A facile method for synthesis of polysubstituted naphthalene derivatives through pyrrolidine catalyzed domino reaction

A novel synthetic method for polysubstituted naphthalene derivatives via a pyrrolidine-mediated cascade Michael/Henry reaction was developed, in which easily prepared 2-(2-oxoethyl)benzaldehydes and nitroalkenes were employed as the starting materials. The reaction consists of four consecutive reactions that include a cascade Michael/Henry reaction, a dehydration reaction, and an aromatization reaction in one pot to afford synthetically important naphthalene derivatives with moderate yields.     

Highly diastereoselective Henry reaction of nitro compounds with chiral derivatives of glyoxylic acid

N-Glyoxyloyl-(2R)-bornane-10,2-sultam and (1R)-8-phenylmenthyl glyoxylate react stereoselectively with simple nitro compounds giving diastereoisomeric nitroalcohols with high asymmetric induction. N-Glyoxyloyl-(2R)-bornane-10,2-sultam 1a is shown to be a highly efficient chiral inducer, superior to (1R)-8-phenylmenthyl glyoxylate 1b. In all cases, the absolute (2S) configuration at the center bearing the hydroxy group and the relative syn configuration for the major diastereoisomers were determined.     

Highly regio- and stereoselective synthesis of tricyclic frameworks using Baylis-Hillman derivatives

A simple and convenient synthetic route for the synthesis of tricyclic chromeno[4,3-b]pyrrolidine frameworks using Baylis-Hillman bromides involving in situ formation of an imine, decarboxylation and a [3+2] cycloaddition sequence is described.     

α-Hydroxymethylation of conjugated nitroalkenes via the Morita-Baylis-Hillman reaction

The Morita-Baylis-Hillman reaction (MBHR) of conjugated nitroalkenes has been successfully carried out for the first time. A variety of aromatic and heteroaromatic nitroalkenes react with formaldehyde at room temperature in the presence of stoichiometric amounts of imidazole and catalytic amounts of anthranilic acid in THF providing moderate to good yields of the multifunctional adducts in most of the cases.     

Sequential Baylis-Hillman reaction and radical cyclization of furanose derivatives: expeditious approach to enantiopure benzo-fused nine-membered oxacycles

A regioselective 9-endo-trig aryl radical cyclization of d-glucose derived diastereomeric Baylis-Hillman reaction products with Bu₃SnH led to highly functionalized tricyclic benzannulated ethers incorporating cis- and trans-9,5 bicyclic systems in good yields. Degradation of one of the products afforded an enantiopure multifunctionalized benzoxonine derivative.     

A convenient stereoselective synthesis of β-lactams from β-hydroxy-α-thioalkylesters prepared from Michael/aldol tandem reaction or stereoselective addition of thiols to the Baylis-Hillman adducts

A convenient stereoselective synthesis of β-lactams from thio-Michael/aldol tandem adduct is described. syn-Selective tandem reaction followed by amidation and intramolecular S_N2 reaction provided β-lactams in diastereomerically pure form. The tandem reaction with aliphatic aldehydes, on the other hand, afforded a mixture of diastereomers of corresponding tandem adducts in about 3:1 ratio so that the conversion to β-lactams afforded a diastereomeric mixture. As an alternative approach to prepare the tandem adducts, the stereoselective Michael addition of aliphatic thiols to Baylis-Hillman adduct was developed. The stereoselectivity was sensitive to the protective group at the hydroxyl group and TBS protection brought the most successful syn-selective formation of the tandem adducts. The procedure could be applied to the ketone derivatives of the Baylis-Hillman adduct but no selectivity was observed for the nitrile-Baylis-Hillman adducts. A similar conversion of the adduct provided desired β-lactams stereoselectively.     

Regioselective construction of polysubstituted pyridine ring from Baylis-Hillman adducts via sequential introduction of tosylamide, Michael reaction, aldol condensation, and elimination of TsH

Facile synthetic method of polysubstituted pyridine derivatives was developed starting from the Baylis-Hillman adducts. The reaction involved sequential introduction of tosylamide, Michael addition, aldol condensation, elimination of p-toluenesulfinic acid, and isomerization process.     

Development of bis-thiourea-type organocatalyst for asymmetric Baylis-Hillman reaction

A new chiral bis-thiourea-type organocatalyst 2 developed for the Baylis-Hillman reaction provided a drastic rate enhancement. Allylic alcohols were obtained with up to 90% ee in the case of cyclohexanecarboxaldehyde (4i).     

