Decarboxylative Allylic Amidation

This observation led to the suggestion that the reacting nucleophile is a tautomer of the anion that is initially formed rather than its decarboxylation product  

In another report of Singh and Han [61], Ir-catalyzed decarboxylative amidations of benzyl allyl imidodicarboxylates derived from enantiomerically enriched branched allylic alcohols are described. This reaction proceeded with complete stereospecificity-that is, with complete conservation of enantiomeric purity and retention of configuration. This result underlines once again (cf. Section 9.2.2) that the isomerization of intermediary (allyl) Ir complexes is a slow process in comparison with nucleophilic substitution. 

Dihydropyrroles and y-Lactams via Allylic Substitution and Ring-Closing Metathesis 

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

Singh, O.V. and Han, H. (2007) Iridium(I)-catalysedregio-and enantioselective decarboxylative allylic amidation of substituted allyl benzyl imidodicarbonates. Journal of the American Chemical Society, 129, 774-775 Singh, O.V. and Han, H. (2007) Iridium(I)-catalysed regio-and enantioselective allylic amidation. Tetrahedron Letters, 48, 7094—7098. 

As a final set of examples, enantioselective allylic substitution of unstabilized eno-lates to form a new stereocenter at the enolate carbon have been developed through the decarboxylative reactions of allyl enol carbonates. - - These reactions are enantioselective versions of reactions closely related to those in Equation 20.18 and Scheme 20.4, and two examples are shown in Equations 20.60 and 20.61. In these cases, a new stereocenter is formed at the a-carbon of the enolate nucleophile. Most of these reactions have been conducted with allyl enol carbonates that generate cyclic ketone enolates, but enantioselective reactions of acyclic allyl enol carbonates have also been reported. Although allyl enol carbonates undergo decarboxylation faster than the 3-keto ester isomers, the 0-allyl p-keto esters are more difficult to prepare, and enantioselective allylations starting with p-ketoesters have been reported. - Decarboxylative reactions of amines and a-amino acids have been conducted to form allylic and homoallylic amines (Equation 20.62), respectively, and enantioselective decarboxylative allylations of amides have been reportedIridium-catalyzed enantioselective decarboxylative allylation of amides starting with 0-allyl imides has also been reported. ... 

J ,J )-configured ligand also attacks the enolate from its 5i-face as well. The cartoons shown in Scheme 5.42 may serve to illustrate why opposite enantiomers of the palladium catalyst both lead to (/ )-allyl tetralone 15. It seems that the t-butyl-PHOX ligand is too sluggish to react with cyclic ally substrates like 127. Therefore, it remains open whether Trost s proof of the outer-sphere mechanism is restricted to the C2-symmetric bis-amide ligands. Despite the discrepancy in the stereochemistry of the mechanism, the asymmetric decarboxylative allylic alkylation enjoyed manifold applications in total synthesis [62]. 

Co-adsorption experiments show a complex role of the nature and concentration of chemisorbed ammonia species. Ammonia is not only one of the reactants for the synthesis of acrylonitrile, but also reaction with Br()>nsted sites inhibits their reactivity. In particular, IR experiments show that two pathways of reaction are possible from chemisorbed propylene (i) to acetone via isopropoxylate intermediate or (ii) to acrolein via allyl alcoholate intermediate. The first reaction occurs preferentially at lower temperatures and in the presence of hydroxyl groups. When their reactivity is blocked by the faster reaction with ammonia, the second pathway of reaction becomes preferential. The first pathway of reaction is responsible for a degradative pathway, because acetone further transform to an acetate species with carbon chain breakage. Ammonia as NH4 reacts faster with acrylate species (formed by transformation of the acrolein intermediate) to give an acrylamide intermediate. At higher temperatures the amide may be transformed to acrylonitrile, but when Brreform ammonia and free, weakly bonded, acrylic acid. The latter easily decarboxylate forming carbon oxides. 

Singh and Han [60] have reported the preparation of another dihydropyrrole by using a N-Cbz derivative obtained by decarboxylative amidation (Scheme 9.27, results line 1) as starting material. N-Alkylation with allyl bromide followed by RCM (Grubbs II catalyst) furnished the dihydropyrrole in excellent yield (95%). Lee et al. have similarly transformed the amination product (Table 9.2, entry 21) into a variety of N-heterocycles [54]. 

Decarboxylation of 117 was effected by treatment of 117 with LiCl in hot, aqueous HMPA at 105 °C providing 118 as a mixture of diastereomers that were separated and carried forward individually. Protection of the secondary amide group as the corresponding methyl lactim ether was accomplished by treating 118 with trimethyloxonium tetrafluoroborate in dichloromethane that contained cesium carbonate. Next, the indole nitrogen atom was protected as the corresponding Boc derivative by treatment with dicarbonic acid bis(rm-butyl)ester in the presence of DMAP and the silyl ether was removed with tetrabutylammonium fluoride to provide diol 119 in 52-78% overall yield from 118. Selective conversion of the allylic alcohol to the corresponding... 

The construction of the maleic anhydride moiety 44 in only five steps starts with the conversion of the amide into an appropriate thioester. Upon treatment with DBU, an aldol-type cyclization occurs to provide the /1-hydroxy thiolactone as a single diastereomer. After removal of the allylic protecting group, dehydration and decarboxylation are carried out simultaneously by simple heating. The thiobutenolide is oxidized to the corresponding thio-... 

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