Intramolecular Nucleophilic Substitution Reaction Research Articles

Surface-induced dissociation of singly and multiply protonated polypropylenamine dendrimers

The ease of fragmentation of various charge states of protonated polypropylenamine (POPAM) dendrimers is investigated by surface-induced dissociation. Investigated are the protonated diaminobutane propylenamines [DAB(PA) n ] DAB(PA) 8 (1+ and 2+), DAB(PA) 16 (2+ and 3+), and DAB(PA) 32 (3+ and 4+). These ions have been proposed to fragment by charge-directed intramolecular nucleophilic substitution (S Ni) reactions. Differences in relative fragment ion abundances between charge states can be related to the occupation of different protonation sites. These positions can be rationalized based on estimates of Coulomb energies and gas-phase basicities of the protonation/fragmentation sites. The laboratory collision energies at which the fragment ion current is ∼50% of the total ion current were found to increase with the size, but to be independent of charge state of the protonated POPAM dendrimers. It is suggested that intramolecular Coulomb repulsion within the multiply protonated POPAM dendrimers selected for activation does not readily result in easier fragmentation, which is in accordance with the proposed fragmentation mechanism.

Synthesis of Optically Active 5-(tert-Butyldimethylsiloxy)-2-cyclohexenone and Its 6-Substituted Derivatives as Useful Chiral Building Blocks for the Synthesis of Cyclohexane Rings. Syntheses of Carvone, Penienone, and Penihydrone

Optically active 5-(tert-butyldimethylsiloxy)-2-cyclohexenone (1) and its 6-substituted derivatives 2a,b were synthesized from the readily available optically active ethyl 3-(tert-butyldimethylsiloxy)-5-hexenoate (4), where the Ti(II)-mediated intramolecular nucleophilic acyl substitution reaction and the FeCl3-mediated ring expansion reaction of a 1-hydroxybicyclo[3.1.0]hexane are the key reactions. The enone 1 reacted with higher-order cyanocuprates with excellent diastereoselectivity to afford the trans-addition products, trans-13, in excellent yields. The reaction of 1 with lower-order cyanocuprates proceeded with moderate to excellent syn-selectivity to afford cis-13. Treatment of trans- and cis-13 with DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) or catalyst p-TSA (p-toluenesulfonic acid) resulted in a β-elimination reaction to furnish the corresponding optically active 5-substituted-2-cyclohexenones 14. The 1,4-addition reaction of 2a and 2b with organocyanocuprates followed by treatment of the resulti...

Stereospecificity in the Carbopalladations of Chiral Allenes Followed by Intramolecular Nucleophilic Substitution Reactions

Stereospecificity in the Carbopalladations of Chiral Allenes Followed by Intramolecular Nucleophilic Substitution Reactions

Efficient and practical method for synthesizing optically active γ-trityloxymethyl-α-alkylidene-γ-butyrolactones using Ti(II)-mediated intramolecular nucleophilic acyl substitution reaction

An efficient and highly stereoselective method for synthesizing optically active γ-trityloxymethyl-α-alkylidene-γ-butyrolactones having a stereodefined mono or disubstituted exocyclic double bond, starting from commercially available non-racemic glycidyl tritylether has been developed in which a titanium(II)-mediated intramolecular nucleophilic acyl substitution reaction is a key reaction.

２価チタン錯体を用いる合成反応

Treatment of Ti (O-i-Pr) 4 with 2 equiv of i-PrMgX (X =Cl or Br) provides (η2-propene) Ti (O-i-Pr) 2 in essentially quantitative yield. This new low-valent titanium complex nicely acts as a versatile titanium (II) equivalent to effect the following unique transformations. Thus, alkynes afforded titaniumalkyne complexes which, in turn, react with aldehydes, ketones, or imines to furnish the corresponding addition products. Allylic or propargylic compounds such as halides and alcohol derivatives gave allylic- or allenylic titanium species, which could be utilized in chemo- and diastereoselective reactions with carbonyl compounds. While acetylenic esters resulted in an intramolecular nucleophilic acyl substitution (INAS) reaction to provide unsaturated ketones, olefinic ones furnished cyclopropanols. 1, 6- or 1, 7-Dienes, enynes, and diynes underwent cyclometallation to give dialkoxytitanacycles, which show some distinctive reactivities among the metallacycles of early transition metal complexes. A few applications to natural product synthesis by taking advantage of these methods are also illustrated.

