Highly stereoselective Saucy-Marbet rearrangement using chiral ynamides. Synthesis of highly substituted chiral homoallenyl alcohols

[reaction: see text] A highly stereoselective Saucy-Marbet rearrangement using chiral ynamides and propargyl alcohols is described here. This rearrangement can be catalyzed by para-nitrobenzenesulfonic acid leading to high diastereoselectivities for a range of different chiral propargyl alcohols and ynamides in a stereochemically intriguing matched, mismatched, or indifferent manner. This provides an excellent entry to highly substituted chiral homoallenyl alcohols.     

Room-temperature highly diastereoselective Zn-mediated allylation of chiral N-tert-butanesulfinyl imines: remarkable reaction condition controlled stereoselectivity reversal

[reaction: see text] An efficient method for the highly diastereoselective synthesis of chiral homoallylic amines by Zn-mediated allylation of chiral N-tert-butanesulfinyl imines at room temperature was developed. By simply tuning the reaction conditions, the method allows the achievement of a highly remarkable opposite stereocontrol, affording the desired stereochemical outcome in good yield and with excellent diastereoselectivity (up to 98% dr). With N-sulfinyl ketimines, the corresponding quaternary carbon-containing chiral homoallylic amines could also be produced.     

Highly diastereoselective and asymmetric Diels-Alder reactions of masked o-benzoquinones with chiral racemic and homochiral furans. Synthesis of optically active tricyclic gamma-lactones

[reaction: see text] The first examples of highly diastereoselective and asymmetric Diels-Alder cycloadditions of in situ generated masked o-benzoquinones (MOBs) with chiral racemic and homochiral furans bearing a chiral center in the alpha-position leading to highly functionalized diastereomeric/enantioselective tricyclic heterocycles and chiral tricyclic gamma-lactones are described.     

Highly enantioselective Diels-Alder reactions of Danishefsky type dienes with electron-deficient alkenes catalyzed by Yb(III)-BINAMIDE complexes

1-Methoxy-3-trimethylsiloxy-1,3-butadiene (Danishefsky's diene) is recognized as a synthetically useful diene due to its high reactivity in the Diels-Alder reaction with electron-deficient alkenes to give oxygen-functionalyzed cyclohexenes and substituted cyclohexenones, which are important building blocks for the total synthesis of natural products. However, the development of catalytic enantioselective versions of Diels-Alder reactions using Danishefsky type dienes with electron-deficient alkenes has been difficult because of the instability of the dienes under Lewis acidic conditions. Only highly reactive CO and CN double bonds are employed in a hetero-Diels-Alder reaction which proceeds under catalysis of chiral Lewis acids. We have developed a new chiral ligand, BINAMIDE, which is easily prepared from 1,1'-binaphtyl-2,2'-diamine by acylation. The highly diastereo- and enantioselective Diels-Alder reaction of Danishefsky type dienes with electron-deficient alkenes in the presence of an Yb(III)-BINAMIDE complex has been developed. The reaction proceeded in an exoselective mode and gave chiral highly functionalized cyclohexene derivatives in good yields.     

Direct enantioselective aldol-Tishchenko reaction catalyzed by chiral lithium diphenylbinaphtholate

Chiral lithium diphenylbinaphtholate is an effective catalyst for the enantioselective aldol-Tishchenko reaction, affording 1,3-diol derivatives with three contiguous chiral centers and high stereoselectivities. Successive aldol-aldol-Tishchenko reactions gave a triol derivative with five consecutive chiral centers. The present reaction was applicable to highly enantioselective Evans-Tishchenko reduction.     

Synthetic control leading to chiral compounds

A highly diastereoselective cross aldol reaction is developed using divalent tin enolates formed from stannous trifluoromethanesulfonate and carbonyl compounds. The reaction is extended to a highly enantioselective cross aldol reaction employing chiral diamines derived from (S)-proline as ligands.     

Side-arm-promoted highly enantioselective ring-opening reactions and kinetic resolution of donor-acceptor cyclopropanes with amines

A Ni-catalyzed asymmetric ring-opening reaction of 2-substituted cyclopropane-1,1-dicarboxylates with aliphatic amines has been accomplished using the chiral indane-trisoxazoline (In-TOX) ligand. This highly enantioselective reaction provides an efficient approach to a variety of chiral γ-substituted γ-amino acid derivatives, which are readily transformed into multifunctionalized piperidines and γ-lactams. The single-crystal X-ray structure of the TOX-Ni complex is provided, and the role of the side arm in the chiral ligand is discussed.     

Axially chiral guanidine as enantioselective base catalyst for 1,4-addition reaction of 1,3-dicarbonyl compounds with conjugated nitroalkenes

A new strategy for designing chiral guanidine molecules is presented, which features the introduction of an axially chiral binaphthyl backbone. The axially chiral guanidine catalysts thus developed facilitated the highly enantioselective 1,4-addition reaction of 1,3-dicarbonyl compounds with a broad range of conjugated nitroalkenes and showed extremely high catalytic activity.     

Design of chiral N-triflyl phosphoramide as a strong chiral Brønsted acid and its application to asymmetric Diels-Alder reaction

A highly reactive and acidic chiral Br?nsted acid catalyst, chiral N-triflyl phosphoramide, was developed. Highly enantioselective Diels-Alder reaction of alpha,beta-unsaturated ketone with silyloxydiene was demonstrated using this chiral Br?nsted acid catalyst.     

Enantioselective total synthesis of (+)-tricycloclavulone

The first total synthesis of (+)-tricycloclavulone having a unique tricyclo[5,3,0,01,4]decane skeleton and six chiral centers was achieved in a highly stereoselective manner. It includes a catalytic enantioselective [2+2]-cycloaddition reaction using novel chiral copper catalyst, extremely effecting an intramolecular ester transfer reaction, and asymmetric reduction of the carbonyl group on the alpha-chain using Noyori's chiral ruthenium catalyst.     

