Palladium-catalyzed enantioselective ring opening of oxabicyclic alkenes with organozinc halides

Palladium-catalyzed asymmetric ring opening of oxabenzonorbornadienes with readily available organozinc halides under mild conditions in the presence of (S)-Pr(i)-PHOX produces the corresponding 1,2-dihydronaphth-1-ols in good yield and high enantioselectivity. [reaction: see text]     

Acid catalyzed ring closure reactions of electrophilic alkenes

Treatment of -acyl-,β-unsaturated ketones with sulfuric acid or dimethylformamide-hydrogen chloride or p-toluenesulfonic acid gave rise to 3-acyl-2-alkyl-4,5-dihydrofurans. Similar cyclization of -acyl-,β-unsaturated esters initially afforded 3-alkoxycarbonyl-2-alkyl-4,5-dihydrofurans which were transformed into 2-acylbutanolides on further reaction with sulfuric acid.

This acid catalyzed cyclization is strongly dependent upon the substitution pattern of the electrophilic alkenes, the acid used and reaction conditions.     

Rhodium-catalyzed asymmetric arylative ring opening of bicyclic hydrazines

The development of a novel asymmetric ring opening of bi- and polycyclic hydrazines with aryl organometallic reagents is presented. The application of this reaction to the most simple bicyclic hydrazine 1a gives a straightforward regio- and diastereoselective access to synthetically useful trans 3,4-disubstituted hydrazinocyclopentenes in an enantioenriched form.     

Tetrathiomolybdate assisted epoxide ring opening with masked thiolates and selenoates: multistep reactions in one pot

Tetrathiomolybdate provides an easy access to beta-hydroxy disulfides, beta-hydroxy sulfides, and selenides from epoxides in a tandem, multistep process in one pot. This strategy has been utilized effectively in the construction of thiabicylo[3.2.2]nonane derivative 24.     

Palladium-catalyzed tandem Heck and aldol reactions between 2-bromobenzaldehydes and functionalized alkenes leading to naphthalenes

2-Bromobenzaldehydes react with an array of suitably functionalized alkenes in the presence of a catalytic amount of a palladium catalyst together with a base to afford the corresponding naphthalenes in moderate to good yields.     

Rhodium-catalyzed asymmetric ring opening of oxabicyclic alkenes with phenols

The scope of the rhodium-catalyzed asymmetric ring opening reaction of oxabenzonorbornadiene has been extended to include phenolic nucleophiles. The enanatioenriched, functionalized dihydronaphthalene products are highly valuable intermediates for which no other practical methods of preparation are available. A new catalyst system has been developed which allows the use of less reactive o-halophenols. The utility of these products has been demonstrated through their application in the synthesis of benzofuran polycyclic materials.     

Iridium-catalyzed asymmetric ring opening of azabicyclic alkenes by amines

The enantioselective ring-opening reactions of azabicyclic alkenes with primary and secondary aromatic amine nucleophiles are reported using an iridium catalyst generated in situ from 1.5 mol % of [Ir(COD)Cl](2) and 3 mol % of (S)-BINAP. The reaction affords the corresponding trans-1,2-diamine derivatives in moderate to good yields with moderate to high enantioselectivities (up to 97% ee). The trans-configuration of the 1,2-diamino product 2g was confirmed by X-ray crystallography.     

Reductive ring opening reactions of diphenyldihydrofullerenylpyrroles

The reductive ring opening reaction conditions for the simple [60]fullerenyldihydropyrrole 1 have been optimized to include acetic acid in the reaction mixture to rapidly protonate the anionic intermediate. Under these conditions, the ring opened dihydrofullerene 2 was obtained in 68% yield. Under slightly modified conditions and at −78 °C, the reductive bis-ring opening of the tethered trans-4 isomer 3 provided the novel racemic bis-dihydrofullerenyl derivative 7.     

Rhodium-catalyzed asymmetric ring opening of oxabicyclic alkenes with organoboronic acids

The first rhodium(I)-catalyzed asymmetric addition of organoboronic acids to oxabicyclic alkenes is reported. This asymmetric ring-opening (ARO) reaction can proceed in high yield under very mild conditions with electronically diverse organoboronic acids, in a highly diastereoselective and enantioselective manner. [structure: see text]     

Copper-catalyzed asymmetric ring opening of oxabicyclic alkenes with Grignard reagents

[reaction: see text] Simple Grignard reagents were applied in copper-catalyzed asymmetric ring-opening reactions of oxabenzonorbornadiene derivatives using spiro phosphoramidite ligands. Excellent anti-stereoselectivities and good enantioselectivities were achieved.     

Copper-catalyzed anti-stereocontrolled ring opening of oxabicyclic alkenes with grignard reagents

[reaction: see text] A general copper-catalyzed procedure for the stereoselective ring opening of [2.2.1]-oxabicyclic alkenes with Grignard reagents is described. In the presence of catalytic amounts of CuCl/PPh(3) the reaction occurs with very high or complete anti selectivity in all cases.     

Rhodium-catalyzed asymmetric ring opening of oxabicyclic alkenes with sulfur nucleophiles

The synthesis of 2-sulfanyl-1,2-dihydro-naphthalen-1-ols is described. This methodology is based on rhodium catalysis and enables various thiols to undergo an asymmetric SN2' ring opening of oxabenzonorbornadiene. Under the reaction conditions ([Rh(COD)Cl](2) (2.5 mol %), (S)-(R)-PPF-P(t)Bu(2) (6 mol %), AgOTf (7 mol %), NH(4)I (1.7 equiv), galvinoxyl (5 mol %), THF, 85 degrees C), aryl- and alkyl-sulfide adducts are obtained in good to excellent yield and in high enantiomeric excess (>90% ee).     

