Undergo Conjugate Addition Reactions Research Articles

A rapid entry into thioflavanones via conjugate additions of diarylcuprates to thiochromones

Thiochromone undergo conjugate addition reactions with arylcuprates to afford 2-substituted thioflavanones, providing an efficient synthetic approach to privileged sulfur-containing structural motifs and valuable precursor for many pharmaceuticals. Excellent yields of substituted thioflavanones are achieved with lithium diarylcuprates, lithium arylcyanocuprates and Grignard reagents with copper catalysis. This method provides a rapid entry to a variety of thioflavanones in excellent yields (up to 92%). The use of commercially available or easily prepared organometallic reagents will expedite the synthesis of a large library of thioflavanones for further synthetic applications and biological studies.

ChemInform Abstract: Hydrometalation‐Asymmetric Conjugate Addition: Application to Complex Molecule Synthesis.

AbstractCu‐catalysis allows alkyl zirconium species, generated in situ from alkenes, to undergo conjugate addition reactions.

Hydrometallation-asymmetric conjugate addition: application to complex molecule synthesis

Copper catalysis allows alkyl zirconium species, generated in situ from alkenes, to undergo conjugate addition reactions. A hydrometallation-catalytic asymmetric 1,4-addition was used to synthesize either enantiomer of a natural product in one step from commercially available materials. Hydrometallation-addition sequences applied to steroids containing a cross-conjugated dienone or 1,6-acceptor give highly functionalized products.

A Convenient Synthesis and Some Characteristic Reactions of Novel Propiolamidinium Salts

Starting from N,N,N′,N′,N′′,N′′-hexaalkylguanidinium chlorides and terminal alkynes, a series of new orthoamide derivatives of alkynecarboxylic acids were prepared. The orthoamides were converted into propiolamidinium chlorides by reaction with benzoyl chloride and into propiolamidinium triflates by reaction with triethylsilyl trifluoromethanesulfonate. Propiolamidinium salts undergo conjugate addition reactions with sec-amines and thiols­. Treatment of terminal alkyne chlorides with silver(I) oxide afforded a silver complex, which can apparently adopt the composition of either a bisalkynyl silver complex [Ag(CCC(NMe2)2)2]AgCl2 or a monoalkynyl silver complex [ClAgCCC(NMe2)2].

Living Group Transfer

Living polymerizations with single-component catalysts represent a desirable method to make polymers of controlled structure. This method allows for the polymerization by what is known as a group transfer polymerization type of method. In this method the growing polymer is connected to the catalyst as an enolate, in the case of methylmethacrylate or an equivalent phoshonate as shown. Coordinated monomers then undergo conjugate addition reactions to ­result in chain growth.

ChemInform Abstract: Synthesis of New 2′,3′-Modified Uridine Derivatives from 2′,3′-Ene-2′- phenylselenonyl Uridine by Michael Addition Reactions.

Abstract The synthetic utilities of 2′,3′-ene-2′-phenylselenones 12 and 13 as synthetic equivalent of a dication [CH2+-CH2+] 5 have been demonstrated. They act as Michael acceptors, and undergo conjugate addition reactions at C-3′ with various sulfur, nitrogen, oxygen and carbon nucleophiles giving various C-3′ substituted-2,2′-O-anhydro-, or 2′,3′-ene-3′-substituted, or 2′,3′-fused nucleoside derivatives. Easy access to these 3′-substituted nucleosides from 2′,3′-ene-2′-phenylselenones 12 and 13 make them powerful complement to the corresponding 2′-substituted derivatives obtainable from 2′,3′-ene-3′-phenylselenonyl nucleoside 4 (ref. 72–74).

Conjugate Addition Reactions ofN-Carbamoyl-4-Pyridones with Organometallic Reagents

N-carbamoyl-4-pyridones undergo conjugate addition reactions with organocuprates and organozincates to afford 2-substituted-2,3-dihydro-4-pyridones providing a direct synthetic approach to substituted piperidines and piperidones. Good to excellent yields of conjugate adducts are achieved with lithium dialkylcuprates, alkylcyanocuprates, RLi/CuCN (0.3 equiv), and trialkylzincates with copper catalysis. Copper catalysis in the conjugate addition of Grignard reagents affords modest yields of conjugate adducts. An enantioenriched phosphoramidite ligand promotes the copper catalyzed conjugate addition of Et(2)Zn to a N-carbamoyl-4-pyridone with an er of 91.5:8.5.

Conjugate addition reactions of alpha-aminoalkylcuprates with alpha, beta-alkenyl-, alpha,beta-alkynyl-, alpha,beta-beta,gamma-allenyl-, and alpha,beta-gamma,delta-dienyl carboxylic acid derivatives, nitriles, and sulfoxides.

alpha-Aminoalkylcuprates prepared from alpha-lithio carbamates and CuCN.2LiCl participate in 1,4-addition reactions with alpha, beta-unsaturated esters, thiol esters, imides, and nitriles in poor to excellent yields depending upon the electron-withdrawing substituent and the substitution pattern of the unsaturated substrate. These reagents also undergo conjugate addition reactions with alpha,beta-alkynyl esters, sulfoxides, and nitriles and with alpha,beta-beta,gamma-unsaturated allenyl esters. Excellent stereocontrol is achieved in the conjugate additions of alpha-aminoalkylcuprates to the allenyl esters, while poor stereoselectivity results in the conjugate additions to the alkynyl derivatives. Deprotection and cyclization of the alkynyl adducts affords pyrrolin-2-ones, while similar treatment of the allenyl adducts affords 4-alkylidine- pyrrolidin-2-ones and pyrrolizidinones.

