The Preparation and Intramolecular Radical Cyclisation Reactions of Chiral Oxime Ethers

Abstract

O éter-oxima quiral 2 e o éster-oxima 4 foram preparados para alquilação e esterificação da oxina 1. Hidroxiamina racêmica 6 e a hidroxiamina 10 foram sintetisadas a partir de N-hidroxipucanimida e o álcool correspondente na presença de di etil azodicarboxilato, e os dois produtos convertidos nos éteres-oximas 7 e 11 respectivamente. As reações de ciclização radicalar intramoleculares desses éteres e ésteres-oxima foram estudadas; a formação das alquil hidróxi-aminas 3, 8 e 12 foi observada nas reações bem sucedidas.Chiral oxime ether 2 and Oxime ester 4 have been prepared by alkylation and esterification of the oxime 1. Racemic hydroxylamine 6 and chiral hydroxylamine 10 have been synthesised from N-hydroxysuccinimide and the corresponding alcohol in the presence of diethylazodicarboxylate, the two products were converted into the oxime ethers 7 and 11 respectively. The intramolecular radical cyclisation reactions of these oxime ethers and esters has been studied, successful reaction was observed to produce alkyl hydroxylamines 3, 8 and 12.

Control of Asymmetry in the Radical Addition Approach to Chiral Amine Synthesis

“…At that time, oxime ethers were the most commonly explored C=N radical acceptors. [22,23,24] We considered that linking an amino or amido substituent to the C=N nitrogen atom could afford the same reactivity enhancement seen in oxime ethers, and would also provide opportunities for superior rotamer control needed for stereoselectivity. Both activation and stereocontrol would be achieved through one removable N -substituent on the imine, and the substituents on the carbon of the C=N bond would then be freed from those roles, offering potential for broader scope.…”

Asymmetric Methods for Radical Addition to Imino Compounds

“…Stereocontrol has been imparted through the substituent on the imino carbon, as exemplified by camphorsultam 4 (Figure 2.2b). Attempts to use chiral O-substituents on oximes for stereocontrol have been ineffective, presumably due to poor rotamer control [8,9].…”

“…Various radical precursors and acceptors may be employed with high enantioselectivity (Table 2. 9). Isopropyl additions to electron-rich and electron-deficient aromatic hydrazones 66b and 66c were all highly enantioselective, as were additions of various radicals, including chloromethyl, to 66a (entries [1][2][3][4][5][6].…”