Stereoselectivity and regioselectivity in the segment-coupling Prins cyclization

The scope of the segment-coupling Prins cyclization has been investigated. The method is outlined in Scheme 1 and involves esterification of a homoallylic alcohol (1), reductive acetylation to give the alpha-acetoxy ether (3), and cyclization on treatment with a Lewis acid to produce a tetrahydropyran (4). Alkene geometries dictate the product configurations, with E-alkenes leading to equatorial substituents and Z-alkenes leading to axial substituents (Table 1). Not unexpectedly, applying the method to allylic alcohols leads to fragmentation rather than a disfavored 5-endo-trig cyclization. Dienols in which one alkene is allylic and the other alkene is homoallylic cyclize efficiently and produce the tetrahydropyrans 49-54, Table 3. Dienols with two homoallylic alkenes cyclize with modest to high regioselectively, generating tetrahydropyrans 40-45, Table 2. The relative rates for cyclization decrease in the order of vinyl > Z-alkene > E-alkene > alkyne. The configurations of the products are consistent with cyclization via a chair conformation, Figure 1. The 2-oxonia Cope rearrangement may be a factor in the regioselectivity of diene cyclizations and in the erosion of stereoselectivity with Z-alkenes. This investigation establishes the stereoselectivity and regioselectivity for a number of synthetically useful segment-coupling Prins cyclizations.     

A Lewis acid-promoted cyclization of ethenetricarboxylate derivative aromatic compounds. Novel syntheses of oxindoles and benzofuranones via Friedel-Crafts intramolecular Michael addition

A novel cyclization reaction of ethenetricarboxylate derivative aromatic compounds in the presence of various Lewis acids gave benzo-annulated cyclic compounds such as oxindole and benzofuran derivatives via Friedel-Crafts intramolecular Michael addition in high yields. For example, the reaction of diethyl 2-[(N-methyl-N-phenylcarbamoyl)methylene]malonate (1a) in the presence of ZnCl2 at room temperature gave diethyl 2-(1-methyl-2-oxoindolin-3-yl)malonate (2a) in 98% yield. The reactions also proceeded with a catalytic amount of a Lewis acid such as AlCl3, ZnCl2, ZnBr2, Sc(OTf)3, or InBr3.     

The effects of Lewis acid on the 1,3-dipolar cycloaddition reaction of C-arylaldonitrones with alkenes

The regio- and stereoselectivity of the 1,3-dipolar cycloaddition reactions of C-aryl-N-alkylaldonitrones (1a-e) with some alkenes were found to be affected significantly by the addition of Lewis acid. The rate of the reaction was also affected by adding the Lewis acid. In the reactions using allyl alcohol as a dipolarophile an addition of Lewis acid caused a remarkable acceleration of the reaction and a great change in the stereoselectivity. In the reactions using ethyl acrylate as a dipolarophile the regioselectivity was reversed whether the reaction was performed in the presence or the absence of Lewis acid; i.e. isoxazolidine-5-carboxylates were obtained mainly in the absence of Lewis acid although isoxazolidine-4-carboxylates were obtained mainly in the presence of Lewis acid. When the reaction of C,N-diarylaldonitrones (1k, 1m, 1n) with ethyl acrylate was carried out in the presence of Lewis acid, the cleavage of the N-O bond of the cycloadducts giving gamma-aminoalcohols was also observed besides a reverse phenomenon of regioselectivity.     

Regioselection and orthogonality of the 1-phenyl-3-butenyl (PBU) protecting group in glucopyranosides

The 1-phenyl-3-butenyl (PBU) protecting group was alternatively introduced in position 4 or 6 by regioselective opening of methyl 2,3-di-O-benzyl-4,6-O-benzylidene-alpha-D-glucopyranose with allyltrimethylsilane in the presence of the Lewis acid promoters TMSOTf or AlCl3. The PBU group was selectively removed, in presence of t-butyldimethylsilyl, trityl or acetyl protecting groups, with acids (TFA) or using Pd(CH3CN)2Cl2.     

