Enantioselective iridium-catalyzed carbonyl allylation from the alcohol or aldehyde oxidation level via transfer hydrogenative coupling of allyl acetate: Departure from chirally modified allyl metal reagents in carbonyl addition

Article abstract of DOI:10.1021/ja805722e

Under the conditions of transfer hydrogenation employing an iridium catalyst generated in situ from [Ir(COd)Cl]₂, chiral phosphine ligand (R)-BINAP or (R)-Cl,MeO-BIPHEP, and m-nitrobenzoic acid, allyl acetate couples to allylic alcohols 1a-c, aliphatic alcohols 1d-1, and benzylic alcohols 1m-u to furnish products of carbonyl allylation 3a-u with exceptional levels of asymmetric induction. The very same set of optically enriched carbonyl allylation products 3a-u are accessible from enals 2a-c, aliphatic aldehydes 2d-1, and aryl aldehydes 2m-u, using iridium catalysts ligated by (-)-TMBTP or (R)-Cl,MeO-BIPHEP under identical conditions, but employing isopropanol as a hydrogen donor. A catalytically active cyclometallated complex V, which arises upon ortho-C-H insertion of iridium onto m-nitrobenzoic acid, was characterized by single-crystal X-ray diffraction. The results of isotopic labeling are consistent with intervention of symmetric iridium π-allyl intermediates or rapid interconversion of σ-allyl haptomers through the agency of a symmetric π-allyl. Competition experiments demonstrate rapid and reversible hydrogenation-dehydrogenation of the carbonyl partner in advance of C-C coupling. However, the coupling products, which are homoallylic alcohols, experience very little erosion of optical purity by way of redox equilibration under the coupling conditions, although isopropanol, a secondary alcohol, may serve as terminal reductant. A plausible catalytic mechanism accounting for these observations is proposed, along with a stereochemical model that accounts for the observed sense of absolute stereoinduction. This protocol for asymmetric carbonyl allylation transcends the barriers imposed by oxidation level and the use of preformed allyl metal reagents.

Full text of DOI:10.1021/ja805722e

Published on Web 10/08/2008
Enantioselective Iridium-Catalyzed Carbonyl Allylation from
the Alcohol or Aldehyde Oxidation Level via Transfer
Hydrogenative Coupling of Allyl Acetate: Departure from
Chirally Modified Allyl Metal Reagents in Carbonyl Addition
In Su Kim, Ming-Yu Ngai, and Michael J. Krische*
Department of Chemistry and Biochemistry, UniVersity of Texas at Austin, Austin, Texas 78712
Received July 22, 2008; E-mail: mkrische@mail.utexas.edu
Abstract: Under the conditions of transfer hydrogenation employing an iridium catalyst generated in situ
from [Ir(cod)Cl]2, chiral phosphine ligand (R)-BINAP or (R)-Cl,MeO-BIPHEP, and m-nitrobenzoic acid, allyl
acetate couples to allylic alcohols 1a-c, aliphatic alcohols 1d-l, and benzylic alcohols 1m-u to furnish
products of carbonyl allylation 3a-u with exceptional levels of asymmetric induction. The very same set of
optically enriched carbonyl allylation products 3a-u are accessible from enals 2a-c, aliphatic aldehydes
2d-l, and aryl aldehydes 2m-u, using iridium catalysts ligated by (-)-TMBTP or (R)-Cl,MeO-BIPHEP
under identical conditions, but employing isopropanol as a hydrogen donor. A catalytically active
cyclometallated complex V, which arises upon ortho-C-H insertion of iridium onto m-nitrobenzoic acid,
was characterized by single-crystal X-ray diffraction. The results of isotopic labeling are consistent with
intervention of symmetric iridium π-allyl intermediates or rapid interconversion of σ-allyl haptomers through
the agency of a symmetric π-allyl. Competition experiments demonstrate rapid and reversible
hydrogenation-dehydrogenation of the carbonyl partner in advance of C-C coupling. However, the coupling
products, which are homoallylic alcohols, experience very little erosion of optical purity by way of redox
equilibration under the coupling conditions, although isopropanol, a secondary alcohol, may serve as terminal
reductant. A plausible catalytic mechanism accounting for these observations is proposed, along with a
stereochemical model that accounts for the observed sense of absolute stereoinduction. This protocol for
asymmetric carbonyl allylation transcends the barriers imposed by oxidation level and the use of preformed
allyl metal reagents.
Introduction
Owing to these outstanding advances, highly enantioselective
allylation is now possible for a diverse assortment of carbonyl
Enantioselective carbonyl allylation ranks among the foremost
methods used for the stereocontrolled synthesis of polyketide
natural products.1 Prevailing protocols typically rely on the use
of preformed allyl metal reagents. The first carbonyl allylations
employing isolable allyl boron reagents and isolable allyl silanes
were described by Mikhailov and Bubnov (1964) and Hosomi
and Sakurai (1976), respectively.2 The first chirally modified
allyl metal reagent, an allylborane derived from camphor, was
reported by Hoffmann (1978).3a,b In the three decades that
followed, increasingly effective protocols for asymmetric car-
bonyl allylation based on chirally modified allyl metal reagents
emerged, including those developed by Kumada (1982),3c
Brown (1983),3d Roush (1985),3e Reetz (1988),3f Masamune
(1989),3g Corey (1989),3h Seebach (1987),3i Duthaler (1989),3j
Panek (1991),3k Leighton (2002),3l,m and Soderquist (2005).3n
compounds (Figure 1). However, as frequently documented,4
the generation of stoichiometric byproducts detracts from the
utility of most chirally modified allyl metal reagents. Further,
the multistep syntheses required to prepare such reagents,
combined with the added effort or inability to recover the chiral
modifier, can pose additional barriers to their use.5
These issues are, in part, addressed by catalytic enantiose-
lective protocols for carbonyl allylation, which circumvent the
stoichiometric use of chiral modifiers. Following groundbreaking
(3) Selected examples of chirally modified allyl metal reagents: (a) Herold,
T.; Hoffmann, R. W. Angew. Chem., Int. Ed. Engl. 1978, 17, 768. (b)
Hoffmann, R. W.; Herold, T. Chem. Ber. 1981, 114, 375. (c) Hayashi,
T.; Konishi, M.; Kumada, M. J. Am. Chem. Soc. 1982, 104, 4963. (d)
Brown, H. C.; Jadhav, P. K. J. Am. Chem. Soc. 1983, 105, 2092. (e)
