Cyclopentane-1,2-dione bis(tert-butyldimethylsilyl) enol ether in asymmetric organocatalytic Mukaiyama–Michael reactions

Cyclopentane-1,2-dione bis(tert-butyldimethylsilyl) enol ether readily undergoes organocatalytic reactions with α,β-unsaturated aldehydes resulting in Mukaiyama–Michael adducts which, after reduction of the aldehyde group and deprotection result in chiral 1,2-diketones (in mono-enolic form) in good yields (up to 66%) and with high stereoselectivity (up to 94% ee).     

Stereocontrolled construction of a spiro fused bicyclo[2.2.2]Octane ring system by the intramolecular double michael reaction

The lithium enolate from the cyclohexenone (8) possessing the α, β-unsaturated ester moiety caused an intramolecular double Michael reaction to produce stereoselectively the spiro fused bicyclo[2.2.2]-octane (10).     

Enantioselective Michael additions of β-keto esters to α,β-unsaturated carbonyl compounds catalyzed by a chiral biquinoline N,N′-dioxide-scandium trifluoromethanesulfonate complex

A catalytic, enantioselective Michael addition of β-keto esters to α,β-unsaturated carbonyl compounds was achieved by using a chiral biquinoline N,N′-dioxide-scandium trifluoromethanesulfonate complex as a catalyst. The corresponding Michael adducts were obtained in high yields and with enantioselectivities up to 84% ee.     

A tandem oximation-cyclization route to Δ-isoxazolines

3,5-Disubstituted Δ²-isoxazolines can be prepared from the corresponding β,γ-unsaturated ketones by treatment with hydroxylamine hydrochloride and sodium hydroxide. Evidence indicates that the mechanism of this reaction involves the formation of three intermediates; oximation of the ketone, rearrangement of the alkene, and intramolecular Michael addition of the resulting α,β-unsaturated oxime.     

Reductive Cleavage of tert-Butyldimethylsilyl Ether via Intramolecular Transfer of Hydride

The cleavage of α-hydroxy tert-butyldimethylsilyl ether to diol takes place efficiently with LAH. It has been proposed that the reaction proceeds via intramolecular hydride transfer from the alkoxy aluminium hydride. In order to substantiate this, reduction of TBDMS ether with LAH in a variety of substrates was studied.     

Intramolecular Michael reactions of aliphatic aldehyde enolates generated by imidazolium carbenes

Due to the high reactivity of the formyl group under either basic or acidic reaction conditions required for the direct generation of aldehyde enolates, intramolecular Michael additions of aldehyde enolates to α,β-unsaturated carbonyl compounds have been underexplored for the stereoselective synthesis of carbocyclic compounds. The intramolecular Michael reaction of aldehyde enolates generated by imidazolium carbenes was explored for the synthesis of cyclopentane aldehydes. The imidazolium carbenes were used as Brønsted bases to directly generate the aldehydes enolates.     

Ionic liquid as catalyst and solvent: the remarkable effect of a basic ionic liquid, [bmIm]OH on Michael addition and alkylation of active methylene compounds

A basic ionic liquid, 1-methyl-3-butylimidazolium hydroxide, [bmIm]OH, catalyzes the Michael addition of active methylene compounds to conjugated ketones, carboxylic esters and nitriles. It further catalyzes the addition of thiols to α,β-acetylenic ketones and alkylation of 1,3-dicarbonyl and -dicyano compounds. The Michael addition to α,β-unsaturated ketones proceeds in the usual way, giving the monoaddition products, whereas addition to α,β-unsaturated esters and nitriles leads exclusively to the bis-addition products. The α,β-acetylenic ketones undergo double conjugate addition with thiols producing β-keto 1,3-dithio-derivatives. In the alkylation reaction the acyclic 1,3-diketones are monoalkylated, whereas cyclic ketones undergo dialkylation under identical conditions. All these reactions were carried out without any organic solvent. The ionic liquid can also be recycled.     

