Catalytic C-C coupling via transfer hydrogenation: Reverse prenylation, crotylation, and allylation from the alcohol or aldehyde oxidation level

Article abstract of DOI:10.1021/ja077389b

We report byproduct-free carbonyl reverse prenylation, crotylation, and allylation from the alcohol oxidation state via alcohol-allene hydrogen autotransfer. Specifically, exposure of alcohols 1a-6a to 1,1-dimethylallene, methylallene, and allene in the presence of [Ir(cod)(BIPHEP)]BARF (5-7.5 mol %) delivers reverse prenylation products 1c-6c, crotylation products 1d-3d, and allylation product 1e. Similarly, under the conditions of transfer hydrogenation employing isopropanol as terminal reductant, aldehydes 1b-6b are converted to the very same adducts 1c-6c, 1d-3d, and 1e. Isotopic labeling studies corroborate a mechanism involving hydrogen donation from the reactant alcohol or sacrificial alcohol (i-PrOH). The ability to achieve carbonyl addition directly from the alcohol oxidation level circumvents the redox manipulations so often required to convert alcohols to aldehydes. Further, through hydrogen autotransfer, there resides the potential to develop myriad byproduct-free carbonyl additions wherein alcohols and π-unsaturated compounds are exploited as coupling partners. Copyright

Full text of DOI:10.1021/ja077389b

Published on Web 11/17/2007
Catalytic C-C Coupling via Transfer Hydrogenation: Reverse Prenylation,
Crotylation, and Allylation from the Alcohol or Aldehyde Oxidation Level
John F. Bower, Eduardas Skucas, Ryan L. Patman, and Michael J. Krische*
UniVersity of Texas at Austin, Department of Chemistry and Biochemistry, Austin, Texas 78712
Received September 24, 2007; E-mail: mkrische@mail.utexas.edu
As first demonstrated by Guerbet (1908),1,2 hydrogen autotransfer
Table 1. Reverse Prenylation via Iridium-Catalyzed Hydrogen
Autotransfer and Transfer Hydrogenationa
processes3 allow diverse nucleophiles (ketones,4 nitriles,5 activated
methylene compounds,6 and stabilized Wittig reagents)7 to be
alkylated by alcohols. To date, all reported hydrogen autotransfer
processes involve three fundamental steps: (a) alcohol dehydro-
genation provides an aldehyde, which (b) undergoes condensation
or olefination to furnish an unsaturated adduct, which (c) hydro-
genates to deliver the saturated product. Such oxidation-condensa-
tion-reduction processes do not produce alcohol containing
products of carbonyl addition. A related class of hydrogen au-
totransfer processes potentially involves hydrogen exchange be-
tween alcohols and π-unsaturated reactants to generate nucleophile-
electrophile pairs. This approach would enable byproduct-free
carbonyl addition from the alcohol oxidation state.
a Cited yields are of isolated material. Standard conditions employ 1 equiv
of alcohol/aldehyde and 4 equiv of allene. See Supporting Information for
detailed experimental procedures. b For 6a and 6b, 10 mol % of precatalyst
and base were used. c Reaction run using 4 equiv IPA and 8 equiv of allene.
absence of gaseous hydrogen. Gratifyingly, the desired allylation
product 1c was observed and, upon further optimization, could be
obtained in excellent yield. These conditions were applied to
alcohols 1a-6a. Good to excellent yields of the reverse prenylation
products 1c-6c were obtained (Table 1, top). The efficiency of
these hydrogen autotransfer processes suggested the feasibility of
related C-C couplings under the conditions of transfer hydrogena-
tion. Accordingly, solutions of dimethylallene and aldehydes 1b-
6b were exposed to standard reaction conditions, but in the presence
of isopropanol (200 mol %). Remarkably, the very same adducts
1c-6c were obtained in comparable yield (Table 1, bottom).
Notably, adducts 1c-6c also were prepared previously via hydro-
genative coupling, meaning that reverse prenylation can be achieved
under three alternate conditions: hydrogenative coupling, hydrogen
autotransfer, and transfer hydrogenation. Unactivated aliphatic
alcohols or aldehydes do not couple efficiently under these
conditions.