Chalcogenide-Lewis acid mediated reactions of electron-deficient alkynes with aldehydes

Reactions of but-3-yn-2-one (2) with aldehydes 1 in the presence of a Lewis acid and dimethyl sulfide (3 a) predominantly gave (E)-alpha-(halomethylene)aldols 4-5 in high yields, while reactions of methyl propiolate (6 a) mainly afforded (Z)-3-halogeno-2-(hydroxymethyl)acrylates 7-8 in low to moderate yields. A reaction of dimethyl acetylenedicarboxylate (10) with 1 a in the presence of TiCl(4) and 1,1,3,3-tetramethylthiourea (3 c) produced maleate (E)-11 (40 %) and butenolide 12 (40 %). When a reaction of 6 a with 1 a was carried out in the presence of TiBr(4) and 3 a (0.2 equiv) at -20 degrees C for 60 h, 3-(methylthio)-2-(hydroxyalkyl)acrylate 9 a was obtained in an 8 % yield. Experiments were conducted in order to elucidate the formation mechanism of 9 a, and it was made clear that 9 a was formed via the processes of the Michael addition of sulfide 3 a to alkynoate 6 a and an aldol reaction with 1 a and demethylation.     

A highly stereoselective construction of beta-glycosyl linkages by reductive cleavage of cyclic sugar ortho esters

The preparation of beta-glycosides by the reductive cleavage of spiro sugar ortho esters is described in this report. This procedure is based on a concept completely different from those of other methods for glycosylation. Twelve sugar ortho esters that commonly possess perhydrospiro[2H-pyran-2,2'-pyrano[3,2-d][1,3]dioxin] ring systems in their molecules were reduced by LiAlH(4)/AlCl(3) or NaCNBH(3)/AlCl(3). Among these ortho esters, those (9a-12a) prepared from the D-sugar lactones (1-4) and 2, 3-di-O-benzyl-alpha-D-glucopyranoside (7) or those (19a, 20a) prepared from the L-sugar lactones (5, 6) and 2, 3-di-O-benzyl-alpha-D-galactopyranoside (8) were selectively converted into beta-(1 --> 4)-glycosides (9b-12b or 19b, 20b) in excellent yields by the treatment of LiAlH(4)/AlCl(3). In contrast, the ortho esters (13a-16a or 17a, 18a) that were prepared from combinations of the D-sugar lactones and 8 or those of the L-sugar lactones and 7 were efficiently reduced with NaBH(3)CN/AlCl(3) to afford beta-(1 --> 6)-glycosides (13b-16b or 17b, 18b) selectively. It was remarkable that the resulting disaccharides were obtained with extremely high beta-selectivity even in the cases with mannosyl or rhamnosyl glycosides. Moreover, these products would be useful units for the construction of branched saccharides, because the newly formed hydroxy groups could be again glycosylated without further deprotection procedures. The high regio- and stereoselectivity was totally explained by considering the structures and the conformations of these ortho ester molecules and the stereoelectoronic effects of their spiro ring systems. In addition, the preparation of the sugar ortho esters with glucosamine derivatives and the reactivity of these ortho esters are described in this report. N-Phthaloyl glucosamine derivatives (21, 22) were efficiently reacted with the benzyl-protected gluconolactone (1) in the presence of TMSOMe and TMSOTf to afford ortho esters (23a-c). After the conversion of the phthalimido functionality to the dibenzyl amino group, glucosylideneglucosamine (25) was reduced with LiAlH(4)/AlCl(3) to afford beta-(1 --> 4)-glycoside (26) selectively.     

TBAF-mediated reactions of 1,1-dibromo-1-alkenes with thiols and amines and regioselective synthesis of 1,2-heterodisubstituted alkenes

An efficient synthesis of trisubstituted alkenes including 1,2-heterodisubstituted alkenes has been described. Reactions of thiols and amines with 1,1-dibromo-1-alkenes in the presence of TBAF·3H(2)O afford (Z)-2-bromovinyl sulfides and (Z)-2-bromovinyl amines regio- and stereoselectively. The reaction proceeds under catalyst-free conditions with high efficiency. The coupling reactions of the obtained products bearing bromine atoms with phenylacetylene and phenylboronic acid gave trisubstituted alkenes in good to excellent yields. Cross-coupling with various N, O, S, and P nucleophiles selectively generated 1,2-N,O, 1,2-N,S, 1,2-S,P, 1,2-S,S, and 1,2-S,O heterodisubstituted alkenes.     

