Lewis acid-catalyzed ring-opening reactions of methylenecyclopropanes with alcoholic or acidic nucleophiles

[reaction: see text] Methylenecyclopropanes can react with various nucleophiles such as alcohols, phenols, carboxylic acids, and thiols to give the corresponding homoallylic esters or ethers in good yields with good stereoselectivities in the presence of Lewis acids.     

Origins of opposite syn-anti diastereoselectivities in primary and secondary amino acid-catalyzed intermolecular aldol reactions involving unmodified alpha-hydroxyketones

The effects of different amino acid catalysts on the stereoselectivity of the direct intermolecular aldol reactions between alpha-hydroxyketones and isobutyraldehyde or 4-nitrobenzaldehyde have been studied with the aid of density functional theory methods. The transition states of the crucial C-C bond-forming step with the enamine intermediate addition to the aldehyde for the proline and threonine-catalyzed asymmetric aldol reactions are reported. B3LYP/6-31+G** calculations provide a good explanation for the opposite syn vs anti diastereoselectivity of these two kinds of amino acid catalysts (anti-selectivity for the secondary cyclic amino acids proline, syn-selectivity for the acyclic primary amino acids like threonine). Calculated and observed diastereomeric ratio and enantiomeric excess values are in good agreement.     

The production of episulfonium complexes from propylene and the regioselectivity of their reactions with nucleophiles

Conclusions The regioselectivity of the reactions of stable S-arylsulfonium complexes prepared from propylene and various nucleophiles corresponds to Markovnikov addition and the degree of selectivity of this reaction depends on the nature of the aromatic substituent. The episulfonium complexes prepared were characterized by¹³C NMR spectra.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 3, pp. 563–572, March, 1979.     

Mechanism of the reactions of synthetic Fe-S-based clusters with PhCOCl: parallel pathways involving free and coordinated thiolate as nucleophiles

Terminal thiolate ligands on the synthetic Fe-S-based clusters [Fe4S4(SR)4]2- (R = Et or SPh) or [{MoFe3S4(SPh)3}2(mu-SPh)3]3- are replaced by chloride in a reaction with PhCOCl to produce [Fe4S4Cl4]2- and [{MoFe3S4Cl3}2(mu-SPh)3]3-, respectively. Kinetic studies using stopped-flow spectrophotometry show that, in general, the mechanisms of these reactions in MeCN occur by two pathways. One pathway is independent of the concentration of PhCOCl and involves rate-limiting dissociation of the thiolate ligand. The free thiolate subsequently reacts with PhCOCl to produce PhCOSR and the Cl- which binds to the vacant site on the cluster. The second pathway exhibits a nonlinear dependence on the concentration of PhCOCl and involves initial, rapid binding of PhCOCl to the cluster followed by intramolecular thiolate ligand attack on the coordinated acid chloride. The intermediate in which PhCOCl is bound to the cluster has been detected spectrophotometrically. The ways in which the rates of the reactions between PhCOCl and Fe-S-based clusters are affected by changes of the terminal thiolate, the metal composition of the cluster core, and the protonation state of the cluster have been investigated and are compared with the effect these same changes have on the rates of nucleophilic substitution.     

Glyconothio-O-lactones. Part I. Preparation and reactions with nucleophiles

Furanoid and pyranoid glyconothio-O-lactones were prepared by photolysis of S-phenacyl thioglycosides or by thermolysis of S-glycosyl thiosulfinates, which gave better results than the thionation of glyconolactones with Lawesson's reagent. Thermolysis of the thiosulfinates obtained from the dimannofuranosyl disulfide 7 or the manofuranosyl methly disulfide 8 (Scheme 2) gave low yields of the thio-O-lactone 2 . However, photolysis of the S-phenacyl thioglycoside 6 obtained by in situ alkylation of the thiolato anion derived from 5 led in 78–89% to 2 . Similarly, the dithiocarbonate 10 was transformed, via 11a , into the ribo-thio-O-lactone 12 (79%). Thermolysis of the peracetylated thiosulfinates 14 (Scheme 3) led to the intermediate thio-O-lactone 15 , which underwent facile β-elimination of AcOH (→ 16 , 75%) during chromatography. The perbenzylated S-glucopyranosyl dithiocarbonate 18 (Scheme 4) was transformed either into the S-phenacyl thioglucoside 19 or into a mixture of the anomeric methyl disulfides 21a/b . Whereas the photolysis of 19 led in moderate yield to 2-deoxy-thio-O-lactone 20 , oxidation of 21b and thermolysis of resulting thiosulfinates gave the thio-O-lactone 4 (79%), which was transformed into 20 (36%) upon photolysis. The pyranoid manno-thio-O-lactone 26 was prepared in the same way and in good yields from 22 via the dithiocarbonate 24b and the disulfide 25 . The ring conformations of the δ-thio-O-lactones, flattened ⁴C₁ for 15 and 4 and B_2,5 for 26 , are similar to the ones of the O-analogous oxo-glyconolactones. The reaction of 2 (Scheme 5) with MeLi and then with MeI gave the thioglycoside 27 (29%) and the dimeric thio-O-lactone 29 (47%). The analogous treatment of 2 with lithium dimethylcuprate (LiCuMe₂) and MeI led to a 4:1 mixture (47%) of 31 and 27 . The structure of 2 was proven by an X-ray analysis, and the configuration at C(6) and C(5) of 29 was deduced from NOE experiments. Substitution of MeI by CD₃I led to the CD₃S analogues of 27 , 29 , and 31 , i.e. 28 , 30 , and 32 , respectively, evidencing carbophilic addition and ‘exo’-attack on 2 by MeLi and the enethiolato anion derived from 2 . The preferred ‘endo’-attack of LiCuMe₂ is rationalized by postulating a single-electron transfer and a diastereoselective pyramidalization of the intermediate radical anion.     

