Access to stereodefined trisubstituted alkenes via rhodium-catalyzed 1,4-addition of potassium trifluoro(organo)borates to Baylis-Hillman adducts

Article abstract of DOI:10.1002/adsc.200505336

In the presence of a rhodium catalyst, unactivated Baylis-Hillman adducts reacted regioselectively with potassium trifluoro(organo)borates to afford stereodefined trisubstituted alkenes with good yields. This highly efficient reaction (aerobic conditions,

Full text of DOI:10.1002/adsc.200505336

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DOI: 10.1002/adsc.200505336
Access to Stereodefined Trisubstituted Alkenes via
Rhodium-Catalyzed 1,4-Addition of Potassium Trifluoro(organo)-
borates to Baylis--Hillman Adducts
Laure Navarre, Sylvain Darses,* Jean-Pierre Genet*
`
´
´
Laboratoire de Synthese Selective Organique (UMR 7573, CNRS), Ecole Nationale Superieure de Chimie de Paris,
11 rue Pierre et Marie Curie, 75231 Paris cedex 05, France
Fax: (þ33)-1-44-27-10-62, e-mail: sylvain-darses@enscp.fr, jean-pierre-genet@enscp.fr
Received: September 1, 2005; Accepted: December 5, 2005
Supporting Information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: In the presence of a rhodium catalyst, un-
activated Baylis–Hillman adducts reacted regioselec-
tively with potassium trifluoro(organo)borates to af-
ford stereodefined trisubstituted alkenes with good
yields. This highly efficient reaction (aerobic condi-
tions, low temperature, absence of added phosphane
ligand) is believed to proceed via a 1,4-addition/b-
hydroxy elimination mechanism.
in the presence of a rhodium complex, affording stereo-
defined trisubstituted (E)-alkenes under mild condi-
tions via an unusual mechanism.[12] In this reaction, the
use of potassium trifluoro(organo)borates would be
more attractive because of their higher stability and
ease of preparation and purification.[8] Moreover, these
compounds have found to be highly suited in rhodium-
catalyzed processes.[10,13]
In this paper, we report for the first time the reaction
of potassium trifluoro(organo)borates with unactivated
BH adducts catalyzed by phosphine ligand-free rhodi-
um complexes under aerobic conditions[14] to afford
(E)-trisubstituted alkenes.
Keywords: alkenes; Baylis–Hillman adduct; conju-
gate addition; homogeneous catalysis; organotri-
fluoroborates; rhodium
In order to determine the optimal parameters for the
addition, several conditions were evaluated using potas-
sium trifluoro(phenyl)borate (2a) and 1a as model reac-
The Baylis–Hillman (BH) reaction is a very useful and tion partners. Among the catalyst precursors tested
operationally simple reaction allowing carbon-carbon (rhodium, palladium and ruthenium complexes) rhodi-
bond formation under mild conditions.[1] The reaction um(I) complexes appeared to be the most suited to ac-
products, called Baylis–Hillman adducts, are highly complish the reaction. Particularly, the commercially
functionalized substrates bearing both allyl alcohol available and easily prepared rhodium dimer
and a,b-unsaturated ester moieties. Indeed, they have [Rh(cod)Cl]2 allowed the reaction to go to completion,
been further functionalized via palladium-catalyzed even in the absence of added phosphane ligand.[15]
Heck reactions[2] or Friedel–Crafts reactions.[3] SN2’[4] With this rhodium pre-catalyst in hand, several condi-
or p-allyl-type[5] reactions have also been described on tions (solvent and temperature) were evaluated to im-
BH adducts, but the allyl alcohol moiety had to be fur- prove the overall efficiency of this catalytic process
ther transformed to carbonate or acetate, which are bet- (see Table 1 for selected examples).
ter leaving groups. For example, Kabalka et al. recently
From these results, it appeared that the presence of a
reported palladium-catalyzed cross-coupling reactions protic solvent was essential to achieve high conversion
of BH acetates with bis(pinacolato)diboron[6] or potassi- of the starting BH adduct (entries 1–3 compared to en-
um trifluoro(organo)borates,[7,8] allowing the formation try 4) but isolated yields were relatively modest, because
of stereodefined alkenes via p-allylpalladium inter- of the decomposition of the substrate with long reaction
mediates. In terms of atom economy,[9] the use of unac- times. The combination of a protic solvent and toluene, a
tivated BH adducts would be more desirable but they solvent usually used in 1,4-addition using potassium tri-
are generally less reactive in transition metal-catalyzed fluoro(organo)borates,[10] as reaction medium afforded
reactions.
