Reaction of acetylenic esters and N-functionalized phosphazenes. 1,2-versus 1,4-addition of N-vinylic phosphazenes

Reaction of phosphazenes derived from aminophosphonates with acetylenic esters leads to conjugated phosphorus ylides. The formation of these stabilized ylides is explained through a [2 + 2] cycloaddition reaction of the P = N linkage of the phosphazene (1,2-addition) and the triple bond of the acetylenic ester followed by ring opening of the azaphosphete intermediate. However, in the case of N-vinylic phosphazenes, the phosphazenes derived from triphenyl- and trimethyl-phosphine react as enamines (1,4-addition) with diacetylenic esters, whereas in phosphazenes derived from trimethylphosphine a 1,2-addition of ethyl propiolate to the P = N linkage of the phosphazene is produced.     

Synthesis of aza polycyclic compounds derived from pyrrolidine, indolizidine, and indole via intramolecular Diels-Alder cycloadditions of neutral 2-azadienes

A method for the preparation of novel oxaza and diaza polycyclic 9-oxa-4-azaphenanthrene, 5H-pyrido[2,3-a]pyrrolizine, 5H,6H-pyrido[3,2-g]indolizine, and 5H,6H-indeno[2,1-a]indole is described, based on tandem reactions: aza-Wittig reaction of N-vinylic phosphazenes with functionalized aldehydes and an intramolecular aza-Diels-Alder reaction.     

Direct amination of homoenolates catalyzed by N-heterocyclic carbenes

N-Heterocyclic carbenes derived from N-mesityl-N-methyltriazolium salts are effective catalysts for generating homoenolate species from alpha,beta-unsaturated aldehydes. The unique intermediate adds to the electrophilic nitrogen of 1-acyl-2-aryldiazenes, and the resulting activated carbonyl unit undergoes an intramolecular acylation event. This formal [3+2] cycloaddition between alpha,beta-unsaturated aldehydes and acylaryldiazenes, catalyzed by an N-heterocyclic carbene, produces substituted pyrazolidinones in good yields. This new NHC-catalyzed reaction accommodates aromatic and alkyl alpha,beta-unsaturated aldehydes and various aromatic diazenes. A chiral triazolium salt catalyzes the formation of the pyrazolidinone product in moderate yield and good enantioselectivity. The pyrazolidinones can undergo reductive N-N bond cleavage to give beta-amino acid derivatives.     

A Pauson-Khand-type reaction between alkynes and olefinic aldehydes catalyzed by rhodium/cobalt heterobimetallic nanoparticles: an olefinic aldehyde as an olefin and CO source

Co/Rh (Co:Rh = 2:2) heterobimetallic nanoparticles derived from Co(2)Rh(2)(CO)(12) react with alkynes and alpha,beta-unsaturated aldehydes such as acrolein, crotonaldehyde, and cinnamic aldehyde and release products resulting from [2 + 2 + 1]cycloaddition of alkyne, carbon monoxide, and alkene. alpha,beta-Unsaturated aldehydes act as a CO and alkene source. These reactions produce 2-substituted cyclopentenones.     

Enantioselective organocatalytic formal [3 + 3]-cycloaddition of alpha,beta-unsaturated aldehydes and application to the asymmetric synthesis of (-)-isopulegol hydrate and (-)-cubebaol

[reaction: see text] The first highly enantioselective organocatalyzed carbo [3 + 3] cascade cycloaddition of alpha,beta-unsaturated aldehydes is reported. Using this methodology, crotonaldehyde is converted to 6-hydroxy-4-methylcyclohex-1-enecarbaldehyde, which is used in the synthesis of (-)-isopulegol hydrate, (-)-cubebaol, and p-tolualdehyde as well as (-)-6-hydroxy-4-methyl-1-cyclohexene-1-methanol acetate, an intermediate in the total synthesis of lycopodium alkaloid magellanine. Other alpha,beta-unsaturated aldehydes give rise to chiral cyclohexadienes via formal [4 + 2] reactions.     

