Chiral Imines Research Articles

(2S)-2-[(2S*,5R*,6R*)-5,6-Dimethoxy-5,6-dimethyl-1,4-dioxan-2-yl]-1-[(S)-1,1-dimethylethylsulfonyl]aziridine

The reaction of a sulfur ylide with a chiral non-racemic sulfinyl imine afforded the desired aziridine in excellent yield and subsequent oxidation of the sulfinyl moiety dissolved in anhydrous dichloro­methane using a 75% aqueous solution of 3-chloro­per­oxy­benzoic acid afforded the title compound, C14H27NO6S. The configuration of the newly formed stereogenic center at the point of attachment of the 1,4-dioxane ring to the aziridine ring is S. The configurations of the pre-existing sites 2-, 5-, and 6-positions of the 1,4-dioxane ring prior to reaction of sulfinyl imine with the sulfur ylide are S, R, and R, respectively. The C—N bond lengths of the aziridine are 1.478 (2) and 1.486 (2) Å.

Preparation of stereodefined homoallylic amines from the reductive cross-coupling of allylic alcohols with imines.

Regio-, diastereo-, and enantioselective coupling reactions between imines and allylic alcohols have been developed. These coupling reactions deliver complex homoallylic amine products through a convergent C-C bond forming process that does not proceed through intermediate allylic organometallic reagents. In general, convergent coupling, by exposure of an allylic alkoxide to a preformed Ti-imine complex, occurs with allylic transposition in a predictable and stereocontrolled manner. While simple diastereoselection in these reactions is high, delivering anti-products with ≥20:1 selectivity, the organometallic transformation described is compatible with a diverse range of functionality and substrates (including aliphatic and aromatic imines, allylic silanes, trisubstituted alkenes, vinyl- and aryl halides, trifluoromethyl groups, thioethers, and aromatic heterocycles). Alkene geometry of the products is a complex function of the allylic alcohol structure and is consistent with a mechanistic proposal based on syn-carbometalation followed by syn-elimination by way of a boat-like transition state geometry. Single asymmetric coupling reactions provide a means to translate the stereochemical information of the allylic alcohol to the homoallylic amine or to control diastereoselection in the coupling reactions of achiral allylic alcohols with chiral imines. Double asymmetric coupling reactions are also described that afford a unique means to control stereoselection in these complex convergent coupling processes. Finally, empirical models are proposed that are consistent with the observed stereochemical course of these coupling reactions en route to chiral homoallylic amines possessing di- or trisubstituted alkenes and anti- or syn- relative stereochemistry at the allylic and homoallylic positions.

ChemInform Abstract: Diastereoselective Addition of Di‐(trimethylsilyl)phosphite to Chiral N‐(R)‐α‐Methylbenzyl and N‐(1‐Methoxycarbonyl‐iso‐pentyl) Schiff Bases of Various Aldehydes.

AbstractThe addition of bis(trimethylsilyl)phosphite, generated in situ by the reaction of diethyl phosphite with bromotrimethylsilane, to two groups of imines is performed, the chiral Schiff bases (I) and imines (III).

Total Syntheses of the Thiopeptides Amythiamicin C and D

The thiopeptides amythiamicin C and D were synthesized by employing amide bond formation, a Stille cross-coupling reaction, and two Negishi cross-coupling reactions as key transformations. The central 2,3,6-trisubstituted pyridine ring of the target compounds was introduced as a 2,6-dibromo-3-iodopyridine, which was selectively metalated at the 3-position and connected to the complete Southern fragment of the amythiamicins by a Negishi cross-coupling. For the synthesis of amythiamicin C, this step was followed by a Negishi cross-coupling at C-6 of the pyridine core. Subsequent attachment of the Eastern fragment was achieved by amide bond formation and macrolactam ring closure by a Stille cross-coupling at C-2. The Eastern bithiazole fragment of the amythiamins was constructed also by regioselective metalation and cross-coupling reactions. The pivotal step involved the diastereoselective addition of 4-bromothiazole-2-magnesium bromide to a chiral sulfinyl imine. For the synthesis of amythiamicin D, the order of cross-coupling at C-6, amide bond formation, and cross-coupling at C-2 was changed. The amide bond formation to the Eastern fragment was performed first and it was subsequently attempted to close the macrolactam by an intramolecular regioselective Stille cross-coupling at C-2. Despite the low regioselectivity of this reaction it paved the way to the immediate completion of the amythiamicin D synthesis when followed by a Negishi cross-coupling at C-6 with 2-zincated methyl thiazole-5-carboxylate.