Regioselective synthesis of 2-(2-hydroxyaryl)pyridines from the reactions of benzynes with pyridine N-oxides

By modifying the conditions from those in Larock's reported synthesis of 3-(2-hydroxyaryl)pyridines from benzynes, and pyridine N-oxides, we altered the regioselectivity of the reaction toward an efficient synthesis of 2-substituted pyridines. The presence of ethyl propiolate altered the regioselectivity to afford 3-substituted pyridine products instead. We conducted appropriate control experiments that enable a full understanding of the mechanism.     

Facial selectivity in the nucleophilic additions of vinylmagnesium bromide to bicyclo[2.2.2]oct-5-en-2-one derivatives

The levels of diastereoselection attainable by addition of vinylmagnesium bromide to a selection of bicyclo[2.2.2]octenone derivatives 1-6 in the presence of various Lewis acids such as LiBr, CeCl3, TiCl4, ZnBr2, MgBr2, and Et2AlCl have been determined. The 1,2-addition of ketone 1 with vinylmagnesium bromide in THF provided a mixture of anti- and syn-isomers. The reactions of 2 with vinylmagnesium bromide at room temperature afforded anti- and syn-isomers with preference to anti-isomers in most cases. These reactions in the presence of Lewis acids afforded anti-isomers as the major product with an excellent stereoselectivity or as single isomers in some cases. The ketones 3 gave surprisingly different results providing anti-isomers predominantly even in the presence of Lewis acids. The bicyclic ketones 4 and 5 and all-carbon tricyclic ketone 6 furnished the syn-isomer as the main product. There is no significant effect of Lewis acid catalysis in the nucleophilic addition reactions of 1, 4, 5, and 6. The use of a preformed vinylmagnesium bromide-CeCl3 reagent for the addition reactions of 2d-f and 3d-f provided almost exclusively syn-isomers. The substituents and reaction conditions can influence facial selectivity in the nucleophilic additions to the bicyclo[2.2.2]oct-5-en-2-one derivatives.     

Lewis Acid promoted tandem intermolecular Diels-Alder/intramolecular allylation reactions of silyl-substituted 1,3-butadienes leading to multisubstituted 7-norbornenones and related polycyclic compounds

7-Norbornenones of exo,exo-disubstituted patterns were formed highly selectively in good yields from Lewis acid-promoted tandem intermolecular Diels-Alder/intramolecular allylation reactions. The intermolecular Diels-Alder reaction between 1,4-bis(trimethylsilyl)-1,3-butadienes or 1-trimethylsilyl-1,3-butadienes with maleic anhydride in the presence of newly sublimed AlCl3 afforded their corresponding cycloaddition adducts, which underwent AlCl3-mediated intramolecular allylation of the carbonyl group by the in situ generated allylsilane moiety affording 7-norbornenones of exo,exo-disubstituted patterns.     

Crystallization-controlled dynamic self-assembly and an on/off switch for equilibration using boronic ester formation

Macrocyclic boronic esters of different sizes can be prepared selectively from the same starting diboronic acid and 1,2-diol by means of an interesting dynamic self-assembly phenomena. More specifically, two kinds of macrocyclic boronic esters could be formed diastereoselectively and nearly quantitatively under neutral conditions by the addition of an appropriate guest molecule that acts as a template. Although a mixture of tetrol 1 and di(boronic acid) 2 in methanol gave only insoluble polymeric boronic esters, a soluble macrocyclic boronic ester, homo-[2+2], was obtained selectively in the presence of toluene as a guest molecule. Furthermore, when benzene was employed as a guest molecule, the selective formation of another macrocyclic boronic ester, hetero-[3+3], occurred. Interestingly, each of these macrocycles could be converted into the other in the presence of methanol and the appropriate guest molecule; however, under aprotic conditions, guest molecules encaged by the macrocyclic boronic ester could be exchanged without affecting its structure. Thus the presence or absence of a protic solvent could be used as a regulator to switch on or off the dynamic equilibrium of the system. In addition, investigation of the effect of reaction time, direct observation of the reaction mixture by NMR spectroscopy, and carrying out the reaction using optically active tetrol suggested that precipitation plays an essentially important role in the selective formation of the macrocyclic boronic esters. Thus, although both of [2+2] and [3+3] were present as solutes in the reaction mixture, the type of added guest molecule induced the selective precipitation of only one form of macrocyclic boronic ester, hence displacing the equilibrium of the system.     