Copper-catalyzed asymmetric ring opening of oxabicyclic alkenes with organolithium reagents

A highly efficient method is reported for the asymmetric ring opening of oxabicyclic alkenes with organolithium reagents. Using a copper/chiral phosphoramidite complex together with a Lewis acid (BF(3)·OEt(2)), full selectivity for the anti isomer and excellent enantioselectivities were obtained for the ring opened products.     

Intramolecular guanidine epoxide ring opening reactions

The synthesis of a range of cyclic guanidines via intramolecular ring opening of epoxides or iodocyclisation is reported. A preliminary investigation of the glycosidase inhibitory activity of these substances is also discussed.     

Deamination,involving ring opening,in reactions of 1-aminopurinium mesitylenesulfonates with methanolic amonia

On reaction of 1-aminopurinium mesitylenesulfonates with methanolec ammonia N-deamintion occurs. For 1-amino-, 1-amino-8-(methylthio)-, 1-amino-8-phenyl-, 1-amino-2-methyl-, 1-amino-6-methyl- and 1-amino-8-phenyl-9-methyl-purinium mesitylenesulfonate this reaction proceeds for at least 75% via ring opening as shown by the isolation of 1-¹⁵N-labelled purines when ¹⁵N-labelled methanolic ammonia was used. 1-Amino-9-methylpurinium mesitylenesulfonate gave N-deamination without ring opening. The reaction of 1-amino-6-(methylthio)purinium mesitylenesulfonate with methanolic ammonia involves, besides deamination, partial substitution of the methylthio group; no ring opening is involved. However, ring opening followed by substitution occurs in the reaction of 1-amino-2-(methylthio)purinium mesitylenesulfonate; the reaction proceeds via an adduct at position 2.     

Ring opening versus ring expansion in rearrangement of bicyclic cyclobutylcarbinyl radicals

Ring opening and expansion of multicyclic cyclobutylcarbinyl radicals provides an appealing method for the construction of heavily substituted ring systems in a stereocontrollable fashion. Here we conducted the first, systematic study on the regioselectivity in the rearrangement of various synthetically relevant cyclobutylcarbinyl radicals. It was found that a two-layer ONIOM method, namely ONIOM(QCISD(T)/6-311+G(2d,2p):B3LYP/6-311+G(2df,2p)), could accurately predict the free energy barriers of the ring openings of cyclobutylcarbinyl radicals with a precision of 0.3 kcal/mol. By using this powerful tool we found that the regiochemistry for the ring opening of monocyclic cyclobutylcarbinyl radicals could be easily predicted by the relative stability of the two possible carbon radical products. A linear correlation was found between the activation and reaction free energies. This observation indicated that the ring opening of cyclobutylcarbinyl radicals was strongly affected by the thermodynamic factors. On the basis of the above results we extended our study to the rearrangement of bicyclic cyclobutylcarbinyl radicals that could undergo both ring opening and expansion. It was found that for bicyclic cyclobutylcarbinyl radicals whose radical center was located at the bridge methyl group, ring expansion was the favored rearrangement pathway unless a strongly radical-stabilizing substituent was placed in the cyclobutyl ring adjacent to the bridge methyl group. On the other hand, for bicyclic cyclobutylcarbinyl radicals whose radical center was located at the 2-position, ring opening was the favored rearrangement pathway unless a strongly radical-stabilizing substituent was placed in the cyclobutyl ring at the bridge position.     

Palladium-catalyzed hydrophosphinylation of alkenes and alkynes

Various palladium catalysts promote the addition of hypophosphorous derivatives ROP(O)H(2) to alkenes and alkynes in good yields and under mild conditions. Particularly, Cl(2)Pd(PPh(3))(2)/2 MeLi, and Pd(2)dba(3)/xantphos allow for phosphorus-carbon bond formation instead of transfer hydrogenation. Commercial aqueous solutions of hypophosphorous acid can be employed successfully at ambient temperature. With styrene and terminal alkynes, the regioselectivity (linear versus branched products) can be controlled to some extent with the catalytic system employed. The methodology considerably extends upon previous routes for the preparation of H-phosphinic acids and other organophosphorus compounds.     

Palladium-catalyzed asymmetric carbamoyl-carbonylation of alkenes

An unprecedented palladium-catalyzed asymmetric carbamoyl-carbonylation of tethered alkenes with CO and alcohols has been developed. This reaction provided an efficient route to access oxindoles and γ-lactams bearing β-carbonyl substituted quaternary carbons in good yields with excellent chemo-, regio-and enantioselectivity. Gram-scale synthetic capability and facile transformations of the products to chiral spirooxindole and other functional molecules further illustrated the practicability of this reaction.     

Palladium-catalyzed intramolecular chloroamination of alkenes

A mild and facile Pd-catalyzed intramolecular chloroamination of unactivated alkenes has been described. This reaction takes place at room temperature and is tolerant of synthetically useful acid-sensitive functional groups. Generally high exo-selectivities are observed in the formation of a variety of 5- and 6-membered rings. This system is unique in its ability to tolerate multidentate ligands on palladium, which opens up the possibility of controlling the absolute sense of induction using a chiral ligand.