Iridium-catalyzed anti -diastereo- and enantioselective carbonyl (Trimethylsilyl)allylation from the alcohol or aldehyde oxidation level

Article abstract of DOI:10.1021/ja103299f

Using the ortho-cyclometalated π-allyl iridium precatalyst (R)-I derived from [Ir(cod)Cl]₂, 4-cyano-3-nitrobenzoic acid, (R)-SEGPHOS, and allyl acetate, enantioselective transfer hydrogenation of α- (trimethylsilyl)allyl acetate in the presence

Full text of DOI:10.1021/ja103299f

Published on Web 06/11/2010
Iridium-Catalyzed anti-Diastereo- and Enantioselective
Carbonyl (Trimethylsilyl)allylation from the Alcohol or
Aldehyde Oxidation Level
Soo Bong Han, Xin Gao, and Michael J. Krische*
Department of Chemistry and Biochemistry, UniVersity of Texas at Austin, Austin, Texas 78712
Received April 19, 2010; E-mail: mkrische@mail.utexas.edu
Abstract: Using the ortho-cyclometalated π-allyl iridium precatalyst (R)-I derived from [Ir(cod)Cl]2, 4-cyano-
3-nitrobenzoic acid, (R)-SEGPHOS, and allyl acetate, enantioselective transfer hydrogenation of R-(trim-
ethylsilyl)allyl acetate in the presence of aldehydes 2a-i mediated by 2-propanol delivers products of
(trimethylsilyl)allylation 4a-i in good isolated yields and with exceptional levels of anti-diastereoselectivity
and enantioselectivity (90-99% ee). In the absence of 2-propanol, but under otherwise identical reaction
conditions, carbonyl (trimethylsilyl)allylation is achieved directly from the alcohol oxidation level to furnish
an equivalent set of adducts 4a-i with roughly equivalent isolated yields and stereoselectivities. To evaluate
the synthetic utility of the reaction products 4a-i, adduct 4g was converted to the 1,4-ene-diol 5g via
dioxirane-mediated oxidative desilylation with allylic transposition, the allylic alcohol 6g via protodesilylation
with allylic transposition, and the γ-lactam 7g via chlorosulfonyl isocyanate-mediated cycloaddition.
Scheme 1. Iridium-Catalyzed Anti-Diastereo- and Enantioselective
Carbonyl (trimethylsilyl)allylation from the Alcohol or Aldehyde
Oxidation Level
Introduction
In connection with studies aimed at the discovery of
hydrogen-mediated reductive C-C bond formations beyond
hydroformylation, we recently uncovered a broad family of C-C
bond forming transfer hydrogenations promoted by iridium and
ruthenium catalysts.1 A remarkable feature of these processes
resides in the ability to achieve carbonyl addition from the
aldehyde or alcohol oxidation level. In the former case,
2-propanol or formic acid mediates reductive C-C coupling.
In the latter case, dehydrogenation of the primary alcohol
reactants generates aldehyde electrophiles, while simultaneously
driving reductive generation of organometallic nucleophiles from
p-unsaturated reactants. Using ortho-cyclometalated iridium
catalysts, highly enantioselective protocols for carbonyl allyl-
ation,2a,b,e-h,j crotylation,2c,f,j and tert-prenylation2d,f,j from the
alcohol or aldehyde oxidation level were devised. More recently,
related catalytic enantioselective methods carbonyl (hydroxy)-
allylation and (hydroxymethyl)allylation were developed.3 Un-
like conventional methods for carbonyl allylation,4 these
processes circumvent the use of premetalated nucleophiles and
metallic reductants.1-3
Here, using the isolated ortho-cyclometalated π-allyl iridium
precatalyst derived from [Ir(cod)Cl]2, 4-cyano-3-nitrobenzoic
acid, (R)-SEGPHOS,5 and allyl acetate, we report that R-(tri-
methylsilyl)allyl acetate6 1a couples to carbonyl compounds
from the aldehyde or alcohol oxidation level, respectively, with
exceptional levels of regio- and anti-diastereo- and enantiose-
(1) For selected reviews, see: (a) Ngai, M.-Y.; Kong, J. R.; Krische, M. J.
