RESUMO
meta-Aminophenols are formed by the action of DBU on 3-amino-2-chlorocyclohex-2-en-1-ones at room temperature in MeCN. The chloro compounds are generated by treating 3-aminocyclohex-2-en-1-ones with the easily prepared halogenating agent BnNMe3·ICl2 in MeOH-CH2Cl2. The amino group must carry two substituents, either two aryl, one aryl and one alkyl, or two alkyl groups; 3-aminocyclohex-2-en-1-ones of this type are readily made from cyclohex-2-en-1-one and a primary or secondary amine.
RESUMO
Enol ethers are formed by radical decarboxylation of α-alkoxy ß-phenylthio acids via the corresponding Barton esters. The phenylthio acids were usually made by the known regioselective reaction of α,ß-epoxy acids with PhSH in the presence of InCl3, followed by O-alkylation of the resulting alcohol. In one case, thiol addition to an α,ß-unsaturated ethoxymethyl ester was used.
RESUMO
Addition of Grignard or other organometallic reagents to 2-halocyclohex-2-en-1-ones bearing an alkyl or aryl group at C-5, followed by mild acid treatment and exposure to 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) at room temperature, generates meta-substituted phenols in which the newly introduced meta substituent originates from the Grignard reagent. The range of effective organometallic reagents includes alkyl, allyl, alkynyl, aryl, and heteroaryl compounds including those with fluorine substituents. The initial halocyclohexenone can be deprotonated at C-6 and reacted with carbon, fluorine, or sulfur electrophiles before the Grignard addition so as to generate highly substituted phenols.
RESUMO
Piperazinedione 13, representing the BC rings of the anti-prostate cancer fungal metabolite MPC1001, was prepared by a route in which a sulfur-stabilized carbanion derived from 22 cyclizes onto the terminal ester of the pendant chain attached to N(1). Another model, 14, was synthesized by cyclization of an α-ketoamide nitrogen onto an ester; 14 represents the BC rings of MPC1001F.
RESUMO
Conjugate addition of Me3SiMe2SiLi to cycloalk-2-en-1-ones, ketalization, Tamao-Fleming oxidation (Bu4NF, then H2O2, KHCO3), TPAP oxidation and acid hydrolysis generates 2-methyl cycloalkane-1,3-diones. Ketalization is needed in order to prevent addition of Me3Si(-) to the carbonyl. The pentamethyldisilanyl group has advantages over other silicon units that are used in Tamao-Fleming procedures.
RESUMO
A new family of routes to substituted phenols has been developed. 2-Bromo-3-methoxycyclohex-2-en-1-ones are readily deprotonated at C-6, and the resulting anions react smoothly with a variety of electrophiles; treatment with DBU in PhMe at room temperature then results in efficient aromatization to benzene derivatives of a regiochemically defined substitution pattern. This sequence affords phenolic azides (ArN3), sulfides (ArSR, ArSAr'), selenides (ArSePh), alcohols [ArCH(OH)R], amino derivatives [ArCH(NHSO2Ar')R), and 1,2-benzenediols. A complementary set of substitution patterns is obtained by DIBAL-H reduction or reaction with a Grignard reagent before aromatization; the latter process gives compounds in which the newly introduced substituent is meta to the phenolic hydroxyl.
RESUMO
N-Boc (S)-proline was converted into (2S)-2-[(phenylselanyl)methyl]pyrrolidine, which was alkylated on nitrogen with 2-bromo-1-(4-methoxyphenyl)ethan-1-one. Reaction with vinyllithium, 6-exo-trig radical cyclization (Bu3SnH, AIBN, PhMe, 110 °C), dehydration (P2O5, H3PO4), and demethylation (BBr3) gave (+)-ipalbidine with ee >99%.
