Chiral 1-acylpyridinium salt

The first asymmetric synthesis of (+)-cannabisativine was achived by D.L. Comins et al. using the addition of metallo enolates to a chiral 1-acylpyridinium salt as one of the key steps.The amide bond was created under the Schotten-Baumann conditions from a bicyclic acid chloride and a 1,4-amino alcohol. 

Kuethe, J. T., Comins, D. L. Addition of Metallo Enolates to Chiral 1-Acylpyridinium Salts Total Synthesis of (+)-Cannabisativine. Ora. Lett. 2000, 2, 855-857. 

A recent synthesis of jV-methylconiine (161) has been reported, based on the addition of n-PrMgCl to a chiral 1-acylpyridinium salt [434]. 

The first, chiral auxiliary mediated, asymmetric synthesis of (+)-luciduline (160) has been accomplished from readily available materials in 14 steps (10% overall) with a high degree of stereocontrol (94). Key steps include an intramolecular Diels-Alder reaction of a chiral dihydropyridine, a subsequent retro-Mannich ring opening, and a novel cationic reductive cyclization reaction. The enantiopure dihydropyridone 164, prepared from the chiral 1-acylpyridinium salt 161, was converted to the 1,2-dihydro-pyridine 166. Intramolecular Diels-Alder reaction and subsequent reduction leads to 168, which, after retro-Mannich ring opening, is converted into the enecarbamate 171. The... 

A study on the effectiveness of various cyclohexyl-based chiral auxiliaries in the asynunetric addition of Grignard reagents to 1-acylpyridinium salts 45 has been published <96TL(37)3807>. 

Zinc enolates have been shown to react with chiral /V-acylpyridinium salts with high diastereo-selectivity (Scheme 24) (93JOC5035). Other metallo enolates gave products with lower diastereoselectivity. Titanium enolates react with /V-acylpyridinium salts to yield 1,4-dihydropyridines, which on subsequent oxidation (aromatization) give 4-(2-oxoalkyl)pyridines (84TL3297). 

Asymmetric synthesis using W-acyl salts of pyridine and derivatives continues to be developed. The chiral. V-acylpyridinium salt 132 reacts with lithiated ethyl propiolate to provide the diastereomer 133 in 70% yield and... 

With an amino acid-derived chiral auxiliary employed in the chloroformate, reaction of silyl enol ethers with isoquinolinium salts showed not only regiospecificity, but some stereoselectivity as well (Equation 61) <1999SL1154>. The addition of ketene silyl acetals to an W-acylpyridinium salt containing a chiral 2,2-dimethylox-azolidine at C-3 gave 1,4-dihydropyridines with excellent stereoselectivity <2002JA8184>. 

Asymmetric synthesis of dihydropyridones. 8-Phcnylmcnthol has been used frequently as a chiral auxiliary, but this derivative (1) is more effective as the chiral auxiliary for cnantioselcctivc reactions of N-acylpyridinium salts with organomctallic reagents. Thus 2, prepared by reaction of 4-methoxy-3-(triisopropylsilyl)pyridine with the chloroformate of 1 reacts with the Grignard reagent 3 to give an adduct that on acidic deprotection provides the dihydropyridone 4 in 94% dc. Conversion of the alcohol to a chloride [P(CftH5)j and NCS] followed by treatment with sodium methoxide in methanol cleaves the chiral auxiliary as the methyl carbonate (94% yield) and at the same time effects cyclization to form the chiral bicyclic dihydropyridone 5 in 84% yield. 

The shortest synthesis of (5Z,9Z)-indolizidine 223AB (1566) was reported in 2007 by Ma and coworkers (Scheme 223, first two lines) In this approach the copper(I) complex of the chiral bis(oxazoline) ligand 1772 catalyzed the enantioselective addition of hept-l-yn-3-one to the N-acylpyridinium salt 1773, producing the (2S)-dihydropyridine adduct (+)-1774 in 70% yield and an ee of 91%. Selective hydrogenation over... 

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