Two Novel Thermal Biradical Cyclizations in Theory and Experiment: New Synthetic Routes to 6H-Indolo[2,3-b]quinolines and 2-Aminoquinolines from Enyne-Carbodiimides

The regioselectivity of the biradical cyclization of enyne-carbodiimides 1 can easily be controlled by variation of R¹ at the alkyne terminus. Attachment of a hydrogen atom (R¹=H) leads to C²–C⁷ cyclization and formation of biradical 2 , whereas C²–C⁶ cyclization to provide biradical 3 is observed with R¹=Me₃Si or Ph.     

Nucleophilic Addition to CC Bonds,Part X

A mechanistic model is presented for the base‐catalyzed intramolecular cyclization of polycyclic unsaturated alcohols of type A to ethers D (Scheme 1). The alkoxide anion B is formed first in a fast acid‐base equilibrium. For the subsequent reaction to D , a carbanion‐like transition state C is proposed. This mechanism is in full agreement with our results regarding the influence of substituents on the regioselectivity and the rate of cyclization. We studied the effect of alkyl substituents in allylic position (alkylated endocylic olefinic alcohols 1 – 3 ) and, especially, at the exocyclic double bond ( 12 – 15 ). The fastest cyclization (k_rel=1) is 12 → 16 , which proceeds via a primary carbanion‐like transition state ( E : R¹=R²=H). The corresponding processes 13 → 17 and 14 → 17 are characterized by a less‐stable secondary carbanion‐like transtition state ( E : R¹=Me, R²=H, or vice versa) and are slower by a factor of 10⁴. The slowest reaction (k_rel ca. 10⁻⁶) is the cyclization 15 → 18 via a tertiary carbanion‐like transition state ( E : R¹=R²=Me).     

Total Synthesis of Pradimicinone,the Common Aglycon of the Pradimicin–Benanomicin Antibiotics

A benzo[ a ]naphthacenequinone core, an amino acid, and a disaccharide are the constituents of pradimicin–benanomicin antibiotics 1 (R¹=disaccharide), a class of natural products with significant antifungal and anti-HIV activities. The first total synthesis of pradimicinone (benanomicinone, 1 ; R¹=H), the common aglycon of this class of natural products, has now been achieved based on the transmission of chirality during the pinacol cyclization of 2,2′-biaryldicarbaldehydes.     

A General Diversified Synthesis of Carbazoles and the First Synthesis of Karapinchamine A

[IPrAuCl]/AgSbF₆‐catalyzed cyclization of the readily available 4‐benzoxyl‐1‐(indol‐2‐yl)‐2‐alkynols occurred smoothly in 1,2‐dichloroethane (DCE) in the presence of 4 Å MS to form a series of differently polysubstituted 2‐oxygenated carbazole derivatives efficiently. Based on mechanistic study, a possible mechanism involving 1,3‐migration of a benzoate group to form the allene, Au⁺‐mediated cyclization–elimination to form a gold–carbene intermediate, and subsequent highly selective 1,2‐migration has been proposed for the formation of carbazoles. Highly selective 1,2‐migration referring to the two substituents R³ and R⁴ (R⁴=H, alkyl, and aryl group) was observed: (1) In the presence of both H and alkyl groups, 1,2‐hydrogen migration is exclusive; (2) in the presence of a methyl group (R³), propyl, isopropyl, 4‐methylphenyl, and 4‐chlorophenyl groups (R⁴) migrate exclusively. Finally, the first total synthesis of the recently isolated naturally occurring carbazole alkaloid karapinchamine A in 5.2 g scale has been realized in 6 steps from commercially available chemicals without need for any protection–deprotection.     