Roush, W. R.; Walts, A. E.; Hoong, L. K. J. Am. Chem. Soc. 1985,
107, 8186. (f) Reetz, M. Pure Appl. Chem. 1988, 60, 1607. (g) Short,
R. P.; Masamune, S. J. Am. Chem. Soc. 1989, 111, 1892. (h) Corey,
E. J.; Yu, C.-M.; Kim, S. S. J. Am. Chem. Soc. 1989, 111, 5495. (i)
Seebach, D.; Beck, A. K.; Imwinkelzied, R.; Roggo, S.; Wonnacott,
A. HelV. Chim. Acta 1987, 70, 954. (j) Riediker, M.; Duthaler, R. O.
Angew. Chem., Int. Ed. Engl. 1989, 28, 494. (k) Panek, J. S.; Yang,
M. J. Am. Chem. Soc. 1991, 113, 6594. (l) Kinnaird, J. W. A.; Ng,
P. Y.; Kubota, K.; Wang, X.; Leighton, J. L. J. Am. Chem. Soc. 2002,
124, 7920. (m) Hackman, B. M.; Lombardi, P. J.; Leighton, J. L. Org.
Lett. 2004, 6, 4375. (n) Burgos, C. H.; Canales, E.; Matos, K.;
Soderquist, J. A. J. Am. Chem. Soc. 2005, 127, 8044.
(1) For reviews on enantioselective carbonyl allylation, see: (a) Yamamoto,
Y.; Asao, N. Chem. ReV. 1993, 93, 2207. (b) Ramachandran, P. V.
Aldrichim. Acta 2002, 35, 23. (c) Kennedy, J. W. J.; Hall, D. G. Angew.
Chem., Int. Ed. 2003, 42, 4732. (d) Denmark, S. E.; Fu, J. Chem.
ReV. 2003, 103, 2763. (e) Yu, C.-M.; Youn, J.; Jung, H.-K. Bull.
Korean Chem. Soc. 2006, 27, 463. (f) Marek, I.; Sklute, G. Chem.
Commun. 2007, 1683. (g) Hall, D. G. Synlett 2007, 1644.
(2) (a) Mikhailov, B. M.; Bubnov, Y. N. IzV. Akad. Nauk SSSR, Ser. Khim.
1964, 1874. (b) Hosomi, A.; Sakurai, H. Tetrahedron Lett. 1976, 17,
1295. (c) Sakurai, H. Pure Appl. Chem. 1982, 54, 1.
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A R T I C L E S
Kim et al.
Figure 1. Top: Representative examples of chirally modified allyl metal reagents for use in enantioselective carbonyl allylation. Bottom: Prototypical
catalytic enantioselective carbonyl allylations.
work by Yamamoto (1991),6 the first highly enantioselective
catalytic carbonyl allylations were described by Umani-Ronchi
(1993) and Keck (1993).7a,b Alternatively, chiral Lewis basic
catalysts enable enantioselective carbonyl allylation, as dem-
onstrated in elegant studies by Denmark (1994).7c,d These
methods are very effective but still rely upon the use of
preformed allyl metal reagents. The allyl stannanes employed
in the Umani-Ronchi-Keck allylation generate stoichiometric
quantities of tin byproducts, and the trichlorosilanes employed
in the Denmark allylation are highly moisture sensitive and upon
hydrolysis generate stoichiometric quantities of hydrochloric
acid (Figure 1).
An alternate approach to catalytic carbonyl allylation involves
the reduction of metallo-π-allyls derived from allylic alcohols
and allylic carboxylates.8-13 To date, palladium,9 rhodium,10
iridium,11 and ruthenium12 complexes have been reported to
catalyze such carbonyl allylations. A related method for carbonyl
allylation is represented by catalytic variants of the Nozaki-
Hiyama-Kishi (NHK) reaction of allylic halides.13,14 With one
exception,12 these processes require stoichiometric quantities
of metallic reductants, such as SmI2, SnCl2, Et2Zn, or Et3B, for
(4) In Brown’s allylation protocol (ref 3d), the stoichiometric generation
of isopinocampheol frequently complicates isolation of the allylation
product: (a) Ireland, R. E.; Armstrong, J. D., III; Lebreton, J.; Meissner,
R. S.; Rizzacasa, M. A. J. Am. Chem. Soc. 1993, 115, 7152. (b) Burova,
S. A.; McDonald, F. E. J. Am. Chem. Soc. 2004, 126, 2495. (c)
Ramachandran, P. V.; Prabhudas, B.; Chandra, J. S.; Reddy, M. V. R.
J. Org. Chem. 2004, 69, 6294. (d) White, J. D.; Hansen, J. D. J. Org.
Chem. 2005, 70, 1963. (e) Gao, D.; O’Doherty, G. A. Org. Lett. 2005,
7, 1069. (f) Gao, D.; O’Doherty, G. A. J. Org. Chem. 2005, 70, 9932.
(g) Liu, D.; Xue, J.; Xie, Z.; Wei, L.; Zhang, X.; Li, Y. Synlett 2008,
1526.
(5) A notable exception involves the chirally modified allyl silanes
developed by Leighton (ref 3l), for which highly efficient recovery of
the chiral auxiliary is possible.
(6) To our knowledge, the first examples of enantioselective Lewis acid-
catalyzed carbonyl allylation were reported by Yamamoto in 1991.
While additions of substituted allylic silanes gave highly optically
enriched product, only a single example of the parent allylation
employing allyltrimethylsilane was given, which proceeds in 55%
enantiomeric excess: Furuta, K.; Mouri, M.; Yamamoto, H. Synlett
1991, 561.
(8) For selected reviews covering carbonyl allylation Via umpolung of
π-allyls, see: (a) Masuyama, Y. In AdVances in Metal-Organic
Chemistry; Liebeskind, L. S., Ed.; JAI Press: Greenwich, CT, 1994;
Vol. 3, p 255. (b) Tamaru, Y. In Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E.-I., de Meijere, A., Eds.;
Wiley: New York, 2002; Vol. 2, p 1917. (c) Tamaru, Y. In
PerspectiVes in Organopalladium Chemistry for the XXI Century;
Tsuji, J., Ed.; Elsevier: Amsterdam, 1999; p 215. (d) Kondo, T.;
Mitsudo, T.-a. Curr. Org. Chem. 2002, 6, 1163. (e) Tamaru, Y. Eur.
