Adam Bieniek

Application of organolithium and related reagents in synthesis. Part 9. Synthesis and metallation of 4-chloropicolin- and 2-chloroisonicotinanilides. A useful method for preparation of 2,3,4-trisubstituted pyridines☆

Abstract The synthesis and metallation (nBuLi) of 4-chloropicolin- and 2-chloroisonicotinanilides ( 1 ) and ( 2 ) as a way of regiospecific transformation of picolinic and isonicotinic acids into 2,3,4-trisubstituted pyridines ( 9 ) and ( 10 ), is described. The anilide moiety (masking group) of the formed C3-substituted chloro-anilides ( 9 ) and ( 10 ) appeared to be effectively removable on acid hydrolysis.

The dual behaviour of N,N-dialkylpyridylcarboxyclic amides in the reaction with lithium diisopropylamide

Abstract The dual behaviour of N,N-diisopropylpyridylcarboxylic amides in the reaction with iPr2NLi depending upon temperature and structure of a given amide, is described.

Application of organolithium and related reagents in synthesis, Part X. Metallation-electrophilic substitution sequence of secondary chlorobenzamides

SummaryThe lithiation (BunLi/THF) of 2-chloro- (1), 3-chloro- (2) and 4-chlorobenzanilides (3) and the subsequent reactions of the corresponding bis-lithiated anilides4–6 with electrophiles (MeI, CH2=CH-CH2Br,Me3SiCl,MeCHO,o-MeOC6H4CHO,p-MeOC6H4CHO,Me2NCHO andp-MeOC6H4CONMe2) towards the synthesis of theortho substituted chlorobenzoesic acids derivatives12–14 have been described. The effect of the chlorine substituent upon the generation and stability of the bis-lithiated chloro-anilides4–6 has been studied. It has been found that the bis-lithiated chloro-anilide5 derived fromm-chloro-benzanilide (2) at a temperature above −30°C converts into the corresponding benzyne9. The anilide moiety (masking group) of the formedortho-substituted chlorobenzanilides appeared to be effectively removable on acid-driven hydrolysis.ZusammenfassungDie Lithiierung (BunLi/THF) der 2-Chlor-(1), 3-Chlor- (2) and 4-Chlorbenzanilide (3) und nachfolgende Reaktion der entsprechenden doppellithiierten Anilide4–6 mit elektrophilen Reagenzien (MeI, CH2=CH-CH2Br,Me3SiCl,MeCHO,o-MeOC6H4CHO,p-MeOC6H4CHO,Me2NCHO undp-MeOC6H4CONMe2) zur Synthese vonortho-substituierten Benzoesäurederivaten12–14 wird beschrieben. Der Einfluß des Chlorsubstituierten auf die Bildung und Stabilität der doppellithiierten Chloranilide4–6 wurde untersucht. Es wurde festgestellt, daß das doppellithiierte, vomm-Chlorbenzanilid erhaltene Chloranilid5 bei Temperaturen über −30°C das entsprechende Arin9 bildet. Der Anilidrest (eine maskierende Gruppe) der gebildetenortho-substituierten Chloranilide kann durch saure Hydrolyse abgespalten werden.

Application of organolithium and related reagents in synthesis. Part 25: Novel specific synthesis of the 4-arylisochroman-3-acetic acids via conversion of benzoic acids ☆

The transformation of the benzanilides 1 into 4-arylisochroman-3-acetic acids 8 applying the following sequence of reactions is described. At first, the 3-arylphthalides 3 were obtained via metallation [n-BuLi] of benzanilides 1 and subsequent treatment of the generated bis-lithiated anilides 2 with aromatic aldehydes. Next, the 3-arylphthalides 3 were reduced [LiBH4] to phthalanes 5 and then, via reductive metallation [Li/C10H8] and reaction of the generated bis-lithiated species 6 with dimethylformamide, 3-hydroxy-4-arylisochromans 7 were produced. In the final step the isochromans 7 were treated with 1-methoxy-1-trimethylsilyloxyethene in the presence of titanium tetrachloride and furnished 4-arylisochromans-3-acetic acid methyl esters 8 as trans stereoisomers (Ψ-e/e).

The conformational analysis of benzocycloalkanones using the lanthanide induced shift msthod

The conformations of the benzocycloalkanones 1a - 1d in solution were estimated by the use of the lanthanide induced shift method (LIS of 1H, 13C NMR spectra). The starting geometry was obtained from MNDO calculations. The torsional angle of the carbonyl group with respect to the benzene ring is 0° for compound 1a, 3° for 1b, 56° for 1c and 67° for the eight-membered ring compound 1d. These results are compared with the data obtained by other methods for similar compounds and are discussed with regard to kinetic measurements for solvolysis of chlorobenzocycloalkanes and oxidation of benzocycloalkanols, respectively.

