Lewis acid-catalyzed conjugate addition-cyclization reactions of ethenetricarboxylates with substituted propargyl alcohols: stereoselectivity in the efficient one-pot synthesis of methylenetetrahydrofurans

Oxygen-containing heterocyclic systems are important structures in organic chemistry because of their presence in many biologically active compounds. In this work, a Lewis acid-catalyzed cyclization of ethenetricarboxylate derivatives 1 with substituted propargyl alcohols to give methylenetetrahydrofurans was investigated. Reaction of 1 and gamma-silicon-substituted propargyl alcohols 4 with ZnBr2 at 80-110 degrees C led to (Z)-silicon-substituted products stereoselectively. Reaction of 1 and gamma-ester-substituted propargyl alcohol 7 in the presence of various Lewis acids gave ester-substituted methylenetetrahydrofurans stereoselectively. Interesting Lewis acid dependency on stereoselectivity for the reaction of 7 was found. Reaction of alpha-substituted propargyl alcohols also gave cyclized products.     

Asymmetric syntheses of dihydroxyhomoprolines via doubly diastereoselective lithium amide conjugate addition reactions

The asymmetric syntheses of novel dihydroxyhomoprolines have been achieved using the doubly diastereoselective conjugate additions of the antipodes of lithium N-benzyl-N-(α-methylbenzyl)amide to a set of four chiral α,β-unsaturated esters (derived from d-pentoses) as one of the key steps. A full account of the diastereoselectivity observed in these conjugate additions is presented and the stereochemical outcomes of these reactions have been established unambiguously via a combination of hydrogenolytic chemical correlation and single crystal X-ray diffraction analyses. A tandem hydrogenolysis/intramolecular reductive amination reaction was then used to create the corresponding enantiopure pyrrolidines, providing access to (2′S,3′S,4′R)-dihydroxyhomoproline and (2′S,3′R,4′S)-dihydroxyhomoproline after deprotection.     

Reactivity of propargylamines in complexation and polymerization reactions

Factors were determined which promote the formation of charge-transfer complexes of propargylamines with organic electron acceptors and a change of the activity of the triple bond in propargylamines under the effect of donor-acceptor interactions. On the basis of data from PMR spectroscopy and quantum-chemical calculations it was shown that the tendency of propargylamines to form charge-transfer complexes depends on the electron-donor properties of the substituents at the nitrogen atom. The values of the effective charges at the atoms and an analysis of the structure of the highest occupied molecular orbitals in the propargylamines and their radical cations indicate that mainly electrons localized on nitrogen atoms participate in the complexation reaction. An increase of the reactivity of the triple bond is related to an increase in its polarity under the effect of complexation.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 25, No. 5, pp. 597–601, September–October, 1989.     

Application of cycloaddition reactions to the syntheses of novel boron compounds

This review covers the application of cycloaddition reactions in forming the boron-containing compounds such as symmetric star-shaped boron-enriched dendritic molecules, nano-structured boron materials and aromatic boronic esters. The resulting boron compounds are potentially important reagents for both materials science and medical applications such as in boron neutron capture therapy (BNCT) in cancer treatment and as drug delivery agents and synthetic intermediates for carbon-carbon cross-coupling reactions. In addition, the use of boron cage compounds in a number of cycloaddition reactions to synthesize unique aromatic species will be reviewed briefly.     

Organometallic reactions in aqueous media: indium-promoted additions to 2-pyridyl and glyoxylic acid oxime ethers

Oxime ethers derived from 2-pyridinecarboxaldehyde and glyoxylic acid can be effectively allylated in water with five differently functionalized allylic bromides promoted by indium. When the metal is positioned in close proximity of flanking heteroatomic centers, chelation by In is indeed operative and affects both reactivity and stereochemistry. Stereochemical assignments in the addition products were based on X-ray crystallographic measurements and spectral correlations.     

