Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
PPh3 (1.5 equiv) Lee, S. J. et al. J. Am. Chem. Soc. 2008, 130, 466.
OH brominating agent (1.0 equiv) Br
Ph Ph
CH2Cl2, rt, 15–30 min
98% (Br3CCO2Et)
trans-2-Bromovinylboronic acid MIDA ester
99% (Br3CCOCBr3)
703478 NCH3 500 mg $120.00
C7H9BBrNO4
O O B 1 g 200.00
Tongkate, P. et al. Tetrahedron Lett. 2008, 49, 1146. O Br
FW: 261.87 O
sigma-aldrich.com
93
Edmond, walking stick in hand, wearing a light-colored straw hat and slacks and a dark
Aldrichimica Acta (ISSN 0002–5100) is a publication jacket in at least two locations. Can you find him?
of Aldrich. Aldrich is a member of the Sigma-Aldrich
Group. © 2008 Sigma-Aldrich Co. This painting is part of the Ailsa Mellon Bruce Collection at the National
Gallery of Art, Washington, DC.
Metal Complexes and Ligands for Enantioselective
Reductive Coupling
Asymmetric hydrogenation is one of the most utilized reactions to induce chirality in a molecule. It is currently widely used in industry. Krische and
co-workers have developed a new type of transformation based on the enantioselective reductive C–C bond formation mediated by hydrogen.
Utilizing a rhodium-, iridium-, or ruthenium-based complex with a variety of ligands, Krische and co-workers demonstrated the potency of this
reaction for the reductive coupling of conjugated enones, dienes, imines, enynes, and carbonyls. Aldrich is offering a series of complexes and ligands
for enantioselective reductive coupling.
H3C R2 H H
NHSO2Ar [Ir(cod)2]BARF (5 mol%) [Rh(cod)2]BARF (5 mol%)
(R)-Cl,MeO-BIPHEP (5 mol%) NSO2Ar (S)-Cl,MeO-BIPHEP (5 mol%) ArO2SHN
H3C R2
Ph3CCO2H (5 mol%) H R1 R1
R1 m-NO2PhCO2H (5 mol%)
Na2SO4 (2 eq.) Na2SO4 (2 eq.)
64-80% yield Toluene, 60 °C Toluene, 45 °C 65-86% yield
94-99% ee H2 (1 atm) 93-98% ee
H2 (1 atm)
Ngai, M.-Y. et al. J. Am. Chem. Soc. 2007, 129, 12644. Skucas, E. et al. J. Am. Chem. Soc. 2007, 129, 7242.
R
R TMS
[Rh(cod)2]OTf (5 mol%) [Rh(cod)2]OTf (5 mol%) R TMS O
R O O
(R)-(3,5-t-Bu-4-MeOPh)-MeO-BIPHEP (5 mol%) (R)-Cl,MeO-BIPHEP (5 mol%)
OEt OEt
Ph3CCO2H (5 mol%) OEt
OH DCE, 40 °C OH
DCE, 25 °C O H2 (1 atm)
70-82% yield H2 (1 atm) 71-84% yield
86-97% ee 90-94% ee
Hong, Y.-T. et al. Org. Lett. 2007, 9, 3745. Cho, C.-W.; Krische, M. J. Org. Lett. 2006, 8, 3873.
Cl
P
H3CO PPh2 H3CO PAr2 H
H3CO PPh2 P
H3CO PPh2 Ar = OCH3
H3CO PPh2 H3CO PAr2 Fe
Cl
sigma-aldrich.com
95
Haber–Bosch process,4 is used to produce over 107 metric tons catalytic process of this type, a rhodium-catalyzed reductive
of ammonia annually. Nitrogenous fertilizer obtained from the cyclization of acetylenic aldehydes mediated by silane, was
Haber–Bosch process is estimated to sustain one-third of the reported in 1994 by Ojima et al.22 In 1995, Crowe and Rachita
Earth’s population.5 The asymmetric hydrogenation of C=X π disclosed related titanium-catalyzed cyclizations mediated by
96
Scheme 2. Direct, Byproduct-Free Hydrogenative Coupling of Carbonyl allylation is employed routinely in synthetic organic
Conjugated Alkynes to Activated Carbonyl Compounds and chemistry.34 Asymmetric allylation has been achieved using
Imines Employing Cationic Rhodium Catalysts. (Ref. 27) chirally modified allyl metal reagents, 35 chiral Lewis acid
catalysts, or chiral Lewis base catalysts. 36 These methods
97
from the alcohol or aldehyde oxidation level in the absense of Scheme 5. Enantioselective Imine Vinylation via Iridium-
preformed allyl metal reagents. More recently, this asymmetric Catalyzed Hydrogenative Coupling of Unconjugated
allylation protocol has been extended to allylic alcohols and Alkynes. (Ref. 32b)
aliphatic alcohols (Scheme 11).46b
98
Formation of C–C Bonds via Catalytic Hydrogenation and Transfer Hydrogenation: Vinylation, Allylation, and Enolate Addition
OH
[Ir(cod)Cl]2 (3.75 mol %)
3 OH
R3 R Rh(cod)2OTf (5 mol %) R R
33 R1 BIPHEP (7.5 mol %) R
R1 +
2-naphthoic acid (5 mol %) R Bu4NI (10 mol %)
Y Y DCE (1 M), 65 oC
(R)-Cl,MeO-BIPHEP (5 mol %) OH
R2 R2 O H2 (1 atm), DCE, 45 oC R2 R2
R Yield 1,4:1,5
R OH
Rh(cod)2OTf (5 mol %) [Ir(cod)Cl]2 (3.75 mol %)
R O BIPHEP (7.5 mol %)
2-naphthoic acid (5 mol %) R
TsN TsN +
BIPHEP (5 mol %) R Bu4NI (10 mol %)
OH
Me O H2 (1 atm), DCE, 45 oC Me
i-PrOH (400 mol %)
PhMe (1 M), 70 oC
[Ir(cod)(BIPHEP)]BARF
O (5 mol %) OH
Me
+
R Li2CO3 (35 mol %) R RuHCl(CO)(PPh3)3
Me Me Me
DCE–EtOAc, 60 oC R1 (5 mol %)
H2 (1 atm) OH R1 OH
R2 ligand (5–15 mol %)
+
R Yield R3 3-O2NC6H4CO2H R3
(2.5 mol %) Me R2
BnOCH2 80%
4-Br-3-O2NC6H3 92% acetone (2.5 mol %)
Cbz 78% THF, 95–110 oC
6-Br-pyridin-2-yl 84%
R1 R2 R3 Yield dr
Scheme 7. Catalytic Carbonyl Addition via Iridium-Catalyzed Scheme 9. Coupling of Dienes to Alcohols or Aldehydes via
Hydrogenative Coupling of Dimethylallene. (Ref. 39) Ruthenium-Catalyzed Transfer Hydrogenation. (Ref. 42a)
99
with exceptional levels of syn-diastereoselectivity. Of note is Scheme 11. Enantioselective Carbonyl Allylation from the
the wide range of potentially “hydrogen-labile” functionality Alcohol or Aldehyde Oxidation Level via Iridium-Catalyzed
that is tolerated, thus enabling the use of substrates containing Transfer-Hydrogenative Coupling of Allyl Acetate. (Ref. 46b)
alkynes, alkenes, benzylic ethers, nitroarenes, and aryl bromides.