Construction of Chiral Tetrahydro‐β‐Carbolines: Asymmetric Pictet–Spengler Reaction of Indolyl Dihydropyridines

A highly efficient synthesis of the enantioenriched tetrahydro‐β‐carbolines was developed by using a chiral phosphoric acid catalyzed Pictet–Spengler reaction of indolyl dihydropyridines. The reaction proceeds under mild reaction conditions to afford the desired chiral tetrahydro‐β‐carbolines in good to excellent yields (up to 96 %) and high enantioselectivities (up to 99 % ee ). With this method, a formal synthesis of tangutorine and a total synthesis of deplancheine were achieved in a highly efficient manner.     

Construction of Chiral Tetrahydro-β-Carbolines: Asymmetric Pictet–Spengler Reaction of Indolyl Dihydropyridines

A highly efficient synthesis of the enantioenriched tetrahydro-β-carbolines was developed by using a chiral phosphoric acid catalyzed Pictet–Spengler reaction of indolyl dihydropyridines. The reaction proceeds under mild reaction conditions to afford the desired chiral tetrahydro-β-carbolines in good to excellent yields (up to 96 %) and high enantioselectivities (up to 99 % ee). With this method, a formal synthesis of tangutorine and a total synthesis of deplancheine were achieved in a highly efficient manner.     

Organocatalytic asymmetric aza-Friedel-Crafts alkylation of furan

A new asymmetric entry of the 1,2-aza-Friedel-Crafts reaction catalyzed by a chiral phosphoric acid is described. The present reaction has provided an atom-economical route to furan-2-ylamine derivatives in a highly enantioselective fashion. The synthetic utility of these products was displayed by oxidative cleavage of the furan ring (aza-Achmatowicz reaction) to form a 1,4-dicarbonyl compound that could be further derivatized to a chiral gamma-butenolid.     

Diastereoselective Pd/In bimetallic inter-intramolecular (class 2) cascade reactions of allenyl-imines and aryl iodides

A new diastereoselective Pd/In bimetallic inter-intramolecular cascade reaction employing allenyl-sulfinimines and aryl iodides is described. The tert-butanesulfinyl chiral auxiliary affords chiral, highly substituted cis-pyrrolidines and piperidines.     

Asymmetric Synthesis of Chiral 1,4‐Enynes through Organocatalytic Alkenylation of Propargyl Alcohols with Trialkenylboroxines

A highly enantioselective synthesis of 1,4‐enynes is described that proceeds through an organocatalytic reaction between propargyl alcohols and trialkenylboroxines. Our strategy relies on acid‐mediated generation of the carbocationic intermediate from propargyl alcohols followed by enantioselective alkenylation with trialkenylboroxines. A range of chiral 1,4‐enynes were obtained in moderate to good yields with high levels of enantioselectivity. Use of a highly acidic chiral N‐triflyl phosphoramide catalyst, which has two distant Lewis basic oxygen atoms, was found to be crucial for both high reactivity and selectivity in the present reaction.     

Chiral Lewis acid-catalyzed highly enantioselective [4 + 3] cycloaddition reactions of nitrogen-stabilized oxyallyl cations derived from allenamides

A chiral Lewis acid-catalyzed highly enantioselective [4 + 3] cycloaddition reaction of allenamide-derived nitrogen-stabilized chiral oxyallyl cations is described here. The use of bisoxazoline ligand and CuOTf2 provides high enantioselectivity, especially with [SbF6]- as the counteranion.     

Chiral Allenes via Alkynylogous Mukaiyama Aldol Reaction

Herein we describe the development of a catalytic enantioselective alkynylogous Mukaiyama aldol reaction. The reaction is catalyzed by a newly designed chiral disulfonimide and delivers chiral allenoates in high yields and with excellent regio‐, diastereo‐, and enantioselectivity. Our process tolerates a broad range of aldehydes in combination with diverse alkynyl‐substituted ketene acetals. The reaction products can be readily derivatized to furnish a variety of highly substituted enantiomerically enriched building blocks.     

Synthesis of a novel sterically hindered chiral cyclic phosphoric acid derived from l-tartaric acid and application to the asymmetric catalytic Biginelli reaction

A novel sterically hindered chiral cyclic phosphoric acid derived from l-tartaric acid was designed and synthesized based on highly regioselective cyclosulfitation of chiral 1,1,4,4-tetraphenylbutanetetraol. The asymmetric Biginelli reaction catalyzed by this newly synthesized chiral phosphoric acid was examined, and enantioselectivities up to 99% ee was obtained.     

Studies on the synthesis of pectenotoxin II: synthesis of a C(11)-C(26) fragment precursor via [3 + 2]-annulation reactions of chiral allylsilanes

[see reaction]. A synthesis of tetracycle 2 corresponding to the C(11)-C(26) fragment of pectenotoxin II is described. The synthesis features two highly stereoselective [3 + 2]-annulation reactions of chiral allylsilanes, generated via allylboration of aldehydes with the chiral gamma-silylallylborane 4 or the gamma-silylallylboronate 19, for construction of the highly substituted C and E rings.     

Highly enantio- and diastereoselective organocatalytic cascade aza-Michael-Michael reactions: a direct method for the synthesis of trisubstituted chiral pyrrolidines

An unprecedented highly enantio- and diastereoselective cascade aza-Michael-Michael reaction of alpha,beta-unsaturated aldehydes with trans-gamma-Ts protected amino alpha,beta-unsaturated ester has been developed; the simple and practical process, efficiently catalyzed by chiral diphenylprolinol TMS ether, serves as a powerful access to highly functionalized trisubstituted chiral pyrrolidines.