Indene-based thiazolidinethione chiral auxiliary for propionate and acetate aldol additions

Article abstract of DOI:10.1021/ol702980p

An indene-based thiazolidinethione chiral auxiliary was prepared in two steps from trans-1-amino-2-indanol. Chlorotitanium enolates of this chiral auxiliary delivered excellent diastereoselectivities in propionate and acetate aldol additions. The chiral a

Full text of DOI:10.1021/ol702980p

ORGANIC
LETTERS
2008
Vol. 10, No. 4
617-620
Indene-Based Thiazolidinethione Chiral
Auxiliary for Propionate and Acetate
Aldol Additions
Antonio Osorio-Lozada and Horacio F. Olivo*
DiVision of Medicinal and Natural Products Chemistry, The UniVersity of Iowa,
Iowa City, Iowa 52242
horacio-oliVo@uiowa.edu
Received December 11, 2007
ABSTRACT
An indene-based thiazolidinethione chiral auxiliary was prepared in two steps from trans-1-amino-2-indanol. Chlorotitanium enolates of this
chiral auxiliary delivered excellent diastereoselectivities in propionate and acetate aldol additions. The chiral auxiliary was easily removed to
deliver several valuable functionalities.
The asymmetric aldol addition mediated by a chiral auxiliary
is one of the most commonly used reactions to form a
carbon-carbon bond and two chiral carbons adjacent to a
carbonyl group stereoselectively.1 Several methodologies and
chiral auxiliaries have been developed for this endeavor; in
particular, dibutylboron enolates of N-acyloxazolidinones
have been valuable to prepare the “Evans” syn-propionate
aldol products.2 Utilizing the same chiral auxiliary, titanium-
(IV) enolates of N-acyloxazolidinones were shown to provide
the “non-Evans” syn-propionate aldol products.3 Recent
reports by Crimmins showed that by using chlorotitanium-
(IV) enolates of N-propionate thiazolidinethiones we can
access the “Evans” syn-aldol product when adding 1 equiv of
sparteine and the “non-Evans” syn-aldol product when adding
2 equiv of the same base.4 This change in facial selectivity
is the result of switching of mechanistic pathways between
chelated and nonchelated transition states. Evans reported
the anti-aldol reaction promoted by catalytic amounts of
magnesium halide in the presence of triethylamine and
chlorotrimethylsilane.5 These conditions deliver the “Evans”
anti-aldol product when using an oxazolidinone and the
opposite aldol product when using a thiazolidinethione.
(1) (a) Arya, P.; Qin, H. Tetrahedron 2000, 56, 917-947. (b) Evans, D.
A.; Nelson, J. V.; Taber, T. R. Top. Stereochem. 1982, 13, 1-115. (c) For
a review on 1,2-amino alcohol derived chiral auxiliaries, see: Ager, D. J.;
Prakash, I.; Schaad, D. R. Chem. ReV. 1996, 96, 835-875.
(2) (a) Evans, D. A.; Bartroli, J.; Shih, T. L. Enantioselective Aldol
Condensations. 2. Erythro Selective Chiral Aldol Condensations via Boron
Enolates. J. Am. Chem. Soc. 1981, 103, 2127-2129. (b) Oppolzer, W.;
Blagg, J.; Rodriguez, I.; Walther, E. J. Am. Chem. Soc. 1990, 112, 2767-
2772. (c) Sibi, M. P.; Deshpande, P. K.; Ji, J. Tetrahedron Lett. 1995, 36,
8965-8968.
(3) . (a) Walker, M. A.; Heathcock, C. H. J. Org. Chem. 1991, 56, 5747-
5750. (b) Bonner, M. P.; Thornton, E. R. J. Am. Chem. Soc. 1991, 113,
1299-1308. (c) Yan, T.-H.; Tan, C.-W.; Lee, H.-C.; Lo, H.-C.; Huang,
T.-Y. J. Am. Chem. Soc. 1993, 115, 2613-2621.
10.1021/ol702980p CCC: $40.75
© 2008 American Chemical Society
Published on Web 01/19/2008

