Asymmetric synthesis of enantio-enriched acyclic α-amino alkylstannanes and rearrangement behavior of carbanions thereof

An efficient stereocontrolled synthesis of enantio-enriched N-Boc-N-allyl-α-amino alkylstannanes and N,N-diallylic α-amino alkylstannanes starting from enantio-enriched α-hydroxy alkylstannane has been developed. The aza-Wittig rearrangement of enantio-defined N,N-diallyl-α-amino alkyllithium, generated by tin-lithium exchange, is shown to proceed predominantly with inversion of configuration at the Li-bearing carbon terminus.     

A highly regioselective hydroformylation of an α-chiral olefin to produce a versatile trifunctionalised orthogonally protected C5 synthon

This paper describes a highly regioselective hydroformylation of (R)-N-phthalimido-vinylglycinol, [(R)-PVG]. By judicious choice of the reaction conditions, catalyst-controlled preferential formation of the linear regioisomer could be achieved in excellent yield. The hydroformylation product cyclised to a hemi-acetal, which is an orthogonally protected trifunctionalised enantio-enriched C5 synthon. The value of this versatile intermediate was demonstrated by the ready formation of enantio-enriched amino-diols, diamino-alcohols and differentially protected (R)-3-aminopiperidine.     

Highly enantioselective synthesis of α-(perfluoroalkyl)amines via hydrogenation of enamide precursors in the presence of chiraphos-rhodium catalyst

Highly (up to 99% ee) enantio-enriched perfluoroalkyl amines can be synthesized by the perfluoroalkylation of nitriles with Lewis acidic perfluoroalkyl titanate reagents and catalytic asymmetric hydrogenation with the chiraphos-Rh catalyst of the resultant perfluoroalkyl enamides via base-mediated tautomerization.     

Enantioselective metallo-organocatalyzed preparation of cyclopentanes bearing an all-carbon quaternary stereocenter

Enantioselective metallo-organocatalyzed carbocyclizations of formyl-alkynes have been developed. The cooperation between aminocatalysis and a chiral copper(I) complex granted access to enantio-enriched cyclopentanes through the challenging formation of all-carbon quaternary stereocenters.     

Enantioselective bromolactonization of cis-1,2-disubstituted olefinic acids using an amino-thiocarbamate catalyst

A facile, highly regio- and enantioselective amino-thiocarbamate-catalyzed bromolactonization of cis-1,2-disubstituted olefinic acids has been developed. The use of the enantio-enriched lactones in the synthesis of chiral synthetic intermediates is also demonstrated.     

Asymmetric radical additions of trialkylboranes to 2H-azirine-3-carboxylates

Asymmetric additions of alkyl radicals, generated from R3B, to chiral 2H-azirine-3-carboxylates offer a new entry to enantio-enriched aziridines, and proceed with high diastereoselectivity when using 8-phenylmenthol as chiral auxiliary.     

Cyclization of enantio-enriched α-(homoallyloxy)alkyllithiums: Evidence for retention of configuration at the carbanion center

The titled cyclization induced by Sn---Li transmetallation of the enantio-defined stannanes is shown to proceed with complete retention of configuration at the Li-bearing sp³-carbon to afford the enantio-enriched α,β-disubstituted tetrahydrofurans.     

A one-pot process for the enantioselective preparation of saturated secondary alcohols from propargyl ketones under hydrogen transfer conditions

Propargyl ketones can be directly transformed to enantio-enriched saturated secondary alcohols in a one-pot reaction using chiral RuCl[N-(tosyl)-1,2-diphenylethylenediamine)(p-cymene) and Pd/BaSO₄ as catalysts, under transfer hydrogenation conditions.     

Enantioselective synthesis of aryl sulfoxides via palladium-catalyzed arylation of sulfenate anions

Arylation of various sulfenate anions generated from beta-sulfinyl esters by retro-Michael reaction in the presence of palladium(0) and enantiopure ligands gave the corresponding aryl sulfoxides in enantio-enriched form. The Josiphos-type ligand (R)-(S)-PPF-t-Bu2 turned out to be the best ligand tested, allowing ee's up to 83% in a predictable sense.     

Sequential perfluoroalkylation and asymmetric reduction of nitriles triggered with perfluoroalkyl titanates: catalytic asymmetric synthesis of perfluoroalkyl amines

Highly enantio-enriched perfluoroalkyl amines are shown to be synthesized by perfluoroalkylation and asymmetric reduction of nitriles. Perfluoroalkylation of nitriles can be attained by the Lewis acidic perfluoroalkyl titanate reagents to give acyclic ketimines. Catalytic asymmetric hydrogenation of the acyclic ketimines affords the perfluoroalkyl amine products in up to 93% ee.     

Enantioselective synthesis of functionalized γ-butyrolactones

Sharpless asymmetric dihydroxylation and aminohydroxylation of (E)-dimethyl-2-alkylidene glutarates 2 were shown to afford enantio-enriched or enantiopure highly functionalized γ-butyrolactones 3 and 7.     

An escapade in the world of sulfenate anions: generation,reactivity and applications in domino processes

An escapade in the world of sulfenate anions is described and shows that these nucleophiles, despite being described as unstable species, are mild and efficient sulfinylating agents, allowing access to a variety of allyl and aryl sulfoxides under smooth and operationally very simple conditions. Their use in asymmetric catalysis is also possible allowing the preparation of enantio-enriched sulfoxides. Moreover, such anions have been involved in the development of two new pseudo–domino processes.     