Assuntos
Aminas/química , Radicais Livres/química , Indolizinas/síntese química , Prolina/química , Pirrolidinas/síntese química , Alquilação , Ciclização , Etano/análogos & derivados , Etano/química , Indolizinas/química , Estrutura Molecular , Compostos Organosselênicos , Pirrolidinas/química , EstereoisomerismoRESUMO
2-Bromo-3-methoxycyclohex-2-en-1-ones are readily alkylated at C-6 with reactive halides, and then treatment with DBU (2 equiv) in PhMe at room temperature results in smooth loss of bromide and aromatization to resorcinol monomethyl ethers of defined substitution pattern.
RESUMO
A general method is described for the synthesis of 1,3'-bipyrroles. The route involves constructing a pyrrole ring on the nitrogen of a substituted 1H-pyrrole, so as to generate the 1,3'-bipyrrole. In this approach the nitrogen of the starting pyrrole was alkylated with a special Michael acceptor having an allylic leaving group, and the product was then modified in such a way that the second pyrrole ring could be formed by a Paal-Knorr reaction. Two variants of this sequence were examined, one of which led to formation of a 3-hydroxypyridine instead of the second pyrrole ring; the other variant used phenacyl bromide instead of the special Michael acceptor.
Assuntos
Pirróis/síntese química , Estrutura Molecular , Pirróis/químicaRESUMO
Intramolecular conjugate displacement (ICD), the process illustrated in , has been applied to the Morita-Baylis-Hillman adducts formed from (5S)-5-(l-menthyloxy)-2(5H)-furanone and aldehydes that are substituted in the γ- or δ-position by geminal phenylthio groups. When the initial Morita-Baylis-Hillman alcohols are acetylated and oxidized to geminal sulfones, deprotonation causes ring closure by ICD (2.5â2.6). Hydrogenation, DIBAL-H reduction and desulfonylation releases an optically pure carbocycle.
Assuntos
Álcoois/química , Hidrocarbonetos Cíclicos/síntese química , Sulfonas/química , Álcoois/síntese química , Ciclização , Hidrocarbonetos Cíclicos/química , Estrutura Molecular , Oxirredução , Sulfonas/síntese químicaRESUMO
An advanced intermediate related to the structures of CP-225,917 and CP-263,114 was constructed by a sequence based on the use of Grob-like fragmentation, intramolecular conjugate displacement, and [2,3]-Wittig rearrangement. A variant of the [2,3]-Wittig rearrangement was developed.
Assuntos
Compostos Heterocíclicos de 4 ou mais Anéis/química , Anidridos Maleicos/síntese química , Espectroscopia de Ressonância Magnética , Anidridos Maleicos/química , EstereoisomerismoRESUMO
The first synthesis of marinopyrrole B, which is highly active against methicillin-resistant Staphylococcus aureus, is described. The route involved constructing a pyrrole ring on the nitrogen of a 3-bromo-4,5-dichloropyrrole by N-alkylation with a special Michael acceptor having an allylic leaving group; the second pyrrole ring was then formed by a Paal-Knorr reaction.
Assuntos
Antibacterianos/síntese química , Pirróis/síntese química , Alquilação , Antibacterianos/química , Antibacterianos/farmacologia , Cristalografia por Raios X , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Conformação Molecular , Pirróis/química , Pirróis/farmacologia , EstereoisomerismoRESUMO
Piperazine-2,5-diones are formed by Dieckmann cyclization (NaH, THF) of substructures of the type CH(2)-N(R)C(O)CH(2)N(R')CO(2)Ph in which the terminal methylene (CH(2)) that is adjacent to nitrogen closes onto the carbonyl group of the phenyl carbamate unit at the other end of the chain. R and R' are alkyl groups, and the terminal methylene is activated by a ketone carbonyl, a nitrile, an ester, or a phosphoryl group. The starting materials are assembled by standard acylation and oxidation processes, starting from a ß-(alkylamino)alcohol, an (alkylamino)acetonitrile, an (alkylamino) ester, or an (alkylamino)methyl phosphonate.
