Aminals as substrates for sulfur ylides: a synthesis of functionalized aziridines and N-heterocycles

Sulfur ylides stabilized by Ar, vinyl, or amide groups react with five-membered-ring tert-butylsulfinyl aminals to give functionalized chiral, nonracemic aziridines in high yield and with good selectivities (up to 15:1 trans:cis, up to >95:5 trans dr, always >95:5 cis dr). The intermediate aziridines can be converted into pyrrolidines or piperidines depending on the reaction conditions.     

Cyclic sulfur ylides derived from Gleason-type chiral auxiliaries for the asymmetric synthesis of epoxy amides

Gleason-type chiral auxiliaries were used for the synthesis of a novel class of sulfonium salts, obtained via methylation of the sulfide with Meerwein's salt. The salts were reacted with aldehydes under basic conditions to provide epoxy amides, which were reduced to their corresponding epoxy alcohols in excellent enantiomeric excesses. Interestingly, it was feasible to synthesize both enantiomeric epoxy alcohols depending on which of the sulfonium salts, prepared from L-amino acids (6 and 9 from L-valine or 15 and 16 from L-serine) was employed.     

Synthesis of chiral sultams and their application as chiral auxiliaries in an asymmetric Diels–Alder reaction

A number of bicyclic chiral sultams were synthesized based on 1,3-dipolar cycloaddition reactions of nitrile oxides and nitrones with prop-1-ene-1,3-sultone. The corresponding N-enoyl sultams were prepared by acylation. Their relative effectiveness as new chiral auxiliaries in asymmetric synthesis was evaluated for the asymmetric Diels–Alder reactions with cyclopentadiene. Good chemical yield and excellent endo selectivity were observed. The relationship between the structure and their effectiveness in promoting asymmetric induction of the synthetic chiral sultams was investigated.     

Menthone and p-menthyl-3-carboxaldehyde as chiral auxiliaries

Two chiral auxiliaries and the role they play in the preparation of chiral carbonyl compounds and heterocyclic compounds are presented. Key reactions include S(N)2' displacements, Mitsunobu with hydrazoic acid, and 3,3-sigmatropic rearrangements. One of the auxiliaries serves many functions and is removed either by oxidative cleavage or RCM reaction.     

Facile preparation and functionalization of chiral stabilized ylides from common chiral auxiliaries using triphenyl- phosphoranylideneketene (the Bestmann ylide) and their use in Wittig reactions

Camphor-derived lactams and other related chiral controllers have been found to react with the Bestmann ylide (triphenylphosphoranylideneketene) upon heating in toluene. The resulting parent ylides provide convenient access to a structurally diverse set of chiral stabilized ylides via functionalization. The utility of these chiral ylides for Wittig reactions has been briefly investigated and the effects of alpha-substitution noted.     

1-O-vinyl glycosides via Tebbe olefination, their use as chiral auxiliaries and monomers

A series of anomerically pure 1-O-formyl glycosides 1 was prepared and converted into the corresponding 1-O-vinyl glycosides 2 by Tebbe olefination. The unsubstituted vinyl glycosides were obtained as anomerically pure compounds in good yields, and the method of preparation was compatible with the presence of a variety of functional groups. Remarkably, the anomeric formate group was regioselectively converted into the corresponding olefin in the presence of acetate and benzoate protecting groups. With the perspective to use the 1-O-vinyl glycosides as monomers for the preparation of glycosylated poly(vinyl alcohol) derivatives with controlled tacticity, their scope as chiral auxiliaries for a stereodifferentiation in addition reactions to the olefin function was investigated by using the [2+2] cycloaddition to dichloroketene as a model reaction. In particular, vinyl 2,3,4,6-tetra-O-benzoyl-alpha-d-mannopyranoside (2i) exhibited excellent diastereoselectivity. Finally, the 1-O-vinyl glycosides were successfully subjected to radical homopolymerization in bulk or used as electron-rich comonomers in radical copolymerizations with maleic anhydride, yielding alternating, glycosylated poly(vinyl alcohol-alt-maleic anhydride).     

Asymmetric reduction of azirines; a new route to chiral aziridines

The first enantioselective reduction of aromatic 2H-azirines yields aziridines in up to 70% ee, using the aminoalcohol-[RuCl2(p-cymene)]2 catalyzed asymmetric transfer hydrogenation reaction.     

Simple camphor derivatives as chiral auxiliaries for asymmetric conjugate addition

The chiral enoates, $\text{4}$, readily available in two simple steps from (+)-camphor, Undergo asymmetric conjugate addition with the Gilman reagent LiBu₂Cu. Chemical yields are high (70–90%) and in the case of the naphthyl-substituted enoate $\text{4e}$ excellent diastereoselectivity (95% $\text{d.e.}$) is observed. 3-Methyl-heptan-l-ol of correspondingly high enantiomeric purity is obtained by reduction of the conjugate adduct with lithium aluminium hydride.     

Synthesis of optically pure arylsilylcarbinols and their use as chiral auxiliaries in oxacarbenium ion reactions

A family of arylsilylcarbinols was synthesized and investigated as chiral auxiliaries for oxacarbenium ion reactions. The optically pure arylsilylcarbinols were prepared using Noyori's transfer hydrogenation catalyst 11. The transfer hydrogenation shows very good enantioselectivities and turnover efficiency for the aryl silyl ketones and is the method of choice for preparing these optically pure alcohols. The diastereoselective addition of allyltrimethylsilane to an in situ generated oxacarbenium ion was explored using Marko's conditions. The selectivity for a representative aliphatic aldehyde was very good, but the selectivity was significantly reduced with unsaturated and aromatic aldehydes. The range of selectivities with different auxiliaries was narrow, and the most practical auxiliary is the phenylsilylcarbinol 2.     

