Iridium-catalyzed hydrocarboxylation of 1,1-dimethylallene: Byproduct-free reverse prenylation of carboxylic acids

Article abstract of DOI:10.1021/ol702914p

Exposure of carboxylic acids 1a-12a to commercially available 1,1-dimethylallene in the presence of substoichiometric quantities of an iridium catalyst prepared in situ from [Ir(COd)Cl]₂ and BIPHEP provides the corresponding 1,1-dimethylallyl (

Full text of DOI:10.1021/ol702914p

ORGANIC
LETTERS
2008
Vol. 10, No. 3
513-515
Iridium-Catalyzed Hydrocarboxylation of
1,1-Dimethylallene: Byproduct-Free
Reverse Prenylation of Carboxylic Acids
In Su Kim and Michael J. Krische*
UniVersity of Texas at Austin, Department of Chemistry and Biochemistry,
Austin, Texas 78712
mkrische@mail.utexas.edu
Received December 3, 2007
ABSTRACT
Exposure of carboxylic acids 1a−12a to commercially available 1,1-dimethylallene in the presence of substoichiometric quantities of an iridium
catalyst prepared in situ from [Ir(cod)Cl]2 and BIPHEP provides the corresponding 1,1-dimethylallyl (reverse prenyl) esters 1b
−
12b in 74 92%
−
isolated yield. This protocol represents the first branch-regioselective allene hydrocarboxylation. Stoichiometric byproducts are not generated
in this process and protecting groups are not required for alcohols, phenols, and indolic amines.
As part of a broad program aimed at the development of
C-C bond-forming hydrogenations,1 we recently demon-
strated that byproduct-free reverse prenylation of carbonyl
compounds could be achieved under the conditions of iridium
catalyzed hydrogenative C-C coupling using 1,1-dimethy-
lallene as an allyl metal equivalent.2 Later, it was found that
carbonyl reverse prenylation, crotylation and allylation could
be achieved under the conditions of transfer hydrogenation
employing 2-propanol as terminal reductant.2b Finally, it was
shown that carbonyl reverse prenylation, crotylation, and
allylation could be achieved from alcohol oxidation leVel
by simply using the alcohol as both terminal reductant and
aldehyde precursor.2b
an iridium catalyst prepared in situ from [Ir(cod)Cl]2 and
BIPHEP enables formation of the corresponding 1,1-dim-
ethylallyl (reverse prenyl) esters. Excluding the results
described herein, only a single example of metal-catalyzed
allene hydrocarboxylation has been reported by Yamamoto
under the conditions of palladium catalysis.3-6 The pal-
ladium-catalyzed hydrocarboxylations are restricted to the
use of arylallenes, as the putative allylpalladium intermediates
are prone to â-hydride elimination to furnish dienes. Ad-
ditionally, under the conditions of palladium catalysis,
hydrocarboxylation occurs at the less substituted allene
terminus to furnish linear allylic esters. The complementary
regiochemistry encountered in our initial observations of the
In the course of these studies, it was found that exposure
of carboxylic acids to 1,1-dimethylallene in the presence of
(3) Al-Masum, M.; Yamamoto, Y. J. Am. Chem. Soc. 1998, 120, 3809.
(4) For reviews, see: (a) Yamamoto, Y.; Radhakrishnan, U. Chem. Soc.
ReV. 1998, 28, 199. (b) Zimmer, R.; Dinesh, C. U.; Nandanan, E.; Khan,
F. A. Chem. ReV. 2000, 100, 3067.
(1) 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. (c) Skucas, E.; Ngai, M.-
Y.; Komanduri, V.; Krische, M. J. Acc. Chem. Res. 2007, 40, 1394.
(2) (a) Skucas, E.; Bower, J.; Krische, M. J. J. Am. Chem. Soc. 2007,
129, 12678. (b) Bower, J.; Skucas, E.; Patman, R. L.; Krische, M. J. J. Am.
Chem. Soc. 2007, 129, 15134.
(5) A single example of palladium-catalyzed cyclohexadiene hydrocar-
boxylation has been reported; see: Utsunomiya, M.; Kawatsura, M.;
Hartwig, J. F. Angew. Chem., Int. Ed. 2003, 42, 5865.
(6) For Brønsted acid catalyzed hydrocarboxylation of unactivated olefins,
see: Li, Z.; Zhang, J.; Brouwer, C.; Yang, C.-G.; Reich, N. W.; He, C.
Org. Lett. 2006, 8, 4175.
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Published on Web 01/09/2008