J. Org. Chem. 2005, 13, 2647. (f) Zanoni, G.; Pontiroli, A.; Marchetti,
A.; Vidari, G. Eur. J. Org. Chem. 2007, 3599.
(7) For catalytic asymmetric carbonyl allylation employing allyl metal
reagents: (a) Costa, A. L.; Piazza, M. G.; Tagliavini, E.; Trombini,
C.; Umani-Ronchi, A. J. Am. Chem. Soc. 1993, 115, 7001. (b) Keck,
G. E.; Tarbet, K. H.; Geraci, L. S. J. Am. Chem. Soc. 1993, 115, 8467.
(c) Denmark, S. E.; Coe, D. M.; Pratt, N. E.; Griedel, B. D. J. Org.
Chem. 1994, 59, 6161. (d) Denmark, S. E.; Fu, J. J. Am. Chem. Soc.
2001, 123, 9489.
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Enantioselective Iridium-Catalyzed Carbonyl Allylation
A R T I C L E S
catalytic turnover. Carbonyl-ene processes represent another
approach to carbonyl allylation and are attractive in view of
their byproduct-free nature.15 Whereas conventional Lewis acid-
catalyzed variants require activated carbonyl electrophiles,
recently developed nickel-catalyzed transformations exhibit
complementary substrate scope.16 Finally, metal-catalyzed allyl
transfer from homoallyl alcohols represents a promising strategy
for carbonyl allylation.17
On the basis of the concepts of hydrogenative and transfer
hydrogenative C-C coupling,18-21 we have developed a new
family of catalytic carbonyl allylation methodologies wherein
allenes,22 dienes,23 and allyl acetate24 serve as precursors to
transient allyl metal nucleophiles. These protocols enable
carbonyl allylation in the absence of preformed organometallic
reagents or metallic reductants. Most remarkably, transfer
hydrogenative C-C coupling promotes carbonyl allylation from
the aldehyde or alcohol oxidation level. In the latter case, the
alcohol reactant serves as both reducing agent and aldehyde
precursor. To our knowledge, these processes are among the
very first examples of direct metal-catalyzed C-C couplings
of alcohol and unsaturates.25,26
In this account, the scope of the enantioselective transfer
hydrogenative carbonyl allylation employing allyl acetate is
evaluated,24 and mechanistic investigations that illuminate key
features of the catalytic cycle are presented. Under the conditions
of iridium-catalyzed transfer hydrogenation, allyl acetate couples
to allylic alcohols 1a-c, aliphatic alcohols 1d-l, and benzylic
alcohols 1m-u to provide homoallylic alcohols 3a-u, respec-
tively, in highly optically enriched form. Under nearly identical
conditions, employing isopropanol as the terminal reductant,
allyl acetate couples to enals 2a-c, aliphatic aldehydes 2d-l,
and aryl aldehydes 2m-u to provide an identical set of
enantiomerically enriched homoallylic alcohols 3a-u, respec-
tively. Thus, through transfer hydrogenative C-C coupling,
carbonyl allylation may be achieved from the alcohol or
aldehyde oxidation level. This methodology circumvents the
redox manipulations often required to convert alcohols to
aldehydes and bypasses the barriers imposed by the use of
stoichiometrically preformed allyl metal reagents.
(9) For catalytic carbonyl allylation via reductive coupling of π-allyls based
on palladium, see: (a) Tabuchi, T.; Inanaga, J.; Yamaguchi, M.
Tetrahedron Lett. 1986, 27, 1195. (b) Takahara, J. P.; Masuyama, Y.;
Kurusu, Y. J. Am. Chem. Soc. 1992, 114, 2577. (c) Kimura, M.;
Ogawa, Y.; Shimizu, M.; Sueishi, M.; Tanaka, S.; Tamaru, Y.
Tetrahedron Lett. 1998, 39, 6903. (d) Kimura, M.; Tomizawa, T.;
Horino, Y.; Tanaka, S.; Tamaru, Y. Tetrahedron Lett. 2000, 41, 3627.
(e) Kimura, M.; Shimizu, M.; Shibata, K.; Tazoe, M.; Tamaru, Y.
Angew. Chem., Int. Ed. 2003, 42, 3392. (f) Zanoni, G.; Gladiali, S.;
Marchetti, A.; Piccinini, P.; Tredici, I.; Vidari, G. Angew. Chem., Int.
Ed. 2004, 43, 846. (g) Kimura, M.; Shimizu, M.; Tanaka, S.; Tamaru,
Y. Tetrahedron 2005, 61, 3709. (h) Howell, G. P.; Minnaard, A. J.;
Feringa, B. L. Org. Biomol. Chem. 2006, 4, 1278. (i) Barczak, N. T.;
Grote, R. E.; Jarvo, E. R. Organometallics 2007, 26, 4863.
(10) For catalytic carbonyl allylation via reductive coupling of π-allyls based
on rhodium, see: Masuyama, Y.; Kaneko, Y.; Kurusu, Y. Tetrahedron
Lett. 2004, 45, 8969.
Results and Discussion
The initially disclosed catalytic system for transfer hydroge-
native carbonyl allylation24 employed an iridium catalyst
generated in situ from [Ir(cod)Cl]2 and a chelating triarylphos-
phine ligand. As illustrated in the coupling of allyl acetate to
p-nitrobenzyl alcohol 1m, it was found that optimal conversions
are obtained using Cs2CO3 (20 mol %) and m-nitrobenzoic acid
(10 mol %) as additives (Table 1, entry 1). Other carbonate
(11) For catalytic carbonyl allylation Via reductive coupling of π-allyls
based on iridium, see: (a) Masuyama, Y.; Chiyo, T.; Kurusu, Y. Synlett
2005, 2251. (b) Banerjee, M.; Roy, S. J. Mol. Catal. A 2006, 246,
231. (c) Masuyama, Y.; Marukawa, M. Tetrahedron Lett. 2007, 48,
5963.
(12) For catalytic carbonyl allylation Via reductive coupling of π-allyls
based on ruthenium, see: (a) Tsuji, Y.; Mukai, T.; Kondo, T.;
Watanabe, Y. J. Organomet. Chem. 1989, 369, C51. (b) Kondo, T.;
Ono, H.; Satake, N.; Mitsudo, T.-a.; Watanabe, Y Organometallics
1995, 14, 1945.