A modular, efficient, and stereoselective synthesis of substituted piperidin-4-ols.

A modular, efficient, and stereoselective synthesis of substituted piperidin-4-ols.

Domino Imino-Aldol−Aza-Michael Reaction: One-Pot Diastereo- and Enantioselective Synthesis of Piperidines

Addition of α-arylmethylidene- or α-alkylidene-β-keto ester enolate to N-activated aldimines via the imino aldol pathway followed by intramolecular aza-Michael reaction in a domino fashion has been developed, and a highly diastereoselective route to substituted piperidines is reported. Enantiopure piperidines are synthesized from chiral sulfinyl imines. Formation and the observed stereoselectivity of the products have been rationalized by mechanistic and computational studies.

ChemInform Abstract: Chiral Ketone and Iminium Catalysts for Olefin Epoxidation

AbstractReview: 159 refs.

Asymmetric hydrophosphylation of chiral N-phosphonyl imines provides an efficient approach to chiral α-amino phosphonates.

Chiral N-phosphonylimines were found to react with lithium phosphites to provide various substituted chiral α-amino phosphonates in excellent yields (94-97%) and diastereoselectivities (93:7-99:1). The types of bases utilized for generating the nucleophile are crucial for the effectiveness of asymmetric induction. In addition, N,N-isopropyl group on chiral N-phosphonylimine auxilliary was proven to be superior to other protecting groups in controlling diastereoselectivity. The absolute configuration was unambiguously determined by converting a chiral α-amino phosphonate into its authentic N-Cbz derivative.

Diastereoselective addition of lithium enolate of γ-substituted α-diazoacetoacetate to N-sulfinyl imines

Highly diastereoselective addition of lithium enolate of γ-substituted α-diazoacetoacetate to chiral N-sulfinyl imines has been developed. The addition products were further subjected to photo-induced Wolff rearrangement or Rh(II)-catalyzed intramolecular N-H insertion to afford chiral 4,5-disubstituted 2-oxo and 3-oxo pyrrolidines, respectively.

ChemInform Abstract: Asymmetric Michael Addition of Chiral Imines to Phenylvinylsulfone: Preparation of Key Chiral Building Blocks for the Synthesis of Aspidosperma and Hunteria Alkaloids.

Abstract Addition of chiral imine 8 to phenylvinylsulfone 9 led, after hydrolytic work-up to adduct 11 (91 % stereoselectivity). This derivative has been converted into target cyclopentanones 14 and 16 .

ChemInform Abstract: Novel Synthesis of Optically Active Lactones from 4-Thianone.

Enantioslective synthesis (>92% e.e.) of quaternary carbon centers through Michael-type alkylation of chiral imines of 3-alkyl-4-thianones with methyl acrylate and successive diastereoselective synthesis of optically active lactones are described

ChemInform Abstract: Asymmetric Synthesis of Bicyclic Amino Acid Derivatives by Aza-Diels- Alder Reactions in Aqueous Solution.

Derivatives 7–10 and 13–16 of methyl and ethyl 2-azabicyclo[2.2.1]heptane-3-carboxylates are synthesized by Aza-Diels-Alder reactions of chiral iminium ions, formed in situ from glyoxylic acid and chiral amines, with cyclopentadiene. Whereas the heterodienophiles derived from phenylglycinol and esters of sterically more demanding amino acids fail to undergo asymmetric cycloadditions, with alanine methyl ester and (R)-1-phenylethylamine hydrochoride the cycloadducts are formed in yields of 15 and 52%, respectively, reaching de values of up to 90:10 for the exo isomers.

