Rhodium-catalyzed formation of stereocontrolled trisubstituted alkenes from Baylis-Hillman adducts

Article abstract of DOI:10.1002/chem.200802276

We report here efficient and general conditions for the formation of stereodefined trisubstituted alkenes using the rhodium-catalyzed reaction of unactivated Baylis-Hillman adducts with either organoboronic acids and potassium trifluoro(organo)borates. Th

Full text of DOI:10.1002/chem.200802276

DOI: 10.1002/chem.200802276
Rhodium-Catalyzed Formation of ACTHUNRTGNEUNGStereocontrolled Trisubstituted Alkenes
from Baylis–Hillman Adducts
Thomas Gendrineau,[a] Nicolas Demoulin,[a] Laure Navarre,[b] Jean-Pierre Genet,[a] and
Sylvain Darses*[a]
Abstract: We report here efficient and
general conditions for the formation of
stereodefined trisubstituted alkenes
using the rhodium-catalyzed reaction
of unactivated Baylis–Hillman adducts
with either organoboronic acids and
reaction conditions (from room tem-
perature up to 508C) and without the
need of additional phosphane ligands.
Based on the new reaction conditions,
the reaction, originally limited to
Baylis–Hillman adducts derived from
esters, could be extended to a large va-
riety of Baylis–Hillman adducts, bear-
ing either keto, cyano or amido func-
tionalities. Moreover, the reaction of
Baylis–Hillman adducts bearing esters
functionality was improved and could
be conducted at lower temperature
using lower catalyst loading.
potassium
trifluoro
ACHTUNGTREN(NUGN organo)borates.
Keywords: alkenes · boron deriva-
tives · conjugate addition · hetero-
geneous catalysis · rhodium
The use of the [{RhACHTUNGTRENNUNG(cod)OH}2] precur-
sor gave very fast coupling reactions
under low catalyst loading, very mild
Introduction
ates.[10] In terms of atom economy,[11] the use of unactivated
Baylis–Hillman adducts, would be more desirable but they
are generally less reactive in transition metal catalyzed reac-
tions.
The Baylis–Hillman reaction is a very useful and operation-
À
ally simple reaction allowing carbon carbon bond formation
under mild conditions.[1,2] The reaction products, called
Baylis–Hillman adducts, are highly functionalized substrates
bearing both allyl alcohol and a,b-unsaturated ester moie-
We recently reported that organoboronic acids[12] and po-
tassium trifluoroACTHNUTRGNEUNG
(organo)borates[13,14] reacted with simple
Baylis–Hillman adducts, derived from a,b-unsaturated esters
in the presence of a rhodium complex, affording stereode-
fined trisubstituted (E)-alkenes[15] under mild conditions via
an unusual mechanism. The initial reported catalyst, [{Rh-
ACHTUNGTRENNUNGties. Indeed, they have been further functionalized by palla-
dium-catalyzed Heck reactions[3] or Friedel–Crafts reac-
tions.[4] SN2’[5,6] or p-allyl-[7] type reactions have also been de-
scribed on Baylis–Hillman adducts, but the allyl alcohol
moiety had to be further transformed to carbonate or ace-
tate, which are better leaving groups. For example, Kabalka
et al. reported palladium-catalyzed cross-coupling reactions
of Baylis–Hillman acetates with bis(pinacolato)diboron[8] or
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
conditions were rather mild, reactions with others Baylis–
Hillman adducts, and particularly those derived from
enones, gave lower yields and the formation of by-products
was observed (see below). During the course of our studies,
we found that even milder conditions could be achieved
using another rhodium catalyst precursor, [{Rh-
potassium trifluoroACHTUNGTRENNUNG
(organo)borates,[9] allowing the formation
of stereodefined alkenes via p-allylpalladium intermedi-
AHCTUNGTRENNUNG
(cod)OH}2],[16] allowing not only to conduct many reactions
[a] T. Gendrineau, N. Demoulin, Prof. J.-P. Genet, Dr. S. Darses
Laboratoire de Synthꢀse Sꢁlective Organique (UMR 7573, CNRS)
Ecole Nationale Supꢁrieure de Chimie de Paris
11 rue P&M Curie, 75231 Paris cedex 05 (France)
Fax : (+33)144-07-10-62
under air at room temperature, but also to extend this reac-
tion to other Baylis–Hillman adducts, and particularly those
derived from enones. Herein, we want to report our results
concerning the development of a very general reaction for
the formation of functionalized stereodefined trisubstituted
alkenes from readily available substrates.
