Iridium-catalyzed hydrohydroxyalkylation of butadiene: Carbonyl crotylation

Article abstract of DOI:10.1002/adsc.201000599

Exposure of alcohols 1a-1i to butadiene in the presence of a cyclometallated iridium catalyst derived from allyl acetate, 4-methoxy-3-nitrobenzoic acid and 2,2′-bis(diphenylphosphino)biphenyl (BIPHEP) results in hydrogen transfer to generate aldehyde-allyliridium pairs, which engage in C-C coupling to form products of carbonyl crotylation. Under related conditions using 1,4-butanediol as hydrogen donor, butadiene reductively couples to aldehydes 2e-2g and 2i to furnish carbonyl crotylation products 3e-3g and 3i. Thus, butadiene-mediated carbonyl crotylation occurs with equal facility from the alcohol or aldehyde oxidation level with complete levels of branched regioselectivity.

Full text of DOI:10.1002/adsc.201000599

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DOI: 10.1002/adsc.201000599
Iridium-Catalyzed Hydrohydroxyalkylation of Butadiene:
Carbonyl Crotylation
Jason R. Zbieg,a Takeo Fukuzumi,a and Michael J. Krischea,*
a
Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX 78712, USA
Fax : (+1)-512-471-8696; e-mail: mkrische@mail.utexas.edu
Received: July 27, 2010; Published online: September 23, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000599.
À
Abstract: Exposure of alcohols 1a–1i to butadiene
in the presence of a cyclometallated iridium catalyst
derived from allyl acetate, 4-methoxy-3-nitrobenzo-
ic acid and 2,2’-bis(diphenylphosphino)biphenyl
(BIPHEP) results in hydrogen transfer to generate
hol-butadiene C C coupling under the conditions of
iridium-catalyzed transfer hydrogenation. Our efforts
were further motivated by the fact that the most
broadly utilized protocol for stereoselective carbonyl
crotylation, the method reported by Brown,[12] is at-
tended by significant preactivation and the superstoi-
chiometric generation of the secondary alcohol by-
product, isopinocampheol, has proven problematic.[13]
In contrast, butadiene is an abundant petrochemical
feedstock that could potentially deliver products of
carbonyl crotylation in the absence of stoichiometric
by-products, while bypassing discrete steps devoted to
alcohol oxidation (Scheme 1).[14]
À
aldehyde-allyliridium pairs, which engage in C C
coupling to form products of carbonyl crotylation.
Under related conditions using 1,4-butanediol as
hydrogen donor, butadiene reductively couples to
aldehydes 2e–2g and 2i to furnish carbonyl crotyla-
tion products 3e–3g and 3i. Thus, butadiene-mediat-
ed carbonyl crotylation occurs with equal facility
from the alcohol or aldehyde oxidation level with
complete levels of branched regioselectivity.
In an initial series of experiments, the coupling of
butadiene to alcohol 1a was explored using the ortho-
cyclometallated iridium complex derived from
Keywords: butadiene; by-product-free process; cro-
tylation; green chemistry; iridium
[Ir
ACHTUNGTRNE(NUNG COD)Cl]2, various 4-substituted 3-nitrobenzoic
acids, allyl acetate and the chelating phosphine ligand
BIPHEP
[2,2’-bis(diphenylphosphino)biphenyl].
À
Unlike other iridium-catalyzed C C couplings devel-
oped in our laboratory,[8–11] reactions attempted in
We have found that hydrogen exchange between alco- THF produced only trace quantities of 3a. Improved
hols and p-unsaturated reactants triggers generation conversion to 3a was observed in non-Lewis basic sol-
of electrophile-nucleophile pairs en route to products vents, and toluene was best among the solvents
[1,2]
À
of C C coupling.
