Highly diastereoselective synthesis of arylglycine derivatives via TFA-promoted Friedel-Crafts reactions of phenols with cyclic glyoxylate imines

Optically active α-arylglycine derivatives were synthesized by Brønsted acid (TFA)-promoted Friedel-Crafts reaction of various phenols with chiral cyclic glyoxylate imines (2a-c), followed by deprotection with Pd(OH)₂/C under H₂. The diastereoselectivities of the initially formed F-C reaction products are up to 99%.     

Highly enantioselective synthesis of 2-furanyl-hydroxyacetates from furans via the Friedel-Crafts reaction

The Friedel-Crafts reaction of alkyl glyoxylates with variously substituted furans was found to be efficiently catalyzed under simple, undemanding conditions by a 6,6'-dibromo-BINOL/Ti(IV) complex with high enantioselectivity. The reaction afforded chiral substituted 2-furanyl-hydroxyacetic acid esters, compounds of high synthetic interest, in good yield and enantiomeric excess, in most examples in the range of 90-97%.     

Highly diastereoselective radical addition to glyoxylate imines of chiral amines without additional heteroatoms

The diastereoselective addition of alkyl radicals to glyoxylate imines of α-alkylbenzylamines has been investigated and it was found that diastereoselectivity improved as the size of the alkyl group increased.     

Highly diastereoselective intramolecular Diels-Alder reaction of chiral silatrienes

New Si-chiral 2-silahexa-3,5-dienyl acrylates were prepared in six steps from dichloro(chloromethyl)methylsilane. The EtAlCl₂ catalysed intramolecular Diels-Alder reaction of these compounds gave chiral 4-sila-4a,7,8,8a-tetrahydroisochroman-1-ones in good yield. Very good diastereoselectivity was observed for a silatriene bearing a methyl and a 2-methoxyphenyl substituent on the chiral silicon atom.     

Highly diastereoselective strecker reaction of enolizable aliphatic sulfinimines

The reaction of chiral sulfinimines 1c-g derived from aliphatic aldehydes with TMSCN in the presence of CsF gave alpha-amino nitriles in high diastereoselectivity and yield. alpha,beta-Diamino acid derivatives were also obtained in high diastereoselectivity from the reaction of 2-aziridinesulfinimines 1h and 1i followed by ring-opening of the products with thiophenol. The presence of hydrogen at the alpha-position of the C=N double bond is crucial in this TMSCN addition reaction.     

Highly diastereoselective switchable enantioselective Mannich reaction of glycine derivatives with imines

Tuning of diastereoselectivity was realized in the Mannich reaction of glycine derivatives with aromatic and aliphatic N-Ts imines using CuClO4-FcPHOX ligand 4b and 4f having an MeO group at the 4-position and F atom at the 3,5-position of the phenyl ring on the P-atom respectively as catalyst, providing either anti- or syn-alpha,beta-diamino acid derivatives in high yields and in high diastereo- and enantioselectivities.     

Highly diastereoselective type-I IMDA reaction forming medium-sized macrolactones

[Structure: see text] Intramolecular Diels-Alder (IMDA) reactions of 2-pyrones containing an alkyne tether occur with remarkably high diastereofacial selectivity to provide medium-sized macrolactones. Because of the strain in the alkyne-tethered macrocyclic system, a single methyl group in the tether provides sufficient conformational bias to generate medium-sized macrocycles with unusually high selectivity.     

Asymmetric nitroaldol reaction. Synthesis of taxotere side chain and (-)-bestatin using (1R)-8-phenylmenthyl glyoxylate

The nitroaldol reaction of (1R)-8-phenylmenthyl glyoxylate (3b) with 1-nitro-1-phenylmethane (4) or with 1-nitro-2-phenylethane (13) led stereoselectively to adducts syn-2b and syn-12b, which were then transformed into the Taxotere side chain and (-)-bestatin hydrochloride in overall yields of 52% and 31%, respectively.     