(20) For hydrogenative aldol and Mannich addition, see: (a) Jung, C.-K.;
Garner, S. A.; Krische, M. J. Org. Lett. 2006, 8, 519. (b) Jung, C.-K.;
Krische, M. J. J. Am. Chem. Soc. 2006, 128, 17051. (c) Garner, S. A.;
Krische, M. J. J. Org. Chem. 2007, 72, 5843. (d) Bee, C.; Han, S. B.;
Hassan, A.; Iida, H.; Krische, M. J. J. Am. Chem. Soc. 2008, 130,
2746.
(13) For selected examples of carbonyl allylation Via catalytic Nozaki-
Hiyama-Kishi coupling of allylic halides, see: (a) Fu¨rstner, A.; Shi,
N. J. Am. Chem. Soc. 1996, 118, 2533. (b) Bandini, M.; Cozzi, P. G.;
Umani-Ronchi, A. Polyhedron 2000, 19, 537. (c) McManus, H. A.;
Cozzi, P. G.; Guiry, P. J. AdV. Synth. Catal. 2006, 348, 551. (d)
Hargaden, G. C.; Mu¨ller-Bunz, H.; Guiry, P. J. Eur. J. Org. Chem.
2007, 4235. (e) Hargaden, G. C.; O’Sullivan, T. P.; Guiry, P. J. Org.
Biomol. Chem. 2008, 6, 562.
(21) For hydrogenative acyl substitution via reductive hydroacylation, see:
Hong, Y.-T.; Barchuk, A.; Krische, M. J. Angew. Chem., Int. Ed. 2006,
128, 6885.
(14) For a recent review of catalytic Nozaki-Hiyama-Kishi coupling, see:
Hargaden, G. C.; Guiry, P. J. AdV. Synth. Catal. 2007, 349, 2407.
(15) For reviews on carbonyl-ene reactions, see: (a) Mikami, K.; Shimizu,
M. Chem. ReV. 1992, 92, 1021. (b) Berrisford, D. J.; Bolm, C. Angew.
Chem., Int. Ed. 1995, 34, 1717. (c) Johnson, J. S.; Evans, D. A. Acc.
Chem. Res. 2000, 33, 325.
(22) For hydrogenative and transfer hydrogenative carbonyl allylations
employing allenes as allyl donors, see: (a) Skucas, E.; Bower, J. F.;
Krische, M. J. J. Am. Chem. Soc. 2007, 129, 12678. (b) Bower, J. F.;
Skucas, E.; Patman, R. L.; Krische, M. J. J. Am. Chem. Soc. 2007,
129, 15134. (c) Ngai, M.-Y.; Skucas, E.; Krische, M. J. Org. Lett.
2008, 10, 2705.
(16) For nickel catalyzed carbonyl-ene reactions, see: (a) Ho, C.-Y.; Ng,
S.-S.; Jamison, T. F. J. Am. Chem. Soc. 2006, 128, 5362. (b) Ng,
S.-S.; Ho, C.-Y.; Jamison, T. F. J. Am. Chem. Soc. 2006, 128, 11513.
(17) Sumida, Y.; Takada, Y.; Hayashi, S.; Hirano, K.; Yorimitsu, H.;
Oshima, K. Chem. Asian J. 2008, 3, 119, and references cited therein.
(18) 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.
(23) For transfer hydrogenative carbonyl allylations employing dienes as
allyl donors, see: (a) Bower, J. F.; Patman, R. L.; Krische, M. J. Org.
Lett. 2008, 10, 1033. (b) Shibahara, F.; Bower, J. F.; Krische, M. J.
J. Am. Chem. Soc. 2008, 130, 6338.
(24) For transfer hydrogenative carbonyl allylations employing allyl acetate
as allyl donor, see: Kim, I. S.; Ngai, M.-Y.; Krische, M. J. J. Am.
Chem. Soc. 2008, 130, 6340.
(25) Formal substitution of alcohols by C-nucleophiles may be achieved
under the conditions of hydrogen auto-transfer by way of oxidation-
condensation-reduction. The alcohol-unsaturate couplings developed
in our laboratory provide products of carbonyl addition, representing
a formal C-H functionalization of the carbinol carbon. For recent
reviews of hydrogen auto-transfer processes, see: (a) Guillena, G.;
Ramo´n, D. J.; Yus, M. Angew. Chem., Int. Ed. 2007, 46, 2358. (b)
Hamid, M. H. S. A.; Slatford, P. A.; Williams, J. M. J. AdV. Synth.
Catal. 2007, 349, 1555.
(19) For hydrogenative CdX vinylation, see: (a) Kong, J.-R.; Ngai, M.-
Y.; Krische, M. J. J. Am. Chem. Soc. 2006, 128, 718. (b) Kong, J.-R.;
Krische, M. J. J. Am. Chem. Soc. 2006, 128, 16040. (c) Komanduri,
V.; Krische, M. J. J. Am. Chem. Soc. 2006, 128, 16448. (d) Cho, C.-
W.; Krische, M. J. Org. Lett. 2006, 8, 3873. (e) Hong, Y.-T.; Cho,
C.-W.; Skucas, E.; Krische, M. J. Org. Lett. 2007, 9, 3745. (f) Ngai,
M.-Y.; Barchuk, A.; Krische, M. J. J. Am. Chem. Soc. 2007, 129,
280. (g) Skucas, E.; Kong, J. R.; Krische, M. J. J. Am. Chem. Soc.
2007, 129, 7242. (h) Barchuk, A.; Ngai, M.-Y.; Krische, M. J. J. Am.
Chem. Soc. 2007, 129, 8432. (i) Ngai, M.-Y.; Barchuk, A.; Krische,
M. J. J. Am. Chem. Soc. 2007, 129, 12644.
(26) For catalytic functionalization of carbinol C-H bonds, see: (a) Shi,
L.; Tu, Y.-Q.; Wang, M.; Zhang, F.-M.; Fan, C.-A.; Zhao, Y.-M.;
Xia, W. J. J. Am. Chem. Soc. 2005, 127, 10836. (b) Jiang, Y.-J.; Tu,
Y.-Q.; Zhang, E.; Zhang, S.-Y.; Cao, K.; Shi, L. AdV. Synth. Catal.
2008, 350, 552.
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A R T I C L E S
Kim et al.
Table 1. Selected Optimization Experiments Illustrating the Effect
of Basic and Acidic Additives and Iridium Source in the Transfer
Hydrogenative Allylation of p-Nitrobenzyl Alcohol 1ma
Table 2. Selected Optimization Experiments Illustrating the Effect
of Allyl Acetate Loading, Solvent, and Ligand in the Transfer
Hydrogenative Allylation of p-Nitrobenzyl Alcohol 1ma
a All reactions were performed in 13 × 100 mm pressure tubes. The
yields cited are of material isolated by silica gel chromatography. THF
)
tetrahydrofuran; DCE
Information for further details.