To assess scope, methylallene was exposed to alcohols 1a, 2a,
and 3a under standard conditions for C-C coupling via hydrogen
autotransfer. The products of crotylation 1d, 2d, and 3d were ob-
tained in 82%, 69%, and 72% yields, respectively (Table 2). Simi-
larly, using methylallene, aldehydes 1b, 2b, and 3b are converted
to the very same products of crotylation 1d, 2d, and 3d in 83%,
77%, and 79% yields, respectively, under standard conditions for
isopropanol-mediated transfer hydrogenation. Finally, allylations
of alcohol 1a or aldehyde 1b are achieved using allene to provide
1e in 23% and 50% yields under autotransfer of transfer hydrogena-
tion conditions, respectively. Diminished efficiency may be due the
presence of propyne, an impurity found in commercial allene gas.
A series of experiments reveal key features of the catalytic
mechanism. Coupling of dimethylallene to deuterio-2a under
We have developed a class of reductive C-C couplings that em-
ploy elemental hydrogen as the terminal reductant.8 These trans-
formations offer a byproduct-free alternative to stoichiometrically
preformed organometallic reagents in a diverse assortment of Cd
X (X ) O, NR) addition processes.9 Most recently, we found that
hydrogenation of 1,1-dimethylallene in the presence of carbonyl
electrophiles delivers products of carbonyl allylation, specifically,
products of reverse prenylation.10,11 However, attempted crotylation
and allylation under conditions employing gaseous hydrogen as the
terminal reductant were foiled by over-reduction of the olefinic
adduct.
Here, we report that carbonyl allylation can be achieVed directly
from the alcohol oxidation state through alcohol-allene hydrogen
autotransfer. This method represents a direct, byproduct-free proto-
col for carbonyl allylation and, to our knowledge, is the first metal-
catalyzed transfer hydrogenation to furnish products of carbonyl
addition. Additionally, we disclose that isopropanol may be used
as a terminal reductant in aldehyde-allene reductive C-C couplings
under transfer hydrogenation conditions. Both protocols circumvent
over-reduction of the product, allowing reverse prenylation, cro-
tylation, and allylation to be achieved from the alcohol or aldehyde
oxidation state in the absence of preformed allyl metal reagents.11-14
To probe the feasibility of allylation by way of alcohol-allene
hydrogen autotransfer, a solution of dimethylallene and p-nitroben-
zyl alcohol 1a was exposed to our initially disclosed conditions
for iridium catalyzed hydrogenative carbonyl allylation, but in the
9
15134
J. AM. CHEM. SOC. 2007, 129, 15134-15135
10.1021/ja077389b CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Crotylation and Allylation via Iridium-Catalyzed Hydrogen
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.
Autotransfer and Transfer Hydrogenationa
References
(1) (a) Guerbet, M. C. R. C. R. Chim. 1908, 146, 298. (b) Machemer, H.
Angew. Chem. 1952, 64, 213. (c) Pratt, E. F.; Kubler, D. G. J. Am. Chem.
Soc. 1954, 76, 52. (d) Ndou, A. S.; Plint, N.; Coville, N. J. Appl. Catal.
A: Gen. 2003, 251, 337.
(2) (a) Gregorio, G.; Pregaglia, G. F.; Ugo, R. J. Organomet. Chem. 1972,
37, 385. (b) Burk, P. L.; Pruett, R. L.; Campo, K. S. J. Mol. Catal. 1985,
33, 1. (c) Cho, C. S.; Kim, B. T.; Kim, H.-S.; Kim, T.-J.; Shim, S. C.
Organometallics 2003, 22, 3608. (d) Carlini, C.; Macinai, A.; Galletti,
A. M. R.; Sbrana, G. J. Mol. Catal. A: Chem. 2004, 212, 65. (e) Fujita,
K.-I.; Asai, C.; Yamaguchi, T.; Hanasaka, F.; Yamaguchi, R. Org. Lett.
2005, 7, 4017. (f) Cho, C. S.; Ren, W. X.; Shim, S. C. Bull. Korean Chem.