E-mail: sylvain-darses@enscp.fr
[b] L. Navarre
Finorga-Novasep, 497 route de Givors
38670 Chasse sur Rhone (France)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200802276.
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Chem. Eur. J. 2009, 15, 4710 – 4715

FULL PAPER
Results and Discussion
slower (at least 24 h for complete conversion). Indeed, in
order to shorten the reaction time, reactions with potassium
aryltrifluoroborates were best conducted at 508C; in all re-
actions examined, complete conversion was observed within
hours.
We have recently shown that, in the presence of commer-
cially available [{Rh
ACHTUNGTRENNUNG
acids and potassium trifluoroAHCNUTGTRENNUNG
Baylis–Hillman substrates derived from a,b-unsaturated
esters via 1,4-addition/b-hydroxyelimination process gave
trisubstituted alkenes with high yields and stereoselectivities
above 96:4 in favor of the E isomer.[12,13] However, when we
wanted to extend these conditions to other Baylis–Hillman
adducts, the results were disappointing. For example, reac-
tion of phenylboronic acid (1a) with 3a under previously
described conditions[12] afforded only 50% yield of the ex-
pected alkene 5aa, even if the conversion was quantitative
(Table 1, entry 1); lower reaction temperatures did not in-
A comparison of the reactivity of the two catalyst precur-
sors, [{RhACHTUNRTGNNEUG(cod)OH}2] and [{RhACHTUTGNREN(NUNG cod)Cl}2], was evaluated in
the reaction of Baylis–Hillman adduct 3a with phenylboron-
ic acid (1a) under optimized conditions (Figure 1). In the
case of the hydroxy–rhodium precursor, the reaction was
completed within a few minutes at room temperature,
whereas more than 5 h were necessary with the chloride–
rhodium precursor. More surprisingly, fast reaction was also
observed using [{RhACTHNURGTNEUNG(cod)OH}2] when the reaction was con-
ducted at 08C (Figure 1). In view of the postulated reaction
mechanism, where a hydroxy–rhodium species is generated
after b-hydroxy elimination,[12,13] the result suggests that the
chloride anion is not a spectator ligand in this reaction, be-
cause, on the contrary, similar reaction rates should be ob-
served with this two catalyst precursors after an inductive
period. Further studies are currently under way in our labo-
ratory in order to investigate the exact role played by the
rhodium counter-anion.
Table 1. Optimization of the reaction conditions for the addition of 1a to
3a.[a]
Entry
[Rh]
Solvent
Conversion[b]
t
1
2
3
4
5
6
7
8
9
[{Rh
[{Rh
N
MeOH
MeOH
MeOH
MeOH
MeOH
isopropanol
toluene
dioxane
DMF
100[c] (50)
100 (60)
100
100 (89)
100[d] (88)
83
72
77
< 10
0
30 min
6 h
[Rh
A
30 min
5 min
5 min
30 min
30 min
30 min
1 h
[{Rh
[{Rh
[{Rh
[{Rh
[{Rh
[{Rh
[{Rh
10
H2O
4 h
[a] Reactions conducted by using 0.5 mmol Baylis–Hillman adduct 3a,
1 mmol of 1a with 2 mol% [Rh] at RT in 2 mL of solvent. [b] Conversion
determined by GC. Isolated yields in brackets. The isomeric ratio was
99:1 in favor of the E isomer. [c] Reaction conducted at 508C. [d] Re-
action conducted with 1 mol% [Rh].