Highly enantioselective conjugate addition of fluoromalonates to nitroalkenes using bifunctional organocatalysts

The enantioselective conjugate addition of fluoromalonates to aromatic nitroalkenes catalyzed by chiral amine-thiourea bifunctional organocatalysts generated a stereocenter at the carbon bearing the aromatic group and an adjacent prochiral center from the fluoromalonate. Treatment of fluoromalonates with aromatic nitroalkenes under mild reaction conditions afforded the corresponding 2-fluoro-2-(2-nitro-1-arylethyl)malonates with high yields (72-93%) and excellent enantioselectivities (91-98% ee).     

The Baylis-Hillman reaction: a strategic tool for the synthesis of higher-carbon sugars

The Baylis-Hillman reaction of acyclic sugar-derived aldehydes is invoked as an attractive synthetic strategy for ready access to higher-carbon sugars.     

Iodotrimethylsilane induced diastereoselective synthesis of tetrahydropyranones by a tandem Knoevenagel-Michael reaction

The synthesis of multifunctionalized tetrahydropyranones has been achieved at room temperature with iodotrimethylsilane by a tandem Knoevenagel condensation of aldehydes with aldol adducts prepared from β-keto esters and aldehydes, followed by a Michael reaction. The reactions are highly diastereoselective affording a single isomer in high yields.     

Conjugate addition nitro-Mannich reaction of carbon and heteroatom nucleophiles to nitroalkenes

The conjugate addition nitro-Mannich reactions of ethyl-β-nitroacrylate (1) and β-nitrostyrene (2) with electron rich aromatic nucleophiles, stabilized carbanions, alcohols, amines, thiols, and diphenyl phosphine oxide were investigated. The one pot conjugate addition nitro-Mannich reaction was unsuccessful except for the addition of alkoxides to 2 in alcohol as solvent. Isolation of the conjugate addition products followed by deprotonation with ⁿBuLi and treatment with a simple imine in the presence of TFA led to β-nitroamine derived products. Products derived from 1 spontaneously cyclised in only a few examples and on the whole led to inherently unstable products. Products derived from 2 were isolated as their trifluoroacetamides, gave good yields of single diastereoisomers for aromatic and alkoxide nucleophiles and the structures were verified by single crystal X-ray crystallography. Products derived from amine nucleophiles were isolated in low yields while sulfur nucleophiles gave poor diastereoselectivities.     

Poly(ethyleneglycol) (PEG): a rapid and recyclable reaction medium for the DABCO-catalyzed Baylis-Hillman reaction

PEG (400) has been used as a rapid and recyclable reaction medium for the Baylis-Hillman reaction with the conventional basic catalyst DABCO (20 mol %) with very good yields of products. Recyclability is achieved with no further addition of DABCO to the reaction medium for over four runs without substantial loss in yields. Incidentally, DABCO is recycled for the first time in this transformation.     

Efficient synthesis of β-nitro amides by aminocarbonylation of ethoxycarbonyl-containing nitroalkenes with carbamoylsilane

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Baylis-Hillman reaction promoted by a recyclable protic-ionic-liquid solvent-catalyst system: DABCO-AcOH-H2O

A recyclable protic-ionic-liquid solvent-catalyst system, DABCO-AcOH-H₂O, has been developed and used in the Baylis-Hillman reaction of aromatic aldehydes, aliphatic aldehydes, and cinnamaldehydes with acrylates and acrylonitrile, showing comparable performance to free DABCO in traditional solvents. The DABCO-AcOH-H₂O solvent-catalyst system could be reused for at least five times without significant loss of activity.     

Pd(0)-catalyzed couplings using bromide and chloride derivatives of Baylis-Hillman adducts with triarylbismuths as atom-efficient multi-coupling nucleophiles

Bromide and chloride derivatives of Baylis-Hillman adducts have been demonstrated to react efficiently with triarylbismuths affording allylic arylated products in high yields under palladium-catalyzed conditions. Triarylbismuths have been employed in sub-stoichiometric amounts as multi-coupling and atom-efficient nucleophiles in these reactions. The reactivity of both allylic bromides and chlorides was found to be facile and equally efficient in couplings with triarylbismuths.     

Baylis-Hillman adducts between pyridine carboxaldehyde derivatives and cyclic enones

Baylis-Hillman (BH) adducts were synthesized using pyridinecarboxaldehyde derivatives and cyclic enones. The Baylis-Hillman reaction was examined by employing various organic tertiary bases and solvents. It was observed that DBU in MeOH as well as imidazole and N-methylimidazole in aqueous MeOH are very effective. These pyridinecarboxaldehydes were reactive and efficient towards the Baylis-Hillman reaction and the resulting adducts are highly stable. The crystal structure for one of the BH adducts was determined.