Carbon dioxide: A reagent for the protection of nucleophilic centres and the simultaneous activation of alternative locations to electrophilic attack. : Part I. A new synthetic method for the 2-substitution of 1-unsubstituted indoles.

Indole was converted into several 2-substituted derivatives by using carbon dioxide both for $\text{N}$-protection and to give an intermediate carbanion stabilizing group. $\text{t}$-Butyllithium was used as a lithiating agent at the $\text{alpha}$-carbon atom of the indole enamino group. The resulting 2-substituted indole-1-carboxylic acids underwent smooth thermal decarboxylation under mild conditions. Alternatively, with longer reaction times the protecting group is lost during the reaction.     

二氧化碳: 一种同时提供亲核中心保护和亲电中心活化的试剂 XI:2-取代四氢噻唑的新合成方法

四氢噻唑和正丁基锂反应生成的N-锂代四氢噻唑(2)与二氧化碳作用生成N-羟酸锂盐3; 3然后在叔丁基锂作用下失去2-位质子形成相应的2-位碳阴离子4; 该碳阴离子和一系列亲电试剂反应, 并在酸性条件下除去保护基团得产物-2-取代四氢噻唑7. 在此过程中, 二氧化碳既是氨基的保护基团, 同时又活化了2-位亲电中心.此方法不需分离各步中间体, 产率中等.     

Carbon dioxide: A reagent for the simultaneous protection of nucleophilic centres and the activation of alternative locations to electrophilic attack: Part 11. A new synthetic route to the 2-substituted thiazolidines

Thiazolidine is readily converted into a range of 2-substituted derivatives in a one-pot lithiation procedure, using carbon dioxide both for N-protection and as an intermediate carbanion stabilizing group.     

DPA-substituted coumarins as chemosensors for zinc(II): modulation of the chemosensory characteristics by variation of the position of the chelate on the coumarin

The sensory capabilities of two novel di(2-picolyl)amine (DPA)-substituted coumarins are described and it is shown that the variation of the point of attachment of the DPA group to the coumarin framework controls their sensing behavior: the 4-substituted system is a CHEF-type sensor that shows a significant increase in fluorescence intensity upon Zn(2+) binding, whereas the 3-substituted system is a ratiometric sensor.     

Highly regioselective synthesis of 2,3,4-trisubstituted 1H-pyrroles: a formal total synthesis of lukianol A

A combined use of alpha-lithiation and nucleophilic substitutions of N,N-dimethyl 3,4-bis(trimethylsilyl)-1H-pyrrole-1-sulfonamide 8c led to several 2-substituted 3, 4-bis(trimethylsilyl)-1H-pyrrole-1-sulfonamides. Utilizing the beta-effect of a trimethylsilyl group, a highly regioselective synthesis of 2,3,4-trisubstituted 1H-pyrroles 23 and 34 was accomplished. The marine natural product lukianol A (3) was prepared utilizing this strategy.     

Studies on organophosphorus compounds: XV. A new method for the synthesis of α-amino-substituted benzylphosphonic acids

A new synthetic method for the preparation of α-amino-substituted benzylphosphonic acids with moderate to good yields was developed by the following sequence of reactions. Diethyl phosphoramide was reacted with substituted benzaldehyde and triphenyl phosphite in the presence of catalytic amount of BF₃·Et₂O. Diphenyl α-(N-phosphorylamino)-substituted benzylphosphonates ( 1 ) thus obtained was then treated with hydrogen bromide in acetic acid to remove selectively the amino-protecting group with the formation of diphenyl α-amino-substituted benzylphosphonates ( 2 ), a key intermediate in phosphorus peptide synthesis, which was then successively hydrolyzed with hydrobromic acid to give corresponding hydrobromide of α-amino-substituted benzylphosphonates with excellent yields. The free aminophosphonic acid ( 3 ) was obatined from the latter by treatment with propylene oxide. ³¹P NMR studies demonstrated that a linear relationship exists in plotting δ versus δ constants of nuclear substituent in 1 series. The p-substituted compounds give, as a rule, higher value in ³¹P NMR spectra than those from meta- and ortho-substituents.     