)
1,2-dichloroethane. See Supporting
The effects of allyl acetate loading, solvent, and ligand were
evaluated under the optimum conditions cited in Table 1.
Reactions conducted using 2 or 5 equiv of allyl acetate were
not as efficient as those employing 10 equiv (Table 2, entries
1-3). Reactions conducted in dioxane proceed as efficiently as
those conducted in THF (Table 2, entries 3 and 4). However,
reactions conducted in toluene or DCE are highly inefficient
(Table 2, entries 5 and 6). Finally, the bidentate phosphine ligand
BIPHEP was far superior to the monodentate phosphine ligand
PPh3 under otherwise identical conditions (Table 2, entries 1
and 7).
a All reactions were performed in 13 × 100 mm pressure tubes. The
yields cited are of material isolated by silica gel chromatography.
Variation in concentration or temperature resulted in diminished isolated
yields of 3m. In all cases, 0.1-5% of the corresponding O-allylation
product is observed. See Supporting Information for further details.
bases (K2CO3, Na2CO3, Li2CO3) used in combination with
m-nitrobenzoic acid are far less effective (Table 1, entries 2-4).
Use of m-nitrobenzoic acid in the absence of any basic additive
gives only trace quantities of allylation product 3m (Table 1,
entry 5), yet use of Cs2CO3 in the absence of an acidic additive
provides allylation product 3m in 47% yield (Table 1, entry 6).
In the absence of any additive, allylation product 3m is generated
in 10% yield (Table 1, entry 7). Logically, it was thought that
Cs2CO3 and m-nitrobenzoic acid react under the coupling
conditions to form cesium m-nitrobenzoate. Indeed, upon use
of cesium m-nitrobenzoate as an additive, the allylation product
3m forms in 72% yield (Table 1, entry 8). Using Cs2CO3 (20
mol %) and m-NO2BzOCs (10 mol %), a 79% yield of allylation
product 3m is obtained (Table 1, entry 9). Thus, it indeed would
appear that Cs2CO3 and m-nitrobenzoic acid serve as a source
of cesium m-nitrobenzoate. However, just as the choice of alkali
ion is critical, so is the choice of carboxylate. Among carboxylic
acids, m-nitrobenzoic acid is unique in its ability to promote
high levels of conversion (Table 1, entries 1 and 10-14).
Interestingly, m-nitrobenzoic acid also is required for high levels
of enantioselection (vide infra, Table 4). To assess whether
π-complexation effects27 account for the unique behavior of
m-nitrobenzoic acid, methyl m-nitrobenzoate was used as an
additive along with Cs2CO3 (Table 1, entry 15). The observed
decrease in yield suggests such effects are not operative. Finally,
cationic iridium complexes display reactivity roughly equivalent
to that of the corresponding neutral complexes in both the
presence and the absence of m-nitrobenzoic acid (Table 1, entries
1, 6, 16, and 17).
The feasibility of highly enantioselective carbonyl allylation
under transfer hydrogenation conditions was rendered uncertain
due to the likelihood of product racemization by way of redox
equilibration. This concern was especially germane to transfer
hydrogenative carbonyl allylations from the aldehyde oxidation
level, where both product and terminal reductant (isopropanol)
are secondary alcohols. Gratifyingly, it was found that high
levels of asymmetric induction are obtained in carbonyl allyl-
ations from the alcohol or aldehyde oxidation level. As revealed
in an assay of chiral bidentate phosphine ligands in the allylation
of cinnamyl alcohol 1a, chelating triarylphosphines are required
(Table 3). Among the chiral bidentate phosphine ligands
screened, reactions conducted using (R)-Cl,MeO-BIPHEP as
ligand proceed with optimal levels of conversion and asymmetric
induction (Table 3, entry 1). Trace conversion to product is
observed using chiral bidentate phosphine ligands possessing
any degree of alkyl substitution at phosphorus. Notably, erosion
of optical purity as a function of reaction time is not observed.
The highly specialized effect of m-nitrobenzoic acid on
catalytic efficiency demanded a deeper understanding of how
the structural and interactional features of this carboxylic acid
are manifested. In the enantioselective coupling of allyl acetate
to cinnamyl alcohol 1a in the presence and in the absence of
m-NO2BzOH using (R)-Cl,MeO-BIPHEP as ligand, one obtains
(R)-3a and (S)-3a, respectively (Table 4, entries 1 and 2). This
inversion in enantioselectivity suggests that m-nitrobenzoic acid
and the iridium center are intimately associated during the
enantiodetermining carbonyl addition event. On the basis of
these data, it was postulated that iridium and m-nitrobenzoic
acid react to form an ortho-cyclometalated complex, which
serves as the active catalyst.28
(27) For a review of the effects of olefinic additives on metal-catalyzed
C-C coupling processes, see: Johnson, J. B.; Rovis, T. Angew. Chem.,
Int. Ed. 2008, 47, 840.
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Enantioselective Iridium-Catalyzed Carbonyl Allylation
A R T I C L E S
Table 3. Selected Results from an Assay of Chiral Ligand in the
Transfer Hydrogenative Allylation of Cinnamyl Alcohol 1a and
Effect of Temperature on Enantiomeric Excessa
Figure 2. Structure assigned to a catalytically active ortho-cyclometalated
iridium(III)-π-allyl complex (V), as determined by single-crystal X-ray
diffraction analysis. The graphics are depictions of crystallographic data
imported into ChemBioDraw Ultra 11.0. For clarity, the binaphthyl moiety
of the structure on the left was omitted.
allylation of aldehyde 2n under standard conditions, suggesting
that complex V is indeed catalytically relevant. In fact, in the
transfer hydrogenative carbonyl allylation of aldehyde 2n,
complex V provides superior conversion and optical enrichment
in comparison to the analogous reaction involving generation
of the catalyst in situ (Scheme 1).
Scheme 1. Experiments Corroborating Intervention of
Ortho-Cyclometalated Iridium(III)-π-Allyl Complex V as a
Catalytically Relevant Entitya
a All reactions were performed in 13 × 100 mm pressure tubes. The
yields cited are of material isolated by silica gel chromatography.
Enantiomeric excess was determined by chiral stationary phase HPLC
analysis. See Supporting Information for further details.
