Ruthenium-catalyzed C-C bond forming transfer hydrogenation: Carbonyl allylation from the alcohol or aldehyde oxidation level employing acyclic 1,3-dienes as surrogates to preformed allyl metal reagents

Article abstract of DOI:10.1021/ja801213x

Under the conditions of ruthenium-catalyzed transfer hydrogenation, commercially available acyclic 1,3-dienes, butadiene, isoprene, and 2,3-dimethylbutadiene, couple to benzylic alcohols 1a-6a to furnish products of carbonyl crotylation 1b-6b, carbonyl isoprenylation 1c-6c, and carbonyl reverse 2-methyl prenylation 1d-6d. Under related transfer hydrogenation conditions employing isopropanol as terminal reductant, isoprene couples to aldehydes 7a-9a to furnish identical products of carbonyl isoprenylation 1c-3c. Thus, carbonyl allylation is achieved from the alcohol or the aldehyde oxidation level in the absence of preformed allyl metal reagents. Coupling to aliphatic alcohols (isoprene to 1-nonanol, 65% isolated yield) and allylic alcohols (isoprene to geraniol, 75% isolated yield) also is demonstrated. Isotopic labeling studies corroborate a mechanism involving hydrogen donation from the reactant alcohol or sacrificial alcohol (i-PrOH). Copyright