J. Org. Chem. 2007, 72, 1063. (b) Skucas, E.; Ngai, M.-Y.; Komanduri,
V.; Krische, M. J. Acc. Chem. Res. 2007, 40, 1394. (c) Shibahara, F.;
Krische, M. J. Chem. Lett. 2008, 37, 1102. (d) Patman, R. L.; Bower,
J. F.; Kim, I. S.; Krische, M. J. Aldrichim. Acta 2008, 41, 95. (e)
Bower, J. F.; Kim, I. S.; Patman, R. L.; Krische, M. J. Angew. Chem.,
Int. Ed. 2009, 48, 34.
(2) For enantioselective carbonyl allylation, crotylation, and reverse
prenylation via iridium-catalyzed C-C bond-forming transfer hydro-
genation, see: (a) Kim, I. S.; Ngai, M.-Y.; Krische, M. J. J. Am. Chem.
Soc. 2008, 130, 6340. (b) Kim, I. S.; Ngai, M.-Y.; Krische, M. J.
J. Am. Chem. Soc. 2008, 130, 14891. (c) Kim, I. S.; Han, S. B.;
Krische, M. J. J. Am. Chem. Soc. 2009, 131, 2514. (d) Han, S. B.;
Kim, I. S.; Han, H.; Krische, M. J. J. Am. Chem. Soc. 2009, 131,
6916. (e) Lu, Y.; Kim, I. S.; Hassan, A.; Del Valle, D. J.; Krische,
M. J. Angew. Chem., Int. Ed. 2009, 48, 5018. (f) Itoh, J.; Han, S. B.;
Krische, M. J. Angew. Chem., Int. Ed. 2009, 48, 6316. (g) Lu, Y.;
Krische, M. J. Org. Lett. 2009, 11, 3108. (h) Hassan, A.; Lu, Y.;
Krische, M. J. Org. Lett. 2009, 11, 3112. (i) For a recent application
in total synthesis, see Harsh, P.; O’Doherty, G. A. Tetrahedron 2009,
65, 5051. (j) Bechem, B.; Patman, R. L.; Hashmi, S.; Krische, M. J.
J. Org. Chem. 2010, 75, 1795.
(3) For enantioselective carbonyl (hydroxy)allylation and (hydroxy-
methyl)allylation via iridium-catalyzed C-C bond-forming transfer
hydrogenation, see: (a) Han, S. B.; Han, H.; Krische, M. J. J. Am.
Chem. Soc. 2010, 132, 1760. (b) Zhang, Y. J.; Yang, J. H.; Kim, S. H.;
Krische, M. J. J. Am. Chem. Soc. 2010, 132, 4562.
(4) For selected reviews on enantioselective carbonyl allylation and
crotylation, see: (a) Hoffmann, R. W. Angew. Chem., Int. Ed. Engl.
1982, 21, 555. (b) Yamamoto, Y.; Asao, N. Chem. ReV. 1993, 93,
2207. (c) Ramachandran, P. V. Aldrichim. Acta 2002, 35, 23. (d)
Kennedy, J. W. J.; Hall, D. G. Angew. Chem., Int. Ed. 2003, 42, 4732.
(e) Denmark, S. E.; Fu, J. Chem. ReV. 2003, 103, 2763. (f) Yu, C.-
M.; Youn, J.; Jung, H.-K. Bull. Korean Chem. Soc. 2006, 27, 463. (g)
Marek, I.; Sklute, G. Chem. Commun. 2007, 1683. (h) Hall, D. G.
Synlett 2007, 1644.
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A R T I C L E S
Han et al.
Table 1. Enantioselective R-(Trimethylsilyl)allylation from the
Table 2. Enantioselective R-(Trimethylsilyl)allylation from the
Aldehyde Oxidation Levela
Alcohol Oxidation Levela
a Yields are of material isolated by silica gel chromatography.
