Conjugate nucleophilic additions enones

The mechanism of the reaction is thought to involve conjugate nucleophilic addition of the diorganocopper anion, R2C1F, to the enone to give a... 

Aside from pregn-16-en-20-ones, no other conjugated steroidal enones that are known to undergo facile nucleophilic addition to the carbon-carbon... 

Diastereoselective conjugate addition of nucleophiles to enones, enals, and enoates occurs with high stereocontrol and constitutes a powerful method in stereoselective synthesis.185... 

Mesylation of the alcohol 65 followed by deprotonation afforded the sul-fone-stabilized carbanion 66 that underwent a macrocyclization to afford the artificial dolabellane 67 in moderate yield (Scheme 9). Hydrolytic cleavage of the ketal (67) followed by a base-mediated double bond isomerization (into conjugation) afforded an enone containing an exocyclic carbonyl group. Nucleophilic 1,2-addition of methyl lithium introduced the missing... 

Thiols may be enantioselectiveiy added in a conjugate fashion to a,p-unsaturated carbonyl compounds in the presence of chiral hydroxyamine catalysts e.g. chinchona alkaloids).242,244 249 252-261-269 In some cases ee of up to >80% were achieved e.g. Scheme 77).242-261-262 This methodology was utilized for the kinetic resolution of compound rat-86 Scheme 34) in a multigram scale.94 Related enantioselective 1,4-additions of thioacetates270-271 and selenophenols272 to enones are also known. Epoxidations, based on the asymmetric nucleophilic addition of peroxide anions to enones, are discussed separately.273... 

The highest enantioselectivity (up to >99%) yet achieved in the addition of S-nucleophiles to enones was reported in 2002 by Deng et al. [59]. By systematic screening of monomeric and dimeric cinchona alkaloid derivatives they identified the dihydroquinidine-pyrimidine conjugate (DHQD PYR (72, Scheme 4.35) as the most effective catalyst. This material is frequently used in the Sharpless asymmetric dihydroxylation and is commercially available. Screening of several aromatic thiols resulted in the identification of 2-thionaphthol as the nucleophile giving best yields and enantioselectivity. Examples for the (DHQD PYR-catalyzed addition of 2-thionaphthol to enones are summarized in Scheme 4.35. 

Keywords Organozinc, Organolithium, Grignard reagent, Copper, Conjugate addition, Nucleophilic addition, Alkylation, Activated olefin, Enone, Nitroalkene, p-Substituted carbonyl... 

The reactions in this section cover the conjugate (Michael) addition of various lithiated nucleophiles to activated olefins such as enones and enoates. Lithium enolates are formed as intermediates during the addition process. They can be treated as such and trapped, for instance, by an electrophile to provide ketones or esters substituted both in the a and positions. We will focus only on the most important information relevant to the intermediate enolates, and those are rarely discussed in the literature on the Michael addition. The reader can advantageously consult Chapter 14 of the first part of this volume133, which is entirely dedicated to the organolithium additions to double bonds, for a more extensive coverage of the topic. 

Ethynyl carbinols (propargylic alcohols) such as 134 (Scheme 2.58) represent another important group of oxidation level 3 compounds. Their preparation involves nucleophilic addition of acetylides to the carbonyl group, a reaction that is nearly universal in its scope. Elimination of water from 134 followed by hydration of the triple bond is used as a convenient protocol for the preparation of various conjugated enones 135. Easily prepared O-acylated derivatives are extremely useful electrophiles in reactions with organocuprates, which proceed with propargyl-allenyl rearrangements to furnish allene derivatives 136. 

The chemical reactivity of propenal is representative of a, -unsaturated carbonyl compounds. The conjugation between a carbon-carbon double bond and a carbonyl group leads to characteristic reactivity, which includes reduced reactivity of the carbon-carbon double bond toward electrophiles and enhanced susceptibility to the addition of nucleophilic reagents at the (3 carbon. The anion formed by addition is a delocalized enolate, with the negative charge shared by oxygen and carbon. The topic of nucleophilic addition to enals and enones is considered further in Section 2.6, Part B. 