Enantiomerically Pure Cyclic trans-1,2-Diols,Diamines, and Amino Alcohols by Intramolecular Pinacol Coupling of Planar Chiral Mono-Cr(CO)3 Complexes of Biaryls

Without any formation of stereoisomers , the intramolecular pinacol cyclization of 1 —planar chiral mono-Cr(CO)₃ complexes of 1,1′-biphenyls with carbonyl functionalities at the 2- and 2′-positions—with samarium diiodide gives cyclic trans-1,2-diols 2 . Upon exposure to sunlight, the chromium-complexed diols 2 produce optically pure chromium-free trans-diols 3 . Similarly, the corresponding enantiomerically pure trans-1,2-diamines and amino alcohols are obtained from the planar chiral chromium complexes of biphenyls with diimino or keto-imino functionalities. R¹=H, OMe; R²=H, Me; R³=H, Me.     

Straight and versatile synthesis of substituted perhydrofuro[2,3-b]pyrans from 2-chloromethyl-3-(2-methoxyethoxy)propene

The reaction of 2-chloromethyl-3-(2-methoxyethoxy)propene with an excess of lithium powder and a catalytic amount of naphthalene (2.5%) in the presence of a carbonyl compound (E¹=R¹R²CO) in THF at −78 to 0°C, followed by the addition of an epoxide [E²=R³R⁴C(O)CHR⁵] at 0 to 20°C leads, after hydrolysis, to the expected methylidenic diols. These diols when subjected to successive hydroboration-oxidation and further oxidation, spontaneous cyclization occurs to furnish a series of differently substituted perhydrofuro[2,3-b]pyrans.     

Highly Enantioselective Catalytic Hetero-Diels–Alder Reaction with Inverse Electron Demand

Valuable substrates for the synthesis of natural products , compounds 3 (R¹=alkyl, aryl, alkoxy; R², R³=alkyl) are formed from β,γ-unsaturated α-keto esters 1 and vinyl ethers 2 by the title reaction [Eq. (1)]. Copper(II ) bisoxazolines act as catalysts, and in many cases enantiomeric excesses higher than 99.5 % are achieved.     

Synthesis of Optically Active α-Amino- phosphinic Acids by Catalytic Asymmetric Hydrogenation in Organic Solvents and Aqueous Micellar Media

Enantiomeric excesses of up to 99 % could be obtained in the synthesis of the biologically interesting acylated α-aminophosphinic acids 1 (R¹=Me, Ph; R²=H, Me, Et; R³=H, F, iPr) by asymmetric hydrogenation with rhodium complex catalysts and subsequent hydrolysis [Eq. (1)]. cod=1,5-cyclooctadiene.     

Synthesis of the sex pheromone of the obscure mealybug, the first example of a new class of monoterpenoids

A diastereoselective synthesis of (1R^∗,2R^∗,3S^∗)-1-acetoxymethyl-2,3,4,4-tetramethylcyclopentane, the sex pheromone of the obscure mealybug Pseudococcus viburni, is described. Key steps included the polyphosphoric acid-catalyzed cyclization of isobutyl methacrylate to form the core five-membered ring, and diastereoselective quenching of an enolate intermediate to give the thermodynamically less favored cis orientation of vicinal methyl groups in a cyclopentanone intermediate.     

An efficient synthesis of 4-alkyl-2(1H)-quinazolinones and 4-alkyl-2-chloroquinazolines from 1-(2-alkynylphenyl)ureas

An efficient synthesis of 4-alkyl-2(1H)-quinazolinones has been achieved by cyclization of 1-(2-alkynylphenyl)ureas (2 R₂ = alkyl) in dichloroethane catalyzed by TfOH. In the case of aryl substitution (2 R₂ = aryl), a mixture of quinazolinone tautomers is obtained in dichloroethane with TFA as co-solvent. Chlorination of the resulting mixture affords 4-alkyl-2-chloro-quinazolines as sole products.     

