Synthesis of N-substituted aziridine-2-carboxylates

The synthesis of the methyl esters of N-methoxycarbonyl- and N-benzyloxycarbonylaziridine-2-carboxylic acid 2 by reacting methyl 2-chloro-N-carbalkoxyglycinate 1 with diazomethane is described. The aziridines were readily converted to derivatives of O-methylserine 5 and S-methylcysteine 6.     

Lewis acid-catalyzed stereospecific ring expansion of aziridine-2-carboxylates to imidazolidin-2-ones

Lewis acid-catalyzed ring expansion reaction of chiral aziridine-2-carboxylate proceeds regio- and stereospecifically to yield enantiomerically pure 4-functionalized imidazolidin-2-ones in high yields.     

Synthesis of alkyl 2-(bromomethyl)aziridine-2-carboxylates and alkyl 3-bromoazetidine-3-carboxylates as amino acid building blocks

A short synthesis of alkyl 2-(bromomethyl)aziridine-2-carboxylates and alkyl 3-bromoazetidine-3-carboxylates was developed involving amination, bromination, and base-induced cyclization of alkyl 2-(bromomethyl)acrylates. These new small ring azaheterocyclic α- and β-amino acid derivatives are promising synthons as demonstrated by their transformation to 2-(aminomethyl)aziridine-2-carboxylates and 3-aminoazetidine-3-carboxylates.     

Lewis acid promoted phenylseleno group transfer tandem radical cyclization reactions

[reaction: see text] A new Lewis acid promoted phenylseleno group transfer tandem radical cyclization method was developed. In the presence of Lewis acids such as Yb(OTf)3 or Mg(ClO4)2, under photolysis condition at low temperature (-45 degrees C), various unsaturated alpha-phenylseleno beta-keto amides underwent radical cyclization reactions to give monocyclic or bicyclic products in a highly efficient, regioselective, and stereoselective manner.     

New methodology for the preparation of N-tosyl aziridine-2-carboxylates

N-Tosyl aziridine-2-carboxylate methyl esters were prepared from methyl N-tosyl-l-serinate or N-tosyl-l-threoninate, tosyl chloride, and K₂CO₃, under phase-transfer catalysis (PTC) conditions. The same methodology, as applied to the tert-butyl N-tosyl-l-serine amide, afforded the corresponding newly prepared aziridine-2-carboxamide, as an enantiomerically pure compound.     

Synthesis of 2H-indazoles via Lewis acid promoted cyclization of 2-(phenylazo)benzonitriles

Lewis-acid promoted "coarctate" cyclization of 10 2-(phenylazo)benzonitrile derivatives furnishes the isoindazole ring system in ca. 65-95% yield. A plausible mechanism for this unusual transformation is proposed.     

Formation of 3-pyrrolin-2-one or imidazolidine derivatives by slow dimerization of N-substituted aziridine-2-carboxylates

Prolonged storage (45–60 days) of N-methyl- or N-cyclopropylaziridine-2-carboxylates leads to their dimerization through the N—C(3) bond cleavage to form 1,3-disubstituted 2-methylimidazolidine-2,4-dicarboxylates in high yields. Prolonged storage of 1-benzyl-aziridine-2-carboxylate (like the reactions of alkyl pyruvates with primary amines) results in cyclocondensation to yield 3-pyrrolin-2-one derivative. Dedicated to Corresponding Member of the Russian Academy of Sciences E. P. Serebryakov on the occasion of his 70th birthday. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 1025–1029, April, 2005.     

Synthesis of medium-sized cyclic γ-haloketones by radical mediated ring-opening reaction of Lewis acid catalyzed (2+2)-cycloaddition products

Novel entry to synthesize medium-sized cycloalkanones is described. Thus, employment of catalytic (2+2)-cycloaddition for cyclic silyl enol ether followed by radical mediated ring-opening reaction provided medium-sized γ-halocycloalkanones.     