ChemInform Abstract: Efficient and Practical Method for Synthesizing N‐Heterocyclic Compounds Using Intramolecular Nucleophilic Acyl Substitution Reactions Mediated by Ti(O‐i‐Pr)4/2i‐PrMgX Reagent. Synthesis of Quinolones, Pyrroles, Indoles, and Optically Active N‐Heterocycles Including Allopumiliotoxin Alkaloid 267 A.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of (9R,12S)- and (9S,12S)-Cycloisodityrosine and Their N-Methyl Derivatives.

Full details of the synthesis of (9R,12S)- and (9S,12S)-cycloisodityrosine and their N-methyl derivatives are detailed based on an intramolecular nucleophilic aromatic substitution reaction for formation of the key biaryl ether with 14-membered ring macrocyclization. Their comparison with prior samples and the documentation of a facile C9 epimerization within the natural 9S series are described.

Effects of cyclodextrin on hydrolysis and the Smiles rearrangement of salicylic acid esters

The effect of β-cyclodextrin (β-CD) on “aqueous” hydrolysis of methyl,p-, andm-nitrophenyl salicylates as well as on the Smiles rearrangement ofp-nitrophenyl salicylate was studied. No effect of β-CD on the pH-independent rate constant of “aqueous” hydrolysis of methyl ester was observed, while β-CD accelerated “aqueous” hydrolysis of nitrophenyl esters byca. 10 times. The inclusion of these esters into the cavity of β-CD is accompanied by a change in the mechanism of hydrolysis: free ester in the deprotonated form undergoes hydrolysis through the mechanism of intramolecular general base catalysis, while the ester bound to cyclodextrin is hydrolyzed due to the nucleophilic attack of the deprotonated hydroxyl group of β-CD at a neutral substrate molecule. The effects of cyclodextrin on the rate constant of borate-catalyzed hydrolysis were interpreted by assuming that the substrate bound to β-CD undergoes borate-assisted attack at the deprotonated cyclodextrin hydroxyl group. The Smiles rearrangement, which is an intramolecular nucleophilic substitution reaction, is accelerated in the presence of β-CD.

ChemInform Abstract: Synthesis of 1‐Hydroxybicyclo(n.1.0)alkanes (n = 3 and 4) and Their Silyl Ethers from Olefinic Esters via Tandem Intramolecular Nucleophilic Acyl Substitution and Intramolecular Carbonyl Addition Reactions Mediated by Ti(O‐iPr)4/i‐Pr‐MgCl Reagent.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Synthesis of Allyltitanium Compounds by Intramolecular Nucleophilic Acyl Substitution Reaction of Alka‐3,5‐dienyl Carbonates and Their Unusual Regioselectivity in Reaction with Aldehydes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of the orienticin C M(2–4) macrocycle utilizing a nucleophilic aromatic substitution strategy

The synthesis of the fully functionalized M(2–4) macrocyclic orienticin C subunit 5 is described utilizing a intramolecular nucleophilic aromatic substitution reaction.

Synthesis of (9 S,12 S)-cycloisodityrosine and its unnatural (9 R,12 S)-diastereomer

A synthesis of the (9 S,12 S)-cycloisodityrosine derivatives and their unnatural (9 R,12 S)-diastereomers are disclosed. The approach is based on an intramolecular aromatic nucleophilic substitution reaction for formation of the macrocyclic biaryl ether and includes the documentation of a remarkably facile base-catalyzed epimerization.

Synthesis of 1-hydroxybicyclo[n.1.0]alkanes (n = 3 and 4) and their silyl ethers from olefinic esters via tandem intramolecular nucleophilic acyl substitution and intramolecular carbonyl addition reactions mediated by [formula omitted] reagent

Treatment of olefinic esters with Ti( OPr- i) 4/2 i- PrMgCl reagent resulted in intramolecular nucleophilic acyl substitution and successive intramolecular carbonyl addition reactions providing 1-hydroxybicyclo[n.1.0]alkanes ( n = 3 and 4) in high yields.

Synthesis of allyltitanium compounds by intramolecular nucleophilic acyl substitution reaction of alka-3,5-dienyl carbonates and their unusual regioselectivity in reaction with aldehydes

Treatment of carbonates of alka-3,5-dien-1-ols with (η2-propene)Ti(OPri)2 resulted in intramolecular nucleophilic acyl substitution (INAS) reaction to afford allyltitanium compounds containing lactone or ester moieties, which add regiospecifically to aldehydes.

Acyloxy-shifts in open and closed shell systems–intramolecular nucleophilic substitution reactions in disguise

The 1,3-acyloxy shift in allyl formate is compared to the 1,2-acyloxy-shift in the 2-formylethyl radical at various theoretical levels. The Becke3LYP hybrid density functional gives the best agreement with experiment. The barrier for the closed shell rearrangement is 22 to 27 kcal mol–1 higher than for the open shell transformation. Both reactions can be described as intramolecular nucleophilic substitution reactions, in which the formyloxy group functions as both the nucleophile and the leaving group. In the framework of the valence bond curve crossing model, the difference in the barriers is mainly due to the energy required to excite the CC double bond to the triplet state.

