Pyridines, olefinic derivatives, synthesis

S l substitution of different compounds by nitronate anions followed by elimination of nitrous acid is a good method for the synthesis of various substituted olefins. A clear example is the base-promoted HN02 elimination from the C-alkylation products formed by the S l reaction between 2-chloromethyl-3-nitroimidazo[l,2-a]pyridine (11) and various aliphatic, cyclic and heterocyclic nitronate anions87, affording new potential pharmacological derivatives with a trisubstituted double bond at the 2-position. A representative example is shown in equation 32. 

The N,P phosphine-oxazoline chelate (59) is chiral, and complexes can act as homogeneous catalysts for asymmetric synthesis the Ir(l) and Pd(II) complexes promote enantioselective olefin hydrogenation and allylic substitution respectively. An N,P analog of the N,N didentate ligand 2,2 -bipyridine is (60), the soft P donor helping to stabilize low-valent metals. Further, 2,2-bipyridine derivatives such as (61) can bind metals such as Ir and Ru as N,C chelates with one pyridine nitrogen rotated to the opposite side, away from the metal ion. 

Synthesis af okfins from stericaUy hindered akohols, Gerlach el al. have reported a successful variation of theChugaev reaction applicable to the preparation oftemperature-sensilive olefins from sterically hindered alcohols. Thus /ron.t,/ran.s-spiro[4.4jnonane-1,6-diol (2) is converted into the thiocarbonate 0-ester (3) by reaction with (1) in pyridine for 4 hr. at room temperature (80% yield). This derivative decomposes smoothly into the diene, 1,6-spiro[4.4]nonadiene (4), at a temperature of > 135 . In this case pyrolysis of the diacetate or of the di-S-methyIxanthate failed to give the diene. 

Michael/Henry/dehydration/aromatisation reaction of 2-(2-oxoethyl) benzal-dehydes and nitroalkenes mediated by pyrrolidine to obtain polysubstituted naphthalene derivatives. DBU catalysed the conjugate additions of alcohols to ot,p-unsaturated nitriles, esters and ketones. Perhaps more important are the aza-Michael addition reactions of amines to a,p-unsaturated ketones, nitriles and esters. Recently, Costa, Vilarrasa and coworkers described the addition of lactams, imides, 2-pyridone, pyrimidine-2,4-diones and inosines to methyl propiolate and other similar compounds, DABCO and DMAP being the best catalysts. As mentioned before, tertiary amines give zwitterionic species with activated allynes. It was as early as 1932 when Diels and Alder used the reaction of pyridine with dimethyl acetylenedicarbojylate (DMAD) for the synthesis of heterocycles. The interception of the corresponding intermediate with Al-tosylimines and activated olefins provided access to l-azadienes ° and highly substituted butadienes (Scheme 2.6). When the quenching species of the zwitterionic intermediate is a 1,2-diketone, dibenzoyl maleates or cyclopentenedione derivatives could be obtained (Scheme 2.6). The interception of the zwitterionic species of N-methyl imidazole (NMI) and DMAD with ketenes to obtain unsaturated esters has also been shown. ... 

In contrast to the Rh-catalyzed asymmetric intramolecular direct C—H bond functionalization reactions described above, their asymmetric inter-molecular variants have been rarely explored. In 2000, Murai and co-workers reported a Rh-catalyzed intermolecular asymmetric C—H activation/olefin coupling reaction of achiral biaryl pyridine (132) or isoquinoline derivatives to deliver axially chiral biaryls (133) (Scheme 5.46a). Although both the efficiency (up to 37% yield) and the enantioselectivity (up to 49% ee) of the reaction were only moderate, this protocol provided an alternative method for the synthesis of optically active biaryl compounds. To some extent, this reaction was similar to a formal dynamic kinetic resolution. The two atropisomers of the biaryl starting materials could interconvert with each other freely due to a low inversion energy barrier. A properly chosen chiral catalyst could react preferentially with one atropisomer. The increased steric bulkiness of the final alkylated products can prevent the epimerization and the biaryl compounds possessing a stable axial chirality are established. However, due to the relatively low efficiency of the catalyst, the yields of the desired products are generally low and the starting materials can be recovered (Scheme 5.46b). 

The first asymmetric synthesis of (20 S)-camptothecin using catalytic asymmetric induction was achieved by Fang et al. in 1994 [74], They carried out a catalytic enantioselective synthesis of Comins s intermediate (23) in order to avoid the use of the expensive chiral auxiliary, 8-phenylmenthol, or similar compound. Intramolecular Heck reaction of pyridine derivative (26) gave the cyclic olefins (27) and (28) in a ratio 1 8. The allylic ether (27) can be isomerized to (28) upon treatment with Wilkinson s catalyst [75], Asymmetric Sharpless dihydroxylation of (28) proceeded successfully when 2,5-diphenyl-4,6-bis(9-0-dihydroquinidyl)pyrimidine [(DHQD)2-PYR] was used as the chiral catalyst [76], and subsequent oxidation gave (29) in 94% ee. Treatment of (29) with acid gave the target molecule (23, Scheme 2.5), which was converted to (20S)-camptothecin in 2 steps using the Comins s procedure [73]. 

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