Chiral auxiliary driven acetate-type aldol reactions have
proven more difficult than their propionate counterpart.
N-Acetate oxazolidinones and other chiral auxiliaries did not
provide the diastereoselectivities achieved with the corre-
sponding N-propionates.6 Several methods and strategies
have been realized to solve this problem. Among them,
Nagao’s acetate aldol reaction with tin enolate of N-acetyl
thiazolidinethione delivered high diastereoselectivities.7 How-
ever, the high price and irreproducibility of the tin triflate
prompted others to investigate other Lewis acids for this aldol
reaction. The more economic titanium(IV) enolate was found
to be highly efficient.8 More sterically encumbered thiazo-
lidinethiones and oxazolidinethiones have also been prepared
to deliver higher diastereoselectivities, albeit at a higher price
for starting materials and or longer reaction sequences.9 In
this paper, we report a new thiazolidinethione analogue of
indene-based Ghosh’s oxazolidinone,10 which was easily
prepared from commercially available trans-1-amino-2-
indanol.11 The rigidity and nature of this chiral auxiliary
promised to deliver high diastereoselectivities in aldol
reactions and crystalline products.
A general procedure for the synthesis of chiral oxazolidi-
nethiones and thiazolidinethiones is to treat 1,2-aminols
derived from R-amino acids with carbon disulfide and base.12
Oxazolidinethiones are obtained preferentially when a mild
base is employed, and thiazolidinethiones can be prepared
in excellent yields when a stronger base is used instead.
However, when this latter method was applied to trans-
amino-2-indanol 1,13 thiazolidinethione 2 was obtained in
poor yield. Instead, we found that the thiazolidinethione 2
was obtained in very good yield when the trans-aminoindanol
1 was first treated with sulfuric acid, and then the crude
sulfated indanol was treated with potassium ethyl xanthate
and aqueous sodium hydroxide and the mixture heated to
75 °C for 16 h, Scheme 1.14 Using this protocol, only one
Scheme 1
purification by column chromatography was required to
obtain clean thiazolidinethione 2.
Acylation of the chiral auxiliary was accomplished in very
good yields by treating the thiazolidinethione with the
corresponding acyl chloride or by coupling with the car-
boxylic acid.15 The titanium enolate derived from N-
propionate derivative 4 was added to cinnamaldehyde to test
its diastereoselectivity using the conditions reported by
Crimmins, Scheme 2.4a Indeed, when 1 equiv of titanium
Scheme 2
(4) (a) Crimmins, M. T.; King, B. W.; Tabet, E. A. J. Am. Chem. Soc.
1997, 119, 7883-7884. (b) Crimmins, M. T.; King, B. W.; Tabet, E. A.;
