1. Organocatalytic Chiral Oxygenations: anti 1,2-Diols from
α-Oxyaldehydes and α,β,-Trioxygenation of Enals
Gayan A. Abeykoon, Shreyosree Chatterjee and Jason S. Chen
Department of Chemistry, Iowa State University, Ames, Iowa, 50010
Abstract
anti 1,2-Diols were prepared by enantioselective α-oxygenation of aldehydes catalyzed by salts of chiral
imidazolidinones using stoichiometric TEMPO followed by organomagnesium or –lithium addition. Excellent
yields and diastereoselectivities were observed regardless of the branched/unbranched nature or hybridization
of the carbon nucleophile. Subjecting an enal to the above α-oxygenation condition led to the first ever α,β,-
trioxygenation of enals. Moderate yields and enantiomeric ratios were observed when a tryptophan-derived
imidazolidinone catalyst in fluorinated aromatic solvents was used. Initial incorporation of TEMPO at  position
was followed by rapid racemization and reversible conjugate addition of water. Finally, α-incorporation of
TEMPO set three chiral centers with double dynamic kinetic resolution to form the α,β,-trioxyaldehyde.
α,β,-Trioxygenation of Enals
• Chiral oxygenations using organocatalysis
• Organocascade reactions
• Catalysis of chiral imidazolidinones
Mismatch in catalytic modes
• What if an enal?
• Discovery of first ever α,β,-Trioxygenation of Enals
• Troubleshooting and optimization of trioxygenation5
• Mechanistic insight5
Dynamic kinetic resolution
12.5% from (R)-A
+
52% from major enantiomer of B with (R) configuration at -position
64.5% combined yields of compounds with (R) configuration at -position
anti-1,2-Diols
• Sharpless Dihydroxylation
• syn 1,2-diols: excellent selectivity from trans alkenes
• anti 1,2-diols: modest selectivity from cis alkenes (major limitation)
• Alternative methods for anti-1,2-Diols
• Published reactions of α-oxyaldehydes to get 1,2-diols1
Stereochemical oddity
• Determination of relative stereochemical outcome of Grignard addition to α-
oxyaldehydes2
Corrected the stereochemical outcome of Grignard addition to α-oxyaldehydes to be anti
Table 1:Tunning the Diastereoselectivity of Grignard addition to α-oxyaldehydes
• anti 1,2-diol synthesis varying the carbon nucleophile2
Grignard Solvent Temp (C) dr Yield %
BuMgCl E2O 0 4:1 60
BuMgCl THF 0 6:1 70
BuMgCl THF -78 10:1 86
BuLi THF -78 6:1 81
BuLi hexanes -78 12:1 84
excellent
diastereoselectivity
Amine Solvent Yield % dr er
Acetone 78 (57) 4.1:1 61:39
THF 39 9.0:1 64:39
DMSO 0 ND ND
CHCl3 0 ND ND
PhMe 42 5.5:1 73:27
PhCF3 69 (52) 5.0:1 71:29
Pentafluoro
benzene
66 (59) >20:1 70:30
PhCF3 45 (36) 6.4:1 84:16
Pentafluro
benzene
59 (51) 8.9:1 85:15
Conclusions
• Developed a method to access anti 1,2-diols with high diastereomeric ratio
• Discovery of the first ever catalytic, enantioselective α,β,-trifunctionalization of enals with moderate ee
• Development of mechanistic insight on the novel trioxygenation.
References
1. Simonovich, S. P.; Van Humbeck, J. F.; MacMillan, D. W. C. Chem. Sci. 2012, 3, 58.
2. Abeykoon, G. A.; Chatterjee, S.; Chen, J. S. Org. Lett. 2014, 16, 3248.
3. Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W.C. J. Am. Chem. Soc. 2000, 122, 4243.
4. Chen, J.S.; Abeykoon G. A. Org. Lett. 2015, 17, 6050.
5. Ho, X.-H.; Jung, W.-J.; Shyam, P. K.; Jang, H.-Y. Catal. Sci.Technol. 2014, 4, 1914.
6. Fought, E. L.; Chatterjee, S.; Windus, T. L.; Chen, J. S. J. Org. Chem. 2015, 80, 9967.
Funding
• National Science Foundation