Tunable chiral monophosphines as ligands in enantioselective rhodium-catalyzed ring-opening of oxabenzonorbornadienes with amines

A new tunable chiral monophosphine was used as a ligand for asymmetric rhodium-catalyzed ring-opening of oxabenzonorbornadiene with amines, providing a series of chiral ring-opened products in high yields (up to 97%) and with high enantioselectivities (>99%).The reaction can be performed at rt to obtain the desired product with high enantioselectivity.     

Syntheses of chiral β- and γ-amino ethers, morpholines, and their homologues via nucleophilic ring-opening of chiral activated aziridines and azetidines

Lewis acid catalyzed quaternary ammonium salt mediated highly regioselective ring-opening of chiral activated aziridines and azetidines with alcohols to nonracemic β- and γ-amino ethers has been developed. The reaction mainly proceeds via an S(N)2 pathway, and the partial racemization of the starting substrate was effectively controlled by using quaternary ammonium salts. β- and γ-amino ethers are obtained with high enantio- and diastereospecificity (ee up to >99%, de up to 99%). The methodology was further extended to synthesize morpholines and their homologues with high enantiospecificity (ee up to 90%) when halo alcohols were employed as the nucleophiles.     

One-pot organocatalytic domino Michael/alpha-alkylation reactions: direct catalytic enantioselective cyclopropanation and cyclopentanation reactions

The development of one-pot organocatalytic domino Michael/alpha-alkylation reactions between bromomalonates or bromoacetoacetate esters and alpha,beta-unsaturated aldehydes is presented. The chiral-amine-catalyzed reactions with bromomalonates as substrates give access to the corresponding 2-formylcyclopropane derivatives in high yields with excellent diastereoselectivity and up to 99 % ee. The catalytic domino Michael/alpha-alkylation reactions between 4-bromo-acetoacetate and enals provide a route for the synthesis of functionalized cyclopentanones in good to high yields with 93-99 % ee. The products from the organocatalytic reactions were also reduced with high diastereoselectivity to the corresponding cyclopropanols and cyclopentanols, respectively. Moreover, one-pot combinations of amine and heterocyclic carbene catalysis (AHCC) enabled the highly enantioselective synthesis of beta-malonate esters (91-97 % ee) from the reaction between bromomalonates and enals. The tandem catalysis included the catalytic domino reaction followed by catalytic in situ chemoselective ring-opening of the 2-formylcyclopropane intermediates.     

Rhodium-catalyzed ring-opening reactions of N-boc-azabenzonorbornadienes with amine nucleophiles

In the presence of a rhodium catalyst (5 mol %) generated in situ from [Rh(cod)Cl](2) and (S,S')-(R,R')-C(2)-ferriphos (4a), the asymmetric ring-opening reaction of azabenzonorbornadienes (1a-m) with various aliphatic and aromatic amines (2a-l) proceeded with high enantioselectivity (up to >99% ee) to give the corresponding 1,2-diamine derivatives 3 in high yields. In the specific case of pyrrolidine as nucleophile, Et(3)NHCl was necessary as an additive for good reactivity and enantioselectivity. Additionally, a practical protocol was developed for the ring-opening of 1a with volatile amines at elevated temperatures and standard pressure, using R(2)NH(2)I and i-Pr(2)NEt. The experimental results showed that the nature of the chiral ligand has the significant impact on the reactivity of the catalyst and the use of excess amount (2.2 eq to Rh) of the chiral ligand plays an important role to improve the enantioselectivity in the present asymmetric reaction.     

Synthesis of new chiral aliphatic amino diselenides and their application as catalysts for the enantioselective addition of diethylzinc to aldehydes

[reaction: see text] A set of chiral aliphatic amino diselenides have been synthesized from readily available starting materials in a straightforward synthetic route via the ring-opening reaction of the parent aziridines. These ligands have been tested as catalysts for the enantioselective addition of diethylzinc to aldehydes. The influence of the alkyl group substituents on the stereoselectivity has been studied, and in the best case, an enantiomeric excess up to 99% could be obtained by using only 0.5 mol % of the chiral diselenide 3a.     

Catalytic asymmetric ring-opening of meso-aziridines with malonates under heterodinuclear rare earth metal Schiff base catalysis

Catalytic asymmetric ring-opening of meso-aziridines with malonates is described. The combined use of two rare earth metal sources with different properties promoted the desired ring-opening reaction. A 1:1:1 mixture of a heterobimetallic La(O-iPr)(3)/Yb(OTf)(3)/Schiff base 1a (0.25-10 mol %) efficiently promoted the reaction of five-, six-, and seven-membered ring cyclic meso-aziridines as well as acyclic meso-aziridines with dimethyl, diethyl, and dibenzyl malonates, giving chiral cyclic and acyclic γ-amino esters in 99-63% yield and >99.5-97% ee.     