Table 4. Selected Optimization Experiments Illustrating the Effects
of Substitution of m-Nitrobenzoic Acid on Conversion and
Enantiomeric Excess in the Transfer Hydrogenative Allylation of
Cinnamyl Alcohol 1aa
a All reactions were performed in 13 × 100 mm pressure tubes. The
yields cited are of material isolated by silica gel chromatography. Enan-
tiomeric excess (ee) was determined by chiral stationary-phase HPLC
analysis. See Supporting Information for further details.
Intervention of complex V as a catalytically relevant species
also is implicated by the results of an assay of methyl-substituted
m-nitrobenzoic acids in the enantioselective coupling of allyl
acetate to cinnamyl alcohol 1a (Table 4, entries 3-5). Whereas
enantioselective coupling of allyl acetate to cinnamyl alcohol
1a in the presence of m-NO2BzOH using (R)-Cl,MeO-BIPHEP
as ligand provides (R)-3a, the enantiomeric adduct (S)-3a is
obtained in reactions conducted in the presence of 2-methyl-
5-nitrobenzoic acid, where a methyl group blocks the preferred
site of cyclometalation (Table 4, entries 1 and 3). Conversely,
using 2-methyl-3-nitrobenzoic acid or 4-methyl-3-nitrobenzoic
acid, where the preferred site of cyclometalation remains free,
(R)-3a is again obtained (Table 4, entries 4 and 5).
a All reactions were performed in 13 × 100 mm pressure tubes. The
yields cited are of material isolated by silica gel chromatography.
Enantiomeric excess (ee) was determined by chiral stationary-phase
HPLC analysis. See Supporting Information for further details.
To challenge this hypothesis, an attempt was made to isolate
a catalytically relevant complex. A THF solution of [Ir(cod)Cl]2
(100 mol %), (R)-BINAP (200 mol %), and m-NO2BzOH (400
mol %) was heated to 80 °C for 3 h in the presence of Cs2CO3
(400 mol %). After cooling and removal of residual solid
m-NO2BzOCs, allyl acetate (200 mol %) was added, and the
solution was heated to 80 °C for 1 h. After cooling, hexane
was added to the solution, which resulted in the formation of a
yellow precipitate. The precipitate was crystallized from
THF-ether. Single-crystal X-ray diffraction analysis revealed
the ortho-cyclometalated iridium(III)-π-allyl complex V (Fig-
ure 2). The stability of complex V cast doubt on its role as a
catalytically relevant species. However, complex V serves as
an active catalyst in the transfer hydrogenative carbonyl
Optimal conditions established for the enantioselective trans-
fer hydrogenative allylation of cinnamyl alcohol 1a were applied
to allylic alcohols 1a-c and aliphatic alcohols 1d-l (Table 5).
(28) The ortho-cyclometalation of C5Me5-iridium complexes onto m-
nitrobenzoate occurs at the para-position with respect to the nitro
moiety: Kisenyi, J. M.; Sunley, G. J.; Cabeza, J. A.; Smith, A. J.;
Adams, H.; Salt, N. J.; Maitlis, P. M. J. Chem. Soc., Dalton Trans.
1987, 2459.
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A R T I C L E S
Kim et al.
Table 5. Ir-Catalyzed Transfer Hydrogenative Allylation of Allylic
Alcohols 1a-c and Aliphatic Alcohols 1d-la
Table 6. Ir-Catalyzed Transfer Hydrogenative Allylation of Enals
2a-c and Aliphatic Aldehydes 2d-la
a All reactions were performed in 13 × 100 mm pressure tubes. The
cited yields are of material isolated by silica gel chromatography.
Enantiomeric excess (ee) was determined by chiral stationary-phase
HPLC analysis. b 40 h. c 120 °C. d Due to volatility, the crude product
was converted to the m-nitrobenzoate. See Supporting Information for
further details.
a All reactions were performed in 13 × 100 mm pressure tubes. The
cited yields are of material isolated by silica gel chromatography.
Enantiomeric excess (ee) was determined by chiral stationary-phase
HPLC analysis. b 40 h. c 120 °C. d Due to volatility, the crude product
was converted to the m-nitrobenzoate. See Supporting Information for
further details.
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Enantioselective Iridium-Catalyzed Carbonyl Allylation
A R T I C L E S
Table 7. Ir-Catalyzed Transfer Hydrogenative Allylation of Benzylic
Alcohols 1m-ua
Scheme 2. Ir-Catalyzed Transfer Hydrogenative Allylation of
Benzylic Alcohol 1n Employing Isotopically Labeled Allyl Acetatea
Entry
Aryl Moiety
Alcohol
Product
Yield (%)
ee (%)
1
2
3
4
5
6
7
8
9
p-NO2Ph
1m
1n
1o
1p
1q
1r
1s
3m
3n
3o
3p
3q
3r
3s
72
77
76
62
74
80
73
61
55
91
93
91
93
93
92
93
92
90
p-(CO2Me)Ph
piperonyl
Ph
a The reaction was performed in a 13 × 100 mm pressure tube. The
cited yield is of material isolated by silica gel chromatography. See
Supporting Information for further details.
p-BrPh
o-MeOPh
p-MeOPh
3,5-CI2Ph
2-(N-Me-indolyl)
1t
1u
3t
3u
Scheme 3. Experiments Establishing Rapid Redox Equilibration in
Advance of Carbonyl Additiona
a All reactions were performed in 13 × 100 mm pressure tubes. The
cited yields are of material isolated by silica gel chromatography.
Enantiomeric excess (ee) was determined by chiral stationary-phase
HPLC analysis. See Supporting Information for further details.
Table 8. Ir-Catalyzed Transfer Hydrogenative Allylation of Aryl
Aldehydes 2m-ua
Entry
Aryl Moiety
Aldehyde
Product
Yield (%)
ee (%)
1
2
3
4
5
6
7
8
9
p-NO2Ph
2m
2n
2o
2p
2q
2r
2s
3m
3n
3o
3p
3q
3r
3s
78
85
83
76
77
86
75
76
82
97
97
94
96
97
95
94
98
94
p-(CO2Me)Ph
piperonyl
Ph
p-BrPh
o-MeOPh
p-MeOPh
3,5-CI2Ph
2-(N-Me-indolyl)
2t
2u
3t
3u
a All reactions were performed in 13 × 100 mm pressure tubes. The
cited yields are of material isolated by silica gel chromatography. See
Supporting Information for further details.
a All reactions were performed in 13 × 100 mm pressure tubes. The
cited yields are of material isolated by silica gel chromatography.