Synthesis of 4‐(trihalomethyl)dipyrimidin‐2‐ylamines from β‐alkoxy‐α,β‐unsaturated trihalomethyl ketones

The synthesis of a novel series of twelve 4‐(trihalomethyl)dipyrimidin‐2‐ylamines, from the cyclo‐condensation reaction of 4‐(trichloromethyl)‐2‐guanidinopyrimidine, with β‐alkoxyvinyl trihalomethyl ketones, of general formula: X₃C‐C(O)‐C(R²)=C(R¹)‐OR, where: X = F, Cl; R = Me, Et, ‐(CH₂)₂‐, ‐(CH₂)₃‐; R¹ = H, Me; R² = H, Me, ‐(CH₂)₂‐, ‐(CH₂)₃‐, is reported. The reactions were carried out in acetonitrile under reflux for 16 hours, leading to the dipyrimidin‐2‐ylamines in 65‐90% yield. Depending on the substituents of the vinyl ketone, tetrahydropyrimidines or aromatic pyrimidine rings were obtained from the cyclization reaction. When X = Cl, elimination of the trichloromethyl group was observed during the cyclization step. The structure of 4‐(trihalomethyl)dipyrimidin‐2‐ylamines was studied in detail by ¹H‐, ¹³C‐ and 2D‐nmr spectroscopy.     

Novel Asymmetric Formylation of Aromatic Compounds: Enantioselective Synthesis of Formyl 7,8‐Dipropyltetrathia[7]helicenes

Asymmetric formylation of aromatic compounds is virtually unexplored. We report the synthesis and evaluation of a library including 20 new chiral formamides in the kinetic resolution of 7,8‐dipropyltetrathia[7]helicene, affording the corresponding formyl‐ or diformylhelicenes in up to 73 % ee, making enantiopure compounds available by recrystallisation. With the N,N‐disubstituted formamides used in this study, the best enantioselectivity has been achieved with R¹=iPr, R²=Me, R³=H, R⁴=1‐naphthyl or its 1‐pyrenyl equivalent.     

An NHC-Stabilized H2GeBH2 Precursor for the Preparation of Cationic Group 13/14/15 Hydride Chains

The synthesis, characterization and reactivity studies of the NHC-stabilized complex IDipp ⋅ GeH₂BH₂OTf ( 1 ) (IDipp=1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene) are reported. Nucleophilic substitution of the triflate (OTf) group in 1 by phosphine or arsine donors provides access to the cationic group 13/14/15 chains [IDipp ⋅ GeH₂BH₂ERR¹R²]⁺ ( 2 E=P; R, R¹=H; R²=^tBu; 3 E=P; R=H; R¹, R²=Ph; 4 a E=P; R, R¹, R²=Ph; 4 b E=As; R, R¹, R²=Ph). These novel cationic chains were characterized by X-ray crystallography, NMR spectroscopy and mass spectrometry. Moreover, the formation of the parent complexes [IDipp ⋅ GeH₂BH₂PH₃][OTf] ( 5 ) and [IDipp ⋅ GeH₃][OTf] ( 6 ) were achieved by reaction of 1 with PH₃. Accompanying DFT computations give insight into the stability of the formed chains with respect to their decomposition.     

Investigation of Phosphorylation of Cyclodextrins and Some their Derivatives

Abstract

Principal regularities of per- and regodirected phosphorylation of α-β-, and γ-cyclodextrins (R=R¹=R²=OH, n= 1–3) by trivalent phosphorus reagents were investigated. As a result, the first representatives of regularly organized phosphites and amidophosphites of cyclodextrins, including ones with interglucoside 2,3′-cyclophosphite bridges [R¹+R²=-P(NR₂′)-], having chiral cavities of different sizes, were obtained. Per-6-deoxy-6-bromocyclodextrins (R=Br) were considered as convenient intermediates for the synthesis of pyndinium salts with amphiphilic properties for the enhanced water-solubility and for the definite orientation at the phase boundary organic liqiud-water.     

Selective method for the preparation of isomeric N-alkyl and N-aryl-3(5)-amino-5(3)-hydroxy-1H-pyrazole-1-carboxamides

As part of a program to develop novel mechanism based skeletal muscle relaxants we identified 5-amino-3-hydroxy-1H-pyrazole-1-carboxamide (1) as a potential structural lead. This highly functionalized pyrazole was prepared via a published procedure [1] (Scheme 1, R¹ = R¹ = H), which utilized 3,5-dimethyl-1H-pyrazole-1-carboxamide as an aminocarbonyl transfer reagent, to give with cyanoacethydrazide the semicarbazide intermediate 6 . Base catalyzed cyclization of 6 afforded the initial lead compound. This reaction scheme was extended to the synthesis of additional 4-alkyl- and 4-aryl-5-amino-3-hydroxy-1H-pyrazole-1-carboxamides (Table 1).     

