Α-alkylated Derivatives Research Articles

Porphyrins as Photoredox Catalysts: Experimental and Theoretical Studies.

Metalloporphyrins not only are vital in biological systems but also are valuable catalysts in organic synthesis. On the other hand, catalytic properties of free base porphyrins have been less explored. They are mostly known as efficient photosensitizers for the generation of singlet oxygen via photoinduced energy transfer processes, but under light irradiation, they can also participate in electron transfer processes. Indeed, we have found that free base tetraphenylporphyrin (H2TPP) is an efficient photoredox catalyst for the reaction of aldehydes with diazo compounds leading to α-alkylated derivatives. The performance of a porphyrin catalyst can be optimized by tailoring various substituents at the periphery of the macrocycle at both the β and meso positions. This allows for the fine tuning of their optical and electrochemical properties and hence their catalytic activity.

Upgrading of Biobased Lactones with Dialkylcarbonates

Four renewable lactones, γ-butyrolactone, γ-valerolactone, δ-valerolactone, and ε-caprolactone (GBL, GVL, DVL, ECL, respectively) were shown to react with dimethyl-, diethyl-, and dibenzyl-carbonate (DMC, DEC, DBnC, respectively) in the presence of K2CO3 as basic catalyst, to yield selectively either the α-alkyl derivatives 1c–6c in the case of the five-membered ring GBL and GVL or the highly oxygenated acyclic monomeric derivatives 7a, 8a, and 9a in the case of the six- and seven-membered rings DVL and ECL. Selectivity and reaction conditions are investigated and a reaction mechanism is proposed. The organic carbonates act both as reagent and as reaction solvents, and the catalyst can be recovered by filtration and recycled.

Synthesis and isomer distribution of 2-alkyltropinones and 2-alkylgranatanones

Tropinone (8-methyl-8-azabicyclo[3.2.1]octan-3-one) metal (Li, Na, K, Mg) enolates were used to achieve α-alkylation. The reactions, regardless of the metal or conditions used, were low-yielding. N,N-Dimethylhydrazones of tropinone and granatanone (pseudopelletierine, 9-methyl-9-azabicyclo[3.3.1]nonan-3-one) were prepared and α-alkylated using n-butyllithium as the lithiating reagent. Lithium amides, including a polymer-supported lithium amide, were less effective. The reactions were modelled using DFT calculations at the B3LYP 6-31G(d) level and the CPCM solvent model, revealing that the face-selective alkylations of tropinone and granatanone hydrazones favoured the exo-isomers. Granatanone and α-isopropyl tropinone derivatives resisted typical mild hydrolytic hydrazone cleavage (aqueous trifluoroacetic acid) and required more forceful conditions (p-TsOH, boiling dioxane). Using the hydrazone alkylation strategy, 16 α-alkyl derivatives (benzyl, methyl, propyl, isopropyl, allyl, pentyl, heptyl, p-methoxybenzyl) were prepared in 52–90% yields overall. For the α-alkylated tropinones and granatanones (10 examples), the DFT calculations and experimental thermodynamic distributions in base catalysed equilibrations showed that except for the α-isopropyl derivatives, the endo-isomers were more stable than the exo-isomers and were the major products. For 2-isopropyltropinone, the bulky substituent favoured the exo (axial) position in the bicyclic skeleton. The thermodynamic distribution for the α,α′-dibenzyl tropinone isomers was also evaluated.

Stereoselective Access to Fluorinated and Non‐fluorinated Quaternary Piperidines: Synthesis of Pipecolic Acid and Iminosugar Derivatives

The preparation of optically pure quaternary piperidines, both fluorinated and non-fluorinated, has been achieved from a chiral imino lactone derived from (R)-phenylglycinol. In the case of the fluorinated derivatives, the addition of (trifluoromethyl)trimethylsilane (TMSCF(3)) followed by iodoamination and migration of the CF(3) group allowed access to four derivatives of α-(trifluoromethyl)pipecolic acid. A theoretical study of the CF(3)-group rearrangement has been carried out to help establish the reaction mechanism of this uncommon transformation. Moreover, a route to trifluoromethyl-substituted iminosugars was also developed through the diastereoselective dihydroxylation of suitable synthetic intermediates. Conversely, alkylation of the starting substrate and subsequent cross-metathesis and aza-Michael reactions led to α-alkyl derivatives of the target compounds.