Assuntos
Nitrilas/química , Organofosfonatos/química , Piperazinas/química , Piperazinas/síntese química , Cristalografia por Raios X , Ciclização , Espectroscopia de Ressonância Magnética , Modelos Moleculares , PiperazinaRESUMO
Intramolecular conjugate displacement (ICD) has been applied to the Morita-Baylis-Hillman adducts formed from (5S)-5-(l-menthyloxy)-2(5H)-furanone and aldehydes that carry a protected ß- or γ-amino group. DIBAL-H reduction of the resulting ICD products releases optically pure six- or seven-membered cyclic amines having a stereogenic center α to nitrogen.
RESUMO
Aromatic and aliphatic thiols can be protected by reaction with t-BuMe(2)SiOCH(2)Cl in DMF in the presence of a base (2,6-lutidine or proton sponge); the resulting t-BuMe(2)SiOCH(2)SR or t-BuMe(2)SiOCH(2)SAr are deprotected by sequential treatment with Bu(4)NF and I(2) to give symmetrical disulfides. Another mode of deprotection involves reaction with a sulfenyl chloride; this process gives an unsymmetrical disulfide and was examined with Me(CH(2))(11)SCH(2)OSiMe(2)Bu-t and three sulfenyl chlorides.
Assuntos
Óxidos/química , Enxofre/química , Antineoplásicos/síntese química , Compostos Heterocíclicos de 4 ou mais Anéis/síntese química , Metilação , Estrutura MolecularRESUMO
Reaction of acetylides with aldehydes to form but-2-yne-1,4-diols, followed by triple bond reduction and oxidation of the hydroxyl groups, gives 1,4-diketones; these react with vinyllithium, and the resulting diols undergo ring-closing metathesis to form 2-cyclohexene-1,4-diols. Dehydration, usually by acid treatment, then gives benzenes carrying substituents in a 1,4 relationship. Use of substituted vinyllithiums provides further substitution on the final benzene rings. The method can be applied to the synthesis of C5-aryl carbohydrates.
RESUMO
Baylis-Hillman alcohols derived from methyl acrylate or acrylonitrile and carrying an N-Boc group ß to the hydroxyl (CH(OH)CHNBoc) can be converted into unusual seven-membered heterocycles containing both nitrogen and sulfur by O-acylation (AcCl or EtOCOCl), N-deprotection (CF(3)CO(2)H), and reaction with CS(2). In a modification of this process, when the original nitrogen is substituted in the form PhSCH(2)CON(Me), an azepine derivative is then generated. The ring closures occur by intramolecular conjugate displacement.
RESUMO
4-Hydroxy-3,4-dihydro-2H-pyridine-1-carboxylic acid benzyl esters, which are readily prepared from serine and terminal acetylenes, undergo Claisen rearrangement to piperidine derivatives when heated with butyl vinyl ether in the presence of Hg(OAc)(2) and Et(3)N. This route to optically pure piperidines having substituents alpha to nitrogen is general, and the rearrangement products are versatile intermediates for making a broad range of amines containing a substituted piperidine subunit.
Assuntos
Piperidinas/síntese química , Serina/química , Espectroscopia de Ressonância Magnética , Oxirredução , Piperidinas/química , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Optically pure gamma-lactones fused onto a cyclohexenone are available by a radical-based method for desymmetrizing 4-hydroxy-2,5-cyclohexadienones.
Assuntos
Cicloexenos/química , Lactonas/síntese química , Ciclização , Radicais Livres/química , Lactonas/química , Estrutura Molecular , EstereoisomerismoRESUMO
Readily accessible 3-alkoxycarbonyl-6-hydroxy-5-halocoumarins can be converted into 4-halo-5-hydroxyindoles by a sequence whose essential steps are conjugate reduction or conjugate addition, decarboxylation, lactone opening with ammonia, phenolic oxygen protection, Hofmann rearrangement to an N-Boc ethylamine, oxidation to a quinone and deprotection of the nitrogen. The resulting beta-aminoethyl quinone cyclizes to a mixture of quinone imine and indole, and the imine tautomerizes to the indole spontaneously or on treatment with rhodium on alumina.