Allyl amides

In contrast to the above additions A-allyl- and substituted A-allyl-amides, -urethanes, -ureas and -thioureas undergo intramolecular cyclization only in 6(3-96% sulfuric acid to give the corresponding oxazolinium and thiazolinium salts. Treatment of these cations with base yields 2-oxazolines and 2-thiazolines in moderate to good yields. The reaction is illustrated by the conversion of A-2-phenylallylacetamide (342) into 2,5-dimethyl-5-phenyl-2-oxazoline (343) in 70% yield 70JOC3768) (see also Chapter 4.19). 

Metathesis of N-tosylated ene-amides and yne-amides has been less extensively investigated. An example of the RCM of ene-amides is a new indole synthesis developed by Nishida [79] metathesis precursor 96 (prepared by ruthenium-catalyzed isomerization of the corresponding allyl amide) is cy-clized to indole 97 in the presence of 56d (Eq. 13). 

A concise total synthesis of the indole alkaloid dihydrocorynantheol (101) (Scheme 19), that features two RCM steps and a zirconocene-catalyzed carbo-magnesation [68], is a further example of Martin s interest in applying RCM as a key reaction for the construction of alkaloid frameworks [69]. The first RCM step was applied to bis-allyl amide 96. The resulting intermediate 97 was directly subjected to carbomagnesation and subsequent elimination to deliver 98 in 71% yield from 96. Amide 98 was then transformed into acrylamide 99 in... 

Caller M, Hollis TK, Overman LE, Ziller J, Zipp GG (1997) First enantioselective catalyst for the rearrangement of allylic imidates to allylic amides. J Org Chem 62 1449-1456... 

O-Allyl imidate esters undergo [3,3]-sigmatropic rearrangements to /V-allyl amides. Trichloromethyl imidates can be made easily from allylic alcohols by reaction with trichloroacetonitrile. The rearrangement then provides trichloroacetamides of IV-allylamines.260... 

The use of ethylene adduct lb is particularly important when the species added to activate catalyst la is incompatible with one of the reaction components. Iridium-catalyzed monoallylation of ammonia requires high concentrations of ammonia, but these conditions are not compatible with the additive [Ir(COD)Cl]2 because this complex reacts with ammonia [102]. Thus, a reaction between ammonia and ethyl ciimamyl carbonate catalyzed by ethylene adduct lb produces the monoallylation product in higher yield than the same reaction catalyzed by la and [Ir(COD)Cl]2 (Scheme 27). Ammonia reacts with a range of allylic carbonates in the presence of lb to form branched primary allylic amines in good yield and high enantioselectivity (Scheme 28). Quenching these reactions with acyl chlorides or anhydrides leads to a one-pot synthesis of branched allylic amides that are not yet directly accessible by metal-catalyzed allylation of amides. 

Scheme 9.27 Decarboxylative allylic amidation. Proton sponge = 1,8-Bis-(dimethylamino)-naphthalene.

Allyl amides (enamides), for example, 225, 228, and 230 cyclize to oxazolines, for example, 226, 229, and 231 when the double bond is activated by an electrophile. The double bond can also be conjugated to a ketone, or present as an allylic epoxide. Reagents commonly used to promote the cyclization include acids,iodine,selenium reagents,and trimethylsilyl triflate (Scheme 8.63). ... 

An interesting transformation of a conformationally restrained allyl amide 232 to an ot-hydroxy-cyclopentenyl hydroxylamine 236 has been reported. The mechanism is thought to involve a series of reversible reactions leading ultimately to 234, which fragments irreversibly to 235. Hydrolysis of the ester accounts for the observed product 236 (Scheme 8.64). 

Nitrene transfer to selenide is also possible. Catalytic asymmetric induction in this process has been studied with Cu(OTf)/bis(oxazoline) catalyst (Scheme 22). When prochiral selenide 206 and TsN=IPh are allowed to react in the presence of Cu(OTf)/chiral bis(oxazoline) 122b, selenimide 207 is obtained with enantioselectivity of 20-36% ee. When arylcinnamyl selenide 208 is applied to this reaction, corresponding selenimide 209 is produced which undergoes [2,3]-sigmatropic rearrangement to afford chiral allylic amides 211 in up to 30% ee. 

Allylic amide isomerization, 117 Allylic amine isomerization ab initio calculations, 110 catalytic cycle, 104 cobalt-catalyzed, 98 double-bond migration, 104 isotope-labeling experiments, 103 kinetics, 103 mechanism, 103 model system, 110 NMR study, 104 rhodium-catalyzed, 9, 98 Allylnickel halides, 170 Allylpalladium intermediates, 193 Allylsilane protodesilylation, 305 Aluminum, chiral catalysts, 216, 234, 310 Amide dimers, NMR spectra, 282, 284 Amines ... 

In the presence of a cationic Rh[((/ )-binap)(cod)] complex, geranyl or neryl amides isomerize slowly to give a mixture of the corresponding enamide and dienamide (Scheme 20) (2). The optical purity of the chiral enamide is high, but the chemical yield is low. Certain cyclic allylic amides give the enamide isomers in a high ee. With a DIOP-Rh catalyst, prochiral allylic alcohols are converted to optically active aldehydes with low ee (31). 

Claisen rearrangement of ally l imidates.1 This Pd(II) catalyst effects exclusive [3, 3] rearrangement of allylic imidates at 25° to allylic amides. Rearrangement of the chiral (E)-allylic imidate 1 results in a mixture of two chiral allyl amides 2 and 3. Thermal rearrangement of 1 results only in 2. 

Also cyclization of a six-membered chain has been reported. By brominating nonconjugated allylic amides, McManus et a/.165-166 obtained 5,6-dihydro- 1,3-oxazine derivative in addition to two other compounds (a five-membered ring and the brominated amide) [Eq. (32)]. 

---