Olefination cyclic amines

The ten-membered cyclic amine 106 was efficiently prepared from quionolizidine derivative 105 by methylation to a nonisolated intermediate followed by an olefin-forming desulfonylation reaction induced by treatment with sodium amalgam (Scheme 11) <20010L2957>. 

The carbonylation of the sp3 C-H bond adjacent to a nitrogen atom is also possible by means of chelation-assisted C-H bond activation.121 The carbonylation reaction of A-(2-pyridyl)pyrrolidine occurs at the a-position of the pyrrolidine ring by using [RhCl(cod)]2 as a catalyst and 2-propanol as a solvent. Cyclic amines exhibit a high reactivity (up to 84%) (Equation (93)), while acyclic amines show relatively low reactivity (18%). The use of Ru3(CO)i2 as a catalyst does not result in a carbonylation reaction, but instead the addition of the sp3 C-H bond across the olefin bond to give an alkylation product, as mentioned before (Section 10.05.4). 

A wide variety of cyclic monomers have been successfully polymerized by the ring-opening process [Frisch and Reegan, 1969 Ivin and Saegusa, 1984 Saegusa and Goethals, 1977]. This includes cyclic amines, sulfides, olefins, cyclotriphosphazenes, and IV-carboxy-oc-amino acid anhydrides, in addition to those classes of monomers mentioned above. The ease of polymerization of a cyclic monomer depends on both thermodynamic and kinetic factors as previously discussed in Sec. 2-5. 

Heteroatoni groups such as boron or silicon can activate or direct synthetic reactions. Use of such activation has become of major importance in organic syntheses. Examples in this volume are BORANES IN FUNCTIONALIZATION OF DIENES TO CYCLIC KETONES BICYCLO[3.3.1]NONAN-9-ONE and BORANES IN FUNCTIONALIZATION OF OLEFINS TO AMINES 3-PINANAMINE. Use of trimethylsilyl or trimethyl-silyloxy groups to activate a 2-butenone or a butadiene are illustrated by the preparations 3-TRIMETHYLSILYL-3-BUTEN-... 

The formylation of phenols with the electron-rich olefin to give imidazolidin-2-yl-phenols is very selective and avoids mixtures of o- and p-isomers which are frequently obtained by methods commonly employed for the synthesis of phenolaldehydes. Para substitution of the cyclic aminal group in the phenol is preferred. If the p-position is blocked or sterically hindered, the reaction proceeds via the ortho- aminals to salicylaldehydes. Incorporation of more than one aldehyde group in the benzene nucleus is often achieved with hydroxy- and aminophenols. 

The olefin metathesis reaction is often used to prepare heterocyclic rings. The mild conditions tolerate a wide variety of oxygen and nitrogen functionalities, such as the epoxide and cyclic amines, as exemplified below. 

Cope, A. C., Ciganek, E., Howell, C. F., Schweizer, E. E. Amine oxides. VIII. Medium-sized cyclic olefins from amine oxides and quaternary ammonium hydroxides. J. Am. Chem. Soc. 1960, 82,4663-4669. 

Other synthetic applications derive from various cyclizations that occur during reduction of the substrates that contain a reactive function at a specific position. These cyclizations proceed through the intermediate imine or amine to the cyclic amine. Various functional units such as olefins, heterocyclic rings, ketones, acids, amides, amines, nitrile, and nitro have been involved. Palladium, Rh, and finely divided Ni (Raney Ni) under more vigorous conditions are commonly used. Reductive cyclization of ketonitrile 1 over Raney Ni gives myosmine 2 along with some nomicotine 3 as overreduced product ... 

Carbonylation of cyclic amines, hydroformylation (CO-H2) of amino olefins catalyzed by metal (Pd, Ru, Rh) complexes (see 1st edition). 

Kawamura S, Egami H, Sodeoka M (2015) Aminotrilluoromethylation of olefins via cyclic amine formation mechanistic study and apphcahon to synthesis of trilluoromethylated pyrrolidines. J Am Chem Soc 137 4865-4873. doi 10.1021/jacs.5b02046... 

HRu(CO)(PCy3)2Cl for the preparation of organoboranes from vinylsubstituted boronates and olefins, for the stereoselective synthesis of carbazoles, for the intermolecular coupling of cyclic amines and alkenes. ... 

It has been shown that the presence of catalytic amounts of carboxylic acid such as trani-l,2-cyclohexyldicarboxylic or 3,4,5-trifluorobenzoic acid improved the ruthenium-catalysed sp C-H bond alkylation of cyclic amines by terminal olefins and allowed reaching full conversion of less reactive A -pyridylpiperidine derivatives. Thus, in the absence of CO but in the presence of tra s-l,2-cyclohexyldi-carboxylic acid, the A -pyridylpiperidine 38 was efficiently hexylated into mono- 39 and dialkylated 40 piperidine derivatives, whereas in the absence of carboxylic acid... 

A mthenium(ll)-catalysed dehydrogenative coupling of saturated cyclic amines with an olefin has been reported using RuH2(CO)(PCy3)2 as catalyst under neutral conditions in THE at 70-120°C (Scheme 36) [29]. 

Imines were preferentially formed and the carbon-carbon bond was selectively formed at the C(2) position of the cyclic amine. With ethylene and propene, only imines were formed but with more bulky olefins and 7-membered cyclic amines, reduction to 2-alkyl cyclic amine took place, and N-alkylation was also observed from bicyclic amine. 

While the usual eonsequence of hydration of enamines is eleavage to a secondary amine and an aldehyde or ketone, numerous cases of stable carbinolamines are known (102), particularly in examples derived from cyclic enamines. The selective terminal hydration (505) of a cross-conjugated dienamine-vinylogous amide is an interesting example which gives an indication of the increased stabilization of the vinylogous amide as compared to simple enamines, which is also seen in the decreased nucleophilicity of the conjugated amino olefin-carbonyl system. 

Olefins are also the products of hydroboratlon of enamines, followed by treatment of the organoborane products with hot acid (543,544). The reduction of enamines with sodium borohydride and acetic acid (545) and the selective reduction of dienamines with sodium borohydride to give homo-allylic tertiary amines (138-140,225,546,547), has been applied to the synthesis of conessine (548) and other aminosteroid analogs (545,549-552). Further examples of the reduction of imonium salts by sodium borohydride can be found in the reduction of Bischler-Napieralski products, and other cyclic imonium salts (102). 

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