Switching from S- to R-selectivity in the Candida antarctica lipase B-catalyzed ring-opening of omega-methylated lactones: tuning polymerizations by ring size

Novozym 435-catalyzed ring-opening of a range of omega-methylated lactones demonstrates fascinating differences in rate of reaction and enantioselectivity. A switch from S- to R-selectivity was observed upon going from small (ring sizes or=8). This was attributed to the transition from a cisoid to a transoid conformational preference of the ester bond on going from small to large lactones. The S-selectivity of the ring-opening of the small, cisoid lactones was low to moderate, while the R-selectivity of the ring-opening of the large transoid lactones was surprisingly high. The S-selectivity of the ring-opening of the small, cisoid lactones combined with the established R-selectivity of the transesterification of (aliphatic) secondary alcohols prevented polymerization from taking place. Ring-opening of the large, transoid lactones was R-selective with high enantioselectivity. As a result, these lactones could be polymerized, without exception, by straightforward kinetic resolution polymerization, yielding the enantiopure R-polyester with excellent enantiomeric excess (>99%).     

A highly reusable rhodium catalyst-organic framework for the intramolecular cycloisomerization of 1,6-enynes

The intramolecular cycloisomerization of 1,6-enynes in 95-99% ee is reported using an immobilized Rh catalyst-organic framework synthesized from alternating ring-opening metathesis polymerization (altROMP) assembly. The framework was reused up to seven times, and it was used in high turnover number (TON) batch reactions. The catalyst provided the highest TONs to date (up to 890) for the cycloisomerizations, with catalyst loadings ranging from 0.2 to 0.06 mol %.     

Enantioselective Radical-Polar Crossover Reactions of Indanonecarboxamides with Alkenes

Highly efficient asymmetric intermolecular radical-polar crossover reactions were realized by combining a chiral N,N′-dioxide/Ni^II complex catalyst with Ag₂O under mild reaction conditions. Various terminal alkenes and indanonecarboxamides/esters underwent radical addition/cyclization reactions to afford spiro-iminolactones and spirolactones with good to excellent yields (up to 99 %) and enantioselectivities (up to 97 % ee). Furthermore, a range of different radical-mediated oxidation/elimination or epoxide ring-opening products were obtained under mild reaction conditions. The Lewis acid catalysts exhibited excellent performance and precluded the strong background reaction.     

Asymmetric synthesis of 3,4-diaminochroman-2-ones promoted by guanidine and bisguanidium salt

A highly enantioselective synthesis of 3,4-diaminochroman-2-ones has been realized via the domino reaction of o-hydroxy aromatic aldimines and azlactones. Notably, a cis-product was obtained as the major product by the use of guanidine 2a whereas a trans-product was the major product with bisguanidium salt 3?HBAr(F)(4). In two cases, various substituted 3,4-dihydrocoumarins were obtained with high yields (up to 99%) as well as excellent enantioselectivities (up to 99% ee) and diastereoselectivities (up to >99:1 cis:trans and 98:2 trans:cis, respectively) under mild reaction conditions.     

Michael additions in water of ketones to nitroolefins catalyzed by readily tunable and bifunctional pyrrolidine-thiourea organocatalysts

An operationally trivial and environmentally benign procedure for direct Michael addition has been developed. The reaction of various ketones with nitroolefins can be performed in water to afford the corresponding nitro compounds in high yields in the presence of a pyrrolidine-thiourea organocatalyst at 35 °C. The reaction exhibits a high stereoselectivity, with high enantioselectivities (up to 99%) as well as diastereoselectivities (up to 99:1) being achieved under the optimal conditions.     

N-heterocyclic carbene (NHC)-catalyzed highly diastereo- and enantioselective oxo-Diels-Alder reactions for synthesis of fused pyrano[2,3-b]indoles

A chiral N-heterocyclic carbene (NHC)-catalyzed Diels-Alder reaction of 2-oxoindolin-3-ylidenes and α-chloroaldehydes was developed for the synthesis of fused pyrano[2,3-b]indoles in good to excellent yields (up to 99%) with high cis-diastereoselectivities (>99:1 dr) and enantioselectivities (up to >99% ee).     