ChemInform Abstract: Reversal of Diastereofacial Selectivity in the Addition Reaction of Organometallics to Chiral Imines.

It was observed that diastereofacial selectivity in the addition reaction of organometallics to the chiral imines derived from (R)-2-methoxy-1-phenylethylamine was regulated under appropriate conditions; i. e., organolithium and organocerium reagents added from the re-face of the chiral imines selectively, while organocopper reagents attacked from the si-face. The utility of the present method was demonstrated in the enantioselective synthesis of solenopsin A.

ChemInform Abstract: A Stereodivergent Construction of β-Lactam Skeletons via Condensation of Ester Enolates and a Chiral Imine.

Abstract Diastereofacial selectivity in an addition reaction of ester enolates to a chiral imine with 1,3-dioxolane, derived from ( S,S )-1,4-dimethoxy-2,3-butanediol as a chiral auxiliary, could be fully regulated by the appropriate selection of metal enolates used. Addition of the lithium enolates provided (4 S )-β-lactams, while the corresponding (4 R )-β-lactams were obtained by the condensation of titanium enolates with the chiral imine.

ChemInform Abstract: Highly Diastereoselective Synthesis of β-Lactams by Addition of Titanium Enolates of 2-Pyridyl Thioesters to Chiral Imines.

Abstract Addition of titanium enolates of 2-pyridyl thioesters to chiral imines derived from alkoxy aldehydes occurs with good diastereofacial control, and opens a simple access to important carbapenem antibiotics.

ChemInform Abstract: A Stereoselective Synthesis of the (2R,3S)- and (2S,3R)-3-Amino-2- hydroxybutyric Acid Derivatives, the Key Components of a Renin Inhibitor and Bestatin.

Abstract The title synthesis was achieved by featuring the [2+2]-cycloaddition reaction of benzyloxyketene with a chiral imine derived from methyl (R)- or (S)-mandelate, alcoholysis of the formed 3,4-cis disubstituted β-lactam under acidic conditions, and reductive removal obtained by the [2+2]-cycloaddition reaction employing achiral and chiral imines derived from benzylamine, p-anisidine, di-panisylmethylamine, and (S)-l-phenylethylamine were also reported. Stereoselectivity of the [2+2]-cycloaddition reaction could be explained by the initial formation of a zwitter-ionic intermediate and its subsequent conrotatory ring closure.

ChemInform Abstract: Novel Asymmetric Synthesis of β-Lactams with 3-(1′-Hydroxyethyl) Substituents: Boron Reagent Mediated Aldol Reaction of Chiral Imines and Silyl Ketene Acetals Derived from 3-Hydroxybutyrate.

Abstract An asymmetric reaction of chiral imines with silyl ketene acetals, prepared from (3R)-hydroxybutyrate, mediated by a boron reagent is described. The method successfully affords β-amino esters with high diastereoselectivity, which can be converted to optically pure β-lactams. This result indicated that a formal total synthesis of (+)-thienamycin is achieved by a simple and practical procedure.

ChemInform Abstract: A New Asymmetric Bridging Annulation Reaction Involving the Intramolecular Michael Addition of Chiral Imines to Enoates.

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ChemInform Abstract: Carbon versus Sulfur Addition of Nucleophiles to Sulfines: The Case of Amines.

Abstract Reaction of dithioester sulfines 4 with amines leads to thioamides 5 . Sulfine 7 , obtained from (−)-thiocamphor, reacts with primary amines at room temperature to afford chiral imines 8 . Carbophilic addition, instead of thiophilic addition, has thus been evidenced.

Chiral N-phosphoryl imines: design, synthesis and direct asymmetric addition reactions with diketones and diesters

Chiral N-phosphoryl imines derived from ( S)-BINOL have been designed and synthesized in good to excellent chemical yields. These N-phosphoryl imines were found to react with diketones smoothly without the use of any bases. They can also serve as electrophiles for the reaction with diethyl malonate in the presence of potassium carbonate. Good yields (62%—quant) and excellent diastereoselectivities (up to 99:1 dr) have been achieved for 10 examples.