Olefination heterocyclic amines

Bicychc pyrazinones foimd in several natural products were synthesized via Michael addition of heterocyclic amines to nitro olefin followed by reduction/cyclization of the nitro group of the adduct [20] (Scheme 5). Further elaboration of the C-6 methoxycarbonyl group in pyrazinone to the n-propyl guanidine group could result in the synthesis of indoloperamine. 

Miscellaneous. Aside from the oxidation chemistry described, only a few catalytic applications are reported, including hydrogenation of olefins (114,115), a, [3-unsaturated carbonyl compounds (116), and carbon monoxide (117) and the water gas shift reaction (118). This is so owing to the kinetic inertness of osmium complexes. A 1% by weight osmium tetroxide solution is used as a biological stain, particulady for preparation of samples for electron microscopy. In the presence of pyridine or other heterocyclic amines it is used as a selective reagent for single-stranded or open-form B-DNA (119) (see Nucleic acids). Osmium tetroxide has also been used as an indicator for unsaturated fats in animal tissue. Osmium tetroxide has seen limited if controversial use in the treatment of arthritis (120,121). 

The phenylselenenyl chloride induced intramolecular ring closure of ro-aminoalkenes can be utilized in the synthesis of nitrogen heterocycles. Olefinic primary amines do not cyclize readily in this reaction, while urethane derivatives and secondary amines cyclize according to the following scheme55 56. 

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 ... 

The pentenamides were then treated with ozone. Changes in solvent and temperature (-78° to room temperature) did not alter significantly the course or yield of this reaction. The ozonolysis of the olefin gave an intermediate aldehyde which could not be isolated but cyclized immediately to the desired hydroxypyrrolidi-none, 2. This general procedure was applicable to a large number of heterocyclic amines (Table II). In all cases, good overall yields were obtained. 

Synthesis of the title compound is representative of a number of syntheses of nonaromatic nitrogen heterocycles via Pd(Ill-catalyzed amination of olefins. These tosylated enamines are not readily available by standard synthetic methods, and show potential for further functionalization of the heterocycle. The saturated amine can be synthesized from the title compound by hydrogenation of the double bond followed by photolytic deprotection. ... 

In the synthesis of N heterocycles, this technique also overcomes competitive retro Michael addition that lowers the yield of 1,4-adduct in the Michael addition of amines to nitro olefins. Thus, a toluene solution of nitro olefin 159 was treated with allylamine 160, EtgN, and TMSCI under nitrogen at ambient tern-... 

Cyclization to six-membered rings (Eq. 15) provided modest diastereoselectivity and required the use of bulkier PhMeSiH2 to prevent olefin hy-drosilylation. Propargyl and homopropargyl amines 94 afforded a variety of heterocycles (Scheme 21), if the catalyst was added slowly over the reaction course to diminish side reactions resulting from metal coordination to the basic amine [56]. The reaction procedure was extended to the diastereoselect-ive bicyclization of dienyne substrate 95, giving 96 as product in a cascade fashion (Eq. 16) [57]. 

A titanium-mediated amination followed by a directed rhodium-catalyzed C-H functionalization of an olefinic C-H leads to heterocycles (Equation (184)).149... 

The reaction was further applied to the synthesis of spiro heterocycles (Scheme 16.4) [8], The oxidative addition of an iodide to a Pd(0) species generates an ArPdl species, into which an internal olefin inserts to form an alkylpalladium complex otherwise difficult to access. Allene participates in the reaction at this stage to provide a jt-allylpalladium complex, which is attacked by the amine intramolecularly to afford the procuct. 

Synthesis of a C(8)-C(18) segment of the larger fragment of lb using the same basic strategy is depicted in Scheme 25. Here, hydroxy ketone 176 was subjected to syn-selective (dr of crude product=90 10) reductive amination [42] with sodium cyanoborohydride and benzylamine followed by tetrahydro-oxazine formation using aqueous formaldehyde. The resulting heterocycle 182 was then converted to unsaturated ester 184 by successive desilylation, oxidation, and entirely (Z)-selective Horner-Wadsworth-Emmons olefination. Re-... 

A significant part of the examples of transition metal catalyzed formation of five membered heterocycles utilizes a carbon-heteroatom bond forming reaction as the concluding step. The palladium or copper promoted addition of amines or alcohols onto unsaturated bonds (acetylene, olefin, allene or allyl moieties) is a prime example. This chapter summarises all those catalytic transformations, where the five membered ring is formed in the intramolecular connection of a carbon atom and a heteroatom, except for annulation reactions, involving the formation of a carbon-heteroatom bond, which are discussed in Chapter 3.4. 

Other heterocyclic tertiary amines show a different behavior. Tertiary amines have been used as catalysts in dichlorocyclopropanation of olefins they probably give an ammonium ylide as the first step in the catalytic cycle.262 These ylides are usually unstable and undergo a variety of transformations such as the Stevens rearrangement and the Hoffmann elimination. 

The cycloaddition of diazomethane to SchifT bases from heterocyclic aldehydes and anilines provides a useful route to heterocyclic substituted triazolines. Unlike olefins bearing heterocyclic substituents, the heterocyclic imines can be obtained readily by reaction of the appropriate aldehyde and amine thus the diazomethane-imine addition has greater scope than the olefin-azide reaction. NMR spectroscopic studies of the orientation of addition are in accord with previously reported mechanistic considerations (see, e.g., Scheme 93).329 In addition to the influence of the N-aryl group, the electron-withdrawing power of the heterocyclic substituent on the Schiff-base carbon also has a substantial effect on imine reactivity, in the order 2-quinolyl 2-, 3-, or 4-pyridyl > phenyl > 2-thienyl as 2-furyl.329... 

As shown in the Section II, A, daphniphylline (1) and daphmacrine (18), whose stereostructures have been unambiguously determined, have the same amine moiety but differ in the oxygen heterocyclic skeleton. Thus, it is quite reasonable to suppose that two different moieties must be constructed from such a common precursor as A which can be derived from squalene via squalene-2,3-oxide, and from a monocyclic olefin (Scheme X). 

The oxidation potentials 170 ——- 777 of a large number of aromatic hydrocarbons, amines, phenols,heterocycles and olefins are tabulated I0,10a>25-48 65,525-528) an(j nee(j not repeated here. Such potentials have been successfully correlated with HMO-parameters 525 530>538) ie in oxidations with the energy of the highest filled MO (HFMO).Adams 25) and Peover 65) have discussed some precaution to which attention should be paid in such correlations, e.g., shifts in potentials due to the irreversibility of the electrode process or due to fast follow-up reactions. 

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