Dynamic Kinetic Resolution in the Asymmetric Synthesis of β‐Amino Acids by Organocatalytic Reduction of Enamines with Trichlorosilane

A new methodology based on the organocatalytic asymmetric hydrosilylation of enamines that allows a direct access to a range of β and β -amino acid derivatives was presented. The results show a successful reduction of aromatic substrates, a sterically more hindered ortho-substituted derivatives, and the thiophenyl analogue exhibiting lower reactivity. Fast enamine-imine equilibration is crucial as imines are chiral but racemic, while α-alkyl β-amino acids can be accessed by the symmetrical Mannich reaction. The α-alkyl derivatives have relative and absolute configuration due to their reduction with LiAlH into a known amino alcohols. Predominant formation of the anti isomer in 3o is consistent with conformation of the imine intermediate in the catalytic reduction.

Stereocontrolled synthesis of enantiomerically pure unsaturated analogues of 2,6-DAP. Part 5

An efficient new stereocontrolled synthesis of (2 R,6 R)-(+)- and (2 S,6 S)-(−)-2,6-diamino-4-methylene-1,7-heptanedioic acid 8a and 9a, respectively, has been accomplished starting from the glycine-derived chiral synthon 1. The enantiomerically pure α-alkyl derivatives 8b– d and 9b– d have also been synthesized. The absolute configuration of the new stereocenters was assigned on the basis of 1H NMR spectra.

Stereoselective synthesis of bis(α-amino acid) derivatives isosteric of cysteine. Part 4

Enantiomerically pure α-alkyl derivatives of α,α′-diaminodicarboxylic acids isosteric of cysteine 8a, b, e, 9a, b, e and 10a, b, e have been synthesized starting from the glycine-derived chiral synthon (1′ S,1″ S)- 1.

α-Pyrones. Part V. Structure effects on the intramolecular cyclization of functionalized 6-pyronylacetamides: Synthesis of new 2,5,7-trioxo-pyrano [3,2- c]pyridines

Reaction of arylisocyanates 2 with methyl 2-oxo-2 H-pyran-6-acetate 1 and with ylide 4 gave two classes of pyronylacetamides 3 and 5, respectively. Phosphoranes 5 were reduced to the corresponding acetamides 6 with zinc and acetic acid. Compounds 6 were alkylated under solid-liquid PTC conditions using anhydrous potassium carbonate as a base to give the C α-alkyl derivatives 7 in good yields. Intramolecular cyclization with different bases and solvents of acetamides 3,5–7 to give the new 2,5,7-trioxo-pyrano[3,2- c]pyridines has been studied.

Catalytic reactions of pyridines. V. Alkylation of .ALPHA.-,.BETA.-,and .GAMMA.-picolines with alcohols catalyzed by ammonium halides.

A new method was found for the homogeneous liquid-phase alkylation of α-, β-, and γ-picolines with either methanol or ethanol. Addition of a catalytic amount of an ammonium halide to a mixture of a picoline and an alcohol resulted in a great increase in the yields of both side-chain-and α-alkylated derivatives of the starting picoline when the reaction was carried out at 320-335°C in an atmosphere of nitrogen. The higher the reaction temperature, the greater the yields of side-chain alkylated derivatives became. In practice, this alkylation gave 2-ethylpyridine and 2, 6-lutidine from α-picoline with methanol, 3-ethylpyridine and 2, 5-lutidine from β-picoline with methanol, 4-ethylpyridine and 2, 4-lutidine from γ-picoline with methanol, 2-propylpyridine and 2-ethyl-6-methyl-pyridine from α-picoline with ethanol, 2-ethyl-5-methylpyridine from β-picoline with ethanol, and 4-propylpyridine and 2-ethyl-4-methylpyridine from γ-picoline with ethanol.