Highly enantioselective Friedel-Crafts reaction of aromatic amines with ethyl glyoxylate catalyzed by chiral titanium(IV) complexes: practical synthesis of aminomandelic acid derivatives

The asymmetric Friedel-Crafts reaction of a variety of N,N-dialkylanilines with ethyl glyoxylate has been achieved by the catalysis of titanium complexes of BINOL derivatives to give corresponding ethyl esters of p-N,N-dialkylaminomandelic acids in high yields (85-99%) and good to excellent enantioselectivities (80-96.6% ee) under the optimized reaction conditions, which has added a new catalyst for this class of reactions. The reaction could also be carried out at a reduced catalyst loading (1 mol %) in gram scale, which provided a practical synthesis of enantiopure aminomandelic acid derivatives.     

Highly regio- and diastereoselective Friedel-Crafts alkylation of phenols. Synthesis of 2-hydroxymandelic esters.

Ortho-hydroxyalkylation of phenol substrates was performed via coordinative complexes of metal phenolates with chiral glyoxylates: optically active 2-hydroxymandelic esters have been obtained with good yields and very high diastereoselectivity (up to 94% d.e.).     

Synthesis of (−)-bestatin and the Taxotere® side-chain via nitroaldol reaction of (1R)-8-phenylmenthyl glyoxylate

The nitroaldol reaction of (1R)-8-phenylmenthyl glyoxylate 6 with 1-nitro-2-phenylethane or with phenylnitromethane led stereoselectively to adducts 4 and 12, which where then transformed into (−)-bestatin hydrochloride and the Taxotere® side-chain in overall yields of 31 and 52%.     

Highly diastereoselective Diels-Alder reaction of optically active ethyl 2-p-tolylsulfinylmethylenepropionate with cyclopentadiene

Stereochemistry of the Diels-Alder reaction of ethyl Z- and E-2-ptolylsulfinylmethylenepropionate with cyclopentadiene has been studied. The high diastereoselectivity was observed especially in the case of exo-cycloaddition.     

Highly diastereoselective Henry reaction of nitro compounds with chiral derivatives of glyoxylic acid

N-Glyoxyloyl-(2R)-bornane-10,2-sultam and (1R)-8-phenylmenthyl glyoxylate react stereoselectively with simple nitro compounds giving diastereoisomeric nitroalcohols with high asymmetric induction. N-Glyoxyloyl-(2R)-bornane-10,2-sultam 1a is shown to be a highly efficient chiral inducer, superior to (1R)-8-phenylmenthyl glyoxylate 1b. In all cases, the absolute (2S) configuration at the center bearing the hydroxy group and the relative syn configuration for the major diastereoisomers were determined.     

Highly functionalized dihydrofuran derivatives: Synthesis by diastereoselective intramolecular Wittig reaction

3a,8a‐Dihydroxy‐1,3,3a,8a‐tetrahydro‐ indeno[1,2‐d]imidazole‐2,8‐dione 3 reacts with dialkyl acetylenedicarboxylates in the presence of triphenylphosphine to produce some novel interesting dihydrofuran derivatives diastereoselectively. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:277–279, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20202     

Highly enantio- and diastereoselective vinylogous aldol reaction by LiCl-assisted BINOL-titanium species

The first highly enantio- and diastereoselective vinylogous aldol reaction between propionyl acetate-derived Brassard's diene and aldehydes was accomplished by titanium-lithium combined Lewis acid, affording δ-hydroxy-γ-methyl-β-methoxy acrylates. This methodology was utilized in convenient and concise construction of the polypropionate moiety in cystothiazole A and melithiazole C.     

Highly diastereoselective Diels-Alder reaction using a chiral auxiliary derived from levoglucosenone

[reaction: see text] A new chiral auxiliary derived from levoglucosenone is reported. The compound is obtained by a cycloaddition reaction with 9-methoxy methylanthracene followed by a diastereoselective reduction of the C-2 keto function. The auxiliary has been used as a chiral template in an asymmetric Diels-Alder reaction of the corresponding acrylic ester derivative with cyclopentadiene. The results showed excellent diastereomeric excess even at room temperature when the reaction was promoted by Et(2)AlCl as the Lewis acid.     

Highly efficient and diastereoselective construction of bispirooxindoles through a cascade Michael-cyclization reaction

A series of bispirooxindole derivatives have been synthesized via a cascade Michael-Cyclization reaction between isothiocyanato oxindoles and methyleneindolinones with high yields (up to 98%) and excellent diastereoselectivities (up to >95:5 dr) under mild conditions. The structure and effect on the reaction of less studied 4-substituted methyleneindolinones have also been investigated.