Preparation and diastereoselective methylation of enantiopure (S)-4-(1-phenylethyl)-1,4-oxazin-2-ones

Abstract

Enantiomerically pure 1,4-oxazin-2-ones (4aS,8aS,1'S)-5, (4aR,8aR,1'S)-5, (5S,1'S)-6, (6R,1'S)-7, and (5S,6R,1'S)-8 were synthesized from the corresponding β-aminoalcohols in the presence of glyoxal, in good yields (65-86 %). These 1,4-oxazin-2-ones were methylated to afford the corresponding alkylated derivatives (3R,4aS,8aS,1'S)-9, (3S,4aR,8aR,1'S)-9, (3R,5S,1'S)-10, (3S,5S,6R,1'S)-12 in moderate yields (25-60 %), and low to excellent diastereoselectivities (up to ca. 100 %). A reasonable interpretation of the experimental results was reached by molecular modeling studies at the AM1 semiempirical level.

Microwave-assisted regioselective ring opening of non-activated aziridines by lithium aluminium hydride

“…b-Amino alcohols are applied extensively in organic chemistry as building blocks in designing natural and biologically active substances, 33a,34-44 and their chiral versions are also used in catalytic asymmetric synthesis. 31, 45 In the next part, 2-aminopropan-1-ols 6 were shown to be good substrates for the construction of 5-methylmorpholin-2-ones, 46 which are known as useful substrates for the synthesis of biologically relevant compounds. 47,48 Thus, 2-(arylmethylamino)propan-1-ols 6 were dissolved in THF and treated with three equiv of glyoxal.…”

“…The reaction showed high stereoselectivity since no diastereomers were detected in the crude 1 H NMR spectra, which is in accordance with previously reported analogous condensation reactions. 46…”

Selective Synthesis of cis- and trans-2-(Methyl/phenyl)-3-(trifluoromethyl)aziridines and Their Regio- and Stereospecific Ring Opening

“…With this method in hand, the synthetic potential of amino alcohols 8c and 9c and amino ethers 10c and 11c was further evaluated (Scheme ). In that respect, trans - and cis -4-benzyl-6-phenyl-5-(trifluoromethyl)morpholin-2-ones 14 and 15 were prepared starting from syn - and anti -2-benzylamino-3,3,3-trifluoro-1-phenylpropan-1-ols 8c and 9c upon treatment with 3 equiv of glyoxal in THF under reflux . The relative stereochemistry as established in morpholinones 14 and 15 can be considered as an indirect proof for the observed stereoselectivity in the S N 2 ring opening of the aziridine substrates 5 and 7 .…”

Chiral 1,2-Amino Alcohols and 1,2-Diamines Derived from Cyclohexene Oxide: Recent Applications in Asymmetric Synthesis

“…Enantiomerically pure 1,4-oxazin-2-ones 51 and 52 were prepared in good yields by the condensation of glyoxal and the corresponding cyclic 1,2-amino alcohols ent-6 and ent-7. 27 These 1,4-oxazin-2-ones were metallated with lithium diisopropylamide (LDA) and alkylated with methyl iodide to afford the corresponding alkylated derivatives 53 and 54 in 80% and 60% yield, respectively, and with excellent diastereoselectivities (Scheme 14). The assignment of the absolute configuration of the new stereo- d The absolute configuration of 1-phenyl-1-propanol was assigned from the sign of the specific optical rotation and from the elution order in HPLC analysis on a Chiracel OD stationary phase column.…”