Catalyst-directed diastereoselectivity in hydrogenative couplings of acetylene to α-chiral aldehydes: Formal synthesis of all eight L-hexoses

Article abstract of DOI:10.1021/ol8018874

(Chemical Equation Presented) Hydrogenative coupling of acetylene to α-chiral aldehydes 1a-4a using enantiomeric rhodium catalysts ligated by (S)-MeO-BIPHEP and (R)-MeO-BIPHEP delivers the diastereomeric products of carbonyl-(Z)-buladienylation 1b-4b and 1c-4c, respectively, with good to excellent levels of catalyst directed diastereofacial selectivity. Diastereomeric L-glyceraldehyde acetonide adducts 1b and 1c were converted to the four isomeric enoates 6b, 8b, 6c, and 8c, representing a formal synthesis of all eight L-hexoses.

Full text of DOI:10.1021/ol8018874

ORGANIC
LETTERS
2008
Vol. 10, No. 18
4133-4135
Catalyst-Directed Diastereoselectivity in
Hydrogenative Couplings of Acetylene
to r-Chiral Aldehydes: Formal Synthesis
of All Eight L-Hexoses
Soo Bong Han, Jong Rock Kong, and Michael J. Krische*
UniVersity of Texas at Austin, Department of Chemistry and Biochemistry,
Austin, Texas 78712
mkrische@mail.utexas.edu
Received August 12, 2008
ABSTRACT
Hydrogenative coupling of acetylene to r-chiral aldehydes 1a-4a using enantiomeric rhodium catalysts ligated by (S)-MeO-BIPHEP and (R)-
MeO-BIPHEP delivers the diastereomeric products of carbonyl-(Z)-butadienylation 1b-4b and 1c-4c, respectively, with good to excellent
levels of catalyst directed diastereofacial selectivity. Diastereomeric L-glyceraldehyde acetonide adducts 1b and 1c were converted to the four
isomeric enoates 6b, 8b, 6c, and 8c, representing a formal synthesis of all eight L-hexoses.
The broad role of carbohydrates in diverse biological
processes evokes a persistent need for efficient synthetic
strategies toward natural and unnatural monosaccharides.1
Beginning with the synthesis of glucose, fructose, and
mannose from glyceraldehyde reported by Emil Fischer
(1890),2 numerous protocols for the synthesis and intercon-
version of monosaccharides have appeared.1 However, nearly
a century elapsed before the first enantioselective de novo
synthesis of a monosaccharide was reported by Sharpless
and Masamune (1983), who prepared all eight L-hexoses
through asymmetric epoxidation.3 Subsequently, elegant
syntheses of various hexose stereoisomers were disclosed
based upon catalytic enantioselective alkene dihydroxyla-
tion,4 catalytic enantioselective Payne rearrangement,5 and
catalytic enantioselective aldol addition.6
Here, using catalytic enantioselective hydrogenative C-C
couplings of acetylene recently developed in our labora-
tory,7,8 we report a concise formal synthesis of all eight
L-hexoses through serial catalyst-directed diastereofacial
selection, the sequential use of transformations wherein the
(3) For monosaccharide synthesis employing alkene enantioselective
epoxidation, see: Ko, S. Y.; Lee, A. W. M.; Masamune, S.; Reed, L. A.,
III; Sharpless, K. B.; Walker, F. J. Science 1983, 949. Also see ref 9a.
(4) For monosaccharide synthesis employing enantioselective alkene
dihydroxylation, see: (a) Harris, J. M.; Keranen, M. D.; O’Doherty, G. A.
J. Org. Chem. 1999, 64, 2982. (b) Takeuchi, M.; Taniguchi, T.; Ogasawara,
K. Synthesis 1999, 341. (c) Harris, J. M.; Keranen, M. D.; Nguyen, H.;
Young, V. G.; O’Doherty, G. A. Carbohydr. Res. 2000, 328, 17. (d) Ahmed,
Md. M.; Berry, B. P.; Hunter, T. J.; Tomcik, D. J.; O’Doherty, G. A. Org.
Lett. 2005, 7, 745. (e) Ermolenka, L.; Sasaki, N. A. J. Org. Chem. 2006,
71, 693.
(1) For selected reviews encompassing de noVo synthetic approaches
to monosaccharides, see: (a) Zamoiski, A.; Banaszek, A.; Grynkiewicz, G.
AdV. Carbohydr. Chem. Biochem. 1982, 40, 1. (b) Hudlicky, T.; Entwistle,
D. A.; Pitzer, K. K.; Thorpe, A. J. Chem. ReV. 1996, 96, 1195. (c) Gijsen,
H. J. M.; Qiao, L.; Fitz, W.; Wong, C.-H. Chem. ReV. 1996, 96, 443. (d)
Vogel, P. In Glycoscience; Fraser-Reid, B. O., Tatsuta, K., Thiem, J., Eds.;
Springer-Verlag: Berlin, 2001; Vol. II, Chapter 4.4, p 1023.
(5) For monosaccharide synthesis employing enantioselective Payne
rearrangement, see: Covell, D. J.; Vermeulen, N. A.; Labenz, N. A.; White,
M. C. Angew. Chem., Int. Ed. 2006, 45, 8217.
(6) For monosaccharide synthesis employing enantioselective organo-
catalyzed aldol addition, see: (a) Northrup, A. B.; MacMillan, D. W. C.
Science 2004, 305, 1752. (b) Enders, D.; Grondal, C. Angew. Chem., Int.
Ed. 2005, 44, 1210.
(2) (a) Fischer, E. Ber. Dtsch. Chem. Ges. 1890, 23, 370. (b) Fischer,
E. Ber. Dtsch. Chem. Ges. 1890, 23, 799.
10.1021/ol8018874 CCC: $40.75
Published on Web 08/26/2008
2008 American Chemical Society