TiCl4-promoted cyclization reactions of aminoacetals and ethenetricarboxylates leading to nitrogen-containing heterocycles

Lewis acid-catalyzed cyclization of aminoacetals 2 and triethyl ethenetricarboxylate (1a) has been examined. The reaction of 3-aminopropionaldehyde diethyl acetal (2a) and 1a in the presence of 1 equiv of TiCl(4) at room temperature gave 4-ethoxypiperidine-2,3,3-tricarboxylate 3a in 92% yield with a 2,4-diastereomer ratio of 1:1. The reaction in the presence of 3 equiv of TiCl(4) gave 2,4-trans-piperidine derivative 3a in 86% yield predominantly. The reaction of aminoacetaldehyde diethyl/dimethyl acetals 2c,d and 1a with 3 equiv of TiCl(4) gave 2,4-trans-4-pyrrolidine-2,3,3-tricarboxylates 5a,b predominantly.     

N-heterocyclic phosphenium cations: syntheses and cycloaddition reactions

A series of trifluoromethanesulfonate (OTf) salts of N-heterocyclic phospheniums (NHP) bearing phenyl (1a), para-methoxyphenyl (1b), 2,6-diisopropylphenyl (1c) and mesityl (1d) substituents is reported. The compounds are made by a modification to a literature procedure that improves the overall yields for and by 15 and 23%, respectively. Two unwanted side-products in the synthesis of , the diammonium salt, [(2,6-iPr-C6H3)N(H)2CH2CH2N(H)2(2,6-iPr-C6H3)]Cl2 (4) and the bisphosphine (2,6-iPr-C6H3)N(PCl2)CH2CH2N(PCl2)(2,6-iPr-C6H3) (5), are crystallographically characterized, as is the intermediate cyclic chlorophosphine, C1PN(4-OMe-C6H4)CH2CH2N(4-OMe-C6H4) (3b). The phenyl-substituted NHP is fully characterized, including by X-ray crystallography, for the first time; this compound contains a short P-O contact of 2.1850(14) A. Cycloaddition reactions of with 2,3-dimethyl-1,3-butadiene give the expected spirocyclic phospholeniums, 7,8-dimethyl-1,4-diaryl-1,4-diaza-5-phopshoniaspiro[4.4]non-7-ene, as their OTf salts (6a-d), while reactions with N,N'-dimesityl-1,4-diaza-1,3-butadiene give, except in the case of , which is too bulky to react, the aza analogues, 1,4-dimesityl-6,9-diaryl-1,4,6,9-tetraaza-5-phosphoniaspiro[4.4]non-2-ene (7a, 7b and 7d). The sterically congested is in thermal equilibrium with and free diazadiene, and undergoes a substitution reaction with 2,3-dimethyl-1,3-butadiene to give .     

Lithium fluoroarylamidinates: syntheses, structures, and reactions

Lithium fluoroarylamidinates [(Ar(F)C(NSiMe(3))(2)Li)(n).xD] (Ar(F) = 4-CF(3)C(6)H(4), n = 2, D = OEt(2), x = 1 (2a); n = 1, D = TMEDA, x = 1 (4a); Ar(F) = 2-FC(6)H(4), n = 2, D = OEt(2), x = 1 (2b); Ar(F) = 4-FC(6)H(4), n = 2, D = OEt(2), x = 2 (2c); Ar(F) = 2,6-F(2)C(6)H(3), n = 2, D = OEt(2), x = 1 (2d); n = 2, D = 2,6-F(2)C(6)H(3)CN, x = 2 (3d); Ar(F) = C(6)F(5), n= 2, D = OEt(2), x = 1 (2e), n = 1, D = TMEDA, x = 1 (4e); n = 1, x = 2, D = OEt(2) (5e); D = THF (6e)) were prepared by the well-known method from LiN(SiMe(3))(2) and the corresponding nitrile in diethyl ether or by addition of the appropriate donor D to the respective diethyl ether complexes. Depending on the substituents at the aryl group and on the donors D, three different types of structures were confirmed by X-ray crystallography. Hydrolysis of 2e gave C(6)F(5)C(NSiMe(3))N(H)SiMe(3) (7e) and C(6)F(5)C(NH)N(H)SiMe(3) (8e). The lithium fluoroarylamidinates 2a-2d react with Me(3)SiCl to give the corresponding tris(trimethylsilyl)fluoroarylamidines Ar(F)C(NSiMe(3))N(SiMe(3))(2) (9a-9d). Attempts to prepare C(6)F(5)C(NSiMe(3))N(SiMe(3))(2) from 2e and Me(3)SiCl failed; however, the unprecedented cage [[C(6)F(5)C(NSiMe(3))(2)Li](4)LiF] (10e) in which a fluoride center is surrounded by a distorted trigonal bipyramid of five Li atoms was obtained from this reaction.     