100
Formation of C–C Bonds via Catalytic Hydrogenation and Transfer Hydrogenation: Vinylation, Allylation, and Enolate Addition
O O (a) O OH
+
O Rh(cod)2OTf (10 mol %) R1 R 2
Rh(cod)2OTf R 1
R2
O OH (5 mol %)
O KOAc (30 mol %) Me
R
R
H2 (1 atm), DCE, 25 oC R1 R2 Yield syn:anti
n n
(4-F3CC6H4)3P (24 mol %)
Me 4-O2NC6H4 91% 16:1
Et 4-O2NC6H4 90% 28:1
n Yield syn:anti a
R 1,4 Me BnOCH2 90% 17:1
Et BnOCH2 88% 18:1
Ph 1 71% 24:1 1% Me PhC≡C 65% 8:1
Ph 2 89% 10:1 0.1% Et PhC≡C 70% 10:1
Me 2 65% 1:5 — Me PhtNCH2 95% 50:1
thien-2-yl 2 76% 19:1 2% Et PhtNCH2 97% >99:1
a
Yield of the 1,4-reduction product.
O O (a) O OH
+
R Rh(cod)2SbF 6 R
(5 mol %) Me
O Rh(cod)2OTf (10 mol %) Me Me
O OH
Me O K2CO3 (80 mol %)
Ar Me
Ar R Yield syn:anti
H2 (1 atm), DCE, 80 oC
n n
Ph3P (24 mol %) 4-O2NC6H4 82% 13:1
BnOCH2 80% 9:1
6-Br-pyridin-2-yl 94% 11:1
Ar n Yielda 1,4b PhtNCH2 85% 13:1
or alcohol oxidation level has broad implications for the field of Ed. 2009, 48, 34.
organic synthesis. These nascent reactivity modes should serve (13) For reviews encompassing the synthesis of allylic alcohols, see:
as the basis for innumerable byproduct-free alcohol–unsaturate (a) Kirk-Othmer Encyclopedia of Chemical Technology, 5th ed.;
and amine–unsaturate coupling processes. Kroschwitz, J. I., Ed.; Wiley-Interscience: Hoboken, NJ, 2004; Vol.
102
2, pp 234–249. (b) Banerjee, A. K.; Poon, P. S.; Laya, M. S.; Vera, 9065. (b) Tang, X.-Q.; Montgomery, J. J. Am. Chem. Soc. 1999,
Formation of C–C Bonds via Catalytic Hydrogenation and Transfer Hydrogenation: Vinylation, Allylation, and Enolate Addition
W. J. Russ. Chem. Rev. (Engl. Transl.) 2004, 73, 621. 121, 6098. (c) Tang, X.-Q.; Montgomery, J. J. Am. Chem. Soc. 2000,
(14) For reviews encompassing the synthesis of allylic amines, see: (a) 122, 6950. (d) Mahandru, G. M.; Liu, G.; Montgomery, J. J. Am.
Cheikh, R. B.; Chaabouni, R.; Laurent, A.; Mison, P.; Nafti, A. Chem. Soc. 2004, 126, 3698. (e) Knapp-Reed, B.; Mahandru, G. M.;
Synthesis 1983, 685. (b) Laurent, A.; Mison, P.; Nafti, A.; Cheikh, Montgomery, J. J. Am. Chem. Soc. 2005, 127, 13156.
R. B.; Chaabouni, R. J. Chem. Res. 1984, 354. (c) Johannsen, M.; (25) (a) Huang, W.-S.; Chan, J.; Jamison, T. F. Org. Lett. 2000, 2, 4221.
Jørgensen, K. A. Chem. Rev. 1998, 98, 1689. (b) Miller, K. M.; Huang, W.-S.; Jamison, T. F. J. Am. Chem. Soc.
(15) For reviews on the metal-catalyzed allylic amination and 2003, 125, 3442. (c) Miller, K. M.; Jamison, T. F. Org. Lett. 2005,
alkoxylation, see: (a) Acemoglu, L.; Williams, J. M. J. In Handbook 7, 3077.
of Organopalladium Chemistry for Organic Synthesis; Negishi, E., (26) Takai, K.; Sakamoto, S.; Isshiki, T. Org. Lett. 2003, 5, 653.
de Meijere, A., Eds.; Wiley: New York, 2002; Vol. 2, pp 1689– (27) (a) Kong, J.-R.; Ngai, M.-Y; Krische, M. J. J. Am. Chem. Soc. 2006,
1705. (b) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 128, 718. (b) Cho, C.-W.; Krische, M. J. Org. Lett. 2006, 8, 3873.
2921. (c) Trost, B. M. J. Org. Chem. 2004, 69, 5813. (d) Miyabe, (c) Hong, Y.-T.; Cho, C.-W.; Skucas, E.; Krische, M. J. Org. Lett.
H.; Takemoto, Y. Synlett 2005, 1641. (e) Takeuchi, R.; Kezuka, S. 2007, 9, 3745. (d) Komanduri, V.; Krische, M. J. J. Am. Chem. Soc.
Synthesis 2006, 3349. 2006, 128, 16448.
(16) For enantioselective catalytic additions of vinylzinc reagents (28) Kong, J.-R.; Cho, C.-W.; Krische, M. J. J. Am. Chem. Soc. 2005,
to aldehydes, see: (a) Oppolzer, W.; Radinov, R. N. Helv. Chim. 127, 11269.
Acta 1992, 75, 170. (b) Oppolzer, W.; Radinov, R. N. J. Am. Chem. (29) Kong, J.-R.; Krische, M. J. J. Am. Chem. Soc. 2006, 128, 16040.
Soc. 1993, 115, 1593. (c) Soai, K.; Takahashi, K. J. Chem. Soc., (30) Skucas, E.; Kong, J.-R.; Krische, M. J. J. Am. Chem. Soc. 2007,
Perkin Trans. 1 1994, 1257. (d) Wipf, P.; Xu, W. Tetrahedron Lett. 129, 7242.
1994, 35, 5197. (e) Oppolzer, W.; Radinov, R. N.; De Brabander, (31) Kirk-Othmer Encyclopedia of Chemical Technology, 5th ed.;
J. Tetrahedron Lett. 1995, 36, 2607. (f) Wipf, P.; Ribe, S. J. Org. Kroschwitz, J. I., Ed.; Wiley-Interscience: Hoboken, NJ, 2004; Vol.
Chem. 1998, 63, 6454. (g) Oppolzer, W.; Radinov, R. N.; El-Sayed, 1, pp 216–217.
E. J. Org. Chem. 2001, 66, 4766. (h) Dahmen, S.; Bräse, S. Org. (32) (a) Barchuk, A.; Ngai, M.-Y.; Krische, M. J. J. Am. Chem. Soc.
Lett. 2001, 3, 4119. (i) Chen, Y. K.; Lurain, A. E.; Walsh, P. J. J. 2007, 129, 8432. (b) Ngai, M.-Y.; Barchuk, A.; Krische, M. J. J. Am.
Am. Chem. Soc. 2002, 124, 12225. (j) Ji, J.-X.; Qiu, L.-Q.; Yip, C. Chem. Soc. 2007, 129, 12644.
W.; Chan, A. S. C. J. Org. Chem. 2003, 68, 1589. (k) Lurain, A. (33) Rhee, J.-U.; Krische, M. J. J. Am. Chem. Soc. 2006, 128, 10674.