Syntheses of Cyclopropylcarbonyl Compounds

There are three important direct routes to cyclopropylcarbonyl compounds: 1. Cyclization of chains of three carbon atoms, the first or third of which is adjacent to a carbonyl or potential carbonyl carbon atom (this type includes syntheses by intramolecular alkylation of γ-halogeno ketones or related compounds in alkaline media); 2. insertion of a methylene group or substituted methylene group into the olefinic double bond of an α,β-unsaturated carbonyl compound; and 3. introduction of an acetonyl group into the double bond of an olefin. However, cyclopropylcarbonyl compounds can also be obtained from 1,2-epoxycyclobutane and 2-bromocyclobutanone derivatives by ring contraction. Another possibility is the dehalogenation of α,α-bis(bromomethyl) cycloalkanones. This review concludes with a discussion of these little known routes and of a particularly suitable method which involves the reaction of methylene iodide, a Zn? Cu couple, and α,β-unsaturated ketones.     

Tandem reactions of 1,2-allenic ketones leading to substituted benzenes and α,β-unsaturated nitriles

One-pot double Michael addition/intramolecular aldol reaction/decarboxylation of 1,2-allenic ketones with cyanoacetate offers an efficient and convenient approach to highly functionalized benzenes. With 2-substituted cyanoacetates, the reaction proceeds via a different tandem process to afford α,β-unsaturated nitriles effectively.     

Stereoselective synthesis of 2,6-cis-substituted tetrahydropyrans: Brønsted acid-catalyzed intramolecular oxa-conjugate cyclization of α,β-unsaturated ester surrogates

Intramolecular oxa-conjugate cyclization (IOCC) of α,β-unsaturated carbonyl compounds, triggered by deprotonation with a base, represents a straightforward method for the synthesis of tetrahydropyrans. However, it has been known that stereochemical outcome of IOCC depends on the local structure of substrates and sometimes requires harsh reaction conditions and/or prolonged reaction times for selective formation of 2,6-cis-substituted tetrahydropyrans. These shortcomings limit the feasibility of IOCC in the context of complex natural product synthesis. In this paper, we describe Br?nsted acid-catalyzed IOCC of α,β-unsaturated ester surrogates (e.g., α,β-unsaturated thioesters, oxazolidinone imides, and pyrrole amides) under mild reaction conditions, which affords a series of synthetically versatile 2,6-cis-substituted tetrahydropyran derivatives with good to excellent stereoselectivity (dr from 7:1 to >20:1). These α,β-unsaturated carbonyl compounds were found to be more reactive than the corresponding oxoesters that are generally unreactive toward Br?nsted acid-catalyzed intramolecular oxa-conjugate additions. The product tetrahydropyrans could be transformed into various derivatives in an efficient manner, highlighting the usefulness of our methodology.     

Bi(OTf)3-catalyed One-pot Synthesis of α-Halo-β-amino Ketones and Acyl Aziridines from 3-Aryl Propargyl Alcohols

A Bi(OTf)₃-catalyed reaction of 3-aryl propargyl alcohols with sulfonamide and halogen source was firstly investigated, which provided a facile route for the synthesis of a large variety of α-halo-β-amino ketones. The key intermediates, β-amino ketones, were obtained through tandem Meyer-Schuster rearrangement reaction of propargyl alcohols and intermolecular Michael addition of α, β-unsaturated ketones and sulfonamide. Then the in situ generated α-halo-β-amino ketones underwent the base-promoted intramolecular cyclization to give diverse acyl aziridines in a one-pot fashion. These transformations are reliable on a large scale. The high yields and convenient experimental operations make it a valuable method for the construction of α-halo-β-amino ketones and acyl aziridine derivatives.     

Preparation of 616X,6Y-Tris-O-(tert-butyldimethyl-silyl)-β-cyclodextrins,and Isolation and Regiochemical Determination of Five Positional Isomers

Abstract

Five positional isomers of 6¹,6^X,6^Y-tris-O-(tert-butyldimethylsilyl)-cyclomaltoheptaose (β-cyclodextrin, βCD) were prepared by reaction of β CD with tert-butyldimethylsilyl chloride in pyridine, and were isolated by HPLC and characterized by ¹³C NMR spectroscopy. The regiochemical determination of those positional isomers was carried out by the extended Körner's method, that is, by comparison with compounds obtained by additional monosilylation of 6¹, 6^X-bis-O-(tert-butyldimethylsilyl)-βCDs, and by conversion to the known compounds, 6¹,6^X,6^Y-tri-O-(toluene-sulfonyl)-βCDs.     