improved isolated yields. Among the binary mixtures
In our continuous interest in rhodium-catalyzed reac- evaluated, a toluene/methanol mixture proved to be
tions with organoboron derivatives,[10,11] we recently highly suited in achieving high yields and isomeric ratios
showed that organoboronic acids added to BH adducts (99/1) in favor of the (E) isomer. Even if the reaction was
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Table 1. Optimization of the reaction conditions.[a]
Entry
Solvent
T [8C]
Time [h]
Conv. (yield) [%]
E/Z
1
2
3
4
5
6
7
Water
Methanol
Ethanol
Toluene
Toluene/MeOH (1: 1)
Toluene/MeOH (1: 1)
Toluene/EtOH (1: 1)
55
55
55
55
55
70
70
26
60
5
40
4
90 (47)
84
61
2
30
98 (86)
45
98/2
98/2
98/2
–
99/1
99/1
98/2
4
5
[a]
Reactions were conducted using 0.5 mmol BH adduct 1a, 1 mmol of 2a with 1.5 mol % [Rh(cod)Cl]2.
Conversion determined by GC. Isolated yield of BH adduct 3a in parentheses.
Determined by GC/MS and H NMR.
[b]
[c]
1
slightly sluggish at 508C (reaction time of 20 h), in- acrylate moiety while maintaining the geometry of the
creased reactivity was achieved at 708C, keeping high incoming organometallic partner. Particularly, potassi-
levels of the E/Z ratio.
um vinyltrifluoroborate[16] also participated in this reac-
The generality of this reaction was evaluated under tion, affording the expected coupling adduct 3q in 44%
these optimized conditions: [Rh(cod)Cl]2 as catalyst yield. Thus, using this efficient catalytic reaction, highly
precursor in toluene/methanol at 708C. It appeared functionalized 1,4-dienes were easily accessible from
that these conditions proved to be general, independent readily available reagents: an aldehyde, a Michael ac-
ofthenatureoftheBHadductorpotassiumaryltrifluoro- ceptor (the BH reagent) and a potassium alkenyltri-
borate employed (Table 2).
fluoroborate.
Very high yields were generally achieved independent
Concerning the mechanism of this rhodium-catalyzed
of the electronic nature ofthe aryltrifluoroborate and, to reaction, it is expected to be analogous to our previously
a given BH adduct, isomeric ratios were constant. Con- described reaction involving trivalent boronic acids de-
cerning the BH adduct partner, either aliphatic (entries rivatives: a tandem 1,4-addition/b-hydroxy elimination-
1–8) or aromatics substrates (entries 9–12) participated type mechanism instead of a p-allyl-type reactivity.[12]
equally well, in sharp contrast with the palladium-cata- The involvement of such a mechanism was confirmed
lyzed reaction of the BH adduct.[7] From these results by the high regioselectivity of the reaction involving
it also appeared that increasing steric hindrance of the deuterated substrate 1f. Indeed, the reaction of potassi-
aliphatic R1 moiety resulted in a slight decrease of the um trifluoro(phenyl)borate (2a) with 1f in the presence
isomeric ratio: from more than 99/1 (entries 1–4) to of the rhodium dimer [Rh(cod)Cl]2 in toluene/methanol
96/4 (entries 5–6), still in favor of the (E) isomer. The afforded exclusively the Michael adduct 3r in 71% yield,
same trend was observed using organoboronic acids as deuterium atoms being positioned on the vinylic moiety
reaction partners.[12] It is also important to note that and not at the benzylic position (Scheme 1).
higher yields, but comparable E/Z ratios, were generally
This high regioselectivity excluded a true p-allyl-type
observed using potassium trifluoro(organo)borates mechanism, where deuterium incorporation should
compared to boronic acids: for example, in the addition have appeared in both positions. Thus, the reaction
to BH substrate 1c, a 70% yield of alkene 3i was ach- should involve regioselective 1,4-addition of the organo-
ieved using phenylboronic acid, whereas the yield was metallic reagent followed by an unusual b-hydroxy elim-
improved to 96% using the potassium trifluoro(phenyl)- ination, generating the expected alkene and a hydroxo-
borate derivative (entry 8).
