Tetrabutylammonium Cyanide
Catalyzed Aldol Self-Condensation of Ley’s Butane-2,3-diacetal
(BDA) Protected Glyceraldehydes. Synthesis of Two New BDA-Protected
Sugar-Derived Scaffolds

Pilar Areces; Esther Carrasco; Mark E. Light; Joaquín Plumet

doi:10.1055/s-0029-1217798

LETTER

Tetrabutylammonium Cyanide Catalyzed Aldol Self-Condensation of Ley’s Butane-2,3-diacetal (BDA) Protected Glyceraldehydes. Synthesis of Two New BDA-Protected Sugar-Derived Scaffolds

Pilar Areces*^a, Esther Carrasco^a, Mark E. Light^b, Joaquín Plumet*^c
^a Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Extremadura, 06071 Badajoz, Spain
Fax: +34(924)271149; e-Mail: pareces@unex.es; e-Mail: esthcar@unex.es;
^b Department of Chemistry, , University of Southampton, Highfield, Southampton, SO17 1BJ, UK
^c Departamento de Química Orgánica, Facultad de Química, Universidad Complutense, 28040 Madrid, Spain
Fax: +34(91)3944103; e-Mail: plumety@quim.ucm.es;

Abstract

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Abstract

The self-aldol reaction of Ley’s protected BDA-(R)- and (S)-glyceraldehydes is described for the first time. The reaction is catalyzed by tetrabutylammonium cyanide.

Key words

Aldol reaction - Ley’s protected glyceraldehydes - catalysis - tetrabutylammonium cyanide

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References

References and Notes

For illustrative reviews on the use of 1,2-diacetals in organic synthesis, see:

<A NAME="RG17809ST-1A">1a</A> Ley SV. Polara A. J. Org. Chem. 2007, 72: 5993

<A NAME="RG17809ST-1B">1b</A> Lence E. Castedo L. González-Bello C. Chem. Soc. Rev. 2008, 37: 1689

<A NAME="RG17809ST-2">2</A> Ley SV. Michel P. Synthesis 2004, 147

Both enantiomers of glyceraldehyde acetonide are prone to racemization and rapid polymerization, see:

<A NAME="RG17809ST-3A">3a</A> Hubscherlen J. Specklin L. Higelin J. Org. Synth. 1995, 72: 1

<A NAME="RG17809ST-3B">3b</A> Schmid CR. Bryant JD. Org. Synth. 1995, 72: 6

<A NAME="RG17809ST-4">4</A> Knudsen KR. Stephan AP. Michael P. Ley SV. Org. Biomol. Chem. 2006, 4: 1741

<A NAME="RG17809ST-5">5</A> This compound, also known as hamamelose, is widely distributed among many plants species. Its solid-state structure has recently been analyzed by CP-MAS NMR and X-ray crystallography, see: Hricoviniová Z. Lamba D. Hricovíni M. Carbohydr. Res. 2005, 340: 455 . References associated with their natural occurrence, biological activity and synthesis may be found in this report

<A NAME="RG17809ST-6">6</A> Córdoba R. Csákÿ AG. Plumet J. ARKIVOC 2004, (iv): 94

<A NAME="RG17809ST-7">7</A> Córdoba R. Csákÿ AG. Plumet J. López-Ortiz F. Herrera A. Jiménez-Vázquez HA. Tamariz J. Tetrahedron 2004, 60: 3825

<A NAME="RG17809ST-8">8</A> Amurrio I. Córdoba R. Csákÿ AG. Plumet J. Tetrahedron 2004, 60: 10521

<A NAME="RG17809ST-9">9</A> Aljarilla A. Córdoba R. Csákÿ AG. Fernández I. López-Ortiz F. Plumet J. Ruiz-Gómez G. Eur. J. Org. Chem. 2006, 3969

These results will be disclosed and analyzed in a later publication.

