Unsaturated ketone, conjugate addition reactions

There are two major reactions of organocuprates, and both give products reminiscent of a carbon nucleophile (1) reaction with alkyl halides and (2) conjugate addition with a,p-unsaturated ketones. Conjugate addition to a, 3-unsaturated ketones is promoted when ether is used as a solvent.381 The substitution reaction is promoted by the use of THF or ether-HMPA as a solvent. l As mentioned earlier, the mechanism of these reactions probably involves a one-electron transfer, although other mechanistic proposals are in the literature,but the synthetic result is that expected of a carbon nucleophile. 85 The general reactivity of organocuprates with electrophiles follows the order ... 

C—C Bond Formation using Organosilanes. Under catalysis by TiCU, allylsilanes transfer the allyl group, with rearrangement, to ketones, a/3-unsaturated ketones (conjugate addition), and quinones (initially giving the carbonyl addition product which then further rearranges to the 2-allyl-l,4-hydroquinone). But-3-enyl-silanes react with acid chlorides to yield cyclopropylmethyl ketones [reaction (3)) under similar conditions. 

Some examples of conjugate addition reactions of allylic silanes are given in Scheme 9.5. Entries 1 to 3 illustrate the synthesis of several (3-allyl ketones. Note that Entry 2 involves the creation of a quaternary carbon. Entry 4 was used in the synthesis of a terpenoid ketone, (+)-nootkatone. Entry 5 illustrates fluoride-mediated addition using tetrabutylammonium fluoride. These conditions were found to be especially effective for unsaturated esters. In Entry 6, the addition is from the convex face of the ring system. Entry 7 illustrates a ring closure by intramolecular conjugate addition. 

A different approach toward highly substituted pyrroles involving a one-pot sila-Stetter/Paal-Knorr strategy was realized by Bharadwaj and Scheidt (Scheme 6.182) [343]. In this multicomponent synthesis, catalyzed by a thiazolium salt, an acyl anion conjugate addition reaction of an acylsilane (sila-Stetter) was coupled in situ with the conventional Paal-Knorr approach. Employing microwave conditions at 160 °C for 15 min, the acylsilane was combined with the cx/l-unsaturated ketone in... 

Muller and coworkers have recently developed a coupling-isomerization reaction, initially identified as a side reaction which occurred under standard Sonogashira conditions [79]. As demonstrated below, the coupling reaction is followed by a shuffling of oxidation states via an alkyne-allene isomerization [80]. The product, a,P-unsaturated ketone 146, is reminiscent of a product which would be obtained from a Heck reaction. The utility of this reaction was further demonstrated when diamine 147 was added to the reaction pot. Following a conjugate addition reaction and imine formation, compound 148 resulted from the three-component, one-pot reaction sequence enabled by the coupling-isomerization reaction. 

The intramolecular version of the Lewis-acid-promoted conjugate addition of allylsilanes to a,/ -unsaturated ketones (Hosomi-Sakurai reaction) has... 

Cho reported the addition of alkyl radicals from alkyl iodide to a,P-unsaturated ketones, esters, and nitriles mediated by indium in aqueous media. Recently, enantiomeiically pure natural and unnatural a-amino acids have been synthesized from a chiral methyleneoxazolidinone by such a highly diastereoselective 1,4-conjugate addition of alkyl iodides in aqueous media (Eq. 10.31). The zinc-copper conjugate addition reaction exhibits high chemoselectivity with the possibility of using functionalized iodides to afford a single diastereomer in short reaction times with good yields. 

Conjugate addition reaction of a thiol group to unsaturated ketone was efficiently applied to a synthesis of ecteinascidin 743 (99) by Corey et al. [54]. Conjugate addition of the... 

A popular and useful application of the conjugate addition reaction is the combined conjugate addition-intramolecular aldol strategy, commonly known as the Robinson annulation. When the Michael donor is a ketone and the Michael acceptor an a,p-unsaturated ketone, the product is a 1,5-diketone which can readily undergo cyclization to a six-membered ring. Typical Michael donor substrates are 2-substituted cyclohexanones, which condense with alkyl vinyl ketones to give the intermediate conjugate addition products 42 (1.52). The subsequent intramolecular... 

Conjugate Addition Reactions. a, 8-Unsaturated ketones undergo conjugate addition with TMS-I to afford the /3-iodo... 

So far we have shown you conjugate additions mainly of a,P-unsaturated aldehydes and unsaturated a,P-ketones. You won t be at all surprised to learn, however, that unsaturated acids, esters, amides, and nitriles—in fact all carboxylic acid derivatives—can also take part in conjugate addition reactions. Two examples, an amide and an ester, are shown on the right below. But notice how the selectivity of these reactions depends on the structure of the unsaturated compound compare the way butyllithium adds to this a,P-unsaturated aldehyde and a,P-unsaturated amide. Both additions are irreversible, and BuLi attacks the reactive carbonyl group of the aldehyde, but prefers conjugate addition to the less reactive amide. Similarly, ammonia reacts with this acyl chloride to give an amide product that derives from direct... 

Sodium borohydride is a nucleophile that you have seen reducing simple aldehydes and ketones to alcohols, but it will also do conjugate addition reactions. Which of the alternatives actually takes place depends on the reactivity of the C=0 group. NaBH4 usually reacts with a,P-unsaturated aldehydes to give alcohols by direct addition to the carbonyl group. 

The silicon works by reacting with the negatively charged intermediate in the conjugate addition reaction to give a silyl enol ether—a type of molecule we met in Chapter 20. Here is a possible mechanism for a reaction between Bu2CuLi and an a, 3-unsaturated aldehyde in the presence of MeaSiCl. The silyl enol ether simply hydrolyses to the ketone at the end of the reaction. 

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