ChemInform Abstract: A Facile Synthesis of Polysubstituted Pyrroles.

α-Aminoalkylcuprates prepared from CuX·2LiCl (X = Cl, CN) and 1 equiv of an α-lithiocarbamate undergo conjugate addition reactions to α,β-alkynyl ketones in moderate to good yields, affording E:Z mixtures of α,β-enones. Treatment of the conjugate adducts with PhOH/TMSCl in CH2Cl2 effected carbamate deprotection and cyclization to afford a flexible two-step synthesis of substituted pyrroles.

A facile synthesis of polysubstituted pyrroles.

alpha-Aminoalkylcuprates prepared from CuX.2LiCl (X = Cl, CN) and 1 equiv of an alpha-lithiocarbamate undergo conjugate addition reactions to alpha,beta-alkynyl ketones in moderate to good yields, affording E:Z mixtures of alpha,beta-enones. Treatment of the conjugate adducts with PhOH/TMSCl in CH(2)Cl(2) effected carbamate deprotection and cyclization to afford a flexible two-step synthesis of substituted pyrroles.

Conjugate Addition Reactions of α-Aminoalkylcuprates with α,β-Enones and Enals

Deprotonation of Boc-protected amines with sec-BuLi or transmetallation of α-aminostannanes with n-BuLi affords α-aminoalkyllithium reagents which can be converted into α-aminoalkylcuprate reagents with CuCN or THF soluble CuCN·2LiCl. These reagents undergo conjugate addition reactions with α,β-enones and enals. Reagents prepared from 2 equiv. of the α-aminoalkyllithium reagent give higher yields of conjugate adducts than those prepared from RCuCNLi, particularly when insoluble CuCN is employed. When CuCN·2LiCl is used, the two cuprate reagents give comparable yields of 1,4-adducts and the RCuCNLi reagent, economical in α-aminoalkyl ligand, is preferred. The Boc protecting group can be removed with PhOH/TMSCl and the amino ketone isolated as the hydrochloride salt.

Functionalised pyrrolidinones by conjugate addition of stabilised enolates and Reformatsky reagents

The α,β-unsaturated lactam 1b has been found to readily undergo conjugate addition reactions with a range of stabilised carbon nucleophiles and Reformatsky reagents under mild conditions in good yield with high diastereoselectivity. This method provides a simple and versalile approach to highly functionalised pyrrolidinones.

Charge-directed conjugate addition reactions of silylated .alpha.,.beta.-unsaturated amidate anions

A variety of N-substituted α-silylated-α,β-unsaturated amidate anions (2) have been found to be excellent Michael acceptors in charge-directed conjugate addition reactions with Grignard and organolithium reagents. The effects of olefin substitution, Si-substitution, N-substitution, and amidate counterion have been studied. Anionic acceptors may be prepared in situ by the addition of silylated vinyllithium reagents to isocyanates and then allowed to undergo conjugate addition reactions with subsequently added nucleophiles, but it was found to be more efficient to isolate neutral acceptors and regenerate the acceptor anion through the use of excess nucleophile. β-Substituted acceptors were found to react only with reactive organolithium reagents while a β,β-disubstituted acceptor failed to undergo conjugate addition reactions

Charge-Directed Conjugate Addition Reactions of Salts of Unsaturated β-Keto-Esters

Abstract Strong nucleophiles undergo conjugate addition reactions with enolates of Nazarov-type reagents. Yields are strongly affected by substitution patterns and the metal cation employed.

Synthesis of new 2′, 3′-modified uridine derivatives from 2′,3′-ene-2′-phenylselenonyl uridine by Michael addition reactions

The synthetic utilities of 2′,3′-ene-2′-phenylselenones 12 and 13 as synthetic equivalent of a dication [CH 2 +-CH 2 +] 5 have been demonstrated. They act as Michael acceptors, and undergo conjugate addition reactions at C-3′ with various sulfur, nitrogen, oxygen and carbon nucleophiles giving various C-3′ substituted-2,2′-O-anhydro-, or 2′,3′-ene-3′-substituted, or 2′,3′-fused nucleoside derivatives. Easy access to these 3′-substituted nucleosides from 2′,3′-ene-2′-phenylselenones 12 and 13 make them powerful complement to the corresponding 2′-substituted derivatives obtainable from 2′,3′-ene-3′-phenylselenonyl nucleoside 4 (ref. 72–74).

A reactivity umpolung route to cyclic homoenolate aldol products [formula omitted] α-alkoxyorganocuprate conjugate additions

Substituted α-alkoxyorganocuprate reagents readily undergo conjugate addition reactions with cyclic enones to provide homoaldol products.