2-取代-环戊烯酮及其衍生物的简易合成

本文报道以2-氯环戊酮的加成重排反应合成2-取代环戊酮。如再引入硫硫双键,则可合成2-取代环戊烯酮。取代环戊酮和取代环戊烯酮是合成药物和合成香料的重要中间体。     

A three-state model for the photophysics of adenine

An ab initio theoretical study at the CASPT2 level is reported on minimum energy reaction paths, state minima, transition states, reaction barriers, and conical intersections on the potential energy hypersurfaces of two tautomers of adenine: 9H- and 7H-adenine. The obtained results led to a complete interpretation of the photophysics of adenine and derivatives, both under jet-cooled conditions and in solution, within a three-state model. The ultrafast subpicosecond fluorescence decay measured in adenine is attributed to the low-lying conical intersection (gs/pipi* La)(CI), reached from the initially populated 1(pipi* La) state along a path which is found to be barrierless only in 9H-adenine, while for the 7H tautomer the presence of an intermediate plateau corresponding to an NH2-twisted conformation may explain the absence of ultrafast decay in 7-substituted compounds. A secondary picosecond decay is assigned to a path involving switches towards two other states, 1(pipi* Lb) and 1(npi*), ultimately leading to another conical intersection with the ground state, (gs/npi*), with a perpendicular disposition of the amino group. The topology of the hypersurfaces and the state properties explain the absence of secondary decay in 9-substituted adenines in water in terms of the higher position of the 1(npi*) state and also that the 1(pipi* Lb) state of 7H-adenine is responsible for the observed fluorescence in water. A detailed discussion comparing recent experimental and theoretical findings is given. As for other nucleobases, the predominant role of a pipi*-type state in the ultrafast deactivation of adenine is confirmed.     

Hydroborations: A New Route for the Preparation of 1-Alkyl- (or Aryl) 2-Tetralones

The hydroboration followed by chromic acid oxidation of 1-alkyl- and 1-aryl-3, 4-dihydronaphthalenes leads to the corresponding 1-alkyl- (or aryl)2-tetralones (1-substituted 3, 4-dihydronaphthalen-2(1H)-ones).     

The photochemistry of 1-alkenylbenzotriazoles : Methodology for the synthesis of indoles

The synthesis of 2-substituted, 3-substituted, and 2,3-disubstituted indoles based on the photolysis of 1-alkenylbenzotriazoles is described along with the application of this method to the synthesis of the 2,3-dihydropyrrolo[1,2-a]indole nucleus of the mitomycin antitumor antibiotics.     

A Cyclodextrin Molecular Reactor for the Regioselective Synthesis of 1,5-disubstituted-1,2,3-triazoles

6^A-Deoxy-6^A-propynamido-β-cyclodextrin reacts with 4-tert-butylphenyl azide in aqueous solution, to form the 5-(aminocarbonyl)-substituted triazole in preference to the 4-(aminocarbonyl)-substituted analogue, in a ratio of 25:1. The cyclodextrin moiety templates the reaction through the formation of a host-guest complex of the dipole with the dipolarophile, controlling the regioselectivity of cycloaddition. In a control reaction under similar conditions, with propiolamide instead of the cyclodextrin derivative, 5- and 4-(aminocarbonyl)-1-(4-tert-butylphenyl)-1,2,3-triazole were formed in a ratio of 1:4. As well as reversing the regioselectivity, the cyclodextrin substituent increases the rate of cycloaddition, by at least two orders of magnitude for the reaction to give the 5-substituted cycloadduct. Even the rate of formation of the 4-substituted cycloadduct is increased by a factor of two. Less marked effects are observed with phenyl azide and 4-tert-butylbenzyl azide as dipoles.     

Cycloadditions of 1-substituted 1,3-butadienes with 4- or 3-substituted 2(1H)-quinolones acting as dienophiles

Cycloadditions of 1,3-butadiene derivatives having an electron-rich group at the 1-position with 4- or 3-substituted 2(1H)-quinolones were carried out to give the richly functionalized phenanthridines under both atmospheric and high pressure conditions. Furthermore, the reactivity of 4- or 3-substituted 2(1H)-quinolones acting as a dienophile with 1-substituted dienes was examined using MO calculation.     

A flexible method for the synthesis of 2-substituted 1,2,5,6-tetrahydropyridines and piperidines from chloro-containing propargylamines

A general approach for the stereoselective synthesis of 2-substituted 1,2,5,6-tetrahydropyridines and piperidines is described. The addition of 4-chloro-1-butyne to Ellman sulfinimines to produce chloro-containing propargylamines, reduction with Lindlar catalyst, and cyclization using LHMDS provides efficient, stereoselective access to diverse 2-substituted 1,2,5,6-tetrahydropyridines. For substrates incompatible with the LHMDS cyclization reaction conditions removal of the sulfinamide moiety and cyclization with Cs₂CO₃ allows the preparation of the corresponding 2-substituted 1,2,5,6-tetrahydropyridines. This method can be extended to the synthesis of 2-substituted piperidines through reduction of the chloro-containing propargylamine with PtO₂.     

Aspirin prodrugs: synthesis of 2-substituted 2-methyl-4H-1,3-benzodioxin-4-ones and their screening for prodrug potential

A series of new 2-substituted 2-methyl-4H-1,3-benzodioxin-4-ones 1 have been synthesized and fully characterized. This study involves fifteen compounds of which fourteen are orthoesters, containing tertiary aliphatic alkoxy groups. One compound contains a tert-butylperoxy group and one a 3 beta-cholesteryloxy group in the 2-position. The hydrolysis of these compounds 1 was followed in enzymatic and non-enzymatic media to clarify whether they are true prodrugs of aspirin. Two compounds 1 were additionally tested in vivo as potential topical keratolytics.     