E.; Walsh, P. J. J. Am. Chem. Soc. 2003, 125, 10677. (l) Ko, D.-H.; (34) For reviews on enantioselective carbonyl allylations, see: (a)
Kang, S.-W.; Kim, K. H.; Chung, Y.; Ha, D.-C. Bull. Korean Chem. Ramachandran, P. V. Aldrichimica Acta 2002, 35, 23. (b) Kennedy,
Soc. 2004, 25, 35. (m) Sprout, C. M.; Richmond, M. L.; Seto, C. T. J. W. J.; Hall, D. G. Angew. Chem., Int. Ed. 2003, 42, 4732. (c)
J. Org. Chem. 2004, 69, 6666. (n) Jeon, S.-J.; Chen, Y. K.; Walsh, P. Denmark, S. E.; Fu, J. Chem. Rev. 2003, 103, 2763. (d) Yu, C.-M.;
J. Org. Lett. 2005, 7, 1729. (o) Lauterwasser, F.; Gall, J.; Höfener, S.; Youn, J.; Jung, H.-K. Bull. Korean Chem. Soc. 2006, 27, 463. (e)
Bräse, S. Adv. Synth. Catal. 2006, 348, 2068. (p) Jeon, S.-J.; Fisher, Marek, I.; Sklute, G. Chem. Commun. 2007, 1683. (f) Hall, D. G.
E. L.; Carroll, P. J.; Walsh, P. J. J. Am. Chem. Soc. 2006, 128, 9618. Synlett 2007, 1644.
(q) Salvi, L.; Jeon, S.-J.; Fisher, E. L.; Carroll, P. J.; Walsh, P. J. J. (35) Chirally modified allyl metal reagents: (a) Herold, T.; Hoffmann,
Am. Chem. Soc. 2007, 129, 16119. (r) Wu, H.-L.; Wu, P.-Y.; Uang, R. W. Angew. Chem., Int. Ed. Engl. 1978, 17, 768. (b) Hoffmann,
B.-J. J. Org. Chem. 2007, 72, 5935. R. W.; Herold, T. Chem. Ber. 1981, 114, 375. (c) Hayashi, T.;
(17) For reviews encompassing catalytic enantioselective aldehyde Konishi, M.; Kumada, M. J. Am. Chem. Soc. 1982, 104, 4963.
vinylations using organozinc reagents, see: (a) Wipf, P.; Kendall, (d) Brown, H. C.; Jadhav, P. K. J. Am. Chem. Soc. 1983, 105,
C. Chem.—Eur. J. 2002, 8, 1778. (b) Wipf, P.; Nunes, R. L. 2092. (e) Roush, W. R.; Walts, A. E.; Hoong, L. K. J. Am. Chem.
Tetrahedron 2004, 60, 1269. Soc. 1985, 107, 8186. (f) Reetz, M. T. Pure Appl. Chem. 1988,
(18) For catalytic enantioselective ketone vinylation using organozinc 60, 1607. (g) Short, R. P.; Masamune, S. J. Am. Chem. Soc. 1989,
reagents, see: (a) Li, H.; Walsh, P. J. J. Am. Chem. Soc. 2004, 126, 111, 1892. (h) Corey, E. J.; Yu, C.-M.; Kim, S. S. J. Am. Chem.
6538. (b) Li, H.; Walsh, P. J. J. Am. Chem. Soc. 2005, 127, 8355. (c) Soc. 1989, 111, 5495. (i) Seebach, D.; Beck, A. K.; Imwinkelzied,
Jeon, S.-J.; Li, H.; García, C.; LaRochelle, L. K.; Walsh, P. J. J. Org. R.; Roggo, S.; Wonnacott, A. Helv. Chim. Acta 1987, 70, 954. (j)
Chem. 2005, 70, 448. Riediker, M.; Duthaler, R. O. Angew. Chem., Int. Ed. Engl. 1989,
(19) Schmidt, F.; Rudolph, J.; Bolm, C. Synthesis 2006, 3625. 28, 494. (k) Panek, J. S.; Yang, M. J. Am. Chem. Soc. 1991, 113,
(20) The catalyzed addition of vinylzirconocenes to imines is known, but 6594. (l) Kinnaird, J. W. A.; Ng, P. Y.; Kubota, K.; Wang, X.;
enantioselective variants have not been developed: (a) Kakuuchi, Leighton, J. L. J. Am. Chem. Soc. 2002, 124, 7920. (m) Burgos,
A.; Taguchi, T.; Hanzawa, Y. Tetrahedron Lett. 2003, 44, 923. (b) C. H.; Canales, E.; Matos, K.; Soderquist, J. A. J. Am. Chem. Soc.
Wipf, P.; Kendall, C.; Stephenson, C. R. J. J. Am. Chem. Soc. 2003, 2005, 127, 8044.
125, 761. (36) Catalytic asymmetric carbonyl allylation: (a) Costa, A. L.; Piazza,
(21) The enantioselective Ni-catalyzed alkyne, imine, and triethylborane M. G.; Tagliavini, E.; Trombini, C.; Umani-Ronchi, A. J. Am. Chem
three-component coupling has been reported, but modest Soc. 1993, 115, 7001. (b) Keck, G. E.; Tarbet, K. H.; Geraci, L. S.
selectivities (51–89% ee’s) are observed. In this method, vinylation J. Am. Chem. Soc. 1993, 115, 8467. (c) Denmark, S. E.; Coe, D.
is accompanied by ethyl transfer: Patel, S. J.; Jamison, T. F. Angew. M.; Pratt, N. E.; Griedel, B. D. J. Org. Chem. 1994, 59, 6161. (d)
Chem., Int. Ed. 2004, 43, 3941. Denmark, S. E.; Fu, J. J. Am. Chem. Soc. 2001, 123, 9488.
(22) Ojima, I.; Tzamarioudaki, M.; Tsai, C.-Y. J. Am. Chem. Soc. 1994, (37) For selected examples of reactions involving nucleophilic π-allyls,
116, 3643. see: Palladium: (a) Tabuchi, T.; Inanaga, J.; Yamaguchi, M.
VOL. 41, NO. 4 • 2008
(23) (a) Crowe, W. E.; Rachita, M. J. J. Am. Chem. Soc. 1995, 117, 6787. Tetrahedron Lett. 1986, 27, 1195. (b) Takahara, J. P.; Masuyama,
(b) For a related study, see Kablaoui, N. M.; Buchwald, S. L. J. Am. Y.; Kurusu, Y. J. Am. Chem. Soc. 1992, 114, 2577. (c) Kimura,
Chem. Soc. 1995, 117, 6785. M.; Ogawa, Y.; Shimizu, M.; Sueishi, M.; Tanaka, S.; Tamaru, Y.
(24) (a) Oblinger, E.; Montgomery, J. J. Am. Chem. Soc. 1997, 119, Tetrahedron Lett. 1998, 39, 6903. (d) Kimura, M.; Shimizu, M.;
103
Shibata, K.; Tazoe, M.; Tamaru, Y. Angew. Chem., Int. Ed. 2003, 130, 6340. (b) Kim, I. S.; Ngai, M.-Y.; Krische, M. J. J. Am. Chem.
5112. (c) Wang, L.-C.; Jang, H.-Y.; Roh, Y.; Lynch, V.; Schultz, A. Keywords: hydrogenation; transfer hydrogenation; allylic
Formation of C–C Bonds via Catalytic Hydrogenation and Transfer Hydrogenation: Vinylation, Allylation, and Enolate Addition
J.; Wang, X.; Krische, M. J. J. Am. Chem. Soc. 2002, 124, 9448. amines; aldol; allylation.