Table 1. Iridium-Catalyzed Hydrocarboxylation of 1,1-Dimethylallene To Furnish Reverse Prenyl Esters 1b-12ba,b
a Representative Procedure. To an oven-dried flask under 1 atm of argon gas charged with carboxylic acid 1a (36.6 mg, 0.3 mmol, 100 mol %),
[Ir(cod)Cl]2 (2.0 mg, 0.003 mmol, 1 mol %), BIPHEP (3.1 mg, 0.006 mmol, 2 mol %), and Cs2CO3 (1.95 mg, 0.006 mmol, 2 mol %) was added 1,2-
dichloroethane (3 mL, 0.1 M) followed by 1,1-dimethylallene (24.5 mg, 0.360 mmol, 120 mol %). The reaction mixture was allowed to stir at 60 °C for a
period of 24 h, at which point the reaction mixture was evaporated onto silica gel. Purification of the product by column chromatography (SiO2: ethyl
acetate/hexanes, 1:30) provides 1b (48 mg, 0.252 mmol) as a clear oil in 84% yield. b Cited yields are of material isolated via silica gel column chromatography.
c For diacids 9a and 11a, 240 mol % of 1,1-dimethylallene was used.
iridium catalyzed allene hydrocarboxylations, along with the
commercial availability of 1,1-dimethylallene, prompted us
to examine the scope of this byproduct-free reverse preny-
lation protocol.
maleic diester 9b is maintained. As demonstrated by the
formation of adducts 10b and 11b, R-hydroxy acids undergo
reverse prenylation in the absence of hydroxyl protecting
groups (Table 1, entries 6 and 7). Finally, the applicability
of this reverse prenylation protocol to R-amino acids is
demonstrated by the formation 12b (Table 1, entry 8).
A plausible catalytic mechanism is as follows: Protonation
of the metal by the carboxylic acid, which is equivalent to
O-H oxidative addition, delivers LnIr(H)(Cl)(O2CR).7 Hy-
drometalation of 1,1-dimethylallene generates an iridium
allyl,8 which upon C-O reductive elimination9 from the
more substituted σ-allyl haptomer delivers the reverse prenyl
ester and releases LnIrCl to close the catalytic cycle (Scheme
1).
Preliminary studies focused on the coupling of 1,1-
dimethylallene to benzoic acid 1a. Eventually, it was found
that the iridium catalyst prepared in situ from [Ir(cod)Cl]2
and BIPHEP (2 mol %) efficiently converts benzoic acid 1a
to the corresponding reverse prenyl ester 1b (84% yield)
using only a modest excess of 1,1-dimethylallene (120 mol
%). These optimized conditions were applied to para-
substituted benzoic acids 2a-5a. The corresponding reverse
prenyl esters 2b-5b were isolated in excellent yields (Table
1, entry 1). Notably, the conversion of p-hydroxy benzoic
acid 5a to reverse prenyl ester 5b does not require protection
of the phenolic hydroxyl moiety. As demonstrated by the
formation of 6b and 7b, heterocyclic aromatic carboxylic
acids participate in the coupling (Table 1, entries 2 and 3).
In the case of 7a, protection of the indolic amine is not
required. R,â-Unsaturated carboxylic acids 8a and 9a are
efficiently transformed to the reverse prenyl esters 8b and
9b, respectively (Table 1, entries 4 and 5). Notably, the
stereochemical integrity of the cis-configured olefin of the
(7) For oxidative addition of carboxylic acid O-H bonds to iridium(I)
complexes, see: (a) Smith, S. A.; Blake, D. M.; Kubota, M. Inorg. Chem.
1972, 11, 660. (b) Kong, P.-C.; Roundhill, D. M. Inorg. Chem. 1972, 11,
1437. (c) Ladipo, F. T.; Kooti, M.; Merola, J. S. Inorg. Chem. 1993, 32,
1681. (d) Ladipo, F. T.; Merola, J. S. Inorg. Chem. 1993, 32, 5201. (e)
Yamagata, T.; Tadaoka, H.; Nagata, M.; Hirao, T.; Kataoka, Y.; Ratovelo-
manana-Vidal, V.; Genet, J. P.; Mashima, K. Organometallics 2006, 25,
2505.
(8) For iridium-mediated allene hydrometalation to form iridium π-allyls,
see: Osakada, K.; Kimura, M.; Choi, J.-C. J. Organomet. Chem. 2000,
602, 144.
514
Org. Lett., Vol. 10, No. 3, 2008

