Amide unsaturated

Unsaturated Amides. - In further examples of conjugate additions to unsaturated amides, various stannyl copper species have been found to add to acetylenic amides (428) to give either (E)- (429) or ( )-3 Stannyl amides, depending on the reaction conditions. 

Over the past few years a number of research groups, especially 

Upon warming, the dianion (435) undergoes a bis-anionic Fries 

Similarly, heterocyclic amides can be bis-metallated the dianion (437) can be coupled with different electrophiles, the first attacking the more reactive 3-position, although perhaps predictably yields of 2,3,5-unsymmetrically substituted thiophenes are only moderate. The ability of amide groups in general to direct metallation to the usually less reactive 3-position in these types of heterocycles has been summarized. 

The sulphone-stabilized dianion (438) undergoes efficient condensations with aldehydes to provide diols (439) after overall 

Unsaturated amides react with carbon monoxide in the presence of cobalt catalysts to give imides [673, 681-683]. Acrylamide reacts with carbon monoxide to give succinimide in 82% yield. N-mono-substituted acrylamides are converted into the corresponding N-substituted sucdnimi-des (see table 63). 

When the starting materials contain halogenated aromatic groups, no dehalogenation takes place. Similarly, methacrylamide and N-substituted methacrylamides give a-methylsuccinimide (see table 63). 

P-Arylated acrylamides also react to give a-substituted succinimides. Thus a-phenylsuccinimide is obtained from cinnamamide. 

The reaction of p-alkylacrylamides leads not only to a-alkylsuccinimides, but also to glutarimides. For example, crotonamide reacts to form a mix- 

The six-membered rings are formed by isomerization of intermediate complexes formed from the olefinic starting material and the catalyst. Similar isomerizations were observed in other reactions with carbon monoxide in the presence of transition metal carbonyls (see the chapter on hydro-formylation and carbonylation reactions). 

Karlsson and Hogberg (291,292) applied the thiocarbonyl ylide 175 in a diastereoselective 1,3-dipolar cycloaddition with 165. The thiocarbonyl yhde was generated in situ by an elimination reaction. The reaction with 165 gave 176 (R = Bu, BnO, Ph) with selectivities of up to 64—80% de. Furthermore, the cycloaddition of a chiral galactose-derived nitrile imine with 165 has been reported (104). 

p-unsaturated amides 180-188a have all been used in 1,3-dipolar cycloadditions with nitrile oxides, and some of them represent the most diastereoselective reactions of nitrile oxides. The camphor derivative 180 of Chen and co-workers (294), the sultam 181 of Oppolzer et al. (295), and the two Kemp s acid derived compounds 186 (296) and 187 (297) described by Curran et al. (296) are excellent partners for diastereoselective reactions with nitrile oxides, as very high diastereos-electivities have been observed for all of them. In particular, compound 186 gave, with few exceptions, complete diastereoselection in reactions with a wide range of different nitrile oxides. Good selectivities were also observed when using compounds 183 (298) and 184 (299-301) in nitrile oxide cycloadditions, and they have the advantage that they are more readily available. Curran and co-workers also studied the 1,3-dipolar cycloaddition of 187 with silyl nitronates. However, compared to the reactions of nitrile oxides, lower selectivities of up to 86% de were obtained (302). 

The amino acid derived chiral oxazolidinone 188 is a very commonly used auxiliary in Diels-Alder and aldol reactions. However, its use in diastereoselective 1,3-dipolar cycloadditions is less widespread. It has, however, been used with nitrile oxides, nitrones, and azomethine ylides. In reactions of 188 (R = Bn, R =Me, R = Me) with nitrile oxides, up to 92% de have been obtained when the reaction was performed in the presence of 1 equiv of MgBr2 (303). In the absence of a metal salt, much lower selectivities were obtained. The same observation was made for reactions of 188 (R = Bn, R = H, R = Me) with cyclic nitrones in an early study by Murahashi et al. (277). In the presence of Znl2, endo/exo selectivity of 89 11 and up to 92% de was observed, whereas in the absence of additives, low selectivities resulted. In more recent studies, it has been shown for 188 (R =/-Pr, R = H, R =Me) that, in the presence of catalytic amounts of Mgl2-phenanthroline (10%) (16) or Yb(OTf)3(20%) (304), the reaction with acyclic nitrones proceeded with high yields and stereoselectivity. Once again, the presence of the metal salt was crucial for the reaction no reaction was observed in their absence. Various derivatives of 188 were used in reactions with an unsubstituted azomethine ylide (305). This reaction proceeded in the absence of metal salts with up to 60% de. The presence of metal salts led to decomposition of the azomethine ylide. 

