Samarium‐Promoted Asymmetric Aldol–Tishchenko Reaction: Synthesis of Amino Acid‐Derived 4‐Amino‐1,3‐diols

A samarium‐mediated novel synthesis of enantiopure 4‐amino‐1,3‐diols is carried out through a samarium‐promoted aldol–Tishchenko reaction starting from chiral α′‐amino‐α‐chloro ketones (derived from natural α‐amino acids) and aldehydes. The process takes place with moderate levels of stereoselectivity and in high yields. A mechanism is proposed to explain these results while the absolute configuration and structure of the aldol–Tishchenko adducts were established by X‐ray analysis. This method has also been utilized for the synthesis of enigmols, 1‐deoxysphingoid base analogues.     

The Stereoselective Ru3(CO)12‐Catalyzed Synthesis of Steroidal 1,3‐Dihydropyrrol‐2‐one Derivatives from α,β‐Unsaturated Imines,Carbon Monoxide and Ethylene

The reaction of α,β‐unsaturated imines, derived from steroidal amines and cinnamaldehyde, with carbon monoxide and ethylene leads to the formation of steroids with a 1,3‐dihydropyrrol‐2‐one ring system attached to the D‐ring of the steroid. In addition, a new stereogenic center at C‐3 of the pyrrolone ring is produced during the reaction sequence. In the case of a 16‐position of the imine moiety the yields are nearly quantitative but the diastereoselectivity is low whereas the sterically more hindered 17‐position shows a decreased reactivity but quite good diastereoselectivities. Complete diastereoselectivity is achieved if the starting compound exhibits an additional silyl ether group in the 17β‐position besides the imine subunit in the 16β‐position. The compound bearing the pyrrolone substituent at 17β‐position was characterized by means of X‐ray crystallography showing that the rotation of the pyrrolone ring is hindered by a strong intramolecular hydrogen bond between the carbonyl oxygen of the pyrrolone moiety and the hydrogen at C‐17. The question of whether this intramolecular hydrogen bond is also responsible for the observed diastereoselectivities is discussed.     

Catalytic Asymmetric Synthesis of Dihydroquinazolinones from Imines and 2‐Aminobenzamides

An unprecedented catalytic asymmetric synthesis of aminal‐containing heterocyclic compounds has been developed from imines and tethered nitrogen/nitrogen nucleophiles. In the presence of 10 mol% of a commercially available chiral phosphoric acid, a range of aromatic, α,β‐unsaturated, and aliphatic imines react with 2‐aminobenzamides to give dihydroquinazolinones in good to excellent yields and ee. The enantioselectivity is significantly affected by the imine N‐substituent through non‐bonding interactions with the chiral phosphoric acid and the 2‐aminobenzamide.     

Stereoselective thia‐Michael 1,4‐Addition to Acyclic 2,4‐Dienones and 2‐En‐4‐ynones

Organocatalyzed highly stereoselective 1,4‐thia‐Michael addition of mercaptans to linear 2,4‐dienones and 2‐en‐4‐ynones was developed using Cinchona alkaloid‐based squaramides. Application of only 0.5–1 mol % loading afforded products in up to 98:2 e.r. and above 99:1 after a single recrystallization. The adducts of allyl mercaptan can be conveniently further transformed to new chiral 2‐substituted 2,5‐dihydrothiophenes by ring‐closing metathesis.

     

Organocatalytic Asymmetric Aldol Reaction of Ketones with β,γ‐Unsaturated α‐Keto Esters: An Efficient Access to Chiral Tertiary Alcohol Skeletons

This update describes a highly efficient organocatalytic aldol reaction of ketones and β,γ‐unsaturated α‐keto esters for constructing the chiral tertiary alcohol motif. With the application of 9‐amino(9‐deoxy)epi‐Cinchona alkaloid and an acidic additive as catalysts, both acyclic and cyclic ketones react with β,γ‐unsaturated α‐keto esters smoothly to afford aldol adducts in good to excellent yields and asymmetric induction. This protocol offers a new pathway for the construction of adjacent chiral carbon centers and the synthesis of chiral β‐hydroxy carbonyl compounds.     

Asymmetric Synthesis of cis‐3,4‐Disubstituted Chromans and Dihydrocoumarins via an Organocatalytic Michael Addition/ Hemiacetalization Reaction

The organocatalytic domino Michael/hemiacetalization reaction between various aldehydes and ortho‐nitrovinylphenols has been developed. Under the catalysis of diphenyl prolinol trimethylsilyl ether, cis‐3,4‐disubstituted chromanols are obtained in high to excellent yields (81–98%) and stereoselectivities (dr: 86:14 to >99:1, ee 96 to >99%). The corresponding disubstituted chromans are available by dehydroxylation of the domino products in good to excellent yields (58–95%). Furthermore, oxidation of the domino products with pyridinium chlorochromate provided 3,4‐dihydrocoumarins in good yields (65–83%) without any epimerization.     