Chemical properties of N-Benzoylimines of quinazoline,quinoxaline, and phthalazine

Reactions of 1-benzoylimino-4-phenylquinazolinium (I), 1-benzoylimino-3-phenylquinox-alinium (II), and 3-benzoylimino-1-phenylphthalazinium betaines (III) with nucleophiles (hydroxide and cyanide ions) and 1,3-dipolarophiles (acetylenic esters and maleimides) were investigated. Heating I in aqueous alkali gave 3-phenylindazole, while similar treatment of II and III resulted in the formation of 1-benzoylamino-2-oxo-3-phenylquinoxaline and 2-benzoylamino-1-oxo-4-phenylphthalazine, respectively. Reaction of II and III with cyanide ion afforded 2-cyano-3-phenylquinoxaline and 1-cyano-4-phenylphthalazine in high yields, respectively. 1,3-Dipolar cycloaddition reactions of I and III with dimethyl acetylenedicarboxylate and ethyl propiolate afforded primary 1:1 cycloadducts, while the reaction of II with dimethyl acetylenedicarboxylate gave a product which is formed by ring opening of a primary adduct. The reaction of I-III with N-methyl and N-phenylmaleimides afforded the corresponding primary 1:1 cycloadducts in high yields, whose stereochemical assignment was made on the basis of nmr spectroscopy.     

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.     

Stereocontrol during the radical polymerization of methyl methacrylates with combined Lewis acids:Aluminium trichloride(AlCl_3) and iron dichloride tetrahydrate

The radical polymerization of methyl methacrylate(MMA) was carried out in the presence of combined Lewis acids of the AlCl3-FeCl2 system.Compared with the polymerization produced in the presence of single Lewis acids,AlCl3 or FeCl2,the MMA polymerization in the presence of AlCl3-FeCl2 composite in CHCl3 or 1-butanol produced a polymer with a higher isotacticity and in toluene produced a polymer with a much higher isotacticity(mm=50%) .The molecular weight and polydispersity of PMMA in the presence of Lewis ...     

全氟和多氟烷基磺酸的研究 IX. 5-卤-3-氧杂-全氟戊磺酰氟的化学转化

5-Halo-3-oxa-perfluoropentanesulfonic acids 2,4 were obtained in high yields by treating the corresponding sulfonyl fluorides successively with KOH and concentrated H2SO4: Treatment of the acids with P2O5 gave corresponding anhydrides 3, 5. 3 reacted with various alcohols in the presence of pyridine to yield sulfonates 6. 5-Iodo-3-oxa-perfluoropentanesulfonyl fluoride (1) was converted to the acyl fluoride 9 by fuming sulfuric acid. Depending on the reaction temperature 9 can be hydrolyzed to fluorosulfonyl perfluoroalkanoic acid 10 and/or mixed dibasic acid 11. A similar phenomenon was also observed in the case of hydrolysis of fluorocarbonyl-perfluoromethanesulfonyl fluoride(13). Alcohol reacted readily with the acyl fluoride group but not with the sulfonyl group in 9 giving carboxylic esters, which can be further transformed to the corresponding sulfonates. Perfluoroalkoxide ion -O(CF2)2O(CF2)2SO2F prepared from 9 and F- reacted with active alkyl halides yielding the corresponding ethers. The interaction of 5-halo-3-oxa-perfluoroalkane-sulfonyl fluoride with AlCl3 was investigated. Friedel-crafts acylation of aromatic compounds with 9 in the presence of anhydrous AlCl3 is also reported. The yields of the desired ketones can be improved by using CCl4 as a solvent and changing the order of addition of reactants.     

Acid-catalyzed reactions of aromatic aldehydes with ethyl diazoacetate: an investigation on the synthesis of 3-hydroxy-2-arylacrylic acid ethyl esters

Several commercial Lewis acids, including those of the Bronsted type, specifically HBF(4).OEt(2), are able to catalyze the reaction between aromatic aldehydes and ethyl diazoacetate to produce 3-hydroxy-2-arylacrylic acid ethyl esters and 3-oxo-3-arylpropanoic acid ethyl esters. Reactions catalyzed by the iron Lewis acid [(eta(5)-C(5)H(5))Fe(+)(CO)(2)(THF)]BF(4)(-) (i.e., 1) have the best yields and greatest ratio of 3-hydroxy-2-arylacrylic acid ethyl ester. The product distribution of 1 is not affected in the presence of Proton Sponge, but is dependent on temperature and the nature of the substrate aldehyde, whereas the activity of HBF(4).OEt(2) is affected by the presence of Proton Sponge and is reactive at temperatures as low as -78 degrees C. Consequently, both 1 and HBF(4).OEt(2) are valuable catalysts in producing important 3-hydroxy-2-arylacrylic acid ethyl esters as precursors to biologically active compounds.     