Enantiomeric excess was determined by chiral stationary phase HPLC
analysis. See Supporting Information for further details.
a As described for Table 1. b The complex modified by (R)-C3-
TUNEPHOS was used as precatalyst.
desilylation with allylic transposition have been identified in
the absence of a hydroxyl protecting group. Finally, upon
exposure to chlorosulfonyl isocyanate, formal [3 + 2] cycload-
dition occurs to deliver γ-lactams possessing three contiguous
stereogenic centers as single diastereomers.
lectivity (Scheme 1). In this fashion, R-(trimethylsilyl)allyl
acetate serves as an alternative to previously reported silicon-
containing 1,3- or 1,1-bimetallic allyl transfer agents.7-11 As
demonstrated in the case of adduct 4g, the products of
(trimethylsilyl)allylation are readily converted to 1,4-ene-diols
upon DMDO oxidation.8h,i Additionally, conditions for proto-
Results and Discussion
Our study began with the attempted (trimethylsilyl)allylation
of benzyl alcohol 3a. Using the ortho-cyclometalated catalyst
generated in situ from [Ir(cod)Cl]2, 4-cyano-3-nitrobenzoic acid,
(R)-SEGPHOS,5 and allyl acetate, neither the desired (trimeth-
ylsilyl)allylation product 4a nor the resulting Peterson olefination
product was detected. Using the isolated π-allyl iridium pre-
catalyst (R)-I in the presence of cesium carbonate, the desired
(5) Saito, T.; Yokozawa, T.; Ishizaki, T.; Moroi, T.; Sayo, N.; Miura, T.;
Kumobayashi, H. AdV. Synth. Catal 2001, 343, 264. For single crystal
x-ray diffraction analysis of a closely related ortho-cyclometalated
iridium π-allyl complex modified by (S)-SEGPHOS, see ref 2d.
(6) Danheiser, R. L.; Fink, D. M.; Okano, K.; Tsai, Y.-M.; Szczepanski,
S. W. Org. Synth. 1988, 66, 14. A modification of this literature
protocol was used to prepare R-(trimethylsilyl)allyl acetate. See
Supporting Information for experimental details.
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Carbonyl (Trimethylsilyl)allylation
A R T I C L E S
Scheme 2. Proposed Catalytic Mechanism and Stereochemical Model for Carbonyl (Trimethylsilyl)allylation from the Alcohol or Aldehyde
Oxidation Level
(trimethylsilyl)allylation product 4a was formed along with
substantial quantities of Peterson olefination product. After
various inorganic bases were screened, it was found that
Peterson olefination is suppressed using K3PO4 (1.0 equiv) in
the presence of water (5.0 equiv) for reactions conducted at 70
°C. Under these conditions, R-(trimethylsilyl)allyl acetate 1a
was coupled to a structurally diverse set of aldehydes 2a-i
(Table 1). In each case, good isolated yields were accompanied
by exceptional levels of diastereo- and enantioselectivity. In the
absence of 2-propanol, but under otherwise identical conditions,
(trimethylsilyl)allylation occurs directly from the alcohol oxida-
tion level to furnish an identical set of adducts 4a-i (Table 2).
Again, good isolated yields were accompanied by exceptional
levels of diastereo- and enantioselectivity. Thus, unlike corre-
sponding protocols involving allylmetal reagents,7-11 carbonyl
(trimethylsilyl)allylation occured with equal facility from the
alcohol or aldehyde oxidation level.
The mechanism for catalytic carbonyl (trimethylsilyl)allyla-
tion is analogous to that previously proposed for related
crotylations.2c However, complete levels of anti-diastereose-
lectivity are observed in nearly all cases, suggesting that
carbonyl addition occurs exclusively from the (E)-σ-allyl
through a chairlike transition structure. Notably, although the
catalyst dehydrogenates primary alcohols 3a-i, the reaction
products 4a-i, which are homoallylic alcohols, are not oxidized
under the coupling conditions and, hence, do not experience
any erosion of enantiomeric purity by way of redox equilibra-
tion. This result is remarkable, as 2-propanol, a secondary
alcohol, is oxidized under the coupling conditions when
aldehydes 2a-i are employed as reactants. As indicated in the
proposed catalytic mechanism (Scheme 2), coordination of
iridium to the homoallylic olefin of reaction products 4a-i
provides a hexacoordinate, 18-electron complex that cannot
engage in ꢀ-hydride elimination due to the absence of an open
coordination site.
(7) For examples of carbonyl additions employing 1,3-bimetallic allyl
transfer agents where M1 ) M2 ) Si, see: (a) Corriu, R.; Escudie, N.;
Guerin, C. J. Organomet. Chem. 1984, 264, 207. (b) Restorp, P.;
Fischer, A.; Somfai, P. J. Am. Chem. Soc. 2006, 128, 12646. (c)
Restorp, P.; Dressel, M.; Somfai, P. Synthesis 2007, 1576. (d) Tuzina,
P.; Somfai, P. Tetrahedron Lett. 2008, 49, 6882.