Figure 1. Compared reactivity of [{RhACHTNUTRGENN(GU cod)OH}2] and [{RhACHTUNGTERN(NUGN cod)Cl}2] in
&
the addition of 1a to 3a (0.5 mol% [{RhACHTNURGTNEUNG(cod)OH}2] at 20 ( ) and at 08C
&
*
(
); 0.5 mol% [{RhACTHGUNTER(NNUG cod)Cl}2] at 208C ( )).
crease the yields that much (entry 2). In order to achieve ac-
ceptable yields on the substrates, other reaction conditions
were evaluated and particularly other rhodium catalyst pre-
cursors. We were pleased to find that a cationic rhodium
(entry 3), and, even better, a hydroxy–rhodium (entry 4)
were particularly suitable for this reaction, which was now
fast even at room temperature. Most impressive, the reac-
tion conducted with 1 mol% [{RhACHTUNRGTNEUNG(cod)OH}2] was finished
in less than five minutes and the expected alkene 5aa was
isolated in 88% yield (entry 5).
Other solvents were also evaluated using the hydroxy–
rhodium catalyst precursor (entries 5–10) but no beneficial
effect was observed in nonprotic solvents. Indeed, as shown
before,[12] alcoholic solvents are also most suitable for the re-
action of Baylis–Hillman adducts with boronic acids using
The generality of the reaction conditions was evaluated
on various Baylis–Hillman adduct with either boronic acids
1 or trifluoroborate species 1’ (Scheme 1). The new opti-
mized experimental conditions were first re-evaluated on
the reaction of Baylis–Hillman adducts 2 derived from ester
(EWG = CO2Me). In reactions with arylboronic acids,
Baylis–Hillman adducts 3 afforded the expected trisubstitut-
ed alkenes in good yields and high stereoselectivity
(Table 2). With all substrates examined, reactions were com-
pleted within a few minutes at room temperature using only
1 mol% of rhodium catalyst precursor. Moreover, faster re-
actions and generally higher yields of alkenes were observed
compared with the reaction using previously published reac-
[{Rh
previously optimized solvent system (toluene/MeOH 1:1),[13]
the addition of potassium trifluoro(phenyl)borate (1a’) to
3a also occurred at room temperature, but the reaction was
ACHTUNGTRENNUNG(cod)OH}2]. Using the same catalyst precursor, and the
tion conditions: [{RhACHTUNTGRENUNG(cod)Cl}2] at 508C (entries 2, 4, 9,
G
14).[12] Once again, it appeared that either aromatic or ali-
phatic Baylis–Hillman adducts show similar reactivity.[17]
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S. Darses et al.
Table 2. Formation of trisubstituted alkenes from Baylis–Hillman adduct
pared with the reaction with boronic acids, these new condi-
tions did not result in increased yields. Identical levels of
isomeric purities were observed in the reactions involving
2 derived from enoates.[a]
Entry 1 or
1’
2
Product Yield[b] with
4
Yield[c] with
R1BF3K [%]
E/Z[d]
R1B(OH)2 [%]
potassium trifluoro
ACHTUNGTRENN(UNG organo)borates compared with those in-
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1g
1h
1i
2a 4aa
2a 4ba
2a 4ca
2a 4da
2a 4ga
2a 4ha
2a 4ia
2a 4la
2a 4oa
2d 4ad
2d 4dd
2e 4ne
2 f 4af
2 f 4ef
2g 4ag
2g 4jg
2g 4og
2h 4ah
86
98 (85)
(95)
(86)[f]
99:1
>99:1
99:1
99:1
99:1
98:2
99:1
99:1
98:2
96:4
94:6
88:12
96:4
97:3
volving boronic acids. Importantly the yields and isomeric
A
ACHTUNGTRENNUNG
purities of the trisubstituted alkenes 4 are not influenced by
the electronic properties (electron-withdrawing or -releasing
substituents) of the arylboron derivative. Overall these new