Generation and Michael Reaction of 1, 3-Bis(trimethylsiloxy)-isoindoles by Reduction of N-Alkylphthalimides with a Zn-Me3SiCl-Lutidine System

Formation and concomitant Michael reaction of 1,3-bis(trimethylsiloxy)isoindoles have been achieved by the reduction of phthalimides with a Zn-Me₃SiCl-lutidine system in the presence of α, β-unsaturated carbonyl compounds under sonication.     

Controlling the α/γ-Reactivity of Vinylogous Ketone Enolates in Organocatalytic Enantioselective Michael Reactions

The first regio-, diastereo-, and enantioselective direct Michael reaction of β,γ-unsaturated ketones with nitroolefins is enabled by Brønsted base/hydrogen-bonding bifunctional catalysis. A squaramide-substituted tertiary amine catalyzes the reaction of a broad range of β,γ-unsaturated ketones to proceed at the α-site exclusively, giving rise to adducts with two consecutive tertiary carbon stereocenters in diastereomeric ratios of up to >20:1 and enantioselectivities generally in the 90–98 % ee range.     

Water Promoted Michael Addition of Secondary Amines to α, β-Unsaturated Carbonyl Compounds Under Microwave Irradiation

A rapid Michael addition of secondary amines to α, β-unsaturated carbonyl compounds has been achieved in good to excellent yields in the presence of water under microwave irradiation. In the absence of water and under conventional method the reaction does not proceed or take place in very low yield after a long reaction time.     

α,β‐Double Electrophilic Addition of Allene‐1,3‐Dicarboxylic Esters for the Construction of Polysubstituted Furans by KI/tert‐Butyl Hydroperoxide (TBHP)‐Promoted Oxidative Annulation

An unprecedented KI/tert‐butyl hydroperoxide promoted tandem Michael addition/oxidative annulation of allene‐1,3‐dicarboxylic esters and 1,3‐dicarbonyl compounds has been developed. This procedure provides a new, facile, and transition‐metal‐free synthetic approach to afford polysubstituted furans in moderate to excellent yields (up to 93 %). This method first establishes a α,β‐double electrophilic reaction mode of allene‐1,3‐dicarboxylic esters to form 1,3‐dicarbonyl compounds.     

Highly stereoselective Michael reduction/intramolecular Michael reaction cascade to synthesize trans-stereodiad comprising an all-carbon quaternary stereogenic center

A highly stereoselective Michael reduction/intramolecular Michael reaction cascade is described. The cascade is initiated by the regioselective Michael reduction of an α-methylidene ester with L-Selectride. This is followed by the highly stereoselective intramolecular Michael reaction which efficiently constructs a six-membered carbocyclic ring with formation of the trans-stereodiad, composed of an all-carbon quaternary center and a tertiary stereogenic center. The stereoselectivity is perfectly controlled by the choice of alkene geometry in the Michael acceptor.     

A Convenient Route to (E)-α,β-Unsaturated Methyl Ketones

Aldehydes are converted into (E)-α,β-unsaturated methyl ketones in good yield and with a high E stereoselectivity using α,α-bis(trimethylsilyl) N-tert-butyl acetimine 3. The reaction was mediated by a catalytic amount of tetrabutylammonium fluoride (TBAF) under mild conditions. The disilylated reagent 3 is easily generated from N-tert-butylacetimine, lithium diisopropylamide (LDA), and chlorotrimethylsilane. The mechanism of the reaction is discussed.     

Microwave-assisted Michael addition of sulfonamides to α,β-unsaturated esters: A rapid entry to protected β-amino acid synthesis

An efficient, clean and very simple procedure for the synthesis of protected β-amino acids is described. Michael addition of sulfonamides to α,β-unsaturated esters in the presence of K₂CO₃ and tetrabutylammonium bromide (TBAB) under microwave irradiation affords the title compounds in good to high yields and short reaction times. This new method affords protected β-amino acids in high yields and short reaction times.     

The intramolecular tandem Michael/Mannich-type reaction of α,β-unsaturated carbonyl compounds with acyliminium ions provides access to chiral indolizidines

The intramolecular tandem Michael/Mannich-type (Michael addition/halo-Mannich-type) reaction using TiCl₄/n-Bu₄NI system between the α,β-unsaturated carbonyl compounds possessing an Evans oxazolidinone as a chiral auxiliary and N-acyliminium ion intermediates is described. The reaction was promoted in a mixed solvent of AcOEt–CH₂Cl₂ to afford indolizidine compounds with three stereogenic centers.