L-prolinamide-catalyzed direct nitroso aldol reactions of alpha-branched aldehydes: a distinct regioselectivity from that with L-proline

The first direct enantioselective N-nitroso aldol reaction of aldehyde with nitrosobenzene catalyzed by an L-prolinamide derivative is presented; the reactions proceed smoothly furnishing the -hydroxyamino carbonyl compounds, the otherwise disfavored products, in good yields with up to 64% ee.     

Regioselectivity in the reactions of polyfunctionalised pyrroles with nucleophiles

The polyfunctionalised pyrrole, 3,5-dichloro-1H-pyrrole-2,4-dicarbaldehyde reacts with secondary amines by condensation with the 2-carbaldehyde to give methylene-substituted pyrroles, while its N-alkyl derivatives undergo substitution of the 5-chloro group to give 5-substituted pyrroles.     

HSAB-driven regioselectivity difference in the Lewis-acid catalyzed reactions of 2-C-substituted glycals with sulfur and oxygen nucleophiles: direct versus allylic substitution

A remarkable regioselectivity difference in the Lewis-acid catalyzed reactions of 2-C-acteoxymethyl glycals with thiophenols and phenols has been observed. The reaction with thiophenols led to preferential formation of a new class of compounds viz. 2-C-arylthiomethyl glycals via direct attack at the C-2 side chain primary carbon bearing the leaving group. In contrast, phenols were reported to afford predominantly 2-C-methylene-O-aryl glycosides via allylic attack at the anomeric carbon. The observed results correlate well with the HSAB principle proposed earlier for similar type of reactions with simple glycals. In addition, formation of an unusual bis-thioarylated product in presence of an excess of thiophenol is also reported.     

Cu(I)-catalyzed diamination of conjugated dienes. Complementary regioselectivity from two distinct mechanistic pathways involving Cu(II) and Cu(III) species

Conjugated dienes can be diaminated at the internal and/or terminal double bonds using Cu(I) as catalyst and N,N-di-t-butyldiaziridinone (1) as nitrogen source. The regioselectivity is highly dependent upon the choice of Cu(I) catalyst and the substituents on diene substrates. The diamination likely proceeds via two mechanistically distinct pathways. The N-N bond of N,N-di-t-butyldiaziridinone (1) is first homolytically cleaved by the Cu(I) catalyst to form four-membered Cu(III) species A and Cu(II) radical species B, which are in rapid equilibrium. The internal diamination likely proceeds in a concerted manner via Cu(III) species A, and the terminal diamination likely involves Cu(II) radical species B. Kinetic studies have shown that the diamination is first-order in N,N-di-t-butyldiaziridinone (1), zero-order in olefin, and first-order in total Cu(I) catalyst, and the cleavage of the N-N bond of 1 by the Cu(I) catalyst is the rate-determining step. The internal diamination is favored by use of CuBr without ligand and electron-rich dienes. The terminal diamination is favored when using CuCl-L and dienes with radical-stabilizing groups.     

Electronic regioselectivity in the reactions of pyridinium ylides with tetracyanoethylene

Highly regioselective reactions of pyridinium ylides with tetracyanoethylene occur via an Ad_N-E mechanism to form Z-isomers of 3-aroyl-3-(1-pyridinio)-1,1,2-tricyano-2-propenides-1, corresponding in structure to 1,4-ylides with maximum charge separation. If the unsaturated nitrite starting material contains a nucleofugal group 1,2-elimination predominates over 1,3-elimination.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1087–1094, August, 1991.     