reaction conditions compare favorably to the previous re-
ported for the reactions of Baylis–Hillman adducts derived
from a,b-unsaturated esters: lower reaction temperature,
comparable yields and selectivities, lower catalyst loading
87 (87)
54 (60)
89 (95)
(65)
74 (83)[f]
(63)[e]
(98)
1l
82 (86)[e]
73
9
1o
1a
1d
1n
1a
1e
1a
1j
10
11
12
13
14
15
16
17
18
93 (61)
82
(91)
for
(organo)borates (1 mol% compared with 3 mol% previous-
ly used).[13]
the
reactions
involving
potassium
trifluoro-
95
AHCTUNGTRENNUNG
(75)
(75)
99 (74)
>99
(70)[f]
Under these optimized conditions, we also evaluated the
generality of the reaction of Baylis–Hillman adducts 3 de-
rived from enones. As mentioned before, under our previous
(98)[f]
45
>99 (98)
(58)
97:3
96:4
97:3
1o
1a
72 (86)
96:4
conditions using [{RhACHTNUGTRNEUNG(cod)Cl}2], low yields were observed
[a] Reactions conducted by using 0.5 mmol Baylis–Hillman adduct 2 and
1 mmol of RBF3K or RB(OH)2. [b] Yields obtained by conducting the re-
despite quantitative conversion. These low yields were at-
tributed to the decomposition of the Baylis–Hillman adduct,
which are prone to polymerization under slow reaction con-
ditions (low catalytic activity). However, when using the
highly efficient hydroxy–rhodium precursor, we were
pleased to find that these sensitive substrates do participate
to the reaction, affording, once again, stereodefined tri-
action in MeOH at RT with 0.5 mol% [{Rh
thesis, yields obtained by using the previous system: MeOH, 508C with
0.5 mol% [{Rh(cod)Cl}2]. [c] Yields obtained by conducting the reaction
in Tol/MeOH 1:1 at 508C with 0.5 mol% [{Rh(cod)OH}2]. Between pa-
renthesis, yields obtained by using the previous system: Tol/MeOH, 708C
with 1.5 mol% [{Rh
(cod)Cl}2]. [d] Determined by GC–MS and 1H NMR
ACHTUNGTERN(NUNG cod)OH}2]. Between paren-
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
spectroscopy. [e] From ref. [12]. [f] From ref. [13].
AHCTUNGTREGsNNUN ubstituted alkenes in good yields and selectivities
(Scheme 1, Table 3). Very high yields were generally ach-
ieved independently to the electronic nature of aryltrifluoro-
borates or arylboronic acids and, to a given Baylis–Hillman
adduct, isomeric ratios were constant. From the results it
also appears, as observed for Baylis–Hillman adduct derived
from a,b-unsaturated esters, that increasing steric hindrance
on the aliphatic R2 moiety resulted in a slight decrease of
the isomeric ratio: from more than 99:1 (entries 1–23) to
merely 97:3 for isopropyl substituted Baylis–Hillman adduct
3c (entries 24–26), still in favor of the E isomer. Notably
higher yields, but comparable E/Z ratios, were generally ob-
served using potassium trifluoroACTHUNTGRNEUNG(organo)borates compared
with boronic acids (entries 1–4, 12, 18): for example, in the
addition to Baylis–Hillman substrate 3a, alkene 5aa was ob-
tained in 89% yield using phenylboronic acid (1a), whereas
the yield was improved to 99% using potassium trifluoro-
AHCTUNGTREG(NNUN phenyl)borate (1a’, entry 1). Indeed, this reaction affords a
straightforward access to highly useful enones, which are
susceptible to further functionalization by Michael-type ad-
dition reactions.[18]
Scheme 1. Rhodium-catalyzed formation of stereodefined trisubstituted
alkenes.
The reaction conditions are not limited to Baylis–Hillman
adducts derived from a,b-unsaturated esters and ketones.