(d) Lam, H. W.; Joensuu, P. M.; Murray, G. J.; Fordyce, E. A. F.;
Prieto, O.; Luebbers, T. Org. Lett. 2006, 8, 3729. (e) Lumby, R. J. R.; About the Authors
Joensuu, P. M.; Lam, H. W. Org. Lett. 2007, 9, 4367. Ryan L. Patman was born in 1982 in Elk City, Oklahoma. In
(56) For iridium-catalyzed reductive aldol reactions, see Zhao, C.-X.; 2006, he received a B.S. degree in chemistry from Oklahoma
Duffey, M. O.; Taylor, S. J.; Morken, J. P. Org. Lett. 2001, 3, 1829. State University, where he conducted undergraduate research
(57) For ruthenium-catalyzed reductive aldol reactions, see Doi, T.; under the supervision of Professor Richard A. Bunce. He is
Fukuyama, T.; Minamino, S.; Ryu, I. Synlett 2006, 3013. currently a doctoral candidate in the research group of Professor
(58) For palladium-catalyzed reductive aldol reactions, see Kiyooka, S.; Michael J. Krische at The University of Texas at Austin.
Shimizu, A.; Torii, S. Tetrahedron Lett. 1998, 39, 5237. John F. Bower was born in 1980 in Chester, England. In 2003,
(59) For copper- promoted reductive aldol reactions, see: (a) Chiu, he obtained an M.Sci. degree in chemistry from the University of
P.; Chen, B.; Cheng, K. F. Tetrahedron Lett. 1998, 39, 9229. (b) Bristol, U.K., where he conducted research under the supervision
Chiu, P. Synthesis 2004, 2210. (c) For copper-promoted reductive of Professor Guy C. Lloyd-Jones. He continued with his doctoral
intramolecular Henry reaction, see Chung, W. K.; Chiu, P. Synlett studies at Bristol under the supervision of Professor Timothy
2005, 55. (d) For copper-promoted and catalyzed reductive Gallagher and, in 2007, received his Ph.D. degree. In May 2007,
cyclizations of α,β-acetylenic ketones tethered to ketones, see he joined the research group of Professor Michael J. Krische at The
Chiu, P.; Leung, S. K. Chem. Commun. 2004, 2308. University of Texas at Austin as a postdoctoral research associate.
(60) For copper- catalyzed reductive aldol reactions, see: (a) Ooi, T.; In Su Kim was born in 1975 in Gapyeong, Republic of Korea.
Doda, K.; Sakai, D.; Maruoka, K. Tetrahedron Lett. 1999, 40, 2133. In 2001, he received a B.S. degree from the College of Pharmacy,
(b) Lam, H. W.; Joensuu, P. M. Org. Lett. 2005, 7, 4225. (c) Lam, H. Sungkyunkwan University, Republic of Korea. He obtained an
W.; Murray, G. J.; Firth, J. D. Org. Lett. 2005, 7, 5743. (d) Deschamp, M.S. degree in 2003 and a Ph.D. degree in 2006, working under
J.; Chuzel, O.; Hannedouche, J.; Riant, O. Angew. Chem., Int. Ed. the guidance of Professor Young Hoon Jung. In September
2006, 45, 1292. (e) Chuzel, O.; Deschamp, J.; Chausteur, C.; Riant, 2007, he joined the group of Professor Michael J. Krische at
O. Org. Lett. 2006, 8, 5943. (f) Zhao, D.; Oisaki, K.; Kanai, M.; the University of Texas at Austin as a postdoctoral fellow of the
Shibasaki, M. Tetrahedron Lett. 2006, 47, 1403. (g) Zhao, D.; Korea Research Foundation (KRF).
Oisaki, K.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2006, 128, Michael J. Krische obtained a B.S. degree in chemistry from
14440. (h) Welle, A.; Díez-González, S.; Tinant, B.; Nolan, S. P.; the University of California at Berkeley, where he performed
Riant, O. Org. Lett. 2006, 8, 6059. research under the guidance of Professor Henry Rapoport as
(61) For nickel-catalyzed reductive aldol reactions, see Chrovian, C. C.; a President’s Undergraduate Fellow. After one year of study
Montgomery, J. Org. Lett. 2007, 9, 537. abroad as a Fulbright Fellow, he initiated graduate research at
(62) For a reductive aldol coupling employing stoichiometric quantities Stanford University under the mentorship of Professor Barry
of indium reagent, see Inoue, K.; Ishida, T.; Shibata, I.; Baba, A. Trost as a Veatch Graduate Fellow. Following receipt of his
Adv. Synth. Catal. 2002, 344, 283. Ph.D. degree, he worked with Jean-Marie Lehn at the Université
(63) For indium-catalyzed reductive aldol reactions, see: (a) Shibata, I.; Louis Pasteur as an NIH Post-Doctoral Fellow. In the fall of
Kato, H.; Ishida, T.; Yasuda, M.; Baba, A. Angew. Chem., Int. Ed. 1999, he was appointed Assistant Professor at the University
2004, 43, 711. (b) Miura, K.; Yamada, Y.; Tomita, M.; Hosomi, A. of Texas at Austin. He was promoted directly to Full Professor
Synlett 2004, 1985. in 2004 and in 2007 he received the Robert A. Welch Chair in
(64) For rhodium-catalyzed reductive aldol reactions mediated by Science. Professor Krische’s research program is focused on the
hydrogen, see: (a) Jang, H.-Y.; Huddleston, R. R.; Krische, M. J. J. development of C–C-bond-forming hydrogenations and transfer
Am. Chem. Soc. 2002, 124, 15156. (b) Huddleston, R. R.; Krische, hydrogenations. Research from his laboratory demonstrates
M. J. Org. Lett. 2003, 5, 1143. (c) Koech, P. K.; Krische, M. J. Org. that hydrogenation and transfer hydrogenation may be used to
Lett. 2004, 6, 691. (d) Marriner, G. A.; Garner, S. A.; Jang, H.-Y.; couple diverse π-unsaturated reactants to carbonyl compounds,
Krische, M. J. J. Org. Chem. 2004, 69, 1380. (e) Jung, C.-K.; Garner, imines, and even alcohols offering a byproduct-free alternative
S. A.; Krische, M. J. Org. Lett. 2006, 8, 519. (f) Han, S. B.; Krische, to stoichiometrically preformed organometallics in a range of
M. J. Org. Lett. 2006, 8, 5657. (g) Jung, C.-K.; Krische, M. J. J. Am. classical C=X (X = O, NR) addition processes. These studies
Chem. Soc. 2006, 128, 17051. (h) Bee, C.; Han, S. B.; Hassan, A.; represent the first systematic efforts to exploit hydrogenation in
Iida, H.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 2746. C–C couplings beyond hydroformylation, and define a departure
(65) Yachi, K.; Shinokubo, H.; Oshima, K. J. Am. Chem. Soc. 1999, 121, from the use of preformed organometallic reagents in carbonyl
9465. and imine additions. His research accomplishments led to the
(66) For tri(2-furyl)phosphine and triphenylarsine effects in metal- receipt of numerous awards and honors: Tetrahedron Young
catalyzed reactions, see: (a) Farina, V.; Krishnan, B. J. Am. Chem. Investigator Award (2009), Novartis Chemistry Lectureship
Soc. 1991, 113, 9585. (b) Farina, V. Pure Appl. Chem. 1996, 68, 73. (2008), Presidential Green Chemistry Award (2007), Dowpharma
(c) Andersen, N. G.; Keay, B. A. Chem. Rev. 2001, 101, 997. Prize (2007), ACS Elias J. Corey Award (2007), Solvias Ligand
(67) Garner, S. A.; Krische, M. J. J. Org. Chem. 2007, 72, 5843. Prize (2006), Society of Synthetic Organic Chemistry, Japan
(68) For metal-catalyzed reductive Mannich couplings mediated by Lectureship (2005), Johnson & Johnson Focused Giving Award
silane, see: (a) Muraoka, T.; Kamiya, S.; Matsuda, I.; Itoh, K. Chem. (2005), Dreyfus Teacher Scholar Award (2003), Alfred P. Sloan
Commun. 2002, 1284. (b) Townes, J. A.; Evans, M. A.; Queffelec, Research Fellowship (2003), Cottrell Scholar Award (2002),
J.; Taylor, S. J.; Morken, J. P. Org. Lett. 2002, 4, 2537. Frasch Foundation Award in Chemistry (2002), Lilly Grantee
VOL. 41, NO. 4 • 2008
(69) For secondary-amine-catalyzed reductive Mannich coupling of enal Award (2002), National Science Foundation-CAREER Award
to imines mediated by Hantzsch ester, see Zhao, G.-L.; Cordova, A. (2000), Maître de Conference, Collège de France (1999), NIH
Tetrahedron Lett. 2006, 47, 7417. Post-Doctoral Fellow (1997), Veatch Graduate Fellow (1995),
(70) Prieto, O.; Lam, H. W. Org. Biomol. Chem. 2008, 6, 55. Sigma Xi Grantee (1991), and Fulbright Fellow (1990).