Chaudhary, K. J. Org. Chem. 2001, 66, 894-902.
(5) (a) Evans, D. A.; Tedrow, J. S.; Shaw, J. T.; Downey, C. W. J. Am.
Chem. Soc. 2002, 124, 392-393. (b) Evans, D. A.; Downey, C. W.; Shaw,
J. T.; Tedrow, J. S. Org. Lett. 2002, 4, 1127-1130. (c) Evans, D. A.; Shaw,
J. T. L’actualite´ Chimique 2003, 35-38.
(6) (a) Nerz-Stormes, M.; Thornton, E. R. Tetrahedron Lett. 1986, 27,
897-900. (b) Masamune, S.; Choy, W.; Petersen, J. S.; Sita, L. R. Angew.
Chem., Int. Ed. 1985, 24, 1-30. (c) Braun, M. Angew. Chem., Int. Ed.
1987, 26, 24-37.
(7) (a) Nagao, Y. Yamada, S.; Kumagai, T.; Ochiai, M.; Fujita, E. J.
Chem. Soc., Chem. Commun. 1985, 1418-1419. (b) Nagao, Y.; Hagiwara,
Y.; Kumagai, T.; Ochiai, M.; Inoue, T.; Hashimoto, K.; Fujita, E. J. Org.
Chem. 1986, 51, 2391-2393. (c) Vela´zquez, F.; Olivo, H. F. Curr. Org.
Chem. 2002, 6, 303-340. (d) Ort´ız, A.; Sansinenea, E. J. Sulfur Chem.
2007, 28, 109-147.
(8) (a) Yan, T.-H.; Hung, A.-W.; Lee, H.-C.; Chang, C.-S.; Liu, W.-H.
J. Org. Chem. 1995, 60, 3301-3306. (b) Gonza´lez, A.; Aiguade´, J.; Urp´ı,
F.; Vilarrasa, J. Tetrahedron Lett. 1996, 37, 8949-8952. (c) Crimmins, M.
T.; Emmitte, K. A. Org. Lett. 1999, 1, 2029-2032. (d) Romero-Ortega,
M.; Colby, D. A.; Olivo, H. F. Tetrahedron Lett. 2002, 43, 6439-6441.
(e) Hodge, M. B.; Olivo, H. F. Tetrahedron 2004, 60, 9397-9403.
(9) (a) Guz, N. R.; Phillips, A. J. Org. Lett. 2002, 4, 2253-2256. (b)
Zhang, Y.; Phillips, A. J.; Sammakia, T. Org. Lett. 2004, 6, 23-25. (c)
Zhang, Y.; Sammakia, T. Org. Lett. 2004, 6, 3139-3141. (d) Crimmins,
M. T.; Shamszad, M. Org. Lett. 2007, 9, 149-152.
tetrachloride and 1 equiv of Hunig’s base were employed, a
closed transition state where both the aldehyde and the
auxiliary are coordinated to the titanium enolate delivered
the “non-Evans” syn-aldol product 5 in 92% yield (98:2 dr).
When 2.5 equiv of (-)-sparteine and 1 equiv of titanium
tetrachloride were employed, an open transition state where
the chiral auxiliary is not coordinated to the titanium enolate
(10) Ghosh, A. K.; Duong, T. T.; McKee, S. P. J. Chem. Soc., Chem.
Commun. 1992, 1673-1674.
(11) (1R,2R)-trans-1-Amino-2-indanol and (1S,2S)-trans-1-amino-2-in-
danol are available from Aldrich, catalog nos. 663336 and 663344.
(12) Delaunay, D.; Toupet, L.; Le Corre, M. J. Org. Chem. 1995, 60,
6604-6607.
(13) Kozhushkov, S. I.; Yufit, D. S.; de Meijere, A. AdV. Synth. Catal.
2005, 347, 255-265.
(14) (a) Yamada, S.; Sugaki, T.; Matsuzaki, K. J. Org. Chem. 1996, 61,
5932-5938. (b) Dewey, C. S.; Bafford, R. A. J. Org. Chem. 1965, 30,
495-500.
(15) Andrade, C. K. Z.; Rocha, R. O.; Vercillo, O. E.; Silva, W. A.;
Matos, R. A. F. Synlett 2003, 15, 2351-2352.
618
Org. Lett., Vol. 10, No. 4, 2008