Organocatalytic Asymmetric Synthesis of Protected α,β‐Diamino Acids

In the presence of the readily available quinine‐derived catalyst 4d , highly diastereo‐ and enantioselective Mannich reactions of tosyl‐protected imines and α‐isothiocyanato imides proceeded to afford the protected α,β‐diamino acids, useful building blocks for natural products and biologically active compounds, in good to excellent yields.     

Copper‐Catalyzed Chloroamination of Alkynes: Highly Regio‐ and Stereoselective Synthesis of (E)‐β‐Chloro‐Enesulfonamides

An efficient copper catalysis system for the chloroamination of alkynes with chlorosulfonamide at room temperature is described, providing a highly regio‐ and stereoselective procedure for the synthesis of (E)‐β‐chloro‐enesulfonamides in moderate to good yields.     

Synthesis of Ruthenium Hydride Complexes Containing beta‐Aminophosphine Ligands Derived from Amino Acids and their use in the H2‐Hydrogenation of Ketones and Imines

The new complexes RuHCl(PPh₂CH₂CHRNH₂)₂ and RuHCl(PPh₂CH₂CHRNH₂)(R‐ binap), R=H (Pgly), R=Me [(R)‐Pala] were prepared by the substitution of the PPh₃ ligands in RuHCl(PPh₃)₃ or RuHCl(PPh₃)[(R)‐binap] with beta‐aminophosphines derived from amino acids. The complex trans‐RuHCl(Pgly)[(R)‐binap] has been characterized by X‐ray crystallography. The complex trans‐RuHCl[(S)‐Ppro]₂ where (S)‐Ppro is derived from proline was also prepared and characterized by X‐ray crystallography. These were used as catalyst precursors in the presence of a base (KOPr‐i or KOBu‐t) for the hydrogenation of various ketones and imines to the respective alcohols and amines with H₂ gas (1–11 atm) at room temperature. Acetophenone was hydrogenated to (S)‐1‐phenylethanol in low ee (up to 40%) when catalyzed by the enantiomerically pure complexes. These complexes are especially active in the hydrogenation of sterically congested and electronically deactivated ketones and imines and are selective for the hydrogenation of CO bonds over CC bonds.     

Synthesis of 2‐(1‐Alkoxyvinyl)anilines by Palladium/Norbornene‐Catalyzed Amination Followed by Termination with Vinyl Ethers

A palladium/norbornene‐catalyzed ortho‐amination and ipso vinyl ether termination reaction of iodoarenes is reported. The benzyl vinyl ether serves as an efficient alternative carbonyl source in palladium/norbornene catalysis for the final ipso termination reaction to give [1‐(benzyloxy)vinyl]arenes, which readily undergo hydrolysis to deliver methyl ketones under aqueous acidic conditions. The final Heck termination reaction with vinyl ethers has high branched/linear selectivity. This reaction tolerates a range of iodoarene and O‐benzoylhydroxylamine substrates, and it provides a convenient way to prepare o‐acetylanilines. The synthetic utility of [1‐(benzyloxy)vinyl]arenes and the corresponding ketones is briefly investigated.

     

Direct Organocatalytic Asymmetric Mannich Addition of 3‐Substituted‐2H‐1,4‐Benzoxazines: Access to Tetrasubstituted Carbon Stereocenters

3‐Substituted‐2H‐1,4‐benzoxazines undergo a highly enantioselective direct Mannich reaction with acetone in the presence of an L ‐proline catalyst at room temperature. The corresponding N‐heterocycles with α‐tetrasubstituted carbon stereocenters were obtained in good yields (48–92%) and excellent enantioselectivity (up to >99% ee). Furthermore, a novel modification involving the diastereoselective reduction of the Mannich adduct was carried out leading to the formation of a 1,3‐amino alcohol with a chiral tetrasubstituted carbon stereocenter in high yield.

     

Ligand‐Free Nickel‐Catalysed 1,4‐Addition of Arylboronic Acids to α,β‐Unsaturated Carbonyl Compounds

A simple and efficient ligand‐free nickel‐based catalytic system has been developed for the 1,4‐addition of arylboronic acids to α,β‐unsaturated carbonyl compounds. With catalyst loadings of 1–2 mol%, a series of 1,4‐adducts from chalcones and cinnamates was obtained in moderate to excellent yields within 5–30 min under a nitrogen atmosphere and microwave irradiation. The 1,4‐addition of arylboronic acids to acrylates is less efficient.