under otherwise standard reaction conditions. The reverse
prenyl ester 2b was recovered in 96% isolated yield. The
reverse prenyl ester 1b was not detected. The absence of
carboxylate exchange suggests irreversible hydrocarboxyla-
tion (Scheme 3).
Scheme 1. Proposed Catalytic Mechanism
Scheme 3. Negligible Carboxylate Exchange Suggests
Irreversible Hydrocarboxylation
To gain further insight into the catalytic mechanism, 1,1-
dimethylallene was coupled to deuteriobenzoic acid (O-2H)-
1a. The product deuterio-1b incorporates deuterium at both
the interior vinylic position (63%) and exterior vinylic
position (9.8%). Additionally, a small quantity of deuterium
is incorporated at the ortho position of the benzoate (0.6%).
Incomplete deuterium incorporation may be due to adventi-
tious moisture or an exchange of 1H-2H between the iridium
hydride intermediate and the o-hydrogens of BIPHEP.10,11
1,1-Dimethylallene also was coupled to benzoic acid-
2,3,4,5,6-d5 (2H)5-1a. The product, d5-deuterio-1b, does not
incorporate deuterium in the reverse prenyl moiety; a small
loss of deuterium at the ortho position of the benzoate was
observed (96%) (Scheme 2).
Owing to the ubiquity of the reverse prenyl moiety in
diverse naturally occurring compounds, the present study
focuses on the hydrocarboxylation of 1,1-dimethylallene.
However, this process is not restricted to 1,1-dimethylallene.
For example, exposure of allenes 13a and 14a to benzoic
acid 1a under the standard conditions cited in Table 1
delivers the tertiary allylic esters 13b and 14b in good yield
and as single regioisomers. A more detailed investigation
into the scope of the allene partner will be published in due
course (Scheme 4).
Scheme 2. Isotopic Labeling Experiments
Scheme 4. Hydrocarboxylation of Allenes 13a and 14a
In summary, we report an efficient byproduct-free conver-
sion of carboxylic acids to reverse prenyl esters through the
branch-regioselective hydrocarboxylation of 1,1-dimethyla-
llene under the conditions of iridium catalysis. Future studies
will focus on the development of related protocols for the
enantioselective hydrocarboxylation and hydroamination of
nonsymmetric 1,1-disubstituted allenes.
To establish whether the hydrocarboxylation is reversible,
the reverse prenyl ester 2b was exposed to benzoic acid 1a
(9) For selected examples of C-O reductive elimination from noble metal
complexes, see: (a) Mann, G.; Hartwig, J. F. J. Am. Chem. Soc. 1996,
118, 13109. (b) Widenhoefer, R. A.; Zhong, H. A.; Buchwald, S. L. J. Am.
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Piero, G.; Perego, G.; Zazzetta, A.; Cesari, M. Crys. Struct. Commun. 1974,
3, 725. (b) Longato, B.; Morandini, F.; Bresadola, S. J. Organomet. Chem.
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(11) For H-D exchange employing elemental deuterium under the
conditions of iridium catalysis, see: (a) Heys, R. J. Chem. Soc., Chem.
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Org. Lett. 2004, 6, 11. (c) Ellames, G. J.; Gibson, J. S.; Herbert, J. M.;
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Acknowledgment is made to the Robert A. Welch
Foundation, Johnson & Johnson, Merck, the NIH-NIGMS
(RO1-GM69445), 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.
Supporting Information Available: 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.
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