Stereoselective, conjugate allylation of more remote positions using allyl trimethylsilane and TiCE is possible. Further transformation by nucleophilic addition and ringclosing metathesis affords fused polycyclic ring systems (Scheme 88). Stabilized anions and organocopper see Copper Organowetallic Chemistry) reagents also participate in Michael-type additions to complexed a ,/3-unsaturated aromatic enones. 

The diastereoselectivity observed for the conjugate addition to the nonchelated enone sulfoxide (98a) was improved by the use of diorganomagnesium reagents with DME as solvent. Under the same reaction conditions, nucleophilic additions to the corresponding cyclohexenone (101) proceeded with moderate stereoselectivity, giving cyclohexanones (102) as products with somewhat lower enantiomeric excesses than for cyclopentanones (99b) (Scheme 5.35 and Table 5.4) [99]. It should also be noted that in several cases the addition of a highly complexing additive such as 18-crown-6 served to raise the amount of asymmetric induction by about 20% (Table 5.4). 

A Knoevenagel condensation is a nucleophilic addition of an active hydrogen compound such as malonates to a carbonyl group followed by a dehydration reaction in which a molecule of water is eliminated (hence condensation). The product is an alpha, beta conjugated enone. 

In 2007, the research groups of Chen and Deng [81] applied the primary amine derived from quinine as an outstanding catalyst for the addition of different nucleophiles to enones. Chen and Deng tested this catalyst in the conjugate addition of dicyanoolefins (44) to enones with excellent results (Scheme 33.28). Chen [82] then... 

Organomagnesiums frequently prove superior also in other types of reactions. They may facilitate the oxidation of a carbon-metal to a carbon-oxygen bond, secure clean monoaddition of an acetylide to an activated ester (a critical issue in a monensin synthesis X favor in the presence of a copper catalyst 1,4-addition onto a conjugated enone over 1,2-addition, reorient the attack of formaldehyde on a benzylic entitiy from the a- to the or /to-position, and provide diastereoselectivity in nucleophilic additions onto aldehydes. Furthermore organomagnesiums combine under carbon-carbon linking with a variety of organic halides, tosylates, and acetates if the process is mediated by transition elements such as palladium(O) copper(I), nickel(II) or iron(II) Organoalkalis are often less fit to enter such catalytic cycles. 

Rhodium(I)-complexes are known to be excellent catalysts for the conjugate additions of aryl- and alkenyl boronic acids to a,/3-unsaturated ketones, esters and amides [73,74]. Batey has recently prepared aryl and alkenyl trifluoroborates as air-and moisture-stable reagents for the nucleophilic addition to enones in the presence of a Rh(I)-catalyst to give /3-functionalized ketones in good yields [75]. A number of aryl fluoroborates with electron-withdrawing substituents were also tolerated in this reaction. An unprecedented Rh-catalyzed 1,4-addition of aryl boro-... 

Addition (Sections 14.2, 19.13) Addition of a reactant to the ends of a conjugated tt system. Conjugated dienes yield 1,4 adducts when treated with electrophiles such as MCI. Conjugated enones yield 1,4 adducts when treated with nucleophiles such as cyanide ion. 

Ferrocen-l,l -diylbismetallacycles are conceptually attractive for the development of bimetal-catalyzed processes for one particular reason the distance between the reactive centers in a coordinated electrophile and a coordinated nucleophile is self-adjustable for specific tasks, because the activation energy for Cp ligand rotation is very low. In 2008, Peters and Jautze reported the application of the bis-palladacycle complex 56a to the enantioselective conjugate addition of a-cyanoacetates to enones (Fig. 31) [74—76] based on the idea that a soft bimetallic complex capable of simultaneously activating both Michael donor and acceptor would not only lead to superior catalytic activity, but also to an enhanced level of stereocontrol due to a highly organized transition state [77]. An a-cyanoacetate should be activated by enolization promoted by coordination of the nitrile moiety to one Pd(II)-center, while the enone should be activated as an electrophile by coordination of the olefinic double bond to the carbophilic Lewis acid [78],... 

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