Classics should be cherished.
sigma-aldrich.com
Accelerate Catalysis
Spiro Ligands
Asymmetric hydrogenation is playing a major role in the creation of chiral centers, and is widely used on a research and industrial production scale.
Some of the most common ligands for asymmetric hydrogenation are C2-symmetrical phosphines, of which the most notable ones are BINAP,
DIPAMP, or TADDOL. Zhou and co-workers have developed a new type of C2-symmetrical ligand with 1,1’-spirobi-indane as backbone, and which
offers higher enantiocontrol. It has shown excellent reactivity and selectivity in a variety of asymmetric hydrogenations. Aldrich is pleased to offer
a library of these new ligands.
NHAc
CO2CH3 O CH3
O CH3 O P N
P N P O O CH3
O O
100%, 90% ee Ts CH3
N
H
OCH3
(R)-SIPHOS (R)-ShiP (R)-SIPHOS-PE
76%, 96% ee
X
700797 700800 700770
H3C
CH3 R1 R2 (S)-SIPHOS (S)-ShiP (S)-SIPHOS-PE
CH3 700789 700819 700762
X= CHR3, O, NR3
84%, 99% ee
OH
P
2
OH P 2 P 2 P
P P
CH3
100%, 99% ee
2 2 2
100%, 99% ee
sigma-aldrich.com
Asymmetric Transfer Hydrogenation of Imines
The use of transfer hydrogenation to reduce alkenes, carboxyl groups, or imines is becoming an increasingly attractive procedure. Uematsu et al.
reported the asymmetric transfer hydrogenation of a variety of imines using a chiral diamine ligand complexed with ruthenium. A low loading of
the catalyst is sufficient, and good yields and excellent stereoselectivities are observed.
SO2
N
Ru SO2 SO2
N Cl N N
H2 Ru Ru
N Cl N Cl
H2 H2
703915
H3CO H3CO
(0.5 mol%)
N NH RuCl(p-cymene)[(S,S)-Ts-DPEN]
H3CO HCO2H-(C2H5)3N, CH3CN H3CO RuCl(p-cymene)[(R,R)-Ts-DPEN]
CH3 CH3 703915 703907
>99%, 95% ee
Uematsu, N. et al. J. Am. Chem. Soc. 1996, 118, 4916. Sold in collaboration with Takasago for research purposes only.
Hydroaminomethylation of Alkenes
The direct hydroamination of terminal alkenes is an interesting reaction due to its atom economy. However, only a few groups have taken advantage
of this reaction. Petricci et al. reported the hydroamination of alkenes using BiPhePhos with a rhodium complex under microwave irradiation. Using this
technique resulted in high conversion and selectivity, and reduced the reaction time.
OCH3 OCH3
O O OCH3 OCH3
O P
P O
O O
O O
O P
P O
Bn Bn 699535 Bn Bn O O
N N
(PPh3)3RhCO(H)
BnOOC + NHR2 BnOOC NR2
EtOH, H2/CO (100 psi), MW,
110 °C, 30 min
BiPhePhos
Bn Bn Bn Bn
N N 699535
Bn Bn BnOOC N BnOOC N
N
N
H3COOC
BnOOC N
OH
H H Unprotected Vicinal 1,2-Amino Alcohols via Allylation
O O
N N with Indium Reagents
R H R N
R
H H
Whereas the reductive amination of protected amino aldehydes has N
O In0, Br N
OH
sigma-aldrich.com
109
cascades have evolved to handle the chemically incompatible largely depends on their structure, especially in terms of inter- or
carbonyl and amine functionalities. The biosynthesis of intramolecular stabilization.5 Ito et al. undertook a comprehensive
retronecine1 is an instructive case: at least two points in its study of the loss of enantiomeric purity of N-protected
biosynthetic cascade incorporate transiently formed intermediates α-amino aldehydes during chromatography on silica gel.5 The
110
N–PG = N3 N–PG = N
DMSO, rt, 0.5 h
O O
NMP, 4 oC
2.5–5.0 h HO NHBoc
PMP PMP n-Pr
O HN O HN
>98% ee
R R (after recrystallization)
N3 N
PG
19, 83–96% 20, 68–88% Scheme 9. β2-Amino Acids by the Diastereoselective Amino
syn:anti = 4:1 to 10:1 77–97% ee
85–99% ee R = CO2Et, Ph, methylation of Aldehydes. (Ref. 36)
R = CO2Et, BnOCH2 4-O2NC6H4,
4-NCC6H4
O
Scheme 6. Amino Ketones by the Organocatalytic Asymmetric S
O H O TIPP NH O
Mannich Reaction. (Ref. 23) LiHMDS
S + Me Me
TIPP N Ph N THF Ph N
OMe –78 oC, 0.5 h OMe
74%
O O TIPP = 2,4,6-triisopropylphenyl syn:anti = 92:5:3:0
R3 direct
+ +
R1 R2 H NH2
eq 5 (Ref. 38)
O NHR3
R1 R2
R3
OR(NR'2) N 1. H2C=CHMgBr
indirect O O
+ THF, rt, 1–6 h
R1 R2 H
R NR1R2 2. H2O R NR1R2
preformed preformed
enolate or imine
enamine 21 22
47–88%
R = Me, Ph, heteroaryl
R1,R2 = Me,OMe; piperidinyl; morpholinyl
Scheme 7. Mannich-Type Reactions in the Synthesis of
β-Amino Carbonyl Compounds. (Ref. 25) eq 6 (Ref. 39)
PMP O HN PG
O HN
A (5 mol %)
Ar R
dioxane, rt H CO2Et
OH
2–24 h R PG = Ph2P(O)
R = Me, Et, i-Pr, n-Bu, 65–86%
n-pent, TBSO(CH2)3 syn cat. (3.5 or anti:syn = 1:1 to 6:1
52 to >95% de O PG 5.0 mol %) 56 to >99% ee (anti)
PMP 91 to >99% ee N
O N OH +
Ar 4 Å MS, THF
+ R
H H CO2Et –24 or 5 oC
R 14–24 h PG = Boc
O HN PG
A= CO2H PMP
N B Ar R
H O HN
(0.5–5 mol %) Ar = Ph, 2-MeOC6H4, 1-Np, 2-Np, furan-2-yl OH
(S)-Proline CO2Et R = i-Pr, c-Pr, i-Bu, Cy, n-Hex, Ph(CH2)2
DMSO or dioxane H 70–77%
rt, 0.5–22 h R syn:anti = 3:1 to 5:1
anti 90–94% ee (syn)
88–96% de
NHSO2R' 97 to >99% ee
COOH Ar Et Ar
R = Me, i-Pr, n-Bu, t-Bu O O
n-pent, allyl Ar Zn Zn Ar
B= NH or
Me N O N
N
H cat. =
Scheme 8. Preparation of β-Amino Aldehydes by the Catalytic, Scheme 10. Trost’s Diastereoselective Synthesis of α-Hydroxy-β-
Asymmetric anti-Mannich Reaction. (Ref. 30g,32,33) amino Ketones. (Ref. 40)
114
O HO 1. NaBH4, MeOH O X
O –10 oC, 1 h
Bn N n-C9H19 Bn N n-C9H19
2. LAH, THF
HN 10% HCl N Me 67 oC, 4 h Boc
Me Me
rt (+)-preussin 34, X = HgCl; 35, X = H
Me Me 48% (overall from 32) 34:35 = 8:1
O O H >95% ee
O
29 30, 85%
7:1 dr
Scheme 17. Amino Carbonyl Compounds in the Synthesis of
TsOH•1H2O Natural Products. (Ref. 62)
PhMe
reflux, 3 h
1. NaBH4
H N MeOH, rt H N
Me Me H2N
2. SOCl2, Py O O 1. MgSO4 O O
OBn rt, 2–3 h
rt, 1.5 h
H O H + O
2. TsOH, 75 oC n-C5H11 N
(±)-porantherine 31
51% (2 steps) 45% PhH, 3 h H
OBn
36
(R)-(–) 37, 61%