Concerning the isomeric E/Z ratio, they are uniformly high
for aliphatic substituted Baylis–Hillman adducts (99:1, en-
tries 1–11), but they are slightly decreased when the steric
hindrance of the substituent is increased: from 96:4 for aro-
matic substituents (entries 15–18) to 88:12 for cyclohexyl
substituents (entry 12). In reactions with potassium trifluoro-
For example, reaction of Baylis–Hillman adduct
6
(Scheme 2), derived from a,b-unsaturated amide also under-
went the coupling reaction to afford functionalized amide 7
with high stereoselectivity (E/Z 99:1). A moderate yield was
achieved using phenylboronic acid as coupling partner,
whereas the use of potassium trifluoroACTHNUTRGNEUNG(phenyl)borate (1a’)
A
allowed the formation of trisubstituted alkene 7 in a 78%
A
yield. The lower yield observed in the reaction with boronic
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Baylis–Hillman Adducts
FULL PAPER
Crafts reaction[20] or uncatalyzed addition of organometal-
lics[5] to acetates of Baylis–Hillman adducts. In our proposed
reaction mechanism,[12,13] which was partially validated by
deuterium labeling studies, after transmetalation of the aryl-
borane moiety insertion of the alkene in the aryl–rhodium
bond occurs, which affords an alkyl–rhodium species bearing
an hydroxy substituent in the b-position of the rhodium
center. Subsequently, b-hydroxy elimination occurs to afford
the trisubstituted alkene and an active hydroxy–rhodium
species.
Table 3. Formation of trisubstituted alkenes from Baylis–Hillman adduct
3 derived from enones.[a]
Entry 1 or
1’
3
Product Yield[b] with
5
Yield[c] with
R1BF3K [%]
E/Z[d]
R1B(OH)2 [%]
1
2
3
4
5
6
7
8
1a
1b
1d
1e
1 f
1g
1i
1j
1k
1l
1n
1o
1a
1b
1d
1e
1g
1i
3a 5aa
3a 5ba
3a 5da
3a 5ea
3a 5 fa
3a 5ga
3a 5ia
3a 5ja
3a 5ka
3a 5la
3a 5na
3a 5oa
3b 5ab
3b 5bb
3b 5db
3b 5eb
3b 5gb
3b 5ib
3b 5jb
3b 5lb
89
71
80
44
72
43
40
85
80
73
82
79
73
80
89
89
99
54
88
76
>99:1
>99:1
>99:1
>99:1
>99:1
99:1
>99:1
>99:1
>99:1
>99:1
99:1
>99:1
>99:1
>99:1
99:1
99:1
>99:1
99:1
36
81
Indeed, the stereoselectivity observed for the obtained tri-
substituted alkenes originates from the complexation of the
starting Baylis–Hillman adduct to the rhodium center, that
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
[16a,21]
À
is, before the irreversible C C bond formation.
More-
over, the stereoselectivity observed is independent of the
configuration of the hydroxyl group (a racemic mixture is
used as starting material). Once transmetalation has oc-
curred, four different complexes can be formed upon com-
plexation of the starting Baylis–Hillman adduct, depending
on the configuration of the hydroxyl substituent and the
face of complexation (Scheme 3), assuming that the hydroxy
52
59
50
70
95
1j
1l
>99:1
>99:1
1m 3b 5mb
48
70
1n
1o
1b
1j
3b 5nb
3b 5ob
3c 5bc
3c 5jc
3c 5kc
68
>99:1
>99:1
96:4
97:3
>99:1
56
83
50
1k
[a] Reactions conducted by using 0.5 mmol Baylis–Hillman adduct 3 and
1 mmol of RBF3K or RB(OH)2 in the presence of 0.5 mol% [{Rh-
ACHTUNGTRENNUNG(cod)OH}2]. [b] Yields obtained by conducting the reaction in MeOH at
RT. [c] Yields obtained by conducting the reaction in Tol/MeOH 1:1 at
1
508C. [d] Determined by GC–MS and H NMR spectroscopy.
