Addition of alcohols to isoprene catalyzed by hydrated rhodium trichloride: A way to improve the 1,4-addition regioselectivity

Synthesis of alkoxyolefins from alcohols and dienes can be achieved in the presence of hydrated rhodium trichloride. Because of the probable intermediate formation of π-allylic rhodium complexes, the regioselectivity of the addition varies according to the reaction conditions. Without any additives, the greatest selectivity in 1,4-addition is 53% for a 78% isoprene conversion. In the presence of zinc chloride, 1,4-addition is significantly increased (68% for a 70% conversion).     

A new type of catalytic tandem 1,4-addition-aldol reaction which proceeds through an (oxa-pi-allyl)rhodium intermediate

The reaction of 9-aryl-9-borabicyclo[3.3.1]nonanes (B-Ar-9BBN) with alpha,beta-unsaturated ketones and aldehydes in the presence of 3 mol % [Rh(OMe)(cod)](2) in toluene at 20 degrees C for 2 h gave high yields of the tandem 1,4-addition-aldol reaction products with high syn selectivity. The reaction proceeds through the catalytic cycle consisting of 1,4-addition of an organorhodium species to an alpha,beta-unsaturated ketone and the aldol addition of the resulting (oxa-pi-allyl)rhodium intermediate to an aldehyde.     

Enantioselective nucleophilic addition to N-(2-pyridylsulfonyl)imines by use of dynamically induced chirality

Enantioselective nucleophilic addition of Grignard reagents to N-(2-pyridylsulfonyl)imines in the presence of bis(oxazoline) afforded products with good enantioselectivity. Dynamically induced chirality on the sulfur by coordination of a chiral Lewis acid to a pyridyl nitrogen and one of the sulfonyl oxygens fixes the conformation of the complex and induces enantioselectivity. Since the 2-pyridylsulfonyl group can be easily removed after the addition reaction, it acts not only as a protecting group but also as an efficient stereocontroller.     

Reaction of N-acetyl- and N-[1-(arylsulfonylimino)ethyl]-1,4-benzoquinone imines with sodium arenesulfinates

N-Acetyl- and N-[1-(arylsulfonylimino)ethyl]-1,4-benzoquinone imines having no substituent in the 2- and/or 6-position of the quinoid ring react with sodium arenesulfinates preferentially according to the 1,4-addition pattern. The presence of an ArSO₂N group favors radical ion reaction with formation of 1,6-addition products.     

Development of catalytic asymmetric 1,4-addition and [3 + 2] cycloaddition reactions using chiral calcium complexes

Catalytic asymmetric 1,4-addition and [3 + 2] cycloaddition reactions using chiral calcium species prepared from calcium isopropoxide and chiral bisoxazoline ligands have been developed. Glycine Schiff bases reacted with acrylic esters to afford 1,4-addition products, glutamic acid derivatives, in high yields with high enantioselectivities. During the investigation of the 1,4-addition reactions, we unexpectedly found that a [3 + 2] cycloaddition occurred in the reactions with crotonate derivatives, affording substituted pyrrolidine derivatives in high yields with high enantioselectivities. On the basis of this finding, we investigated asymmetric [3 + 2] cycloadditions, and it was revealed that several kinds of optically active substituted pyrrolidine derivatives containing contiguous stereogenic tertiary and quaternary carbon centers were obtained with high diastereo- and enantioselectivities. In addition, optically active pyrrolidine cores of hepatitis C virus RNA-dependent polymerase inhibitors and potential effective antiviral agents have been synthesized using this [3 + 2] cycloaddition reaction. NMR spectroscopic analysis and observation of nonamplification of enantioselectivity in nonlinear effect experiments suggested that a monomeric calcium species with an anionic ligand was formed as an active catalyst. A stepwise mechanism of the [3 + 2] cycloaddition, consisting of 1,4-addition and successive intramolecular Mannich-type reaction was suggested. Furthermore, modification of the Schiff base structure resulted in a modification of the reaction course from a [3 + 2] cycloaddition to a 1,4-addition, affording 3-substituted glutamic acid derivatives with high diasterero- and enantioselectivities.     

Stereoselective one-pot three-component coupling approach towards the synthesis of the AC ring system of taxanes

The stereoselective one-pot three-component coupling reaction was accomplished by 1,4-addition of the protected cyanohydrin ether 9f to cyclohexenone 10g and subsequent addition of the resulting enolate to formaldehyde in high yield for the formation of the AC ring system of taxanes. We found that the bulky substituents at the 10-position in the A ring prevent the desired 1,4-addition. Similarly, the bulky trialkylsiloxy groups at the 4-position in the C ring prevent the 1,4-addition and electron-donating alkoxy groups at the same position induce the undesired retro-Michael reaction.     

