F. L. Merchan

Synthesis of N-Benzyl Nitrones

Abstract A general procedure for the synthesis of twenty-seven chiral and achiral N-benzyl nitrones 1 is described.

Totally stereocontrolled synthesis of α,β-diamino acids by addition of Grignard reagents to nitrones derived from l-serine

Abstract The asymmetric synthesis of protected (2R,3S)- and (2R,3R)-3-substituted 2,3-α-amino acids is reported. The key step in the synthesis of these compounds is the diastereoselective addition of Grignard reagents to α-amino nitrones derived from l -serine. Total stereocontrol of the addition step is achieved by changing the protecting groups in the starting material. The predominant selectivity in each case can be reasonably interpreted in terms of steric effects of the substituents.

Stereocontrol by diethylaluminum chloride in the addition of 2-lithiofuran and N-methyl-2-lithioimidazole to α-alkoxy nitrones. Total synthesis of 5-O-carbamoylpolyoxamic acid

Abstract The addition of the title metalated heterocycles 1 to the nitrone 2 derived from D -glyceraldehyde acetonide leads to the corresponding syn-adducts as major products (ds 88–96 %) while the reaction in the presence of Et 2 AlCl leads to anti isomers (ds 79–95 %); the synthesis of 5-O-carbamoylpolyoxamic acid from 4-O-benzyl-2,3-O-isopropylidene-L-threose via the nitrone-furan adduct is described

1,3-Dipolar cycloaddition of C-(2-thiazolyl)nitrones to chiral acrylates. Synthesis of enantiopure α-amino-2-alkylthiazoles and 5-formylpyrrolidin-2-ones

Abstract The 1,3-dipolar cycloaddition of thiazolyl nitrones with chiral acrylates has been studied. The use of the Oppolzers camphor sultam as chiral inductor provided isoxazolidines with excellent regio- and diastereoselectivities and good asymmetric induction. The cycloadducts were converted into homochiral α-amino-2-alkylthiazoles and 5-(2-thiazolyl)-3-hydroxy-2-pyrrolidinones. The latter compounds were precursors of highly functionalized pyrrolidines by the aldehyde unmasking from the thiazole ring and subsequent reactions of the formyl group.

Direct vinylation and ethynylation of nitrones. Stereodivergent synthesis of allyl and propargyl amines

Abstract The addition of vinyl and ethynyl organometallic reagents to the nitrone derived from D-glyceraldehyde affords allyl and propargyl hydroxylamines which are easily converted into the corresponding allyl and propargyl amines. The stereoselectivity of the addition step can be controlled by the presence (or absence) of diethyl aluminium chloride.

AN IMPROVED SYNTHESIS OF KETONITRONES

Abstract A general procedure for the synthesis of ketonitrones 2 starting from the corresponding ketones is described.

Lewis acid stereocontrolled additions of a silyl ketene acetal to 2,3-di-O-isopropylidene-d-glyceraldehyde nitrones. Synthesis of l-isoxazolidinyl nucleosides

The reaction of O -methyl- O - tert -butyldimethylsilyl ketene acetal with N -benzyl and N -methyl-2,3- O -isopropylidene- d -glyceraldehyde nitrones in the presence of boron trifluoride etherate afforded the corresponding isoxazolidin-5-ones in excellent yields and anti -selectivities. The obtained compounds were used as key intermediates for the synthesis of isoxazolidinyl nucleosides of the l -series.

Diastereoselective nucleophilic addition of acetylide to N-benzyl-2, nitrone (BIGN). Stereodivergent synthesis of β-hydroxy-α-(hydroxyamino)- and β-hydroxy-α-amino acids

Abstract The stereocontrolled nucleophilic addition of lithium trimethylsilyl acetylide to the N-benzyl nitrone (BIGN) derived from 2,3-O- isopropylidene- d -glyceraldehyde , followed by oxidative cleavage of the ensuing propargyl hydroxylamines resulted in an efficient stereodivergent synthesis of fully protected epimeric N-hydroxy α-amino esters 8 and 13 as well as the corresponding α-amino esters 9 and 14.

Stereoselective aminohomologation of chiral α-alkoxy aldehydes via thiazole addition to nitrones. Application to the synthesis of N-acetyl-D-mannosamine

Abstract The addition of 2-lithiothiazole to nitrones derived from d -glyceraldehyde and d -arabinose affords anti-adducts from which α-amino aldehydes are revealed by thiazole-to-formyl deblocking. The methodology provides a new synthesis of N-acetyl d -mannosamine and d -mannosamine hydrochloride.

Stereoselective grignard reactions to α-amino nitrones. Synthesis of optically active α-aminohydroxylamines and 1,2-diamines

Abstract α-Aminohydroxylamines are formed stereoselectively from the nucleophilic addition of phenylmagnesium bromide to α-amino nitrones. In contrast, the addition of methylmagnesium bromide occurs in a stereorandom fashion. Nevertheless it is possible to achieve a complete syn selectivity by diprotecting the α-amino group in the starting nitrone. Hydrogenation of the obtained α-amino hydroxylamines followed by deprotection of the tert-butoxycarbonyl group affords optically active 1,2-diamines.