Soc. 2005, 26, 1611. (g) Carlini, C.; Marchionna, M.; Noviello, M.;
Galletti, A. M. R.; Sbrana, G.; Basile, F.; Vaccari, A. J. Mol. Catal. A:
Chem. 2005, 232, 13. (h) Matsu-ura, T.; Sakaguchi, S.; Obora, Y.; Ishii,
Y. J. Org. Chem. 2006, 71, 8306. (i) Mart´ınez, R.; Ramo´n, D. J.; Yus,
M. Tetrahedron 2006, 62, 8982.
(3) For a recent review, see: Guillena, G.; Ramo´n, D. J.; Yus, M. Angew.
Chem., Int. Ed. 2007, 46, 2358.
a Cited yields are of isolated material; 1 equiv of alcohol or aldehyde
and 4 equiv of methylallene were used.
(4) (a) Chabardes, P.; Querou, Y. (Rhone-Poulenc SA), FR1582621, 1969;
Chem. Abstr. 1970, 73, 61760. (b) Cho, C. S.; Kim, B. T.; Kim, T.-J.;
Shim, S. C. J. Org. Chem. 2001, 66, 9020. (c) Cho, C. S.; Kim, B. T.;
Lee, M. J.; Kim, T.-J.; Shim, S. C. Angew. Chem., Int. Ed. 2001, 40, 958.
(d) Cho, C. S.; Kim, B. T.; Kim, T.-J.; Shim, S. C. Tetrahedron Lett.
2002, 43, 7987. (e) Mart´ınez, R.; Brand, G. J.; Ramo´n, D. J.; Yus, M.
Tetrahedron Lett. 2005, 46, 3683. (f) Cho, C. S. J. Mol. Catal. A: Chem.
2005, 240, 55. (g) Kwon, M. S.; Kim, N.; Seo, S. H.; Park, I. S.;
Cheeddrala, R. K.; Park, J. Angew. Chem., Int. Ed. 2005, 44, 6913. (h)
Cho, C. S.; Shim, S. C. J. Organomet. Chem. 2006, 691, 4329. (i) Onodera,
G.; Nishibayashi, Y.; Uemura, S. Angew. Chem., Int. Ed. 2006, 45, 3819.
(j) Mart´ınez, R.; Ramo´n, D. J.; Yus, M. Tetrahedron 2006, 62, 8988. (k)
Yamada, Y. M. A.; Uozumi, Y. Org. Lett. 2006, 8, 1375.
Table 3. Isotopic Labeling Studies and Competition Experimentsa
(5) (a) Miyano, S.; Abe, N. J. Org. Chem. 1971, 36, 2948. (b) Grigg, R.;
Mitchell, T. R. B.; Sutthivaiyakit, S.; Tongpenyai, N. Tetrahedron Lett.
1981, 22, 4107. (c) Motokura, K.; Nishimura, D.; Mori, K.; Mizugaki,
T.; Ebitani, K.; Kaneda, K. J. Am. Chem. Soc. 2004, 126, 5662. (d)
Lo¨fberg, C.; Grigg, R.; Whittaker, M. A.; Keep, A.; Derrick, A. J. Org.
Chem. 2006, 71, 8023. (e) Motokura, K.; Fujita, N.; Mori, K.; Mizugaki,
T.; Ebitani, K.; Jitsukawa, K.; Kaneda, K. Chem. Eur. J. 2006, 12, 8228.
(6) (a) Lo¨fberg, C.; Grigg, R.; Keep, A.; Derrick, A.; Sridharan, V.; Kilner,
C. Chem. Commun. 2006, 5000. (b) Slatford, P. A.; Whittlesey, M. K.;
Williams, J. M. J. Tetrahedron Lett. 2006, 47, 6787.
(7) (a) Edwards, M. G.; Williams, J. M. J. Angew. Chem., Int. Ed. 2002, 41,
4740. (b) Edwards, M. G.; Jazzar, R. F. R.; Paine, B. M.; Shermer, D. J.;
Whittlesey, M. K.; Williams, J. M. J.; Edney, D. D. Chem. Commun.
2004, 90. (c) Black, P. J.; Cami-Kobeci, G.; Edwards, M. G.; Slatford, P.
A.; Whittlesey, M. K.; Williams, J. M. J. Org. Biomol. Chem. 2006, 4,
116. (d) Black, P. J.; Edwards, M. G.; Williams, J. M. J. Eur. J. Org.