Rhodium-Catalyzed Asymmetric Conjugate Additions of Boronic Acids to enones using DIPHONANE: a novel chiral bisphosphine ligand

[reaction: see text] The synthesis of a novel enantiopure C2-symmetric bisphosphine, DIPHONANE, was accomplished starting from 2,5-norbornadione, utilizing (R,R)- and/or (S,S)-(2,3-O-di[(phenylamino)carbonyl]tartaric acid for the resolution of an intermediate phosphineoxide. The application of this ligand in the rhodium-catalyzed asymmetric conjugate addition of boronic acids to cyclic enones provides the 1,4-addition products in good yields (69-98%) and high ee's (78-95% ee). A byproduct arising from a consecutive 1,4-addition and 1,2-addition was also observed.     

Reaction of 2-mercaptobenzimida(thia)zole with 1,4-naphthoquinone and its oxide

The reaction of 2-mercaptobenzimida(thia)zole with 1,4-naphthoquinone proceeds as nucleophilic 1,4-addition to give the corresponding thioethers. The reaction of 1,4-naphthoquinone oxide with 2-mercaptobenzimidazole leads to benzimidazonaphthothiazole, while the reaction of the oxide with 2-mercaptobenzothiazole leads to a thioether as a consequence of the addition of the mercapto-substituted heterocycle at the oxide ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 121–124, January, 1992.     

Some Features of the Reactions of 3-Nitro-6-phenylhexa-3,5-dien-2-one with Thiophenols

The reaction of 3-nitro-6-phenylhexa-3,5-diene-2-one with 4-methyl- and 4-chlorothiophenols yields 1,4- and 1,6-addition products at conjugated dienone system. By the example of the 1,4-addition adduct of 4-methylthiophenol, its conversion in solution to the 1,6-addition product was shown. 4-Methyl-3-nitro-2-styryl-2,3-dihydrobenzo[b][1,4]thiazepine was synthesized by reacting 3-nitro-6-phenylhexa-3,5-dien-2-one with o-aminothiophenol.     

Reactions of ethyl bromodifluoroacetate in the presence of copper powder

We have examined the reaction of ethyl bromodifluoroacetate (1) in the presence of copper powder as a procedure for the synthesis of compounds containing a CF₂ group. The complex formed in the above reaction reacted with vinyl or aryl iodides to give cross-coupling products, with Michael acceptors to give 1,4-addition products and with olefins to give radical addition products. The cross-coupling reaction was applied to the synthesis of 4,4-difluoro-α-tocopherol.     

A Mechanism Study of a Novel Acid-Activatable Michael-Type Fluorescent Probe for Thiols

A Michael addition is usually taken as a base-catalysed reaction. However, our synthesized 2-(quinolin-2-ylmethylene) malonic acid (QMA) as a Michael-type thiol fluorescent probe is acid-active in its sensing reaction. In this work, based on theoretic calculation and experi-mental study on 7-hydroxy-2-(quinolin-2-ylmethylene) malonic acid, we demonstrated that QMA as a Michael acceptor is acid-activatable, i.e., it works only in solutions at pH<7, and the lower the pH of solutions is, the higher reactivity QMA has. In alkaline solution, the malonate QMA[-2H⁺]^2- cannot react with both RS^- and RSH. In contrast, 2-(quinolin-2-ylmethylene) malonic ester (QME), the ester of QMA, reveal a contrary pH effect on its sensing reaction, that is, it can sense thiols in alkaline solutions but not in acidic solutions, like a normal base-catalysed Michael addition. The values of activation enthalpies from theoretic calculation support the above sensing behavior of two probes under different pH conditions. In acidic solutions, the protonated QMA is more highly reactive towards elec-trophilic attack over its other ionized states in neutral and alkaline solutions, and so can react with lowly reactive RSH. In contrast, there is a big energy barrier in the interaction of QME with RSH (acidic solutions), and the reaction of QME with the highly reactive nucle-ophile RS^- is a low activation energy process (in alkaline solutions). Theoretic calculation reveals that the sensing reaction of QMA undergoes a 1,4-addition process with neutral thiols (RSH), and a 1,2-addition pathway for the sensing reaction of QME with RS^-. Therefore, the sensing reaction of QMA is an acid-catalysed Michael addition via a 1,4-addition, and a normal base-catalysed Michael addition via a 1,2-addition.     

Regioselectivity in the ligand-assisted addition of vinylmagnesium bromide: an experimental and theoretical study on the gamma-alkoxycyclobutenone model

Compounds 2 (M = Mg) obtained in the mono addition of vinylmagnesium bromide to squarates are attractive structural models to determine the influence of complexation between magnesium(II) and the alkoxide group on the regioselectivity of the 1,2- versus 1,4-addition of organomagnesium by complex induced proximity effects (CIPE). The 1,4-addition is observed almost exclusively in the case of vinylmagnesium in THF solution with formation of hydroxyketones type 5, which are always side or minor products in the known reaction of alkenyllithium derivatives. A comparative study on the reactivity of alkenyllithium and magnesiun derivatives is reported. The high regioselectivitity observed in the 1,4-addition of vinylmagnesium bromide is fully understood by computational studies of compounds 2 (M = Mg) at the DFT level with the density functional B3LYP.     