Scheme 3. Tentative explanation of the observed stereoselectivities.
substituent is also partially complexed to the rhodium(I)
center. We believe that steric interaction between R2 and
EWG substituents is responsible of the lowest stability of
complexes Re,R and Si,S, which should have resulted in the
formation of (Z)-trisubstituted alkenes. Indeed, depending
on the configuration of the hydroxy substituent of the start-
ing Baylis–Hillman adduct, two equivalent complexes Re,S
or Si,R can be formed, which leads to the formation to the
(E)-trisubstituted alkenes. The lowest and slightly reversed
stereoselectivities obtained with cyano Baylis–Hillman de-
rivatives can be explained by lowest interaction between R2
and EWG, resulting in the formation of the different rhodi-
um isomers in variable proportions. Further studies, and par-
ticularly DFT studies, are currently conducted in our labora-
tory.
Scheme 2. Extension to other Baylis–Hillman adducts.
acid 1a can be attributed to the lower reaction temperature,
as well as the lower reactivity of such a Baylis–Hillman
adduct. Similarly, cyano derivative Baylis–Hillman adduct 8
also participated in the reaction. The coupling with phenyl-
boronic acid afforded the cyano-alkene 9 in 68% yield. In-
terestingly, and as observed in Friedel–Crafts reactions with
such adducts,[19] reversed, although moderate, selectivity was
observed and the Z isomer was the major isomer formed.
Although we donꢃt have any supported explanation to ac-
count for the observed stereoselectivities, it is surprising that
the stereoselectivities observed in this rhodium-catalyzed re-
action are very similar to Lewis acid catalyzed Friedel–
Due to their ready availability and higher stability com-
pared with trivalent organoboron derivatives, the reactivity
of potassium alken-1-yltrifluoroborates[14] was also evaluated
under these reaction conditions, using either Baylis–Hillman
adducts bearing ketone (Table 4, entries 1–4) or ester func-
tionalities (entries 5–13). Indeed, in the presence of
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S. Darses et al.
Table 4. Rhodium-catalyzed formation of 1,4-dienes.[a]
ganometallic partner. Compared with previous reaction con-
ditions, similar or slightly higher yields were obtained, while
using lower catalytic loading (three times less). More partic-
ularly, useful potassium vinyltrifluoroborate[22,14] also partici-
pated in this reaction, which afforded the expected 1,4-
dienes in good yields (entries 8–9, 11,13). Once again lower
stereoselectivities were observed when the steric hindrance
on the R2 substituent was increased (entries 9–10). Thus,
using this efficient catalytic reaction, highly functionalized
1,4-dienes were easily accessible from readily available re-
agents: an aldehyde, a Michael acceptor (the Baylis–Hill-
Entry
1
Product
Yield [%]
70
E/Z[b]
99:1
2
3
80[c]
99:1
97:3
man reagent) and potassium alkenyltrifluoACTHNUTRGENNUrG oACHUTGTNRENNbGU orate.
Conclusion
86
We have described and extended an highly efficient reaction
to access stereodefined trisubstituted alkenes from the cou-
pling of readily available Baylis–Hillman adducts with either
4
93 (84)
99:1
organoboronic acids or potassium trifluoroACTHNUGRTENUNG(organo)borates.
Compared with their trivalent congeners, trifluoroborate de-
rivatives show several advantages in terms of stability and
ease of preparation and purification.[14] High yields were
generally achieved using a large variety of Baylis–Hillman
adducts derived from a,b-unsaturated esters, ketones,
amides and cyano derivatives. This reaction, involving a 1,4-
addition/b-hydroxy elimination mechanism, presents several
attractive features, not only because of the simple reaction
conditions (low temperature, aerobic conditions) but also by
the use of easily accessible Baylis–Hillman adducts as start-
ing materials. We hope that this methodology will provide
new opportunities in organic synthesis due to its high versa-
tility and the ready availability of the reagents.
