Ayako Toda

Stereoselective Synthesis of Chiral Amino Allenes by Organocopper-Mediated anti-SN2′-Substitution Reaction of Chiral Ethynylaziridines

Abstract Chiral N-protected amino allenes have been synthesized from 3-alkyl-2-ethynylaziridines via organocopper-mediated reactions. Treatment of enantiomerically pure (2R,3S)-2,3-trans-3-alkyl-2-ethynylaziridines with RCu(CN)M (M=Li or MgX) in THF at −78°C affords exclusively the expected (S,S)-amino allenes in high yields in a regio- and stereoselective manner. On the other hand, (2S,3S)-2,3-cis-3-alkyl-2-ethynylaziridines give stereoisomeric (S,R)-amino allenes in comparable high yields.

SYNTHESIS OF CHIRAL AMINO ALLENES VIA AN ORGANOCYANOCUPRATE-MEDIATED RING-OPENING REACTION OF ENANTIOPURE ETHYNYLAZIRIDINES

Amino allenes have been synthesized from 2-ethynylaziridines via organocopper-mediated reactions. Whereas treatment of enantiomerically pure (2 R ,3 S )-2,3- trans -3-alkyl-2-ethynylaziridines with RCu(CN)M (M = Li or MgX) yield exclusively (S,S) -allenylamines in high yields, isomeric (2 S ,3 S )-2,3- cis -3-alkyl-2-ethynylaziridines afford (S,R) -allenylamines in comparable high yields.

Regio- and stereoselectivity in reactions of 2,3-cis- and trans-3-alkyl-2-vinylaziridines with organocopper reagents: Importance of 2,3-cis-stereochemistry in controlling selectivity

Abstract By treatment with organocopper reagents, N -activated 2,3- cis -3-alkyl-2-vinylaziridines produced exclusively ( E )-allyl amines in high yields, presumably via an anti -S N 2′ reaction pathway. On the other hand, under otherwise identical conditions, N -activated 2,3- trans -3-alkyl-2-vinylaziridines gave an 85-96:15-4 mixture of ( E )- and ( Z )-allyl amines. In reactions of certain N -activated2,3- trans -3-alkyl-2-vinylaziridines S N 2 reaction products were obtained in only 2–3% yield.

PALLADIUM-CATALYZED REGIO- AND STEREOSELECTIVE SYNTHESIS OF N-PROTECTED 2,4-DIALKYLATED AZACYCLOBUTANES FROM AMINO ALLENES

Abstract Palladium-catalyzed reaction of N-arylsulfonyl-1-alkyl-3,4-dienylamines with an aryl iodide in the presence of potassium carbonate in DMF at around 70°C affords most predominantly the 2,4-cis-disubstituted azacyclobutanes bearing an aryl group on the double bond in good yields.

A convenient synthesis of activated enantiomerically pure 2-ethynylaziridines

Abstract 2,3-cis- and 2,3-trans-N-Arylsulfonyl-2-ethynylaziridines with high enantiomeric purity have been synthesized. N-Protected amino aldehydes synthesized from natural α-amino acids were successively treated with Ph3PC(Br)CO2Me, DIBAL, MsCl–Et3N, NaH in DMSO, and tert-BuOK in THF to yield 2-ethynylaziridines in good to high yields.

Sterically congested chiral activated aziridines: Synthesis of both 2,3-cis- and 2,3-trans-2-alkenyl-3-alkylaziridines from common intermediates

Whereas treatment of the allylic mesylates of N -protected 2-alkyl-4-amino-( E )-2-alken-1-ols with sodium hydride in DMF yields exclusively the corresponding 2,3- trans -2-alkenyl-3-alkylaziridines, exposure of the methyl carbonates of N -protected 2-alkyl-4-amino-( E )-2-alken-1-ols to Pd(PPh 3 ) 4 (5–20 mol%) in THF or 1,4-dioxane affords predominantly the corresponding 2,3- cis -2-alkenyl-3-alkylaziridines. These reactions can be used to synthesize either of two diastereomers from single common intermediates.

Novel synthesis of chiral terminal allenes via palladium(0)-catalyzed reduction of mesylates of 2-bromoalk-2-en-1-ols bearing a protected amino group, using diethylzinc

Abstract A novel palladium(0)-catalyzed synthetic route to a series of chiral terminal allenes bearing an N -protected amino alkyl group has been developed. The palladium(0)-catalyzed reaction of mesylates of 2-bromoalk-2-en-1-ols bearing an amino functionality, with diethylzinc affords the corresponding terminal allenes in good yields. Both ( E )- and ( Z )-bromomesylates can equally be used for the present reaction, yielding the desired allenes in comparable yields.

Convenient syntheses of chiral 3-substituted 2-ethynylaziridines

Two convenient methods for the synthesis of chiral 2-ethynylaziridines from natural α-amino acids are described. Sodium hydride-promoted aziridination of mesylates of 4-arylsulfonylamino-2-bromoalk-2-en-1-ols yields trans-2-(1-bromovinyl)aziridines in a highly stereoselective manner, and subsequent dehydrobromination of the aziridines by potassium tert-butoxide gives separable stereoisomeric mixtures of trans- and cis-2-ethynylaziridines in enantiomerically pure forms (>98% ee). Simple synthesis of 2-ethynylaziridines with high optical purities (91–98% ee) from chiral amino alcohols bearing an ethynyl group under Mitsunobu conditions is also presented.