A new entry to the synthesis of 2,3-disubstituted indoles

[reaction: see text] The Stille coupling of N-acyl-2-iodoanilines with the 1-(tributylstannyl)-1-substituted allenes affected the successive one-step formation of the 2-methyl-3-substituted indoles. Alternatively, the other type of 2-alkyl-3-substituted indoles could be synthesized in a one-pot operation, which consists of the Stille coupling reaction with the 1-(tributylstannyl)-1,3-disubstituted allenes, followed by TBAF treatment. This procedure could be applied to the synthesis of indomethacin.     

Pd-catalyzed ring opening of oxa- and azabicyclic alkenes with aryl and vinyl halides: efficient entry to 2-substituted 1,2-dihydro-1-naphthols and 2-substituted 1-naphthols

An efficient syntheses of 2-substituted 1,2-dihydro-1-naphthols and 2-substituted 1-naphthols has been developed that involves the sequential palladium-catalyzed ring opening of oxabicyclic alkenes with aryl and vinyl halides followed by oxidation of with IBX. In the first step of the sequence, a combination of Pd(OAc)2, PPh3, Zn, and PMP in dry DMF was employed to catalyze the ring opening of 7-oxabenzonorbornadienes with aryl and vinyl halides to afford the corresponding cis-2-substituted 1,2-dihydronaphthols in good to excellent yields. These reactions occurred under very mild conditions with a variety of aryl halides bearing electron-withdrawing or -donating groups. Similarly, a 7-azabenzonorbornadiene substituted with an electron-withdrawing group on the nitrogen atom underwent facile ring-opening reaction with aryl halides to provide cis-2-substituted (1,2-dihydro-1-naphthyl)carbamates in excellent yields. Oxidation of the intermediate 1,2-dihydro-1-naphthols using IBX yielded the corresponding 2-substituted 1-naphthols in good to excellent yields.     

Morita-Baylis-Hillman reaction of indole-2-carboxaldehyde: new vistas for indole-annulated systems

DABCO-mediated Morita-Baylis-Hillman reactions of several 1-substituted-indole-2-carboxaldehydes are disclosed. It was discovered that carboethoxy or tert-butoxycarbonyl groups installed at N-1 undergo cleavage under the reaction conditions to afford 2-substituted indoles. Utility of the N-substituted adducts for preparing a variety of annulated indoles has been exemplified.     

Remarkable regioselectivities in the course of the synthesis of two new Luotonin A derivatives

Ethyl 4-oxo-3,4-dihydroquinazoline-2-carboxylate reacts selectively with trimethylaluminium-activated 2-amino- or 4-aminobenzoic acid ethyl esters to give the corresponding anilides without self-condensation of the aminobenzoate building blocks. After propargylation, the quinazolinones were treated with Hendrickson's reagent, but only the para-substituted ester was found to undergo the expected [4 + 2] cycloaddition reaction, affording a new Luotonin A derivative. A different regioselectivity was observed with the ortho-substituted ester which affords a benzoxazinone under identical conditions. When the ester group in the ortho-substituted intermediate is replaced with a nitrile function, the outcome of the reaction with Hendrickson's reagent depends on the absence or presence of a base (DBU), yielding either a triphenylphosphonium-substituted iminobenzoxazine or a 4-cyano-substituted Luotonin A derivative.     

Aroylthioureas: new organic ionophores for heavy metal ion selective electrodes. A nuclear magnetic resonance study

The 1H and 13C NMR spectra of four series of 1-aroylthiourea derivatives in DMSO-d6 are reported. The NH signals for 3-alkyl substituted aroylthioureas are identified by their multiplicity and by homonuclear irradiation experiments. Correlation analyzes are made for NH, CO and CS signals in order to determine the best way to modulate the nucleophilic character of the CS group, as thioureas are well-known ionophore groups. Almost all 1,3-substituted thioureas (Series 2-4) show the reported chelated structure with the exception of those with CF3, CN and NO2 groups. Pyridine group promote a different equilibrium in solution. The fragment -CO-NH- transmits poorly the electronic effects of substituents in the aroylgroup.     

2-Trifluoroacetyl aminoindoles as useful intermediates for the preparation of 2-acylamino indoles

A three-step method was developed to convert N-1 unprotected 3-substituted indoles to 3-substituted 2-acylaminoindoles. Established indole chlorination chemistry was employed to generate stable 2-trifluoroacetylamino indoles, which were subsequently deprotected and selectively acylated.