General procedure: To a solution of aldehyde 1 or 2 (0.588 mmol, 1.0 equiv) in freshly distilled CH₂Cl₂ (1.2 mL) under Ar at 0 ˚C, TBACN (0.0588 mmol, 0.1 equiv) in anhydrous CH₂Cl₂ (1.2 mL) was added at 0 ˚C. After stirring at r.t. (17-22 ˚C) for the indicated reaction time (see Table [¹] ), the reaction mixture was diluted with H₂O and extracted with CH₂Cl₂ (2 × 3 mL). The organic layer was dried over MgSO₄ and the solvent was distilled in vacuo. Compound 5 was isolated from the reaction mixture by precipitation from hexane-EtOAc (3:1). Crystallization of this solid from the same mixture of solvents yielded pure 5 as a white solid. Compound 6 was isolated as a colorless oil by column chromatography from the mother liquors (SiO₂; hexane-EtOAc, 2:19).
Compound 5: mp 194-195 ˚C; [α]_D -214.9; [α]₅₇₈ -224.2; [α]₅₄₆ -253.2; [α]₄₃₆ -416.9 (c 0.54, CH₂Cl₂, 25 ˚C). ^¹H NMR (400 MHz, CDCl₃): δ = 9.65 (d, J _CHO,1 = 2.0 Hz, 1 H, CHO), 4,19 (d, J ₃ _′ _ax,3 _′ _eq = 12.0 Hz, 1 H, H-3′ax), 4.05-3.99 (m, 1 H, H-2′′), 3.91 (dd, J ₃ _′ _ax,3 _′ _eq = 11.6 Hz, J ₃ _′ _eq,CHO = 1.6 Hz, 1 H, H-3′eq), 3.73 (dd, J ₃ _′′ _eq,2 _′′ = 3.6 Hz, J ₃ _′′ _ax,3 _′′ _eq = 11.6 Hz, 1 H, H-3′′eq), 3.63 (t, J ₃ _′′ _ax,2 _′′ = J ₃ _′′ _ax,3 _′′ _eq = 11.6 Hz, 1 H, H-3′′ax), 3.42-3.37 (m, 1 H, H-1), 3.39 (s, 3 H, CH₃O), 3.37 (s, 3 H, CH₃O), 3.26 (s, 3 H, CH₃O), 3.24 (s, 3 H, CH₃O), 2.71 (d, J _1,OH = 7.6 Hz, 1 H, OH), 1.39 (s, 3 H, CH₃), 1.27 (s, 3 H, CH₃), 1.26 (s, 3 H, CH₃), 1.25 (s, 3 H, CH₃). ^¹³C NMR (100 MHz, CDCl₃): δ = 200.5 (CHO), 99.5, 99.3, 98.0, 97.7 (C-5′, C-5′′, C-6′, C-6′′), 79.4 (C-2′), 74.4 (C-1), 65.5 (C-2′′), 61.7 (C-3′), 58.7 (C-3′′), 50.3, 48.8, 48.3, 47.8 (4 × CH₃O), 17.8, 17.6, 17.5 (4 × CH₃).
X-ray crystal structure data for compound 5 have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC-626723.
Compound 6: colorless oil; [α]_D -173.9; [α]₅₇₈ -180.6; [α]₅₄₆ -204.1; [α]₄₃₆ -333.2 (c 2.5, CH₂Cl₂, 22 ˚C). ^¹H NMR (400 MHz, CDCl₃): δ = 9.64 (s, 1 H, CHO), 4.38 (d, J ₃ _′ _ax,3 _′ _eq = 12.0 Hz, 1 H, H-3′ax), 4.38-4.35 (m, 1 H, H-2′′), 3.89 (t, J ₃ _′′ _ax,3 _′′ _eq = J ₃ _′′ _ax,2 _′′ = 11.6 Hz, 1 H, H-3′′ax), 3.64 (dd, J ₃ _′ _ax,3 _′ _eq = 11.6 Hz, 1 H, H-3′eq), 3.45 (dd, J ₃ _′′ _eq,2 _′′ = 4.0 Hz, J ₃ _′′ _ax,3 _′′ _eq = 12.0 Hz, 1 H, H-3′′eq), 3.47-3.36 (m, 1 H, H-1), 3.37 (s, 3 H, CH₃O), 3.36 (s, 3 H, CH₃O), 3.26 (s, 3 H, CH₃O), 3.23 (s, 3 H, CH₃O), 2.71 (d, J _1,OH = 7.6 Hz, 1 H, OH), 1.34 (s, 3 H, CH₃), 1.27 (s, 3 H, CH₃), 1.26 (s, 3 H, CH₃), 1.25 (s, 3 H, CH₃). ^¹³C NMR (100 MHz, CDCl₃): δ = 200.6 (CHO), 99.7, 99.6, 97.9, 97.6 (C-5′, C-5′′, C-6′, C-6′′), 77.8 (C-2′), 74.5 (C-1), 63.7 (C-2′′), 61.1 (C-3′), 59.6 (C-3′′), 50.2, 48.9, 48.2, 48.0 (4 × CH₃O), 17.8, 17.7, 17.6, 17.5 (4 × CH₃).

Although reports concerning cyanide ion catalyzed aldol reactions are scarce, the first cases were reported as far back as 1892, see:

<A NAME="RG17809ST-12A">12a</A> Claisen L. Ber. Dtsch. Chem. Ges. 1892, 25: 3164

<A NAME="RG17809ST-12B">12b</A> See also: Kohn L. Monatsh. Chem. 1898, 19: 519

<A NAME="RG17809ST-12C">12c</A> Recently, the aldol reactions of aldehydes catalyzed by HCN-tetramer (‘a classic of prebiotic chemistry of HCN’) have been reported, see: Koch B. Scheizer WB. Eschenmoser A. Chem. Biodiversity 2007, 4: 541

General procedure: To a solution of aldehydes 1 or 2 (0.504 mmol, 1.0 equiv) in CH₂Cl₂ (1.0 mL) under Ar, a mixture of KCN (0.0504 mmol, 0.1 equiv) and 18-crown-6 (0.0504 mmol, 0.1 equiv) in CH₂Cl₂ (1.0 mL) was added at 0 ˚C. After stirring for 30 min at r.t., the reaction mixture was diluted in CH₂Cl₂ (5 mL), washed with H₂O and the organic layer was dried over MgSO₄. After removing the solvent in vacuo, a 1.2:1 mixture of compounds 5 and 6 was isolated in 76% overall yield.