stereochemical bias of an enantiomeric catalyst overrides the
diastereofacial bias of a chiral nonracemic substrate.9 Ad-
ditionally, catalyst-directed diastereofacial selection in hy-
drogenative couplings of acetylene to R-chiral aldehydes
1a-4a is described. In each case, the stereochemical bias
of the catalyst was found to override the inherent diastereo-
facial bias of the R-chiral aldehyde.
Table 1. Catalyst-Directed Diastereofacial Selection in
Hydrogenative Couplings of Acetylene to R-Chiral Aldehydes
Initial studies focused on catalyst-directed stereoinduction
in the hydrogenative coupling of acetylene to L-glyceralde-
hyde 1a. Under previously disclosed conditions using the
achiral ligand BIPHEP,7 an equimolar distribution of dia-
stereomers 1b and 1c is formed. This absence of substrate-
directed diastereofacial selectivity suggested the feasibility
of catalyst-directed diastereofacial selection. Indeed, employ-
ing a chiral rhodium catalyst ligated by (S)-MeO-BIPHEP,
a g 20:1 diastereomeric ratio of adducts 1b and 1c is
obtained, as determined by 1H NMR. Using the enantiomeric
rhodium catalyst ligated by (R)-MeO-BIPHEP, a 1:7 dia-
stereomeric ratio of adducts 1b and 1c is obtained, represent-
ing an inversion in diastereofacial selectivity (Table 1, entry
1).
Based on these results, catalyst-directed diastereofacial
selection was explored in hydrogenative couplings of acety-
lene to aldehydes 2a-4a using enantiomeric rhodium catalysts
ligated by (S)-MeO-BIPHEP and (R)-MeO-BIPHEP. For
each aldehyde, good to excellent levels of catalyst-directed
stereoinduction are observed in both the matched and
mismatched cases. For R-alkoxy aldehydes 1a and 2a and
N-Boc-L-alaninal 3a, anti-Felkin-Anh addition represents the
matched mode of C-C coupling. In the case of N-Boc-L-
phenylalaninal 4a, equivalent levels of diastereofacial se-
lectivity are observed in additions employing enantiomeric
rhodium catalysts. To corroborate the relative stereochemical
assignment of adducts 1b, 2c, 3b, and 4b, the diene side
chain of these materials was exhaustively hydrogenated under
the conditions of iridium catalysis10 to furnish the corre-
sponding n-butyl adducts, which were correlated to authentic
samples.11
To showcase the utility of this methodology, the L-
glyceraldehyde acetonide adducts 1b and 1c were trans-
formed to cis-enoates 6b and 6c and trans-enoates 8b and
8c, representing a formal synthesis of all eight L-hexoses
(Scheme 1). Oxidative cleavage of diene termini of 1b and
a Cited yields are of isolated material. Best results are obtained using
an apparatus in which mixtures of hydrogen and acetylene are delivered
from a gas bag via cannula. See Supporting Information for detailed
experimental procedures. b Reaction was performed at 4 °C.
(7) For hydrogen-mediated couplings of acetylene to carbonyl com-
pounds and imines, see: (a) Kong, J.-R.; Krische, M. J. J. Am. Chem. Soc.
2006, 128, 16040. (b) Skucas, E.; Kong, J.-R.; Krische, M. J. J. Am. Chem.
Soc. 2007, 129, 7242.
1c using the Johnson-Lemieux protocol12 delivers cis-enals
5b and 5c, respectively. Under the oxidative cleavage
(8) For selected reviews of hydrogenative C-C coupling, see: (a) Ngai,
M.-Y.; Kong, J.-R.; Krische, M. J. J. Org. Chem. 2007, 72, 1063. (b) Iida,
H.; Krische, M. J. Top. Curr. Chem. 2007, 279, 77. (c) Skucas, E.; Ngai,
M.-Y.; Komanduri, V.; Krische, M. J. Acc. Chem. Res. 2007, 40, 1394.
(9) For selected examples of catalyst directed diastereofacial selection,
see: (a) Minami, N.; Ko, S. S.; Kishi, Y. J. Am. Chem. Soc. 1982, 104,
1109. (b) Kobayashi, S.; Ohtsubo, A.; Mukaiyama, T. Chem. Lett. 1991,
831. (c) Hammadi, A.; Nuzillard, J. M.; Poulin, J. C; Kagan, H. B.
Tetrahedron: Asymmetry 1992, 3, 1247. (d) Doyle, M. P.; Kalinin, A. V.;
Ene, D. G. J. Am. Chem. Soc. 1996, 118, 8837. (e) Trost, B. M.; Calkins,
T. L.; Oertelt, C.; Zambrano, J. Tetrahedron Lett. 1998, 39, 1713. (f)
Balskus, E.; E. P.; Jacobsen, E. N. Science 2007, 317, 1736. Also, see ref
3.
(11) O-Benzyl derivative of adduct 1b: (a) Ito, M.; Kibayashi, C.
Tetrahedron 1991, 45, 9329. Adduct 2c: (b) Fujita, M.; Hiyama, T. J. Org.
Chem. 1988, 53, 5415. Adduct 3b: (c) Reetz, M. T.; Rolfing, K.; Greibenow,
N. Tetrahedron Lett. 1994, 35, 1969. Adduct 4b: (d) Barrow, J. C.; Coburn,
C. A.; Nantermet, P. G.; Selnick, H. G.; Stachel, S. J.; Stanton, M. G.;
Stauffer, S. R.; Zhuang, L.; Davis, J. R. International Patent WO 2005/
065195, 2005.
(12) For Johnson-Lemieux reaction of conjugated dienes, see: (a) Sakya,
S. M.; Suarez-Contreras, M.; Dirlam, J. P.; O’Connell, T. N.; Hayashi, S. F.;
Santoro, S. L.; Kamicker, B. J.; George, D. M.; Ziegler, C. B. Bioorg. Med.
Chem. Lett. 2001, 11, 2751. (b) Cho, C.-W.; Krische, M. J. Org. Lett. 2006,
8, 891.
(10) For exhaustive hydrogenation of conjugated dienes catalyzed by
iridium, see: Cui, X.; Burgess, K. J. Am. Chem. Soc. 2003, 125, 14212,
and references therein.
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Org. Lett., Vol. 10, No. 18, 2008