Copper(I) catalyzed asymmetric 1,2-addition of Grignard reagents to α-methyl substituted α,β-unsaturated ketones

The first catalytic enantioselective 1,2-addition of Grignard reagents to ketones is presented. This additive-free copper(I) catalyzed 1,2-addition provides chiral allylic tertiary alcohols with an er of up to 98:2 and excellent yields due to the complete shift of overwhelming 1,4-selectivity of copper(I)-catalysts towards 1,2-selectivity in the addition reaction to enones.     

Chemoselective,accelerated and stereoselective aza-Michael addition of amines to N-phenylmaleimide by using TMEDA based receptors

An aza-Michael addition between a maleimide and amines is described in which the presence of simple amine receptors (TMEDA or trans-TMCDA) promote the chemoselectivity of the reaction (respectively, 1,2- and 1,4-addition). Additionally, both receptors are able to accelerate the reaction. Stoichiometries of complexes between receptors and amines were determined by ¹H NMR dilution experiments while enantiomeric excesses were observed on 1,4-adducts by using (1R,2R)-TMCDA.     

A rapid divergent synthesis of highly substituted delta-lactones

[reaction: see text] Nucleophilic 1,2-addition of (Z)-gamma-silyloxyvinylzinc reagents to ethyl glyoxylate followed by desilylation and cyclization affords 3,6-dihydro-3-hydroxypyran-2-ones in good chemical yields. In situ formation of allylic phosphates followed by reaction with RCu(CN)Li reagents affords substituted 5,6-dihydropyran-2-ones. The parent compound, 3,6-dihydro-3-hydroxypyran-2-one, undergoes allylic phosphate formation, cuprate-mediated allylic substitution, and 1,4-conjugate addition to afford trans-4,5-disubstituted tetrahydropyran-2-ones in a one-pot process.     

Reaction of [60]fullerene with free radicals generated from active methylene compounds by manganese(III) acetate dihydrate

The reaction of [60]fullerene with dimethyl malonate and diethyl malonate in the presence of manganese(III) acetate dihydrate (Mn(OAc)3.2H2O) for 20 min afforded singly bonded [60]fullerene dimers 1a and 1b in a 1,4-addition pattern. When the reaction time was extended to 1 h, 1,4-bisadducts 2a and 2b were obtained. Unsymmetrical 1,4-adduct 5 and C2 symmetrical 1,16-bisadduct 6 were obtained when diethyl bromomalonate was used as the active methylene compound. Reaction of [60]fullerene with malononitrile and ethyl cyanoacetate with the aid of Mn(OAc)3.2H2O produced methanofullerenes 7 and 8. It is proposed that all these products were formed the addition of free radicals from the active methylene compounds generated by Mn(OAc)3.2H2O.     

Anionic polymerization of butadiene: A MNDO study of the potential energy surface of the propagation reaction in polar and non-polar media

The anionic polymerization of butadiene, to both the 1,2- and 1,4-addition products, is an important industrial process. It is known that the reaction can be steered to either the 1,2- or 1,4-product by the addition, or absence, of a complexing solvent such as ether. The goals of the current study were to map the MNDO Potential Energy Surfaces (PES) of the propagation reactions both in the presence and absence of dimethyl ether to gain insight into the factors influencing the reaction's selectivity. Single point ab initio calculations at the DZP level were run on all reactants, products and transition states as a cross check on the MNDO results.     

Conjugate Addition Reactions of Functionalized Organozinc-copper Reagents to α,β-Unsaturated Esters

Theconjugateadditionoforganometal1icstoMichaelacceptorsisanimportantsyntheticmethodforcarbon-carbonbondformation'.FunctionalizedorganozincreagentsaremoreusefulinthatfleldbecausetheytolerateabroadrangeoffunctionalitiesandreactinthepresenceofCuCN'2LiClwithvariouselectrophilesinexcellentyields"'.Thus,apolyfunctionalizedorganicmoleculecanbeformedinonestep.However,CuCNhasbeentheonlycoppersaltsinceitwasfirstusedinl988,',andunsaturatedestersdonotreactwithfunctionalizedorganozincreagentsundergener…     

Asymmetric synthesis of 2-aryl-2,3-dihydro-4-quinolones by rhodium-catalyzed 1,4-addition of arylzinc reagents in the presence of chlorotrimethylsilane

[reaction: see text] The first catalytic asymmetric synthesis of 2-aryl-2,3-dihydro-4-quinolones has been developed by way of a rhodium-catalyzed 1,4-addition of arylzinc reagents to 4-quinolones. These 1,4-adducts can be obtained with high enantioselectivity by the use of (R)-binap as a ligand, and high yields are realized by conducting the reactions in the presence of chlorotrimethylsilane.     

The Copper Mediated Barbier Reactions of α,β-Unsaturated Ketones: Regioselective Conjugate and 1,2-Addition

The one-pot reaction of isophorone and other α, β,-unsaturated ketones with alkyl and aryl halides in the presence of magnesium and a copper salt (“Barbier” conditions) leads to the regiospecific formation of 1,4-addition products; the use of lithium leads to regioselective 1,2-addition.