Intramolecular Nucleophilic Acyl Substitution Reaction of 3,4-Alkadienyl Carbonates Mediated by Ti(O-i-Pr)(4)/2 i-PrMgCl Reagent. Efficient Synthesis of Optically Active beta,gamma-Unsaturated Esters with an alpha-Substituent.

Treatment of 3,4-alkadienyl carbonates 2a-i with a low-valent titanium reagent diisopropoxy(eta(2)-propene)titanium (1), readily generated by the reaction of Ti(O-i-Pr)(4) with 2 i-PrMgCl, resulted in an intramolecular nucleophilic acyl substitution (INAS) reaction to afford vinyltitanium compounds 3 which, in turn, reacted with H(3)O(+), D(2)O, or iodine to give alpha-substituted beta,gamma-unsaturated esters 4 in good to excellent yields. The olefin moiety of the hydrolysis product 4 has (Z)-geometry mainly except for 4h. Starting from chiral 2f or 2g, the reaction proceeded stereospecifically to give optically active alpha-substituted beta,gamma-unsaturated ester 4f or 4g having (Z)-olefin geometry exclusively.

Intramolecular Nucleophilic Acyl Substitution Reactions Mediated by XTi(O-i-Pr)3 (X = Cl, O-i-Pr)/2i-PrMgBr Reagent. Efficient Synthesis of Functionalized Organotitanium Compounds from Unsaturated Compounds

Treatment of acetylenic or olefinic carbonates and esters with a low-valent titanium reagent diisopropoxy(η2-propene)titanium (1), readily generated by the reaction of Ti(O-i-Pr)4 or ClTi(O-i-Pr)3 with 2i-PrMgX, resulted in an intramolecular nucleophilic acyl substitution (INAS) reaction to afford organotitanium compounds having a carbonyl functional group, in good to excellent yields. Thus, the treatment of alkyl alkynyl carbonates 2 or alkyl alkenyl carbonates 4 with 1 gave organotitanium compounds having a lactone and/or ester group. Similarly, alkyl alkynoates 10 or alkynyl esters 14 of carboxylic acids reacted with 1 to give organotitanium compounds having a cyclic or acyclic ketone group, respectively. Thus, the reaction provides, after hydrolysis, five- or six-membered α-alkylidene lactones and/or α,β-unsaturated esters from 2, γ-butyrolactone derivatives from 4, five- or six-membered α-alkylidene cyclic ketones from 10, and acyclic α,β-unsaturated ketones 15 from 14. In all cases, the yields are excellent and the generation of the organotitanium compounds was confirmed by deuterolysis. The organotitaniums 6 and 11c reacted smoothly with iodine to afford 2-(iodomethyl)-4-butanolide (9) and α-[iodo(trimethylsilyl)methylidene]cyclopentanone, respectively. The organotitanium compounds obtained here also reacted with aldehydes to give the corresponding adducts, thus opening up a new access to substituted α,β-butenolides from 2, to γ-butyrolactones from 4, and to the corresponding tetrasubstituted furan from 10 and 14.

ChemInform Abstract: Intramolecular Nucleophilic Acyl Substitution Reactions Mediated by Ti( OiPr)4/2 iPrMgBr Reagent. Synthesis of Vinyltitanium Compounds Having a Lactone and/or an Ester Group from Acetylenic Carbonates.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Diastereoselective Synthesis of trans‐1,2‐Disubstituted Cyclopropanols from Homoallyl or Bis‐Homoallyl Esters via Tandem Intramolecular Nucleophilic Acyl Substitution and Intramolecular Carbonyl Addition Reactions Mediated by Ti(OiPr)4/2iPrMgBr Reagent.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Diastereoselective synthesis of trans-1,2-disubstituted cyclopropanols from homoallyl or bis-homoallyl esters via tandem intramolecular nucleophilic acyl substitution and intramolecular carbonyl addition reactions mediated by Ti(OPr- i) 4 / 2 i-PrMgBr reagent

Reactions of homoallyl or bis-homoallyl esters with Ti( OPr- i) 4/2 i- PrMgBr reagent resulted in intramolecular nucleophilic acyl substitution reaction and successive intramolecular carbonyl addition reaction providing trans-1,2-disubstituted cyclopropanols stereoselectively in excellent yields.