The preparation of α-substituted acrylic esters

Treatment of the lithium enolates of cyclopentadiene-blocked acrylates with various electrophilic reagents, such as alkyl chloroformates, α,β-unsaturated carbonyl compounds, epoxides, episulfides, and α-halocarbonyl compounds, has led to a convenient synthetic method for the preparation of α-substituted acrylic esters.     

Amine-induced rearrangements of 2-bromo-1-(1H-indol-3-yl)-2-methyl-1-propanones: A new route to α-substituted indole-3-acetamides, β-substituted tryptamines, α-substituted indole-3-acetic acids and indole β-aminoketones

The reaction of 2-bromo-1-(1H-indol-3-yl)-2-methyl-1-propanone ( 1 ) and 2-bromo-1-(1-methyl-1H-indol-3-yl)-2-methyl-1-propanone ( 2 ) with primary amines proceeds in good yields to produce rearranged amides by a proposed pseudo-Favorskii mechanism. These amides in turn can either be reduced to produce β-substituted tryptamines or hydrolyzed to produce substituted indole-3-acetic acids. When the reaction is carried out using bulky primary or secondary amines, β-aminoketones are produced by elimination of hydrogen bromide followed by Michael addition. When hindered secondary amines or tertiary amines are used, elimination to the α,β-unsaturated ketones occurs.     

A new synthetic route to α-alkylacrylic esters and α-alkylacrylonitriles

α-Alkylacrylic esters and α-alkylacrylonitriles have been synthesized by cracking their cyclopentadiene adducts. The latter were derived by treatment of the lithium enolates of cyclopentadiene-blocked acrylates or acrylonitriles with alkyl halides.     

Studies on furan derivatives IV. A simple preparation of α-substituted β-(5-nitro-2-furyl)ethynyls from α-substituted β-(5-nitro-2-furyl)vinylamines

α-Substituted β-(5-nitro-2-furyl)ethynyls were conveniently prepared by the deamination of α-substituted β-(5-nitro-2-furyl)vinylamines. Also the application of this reaction toward α,β-bis(p-nitrophenyl)vinylamine was examined and afforded α,β-bis(p-nitrophenyl)ethynyl as the main product.     

Stereoselective reduction of α-substituted β-keto esters by hydrostannane/organotin triflate

Stereoselective reduction of α-substituted β-keto esters is achieved by the combined use of hydrostannane/organotin triflate. syn-Aldols are obtained with more than 90% selectivities.     

A new synthesis of α-substituted δ-carbolines

The paper describes a new general synthesis of α-substituted δ-carbolines based on key steps such as metalation, cross-coupling and cyclization.     

Polymers of α- and β-substituted acrylates with controlled structures

Isotactic and syndiotactic living polymerizations of methacrylates with t-C₄H₉MgBr and t-C₄H₉Li-R₃Al (Al/Li≥2), respectively, were utilized to prepare highly stereoregular block and random copolymers, stereoblock PMMAs, highly branched star polymers with stereoregular arms, stereoregular PMMA macromonomers with methacryloyl functions and stereoregular comblike and graft polymers derived therefrom. A combination of t-C₄H₉Li and bis(2,6-di-t-butylphenoxy) methylaluminum was found to be an efficient initiator for heterotactic living polymerization of methacrylates in toluene at −78°C; e.g. ethyl methacrylate gave a polymer with mr content of 87%. Polymerization of triphenylmefhyl crotonate (TrC) with fluorenyllithium (FILi)/N,N,N′,N′-tetramethylethylenediamine in toluene at −78°C gave a threodiisotactic polymer with narrow MWD, whose stereochemistry was confirmed from the x-ray analysis of the pentamer of methyl crotonate (MeC) derived from the TrC pentamer and ¹H NMR spectral comparison of the pentamer and the poly(MeC). The poly(TrC) prepared with FILi/(S,S)-(+)-2,3-dimethoxy-1,4-bis(dimethylamino) butane also gave a threodiisotactic polymer which showed optical activity due to the one-handed helix. Polymerization of t-butyl crotonate was also discussed in some detail.     

A theoretical study of α-substituted cyclopropyl and isopropyl radicals

The structures of α-X-cyclopropyl and α-X-isopropyl radicals (X = H, CH₃, NH₂, OH, F, CN, and NC) are reported at the RHF 3-21G level of theory. The isopropyl radicals are pyramidal with out-of-plane angles varying from 12° (X = CN) to 39° (X = NH₂), and barriers to inversion ranging from 0.4 kcal/mol (X = H) to 4.0 kcal/mol (X = NH₂). The cyclopropyl radicals have larger out-of-plane angles, from 39.9° (X = CN) to 49.4° (X = NH₂), and their barriers to inversion, which increase with the inclusion of polarization functions, vary from 5.5 kcal/mol (X = H) to 16.7 kcal/mol (X = F). In both types of radicals the amino group is the most stabilizing substituent, while the α-fluoro has little effect. The β-fluoro group is weakly destabilizing in the cyclopropyl radical. The strain energies of the cyclopropyl radicals (36–43 kcal/mol) are compared with those of similarly substituted anions, cations, and cyclopropanes.     