5
6
(84)[d]
98:2
98:2
93 (91)[d]
7
8
9
93
99:1
98:2
90:10
75[c]
80
Experimental Section
10
11
12
95
97
43
92:8
99:1
96:4
Typical procedure for the reaction of organoboronic acids or potassium
trifluoro
Baylis–Hillman adduct (0.5 mmol), potassium trifluoro
organoboronic acids (2 equivalents), [{Rh(cod)OH}2] (2.2 mg, 0.5 mol%)
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
were placed in a flask and then a toluene/methanol mixture (1 mL, for
RBF3K) or methanol (1 mL, for RB(OH)2) were added at room tempera-
ture. The flask was closed and the reaction mixture was stirred at the in-
dicated temperature until completion of the reaction (followed by GC
analysis). Purification by silica gel chromatography afforded analytically
pure products.
13
57 (44)[d]
96/4
[a] Reactions conducted by using 0.5 mmol Baylis–Hillman adduct 2 or 3
and 1 mmol of RBF3K in the presence of 0.5 mol% [{RhACHTUNTRGENUG(N cod)OH}2] in
Tol/MeOH 1:1 at 508C. [b] Determined by GC–MS and 1H NMR spec-
troscopy. [c] Reaction conducted at 808C. [d] From ref. [13].
Acknowledgement
This work was supported by the Centre National de la Recherche Scien-
ACHUTNGRENUtNG ifACTHUGNRTENNUiG que (CNRS). T.G. thanks the Ministꢀre de l’Education et de la Re-
cherche for a grant.
0.5 mol% [{Rh
rates added smoothly to Baylis–Hillman adducts affording
useful 1,4-dienes in high yields and high stereoselectivities
on both double bonds: (E)-alkene from the a,b-unsaturated
moiety while maintaining the geometry of the incoming or-
ACHTUNGTRENNUNG(cod)OH}2], potassium alkenyltrifluorobo-
A
ACHTUNGTRENNUNG
[1] a) K. I. Morita, Z. Suzuki, H. Hirose, Bull. Chem. Soc. Jpn. 1968, 41,
2815–2815; b) A. B. Baylis, M. E. D. Hillman, Patent DE2155113,
1972.
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ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 4710 – 4715

Baylis–Hillman Adducts
FULL PAPER
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[4] See for example: a) D. Basavaiah, M. Krishnamacharyulu, R. Sugu-
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[5] a) H. Amri, M. Rambaud, J. Villiꢁras, Tetrahedron 1990, 46, 3535–
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Chandrasekhar, Tetrahedron Lett. 2007, 48, 215–218.
[6] For an example of SN2’ reaction involving unprotected Baylis–Hill-
man adducts, see: S. Chandrasekhar, B. Saritha, V. Jagadeshwar, C.
Narsihmulu, D. Vijay, G. Dattatreya Sarma, B. Jagadeesh, Tetrahe-
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5442; b) O. Roy, A. Riahi, F. Hꢁnin, J. Muzart, Tetrahedron 2000,
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Soc. 2000, 122, 3534–3535; d) B. M. Trost, O. R. Thiel, H. C. Tsui, J.
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[8] G. W. Kabalka, B. Venkataiah, G. Dong, J. Org. Chem. 2004, 69,
5807–5809.
[9] G. W. Kabalka, B. Venkataiah, G. Dong, Org. Lett. 2003, 5, 3803–
3805.
[13] L. Navarre, S. Darses, J. P. Genet, Adv. Synth. Catal. 2006, 348, 317–
322.
[14] Reviews on potassium organotrifluoroborate chemistry: a) S.
Darses, J. P. Genet, Eur. J. Org. Chem. 2003, 4313–4327; b) G. A.
Molander, R. Figueroa, Aldrichimica Acta 2005, 38, 49–56; c) G. A.
Molander, N. M. Ellis, Acc. Chem. Res. 2007, 40, 275–286; d) H. A.
Stefani, R. Cella, A. S. Vieira, Tetrahedron 2007, 63, 3623–3658;
e) S. Darses, J. P. Genet, Chem. Rev. 2008, 108, 288–325.