Zinc- and indium-mediated ring-expansion reaction of alpha-halomethyl cyclic beta-keto esters in aqueous alcohol

Radical ring-expansion reaction of various alpha-halomethyl cyclic beta-keto esters and alpha-halomethyl benzocyclic beta-keto esters and chain-extension reaction of alpha-halomethyl beta-keto esters with zinc powder and indium powder in refluxing aqueous alcohol were carried out to generate the corresponding ring-expansion and chain-extension products. As the results indicate, it was found zinc powder was more effective than indium powder to give the corresponding ring-expanded products in quite good yields. Moreover, the addition of zinc bromide as Lewis acid showed an increase of the yields, depending on the substrates. The present reaction conditions are highly effective, simple, and environmentally friendly.     

Enantioselective Friedel–Crafts reactions of ethenetricarboxylates and substituted pyrroles and furans and intramolecular reaction of benzene derivatives

Compared to enantioselective Friedel–Crafts reactions of indoles, reactions of alkylidene malonates with monocyclic aromatic compounds generally proceed with low enantioselectivity. The Friedel–Crafts reactions of ethenetricarboxylates 1 and monocyclic heteroaromatic compounds, such as substituted pyrroles and furans were investigated. The reaction of 1 with 2,4-dimethylpyrrole in the presence of a chiral bisoxazoline–copper(II) complex (10 mol %) in tetrahydrofuran at room temperature gave alkylated products in up to 72% ee. The reaction of 1 with 2-substituted furans gave alkylated products in 46–62% ee. The absolute stereochemistry of the furan Friedel–Crafts product 7e was determined by transformation to the known 2,3-dimethylbutyric acid. The intramolecular reaction of benzene derivatives gave cyclized products up to 56% ee.     

Synthesis of tertiary propargylamines by sequential reactions of in situ generated thioiminium salts with organolithium and -magnesium reagents

Sequential reactions of thioiminium salts generated from thioamides and methyl triflate with organolithium and -magnesium reagents proceed smoothly to give tertiary propargylamines in moderate to high yields. In all cases, two different organometallic reagents are incorporated into the starting thioamides.     

Recent syntheses and reactions of cyclic imidic esters

Δ²-Oxazolines and 4H-5,6-dihydrooxazines are readily obtainable from carboxylic acids and 2- or 3-amino alcohols by gas-phase dehydration, and 4H-dihydrooxazines can also be obtained by condensation of N-(hydroxymethyl) carboxamides with olefins. These cyclic imidic esters undergo reactions in which the ring is cleaved; these reactions include a new type of polymerization. The behavior of alkyl groups in position 2 and the cyclodditions in the 2,3-position also have been studied. Reactions in side chains on position 2 and addition experiments on the sulfur analogues of the cyclic imidic esters are also reported. A table shows the principal infrared bands of substituted Δ²-oxazolines.     

The stereoselective syntheses and reactions of 5,6-epoxy-perhydroisoindolines

Stereo-selective syntheses of 2,5,6-trisubstituted perhydroisoindolines are achieved by preparation of the three diastereoisomeric 5,6-epoxy-perhydroisoindolines and their reactions with nucleophiles, e.g. amines. The transformation of trans-amino alcohols obtained in this way into cis-amino alcohols is described.