Enantiomeric excess (ee) was determined by chiral stationary-phase
HPLC analysis. See Supporting Information for further details.
the homoallylic alcohols 3i and 3k are generated inefficiently,
presumably due to elimination of the ꢀ-heteroatom group (Table
6, entries 8 and 9). Here, improved isolated yields of homoallylic
alcohols 3i,k are achieved by simply conducting the allylation
from the alcohol oxidation level (Table 5, entries 8 and 9).
The desired homoallylic alcohols 3a-l were generated in good
yield and with optical enrichments ranging from 86 to 95%
enantiomeric excess. Remarkably, as demonstrated by the
formation of homoallylic alcohols 3e-g, aliphatic alcohols
possessing secondary, tertiary and quaternary centers adjacent
to the transient carbonyl moiety couple in a highly enantiose-
lective fashion (Table 5, entries 5-7). Additionally, as dem-
onstrated by the formation of homoallylic alcohols 3h-k,
aliphatic alcohols possessing both nitrogen and oxygen atoms
at the carbon atoms R or ꢀ to the transient carbonyl moiety
couple efficiently (Table 5, entries 8 and 9).
Under identical conditions, but employing isopropanol as a
hydrogen donor, allyl acetate couples to enals 2a-c and aliphatic
aldehydes 2d-l to furnish an identical set of homoallylic
alcohols, 3a-l (Table 6). In general, the aldehyde couplings
provide slightly higher enantioselectivities. For example, forma-
tion of the homoallylic alcohol 3b occurs in 76% isolated yield
and 86% enantiomeric excess from the alcohol 1b (Table 5,
entry 2); this adduct is obtained in 77% isolated yield and 96%
enantiomeric excess from the aldehyde 2b (Table 6, entry 2).
In the case of ꢀ-heteroatom-substituted aldehydes 2i and 2k,
Benzylic alcohols 1m-u and aryl aldehydes 2m-u also
participate in transfer hydrogenative carbonyl allylation. As
disclosed in our initial communication of this work,24 benzylic
alcohols 1m-u are subject to allylation using an iridium catalyst
generated in situ from [Ir(cod)Cl]2, (R)-BINAP, and m-NO2-
BzOH in the presence of Cs2CO3 (Table 7). Using iridium
catalysts ligated by (-)-TMBTP29 under identical conditions,
but employing isopropanol as a hydrogen donor, an identical
set of homoallylic alcohols, 3m-u, are prepared from the
corresponding aryl aldehydes 2m-u (Table 8).
Additional experiments aimed at illuminating features of the
catalytic mechanism were undertaken. Transfer hydrogenative
allylation of benzylic alcohol 1n using isotopically labeled allyl
(29) (a) Benincori, T.; Cesarotti, E.; Piccolo, O.; Sannicolo`, F. J. Org. Chem.
2000, 65, 2043. (b) Shimizu, H.; Nagasaki, I.; Saito, T. Tetrahedron
2005, 61, 5405.
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A R T I C L E S
Kim et al.
Scheme 4. Postulated Catalytic Mechanisms for the Iridium-Catalyzed Transfer Hydrogenative Coupling from the Alcohol or Aldehyde
Oxidation Level (Ln ) Chelating Triaryl Phosphine, e.g., (R)-BINAP or (R)-Cl,MeO-BIPHEP)
acetate30 provides equimolar quantities of deuterio-3n and iso-
deuterio-3n (Scheme 2). These results are consistent with
intervention of symmetric iridium π-allyl intermediates or rapid
interconversion of σ-allyl haptomers through the agency of a
symmetric π-allyl. Competition experiments involving exposure
of allyl acetate to equimolar quantities of 1p and 2m under
standard conditions, employing BIPHEP as ligand, provide 3p
and 3m in 95% yield in a 1:3.7 ratio, respectively. A very similar
product distribution and yield are obtained in the analogous
coupling employing equimolar amounts of 2p and 1m, estab-
lishing rapid redox equilibration in advance of C-C coupling
(Scheme 3).
The following mechanism for iridium-catalyzed transfer
hydrogenative allylation appears plausible, based upon the
collective data. Association of the chelating phosphine ligand
and m-NO2BzOH to [Ir(cod)Cl]2 delivers the iridium carboxylate
IIa, which is in equilibrium with the ortho-cyclometalated
complex I. Oxidative addition of allyl acetate to complex IIa
should deliver an iridium carboxylate (not shown), which should
be predisposed to acetate-assisted ortho-metalation through the
six-centered transition structure IIIa to furnish the σ-allyl C,O-
benzoate complex IV.31,32 Rapid equilibration of the five-
coordinate complex IV with the corresponding π-allyl haptomer
V is consistent with the results of isotopic labeling (vide supra,
Scheme 2). The π-allyl haptomer V has been characterized by
single-crystal X-ray diffraction analysis (vide supra, Figure 2).
Allyl transfer to the aldehyde through a closed chairlike
transition structure delivers the homoallyl iridium alkoxide VI.11
The configurational stability of the homoallylic alcohol is
presumably due to occupation of the remaining coordination
site at iridium(III) by the olefin moiety of the homoallylic
(31) For acetate-assisted cyclometalation of iridium complexes, see: (a)
Davies, D. L.; Donald, S. M. A.; Al-Duaij, O.; Macgregor, S. A.;
Po¨lleth, M. J. Am. Chem. Soc. 2006, 128, 4210. (b) Davies, D. L.;
Donald, S. M. A.; Al-Duaij, O.; Fawcett, J.; Little, C.; Macgregor,
S. A. Organometallics 2006, 25, 5976.
(32) For selected examples of carboxylate assisted cyclometalation involving
other transition metal complexes, see the following. Rhodium: (a) Ito,
J.-I.; Nishiyama, H. Eur. J. Inorg. Chem. 2007, 1114Palladium: (b)
Davies, D. L.; Donald, S. M. A.; Macgregor, S. A. J. Am. Chem. Soc.
2005, 127, 13754. (c) Garcia-Cuadrado, D.; Braga, A. A. C.; Maseras,
F.; Echavarren, A. M. J. Am. Chem. Soc. 2006, 128, 1066. (d) Lafrance,
M.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 16496. Carboxylate-
assisted metalation of arenes exhibits acid-base character, requiring
a certain level of electron deficiency at the carbon undergoing
substitution. Our data suggest that cyclometalation of m-nitrobenzoic
acid is especially facile due to the confluence of the following effects.