Using ruthenium catalysts, the screened (Table 1, entries 1–5). Additionally, a dra-
“transfer hydrogenative coupling” of alcohols to matic electronic effect involving the C,O-benzoate
dienes,[3] enynes,[4] alkynes,[5] and allenes[6] delivers was evident: whereas the catalyst derived from 4-
À
products of carbinol C H functionalization or “hydro- cyano-3-nitrobenzoic acid “BIPHEP-I-CN” provides
hydroxyalkylation”. Recently, related alcohol-enal only an 8% yield of C C coupling product 3a, the cat-
couplings catalyzed by ruthenium were reported alyst derived from 4-methoxy-3-nitrobenzoic acid
À
À
where C C bond formation is followed by redox iso- “BIPHEP-I-OMe” delivers 3a in 62% yield (Table 1,
merization.[7] Using ruthenium-based catalysts, diaste- entries 5–7). Finally, mild basic additives, in particular
reoselective hydrohydroxyalkylation only has been sodium acetate, were found to enhance conversion
achieved in one isolated case[6c] and, to date, enantio- (Table 1, entries 5, 8–11). Under optimal conditions
selective variants have proven elusive. In contrast, ex- employing “BIPHEP-I-OMe” as precatalyst in tolu-
cellent levels of relative and absolute stereocontrol ene solvent and sodium acetate as base, butadiene
À
À
have been achieved in the iridium catalyzed C C cou- and alcohol 1a are converted to the product of C C
pling of alcohols to p-unsaturated reactants, including coupling 3a in 80% isolated yield. Notably, a single
allylic acetates,[8,9] dimethylallene[8e,g,10] and 1,3-cyclo- regioisomer is formed (Table 1).
hexadiene.[11] This fact prompted us to explore alco-
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Iridium-Catalyzed Hydrohydroxyalkylation of Butadiene: Carbonyl Crotylation
Scheme 1. Metal-catalyzed hydrohydroxyalkylation of butadiene circumvents the preactivation and by-product generation
that attends “state-of-the-art” carbonyl crotylation methodology.
Table 1. Selected experiments in the optimization of the iridium catalyzed
hydrohydroxyalkylation of butadiene.[a]
[a]
Reactions were performed in 13ꢁ100 mm pressure tubes. The cited
yields are of material isolated by silica gel chromatography. See Sup-
porting Information for experimental details.
Under these optimized conditions, butadiene was mixtures of syn- and anti-diastereomers, only a single
coupled to alcohols 1a–1i. Benzylic alcohols 1a–1f regioisomer is formed in each case (Table 2).
were converted to the products of carbonyl crotyla-
The modest levels of syn-diastereoselectivity sug-
tion 3a–3f in good yield. Allylic alcohols 1g and 1h gests a kinetic preference for butadiene hydrometalla-
also couple to butadiene to provide homoallylic alco- tion from the s-cis conformer to deliver the anti-p-
hols 3g and 3h in moderate yields. Finally, the unacti- allyl which, in turn, provides the (Z)-s-allyl stereoiso-
vated aliphatic alcohol 1i combines with butadiene to mer. It is likely that conversion of the kinetically pre-
provide a 52% yield of the hydrohydroxyalkylation ferred (Z)-s-allyl stereoisomer to the thermodynami-
product 3i. Although products 3a–3i are obtained as cally preferred (E)-s-allyl stereoisomer occurs at a
rate comparable to carbonyl addition. Alternatively, a
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Jason R. Zbieg et al.
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Table 2. Iridium catalyzed hydro-hydroxyalkylation of butadiene employ-
ing alcohols 1a–1i.[a]
[a]
As described in Table 1.
At 958C.
For 72 h.
[b]
[c]
Curtin–Hammett scenario might be operative, where- modynamically less stable (Z)-s-allyl stereoisomer
in full equilibration between the (Z) and (E)-s-allyl (Scheme 2).
À
stereoisomers is achieved, yet there exists a slight ki-
For nearly all the C C bond forming transfer hy-
netic preference for carbonyl addition from the ther- drogenations we have developed,[3–11] carbonyl addi-
tion may be achieved from both the alcohol or alde-
Scheme 2. Proposed catalytic mechanism for iridium-catalyzed hydrohydroxyalkylation of butadiene.
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Iridium-Catalyzed Hydrohydroxyalkylation of Butadiene: Carbonyl Crotylation
Scheme 3. Iridium-catalyzed reductive coupling of butadiene to aldehydes 2e–2g and 2i.
hyde oxidation levels. In the latter case, a stoichio-
metric reductant such as isopropyl alcohol or formic
acid is required. Using BIPHEP-I-OMe as precata-
lyst, the reductive coupling of butadiene to aldehydes
mediated by 1,4-butanediol[14] occurs smoothly, as
demonstrated by the conversion of aldehydes 2e–2g
and 2i to crotylation products 3e–3g and 3i. Thus, bu-
tadiene-mediated carbonyl crotylation occurs with
equal facility from the alcohol or aldehyde oxidation
level (Scheme 3).
Having established favorable reactivity, a prelimi-
nary evaluation of chirally modified catalysts was un-
dertaken. Toward this end, the ortho-cyclometallated
iridium C,O-benzoates derived from (S)-SEGPHOS
and (R)-WALPHOS (SL-W002-1) were prepared and
assayed in the coupling of butadiene to alcohol 1a.