Applications of organolithium and related reagents in synthesis. Part 3. A general study of the reaction of lithium alkyls with pyridine ketones

The reaction of MeLi and PhLi with acetylpyridines (1a–c) and their annelated derivatives (2a), (2b), (3), and (4) has been examined. The 3- and 4-pyridyl ketones (1b), (1c), (3), and (4) gave similar results to acetophenone and 3,4-dihydronaphthalen-1(2H)-one. In the case of the 2-pyridyl ketones (1a), (2a), and (2b) unexpectedly low yields of products resulted from the addition of RLi to the carbonyl group; the reaction was efficiently enhanced by initially adding an additional amount of LiBr. These results were accounted for by the chelation of RLi or LiBr by the 2-pyridyl ketones.

Application of Organolithium and Related Reagents in Synthesis. XXVII.[1] Effect of the Nucleophilic Character of Silyl Enol Ethers Upon the Conversion of 3-Arylphthalides into 2-(1-Aryl-2-methoxycarbonyl) Benzoic Acids

Abstract A convenient two step protocol preparation of the ortho-alkylated (by secondary substituent with the carbomethoxy group at the end of alkyl chain) aromatic carboxylic acids 6 from benzoic acids anilides 1 was developed, which exploited the reductive alkylation of phthalides 4 with silyl vinyl ethers 5a–b or silyl ketene acetals 5c–g as a key step, is described.

Application of organolithium and related reagents in synthesis XVI: Synthetic strategies based on aromatic metallation. A concise regiospecific conversion of chlorobenzoic acids into their benzylated derivatives

SummaryThe reaction of benzyl bromide withbis-(N- and C-ortho)-lithiated chloroanilides4,5, and6 has been examined. It has been found that in the case where the lithiated compound was derived frommeta-methoxyanilides, pre-addition of LiBr orTMEDA was required to achieve C-benzylation. These results were accounted for by the conversion of the usually formed dimer into a mixed dimer with the LiBr orTMEDA complex in which the C-lithium bond appears to be more accessible towards electrophiles. The practical synthesis of σ-benzylchlorobenzoic acids10,11, and12 was accomplishedvia ionic reductive cleavage (Et3SiH/TiCl4) of the corresponding phthalides18,19, and20. The acids10,11b, and11c afforded the corresponding anthrones, upon treatment with trifluoroacetic anhydride which were oxidized by chromium trioxide to the new chloroantraquinones21,22, and23.ZusammenfassungDie Reaktion von Benzylbromid mit denbis-(N- und C-ortho)-lithiierten Chloraniliden4,5 und6 wurde untersucht. Im Falle lithiierter Verbindungen ausmeta-Methoxyaniliden ist die Zugabe von LiBr oderTMEDA während des Lithiierungsprozesses für die C-Benzylierung erforderlich. Diese Ergebnisse werden durch Umwandlung des gewöhnlich enstehenden Dimers in ein gemischtes Dimer mit dem LiBr- oderTMEDA-Komplex erklärt, in welchem die C-Li-Bindung für Elektrophile leichter zugänglich ist. Diese praktische Synthese dero-Benzylchlorbenzoesäuren10,11 und12 wird durch reduktive Spaltung der entsprechenden Phthalide18,19 und20 mit Et3SiH/TiCl4 ergänzt. Bei der Reaktion der Säuren10,11b und11c mit Trifluoressigsäureanhydrid entstehen die erwarteten Anthrone, die durch Oxidation mit Chromtrioxid in die neuen Chloranthrachinone21,22 und23 umgewandelt wurden.

Application of Organolithium and Related Reagents in Synthesis, Part 31: Effective Conversion of 3‐Arylphthalides into 2‐(1‐Aryl‐3‐oxo‐4‐alkoxycarbonyl‐butyl)benzoic Acids

Abstract A convenient three‐step protocol preparation of the ortho‐alkylated (long‐chain substituent with terminal methylcarbonyl or acetoacetate moiety) aromatic carboxylic acids 15 or 16 from benzoic acids anilides 10 was developed, which exploited the reductive alkylation of phthalides 13 with dimethyl‐6‐methylene‐4‐(trimethoxysiloxy)‐1,3‐diox‐4‐ene (9) as a key step.

Application of organolithium and related reagents in synthesis. Part XXVIII [1]. Synthesis strategies based on aromatic metallation: A conversion of benzoic acids into arylthiomethyl aromatic carboxylic acids

Summary. A convenient two step protocol preparation of ortho-phenylthiomethyl aromatic carboxylic acids from aromatic carboxylic acids anilides is reported. The phenylthiolation of phthalides with benzenethiol as a key step is described.