Direct Chemoselective Synthesis of N-3-Substituted Pyrimidinones in a Microwave-Assisted Method

Synthesis of selectively N-3-substituted pyrimidine nucleobases or pyrimidinones has always been a challenge because of poor regioselectivity and chemoselectivity. In this article we demonstrate a single-step, de novo synthesis of selectively N-3-substituted modified pyrimidinones. We have developed a microwave-assisted methodology for direct, chemoselective alkylation, benzylation, and arylation of C-5 and C-6 substituted pyrimidine nucleobases selectively at the N-3 position. The reactions were found to proceed, with high efficiency, without the requirement of solvent and were complete within 10–15 min of irradiation. The efficiency of the method was further improved by addition of a Lewis acid, which not only increases the yield significantly but also accelerates the reaction rate.     

Simple,One-Pot,and Three-Component Coupling Reactions of Azaarenes (Phenanthridine,Isoquinoline, and Quinoline), with Acetylenic Esters Involving Methyl Propiolate or Ethyl Propiolate in the Presence of NH-Heterocyclic or 1,3-Dicarbonyl Compounds

Three-component reactions involving azaarenes (quinoline, isoquinoline, and phenanthridine) with acetylenic esters such as methyl propiolate or ethyl propiolate in the presence of NH-heterocyclic compounds (carbazole, maleimide, 5-nitroindazole, 2-benzoxazolinone, indole, and 2-methylindole) or 1,3-dicarbonyl compounds involving acetylacetone and N,N′-dimethylbar bituric acid are described. The reactions proceeded smoothly at room temperature without a catalyst and with excellent yields. This method is very useful for functionalizing aza-aromatic compounds in a one-pot operation.     

Formation of 4-methylphenanthrenes in palladium-catalyzed annulation of diethyl 2,2'-diiodo-4,4'-biphenyldicarboxylate with internal alkynes, using methyl nitrobenzoates as the methylating agent

The reaction of diethyl 2,2'-diiodo-4,4'-biphenyldicarboxylate (7) with diarylacetylenes in the presence of 3, 5-(NO(2))(2)C(6)H(3)CO(2)Me (MeDNB) or 4-(NO(2))C(6)H(4)CO(2)Me (MePNB), Pd(OAc)(2) (10 mol %), K(2)CO(3), and Bu(4)NBr, in DMF at 100 degrees C, gives 4-methyl-9,10-diaryl-2, 7-phenanthrenedicarboxylic acid diethyl esters in good yields. The methyl group at position 4 originates from the electron-deficient methyl nitrobenzoates. High regioselectivity for the annulation of 7 with nonsymmetrical diarylalkynes was observed with the selectivity controlled mainly by electronic factors rather than by steric factors. A competitive kinetic isotope study was carried out using a 1:1 mixture of MePNB and MePNB-d(3) in the annulation reaction of 7 which gave 4-methyl- and 4-(methyl-d(3))phenanthrene in a 67:33 ratio, leading to an apparent value of k(H)/k(D) = 1.26. Possible mechanisms for the methyl transferring process are discussed.     

Differences in reactions of vinyl derivatives of pyrrole and thiophene with acetylenic esters

1-Methyl-2-vinylpyrrole and 2-vinylthiophene showed remarkable differences in reactivity and regioselectivity upon reaction with methyl propiolate, respectively forming dimethyl 1-methylindole-4,7-dicarboxylate and dimethyl benzo[b]thiophene-4,6-dicarboxylate. 1-Methyl-2-(1-propenyl)pyrrole reacted with dimethyl ace-tylenedicarboxylate to give Diels-Alder and Michael-type adducts. On the other hand, 2-(1-propenyl)thiophene gave a 1:2 adduct which results via an initial cycloaddition and subsequent ene reaction.