Metathesis with allyl amines

Basset and co-workers (91) found that amino olefins such as allyl amine and the /V.N-dimethyl derivative failed to undergo metathesis, but that unsaturated quaternary ammonium salts were active at 25°C with zero-valent tungsten and molybdenum catalysts when activated with molecular oxygen. Molar ratios of olefin/(mesitylene)W(CO)3/C2H5AlCl2/02 and olefin/Mo(NO)2Cl2[P(Ph)3]/C2H5AlCl2 were 20/1/24/80 and 20/1/24, respectively. Yields were in the 8-23% range. 

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]. 

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. 

We found that under the conditions of the Wacker oxidation,27 the terminal double bonds of the metathesis products were cleanly transformed to the corresponding aldehydes. While the regioselective oxidation of protected allylic alcohols has been reported,28 the selective Wacker oxidation of an allylic amine derivative to the aldehyde is unprecedented. The Ns protected precursor 19 produced only the starting amine (NsN(H)CH2CH2CH2CH(OEt)2). Consequently, the Ns protecting groups were exchanged with Cbz (27) which successfully led to the desired aldehyde 28. 

Hebach and Kazmaier reported the synthesis of cyclic peptidomimetics containing an alkylated amino acid via Ugi-4CR of N-terminal-protected aloc-amino acids, allyl isocyanoacetate, and chiral amines in trifluoroethanol. Allylic esters of tripeptides 193 were obtained in high yields and good stereoselectivity. Metathesis with 5% of Grubbs first-generation catalyst gave 16-membered cyclic peptides 194 in 30-50% yield (Scheme 2.69) [101]. 

Enines derived from allylic substitution products by propargylation offer many possibilities in organic synthesis. We have pursued Au-catalyzed cycloadditions with carbonyl compounds [31], enyne metathesis reactions in combination with Diels-Alder reactions [32], and a Pauson-Khand reaction as part of a synthesis of kainic acid [33]. The latter synthesis is described in Scheme 11.16 as a ret-rosynthetic scheme. The Ir-catalyzed allylic amination under in situ conditions proceeded with excellent enantioselectivity. Overall, our synthesis required 12 steps and gave a total yield of 12%. 

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... 

The first step consisted of the Mitsunobu etherification of an allyl alcohol with the resorcinol monoester, which afforded 102. Cleavage of the benzoyl protecting group released the phenol, which was then attached to the solid support. One-step cleavage of the THP group and bromination was achieved with PPhs/C Br4 to furnish 103. Nucleophilic substitution of the bromide with benzylamine was followed by acylation of the secondary amine wtith N-Boc-allylglycine 104, which resulted in the precursor 105, ready for the metathesis reaction this was performed with catalyst 101 to yield the final product 106. Either 1-octene or ethene was employed to generate 101. 

The synthesis of pyrrolidines demands first of all the movement of one of the alkenes closer to the nitrogen atom. This can be done by equilibration of the allyl sulfone in 227 to the more stable conjugated vinyl sulfone 228 with catalytic base. Then allylation at nitrogen gave a possible metathesis substrate 229. In this series neither the amine 229, nor the corresponding benzamide would undergo metathesis. 

Carbamoyl complexes from metal carbonyls and amines 5.8.2.12.4 Carbanions reactions with alkene complexes 5.8.2.3,4 metal carbonyls 5.8.2.S.5 Carbene complexes by alkene metathesis 5.8.2.3.11 formation 5.8.2.8.5 Carbides alkali metal formation 5.10.2.1 bonding 5.10.2 formation 5.10.2 industrial uses 5.10.2 interstitial formation 5.10.2 Carbometallacycle formation 5.S.2.2.2 Carbometallacycles from n-allyl complexes 5.S.2.3.9 Carbon reaction with alkali metals 5.10.2.1 Carbon dioxide complexes formation 5.8.2.14.1 Carbon monoxide displacement by alkenes 5.8.2.3.1 Carbonyl complexes by ligand exchange 5.8.2.12.2 from carbon monoxide 5.8.2.12.1, 5.8.2.12.2... 

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