(2S,3S,6R)-(–)
1. (HSCH2)2
F3B•OEt2 O O
CH2Cl2, rt, 2.5 h
OH O
H H n-C5H11 N 2. Ra®-Ni, EtOH n-C5H11 N
O R2O 80 oC, 2 h
cat = N
D-proline R1 (–)-indolizidine 209B 38, 74%
O 69% (2S,3S,6R)-(–)
H H
2 cat. (10 mol %) up to 91%
R O O up to 85:15 dr
N 1 DMSO, DMF,
R
O or neat
cat = OH O Scheme 18. β-Amino Ketones in the Synthesis of
rt, 48–72 h H H
L-proline
R2O (–)-Indolizidine 209B. (Ref. 63)
1
R = Me, Ph, 4-MeOC6H4CO
R2 = 4-MeOC6H4, allyl, 2-Br-allyl N
O R1
ketone = acetone, cyclopentanone
up to 100%
up to 100:0 dr O asymmetric OH
reduction
Ar NHMe Ar * NHMe
R + 2 R
R solvent
NH2 N R2
R1
R1 [H– ] H +
R1 1. AlCl3, anhyd PhMe R1 OH N CONHR2
rt, 1–3 h H H2N CONHR2 H –
Cl O O
FmocHN H2N N N
2. HCl (1 N)
O O R N R N R
3. Na2CO3, H2O R ZnCl2, NaBH3CN
39 CHCl3 40 THF–MeOH (1:1)
rt
R2
Cl CHCl3
1
R = Me, i-Pr, i-Bu, s-Bu FmocHN rt, 1 h
R2 = Me, i-Pr, i-Bu, s-Bu, Bn O
R = H, Me, Ph, TBDMSO
R2 O NH R1 = i-Pr, i-Bu, Bn R1
H
N R O R2 = Ph, i-Pent NH
FmocHN R N CONHR2
O R1 H
51–92%
41
80–96%
In general, β-lactams are important pharmacophores for the 3.2. Applications as Building Blocks in the
treatment of diseases caused by bacterial infections.58 Pharmaceutical Industry
An important use of amino ketones is in the synthesis of Amino ketones have served as important building blocks in the
quinolines and their derivatives,59 which have a wide range of synthesis of a variety of marketed pharmaceuticals. Through
biological activities including antimalarial, anti-inflammatory, catalytic asymmetric hydrogenation, amino ketones can be
antihypertensive, and antibacterial ones. Tyrosine kinase converted into enantiomerically pure amino alcohols exhibiting
inhibitors and histamine H3 receptor antagonists were prepared various pharmacological activities. The pharmaceutical industry
from amino carbonyl compounds.60 In general, quinolines can has implemented this strategy in the enantioselective preparation
be obtained using Skraup, Doebner–Von Miller, and Friedländer of several adrenergic receptor agonists including phenylephrine
methods. Among these procedures, the Friedländer method is hydrochloride, etilefrine hydrochloride, salbutamol hydrochloride,
best for the synthesis of quinolines involving amino carbonyls as and adrenaline sulfate.
substrates (eq 8). (–)-Lobeline, an alkaloid isolated from Lobelia inflate (Indian
Elmaaty and Castle have reported a facile, regiocontrolled tobacco), has been prepared by the asymmetric monoreduction of
synthesis of trialkyl-substituted pyrazines.61 α-Nitro ketones lobalanine. It is a known nicotinic agonist and has been employed
were reacted with α-amino ketones in the presence of hydrogen as an antiasthmatic, expectorant, respiratory stimulant,64 and
sulfite and octyl viologen as an electron-transfer reagent (eq 9). smoking-cessation aid, with more recent applications in the
Alkylpyrazines have found utility as flavor components in food, treatment of psychostimulant abuse.65
as pheromones, and as versatile synthetic intermediates. The amino alcohols derived from the selective reduction of the
corresponding amino ketones can also serve as chiral building
3.1. Selected Examples from Natural Product blocks for the industrial-scale synthesis of other pharmaceutical
Synthesis compounds. In the preparation of the immunoregulating drug
(+)-Preussin, an antifungal agent, was synthesized in five levamisole, the intermediate amino alcohol was obtained through
steps from t-Boc-(S)-phenylalanine via Weinreb amide 32 selective reduction of the corresponding amino carbonyl.66
(Scheme 17).62 When treated with undecynyllithium (THF, Fluoxetine (a selective serotonin-reuptake inhibitor),
–23 ºC, 1 h), compound 32 furnished ynone 33 in 87% yield. atomoxetine (a selective noradrenaline-reuptake inhibitor),
Reaction of 33 with Hg(OAc)2 induced 5-endo-dig cyclization to nisoxetine (inhibitor of norepinephrine), and duloxetine
give pyrrolinones 34 and 35 in an 8:1 ratio. The mixture of 34 and hydrochloride (a dual inhibitor of serotonin and noradrenaline
35 reacted directly with NaBH4 in methanol at –10 ºC to give the reuptake) are important pharmaceuticals, which have been
Boc-protected preussin, which was reduced with LAH to afford obtained from the corresponding amino ketones by asymmetric
preussin. reduction (Scheme 19).64 Duloxetine was approved by the U.S.
Davis and Yang reported the synthesis of indolizidine 209B FDA in 2004 for the treatment of major depressive disorder.67
via a β-amino ketone intermediate (Scheme 18).63 The starting
amino ketal 36 was obtained from a chiral sulfonamide in three 3.3. Applications in Biochemistry and Chemical
steps and, upon stirring with anhydrous MgSO 4 and (E)-4- Biology
benzyloxy-2-butenal, gave an unstable imine intermediate. The Di Gioia et al. employed stable and enantiomerically pure
Mannich product 37 was obtained as a single diastereoisomer Fmoc-protected acid chlorides 39 in a Friedel–Crafts-type
by heating the intermediate imine in the presence of anhydrous reaction to generate chiral α-amino ketones 40, which reacted
VOL. 41, NO. 4 • 2008
TsOH. Debenzylation of 37 followed by hydrogenation provided in situ with another equivalent of 39 to yield peptidyl ketones
bicyclic compound 38. Treatment of 38 with ethanedithiol in the 41 (Scheme 20).68 Later, the authors extended this strategy to
presence of F3B•OEt2, followed by reduction with Raney®-Nickel the preparation of various monopeptidyl ketones and dipeptidyl
led to indolizidine 209B. ketones.