delivered the “Evans” syn-aldol product 6 in 92% yield (94:6
dr). Employing 1.2 equiv of sparteine and 1.2 equiv of
N-methylpyrrolidinone, we also obtained aldol product 6
(92% yield), as reported by Crimmins.4b Using the conditions
reported by Evans for anti-aldol reaction,5 catalytic amounts
of magnesium bromide, trimethylsilyl chloride, and triethy-
lamine, the anti-aldol product 7 was isolated in 87% yield.
To confirm the relative stereochemistry of the aldol
products, compounds 5-7 were reduced with sodium boro-
hydride to the corresponding diols and treated with 2,2-
dimethoxypropane to obtain acetonides 8 and 9. Analysis
reaction mixture at -78 °C. These reaction conditions
worked very well with aliphatic, R,â-unsaturated, and
aromatic aldehydes. Yields of aldol products ranged between
90 and 98% and diastereoselectivities from 91:9 to 98:2. The
stereochemistry of the aldol products was confirmed by X-ray
crystallographic analyses of products 10b and 10i. In
addition, aldol product 10c was reduced to (+)-(R)-4-
methylpentane-1,3-diol, confirming the stereochemistry of
the product.
The versatility of the new chiral auxiliary was investigated
by the conversion of the aldol products into other functional
groups, Scheme 4. As mentioned previously, aldol product
1
of the H NMR coupling constants of acetonides 8 and 9
was valuable to establish their stereochemistry, Scheme 3.
Scheme 4
Scheme 3
The acetate aldol reaction employing N-acetylthiazolidi-
nethione 3 was investigated with different types of aldehydes,
Table 1. Following the optimized procedure reported by
Table 1. Acetate Aldol Additions of Thiazolidinethione 3
5 was reduced with sodium borohydride to diol 12. Reduction
of the TES-protected aldol product 5 with Dibal-H delivered
aldehyde 13. Hydrolysis of the aldol product 5 with lithium
hydroxide gave carboxylic acid 14. Displacement of the
thiazolidinethione auxiliary with ethanol and benzyl alcohol
mediated by DMAP was carried out smoothly under mild
conditions.16 Ammonolysis of the chiral auxiliary provided
amide 17.17 As shown with other thiazolidinethiones, the
indene-based thiazolidinethione can be easily removed to
furnish different functionalities.
In summary, we have prepared a valuable indene-based
thiazolidinethione chiral auxiliary from trans-1-amino-2-
indanol. Propionate and acetate aldol reactions with different
types of aldehydes delivered products with high diastereo-
selectivity. The chiral auxiliary of the aldol products was
removed under mild conditions to provide other function-
entry
aldehyde
yielda (%)
drb (10/11)
1
2
3
4
5
6
7
8
9
propionaldehyde
butyraldehyde
isobutyraldehyde
isovaleraldehyde
acrolein
2-methyl-2-pentenal
cinnamaldehyde
benzaldehyde
98
94
92
97
93
91
90
91
93
93:7
93:7
94:6
93:7
98:2
91:9
98:2
93:7
98:2
3-furaldehyde
a Combined yield of diastereomers after purification. b Obtained by H
NMR spectroscopy of crude reaction mixtures.
1
Crimmins,9d 1 equiv of N-acetyl thiazolidinethione 3 was
treated with 1 equiv of titanium(IV) chloride and 1 equiv of
(-)-sparteine, and 0.9 equiv of aldehyde was added to the
(16) Wu, Y.; Sun, Y.-P.; Yang, Y.-Q.; Hu, Q.; Zhang, Q. J. Org. Chem.
2004, 69, 6141-6144.
(17) Osorio-Lozada, A. Prisinzano, T.; Olivo, H. F. Tetrahedron:
Asymmetry 2004, 15, 3811-3815.
Org. Lett., Vol. 10, No. 4, 2008
619

alities in high yields. This new chiral auxiliary is more
economic than other sterically encumbered ones and should
find use in the syntheses of natural products.
also thank Drs. Nataraj Kalyanaraman and Raju Subramanian
(Amgen, Thousand Oaks, CA) for obtaining the HRMS
spectra.
Supporting Information Available: Spectroscopic data
Acknowledgment. This research was supported with
funds provided by the Center for Environmentally Beneficial
Catalysis under the National Science Foundation Engineering
Research Grant (EEC-0310689) and the ACS-GCI-PRF. We
thank Dr. Dale Swenson (University of Iowa) for obtaining
the X-ray crystal analysis of aldol products 10b and 10i. We
1
for all new compounds (2-17) and copies of H and 13C
NMR spectra. Crystallographic information (CIF) for com-
pounds 10b and 10i. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL702980P
620
Org. Lett., Vol. 10, No. 4, 2008