Carbonylation reactions unsaturated amides

Thus unsubstituted (R=H) and substituted (R = alkyl) non-stabilized diyiides 1 react with phenylisocyanate and dicyclohexylcarbodiimide (R NCX), leading to the formation of new monoylide type intermediates. These last ones react in situ with carbonyl compounds through a Wittig type reaction leading respectively to a,)8-unsaturated amides 2 and amidines 3, with a high E stereoselectivity, the double bond being di- or tri-substituted [48,49]. By a similar reactional pathway, diyiides also react with carbonic acid derivatives, with the synthesis as final products of -a,/l-unsaturated esters 4 and acids 5 [50]. 

The reaction of but-l-en-3-yl diethyl phosphate with diethylamine produces N,N-diethylpent-3-enamide (86%), indicating that a Ji-allyl complex is involved in the carbonylation reaction. No isomerism to the a,p-unsaturated amides was observed. 

Allylamines cyclize readily with a dicobalt octacarbonyl catalyst (equation 55).1,2 Rhodium catalysis generally allows the carbonylative cyclization to be carried out under milder conditions.86 Application of this reaction to unsaturated amides yields the corresponding imides, the best yields arising when R1 = H and R2 = allyl (equation 56).I>2... 

Michael addition of metal enolates to a,/3-unsaturated carbonyls has been intensively studied in recent years and provides an established method in organic synthesis for the preparation of a wide range of 1,5-dicarbonyl compounds (128) under neutral and mild conditions . Metal enolates derived from ketones or esters typically act as Michael donors, and a,-unsaturated carbonyls including enoates, enones and unsaturated amides are used as Michael acceptors. However, reaction between a ketone enolate (125) and an a,/3-unsaturated ester (126) to form an ester enolate (127, equation 37) is not the thermodynamically preferred one, because ester enolates are generally more labile than ketone enolates. Thus, this transformation does not proceed well under thermal or catalytic conditions more than equimolar amounts of additives (mainly Lewis acids, such as TiCU) are generally required to enable satisfactory conversion, as shown in Table 8. Various groups have developed synthons as unsaturated ester equivalents (ortho esters , thioesters ) and /3-lithiated enamines as ketone enolate equivalents to afford a conjugate addition with acceptable yields. 

Vinyl bromides are directly aminocarbonylated by nickel carbonyl and amines. Very similarly, Rh (CO)i6 and BU4NCI as cat yst convert allylphosphates to. -y-unsaturated amides via rr-allylrhodium complexes (equation 43). Although palladium(O) complexes are more reactive than rhodium(I) complexes, palladium(O) complexes undergo side reactions, like reductive elimination in the presence of carbon monoxide, and direct nucleophilic attack by amines. 

Catalytic hydrocarboxylations and related esterifications as well as amidations of alkenes belong to a family of carbonylation reactions which has attracted considerable industrial interest. Minor changes in the catalyst system as well as in reaction conditions can lead to simple carboxylic acids, diacids, polyketones, or unsaturated acids as products (Scheme 1). Most importantly, these methods provide routes to monocarboxylic acids, e.g., ethylene to propanoic acid (see Section 2.1.2.2), or 1-olefins (readily available from the oligomerization of ethylene discussed in Section 2.3.1.3) to higher carboxylic acids. 

Reaction with amides. Benzamides and thiobenzamides are converted to a,a-disubstituted benzylamines. Tertiary amides form ketones on reaction with RCeCl even when the reagent is present in large excess, therefore Weinreb amides are not necessary for the ketone synthesis. Enaminones are also attacked at the carbonyl group, and in the cases of a -silylated derivatives the reaction products are 3,y-unsaturated ketones. ... 

Since conjugate (Michael) addition and Diels-Alder reactions use a,p-unsat united carbonyl compounds, asymmetric versions of these reactions could use the auxiliaries that we have seen in aldol reactions in the form of 118 and 119. Diels-Alder reactions work very well with these unsaturated amides and also with amides 121 derived from Oppolzer s chiral sultam14 120, prepared simply from camphorsulfonyl chloride. 

In general, lower regioselectivities were observed with chiral p-substituted a,P-unsaturated carbonyl compounds compared to reactions involving acrylic derivatives. a,p-Unsaturated amides proved to be most effective. 

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... 

Perhydrobenzoxazine 73 was reported as being a chiral auxiliary used to control the stereoselectivity of a thermally induced Alder-Ene reaction. In this instance, both endo- or exo-transition states seemed plausible to provide the observed products. Both TS minimize non-bonding steric interactions and were used to explain the selectivity observed. Ultimately, 74 was used to prepare cw-3,4-disubstituted pyrrolidines. For the conversion of 73 into 74, it should be noted that the enophile was the a,P-unsaturated amide and that the new C-C bond formed was alpha to the carbonyl. This appeared counter-intuitive for a LUMO enophile controlled reaction. 

Yamamoto and co-workers have reported the decarboxylation-carbonylation reaction of aUyl carbamates to afford /3,y-unsaturated amides (Scheme 57),... 

The carbonylation of allylic amines proceeds under severe reaction conditions to give )8, y-unsaturated amides by using dppp as a ligand (Scheme Decarboxyla-... 

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