     

Organocatalytic and Stereoselective [3 + 2] Cycloadditions of Azomethine Imines with α,β‐Unsaturated Aldehydes

Bipyrazolidin‐3‐one derivatives are biologically significant compounds and their importance has increased in the past decades. In this paper, the first stereoselective [3 + 2] dipolar cycloadditions of azomethine imines with α,β‐unsaturated aldehydes catalyzed by readily available α,α‐diarylprolinol salts are reported, providing a facile route to the synthesis of various chiral bipyrazolidin‐3‐one derivatives under mild conditions. The organocatalyst 1 g with strongly electron‐withdrawing groups exhibited the best stereoselectivity (exo:endo up to 98:2, for exo product up to 97 % ee), in the combination with trifluoroacetic acid.     

Enantioselective Addition of Malonates and β‐Keto Esters to Nitroalkenes over an Organonickel‐Functionalized Periodic Mesoporous Organosilica

A periodic mesoporous organosilica (PMO) with chiral cyclohexyldiamine‐based nickel(II) complexes incorporated within the silica framework was prepared through a co‐condensation of (1R,2R)‐cyclohexyldiamine‐derived silane and Ph‐bridged silane followed by complexation of nickel(II) bromide in the presence of (1R,2R)‐N,N′‐dibenzylcyclohexyldiamine. Structural analyses by X‐ray powder diffraction, nitrogen sorption and transmission electron microscopy disclosed its orderly mesostructure while characterization by solid‐state NMR and X‐ray photoelectron spectroscopy demonstrated the well‐defined single‐site chiral bis(cyclohexyldiamine)‐based nickel(II) active centers incorporated within the PMO material. In particular, as a heterogeneous chiral catalyst, this periodic mesoporous organosilica showed high catalytic activity and excellent enantioselectivity in asymmetric Michael addition of 1,3‐dicarbonyl compounds to nitroalkenes (more than 92% conversions and up to 99% ee values). More importantly, this heterogeneous catalyst could be recovered easily and reused repeatedly nine times without obviously affecting its ee value, showing good potential for industrial applications.     

Iron‐Catalyzed Regio‐ and Stereoselective Conjugate Addition of Aryl‐Grignard Reagents to α,β,γ,δ‐Unsaturated Sulfones and its Synthetic Application

The iron‐catalyzed δ‐addition of aryl‐Grignard reagents to α,β,γ,δ‐unsaturated sulfones proceeded in a regio‐ and stereoselective manner to give cis‐4‐aryl‐2‐alkenyl sulfones. Allylic alkylation of the resultant products was performed without isomerization of the cis‐olefin to give cis‐4‐aryl‐1,1‐dialkyl‐2‐alkenyl sulfones, which upon intramolecular Friedel–Crafts reaction with aluminum chloride gave 1,4‐dihydronaphthalenes having a quaternary carbon center.     

Iron‐Catalyzed Tandem One‐Pot Addition and Cyclization of the Blaise Reaction Intermediate and Nitroolefins: Synthesis of Substituted NH‐Pyrroles from Nitriles

The iron‐catalyzed addition and cyclization of the Blaise reaction intermediate and nitroolefins to synthesize highly functionalized NH‐pyrroles in a tandem one‐pot manner from nitriles has been developed. This reaction shows good functional group tolerance and affords a broad spectrum of substituted NH‐pyrroles in good yields.     

Formal [3+2] Annulation Involving Allylic Bromides and Thioureas. Synthesis of 2‐Iminothiazolidines through a Base‐Catalyzed Intramolecular anti‐Michael Addition

A simple and efficient protocol was developed for the synthesis of 2‐iminothiazolidines through a base‐mediated [3+2] annulation involving substituted thioureas and allylic bromides bearing electron‐withdrawing groups. This domino process consists of nucleophilic displacement, followed by intramolecular anti‐Michael addition of the preformed allylic isothiourea under mild conditions to give the thiazolidine core.

     

A Stereocontrolled 1,2‐Addition Reaction of Tetrazoles with Alkyl Propiolates for the Synthesis of Highly Functionalized Enamines

A stereocontrolled 1,2‐addition reaction of 1‐aryl‐1H‐tetrazoles with alkyl propiolates for the synthesis of highly functionalized enamines was developed. In the presence of silver oxide (Ag₂O), the 1,2‐addition reaction generated (Z)‐N‐cyano enamines in good yields with exclusive formation of the Z‐isomers. Meanwhile, the 1,2‐addition reaction generated (E)‐N‐cyano enamines in the presence of Ag₂O and potassium carbonate (K₂CO₃) with high stereoselectivity and yields.