A mild procedure for the Lewis acid-catalyzed ring-opening of activated cyclopropanes with amine nucleophiles

The Lewis acid-catalyzed ring-opening of methyl 1-nitrocyclopropanecarboxylates with amine nucleophiles is described. The reaction proceeds at room temperature and with complete preservation of the enantiomeric purity from the electrophilic center of the cyclopropane to the acyclic product. The methodology was applied in an enantioselective synthesis of the dual serotonin/norepinephrine reuptake inhibitor (3R)-3-(1 H-indol-1-yl)- N-methyl-3-phenylpropan-1-amine.     

1,2-rearrangement of N-Chloro-N-alkoxyamines in reactions with nucleophiles

Conclusions We discovered 1,2-rearrangements of N-chloro-N-alkoxyamines with migration of phenyl, alkyl, and carbomethoxy groups to the nitrogen atom.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1065–1069, May, 1981.     

The cyclopropyl effect on the regioselectivity of coupling reactions involving the lithiation of 1-cyclopropyl-2-arylacetylenes

The cyclopropyl effect controlled the regioselectivity of the cross coupling reactions of propargylic/allenylic metallic species with electrophiles affording alkynic cyclopropanes. It was proposed that the strain in cyclopropyl ring, which makes the formation of vinylidenecyclopropanes unfavorable, determined the regioselectivity. Control experiment of i-propyl, cyclobutyl, and cyclohexyl- phenylacetylenes were conducted to support the above speculation.     

Chemo- and regioselectivity in the reactions of polyfunctional pyrroles

The chemo- and regioselectivity of the reduction, oxidation and Wittig reaction of polyfunctional pyrroles, containing a variety of reactive centres was investigated. The reaction of 3,5-dichloropyrrole-2,4-dicarboxaldehydes with potassium permanganate leads to regioselective oxidation of the 2-formyl group, while the Wittig reaction with 1 equiv of a triphenylphosphorane produced the 2-alkenyl substituted pyrroles.     

Two novel 1,2,4,5-tetrazines that participate in inverse electron demand Diels-Alder reactions with an unexpected regioselectivity

[reaction: see text] Two new unsymmetrical 1,2,4,5-tetrazines, 3-methylsulfinyl-6-methylthio-1,2,4,5-tetrazine (4) and 3-(benzyloxycarbonyl)amino-6-methylsulfinyl-1,2,4,5-tetrazine (5), were prepared, and the scope of their participation in intermolecular inverse electron demand Diels-Alder reactions was defined. As anticipated, sulfoxides 4 and 5 (4 > 5) display a reactivity that is substantially greater than that of their corresponding sulfides (2 and 3), being derived from their enhanced electron-deficient character and resulting in a wider range of potential dienophile choices or the use of milder reaction conditions. The cycloaddition reactions were expectedly regioselective, typically producing a single cycloadduct, ensuring their synthetic utility, but both were found to proceed with a regioselectivity opposite what would be anticipated and complementary to that observed with 2 and 3.     

The regioselectivity in the reactions of N-aryl-C-ethoxycarbonylnitrilimines with acrylic acid derivatives

The cycloaddition of a series of C-ethoxycarbonyl-N-arylnitrilimines 5a-f to acrylic acid derivatives namely acrylamide, acrylonitrile and ethyl acrylate has been studied. Under thermal conditions 1,3-dipolar cycloadditions proceed with complete regioselectivity to give 5-R substituted 2-pyrazolines 8–10 in high yield. The structures of the cycloadducts 8–10 were confirmed by ¹³C nmr, ¹H nmr and ir spectra. The regioselectivity is interpreted in terms of HOMO(nitrilimine)-LUMO(dipolarophile) interaction.     

Effect of methoxyl group position on the regioselectivity of ammonia substitution reactions involving 3,3'-dichloro-2,2'-binaphthoquinones

A series of methoxyl-substituted 3,3'-dichloro-2,2'-binaphthoquinones 2 were prepared and evaluated for regioselectivity in ammonia substitution reactions. Biquinone 2b underwent regiospecific amination at the unsubstituted chloronaphthoquinone unit whereas the isomeric biquinone, 2c, produced moderate regioselectivity (85:15). Biquinone 2d, however, showed no level of regioselectivity demonstrating that the position of the methoxyl group influences the regiochemistry. The intramolecular hydrogen bond in biquinone 5 altered the regioselectivity. Semiempirical calculations revealed comparatively larger LUMO coefficients at the chlorinated carbons that underwent preferential substitution.