Guanidines as a nitrogen source for direct conversion of epoxides to aziridines

Direct conversion of epoxides to aziridines was achieved with guanidines as a nitrogen source. Stereochemical inversion at the chiral centers of epoxides was observed without loss of optical purity.     

Conformationally rigid chiral [4+2]cycloadduct-based 2-oxazolidinones as new auxiliaries

Newly introduced enantiomerically pure [4+2]cycloadduct-based 2-oxazolidinones which are conformationally fixed by bicyclo[2.2.2] and [2.2.1] ring systems, serve well as exellent chiral auxiliaries in the Evans' asymmetric strategy.     

Application of meso-hydrobenzoin-derived chiral auxiliaries for the stereoselective synthesis of highly substituted pyrrolidines by 1,3-dipolar cycloaddition of azomethine ylides

The metal-catalyzed stereoselective 1,3-dipolar cycloaddition of azomethine ylides and acrylates using recyclable meso-hydrobenzoin-derived chiral auxiliaries is described. Cleavage of the auxiliary leads to highly substituted pyrrolidines in up to 87% enantiomeric excess.     

Regioselective ring-opening of aziridines with potassium thiocyanate and thiols using sulfated zirconia as a heterogeneous recyclable catalyst

Ring-opening of aziridines with potassium thiocyanate and thiols has efficiently been carried out at room temperature in the presence of sulfated zirconia to give the corresponding β-aminothiocyanates and β-aminosulfides, respectively, in high yields within 2 h and with high regioselectivity. The catalyst, a solid acid, functions under heterogeneous conditions.     

Orthoacylimines: a new class of chiral auxiliaries for nucleophilic addition of organolithium reagents to imines

A new class of orthoacylimine-derived chiral auxiliaries has been synthesized and tested in the nucleophilic addition of organolithium reagents to imines. The precursors can be prepared by an aza-Wittig reaction between the corresponding orthoacyl azide and a variety of aldehydes in the presence of trialkylphosphines. The nucleophilic addition of organolithium reagents led to the addition products in good yields and with good to excellent diastereoselectivities (from 85:15 to 99:1). The chiral, nonracemic secondary amines could be readily obtained under mild hydrolytic condition. Furthermore, the chiral auxiliary can be recovered in quantitative yield and reconverted to the starting orthoacyl azide precursor. This method was applied to the synthesis of (S)-t-leucine.     

Diastereoselective conjugate addition with acetals,oxazolidines and imidazolidines as chiral auxiliaries

Organocopper reagents undergo highly diastereoselective conjugate addition on cinnamates bearing a chiral oxazolidine or imidazolidine ring.     

Synthesis of new C2 symmetrical dibenzospirodiamide and dibenzospirodiamine as potential chiral auxiliaries and building blocks of ionophores

2,8‐Diazadibenzo[c,i]spiro[5,5]undecan‐1,7‐dione 3 are synthesized via reaction of malonic ester with 2‐nitrobenzyl bromide, followed by reduction‐cyclization in 86% overall yield. 2,8‐Diazadibenzo[c,i]‐spiro[5,5]undecane 4 was obtained by reduction of 3 with LiAIH₄ in 90% yield. N‐Alkylation of 3 with various alkylating reagents is studied.     

Chiral 1,3-diamines from a lithiated isocyanide and chiral aziridines

Reaction of lithiated 4-methoxybenzylisocyanide with homochiral amino acid derived N-tosyl- and N-diphenylphosphinoylaziridines proceeds diastereoselectively to provide N-protected 3-isocyanoamines. Separation of the diastereomers of these adducts or the corresponding formamides, and subsequent transformations, lead to 1,3-diamines and their monoprotected and differentially bisprotected derivatives.     

Dendritic chiral auxiliaries on silica: a new heterogeneous catalyst for enantioselective addition of diethylzinc to benzaldehyde

This article reports the first work on the use of silica supported dendritic chiral auxiliaries for the enantioselective addition of diethylzinc to benzaldehyde: the control of dendrimer propagation on the silica surface is of prime importance to obtain enhanced conversion, selectivity, and enantioselectivity.     

Asymmetric synthesis of 3-butylphthalide using isomannide and isosorbide as chiral auxiliaries

A new approach for asymmetric syntheses of (S) and (R)-3-n-butylphthalide (NBP) is presented.The diastereoselective addition of dibutylzinic to aromatic aldehyde 10 or 11 generated from isomannide-or isosorbide-derived chiral auxiliary afforded S-NBP or R-NBP in high optical yields.     

A fluorous chiral dirhodium(II) complex as a recyclable asymmetric catalyst

[reaction: see text] The chiral fluorous complex tetrakis-dirhodium(II)-(S)-N-(n-perfluorooctylsulfonyl)prolinate has been prepared and used as a catalyst in homogeneous or fluorous biphasic fashion. The catalyst displays good chemo- and enantioselectivity in intermolecular cyclopropanation and C-H bond activation reactions. The catalyst can be simply and thoroughly separated from the reaction mixture and is recyclable.