Ring-closing metathesis, allylic amination

The ruthenium-catalyzed isomerization of aryl allyl ethers or amines followed by ring-closing metathesis with ruthenium catalyst 1 furnishes fused benzo-heterocycles in good yield (Scheme 40).66 67... 

Scheme 9.42 (Sj-Nicotine via allylic amination in combination with ring-closing metathesis.

The combination of allylic amination, ring-closing metathesis, and a free radical cyclization provides a convenient approach to the dihydrobenzo[b]indoline skeleton, as illustrated in Scheme 10.10. The rhodium-catalyzed aUylic amination of 43 with the lithium anion of 2-iodo-(N-4-methoxybenzenesulfonyl)arrihne furnished the corresponding N-(arylsulfonyl)aniline 44. The diene 44 was then subjected to ring-closing metathesis and subsequently treated with tris(trimethylsilyl)silane and triethylborane to afford the dihydrobenzojhjindole derivative 46a in 85% yield [14, 43]. 

Tricyclic amine 259 forms by allylation and ring-closing metathesis from optically enriched precursor 258 that itself is the product of asymmetric RCM (03OL4899). 

Scheme 5 Allylation of Alloc-derived sulfones and ring-closing metathesis of an Alloc-protected homoallylic amine...

Dihydropyrroles have recently become readily available by ring-closing metathesis. For this purpose, N-acylated or N-sulfonylated bis(allyl)amines are treated with catalytic amounts of a ruthenium carbene complex, whereupon cyclization to the dihydropyrrole occurs (Entries 6 and 7, Table 15.3 [30,31]). Catalysis by carbene complexes is most efficient in aprotic, non-nucleophilic solvents, and can also be conducted on hydrophobic supports such as cross-linked polystyrene. Free amines or other soft nucleophiles might, however, compete with the alkene for electrophilic attack by the catalyst, and should therefore be avoided. 

A two-step stereoselective strategy for converting glycine-derived aminoesters into unnatural cyclic amino acids has been reported. The process involves a palladium-catalysed tandem allylic amination/[2,3]-Stevens rearrangement followed by a ruthenium-catalysed ring-closing metathesis (Scheme 175). " ... 

Complex molecules have also been synthesized by sequential use of the orga-nocatalytic a-amination of aldehydes by azodicarboxylates catalyzed by some of the systems shown above and by other reaction processes, such as the Passerini reaction [40], Homer-Wadsworth-Emmons olefination [41], Wittig olefination [42], and allylation reaction followed by a ring-closing metathesis [43], In addition, the combination of catalysts in cycle-specific organocascade processes [44] has allowed the synthesis of chiral complex molecules with good results. 

Grigg et al. reported a successful four-component domino reaction for the synthesis of functionalized dienes 316 from aryl iodides, allyl amine derivative, allene, and carbon monoxide [110] (Scheme 6.83). Carbon monoxide could insert into the C—Pd bond of arylpalladium(II) iodides to generate a carbonylpalladium species, which is followed by allenylation to form n-allylpalladium species. Finally, the attack of the nitrogen nucleophile produces the product observed. The products of this domino multicomponent reaction could be subjected efficiently to ring-closing metathesis in the presence of Grubbs second-generation catalyst. 

Very recently, Compain proposed an approach to spirocyclic imino sugars (Scheme 41). The synthetic route started from known cyclobutanol 208, which was transformed into carbamate 209. Rhodium-catalyzed intramolecular C-H amination performed on that compound led to oxazolidinone 211. Subsequently, this compound was Al-allylated and subjected to the ring-closing metathesis with the Grubbs II cat. As a... 

This method can be exploited for the synthesis of 3-substituted N-Boc protected pyrrolidines. Boc-protected )V-allyl-A -(2-bromoallyl)amine is coupled with alkyl or phenylmagnesium chloride using tris(acetylacetonato)iron as a catalyst. Subsequent ring closing metathesis gives pyrrolines that upon hydrogenation afford pyrrolidines (Scheme... 

The use of a sequential a-amination-allylation one-pot sequence of aldehydes followed a ring-closing metathesis strategy has permitted the synthesis of chiral cyclic hydrazines [30]. Thus, the a-amination of several unbranched aldehydes using (5)-proline as catalyst (10 mol%) and dibenzylic azodicarboxylate (18b) in acetonitrile at -20°C for 12 h, followed by the addition of indium powder and allyl bromide at room temperature gave the corresponding 1,2-aUylic amino alcohols in high yields (67-88%) and diastereoselectivities (62-98% de) and excellent... 

The product of the allylic amination process is set up for a ring-closing-ring-opening metathesis process, and subsequent elaboration to alkaloid derivatives. 

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