[15] For another example: M. L. Kantam, K. B. S. Kumar, B. Sreedhar, J.
Org. Chem. 2008, 73, 320–322.
[16] Hydroxy–rhodium precursor has been shown to be one of the most
active precursor in rhodium-catalyzed reactions involving boron re-
agents, see for example: a) T. Hayashi, M. Takahashi, Y. Takaya, M.
Ogasawara, J. Am. Chem. Soc. 2002, 124, 5052–5058; b) A. Kina, H.
Iwamura, T. Hayashi, J. Am. Chem. Soc. 2006, 128, 3904–3905;
c) R. Shintani, K. Takatsu, T. Hayashi, Angew. Chem. 2007, 119,
3809–3811; Angew. Chem. Int. Ed. 2007, 46, 3735–3737; d) S.
Brock, D. R. J. Hose, J. D. Moseley, A. J. Parker, I. Patel, A. J. Wil-
liams, Org. Process Res. Dev. 2008, 12, 496–502; e) T. Gendrineau,
O. Chuzel, H. Eijsberg, J. P. Genet, S. Darses, Angew. Chem. 2008,
120, 7783–7786; Angew. Chem. Int. Ed. 2008, 47, 7669–7672.
[17] Under palladium-catalyzed p-allylic activation of acetates of aliphat-
ic Baylis–Hillman adducts, lower reactivity and stereoselectivity was
observed: see refs. [8] and [9].
[18] For some recent reviews: a) T. Hayashi, K. Yamasaki, Chem. Rev.
2003, 103, 2829–2844; b) G. S. C. Srikanth, S. L. Castle, Tetrahedron
2005, 61, 10377–10441; c) H. C. Guo, J. A. Ma, Angew. Chem. 2006,
118, 362–375; Angew. Chem. Int. Ed. 2006, 45, 354–366; d) Y. Ya-
mamoto, T. Nishikata, N. Miyaura, J. Synth. Org. Chem. Jpn. 2006,
64, 1112–1121; e) A. Alexakis, J. E. Bꢅckvall, N. Krause, O. Pꢆlmies,
M. Diꢁguez, Chem. Rev. 2008, 108, 2796–2823; f) Y. Yamamoto, T.
Nishikata, N. Miyaura, Pure Appl. Chem. 2008, 80, 807–817; g) S. R.
Harutyunyan, T. den Hartog, K. Geurts, A. J. Minnaard, B. L. Ferin-
ga, Chem. Rev. 2008, 108, 2824–2852.
[19] a) D. Basavaiah, M. Krishnamacharyulu, R. Suguna Hyma, S. Pan-
diaraju, Tetrahedron Lett. 1997, 38, 2141–2144; b) H. J. Lee, T. H.
Kim, J. N. Kim, Bull. Korean Chem. Soc. 2001, 22, 1063–1064.
[20] a) D. Basavaiah, R. M. Reddy, Tetrahedron Lett. 2001, 42, 3025–
3027; b) ref. [2].
[10] For another example see: B. C. Ranu, K. Chattopadhyay, R. Jana,
Tetrahedron Lett. 2007, 48, 3847–3850.
[21] L. Navarre, R. Martinez, J. P. Genet, S. Darses, J. Am. Chem. Soc.
2008, 130, 6159–6169.
[11] a) B. M. Trost, Science 1991, 254, 1471–1477; b) B. M. Trost, Angew.
Chem. 1995, 107, 285–307; Angew. Chem. Int. Ed. Engl. 1995, 34,
259–281.
[22] a) S. Darses, G. Michaud, J. P. Genet, Tetrahedron Lett. 1998, 39,
5045–5048; b) S. Darses, G. Michaud, J. P. Genet, Eur. J. Org.
Chem. 1999, 1875–1883.
[12] L. Navarre, S. Darses, J. P. Genet, Chem. Commun. 2004, 1108–
1109.
Received: November 3, 2008
Published online: March 19, 2009
Chem. Eur. J. 2009, 15, 4710 – 4715
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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