Stereoselective synthesis of (+)-sordidin, the male-produced aggregation pheromone of the banana weevil Cosmopolites sordidus

Stereoselective synthesis of (1S,3R,5R,7S)-(+)-sordidin, the natural male-produced aggregation pheromone of the banana weevil Cosmopolites sordidus (Germar) starting from 5-benzyloxy-(2E)-pentene-1-ol is described. The key transformations employed in the synthesis are Sharpless asymmetric epoxidation, Ueno-Stork cyclization, and Jacobsen kinetic resolution.     

SYNTHESIS OF THE FIRST BENZODISELENAGERMOLES AND ONE SPIROBISDISELENAGERMOLE

Abstract

The first examples of compounds R¹R²GeSe₂C₆H₄R³ (R¹,R²=CH³ C₂H₅, C₃H₂, n-C₄H₉, i-C₅H₁₁, Ph, p-CH₃Ph. R³=H, CH₃, OCH₃) were easily obtained (40–80% yield) from electrophilic cleavage of diselenophenylene zirconocenes by dialkyl or diaryl dichlorogermanes. The synthesis of a spirodi-selenagermole was achieved in the same way using germanium tetrachloride. Analytical data, ¹H and ⁷⁷Se NMR. mass spectra are perfectly consistent with the expected structures.     

Polarity and Conformatios of Phosphorylethylenes and Phosphorylacetates in Solution

Abstract

A series of derivatives R¹R²P(X)R³, where R¹=R²=Ph. R³= -CH=CH-Me, X=O(I); R¹=Me, R²=Ph, R³= -CH=CH₂, X=O(II); R¹=R²=Ph, R³= -CH=CH₂, X=Se(III) and R¹R²P(O)-CH₂C(O)OX, where R¹=Ph, R²= -CH=CH₂, X=Ment?(IV); R¹=Ph-2-OMe, R²=Ph, X=Ment?(V); R¹=R²=CH₂Ph, X=Et(I), were investigated by means of dipole moments method. The problem of conjugation in phosphorylethylenes and conformation behaviour of phosphorylacetates was considered. DM (exp.) of (I-IV), determined in CC1₄ solution are 4.48(I), 4.27(II), 4.97(III), 4.21(IV), 5.21(V) and 4.02 D (VI). The intramolecular electronic interactions of phosphoryl group with unsaturated fragment did not displays in polarity properties of compounds (I-III). The experimental dipole moments of derivatives (I-III) are equal to the calculated values of DM. DM (IV-VI) is very sensitive to orientation of the P=O and C=O polar bonds. Because DM (exp.) of these compounds very sensitive to its orientation. DM (calc.) for cis- and trans- orientation of P=O and C=O dipoles are really different, that allows to drow the conclution that, in the contrast to the crystal state, the corresponded dipoles prefer an anti array in solution.     

Synthesis and reactions of fluorinated iminium salts

Different methods for the preparation of fluorinated iminium salts RR¹CNR²R³⁺MF₆^? (R=R¹=F ; R²=R³=CH₃, C₂H₅ M=As, Sb 4a ? c R=H, R¹=F; R²=R³=CH₃ M=As, Sb 5a, b R=R¹=CF₃; R²=H, R³=CH₃ M=Sb 12 R=R¹=CF₃; R²=R³=CH₃ M=As 14) are reported, the spectroscopic properties (IR, NMR) of the cations of these salts are briefly discussed. By F^?-addition to these salts, $\text{e.g.}$ to 16, perfluoroalkyl-bis(alkyl)-amines ($\text{e.g.}$ (CF₃)₂CFN(CH₃)₂ 15) can be prepared; from the methylation of CF₃NCF₂ bis(trifluoromethyl) methylamine (CF₃)₂NCH₃ (11) was obtained.