Recent Advances in the Baylis−Hillman Reaction and Applications

Evolution in the field of the total synthesis of natural products has led to exciting developments over the last decade. Numerous chemoselective and enantioselective methodologies have emerged from total syntheses, resulting in efficient access to many important natural product targets. This Review highlights recent developments concerning dearomatization, a powerful strategy for the total synthesis of architecturally complex natural products wherein planar, aromatic scaffolds are converted to three-dimensional molecular architectures.

Dearomatization Strategies in the Synthesis of Complex Natural Products

The baylis-hillman reaction : a novel carbon-carbon bond forming reaction

Stereoselective Addition to N-Activated Pyridines James A. Bull,‡ James J. Mousseau, Guillaume Pelletier,† and Andre ́ B. Charette*,† †Department of Chemistry, Universite ́ de Montreál, P.O. Box 6128, Station Downtown, Montreál, Queb́ec, Canada H3C 3J7 ‡Department of Chemistry, Imperial College London, South Kensington, London SW7 2AZ, U.K. Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA

Synthesis of Pyridine and Dihydropyridine Derivatives by Regio- and Stereoselective Addition to N-Activated Pyridines

Synthetic potential of the tertiary-amine-catalysed reaction of activated vinyl carbanions with aldehydes

On the regioselectivity of the reaction of N-methoxycarbonylpyridinium chloride with Grignard reagents: highly regioselective synthesis of 2-substituted N-methoxycarbonyl-1,2-dihydropyridines.

Photochemical reaction of benzopyridines with alkanoic acids

Des substituants tels que les groupes halogeno, acetoxy, et formyl sont toleres, demontrant ainsi la haute chimioselectivite de cette reaction. Cette methode d'allylation peut etre etendue aux quinoleines et isoquinoleines

Reaction of allylic tin reagents with nitrogen heteroaromatics activated by alkyl chloroformates: regioselective synthesis of .alpha.-allylated 1,2-dihydropyridines and change of the regioselectivity depending on methyl substituents at the allylic moiety

Nucleophilic addition of a variety of alkynyl and alkenyl Grignard reagents to 1-methoxycarbonylpyridinium chloride takes place at the α-position in a highly regioselective manner to give 2-substituted 1-methoxycarbonyl-1,2-dihydropyridines exclusively, while, with alkyl Grignard reagents, a lack of the regioselectivity is observed. These results may be explained by the HSAB principle. The high α-regioselectivity is preserved in the cases of 2-substituted pyridines as well, giving 2,6-disubstituted 1,2-dihydropyridines exclusively, which can be transformed stereoselectively into cis- and trans-2,6-dialkylated piperidines. These highly regioselective α-alkynylations of 1-methoxycarbonylpyridinium salts are exploited in synthesis of 1-azabicycloalkanes as well as (±)-solenopsin A.

Highly Regioselective α-Addition of Alkynyl and Alkenyl Grignard Reagents to 1-Alkoxycarbonylpyridinium Salts and Its Application to Synthesis of 1-Azabicycloalkanes and (±)-Solenopsin A

The preparative method of iodonium ylides, Ph–\overset⊕I–\overset\ominusC(COR)(COR′), is improved by condensation of active methylene compounds, H2C(COR)(COR′), with iodosobenzene in the presence of acetic anhydride. Thermal and Cu-catalyzed decomposition of iodonium ylides can be differentiated and both are explained in terms of diacylcarbene intermediate with different multiplicity. For the sake of comparison diazodimedone and related compounds are also decomposed by Cu-catalysis as well as by photochemical reaction. Carbene is also found to be a highly probable intermediate. Throughout these investigations the spin multiplicity of the carbene is discussed on the basis of product distributions. Notably in the presence of homogeneous Cu-catalyst in ethanol, diazodimedone gives an insertion product to O–H bond, 2-ethoxy-3-hydroxy-5,5-dimethyl-2-cyclohexenone (XVII), whereas the iodonium ylides do not give such a compound. The formation of XVII is explained by assuming a ketocarbene-Cu-chelate complex.

Mituyosi Kawanisi

Papers

On the regioselectivity of the reaction of N-methoxycarbonylpyridinium chloride with Grignard reagents: highly regioselective synthesis of 2-substituted N-methoxycarbonyl-1,2-dihydropyridines.

Photochemical reaction of benzopyridines with alkanoic acids

Reaction of allylic tin reagents with nitrogen heteroaromatics activated by alkyl chloroformates: regioselective synthesis of .alpha.-allylated 1,2-dihydropyridines and change of the regioselectivity depending on methyl substituents at the allylic moiety

Highly Regioselective α-Addition of Alkynyl and Alkenyl Grignard Reagents to 1-Alkoxycarbonylpyridinium Salts and Its Application to Synthesis of 1-Azabicycloalkanes and (±)-Solenopsin A

Cyclic Diacylcarbene Generated from Iodonium Ylides and Diazodiketones