A theoretical study of α-substituted isopropyl and cyclopropyl anions

Ab initio molecular orbital theory has been used to probe the effect of the substituent X on the structures, strain energies, stabilization energies, inversion barriers, and proton affinities of carbanions CH₃CX CH and cis-C₃H₄X^?, where X = H, F, CN, and NC. All geometries have been optimized with a 3-21G basis set, and the parent anions (X = H) were also optimized with the same basis set with a diffuse function added (i.e. the 3-21 + G basis set). The anions, with the exception of the α-cyanoisopropyl anion, are pyramidal. The out-of-plane angle, α, for the pyramidal anions decreases in the order F > H ≈ NC > CN, and the barriers to inversion follow the same order with the cyclopropyl anions consistently having higher barriers than the isopropyl anions. The substituents strongly stabilize the anions with the stabilization energy following the order CN > NC > F. The cyano group slightly reduces the strain energy of cyclopropane, but the isocyano and fluoro substituents are weakly and strongly destabilizing, respectively. The pyramidal cyclopropyl anions are less strained than the cyclopropanes except when the substituent is a cyano group where the strain energies are reversed but are very similar. The planar anions all have higher strain energies than the cyclopropanes.     

New synthesis of α-nitroalkyl- and α-nitroaralkylcarboxylic esters from α-nitroalkyl- and α-nitroaralkyl-2-oxazolines

2-Nitroalkyl- and 2-nitroaralkyl-2-oxazolines are readily converted, in one step, to α-nitroalkyl- and α-nitroaralkylcarboxylic esters on treatment with the appropriate alcohol and trifluoroacetic acid (TFA). The initial products of the ring cleavage are the TFA salts of the ammonioalkyl esters of α-nitroalkyl- and α-nitroaralkylcarboxylic acids. These salts undergo facile transesterification to the α-nitrocarboxylic esters on refluxing with the appropriate alcohol.     

An approach to α-substituted amines

A number of amines have been alkylated at the position alpha to nitrogen via free radical methodology. N-(2-Iodobenzyl) and N-(2-iodobenzoyl)‘protected’ amines have been used to generate radicals which rapidly undergo a 1,5-hydrogen shift to give more stable α-amino radicals. These can subsequently be trapped by electron deficient alkenes to give α-alkylated amines.     

Facile stereoselective syntheses of aryl substituted α,β‐unsaturated esters containing a trifluoromethyl group

The Suzuki‐type cross‐coupling reaction of arylboronic acids 3 with ethyl (Z)‐3‐iodo‐4,4,4‐trifluoro‐2‐butenoate 2 , which was generated by hydroiodination of available ethyl 4,4,4‐trifluoro‐2‐butynoate 1 , to afford ethyl (E)‐3‐aryl‐4,4,4‐trifluoro‐2‐butenoates 4 , was studied for the first time. It was found that under the optimum conditions the cross‐coupling reaction could readily give 4 as the sole E‐isomer in 76–91% yields. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:287–290, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10032     

Highly stereoselective addition of organometallic reagents to N-tert-butanesulfinyl imines derived from 3- and 4-substituted cyclohexanones

Addition of alkyl or aryl Grignard reagents to N-sulfinyl imines derived from 3- and 4-substituted cyclohexanones proceeds with good yields and with excellent diasteroselectivity. The selectivity of the reaction is controlled by the ring substituent rather than the sulfinyl group stereochemistry, and therefore racemic tert-butanesulfinamide can be employed.     

Regioselective SN′ allylic substitution versus 1,4-addition: Synthesis of α-substituted β,γ-unsaturated esters

The reaction of the higher order organocuprate reagents R₂Cu(CN)Li₂-BF₃ with γ-bromo α,β-unsaturated esters gives with very high selectivity α-substituted β,γ-unsaturated esters arising from a SN′ allylic substitution. This reaction allows an easy access to α-silyl β,γ-unsaturated esters.     

Palladium-catalysed synthesis of α-methylene γ-butyrolactams via cyclisation of homoallylic chloroformamides

3-Methylene 2-pyrrolidinones were prepared by intramolecular cyclisation of homoallylic chloroformamides catalysed by Pd^II or Pd° complexes.     

A highly stereoselective synthesis of α,β-unsaturated oxazolines

Lithiated 2,4,4-trimethyl-2-oxazoline 2a and 2-chloromethyl-4,4-dimethyl-2-oxazoline 2b react smoothly with a number of nitrones 3 to produce α,β-unsaturated oxazolines 6 and 7 highly stereoselectively.     

Synthesis of heterocyclic compounds. XXIV. Synthesis of pyridines from β-substituted α-phenylacrylonitriles

The reaction of malononitrile with α-phenylcinnamonitriles in ethanolic sodium ethanethiolate is studied as a convenient route to 2-amino-4-aryl-5-cyano-6-ethylthio-3-phenyl-3,4-dihydropyridines ( 5 ) and the corresponding pyridines 6 . From the study of the structure of 5a (Ar = Ph) we can conclude that this cyclization reaction proceeds via a site-selective addition of the ethanethiolate to the cyano group i of the 1,3-tricarbonitrile ( 2 ).     

Polymerization photoinitiated by carbonyl compounds. IV. α-diketones and α-substituted alkanones

The photoinitiation efficiency of the free-radical polymerization of methyl methacrylate and styrene by several carbonly compounds has been determined. The compounds considered were α-substituted ketones and α-dicarbonyl compounds. For the ketones, the initiation efficiency employing methyl methacrylate depends on the α substitution; the values obtained change from less than 10^?3 (acetone) to 0.65 (3-hydroxy-3-methyl-2-butanone). All ketones are more efficient towards methyl methacrylate than styrene. This result can be explained in terms of triplet quenching by the last monomer. The results obtained employing α-dicarbonyl compounds do not conform to a simple pattern. In particular, benzil shows a considerably larger efficiency towards styrene than for methyl methacrylate. Since benzil is efficiently quenched by styrene, the initiation must involve the interaction of an excited benzil molecule and the monomer.