Synthesis of methyl 1,5-diaryl-1H-pyrrole-2-carboxylates via acid-catalyzed ring-opening/ring-closure sequence

A facile synthesis of methyl 1,5-diaryl-1H-pyrrole-2-carboxylates was reported in this article. Acid-catalyzed reaction of methyl 2-aroyl-1-phenoxycyclopropanecarboxylates with aromatic amines underwent smoothly to give methyl 1,5-diaryl-1H-pyrrole-2-carboxylates in high to excellent yields under mild conditions.     

Chiral aziridine-2-carboxylates: versatile precursors for functionalized tetrahydroisoquinoline (THIQ) containing heterocycles

Preparation of functionalized 3,4-dihydroisoquinolines 17a–j from (S)-N-methoxy-N-methyl-1-[(R)-1-phenylethyl]aziridine-2-carboxamide 4 is an effective route for the synthesis of 3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinolin-4-ols. Stereoselective reduction of the cyclic imines 17a–j resulted in (1S,3S,4R)-4-(tert-butyldimethylsilyl-oxy)-3-[(tert-butyldimethylsilyloxy)methyl]-6,7-dimethoxy-1,2-disubstituted-1,2,3,4-tetrahydroisoquinolines and the desilylation of the TBS groups afforded (1S,3S,4R)-3-(hydroxymethyl)-6,7-dimethoxy-1,2-disubstituted-1,2,3,4-tetrahydroisoquinolin-4-ols 19a–i in good yields. Also, an asymmetric synthesis of novel tetracyclic 3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinolin-4-ols 23 and 25 was successfully achieved via Pd-catalyzed N-arylation and C–C coupling reaction.     

Catalytic asymmetric Nazarov reactions promoted by chiral Lewis acid complexes

Divinyl ketones bearing alpha-ester or alpha-amide groups undergo Nazarov cyclizations to give cylopentenones using copper-bisoxazoline Lewis acid complexes with moderate to good ees. [reaction: see text]     

Vanadium-catalyzed oxidative bromination promoted by Brønsted acid or Lewis acid

The oxidative bromination of arenes was induced by a vanadium catalyst in the presence of a bromide salt and a Brønsted acid or a Lewis acid under molecular oxygen, which provides an eco-friendly bromination method as compared with a conventional bromination one with bromine. This catalytic reaction could be applied to the bromination of alkenes and alkynes to give the corresponding vic-bromides. Use of aluminum halide as a Lewis acid in place of a Brønsted acid was demonstrated to provide a more practical protocol for the oxidative bromination. From ketones, α-bromination products were obtained. AlBr₃ was found to serve as both a bromide source and a Lewis acid to induce the bromination smoothly. ⁵¹V NMR experiment showed that this catalytic bromination is likely to depend on the redox cycle of a vanadium catalyst under molecular oxygen.     

Synthesis of beta-substituted alpha-amino acids via Lewis acid promoted enantioselective radical conjugate additions

[Chemical reaction: See text] Lewis acid promoted radical conjugate additions to beta-substituted alpha,beta-unsaturated alpha-nitro esters and amides were investigated. With achiral Lewis acids, there was competition between the desired radical conjugate addition and undesired alkene reduction mediated by Bu3nH. Zinc Lewis acids provided the greatest amounts of addition products with both substrate classes. Studies with Bu3nD indicated that the acidic alpha-stereocenter of the alpha-nitro ester products does not racemize under controlled workup conditions. The corresponding alpha-nitro amides racemized significantly during chromatography, but this problem could be greatly minimized by subjecting the crude adducts to subsequent transformations. Indium-mediated reduction of the nitro group followed by acylation of the resulting amine provided good yields of beta-substituted alpha-amino acid derivatives with mimimal levels of racemization. Attempts to use chiral Lewis acids in a stereoselective variant of this process revealed that Kanemasa's DBFOX/Ph ligand (14a) was uniquely effective. Moderate to good ee's and low dr's were obtained with amide substrates. Determination of the absolute configurations of the syn and anti isomers of adduct 7b showed that the hydrogen atom abstraction step was significantly more stereoselective than the radical conjugate addition step. A model for substrate binding to the chiral Lewis acid is presented.     