(8) For examples of carbonyl additions employing 1,3-bimetallic allyl
transfer agents where M1 ) B, M2 ) Si, see: (a) Yatagai, H.;
Yamamoto, Y.; Maruyama, K. J. Am. Chem. Soc. 1980, 102, 4548.
(b) Tsai, D. J. S.; Matteson, D. S. Tetrahedron Lett. 1981, 22, 2751.
(c) Yamamoto, Y.; Yatagai, H.; Maruyama, K. J. Am. Chem. Soc.
1981, 103, 3229. (d) Tsai, D. J. S.; Matteson, D. S. Organometallics
1983, 2, 236. (e) Hoffmann, R. W.; Brinkmann, H.; Frenking, G. Chem.
Ber. 1990, 123, 2387. (f) Roush, W. R.; Grover, P. T.; Lin, X.
Tetrahedron Lett. 1990, 31, 7563. (g) Roush, W. R.; Grover, P. T.
Tetrahedron Lett. 1990, 31, 7567. (h) Barrett, A. G. M.; Malecha,
J. W. J. Org. Chem. 1991, 56, 5243. (i) Roush, W. R.; Grover, P. T.
Tetrahedron 1992, 48, 1981. (j) Hunt, J. A.; Roush, W. R. Tetrahedron
Lett. 1995, 36, 501. (k) Marron, T. G.; Roush, W. R. Tetrahedron
Lett. 1995, 36, 1581. (l) Hunt, J. A.; Roush, W. R. J. Org. Chem.
1997, 62, 1112. (m) Micalizio, G. C.; Roush, W. R. Org. Lett. 2000,
2, 461. (n) Roush, W. R.; Pinchuk, A. N.; Micalizio, G. C. Tetrahedron
Lett. 2000, 41, 9413. (o) Shimizu, M.; Kitagawa, H.; Kurahashi, T.;
Hiyama, T. Angew. Chem., Int. Ed. 2001, 40, 4283. (p) Micalizio,
G. C.; Roush, W. R. Org. Lett. 2001, 3, 1949. (q) Tinsely, J. M.;
Roush, W. R. J. Am. Chem. Soc. 2005, 127, 10818. (r) Va, P.; Roush,
W. R. J. Am. Chem. Soc. 2006, 128, 15960. (s) Lira, R.; Roush, W. R.
Org. Lett. 2007, 9, 4315. (t) Huh, C. W.; Roush, W. R. Org. Lett.
2008, 10, 3371.
To evaluate the utility of the coupling products 4a-i, adducts
4a, 4f, 4g, and 4i were subjected to DMDO-mediated oxidative
elimination.8h,i The 1,4-ene-diols 5a, 5f, 5g, and 5i were
produced in excellent yield with high levels of (E:Z)-selectivity
(Scheme 3). Proto-desilylation was attempted next. Under nearly
all conditions assayed, exclusive formation of Peterson olefi-
nation products was observed. However, upon exposure of
adduct 4g to TiCl4 in the presence of exogenous aldehyde, the
product of proto-desilylation 6g was generated in 73% yield
with complete (E:Z)-selectivity (Scheme 4). In the absence of
aldehyde, Peterson olefination was again the exclusive reaction
product, suggesting that exogenous aldehyde protects the
hydroxyl moiety of 4g through formation of a titanium-bound
hemiacetal. Notably, compound 6g was previously prepared in
seven steps from malic acid.12 Thus far, the proto-desilylation
is most efficient for the benzyl ether-containing adduct 4g
(Scheme 4).
(9) For examples of carbonyl additions employing 1,3-bimetallic allyl
transfer agents where M1 ) Si, M2 ) Ti, see: (a) Sato, F.; Suzuki, Y.;
Sato, M. Tetrahedron Lett. 1982, 23, 4589. (b) Reetz, M. T.;
Wenderoth, B. Tetrahedron Lett. 1982, 23, 5259. (c) Reetz, M. T.;
Steinbach, R.; Westerman, J.; Peter, R.; Wenderoth, B. Chem. Ber.