Organocatalytic asymmetric robinson annulation of alpha,beta-unsaturated aldehydes: applications to the total synthesis of (+)-palitantin

The highly enantioselective organocatalytic Robinson annulation of alpha,beta-unsaturated aldehydes was achieved, catalyzed by l-proline and trialkylamines and providing the formal [4 + 2] cycloaddition adducts. Additionally, in some examples in the catalysis with diarylpyrrolinol silyl ethers, the reactions afforded the [4 + 2] adducts with high enantioselectivity (>99.5% ee). The structure of the adduct, obtained from the reaction of 3-methylbut-2-enal and (E)-3-(2-nitrophenyl)acrylaldehyde, was confirmed by X-ray analysis. The absolute configurations of some [4 + 2] cycloadducts were investigated, and the methodology was applied in the synthesis of (+)-palitantin.     

A new type of catalytic tandem 1,4-addition-aldol reaction which proceeds through an (oxa-pi-allyl)rhodium intermediate

The reaction of 9-aryl-9-borabicyclo[3.3.1]nonanes (B-Ar-9BBN) with alpha,beta-unsaturated ketones and aldehydes in the presence of 3 mol % [Rh(OMe)(cod)](2) in toluene at 20 degrees C for 2 h gave high yields of the tandem 1,4-addition-aldol reaction products with high syn selectivity. The reaction proceeds through the catalytic cycle consisting of 1,4-addition of an organorhodium species to an alpha,beta-unsaturated ketone and the aldol addition of the resulting (oxa-pi-allyl)rhodium intermediate to an aldehyde.     

Lewis acid-Lewis base catalyzed enantioselective hetero-Diels-Alder reaction for direct access to delta-lactones

A complex formed in situ from Er(OTf)3 and a simple commercially available norephedrine ligand promotes an unprecedented [4 + 2] cycloaddition of alpha,beta-unsaturated acid chlorides with a broad range of aromatic and heteroaromatic aldehydes by a cooperative bifunctional Lewis acid-Lewis base catalytic mode of action providing valuable delta-lactone building blocks with excellent enantioselectivity.     

Palladium-catalyzed enantioselective conjugate addition of arylboronic acids

[reaction: see text] The first asymmetric palladium-catalyzed conjugate addition of arylboronic acids to alpha,beta-unsaturated aldehydes, ketones, and esters is described. For cyclic substrates, excellent chemo-, regio-, and enantioselectivities are achieved when a Pd(O2CCF3)2/DuPHOS catalyst is applied.     

Conversion of alpha,beta-unsaturated aldehydes into saturated esters: an Umpolung reaction catalyzed by nucleophilic carbenes

N-Heterocyclic carbenes derived from benzimidazolium salts are effective catalysts for generating homoenolate species from alpha,beta-unsaturated aldehydes. These nucleophilic intermediates can be protonated, and the resulting activated carbonyl unit is trapped with an alcohol nucleophile, thereby promoting a highly efficient conversion of an alpha,beta-unsaturated aldehyde into a saturated ester. A kinetic resolution of secondary alcohols can be achieved using chiral imidazoylidene catalysts. [reaction: see text]     

Enantioselective 1,3-dipolar cycloaddition of nitrones catalyzed by optically active cationic cobalt(III) complexes

[reaction: see text] The optically active beta-ketoiminato cationic cobalt(III) complexes were employed as efficient Lewis acid catalysts for the enantioselective 1,3-dipolar cycloaddition reaction of alpha,beta-unsaturated aldehydes with nitrones. Excellent endo selectivities and high enantioselectivities were achieved in the cycloaddition reaction of 1-cyclopentene-1-carbaldehyde and the nitrones derived from 2-halobenzaldehyde.     

Lewis acid induced tandem Diels-Alder reaction/ring expansion as an equivalent of a [4 + 3] cycloaddition

Aluminum chloride induced reaction between cyclopentadiene and alpha,beta-unsaturated aldehydes results in the stereoselective formation of the products of a formal [4 + 3] cycloaddition. The reaction proceeds by a tandem Diels-Alder reaction/ring expansion.     

Enantioselective organocatalytic Mukaiyama-Michael addition of silyl enol ethers to alpha,beta-unsaturated aldehydes

[reaction: see text] A highly enantioselective, organocatalytic Mukaiyama-Michael addition reaction of silyl ethers and alpha,beta-unsaturated aldehydes has been developed. The process, catalyzed by MacMillan's chiral imidazolidinone, affords delta-keto aldehydes in high yields (56-87%) and high enantioselectivities (85-97% ee). Moreover, the reaction is applicable to a wide range of silyl ethers and alpha,beta-unsaturated aldehydes and, as such, provides access to a range of important synthetic building blocks.     