117
The synthesis of peptidomimetic agents has been an active (12) For reviews, see: (a) Reetz, M. T. Angew. Chem., Int. Ed. Engl.
(c) Hili, R.; Baktharaman, S.; Yudin, A. K. Eur. J. Org. Chem. Trost, B. M.; Terrell, L. R. J. Am. Chem. Soc. 2003, 125, 338. (e)
2008, 5201. Kobayashi, S.; Matsubara, R.; Nakamura, Y.; Kitagawa, H.; Sugiura,
(11) For a review, see Liang, X.; Andersch, J.; Bols, M. J. Chem. Soc., M. J. Am. Chem. Soc. 2003, 125, 2507. (f) Josephsohn, N. S.; Snapper,
Perkin Trans. 1 2001, 2136. M. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2004, 126, 3734.
118
(30) (a) Hayashi, Y.; Urushima, T.; Tsuboi, W.; Shoji, M. Nature C.; Kim, K. H.; Henkin, J.; Lesniewski, R. Bioorg. Med. Chem.
Amino Carbonyl Compounds in Organic Synthesis
Protocols 2007, 2, 113. (b) Notz, W.; Watanabe, S.; Chowdari, Lett. 2004, 14, 865. (c) Baktharaman, S.; Selvakumar, S.; Singh,
N. S.; Zhong, G.; Betancort, J. M.; Tanaka, F.; Barbas, C. F., V. K. Org. Lett. 2006, 8, 4335.
III. Adv. Synth. Catal. 2004, 346, 1131. (c) Wang, W.; Wang, J.; (51) (a) Kotkar, S. P.; Chavan, V. B.; Sudalai, A. Org. Lett. 2007, 9,
Li, H. Tetrahedron Lett. 2004, 45, 7243. (d) Zhuang, W.; Saaby, 1001. (b) Concellón, J. M.; Méjica, C. Eur. J. Org. Chem. 2007,
S.; Jorgensen, K. A. Angew. Chem., Int. Ed. 2004, 43, 4476. (e) 5250. (c) Davies, S. B.; McKervey, M. A. Tetrahedron Lett. 1999,
Westermann, B.; Neuhaus, C. Angew. Chem., Int. Ed. 2005, 44, 40, 1229.
4077. (f) Enders, D.; Grondal, C.; Vrettou, M.; Raabe, G. Angew. (52) (a) Abdel-Magid, A. F.; Mehrman, S. J. Org. Process Res. Dev.
Chem., Int. Ed. 2005, 44, 4079. (g) Notz, W.; Tanaka, F.; Watanabe, 2006, 10, 971. (b) Liu, D.; Gao, W.; Wang, C.; Zhang, X. Angew.
S.; Chowdari, N. S.; Turner, J. M.; Thayumanavan, R.; Barbas, C. Chem., Int. Ed. 2005, 44, 1687. (c) Jung, C.-K.; Krische, M. J. J.
F., III. J. Org. Chem. 2003, 68, 9624. (h) Ollevier, T.; Nadeau, E. Am. Chem. Soc. 2006, 128, 17051.
J. Org. Chem. 2004, 69, 9292. (i) Sueki, S.; Igarashi, T.; Nakajima, (53) (a) Kiyooka, S.; Shiomi, Y.; Kira, H.; Kaneko, Y.; Tanimori, S. J.
T.; Shimizu, I. Chem. Lett. 2006, 35, 682. Org. Chem. 1994, 59, 1958. (b) Restorp, P.; Fischer, A.; Somfai, P.
(31) (a) List, B. J. Am. Chem. Soc. 2000, 122, 9336. (b) List, B.; J. Am. Chem. Soc. 2006, 128, 12646.
Pojarliev, P.; Biller, W. T.; Martin, H. J. J. Am. Chem. Soc. 2002, (54) (a) Palomo, C.; Miranda, J. I.; Cuevas, C.; Odriozola, J. M. J.
124, 827. Chem. Soc., Chem. Commun. 1995, 1735. (b) Palomo, C.; Cossio,
(32) Mitsumori, S.; Zhang, H.; Cheong, P. H.-Y.; Houk, K. N.; Tanaka, F. P.; Cuevas, C.; Lecea, B.; Mielgo, A.; Román, P.; Luque, A.;
F.; Barbas, C. F., III. J. Am. Chem. Soc. 2006, 128, 1040. Martinez-Ripoll, M. J. Am. Chem. Soc. 1992, 114, 9360.
(33) Kano, T.; Yamaguchi, Y.; Tokuda, O.; Maruoka, K. J. Am. Chem. (55) (a) Angle, S. R.; Belanger, D. S. J. Org. Chem. 2004, 69, 4361.
Soc. 2005, 127, 16408. (b) Steurer, S.; Podlech, J. Eur. J. Org. Chem. 1999, 1551. (c)
(34) Chen, Y. K.; Yoshida, M.; MacMillan, D. W. C. J. Am. Chem. Soc. Shono, T.; Kise, N.; Tanabe, T. J. Org. Chem. 1988, 53, 1364. (d)
2006, 128, 9328. Hormuth, S.; Reissig, H.-U.; Dorsch, D. Angew. Chem., Int. Ed.
(35) For an example, see Shih, C.; Gossett, L. S.; Gruber, J. M.; Engl. 1993, 32, 1449. (e) Reetz, M. T.; Schmitz, A.; Holdgrün, X.
Grossman, C. S.; Andis, S. L.; Schultz, R. M.; Worzalla, J. F.; Tetrahedron Lett. 1989, 30, 5421. (f) Pugin, B.; Venanzi, L. M. J.
Corbett, T. H.; Metz, J. T. Bioorg. Med. Chem. Lett. 1999, 9, 69. Am. Chem. Soc. 1983, 105, 6877.
(36) (a) Chi, Y.; Gellman, S. H. J. Am. Chem. Soc. 2006, 128, 6804. (b) (56) Clive, D. L. J.; Li, Z.; Yu, M. J. Org. Chem. 2007, 72, 5608.
Chi, Y.; English, E. P.; Pomerantz, W. C.; Horne, W. S.; Joyce, L. (57) Alcaide, B.; Almendros, P.; Luna, A.; Torres, M. R. J. Org. Chem.
A.; Alexander, L. R.; Fleming, W. S.; Hopkins, E. A.; Gellman, S. 2006, 71, 4818.
H. J. Am. Chem. Soc. 2007, 129, 6050. (58) See for example: (a) Niccolai, D.; Tarsi, L.; Thomas, R. J. Chem.
(37) See for example: (a) Ibrahem, I.; Dziedzic, P.; Córdova, A. Commun. 1997, 2333. (b) Southgate, R. Contemp. Org. Synth.
Synthesis 2006, 4060. (b) Ibrahem, I.; Zhao, G.-L.; Córdova, A. 1994, 1, 417.
