Cyclizations 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). 

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). ... 

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)]. 

The two products 6 and 7 are formed in a 1 1 mixture however, the stereochemistry of the side-chain is controlled effectively, so that after decomplexation and further manipulations both products can be applied in the synthesis of deoxycytochalasin. When pendant dienes were used instead of the allyl amide side-chain after the initial step of the formal [6 + 2]-Alder-ene reaction (Scheme 9.10), the intermediate 8 undergoes another reductive cyclization to the final polycyclic product 9 in quantitative yield as a single diastereomer, as reported by Pearson and Wang [22], The overall process can be seen as a formal [4 + 4]-cycloaddition reaction of the cyclohexadiene with the pendant diene. 

The thermal rearrangement of O-allyl trichloroacetimidates 1 affords the corresponding 7V-allyl amides 31 2, which have been cyclized with the aim of obtaining amino diols or amino alcohols different to those from the cyclization of the trichloroacetimidates. Cyclization of these latter substrates 1 leads to 4,5-dihydro-4-(l-iodoalkyl)oxazoles 2, while treatment of unsaturated trichloroacetamides 3 with /V-iodosuccinimide3 in chloroform affords the corresponding 4,5-dihydro-5-(l-iodoalkyl)oxazoles 4 in high yield. These heterocyclic products are protected forms of the corresponding amino alcohols. 

Intramolecular cyclization of allylic amide 772 in the presence of strong acid gives oxazoline 773 in high yield. Hydrolysis of 773 in aqueous acid leads to the formation of 774 (Scheme 189) <20000L3443>. 

Hydroformylation of allyl amides catalyzed by Rh(BIPHEPHOS) in acetic acid (reaction in toluene failed) can be utilized as the initial step of a cyclization reaction (Scheme 4.43) [88]. Under the described conditions, the intermediate aldehyde undergoes ring closure with the participation of the aromatic ring. 

The bicyclization commences with the hydroformylation of an appropriate N-substituted allyl amide, producing the linear aldehyde as the main product. The compound undergoes spontaneous intramolecular cyclization. The final product of this domino reaction is formed by the reaction with the solvent (AcOH). Subsequent oxidation of the acylic keto group to the corresponding ester and reduction with LiAlH produced the targeted racemic natural compound with 33% overall yield over four steps. 

Scheme 232 Sequential allylic amidation and atom-transfer radical cyclization.

Atom-transfer radical cyclization (ATRC) is an atom-economical method for the formation of cyclic compounds, which proceeds under mild conditions and exhibits broad functional group tolerance. Okamura and Onitsuka described a planar-chiral Cp-Ru complex 124-catalyzed asymmetric auto-tandem allylic amidation/ATRC reaction in 2013. This protocol proceeds highly regio, diastereo, and enantioselec-tively to construct optically active y-lactams from readily available substrates in a one-pot manner (Scheme 2.32). In this process, a characteristic redox property of ruthenium complexes would work expediently in different types of catalyzes involving mechanistically distinct allylic substitutions (Ru /Ru ) and atom-transfer radical cyclizations (Ru /Ru ), thus leading to the present asymmetric auto-tandem reaction [48]. 

The cyclization of IV-allyl-o-haloanilines was adapted to the solid phase for both indoles [332, 333] and oxindoles [334]. For example, as illustrated below, a library of l-acyl-3-aIkyl-6-hydroxyindoles is readily assembled from acid chlorides, allylic bromides, and 4-bromo-3-nitroanisole [332], Zhang and Maryanoff used the Rink amide resin to prepare Af-benzylindole-3-acetamides and related indoles via Heck cyclization [333], and Balasubramanian employed this technology to the synthesis of oxindoles via the palladium cyclization of o-iodo-N-acryloylanilines [334], This latter cyclization route to oxindoles is presented later in this section. 

A more traveled route to the absolute configuration represented by cyclohexa-1,4-diene 8 involves Birch reduction-alkylation of benzoxazepinone 9.2.5 heterocycle is best prepared by the base-induced cyclization of the amide obtained from 2-fiuorobenzoyl chloride and (5)-pyrrolidine-2-metha-nol. o The molecular shape of enolate 10 is such that the hydrogen at the stereogenic center provides some shielding of the a-face of the enolate double bond. Thus, alkylation occurs primarily at the 3-face of 10 to give 11 as the major diastereomer. The diastereoselectivity for alkylation with methyl iodide is only 85 15, but with more sterically demanding alkyl halides such as ethyl iodide, allyl bromide, 4-bromobut-1-ene etc., diastereoselectivities are greater than 98 2. 

For example, the allyl-substituted amide 26 cyclizes to the 6-membered lactone 27 in refluxing 6M HCl (Scheme 15) . 

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