Due to their ready availability and higher stability with an organoboron species[17] (Scheme 2).
compared to trivalent organoboron derivatives, the re- In this reaction on BH adducts, an a,b-unsaturated es-
activity of potassium alken-1-yltrifluoroborates[8] was ter is generated which could participate to a novel rhodi-
also evaluated in this reaction (Table 3).
um-catalyzed 1,4-addition[10,11g] with remaining potassi-
rhodium complex suited for a transmetallation reaction
Indeed, under the current aerobic conditions, alkenyl- um trifluoro(organo)borate present in the reaction me-
trifluoroborates added smoothly to BH adducts afford- dium. However, in all the reactions examined, the bis-
ing useful 1,4-dienes in high yields and high stereoselec- addition compound was never observed on substituted
tivity on both double bonds: the (E)-alkene from the BH adducts, probably because the generated trisubsti-
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1,4-Addition of Potassium Trifluoro(organo)borates to Baylis–Hillman Adducts
Table 2. Aerobic rhodium-catalyzed addition of potassium aryltrifluoroborates to BH adducts.[a]
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Entry
1
Product
Yield[b] [%]
63
E/Z[c] [%]
99/1
2
3
58
85
99/1
99/1
4
5
98
70
99/1
96/4
6
7
91
90
96/4
96/4
8
96
98
98
96/4
97/3
98/2
9
10
11
98
98
98/2
97/3
12
[a]
Reactions were conducted using 0.5 mmol BH adduct 1, 1 mmol of R2-BF3K 2 with 1.5 mol % [Rh(cod)Cl]2 at 708C in 2 mL
toluene/methanol (1: 1).
Isolated yield of adduct 3.
Determined by GC/MS and H NMR.
[b]
[c]
1
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Laure Navarre et al.
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Table 3. Aerobic rhodium-catalyzed addition of potassium alkenyltrifluoroborates to BH adducts.[a]
Entry
1
Product
Yield[b] [%]
E/Z[c] [%]
91
99/1
2
3
84
94
98/2
96/4
4
44[d]
99/1
[a]
Reactions were conducted using 0.5 mmol BH adduct 1, 1 mmol of R2-BF3K 2 with 1.5 mol% [Rh(cod)Cl]2 at 708C in 2 mL
toluene/methanol 1: 1.
Isolated yield of adduct 3.
Determined by GC/MS and H NMR.
Reaction conducted with three equivalents of potassium trifluoro(vinyl)borate.
[b]
[c]
[d]
1
Scheme 1. Regioselectivity of the addition.
tuted alkene intermediate is too crowded to participate Scheme 2. Proposed mechanism.
in a novel insertion.[18]
To further demonstrate the utility of the present pro-
cedure for the formation of (E)-trisubstituted alkenes, um and unchanged isomeric ratio (99/1) in favor of the
larger scale reaction was conducted with low catalyst (E) isomer.
loading (Scheme 3). Reaction of BH adduct 1a
We have thus described an highly efficient reaction al-
(5 mmol) with potassium trifluoro(phenyl)borate 2a lowing an access to stereodefined trisubstituted alkenes
furnishes 3a in 90% yields and using 0.1 mol % of rhodi- from easily available BH adducts and potassium trifluoro-
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1,4-Addition of Potassium Trifluoro(organo)borates to Baylis–Hillman Adducts
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A mixture of the Baylis–Hillman adduct (0.5 mmol), potassi-
um trifluoro(organo)borate (2 equivalents), [Rh(cod)Cl]2
(3.6 mg, 1.5 mol %) were placed in a flask and then methanol
(1 mL) and toluene (1 mL) were added at room temperature.
The flask, equipped with a condenser, was placed in a preheat-
ed oil bath at 708C and the mixture was stirred until completion
of the reaction (followed by GC analysis). Purification by silica
gel chromatography (cyclohexane/ethyl acetate) afforded ana-
lytically pure products.
Acknowledgements
[12] L. Navarre, S. Darses, J.-P. Genet, Chem. Commun. 2004,
1108.
This work was supportedbythe Centre Nationalde la Recherche
`
Scientifique (CNRS). L. Navarre thanks the Ministere de lꢀEdu-
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cation et de la Recherche for a grant.
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