Enantioselective aldol reaction of silyl ketene acetals promoted by a Lewis base-activated Lewis acid catalyst

The enantioselective aldol reaction of a silyl ketene acetal was promoted by chiral phosphine oxide-activated tetrachlorosilane to afford the corresponding adduct in high yield with moderate enantioselectivity.     

Lewis acid promoted cyclization of enyne triesters and diesters

Reactions of enynes with three or two ester groups (1-4) in the presence of halogen-ligand Lewis acids gave cyclized products with halide incorporation (5-8) with high generality. The cyclization process was also analyzed in a theoretical study. Facile isomerization and dehydrohalogenation of five-membered products 5 and 8 by Al(2)O(3) or Et(3)N were also observed; this process introduces conjugated moieties into the products.     

Lewis acid promoted carbon-carbon bond cleavage of gamma-silyloxy-beta-hydroxy-alpha-diazoesters

Cyclic gamma-silyloxy-beta-hydroxy-alpha-diazoesters undergo efficient rupture of the Cbeta-Cgamma bond when treated with tin tetrachloride to provide tethered aldehyde ynoate products in high yield.     

Reactions of 2-(trifluoromethyl)-2-hydroxy-2H-chromenes with thiophenols promoted by Lewis acid

A Lewis acid promoted nucleophilic substitution reaction between 2-(trifluoromethyl)-2-hydroxy-3-ethoxycarbonyl-2H-chromenes 1 and thiophenols affording thiophenyl substituted products, that is, 4-thiophenyl-2-trifluoromethyl-3-ethoxycarbonyl-4H-chromene and 2-thiophenyl-2-trifluoromethyl-3-ethoxycarbonyl-2H-chromene.     

Straightforward synthesis of 4,5-bifunctionalized 1,2-oxazinanes via Lewis acid promoted regio- and stereo-selective nucleophilic ring-opening of 3,6-dihydro-1,2-oxazine oxides

Functionalized 1,2-oxazinanes are interesting and valuable heterocycles with potential applications in synthetic and medicinal chemistry. A straightforward strategy for quick access to unprecedented trans-4-hydroxyl-5-azido/cyano/amino 1,2-oxazinanes are developed: N-COR 3,6-dihydro- 1,2-oxazine oxides are prepared with ease from related dihydro- 1,2-oxazines and opened by nucleophiles TMSN₃, TMSCN and aryl/alkyl amines. Appropriate Lewis acid catalysts are found playing a vital role for both reaction rate and regioselectivity. The N-COR group can be removed under mild conditions to provide highly desirable NH 1,2-oxazinanes inaccessible via previous methods.     

Synthesis of alpha-glucuronic acid and amide derivatives in the presence of a participating 2-acyl protecting group

[reaction: see text] Participating acyl groups located at C-2 in glucosyl and related donors generally promote formation of 1,2-trans-glycosides. Reactions of some glucuronic acid donors with TMSN(3)/SnCl(4) or ROH/SnCl(4) gave only the 1,2-cis-glycoside. The stereoselectivity is consistent with participation of the C-6 group. The methodology was used for the synthesis of a Kdn2en mimetic with the alpha-configuration.     

Synthesis and absolute configurations of diastereomeric aziridine-2-carboxylic acid derivatives containing valine and hexafluorovaline fragments

Individual diastereomers of aziridine-2-carboxylic acid esters that contain R- and S-valine and R- and S-hexafluorovaline fragments were isolated by high-performance liquid chromatogrpahy (HPLC). The absolute configurations of both asymmetric centers of the diastereomeric esters were determined on the basis of the parameters of the PMR spectra (AB) and circular dichroism (the sign of the cotton effect at 200–220 nm).Communication 44 from the series Asymmetric unbridged nitrogen. See [1] for communication 43.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1355–1358, October, 1985.