Organocatalyzed stereoselective construction of N-formylpiperidines via a Michael-aza-Henry-hemiaminalization reaction cascade

An efficient asymmetric synthesis of N-formylpiperidines via an organocatalytic Michael-aza-Henry-hemiaminalization reaction cascade of an aldehyde, a nitroalkene, and an N-arylideneformamide is reported. The reaction is triggered by diphenylprolinol trimethylsilyl ether and creates two C-C and one C-N bonds leading to the formation of highly enantio-enriched N-formylpiperidines with five contiguous chiral centers in a one-pot operation.     

Efficient stereoselective nucleophilic addition of pyrroles to chiral nitrones

Regioselective additions of pyrroles to a variety of optically active nitrones under smooth acidic conditions lead to chiral pyrrolic N-hydroxylamines in good to excellent yields. Depending on the position of the chirality on the nitrone partner, the addition products have been isolated with high diastereoselectivity levels. Reaction of glyoxylate based chiral nitrones either at the C-2 or at the C-3 position of the pyrrole nucleus afforded N-hydroxyamino esters in high yields as single diastereoisomers. These adducts allow access to enantio-enriched non proteinogenic 2'- and 3'-pyrrolylglycines (13 and 19 respectively).     

Electrophilic fluorination of organosilanes

The fluorination of organosilanes with the silyl groups directly attached or adjacent to an aryl or alkenyl group has been only very recently examined despite the fact that the corresponding fluorinated products are synthetically useful building blocks. In these reactions, the silyl group enhances the reactivity of the pi-nucleophile and controls the sense of regiochemistry upon addition of the electrophilic source of fluorine. These reactions take advantage of the beta effect of the silicon-carbon bond and recent results from the literature revealed that this chemistry allows for the preparation of a variety of novel fluorinated building blocks including enantio-enriched derivatives.     

Asymmetric synthesis of 5-(1-hydroxyalkyl)-5-methyl-5H-furan-2-ones

The reactivity of 5-methyl-4-(pyrrolidin-1-yl)-5H-furan-2-one with aldehydes and with acyl chlorides followed by reduction was studied. The aldol condensation gave predominantly the anti aldol product when the acylation-reduction sequence led exclusively to the syn product. The use of a chiral pyrrolidine, (S)-2-methoxymethylpyrrolidine (SMP), allowed the synthesis of enantio-enriched compounds, the acylation-reduction leading to the (R,R) addition product.     

Application of the photocyclization reaction of 1,2-cyclopenta-fused pyridinium perchlorate to formal total syntheses of (−)-cephalotaxine

Two strategies for the formal total synthesis of (−)-cephalotaxine, based on pyridinium salt photochemistry, are described. The routes begin with photocyclization reaction of 1,2-cyclopenta-fused pyridinium perchlorate. This process efficiently and regioselectively produces a tricyclic aziridine, which undergoes sequential aziridine ring opening and enzymatic desymmetrization to generate enantio-enriched intermediates that contain the spirocyclic D,E-ring system found in cephalotaxine. These substances serve as precursors to late stage key intermediates used by Mori, Tietze, and Yoshida in earlier syntheses of (−)-cephalotaxine.     

Enantioselective Mannich reaction of γ-malonate-substituted α,β-unsaturated esters with N-Boc imines catalyzed by chiral bifunctional thiourea-phosphonium salts

A novel enantioselective Mannich reaction of γ-malonate-substituted α, β-unsaturated esters with N-protected arylaldimines was realized by using asymmetric phase-transfer catalysis (APTC). With amino acid-derived bifunctional thiourea-phosphonium salts as a catalyst, a series of enantio-enriched Mannich products could be synthesized under very mild and simple reaction conditions with high yields and enantioselectivities.     

Autocatalytic asymmetric reduction of 2,6-diacetylpyridine

[reaction: see text] We report here that the C(2)-symmetric diol 2,6-bis(1-hydroxyethyl)pyridine (2) can effect chiral-catalyzed reduction of 2,6-diacetylpyridine (1) and produce more of the diol (2) with the same configuration in an enantiomerically enriched form. The two carbonyl functionalities of (1) are reduced in 90% conversion to produce the enantio-enriched C(2)-symmetric diol (40% ee, 47% de) using zinc trifluoromethanesulfonate and a catalytic amount of the chiral C(2)-symmetric diol (2).     

Formal Umpolung Addition of Phosphites to 2-Azaaryl Ketones under Chiral Brønsted Base Catalysis: Enantioselective Protonation Utilizing [1,2]-Phospha-Brook Rearrangement

The formal enantioselective umpolung addition of dialkyl phosphites to 2-azaaryl ketones was developed under Brønsted base catalysis. The reaction involves the enantioselective protonation of the transient α-oxygenated (2-azaaryl)methyl anion generated through the 1,2-addition of the anion of dialkyl phosphite to the 2-azaaryl ketone and the subsequent [1,2]-phospha-Brook rearrangement. A chiral bis(guanidino)iminophosphorane organosuperbase efficiently catalyzed the reaction to provide enantio-enriched phosphates in high yields with good to high enantioselectivities. This is a rare example of the catalytic enantioselective protonation of transient carbanions other than enolates, constructing a trisubstituted stereogenic center α to 2-azaarenes.