Download PDF
Synlett 2006(12): 1895-1898  
DOI: 10.1055/s-2006-947361
LETTER
© Georg Thieme Verlag Stuttgart · New York

New Stereoselective Approach to 1,2,3-Triols: Application to a Straight forward Access to Polyoxamic Acid Array

Jérémie Boyer, Yves Allenbach, Xavier Ariza*, Jordi Garcia*, Yohan Georges, Mar Vicente
Departament de Química Orgànica, Fac. Química, Universitat de Barcelona, C/ Martí i Franquès 1-11, 08028-Barcelona, Catalonia, Spain
Fax: +34(93)3397878; e-Mail: jordigarciagomez@ub.edu;
Further Information

Publication History

Received 14 April 2006
Publication Date:
24 July 2006 (online)

    Permissions and Reprints All articles of this category

Abstract

An efficient approach to alk-4-yne-1,2,3,6-tetraols is described by stereoselective addition of terminal 2-alkyn-1-yl ­esters to Ley’s butane-2,3-diacetal-protected glyceraldehyde. The application of this methodology to a convenient synthesis of a (-)-polyoxamic acid derivative is disclosed herein.

Key words

stereoselective synthesis - alkynes - natural products - addition reactions - palladium

9

As far as the reactivity of aldehyde 7 is concerned, the only reported data of addition of nucleophiles were found in ref. 8a where it was stated that: ‘preliminary studies concerned with the addition of organomagnesium reagents to aldehyde 7 indicated that the syn/anti selectivity of addition is similar to that observed with dispiroketalaldehyde 8.’

10

Synthesis of ( R , R , R , R )-4-Hydroxy-4-(5,6-dimethoxy-5,6-dimethyl-1,4-dioxan-2-yl)but-2-ynyl Benzoate ( 9a).
Zn(OTf)2 was previously activated by heating under vacuum for 15 min. A slurry mixture of dry Zn(OTf)2 (1.590 g, 4.29 mmol) and (-)-N-methylephedrine (0.784 g, 4.28 mmol) in toluene (5 mL) was heated for 30 min at 50 °C. Then, Et3N (0.65 mL, 4.66 mmol) was added and the mixture was stirred at 50 °C until the formation of a biphasic system (2.5 h). After cooling down to r.t., propargyl benzoate (0.632 g, 3.95 mmol) was added and the mixture was further stirred for
5 min. Then, aldehyde 7 (0.950 g, 4.66 mmol) was added dropwise (ca. 5-10 min) at r.t. The reaction was monitored by TLC and, after completion (3.5 h), the reaction was quenched with 5 mL of a sat. solution of NH4Cl. The mixture was extracted with Et2O (30 mL) and EtOAc (2 × 30 mL). The combined organic layers were dried over Na2SO4. After filtration and evaporation of the solvent, the residue was purified by column chromatography on silica gel (hexane-EtOAc, 75:25) to afford pure 9a (1.366 g, 3.75 mmol, 95% yield) as colorless oil; [α]D 20 -120 (c 0.5, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 1.29 (s, 3 H), 1.31 (s, 3 H), 2.40 (s, 1 H), 3.26 (s, 3 H), 3.28 (s, 3 H), 3.63 (m, 1 H), 3.98 (m, 1 H), 4.35 (m, 1 H), 4.95 (d, J = 2.0 Hz, 2 H), 7.45 (m, 2 H), 7.56 (m, 1 H), 8.04 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 17.7, 17.9, 48.3, 48.4, 52.7, 60.1, 62.5, 70.5, 80.7, 83.8, 98.2, 99.7, 128.7. 129.6, 130.0, 133.6, 165.9. IR (NaCl): 3438, 2940, 2833, 1726, 1260 cm-1. HRMS (ESI+): m/z calcd for C19H24NaO7 [M + Na]+: 387.1408; found: 387.1414.

12

It is noteworthy that reactions of aldehyde 2 with nucleophilic reagents predominantly give the anti-isomer. A delicate balance of α-coordination (pro syn) and β- or α,β-coordination (both pro anti) is probably involved, leading to a broad range of selectivities depending of the reagent and experimental conditions: see ref. 5, pp. 456-458.

21

Synthesis of (2 R ,3 R ,4 R )-(+)-3-Hydroxy-4-hydroxy-methyl-2-tosylaminobutyrolactone ( 12).
To a solution of 15 (256 mg, 0.56 mmol) in THF (12 mL), 5 mL of 6 M LiOH were added. The mixture was then heated to reflux for 3 h. After cooling down to r.t., the mixture was acidified with 0.2 M HCl to pH 2. This solution was then extracted with CH2Cl2 (3 × 10 mL) and EtOAc (1 × 10 mL). The organic layers were then dried over anhyd MgSO4, filtrated and concentrated under reduced pressure. The crude was dissolved in THF (40 mL) and 2 M HCl (10 mL) and the mixture was heated for 2.5 h at 60 °C. After cooling down, the mixture was extracted with CH2Cl2 (3 × 30 mL) and EtOAc (1 × 20 mL). The combined organic layer was dried over MgSO4. After filtration and evaporation of solvent, the residue was purified by column chromatography on silica gel (CH2Cl2-MeOH, 95:5) to afford pure lactone 12 (106 mg, 0.35 mmol, 63% yield); mp 167-168 °C; [α]D 20 +26.1 (c 1.0, MeOH). 1H NMR (400 MHz, CDCl3): δ = 2.32 (s, 3 H), 3.75 (m, 2 H), 4.30 (m, 2 H), 4.36 (m, 1 H), 7.25 (dd, J = 7.4, 1.8 Hz, 2 H), 7.70 (dd, J = 7.4, 1.8 Hz, 2 H). 13C NMR (100.6 MHz, CDCl3): δ = 24.3, 62.9, 63.2, 79.9, 84.6, 131.0, 133.3, 142.8, 147.5, 177.4. IR (KBr): 3487, 3292, 2935, 1781, 1598, 1453, 1331, 1094, 922, 814, 664 cm-1. HRMS (FAB+): m/z calcd for C12H16NO6S [M + 1]+: 302.0698; found: 302.0697.