Using (S)-SEGPHOS-I-OMe, the crotylation product
3a was obtained in 80% yield as a 1.4:1 mixture of
syn- and anti-diastereomers, respectively. High levels
Scheme 4. Preliminary evaluation of chirally modified cata-
lysts.
of enantiomeric enrichment were observed for the Experimental Section
syn-stereoisomer (87% ee). Using (R)-WALPHOS-I-
OMe, the crotylation product 3a was obtained in 40% Procedure for the Synthesis of BIPHEP-I-OMe
yield as a 1:2.2 mixture of syn- and anti-diastereomers,
respectively. High levels of enantiomeric enrichment
were observed for the major anti-diastereomer (88%
ee) (Scheme 4).
To an oven-dried sealed tube under an atmosphere of nitro-
gen charged with [IrACTHNUTRGNE(NUG cod)Cl]2 (100 mg, 0.15 mmol,
100 mol%), BIPHEP (156 mg, 0.3 mmol, 200 mol%),
Cs2CO3 (195 mg, 0.6 mmol, 400 mol%) and 4-methoxy-3-ni-
trobenzoic acid (100 mg, 0.6 mmol, 400 mol%) was added
THF (3 mL, 0.05M). The reaction mixture was heated at
808C for 30 min and was then allowed to cool to ambient
temperature. Allyl acetate (75 mg, 0.75 mmol, 500 mol%)
was added and the reaction mixture was allowed to stir for
an additional 90 min at 808C, at which point the reaction
mixture was allowed to cool to ambient temperature. The
reaction mixture was filtered and washed with THF (15 mL)
until all yellow residue had dissolved. The filtrate was con-
centrated under vacuum and hexanes (50 mL) was added.
The resulting yellow precipitate was collected by filtration
and dried under vacuum; yield: 253 mg (80.266 mmol, 90%).
In summary, we report the iridium-catalyzed hydro-
hydroxyalkylation of butadiene employing alcohols
1a–1i to furnish products of carbonyl crotylation 3a–
3i. Using 1,4-butanediol as hydrogen donor, butadiene
couples to aldehydes 2e–2g and 2i to provide the
products of carbonyl crotylation 3e–3g and 3i. Thus,
butadiene-mediated carbonyl crotylation occurs with
equal facility from the alcohol or aldehyde oxidation
level. Although products 3a–3i are obtained as diaste-
reomeric mixtures, preliminary studies employing
chiral iridium catalysts modified by (S)- SEGPHOS
and (R)-WALPHOS (SL-W002-1) reveal promising
levels of asymmetric induction and catalyst-directed
diastereocontrol. Future studies will focus on the de-
velopment of second-generation catalysts that pro-
mote butadiene-mediated carbonyl crotylation with
control of relative and absolute stereochemistry.
General Procedure for Iridium-Catalyzed
Hydrohydroxyalkylation of Butadiene
To an oven-dried sealed tube under an atmosphere of nitro-
gen charged with alcohol 1a (50 mg, 0.30 mmol, 100 mol%),
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Jason R. Zbieg et al.
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Ir-BIPHEP-1-OMe (14 mg, 0.015 mmol, 5 mol%) and
sodium acetate (25 mg, 0.30 mmol, 100 mol%) were added
toluene (1.0m, 0.3 mL) followed by 1,3-butadiene (0.1 mL,
1.2 mmol, 400 mol%, chilled at À788C). The reaction mix-
ture was placed in a 708C oil bath and was allowed to stir
for 48 h, at which point the reaction mixture was concentrat-
ed under vacuum. Purification of the product by column
chromatography (SiO2; ethyl acetate:hexanes, 1:10) provides
the product of carbonyl crotylation, methyl 4-(-hydroxy-2-
methylbut-3-enyl)benzoate (3a), as a colorless oil, as a
single regioisomer and as a 1.4:1 mixture of syn/anti diaste-
reomers; yield: 53 mg (80%).
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[8] a) I. S. Kim, M.-Y. Ngai, M. J. Krische, J. Am. Chem.
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Supporting Information
Spectral data for all new compounds (1H NMR, 13C NMR,
1
IR, HR-MS), including scanned images of H and 13C NMR
spectra. Scanned images of HPLC traces corresponding to
racemic and enantiomerically enriched products.
Acknowledgements
Acknowledgements is made to the Robert A. Welch Founda-
tion (F-0038) and the NIH-NIGMS (RO1-GM069445) for
partial support of this research.
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