Scheme 1
.
Conversion of D-Glyceraldehyde Adducts 1b and 1c to Isomeric Enoates 6b, 8c and 8b, 8c Representing a Formal Synthesis
of All Eight L-Hexoses via Serial Catalyst-Directed Diastereofacial Selectiona
aCited yields are of isolated material.
conditions, olefin isomerization to form the corresponding
trans-enals was not detected by H NMR. Exposure of cis-
In summary, we report catalyst-directed diastereoselectivity
in the hydrogenative coupling of acetylene to aldehydes
1a-4a. Further, through sequential catalyst-directed diaste-
reoselective hydrogenative carbonyl-(Z)-butadienylation-ole-
fin asymmetric dihydroxylation, a concise formal synthesis
of all eight L-hexoses is achieved from L-glyceraldehyde
acetonide 1a. These studies demonstrate the utility of serial
catalyst-directed diastereofacial selection as a means for the
controlled preparation of contiguous stereochemical arrays.
1
enals 5b and 5c to manganese oxide in the presence of
sodium cyanide in methanol provides the methyl cis-enoates
6b and 6c, respectively. The stereochemical integrity of the
cis-olefin moieties of 6b and 6c is retained in the presence
of cyanide, a nucleophilic catalyst. The corresponding ethyl
trans-enoates 8b and 8c were prepared in a similar fashion.
Exposure of cis-enals 5b and 5c to manganese oxide in the
presence of sodium cyanide in ethanol provides the ethyl
cis-enoates 7b and 7c, respectively. Exposure of 7b and 7c
to trimethylphosphine in dilute butanol results in formation
of the corresponding ethyl trans-enoates 8b and 8c.
Acknowledgment. Acknowledgment is made to the Welch
Foundation, the NIH-NIGMS (RO1-GM069445) and the
ACS-GCI Pharmaceutical Roundtable for partial support of
this research. Oliver Briel of Umicore is thanked for the kind
donation of [Rh(cod)2]BARF.
As reported by Sasaki,4e Sharpless asymmetric dihydroxy-
lation of the diastereomeric methyl cis-enoates 6b and 6c
delivers diols 9a, 9b, 9e, and 9f, which have been trans-
formed to L-talose, L-gulose, L-mannose and L-allose, re-
spectively. Sharpless asymmetric dihydroxylation of the
diastereomeric ethyl trans-enoates 8b and 8c delivers diols
9c, 9d, 9g, and 9h, which have been transformed to L-idose,
L-galactose, L-altrose, and L-glucose, respectively. Diaste-
reofacial selectivities obtained using the indicated pseudoe-
nantiomeric osmium-based catalysts are indicated explicitly
for the convenience of the reader.
Supporting Information Available: Experimental pro-
cedures and tabulated spectral data and scanned images of
1H and 13C NMR spectra for all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL8018874
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