deuterolysis 4-deutero-2-(deuteromethyl)butyl-substituted amines. Cycloalumination of alkyl allyl sulfide is accompanied by a side process of the C-S bond cleavage. In the case of allyl and vinyl ethers, no cycloalumination products are formed under the reaction conditions. However, the reactions with homoallylic alcohol and amine after deuterolysis gave the corresponding dideutero-containing compounds in good yields.     

Investigation of the Chemo- and Stereoselectivity of the Ketene-Claisen Rearrangement

A novel type of ketene-Claisen rearrangement in which the precursor of the rearrangement is generated in situ by reaction of optically active allyl thioethers with dichloroketene is described. A characteristic feature of this rearrangement is the excellent chemoselectivity in favor of allyl thioethers vs. allyl ethers, i.e., exclusive chirality transfer of the allylic sulfur moiety is observed with 12, 13 , and 25--27 . The cyclic, optically active allyl thioethers (+)-(R)- 4 and (?)-(S)- 4 and the open-chain allyl thioethers 11--13 rearrange with in situ generated dichloroketene to the optically active thioesters (?)-(S)- 28 , (+)-(R)- 28 , and 31-33 , respectively. A chirality-transfer of > 99% in the cyclic cases (+)-(R)- 4 and (?)-(S)- 4 , and 96--98 % in the open-chain cases 11--13 is observed. Furthermore, the dichloroketene-Claisen rearrangement is characterized by a high asymmetric 1,2-induction. The chiral allylic sulfides 25--27 give the optically active thioesters 36--38 with a 1,2-induction > 99% as determined by NMR-shift experiments.     

Hydrogen cyanide elimination and rearrangement upon electron-impact from schiff bases of benzaldehyde and aliphatic amines

The Schiff bases of benzaldehyde and aliphatic amines form immonium ions on electron-impact, which rearrange and eliminate hydrogen cyanide in a different way than the corresponding derivatives of pyridine-2-aldehyde. The presence of at least one hydrogen on the α-carbon atom in the amine moiety is a necessary condition for this rearrangement. A mechanism is suggested for this process.