O,j8-Unsaturated Ketone

An example of attaching a carbon nucleophile to an o, j8-unsaturated ketone is the Sakurai reaction. This involves the reaction of allyltrimethylsilane with an a,fi-unsaturated ketone to form a -unsaturated ketone in the presence of a Lewis acid. Howarth used indium(iii) chloride to catalyze this reaction in the ionic liquids [BMIM][BF4] and [BMIM][PF6] [207]. An example ofthis is shovm in Scheme 5.2-83. 

Scheme 2.9. In cyclohexane derivatives, equatorial attack dominates. With o ,j8-unsaturated ketones, the reaction occurs by conjugate addition. The addition step is...

The reduced reactivity of o,j8-unsaturated ketones towards 3-mercapto-ethanol allows preferential formation of the hemithioacetal of an unconjugated carbonyl present in the molecule. One example of this general... 

The thioenol ethers are stable towards base and lithium aluminium hydride , but are reconverted to the parent compound on dilute acid hydrolysis. Raney nickel desulphurization can be used to form the diene . Hydrogen peroxide oxidation will convert the acid-labile thioenol ether to an acid-stable sulphoxidoenol ether > . The sulphoxidoenol ether may be desulphurized with Raney nickel to the diene, or with lithium aluminium hydride reconverted to the thioenol ether for hydrolysis to the o,j8-unsaturated ketone . These reactions are depicted in equation (80). 

How would you prepare the following compound using a Robinson annulation reaction between a 8-diketone and an o ,j8-unsaturated ketone Draw the structures of both reactants and the intermediate Michael addition product. 

The Mannich reaction is another version of an aldol reaction that takes place under mildly acidic conditions. There are several variants, but all of them involve the reaction of a nucleophilic ketone with a primary or secondary ammonium ion (RNH3 or R2NH2) and an aldehyde, usually formaldehyde (CH2O). The Mannich reaction proceeds via an iminium ion (RNH=CH2 or R2N=CH2), an electrophilic species that reacts with the enol form of the ketone to give a j8-aminoketone. Sometimes El elimination of the amine (via the enol) follows to give an o./l-unsaturated ketone. 

The use of oxirane together with Na2HP03 to prepare (2-hydroxyethyl)phosphonic acid as its disodium salt is of historical interest. Other poorly exploited, yet interesting and potentially valuable, reactions include the combination of a trialkyl phosphite and dialkyl chlorophosphate with an oxirane to yield O-phosphorylated derivatives of (2-hydrox-yalkyl)phosphonic diesters (reaction 10)" and, following the initial reaction of an a,j8-unsaturated ketone with a phosphorus(III) triester to give the cyclic phosphorane 272, the subsequent further reaction of the latter with an aldehyde followed by hydrolysis (reaction 11)" Dialkyl acetyl phosphites are reported to react with oxirane through anionic intermediate species with the formation, albeit in low yields, of dialkyl (2-acetyloxyethyl)phos-phonates hydrolysable with concentrated HCl, to give (2-hydroxyethyl)phosphonic acid ... 

Halogenated-a,)8-unsaturated ketones or aldehydes are reacted with methyl thioglycolate and cyclized with alkali alcoholate. Thus j8-bromobenzalacetone (75) gives methyl 3-methyl-6-phenyl-2-thio-phenecarboxylate (76) and from o-methyl-y -chlorocrotonaldehyde (77), 4,5-dimethyl-2-thiophenecarboxylate (78) is obtained. 

Enamines behave in much the same way as enolate ions and enter into many of the same kinds of reactions. In the Stork reaction, for example, an enamine adds to an a,/3-unsaturated carbonyl acceptor in a Vlichael-like process. The initial product is then hydrolyzed by aqueous acid (Section 19.8) to yield a 1,5-dicarbonyl compound. The overall reaction is thus a three-step sequence of (1) enamine formation from a ketone, (2) Michael addition to an o ,j8-unsaturatcd carbonyl compound, and (3) enamine hydrolysis back to a ketone. 

This reaction was initially reported by Doebner and von Miller in 1881 as a modification of the original Skraup Reaction, and it was subsequently modified by Beyer in 1886 It is an acidic condensation between primary aromatic amines (e.g., anilines) and Q ,j8-unsaturated carbonyl compounds (mostly o ,y3-unsaturated aldehydes) to give 2,3-disubstituted quinolines. Therefore, this reaction is generally known as the Doebner-Miller reaction, or Doebner-Miller synthesis." In addition, this reaction is also referred to as the Doebner-von Miller quinoline synthesis, Skraup-Doebner-von Miller reaction, Skraup-Doebner-von Miller quinoline synthesis, Doebner-Miller condensation, and Doebner-Miller Quinaldine Synthesis. For comparison, the modification from Beyer, known as the Beyer method for quinoline, is an acidic condensation between anilines and Q ,j8-unsaturated carbonyl compounds generated in situ from aldehyde or aldehyde and methyl ketone to afford 2,4-disubstituted quinolines." The optimal condition of this reaction is to heat the mixture of aniline/aldehyde (1 2) at 100°C for 6 h with hydrochloric acid and zinc chloride in addition, an oxidizing reagent is also needed in this reaction, such as nitrobenzene. However, it has been reported that A -alkylanilines are also formed in this reaction. The nature and... 

Thus, the interaction of a-haloalkylnitrones 64a,b with amines and hydrazine leads to products that contain no iV-oxide oxygen atom. This allows aldehyde and ketone derivatives of 3-imidazoline nitroxide to be synthesized the latter are of interest as spin labels for biological systems (Schlude, 1973). The interaction of the same compounds (64a,b) with nitrogenous nucleophiles, which contain a more electronegative nitrogen atom than that in amines or hydrazine, as well as the interaction with C-, S-, and O-nucleophiles, proceeds with the preservation of the nitrone group and leads to nucleophilic substitution products. Dehydrobromination of 4-bromoalkyl derivatives leads to reactive a,j8-unsaturated nitrones... 

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