3-dipolar cycloaddition of 189 with metalla-azomethine ylides was described by Waldmann et al. and others (306-309). In some cases, the reactions proceeded with almost complete endo/exo selectivity ( 99 1) and with de values of up to 98%. 

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Allylamines are not easily cleaved with Pd catalysts, but the carbonylation of the allylic amine 395 proceeds at 110 C to give the /3,7-unsaturated amide 396 by using dppp as a ligand[252], Dccarboxylation-carbonylation of allyl diethyl-carbamate under severe conditions (100 C, 80 atm) affords /3,7-unsaturated amides[2531. The 3-vinylaziridine 397 is converted into the a-vinyl-J-lactam 398 under mild conditions[254]. 

Alternative degradation pathways are operative when the initial aziridines bear (3-hydrogen atoms. In these instances a,(3- unsaturated amides (322) (from aziridinones) and amidines, e.g. (320), from aziridinimines are frequently isolated as the major products. 

Electrophilic cyclizations of unsaturated amides to form 5- and 6-member lactams 98T13681. 

N,O-acetal intermediate 172, y,<5-unsaturated amide 171. It is important to note that there is a correspondence between the stereochemistry at C-41 of the allylic alcohol substrate 173 and at C-37 of the amide product 171. Provided that the configuration of the hydroxyl-bearing carbon in 173 can be established as shown, then the subsequent suprafacial [3,3] sigmatropic rearrangement would ensure the stereospecific introduction of the C-37 side chain during the course of the Eschenmoser-Claisen rearrangement, stereochemistry is transferred from C-41 to C-37. Ketone 174, a potential intermediate for a synthesis of 173, could conceivably be fashioned in short order from epoxide 175. 

Vinylepoxides from Functionalized Dienes 9.1.2.1 From Dienones or Unsaturated Amides... 

A limited number of examples only exist for the Michael addition of lithium enolates to a,)3-unsaturated amides high stereocontrol was observed in only a few cases62-67,379. 

The compound R2CuLi also adds to N-tosylated a,P-unsaturated amides Nagashima, H. Ozaki, N. Washiyama, M. Itoh, K. Tetrahedron Lett., 1985, 26, 657. 

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]. 

Conjugate reductions of unsaturated amides are listed in Section 74D (Alkyls from Alkenes). 

Ruthenium complexes containing this ligand are able to reduce a variety of double bonds with e.e. above 95%. In order to achieve high enantioselectivity, the reactant must show a strong preference for a specific orientation when complexed with the catalyst. This ordinarily requires the presence of a functional group that can coordinate with the metal. The ruthenium-BINAP catalyst has been used successfully with unsaturated amides,23 allylic and homoallylic alcohols,24 and unsaturated carboxylic acids.25... 

A. Claisen Rerrangements of Ketene Aminats and Imidates. A reaction that is related to the orthoester Claisen rearrangement utilizes an amide acetal, such as dimethylacetamide dimethyl acetal, in the exchange reaction with allylic alcohols.257 The products are y, 8-unsaturated amides. The stereochemistry of the reaction is analogous to the other variants of the Claisen rearrangement.258... 

Imidate esters can also be generated by reaction of imidoyl chlorides and allylic alcohols. The lithium anions of these imidates, prepared using lithium diethylamide, rearrange at around 0°C. When a chiral amine is used, this reaction can give rise to enantioselective formation of 7, 8-unsaturated amides. Good results were obtained with a chiral binaphthylamine.265 The methoxy substituent is believed to play a role as a Li+ ligand in the reactive enolate. 

Scheme 33 Cu-catalyzed reaction of keto-unsaturated amides...

Further attempts to effect a one-step synthesis of the hasubanan skeleton via acid-catalyzed cyclization of urethane 28 and unsaturated amides 31 and 32 were explored, using trifluoroacetic acid (TFA) (Scheme 1). Treatment of... 

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