Regioselective cycloaddition of 3-azatrienes with enamines. Synthesis of pyridines derived from β-aminoacids

Aza-Wittig reaction of N-vinylic phosphazenes with α,β-unsaturated aldehydes leads to the formation of 3-azatrienes through a [2+2]-cycloaddition-cycloreversion process. Subsequent, regioselective [4+2]-cycloaddition of 3-azatrienes with pyrrolidinocycloalkanone affords bicyclic dihydropyridines and pyridines in a regioselective fashion. 2-Heterodiene moiety of azatriene is involved in the formation of the six-membered ring skeleton of pyridine derivatives.     

Diarylprolinol silyl ether as catalyst of an exo-selective, enantioselective Diels-Alder reaction

In combined use with CF3CO2H, 2-[bis(3,5-bis-trifluoromethylphenyl) triethylsiloxymethyl]pyrrolidine was found to be an effective organocatalyst of an exo-selective, enantioselective Diels-Alder reaction of alpha,beta-unsaturated aldehydes.     

Chirality transfer from guanidinium ylides to 3-alkenyl (or 3-alkynyl) aziridine-2-carboxylates and application to the syntheses of (2R,3S)-3-hydroxyleucinate and D-erythro-sphingosine

[Reaction: see text]. Reaction of chiral guanidinium ylides with alpha,beta-unsaturated aldehydes gives 3-(alpha,beta-unsaturated) aziridine-2-carboxylates in high diastereo- and enantioselectivities (up to 93% diastereomeric excess and 98% enantiomeric excess). 3-(1-methylvinyl)- and 3-[(E)-pentadec-1-enyl]aziridine-2-carboxylates were successfully employed to prepare (2R,3S)-3-hydroxyleucinate and d-erythro-sphingosine, respectively.     

A novel approach of cycloaddition of difluorocarbene to alpha,beta-unsaturated aldehydes and ketones: synthesis of gem-difluorocyclopropyl ketones and 2-fluorofurans

A series of gem-difluorocyclopropyl acetals and ketals are easily obtained in moderate yields from the [1 + 2] cycloaddition of difluorocarbene to 1,3-dioxolanes of alpha,beta-unsaturated aromatic aldehydes and ketones. Hydrolysis of these fluorinated compounds under acidic conditions either gives the corresponding gem-difluorocyclopropyl ketones or 1-aryl-2-fluorofuran derivatives through intramolecular carbonium rearrangement with simultaneous ring cleavage.     

Iron and ruthenium Lewis acid catalyzed asymmetric 1,3-dipolar cycloaddition reactions between nitrones and enals

The single coordination-site transition metal Lewis acids [CpM(BIPHOP-F)][SbF6] (M = Fe, Ru) catalyze the [3+2] dipolar cycloaddition reaction between reactive nitrones and alpha,beta-unsaturated aldehydes to give chiral isoxazolidines with ee values of 75 to >96%. The stereochemistry of the major enantiomer is consistent with an endo approach of the nitrone to the Calpha-Si-face of the enal in the s-trans conformation in the (R,R)-catalyst site. The absolute configuration is based on an X-ray structure determination.     

Hetero-Diels-Alder reactions of 2H-phospholes with aldehydes

Transient 2-phenyl-3,4-dimethyl-5H-phosphole reacts at 150 degrees C with aldehydes RCH=O to give the corresponding [4 + 2] P-O cycloadducts with endo- (major) and exo-R-substituents. The cycloaddition with alpha,beta-unsaturated aldehydes takes place both at the C=O (major) and C=C bonds. Upon heating under reduced pressure, the benzaldehyde cycloadduct dissociates to give back the 2H-phosphole, which either dimerizes, is trapped by diphenylacetylene, or is deprotonated by (t)BuOK.     

Regioselective synthesis of fluoroalkyl pyridine derivatives from 3-fluoroalkyl substituted 2-aza-1,3-butadienes

A method for the preparation of 3-fluoroalkyl substituted 2-aza-butadienes by aza-Wittig reaction of N-vinylic phosphazenes and aldehydes is reported. [4+2] Cycloaddition reaction with enamines affords fluoralkyl substituted pyridine derivatives in a regioselective fashion.