Double axially chiral bisphosphorylimides as novel Brønsted acids in asymmetric three-component Mannich reaction

A double axially chiral bisphosphorylimide has been demonstrated to be an efficient and highly sterically hindered Brønsted acid in asymmetric three-component Mannich reactions. Optically active syn-β-amino ketones were obtained in high yields (up to 99%) with excellent diastereoselectivity (99:1) and enantioselectivity (up to 99% ee). A gram-scale reaction was also performed to prove the synthetic application value of this reaction.     

Very efficient phosphoramidite ligand for asymmetric iridium-catalyzed allylic alkylation

[reaction: see text] Linear or branched allylic carbonates or acetates undergo enantioselective iridium-catalyzed allylic substitution with sodium malonate. The reaction is wide in scope and affords the branched product in high yield and with high regio- (up to >99:1) and enantioselectivity (up to 98%). Ten aromatic or aliphatic substrates were successfully tested.     

Synthesis of geminal bisphosphonates via organocatalyzed enantioselective Michael additions of cyclic ketones and 4-piperidones

A Michael addition reaction of cyclic ketones and piperidones to a vinyl phosphonate is described. The reaction, catalyzed by chiral diamines, produced geminal γ-oxobisphosphonates in high yields (up to 92%) and very high ees (up to >99%). Disubstituted ketones gave drs of up to 8?:?92. The synthesis and characterization of several new compounds with potential biological activity is described.     

Pyrrolidine-thioxotetrahydropyrimidinone as an efficient organocatalyst for the enantioselective Michael addition of cyclic ketones to nitrodienes

Among the various Michael additions, the enantioselective reaction between cyclic ketones and nitrodienes has received little attention in comparison to the corresponding reaction with nitroolefins. A bifunctional organocatalyst consisting of the pyrrolidine moiety and a thioxotetrahydropyrimidinone ring successfully catalyzed this asymmetric transformation. The products of the reaction between various ketones and nitrodienes were obtained in high yields (up to 96%) with excellent diastereo- (up to >98:2 dr) and enantioselectivities (up to 99:1% er).     

Highly enantioselective Michael addition of cyclic ketones to chalcones catalyzed by pyrrolidine-based imides

An efficient procedure for asymmetric Michael addition reaction of cyclic ketones with low activated chalcones catalyzed by pyrrolidine-based phthalimide and 1,8-Naphthalimide catalysts was developed. The corresponding products were obtained in high yields with high diastereoselectivities (up to 99:1 dr) and high enantioselectivities (up to 96% ee) under mild conditions.     

4-(2-羧基苄氧基)苯乙酸的合成工艺改进

对羟基苯乙酸二钠盐与苯酞在N,N-二甲基乙酰胺中完成开环反应,合成了抗过敏药盐酸奥洛他定的重要中间体——4-(2-羧基苄氧基)苯乙酸,其结构经1H NMR确证,收率78%,纯度99%(HPLC)。     

A convenient route to enantiopure 3-aryl-2,3-diaminopropanoic acids by diastereoselective Mannich reaction of camphor-based tricyclic iminolactone with imines

A novel and convenient route to the asymmetric synthesis of 2,3-diamino acids via Mannich reaction of iminolactones 1a and 1b with N-protected imines has been achieved in good yields (up to 95%) and high diastereoselectivity (dr: >99:1). Hydrolysis of the Mannich adducts under acidic conditions furnished the desired 3-aryl-2,3-diaminopropanoic acids in good yields (up to 85%) with excellent enantiomeric excesses (99% ee).     

L-tert-Leucine derived urea-ammonium salts: Efficient bifunctional phase transfer catalysts for highly diastereo- and enantioselective aza-Henry reaction of isatin-derived N-Boc ketimines with α-aryl nitromethanes

An efficient way of aza-Henry reaction between isatin-derived N-Boc ketimines and α-aryl nitromethanes catalyzed by bifunctional phase transfer catalysts with a quaternary ammonium center derived from L-tert-Leucine has been developed. A series of 3-substituted 3-amino-oxindoles were constructed by this catalytic protocol in excellent yields (90–99%), with high enantioselectivities (83–95%) and diastereoselectivities (79:21–97:3). The asymmetric aza-Henry reaction of N-Boc amidosulfones and α-aryl nitromethanes were also investigated and gave the corresponding products in high to excellent yields (72–97%) with high enantioselectivities (up to 99%) and diastereoselectivities (up to >99:1).