ChemInform Abstract: LONE‐PAIR INTERACTIONS IN THE PHOTOELECTRON SPECTRA OF DICARBOXYLIC ACIDS: MALONIC ACID AND ITS α‐ALKYL DERIVATIVES

Chemischer InformationsdienstVolume 11, Issue 22 Physical Organic Chemistry ChemInform Abstract: LONE-PAIR INTERACTIONS IN THE PHOTOELECTRON SPECTRA OF DICARBOXYLIC ACIDS: MALONIC ACID AND ITS α-ALKYL DERIVATIVES D. AJO, D. AJOSearch for more papers by this authorE. CILIBERTO, E. CILIBERTOSearch for more papers by this authorI. FRAGALA, I. FRAGALASearch for more papers by this authorG. GRANOZZI, G. GRANOZZISearch for more papers by this author D. AJO, D. AJOSearch for more papers by this authorE. CILIBERTO, E. CILIBERTOSearch for more papers by this authorI. FRAGALA, I. FRAGALASearch for more papers by this authorG. GRANOZZI, G. GRANOZZISearch for more papers by this author First published: June 3, 1980 https://doi.org/10.1002/chin.198022042Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume11, Issue22June 3, 1980 RelatedInformation

ChemInform Abstract: REGIOSELECTIVE CARBON‐CARBON BOND FORMATION AT THE α‐POSITION OF A SULFUR STABILIZED ALLYL CARBANION VIA AN ALKYLTHIOALLYLBORON “ATE” COMPLEX

Reaction of lithium alkylthioallylboron “ate” complexes (3), prepared from alkylthioallyllithium (1) and triethylborane at −78°C in ether, with carbonyl compounds proceeds via the attack at the α-position to produce the corresponding α-alkylated derivatives (4) in good yields.

Lone-pair interactions in the photoelectron spectra of dicarboxylic acids: malonic acid and its α-alkyl derivatives

Photoelectron spectra of malonic, methylmalonic and diethylmalonic acids are reported. The energy splitting of photoelectron bands representing carbonyl oxygen lone pairs is due to a “through-bond” interaction mechanism. The magnitude of the splitting depends upon the α-alkyl substitution because of conformational effects.

Danazol and stanozolol in long-term prophylactic treatment of hereditary angioedema

Treatment with 17 α-methyltestosterone and with some synthetic androgens prevents attacks of hereditary angioedema (HAE). However, the potential hepatotoxicity of 17 α-alkylated androgens raises the problem of long-term prophylactic use of these agents. Therefore we compared the efficacy in preventing HAE attacks of 17 α-alkylated steroids (danazol and stanozolol) with non-17 α-alkylated derivatives (quinbolone, nandrolone decanoate and mesterolone). As the latter group proved ineffective, it seems that a drug's efficacy in preventing HAE attacks is connected to its 17 α-alkylation. Moreover, our long-term observations with the minimum effective dose of danazol seem to indicate the absence of important collateral effects.

REGIOSELECTIVE CARBON-CARBON BOND FORMATION AT THE α-POSITION OF A SULFUR STABILIZED ALLYL CARBANION VIA AN ALKYLTHIOALLYLBORON “ATE” COMPLEX

Abstract Reaction of lithium alkylthioallylboron “ate” complexes (3), prepared from alkylthioallyllithium (1) and triethylborane at −78°C in ether, with carbonyl compounds proceeds via the attack at the α-position to produce the corresponding α-alkylated derivatives (4) in good yields.

The Reaction between β-Keto Esters and Arylamines in the Presence of Polyphosphoric Acid. II.1 Ethyl Acetoacetate and Its α-Alkyl Derivatives and Arylamines

The Reaction between β-Keto Esters and Arylamines in the Presence of Polyphosphoric Acid. II.¹ Ethyl Acetoacetate and Its α-Alkyl Derivatives and Arylamines

267. Steric effects in di- and tri-arylmethanes. Part IV. Electronic absorption spectra of α-alkyl derivatives of Michler's Hydrol Blue

267. Steric effects in di- and tri-arylmethanes. Part IV. Electronic absorption spectra of α-alkyl derivatives of Michler's Hydrol Blue