1985, 118, 1441. (d) Ikeda, Y.; Yamamoto, H. Bull. Chem. Soc. Jpn.
1986, 59, 657. (e) Ducray, R.; Ciufolini, M. A. Angew. Chem., Int.
Ed. 2002, 41, 4688. (f) de Fays, L.; Adam, J.-M.; Ghosez, L.
Tetrahedron Lett. 2003, 44, 7197.
(10) For examples of carbonyl additions employing 1,3-bimetallic allyl
transfer agents where M1 ) Si, M2 ) Cr, see: (a) Hodgson, D. M.;
Wells, C. Tetrahedron Lett. 1992, 33, 4761. (b) Paterson, I.; Schlap-
bach, A. Synlett 1995, 498.
(11) For examples of carbonyl additions employing 1,3-bimetallic allyl
transfer agents where M1 ) Si, M2 ) Sn, see: (a) Lautens, M.; Ben,
R. N.; Delanghe, P. H. M. Tetrahedron 1996, 52, 7221.
(12) Austad, B. C.; Hart, A. C.; Burke, S. D. Tetrahedron 2002, 58, 2011,
and references cited therein.
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Scheme 3. Dioxirane-Mediated Oxidative Desilylation of Adducts
4a, 4f, 4g, and 4i to Furnish the Corresponding 1,4-Ene-diols 5a,
5f, 5g, and 5i
Scheme 5. Reaction of Adduct 4g with Chlorosulfonyl Isocyanate
to Furnish the Product of Formal [3 + 2] Cycloaddition 7g
Conclusion
Scheme 4. Protodesilylation of 4g Requires Exogenous Aldehyde
to Suppress Peterson Olefination
In summary, we report a highly anti-diastereo- and enanti-
oselective carbonyl (trimethylsilyl)allylation under the conditions
of iridium catalyzed transfer hydrogenation employing a single-
component catalyst, the ortho-cyclometalated complex (R)-I.
Notably, identical sets of adducts 4a-i were formed with
comparable levels of selectivity from the aldehyde or alcohol
oxidation level in the absence of Peterson olefination. Oxidative
desilylation of adducts 4a, 4f, 4g, and 4i employing DMDO
provided access to highly enantiomerically enriched 1,4-ene-
diols 5a, 5f, 5g, and 5i.8h,i Conditions for proto-desilylation with
allylic transposition were identified for adduct 4g in the absence
of a hydroxyl protecting group. Finally, exposure of adduct 4g
to chlorosulfonyl isocyanate delivered 4,5-trans-disubstituted
pyrrolidinone 7g as a single diastereomer. Future studies will
focus on the development of related unsaturated alcohol C-C
couplings and related imine additions from the amine oxidation
level.
Finally, under conditions similar to those described by
Woerpel,13 exposure of 4g-OAc to chlorosulfonyl isocyanate
delivers the product of [3 + 2] cycloaddition, the 4,5-trans-
disubstituted pyrrolidinone 7g, as a single diastereomer. Lactone
formation is not observed. Formation of the 7g suggests a
mechanism involving stereoselective addition of chlorosulfonyl
isocyanate to the allylsilane antiperiplanar with respect to the
silyl group to generate the indicated ꢀ-silyl carbocation.
Exclusive N-cyclization accompanied by 1,2-silyl migration
delivers the 4,5-trans-substituted pyrrolidinone 7g. In the absence
of NaHCO3, a mixture of lactone and lactam products are
observed. These data suggest that partitioning of the N- and
O-cyclization pathways is not dictated primarily by steric factors
as proposed by Woerpel,13b but that the acidity of the medium
plays a dominant role (Scheme 5).
Acknowledgment. Acknowledgment is made to the Robert A.
Welch Foundation and the NIH-NIGMS (RO1-GM069445). Dr.
Yasunori Ino and Dr. Wataru Kuriyama of Takasago are thanked
for the generous donation of (R)-SEGPHOS.
Supporting Information Available: Experimental procedures
and spectral data for all new compounds (1H NMR, 13C NMR,
IR, HRMS). This material is available free of charge via the
Internet at http://pubs.acs.org.
(13) (a) Roberson, C. W.; Woerpel, K. A. J. Org. Chem. 1999, 64, 1434,
and references cited therein. (b) Peng, Z.; Woerpel, K. A. Org. Lett.
2001, 3, 675.
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