Chem.—Eur. J. 2007, 13, 683. (59) Balasubramanian, M.; Keay, J. G. In Six-Membered Rings with One
(38) Davis, F. A.; Song, M. Org. Lett. 2007, 9, 2413. Heteroatom and Fused Carbocyclic Derivatives; McKillop, A.,
(39) Gomtsyan, A. Org. Lett. 2000, 2, 11. Ed.; Comprehensive Heterocyclic Chemistry II Series; Katritzky,
(40) Trost, B. M.; Jaratjaroonphong, J.; Reutrakul, V. J. Am. Chem. A. R., Rees, C. W., Scriven, E. F. V., Series Eds.; Pergamon: New
Soc. 2006, 128, 2778. York, 1996; Vol. 5, p 245.
(41) (a) Favino, T. F.; Fronza, G.; Fuganti, C.; Fuganti, D.; Grasselli, (60) (a) Chen, Y.-L.; Fang, K.-C.; Sheu, J.-Y.; Hsu, S.-L.; Tzeng, C.-C.
P.; Mele, A. J. Org. Chem. 1996, 61, 8975. (b) Beausoleil, E.; J. Med. Chem. 2001, 44, 2374. (b) Zaragoza, F.; Stephensen, H.;
L’ Archevêque, B.; Bélec, L.; Atfani, M.; Lubell, W. D. J. Org. Peschke, B.; Rimvall, K. J. Med. Chem. 2005, 48, 306.
Chem. 1996, 61, 9447. (c) Nagafuji, P.; Cushman, M. J. Org. (61) Elmaaty, T. A.; Castle, L. W. Org. Lett. 2005, 7, 5529.
Chem. 1996, 61, 4999. (d) Bodmann, K.; Bug, T.; Steinbeisser, S.; (62) Overhand, M.; Hecht, S. M. J. Org. Chem. 1994, 59, 4721.
Kreuder, R.; Reiser, O. Tetrahedron Lett. 2006, 47, 2061. (63) Davis, F. A.; Yang, B. Org. Lett. 2003, 5, 5011.
(42) (a) Okamoto, S.; Teng, X.; Fujii, S.; Takayama, Y.; Sato, F. J. Am. (64) Klingler, F. D. Acc. Chem. Res. 2007, 40, 1367.
Chem. Soc. 2001, 123, 3462. (b) Aschwanden, P.; Kværnø, L.; (65) Felpin, F.-X.; Lebreton, J. Tetrahedron 2004, 60, 10127.
Geisser, R. W.; Kleinbeck, F.; Carreira, E. M. Org. Lett. 2005, 7, (66) Takeda, H.; Tachinami, T.; Aburatani, M.; Takahashi, H.;
5741. (c) Labonne, A.; Zani, L.; Hintermann, L.; Bolm, C. J. Org. Morimoto, T.; Achiwa, K. Tetrahedron Lett. 1989, 30, 363.
Chem. 2007, 72, 5704. (67) Waitekus, A. B.; Kirkpatrick, P. Nature Rev. Drug Disc. 2004,
(43) Pan, Q.; Zou, B.; Wang, Y.; Ma, D. Org. Lett. 2004, 6, 1009. 3, 907.
(44) (a) Chowdari, N. S.; Ramachary, D. B.; Barbas, C. F., III . Org. (68) Di Gioia, M. L.; Leggio, A.; Liguori, A.; Napoli, A.; Siciliano, C.;
Lett. 2003, 5, 1685. (b) Vicario, J. L.; Rodriguez, M.; Badia, D.; Sindona, G. J. Org. Chem. 2001, 66, 7002.
Carrillo, L.; Reyes, E. Org. Lett. 2004, 6, 3171. (69) For a review, see Fauchère, J.-L. In Advances in Drug Research;
(45) Ryu, I.; Yamamura, G.; Omura, S.; Minakata, S.; Komatsu, M. Testa, B., Ed.; Academic Press: New York, 1986; Vol. 15, pp
Tetrahedron Lett. 2006, 47, 2283. 29–69.
(46) Giovannini, A.; Savoia, D.; Umani-Ronchi, A. J. Org. Chem. (70) Szelke, M.; Leckie, B.; Hallett, A.; Jones, D. M.; Sueiras, J.;
1989, 54, 228. Atrash, B.; Lever, A. F. Nature 1982, 299, 555.
(47) Smirnova, Y. V.; Krasnaya, Z. A. Russ. Chem. Rev. (Engl. Transl.) (71) Li, X.; Yudin, A. K. J. Am. Chem. Soc. 2007, 129, 14152.
2000, 69, 1021.
(48) Asensio, G.; González-Núñez, M. E.; Bernardini, C. B.; Mello, R.; 6. Notes Added in Proof
Adam W. J. Am. Chem. Soc. 1993, 115, 7250. (a) Recently, Soderquist and co-workers have developed a novel
VOL. 41, NO. 4 • 2008
(49) Corey, E. J.; Balanson R. D. J. Am. Chem. Soc. 1974, 96, 6516. borane-based approach to convert a-amino acids into N-TIPS-
(50) (a) Restorp, P.; Somfai, P. Org. Lett. 2005, 7, 893. (b) Sheppard, G. a-amino aldehydes, which were found to be resistant to both
S.; Wang, J.; Kawai, M.; BaMaung, N. Y.; Craig, R. A.; Erickson, degradation and racemization. (Soto-Cairoli, B.; Justo de
S. A.; Lynch, L.; Patel, J.; Yang, F.; Searle, X. B.; Lou, P.; Park, Pomar, J.; Soderquist, J. A. Org. Lett. 2008, 10, 333.)
119
O 1. (i-Pr)2NEt, THF O Trademarks: Raney® (W. R. Grace and Co.); Red-Al® (Sigma-
O
N For more information, please visit sigma-aldrich.com/cpc
H
(–)-secu'amamine A
9% (overall yield)
sigma-aldrich.com
New Products for Chemistry
Pigment-Free, Filler-Free Sleeve Stopper Septa
Sleeve stopper septa are manufactured from pure natural rubber without
fillers or pigments for super tactility and resealability. Less additives in the
rubber lowers the potential for contamination during use.
To learn more about our new products or to order, please visit sigma-aldrich.com/labware
Precision Seal is a registered trademark of Sigma-Aldrich Biotechnology, L.P., and Sigma-Aldrich Co.
sigma-aldrich.com
New Aldrich Handbook!
®
sigma-aldrich.com
PRESORTED
STANDARD
U.S. POSTAGE
P.O. Box 14508 PAID
SIGMA-ALDRICH
St. Louis, MO 63178 CORPORATION
USA
World Headquarters Order/Customer Service (800) 325-3010 • Fax (800) 325-5052 Accelerating Customers’
3050 Spruce St., St. Louis, MO 63103
Technical Service (800) 325-5832 • sigma-aldrich.com/techservice Success through Innovation and
(314) 771-5765
sigma-aldrich.com Development/Bulk Manufacturing Inquiries (800) 244-1173 Leadership in Life Science,
High Technology and Service
©2009 Sigma-Aldrich Co. All rights reserved. SIGMA, , SAFC, , SIGMA-ALDRICH, ALDRICH, , FLUKA, , and SUPELCO, are trademarks belonging to Sigma-Aldrich Co.
and its affiliate Sigma-Aldrich Biotechnology, L.P. Sigma brand products are sold through Sigma-Aldrich, Inc. Sigma-Aldrich, Inc. warrants that its products conform to the information
contained in this and other Sigma-Aldrich publications. Purchaser must determine the suitability of the product(s) for their particular use. Additional terms and conditions may apply.
Please see reverse side of the invoice or packing slip.
LBC
05056-503200
0029