The nitro moiety withdraws electron density through the π-system
and the σ-framework, activating the positions ortho and para to the
nitro moiety. The carboxy moiety assists ortho-metalation by reducing
the entropy of activation and through enthalpic stabilization of the
product through chelation.
(30) Schuetz, R. D.; Millard, F. W. J. Org. Chem. 1959, 24, 297.
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Enantioselective Iridium-Catalyzed Carbonyl Allylation
A R T I C L E S
of allyl acetate to allylic alcohols 1a-c, aliphatic alcohols 1d-l,
and benzylic alcohols 1m-u, a broad range of alcohols are
efficiently converted to highly optically enriched homoallyl
alcohols 3a-u. An identical set of adducts 3a-u may be
obtained from the aldehyde oxidation level simply by employing
isopropanol as a terminal reductant. Thus, enals 2a-c, aliphatic
aldehydes 2d-l, and aryl aldehydes 2m-u are converted to
adducts 3a-u.
Key features of the catalytic mechanism have been elucidated.
The cyclometalated complex V, which has been characterized
by single-crystal X-ray diffraction, has been established as a
catalytically relevant species. Isotopic labeling studies implicate
intervention of a symmetric iridium π-allyl intermediates or
rapid interconversion of σ-allyl haptomers through the agency
of a symmetric π-allyl. Finally, competition experiments
demonstrate rapid and reversible hydrogenation-dehydrogenation
of the carbonyl partner in advance of C-C coupling. Despite
facile redox equilibration of the starting alcohol and the fact
that isopropanol, a secondary alcohol, may serve as terminal
reductant, the resulting homoallylic alcohols 3a-u experience
almost no erosion of optical purity by way of redox equilibration
under the coupling conditions. Plausible catalytic mechanisms
that account for these observations and a stereochemical model
explaining the observed sense of absolute stereoinduction are
proposed.
Figure 3. Proposed stereochemical model accounting for the observed sense
of absolute stereoinduction, based on single-crystal X-ray diffraction data
corresponding to complex V. The graphics are modifications based on single-
crystal X-ray diffraction data corresponding to complex V, which were
imported into ChemBioDraw Ultra 11.0. For clarity, the binaphthyl moiety
has been truncated.
alcohol, which disables ꢀ-hydride elimination pathways. How-
ever, upon exchange of the homoallyl alcohol for isopropanol
or a reactant alcohol, as in the conversion of VI to VII, a
coordination site becomes available and ꢀ-hydride elimination
ensues to deliver complex VIII. Dissociation of aldehyde
regenerates the ortho-cyclometalated complex I (Scheme 4, top).
A related pathway that appears plausible involves proton loss
from the ortho-cyclometalated complex I to deliver the anionic
iridium(I) C,O-benzoate IIb. Such proton loss may be facilitated
by stabilization of the nascent anion by the ortho-carboxy and
the para-nitro moieties of the C,O-benzoate. Oxidative addition
of allyl acetate provides the anionic iridium(III) σ-allyl complex
IIIb, which upon loss of acetate delivers the neutral σ-allyl and
π-allyl complexes IV and V, respectively. The remainder of
the catalytic mechanism is identical to that previously described.
A primary distinction between the two mechanisms resides in
the fluxional versus fixed attachment of the ortho-C-benzoate
linkage. In the latter mechanistic hypothesis, the ortho-C,O-
benzoate remains intact throughout the duration of the catalytic
cycle (Scheme 4, bottom).
A stereochemical model accounting for the observed sense
of absolute stereoinduction is based upon the coordination mode
revealed in the crystal structure of complex V. Complexation
of aldehyde by the σ-allyl haptomer IV is postulated to occur
at the indicated position adjacent to the C,O-benzoate. In this
way, the sterically less demanding allyl moiety is placed between
the naphthyl and phenyl moieties of the ligand, allowing the
aldehyde to reside in a more open environment. In the favored
mode of addition, the aldehyde is bound such that the aldehydic
C-H bond projects into the π-face of a phenyl moiety of the
ligand, giving rise to a weakly attractive aldehyde C-H
π-interaction.33 In the disfavored mode of addition, the aldehyde
is bound such that the aldehydic “R group” projects into the
π-face of a phenyl moiety of the ligand, giving rise to a severe
nonbonded interaction (Figure 3).
Organic molecules, by definition, are composed of carbon
and hydrogen. Hence, the ability to direct C-C coupling
through the use of catalytic hydrogenation and transfer
hydrogenation evokes numerous possibilities for the con-
struction of diverse molecular architectures, circumventing
use of preformed organometallic reagents. In the present case,
allyl acetate serves as a surrogate to preformed allyl metal
reagents in carbonyl addition. Rather than generating sto-
ichiometric quantities of metallic byproductssfor example,
molar equivalents of tin waste emanating from the use of
allyl stannanessone instead generates 1 equiv of acetic acid.
Because one may conduct carbonyl addition from the alcohol
oxidation level, one avoids redox manipulations often
required to convert alcohols to aldehydes, thus enhancing
step economy. Future studies will focus on the development
of related hydrogenative and transfer hydrogenative cou-
plings, including diastereo- and enantioselective crotylations,
based on insights garnered herein.
Acknowledgment is made to Merck, the Robert A. Welch
Foundation, the ACS-GCI Pharmaceutical Roundtable, the NIH-
NIGMS (RO1-GM069445), and the Korea Research Foundation
(Grant No. KRF-2007-356-E00037) for partial support of this
research. Dr. Oliver Briel of Umicore is thanked for the generous
donation of [Ir(cod)Cl]2.
Summary
Supporting Information Available: Experimental details and
spectroscopic data; 1H NMR, 13C NMR, IR, HRMS, and
HPLC data for unknown compounds 3f, 3h, and 3i; 1H NMR,
13C NMR, and HPLC data for known compounds 3a-e, 3g,
and 3j-u; and single-crystal X-ray diffraction data for
complex V. This material is available free of charge via the
Internet at http://pubs.acs.org.
A protocol for enantioselective carbonyl allylation from the
alcohol or aldehyde oxidation level has been developed. An
ortho-cyclometalated iridium complex has been established as
the active catalyst. As demonstrated by the reductive coupling
(33) (a) Gallivan, J. P.; Dougherty, D. A. Proc. Natl. Acad. Sci. U.S.A.
1999, 96, 9459. (b) Tatko, C. D.; Waters, M. L. J. Am. Chem. Soc.
2004, 126, 2028.
JA805722E
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