Chem. 2006, 4367.
a All reactions were performed under standard conditions cited in Table
1. PNP ) p-nitrophenyl.
(8) For reviews on 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.
standard conditions provides deuterio-2c, which incorporates
deuterium at the benzylic (>95%) and internal vinylic positions
(85%) (Table 3). Coupling of dimethylallene to aldehyde 2b under
standard conditions using d8-isopropanol as terminal reductant
provides deuterio-2c′, which incorporates deuterium primarily at
the internal vinylic position (85%). In this case, deuterium at the
hydroxylic position exchanges out during chromatographic isolation
of the product. Competition experiments involving exposure of
dimethylallene to equimolar quantities of 1a and 2b under standard
conditions provide 2c and 1c in 94% yield in a 1:4 ratio,
respectively. An identical product distribution and yield is observed
upon exposure of dimethylallene to equimolar quantities of 1b and
2a under standard conditions, suggesting rapid redox equilibration
of alcohol and aldehyde partners in advance of C-C coupling.
Indeed, upon exposure of equimolar quantities of 1a and 2b or 1b
and 2a to standard conditions in the absence of allene, an identical
4:1:1:4 mixture of 1a, 1b, 2a, and 2b, respectiVely, is formed.
The ability to achieve carbonyl addition directly from the alcohol
oxidation level circumvents the redox manipulations so often
required to convert alcohols to aldehydes. Further, through hydrogen
autotransfer, there resides the potential to develop myriad byproduct-
free carbonyl additions, wherein alcohols and π-unsaturated
compounds are exploited as coupling partners.
(9) For recent examples, see: (a) CdX vinylation: Kong, J.-R.; Ngai, M.-
Y.; Krische, M. J. J. Am. Chem. Soc. 2006, 128, 718. (b) Skucas, E.;
Kong, J.-R.; Krische, M. J. J. Am. Chem. Soc. 2007, 129, 7242. (c)
Barchuk, A.; Ngai, M.-Y.; Krische, M. J. J. Am. Chem. Soc. 2007, 129,
8432. (d) Aldol and Mannich addition: Jung, C.-K.; Garner, S. A.; Krische,
M. J. Org. Lett. 2006, 8, 519. (e) Jung, C.-K.; Krische, M. J. J. Am. Chem.
Soc. 2006, 128, 17051. (f) Garner, S. A.; Krische, M. J. J. Org. Chem.
2007, 72, 5843.
(10) Skucas, E.; Bower, J. F.; Krische, M. J. J. Am. Chem. Soc. 2007, 129,
12678.
(11) For reviews on carbonyl allylation, see: (a) Kennedy, J. W. J.; Hall, D.
G. Angew. Chem., Int. Ed. 2003, 42, 4732. (b) Denmark, S. E.; Fu, J.
Chem. ReV. 2003, 103, 2763.
(12) Carbonyl allylation in the absence of preformed allyl metal reagents may
be achieved via ene-type reaction: (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.
(13) Carbonyl allylation via intermolecular allene-carbonyl-arene coupling:
(a) Anwar, U.; Grigg, R.; Rasparini, M.; Savic, V.; Sridharan, V. Chem.
Commun. 2000, 645. (b) Takimoto, M.; Kawamura, M.; Mori, M. Org.
Lett. 2003, 5, 2599. (c) Hopkins, C. D.; Malinakova, H. C. Org. Lett.
2004, 6, 2221. (d) Hopkins, C. D.; Guan, L.; Malinakova, H. C. J. Org.
Chem. 2005, 70, 6848.
(14) Carbonyl allylation via intramolecular allene-carbonyl-arene coupling:
(a) Chevliakov, M. V.; Montgomery, J. J. Am. Chem. Soc. 1999, 121,
11139. (b) Montgomery, J.; Song, M. Org. Lett. 2002, 4, 4009. (c) Kang,
S.-K.; Yoon, S.-K. Chem. Commun. 2002, 2634. (d) Ha, Y.-H.; Kang,
S.-K. Org. Lett. 2002, 4, 1143. (e) Song, M.; Montgomery, J. Tetrahedron
2005, 61, 11440.
Acknowledgment is made to Johnson & Johnson, Merck, the
Welch Foundation, and the NIH-NIGMS (Grant RO1-GM069445)
for partial support of this research.
JA077389B
9
J. AM. CHEM. SOC. VOL. 129, NO. 49, 2007 15135