Full text of DOI:10.1021/ja801213x

Published on Web 04/29/2008
Ruthenium-Catalyzed C-C Bond Forming Transfer Hydrogenation: Carbonyl
Allylation from the Alcohol or Aldehyde Oxidation Level Employing Acyclic
1,3-Dienes as Surrogates to Preformed Allyl Metal Reagents
Fumitoshi Shibahara, John F. Bower, and Michael J. Krische*
Department of Chemistry and Biochemistry, UniVersity of Texas at Austin, Austin, Texas 78712
Received February 18, 2008; E-mail: mkrische@mail.utexas.edu
Table 1. Ruthenium-Catalyzed Coupling of Acyclic Dienes to
Alcohols 1a-6aa
Ruthenium-catalyzed transfer hydrogenation ranks among the most
powerful methods available for the reduction of polar functional
groups,1 yet reductive C-C bond formations catalyzed by ruthenium
are highly uncommon.2–4 We have shown that reductive C-C bond
formation may be achieved under the conditions of catalytic
hydrogenation5,6 and, more recently, under the conditions of iridium-
catalyzed transfer hydrogenation.7 The iridium-catalyzed processes
enable direct coupling of allenes7a and 1,3-cyclohexadiene7b to
aldehydes or alcohols to furnish products of carbonyl allylation. While
these proof of concept studies establish the use of allenes and dienes
as surrogates to preformed allyl metal reagents, the iridium-catalyzed
couplings were not applicable to acyclic 1,3-dienes.
Here, we report that under the conditions of ruthenium-catalyzed
hydrogen autotransfer8,9 1,3-butadiene, isoprene, and 2,3-dimethyl-
butadiene couple to alcohols 1a-6a to furnish products of carbonyl
allylation 1b-6b, 1c-6c, and 1d-6d, respectively. Under related
transfer hydrogenation conditions employing isopropanol or formic
acid as terminal reductant, aldehydes 7a-9a couple to isoprene to
furnish products of carbonyl allylation 1c-3c, respectively. Thus,
carbonyl allylation is achieved from the alcohol or aldehyde oxidation
level. To our knowledge, these are the first examples of ruthenium-
catalyzed C-C bond formation under the conditions of alcohol-
mediated transfer hydrogenation.2–4 The branched regioselectivity
observed in these couplings complements the linear regioselectivity
observed in nickel-catalyzed diene-aldehyde reductive couplings.10–12
The transfer hydrogenative couplings reported in this account enable
byproduct-free carbonyl allylation that transcends the boundaries of
oxidation level and represent an important step in the departure from
preformedorganometallicreagentsincarbonyladditionchemistry.6h,7,13,14
a Cited yields are of isolated material. Conditions A employ no added
ligand. Conditions B employ (p-MeOPh)3P (15 mol %) as ligand.
Conditions C employ rac-BINAP (5 mol %) as ligand. See Supporting
Information for detailed experimental procedures.
to isoprene to furnish products of carbonyl isoprenylation 1c-6c in
good to excellent yield. Similarly, benzylic alcohols 1a-6a couple to
butadiene to furnish products of crotylation 1b-6b, and use of 2,3-
dimethylbutadiene as an allyl donor delivers products of reverse
2-methyl prenylation 1d-6d (Table 1). Aliphatic alcohols couple in
diminished yield, however, allylic alcohols couple more efficiently.
For example, isoprene couples to 1-nonanol and geraniol in 65% and
75% isolated yields, respectively.
Initially, a range of commercially available ruthenium catalysts were
evaluated for their potential to couple isoprene to p-nitrobenzylalcohol
under the conditions of hydrogen autotransfer. It was found that
RuHCl(CO)(PPh3)3 promotes formation of the desired adduct with
excellent levels of regioselectivity (>95:5) and in good isolated yield
using only 2.5 equiv of diene. The addition of m-nitrobenzoic acid
(2.5 mol %) proved to be critical as only trace quantities of product
are observed in the absence of acid. Additionally, acetone (2.5 mol
%) was found to confer a small but reproducible improvement in
reaction efficiency. Finally, in most cases, isolated yields are improved
upon addition of exogenous phosphine ligand, (p-MeOPh)3P or rac-
BINAP.15 Under optimal conditions, benzylic alcohols 1a-6a couple
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6338 J. AM. CHEM. SOC. 2008, 130, 6338–6339
10.1021/ja801213x CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Carbonyl allylation can also be achieved from the aldehyde oxidation
level employing isopropanol or formic acid as terminal reductant,
although increased loadings of diene are required. For example, under
standard conditions, aldehydes 7a-9a couple to isoprene to furnish
products of carbonyl allylation 1c-3c, respectively, in good to excellent
yield. Thus, carbonyl allylation from the alcohol or aldehyde oxidation
level is possible (Table 2).
References
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Table 2. Coupling of Isoprene to Representative Aldehydes under
Conditions of Ruthenium-Catalyzed Transfer Hydrogenationa
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a See Table 1 footnotes for details. m-NO2BzOH and acetone were
not employed as additives.
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Bower, J. F.; Krische, M. J. J. Am. Chem. Soc. 2007, 129, 12678.
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A plausible mechanism involves alcohol dehydrogenation to gener-
ate a ruthenium hydride, which hydrometalates the less substituted
olefin of isoprene to deliver the secondary σ-allyl metal haptomer.
Carbonyl addition from the more stable primary σ-allyl haptomer
through a six-centered transition structure accounts for branched
regioselectivity. Consistent with this interpretation, coupling of isoprene
to deuterio-2a provides deuterio-2c, with deuterium at the benzylic
position (>95%), the allylic methyl (32%), and the allylic methine
(14%). Coupling of isoprene to aldehyde 8a using isopropanol-d8 as
terminal reductant provides deuterio-2c′, which incorporates deuterium
at the allylic methyl (19%) and the allylic methine (10%). Incomplete
deuterium incorporation likely stems from reversible hydrometalation
of isoprene. Mechanisms involving reversible diene hydrometalation
in advance of diene-aldehyde oxidative coupling cannot be excluded
on the basis of available data.
In summary, we report the first C-C couplings under the conditions
of ruthenium-catalyzed transfer hydrogenation employing alcohols as
terminal reductants. For such transfer hydrogenative couplings, hy-
drogen embedded within isopropanol or an alcohol substrate is
redistributed among reactants to generate nucleophile-electrophile
pairs, enabling carbonyl addition from the aldehyde or alcohol oxidation
level. Stereoselective variants of these and other alcohol-unsaturate
couplings are currently under investigation.
Acknowledgment is made to Johnson & Johnson, Merck, the
Welch Foundation, the ACS-GCI, the NIH-NIGMS (RO1-GM069445)
and the Donald D. Harrington Faculty Fellows Program for partial
support of this research.
(11) For reviews encompassing nickel-catalyzed diene-aldehyde reductive
coupling, see: (a) Tamaru, Y. J. Organomet. Chem. 1999, 576, 215. (b)
Ikeda, S.-i. Angew. Chem., Int. Ed. 2003, 42, 5120. (c) Montgomery, J.
Angew. Chem., Int. Ed. 2004, 43, 3890. (d) Modern Organo Nickel
Chemistry; Tamaru, Y., Ed.; Wiley-VCH: Weinheim, Germany, 2005. (e)
Kimuara, M.; Tamaru, Y. Top. Curr. Chem. 2007, 279, 173.
(12) For ruthenium-catalyzed hydroacylation of 1,3-dienes empolying aldehydes
as acyl donors, see: Mitsudo, T.-a.; Kondo, T.; Hiraishi, N.; Morisaki, Y.;
Wada, K.; Watanabe, Y. Organometallics 1998, 17, 2131.
(13) Carbonyl allylation via ene-type reaction typically requires highly activated
aldehydes: (a) Mikami, K.; Shimizu, M. Chem. ReV. 1992, 92, 1021. (b)
Berrisford, D. J.; Bolm, C. Angew. Chem., Int. Ed. Engl. 1995, 34, 1717.
(c) Johnson, J. S.; Evans, D. A. Acc. Chem. Res. 2000, 33, 325.
(14) Carbonylallylationemployingallylicacetatesrequiresmetallicreductants:Tamaru,
Y. In Handbook of Organopalladium Chemistry for Organic Synthesis;
Negishi, E.-i., Ed.; Wiley-Interscience: New York, 2002; Vol. 2, p 1917.
Also, see ref 4b.
(15) RuHCl(CO)(L)3 (L ) (p-MeOPh)3P) is not an efficient catalyst, suggesting
Supporting Information Available: Experimental procedures and
spectral data for new compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
the active catalyst is ligated to both Ph3P and (p-MeOPh)3P.
JA801213X
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