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Olsson and Szabo
JOCArticle
crude reaction mixture was evaporated and the residue was
purified by silica gel column chromatography.
Method B: General Procedure for Vinylic Functionalization.
Iridium catalyst 2 (0.003 mmol, 2 mol %, 2 mg) and 3a (0.15
mmol, 38 mg) were dissolved in neat alkene (0.1 mL). The
reaction mixture was stirred for the given times and tempera-
tures in Table 1 (cond. 1). After cooling to room temperature the
reaction mixture was diluted with a THF/water (4:1) mixture
(0.25 mL), whereafter 8a-b, 9a-d (0.15 mmol), Pd(OAc)2
(0.0075 mmol, 5 mol %, 1.8 mg), PPh3 (0.015 mmol, 20
mol %, 8 mg), and Cs2CO3 (0.30 mmol, 97 mg) were added.
Then stirring was continued for the allotted times and tempera-
tures given in Table 1. (cond. 2). The crude reaction mixture was
evaporated and the residue was purified by silica gel column
chromatography.
Synthesis of 2-Cyclopentenyl-4,4,5,5-tetramethyl-1,3,2-dioxa-
borolane (6a). Iridium-catalyst 2 (0.003 mmol, 2 mol %, 2 mg)
and 3 (0.15 mmol, 38 mg) were dissolved in neat 1a (0.1 mL). The
reaction mixture was stirred at 60 °C for 24 h whereafter the
crude reaction mixture was evaporated and the residue was
purified by silica gel column chromatography. The NMR data
obtained for 6a are identical with the literature values.51
1H NMR (CDCl3) δ 6.53 (t, J = 1.9 Hz, 1H), 2.40 (m, 4H),
1.81 (p, J=7.5 Hz, 2H), 1.26 (s, 12H); 13C NMR (CDCl3) δ
147.7, 83.2, 34.9, 34.6, 24.9, 24.0; HRMS (ESI) calcd for [C11-
H19BO2Na]þ m/z 217.1370, found 217.1379.
2-Cyclopentenyl(phenyl)methanol (10a). This compound was
prepared according to method A from 1a. The NMR data
obtained for 10a are identical with the literature values.52
1H NMR (CDCl3) δ 7.35 (m, 4H), 7.28 (m, 1H), 5.86 (dd, J =
2.2, 5.7 Hz, 1H), 5.41 (dt, J = 2.2, 5.7 Hz, 1H), 4.58 (d, J = 6.5
Hz, 1H), 3.11 (m, 1H), 2.34 (m, 2H), 1.90 (m, 2H); 13C NMR
(CDCl3) δ 143.6, 133.8, 131.4, 128.4, 127.5, 126.4, 77.1, 54.1,
32.4, 25.2; HRMS (ESI) calcd for [C12H14ONa]þ m/z 197.0937,
found 197.0939.
FIGURE 14. Catalytic cycle of the borylation of acyclic substrates
with vinylic C-H bond functionalization.
bond functionalization of unactivated alkenes. The key step
of this procedure is iridium-catalyzed borylation of the C-H
bond followed by coupling reactions. For cyclic alkenes,
such as cyclopentene and cyclohexene, the regioselectivity of
the C-H bond functionalization can be controlled by proper
choice of the reaction conditions. In the presence of 4a,b the
reaction will be selective for the formation of the allyl
boronate product. This allyl boronate product readily reacts
with aldehydes affording stereodefined allylic alcohols. As
far as we know, this is the first synthetic application for
allylic functionalization of cyclic alkenes based on catalytic
borylation reactions. In the absence of additives, as well as
for acyclic substrates, vinylic C-H bond functionalization
can be carried out. The in situ formed vinyl boronates readily
react with aryl halides in the Suzuki-Miyaura reaction.
These processes can be exploited for the synthesis of stereo-
defined allyl- and vinyl-silylbutadienes. The reactions take
place under milder conditions than the corresponding Heck
coupling offering an attractive, highly selective synthetic
route for the preparation of regio- and stereodefined func-
tionalized butadienes. Our mechanistic studies strongly in-
dicate that the reaction proceeds via a dehydrogenative
borylation mechanism, which in many mechanistic features
is similar to the Heck coupling reaction. The presented
synthetic and mechanistic results open new routes to densely
functionalized butadiene derivatives and stereodefined
homoallyl alcohols, which are useful building blocks in
natural product synthesis and also may serve as drug inter-
mediates.39,40 By application of appropriate ligands or ad-
ditives the process has a high potential in asymmetric
synthesis. In this respect two strategies can be employed:
diastereoselective boronation of cycloalkenes by application
of chiral boronates (such as 3b) or synthesis of chiral allyl
boronates by asymmetric catalysis.
1-(Cyclopent-2-enyl)heptan-1-ol (10b). This compound was
prepared according to method A from 1a. The diastereoselec-
tivity of 10b is assigned on the basis of 1H NMR data given in the
literature for analogous stereodefined homoallyl alcohols.52 1
H
NMR (CDCl3) δ 5.88 (dd, J = 2.2, 5.8 Hz, 1H), 5.60 (dt, J = 2.2,
5.8 Hz, 1H), 3.59 (m, 1H), 2.81 (m, 1H), 2.34 (m, 2H), 1.90 (m,
1H), 1.77 (m, 1H), 1.46 (m, 3H), 1.30 (m, 8H), 0.89 (t, J = 6.8
Hz, 3H); 13C NMR (CDCl3) δ 133.7, 131.8, 73.9, 52.2, 35.1, 32.5,
32.0, 29.6, 26.1, 23.7, 22.8, 14.2; HRMS (ESI) calcd for
[C12H22ONa]þ m/z 205.1563, found 205.1564.
(E)-1-(2-Cyclopentenyl)-3-phenyl-2-propen-1ol (10c). This
compound was prepared according to method A from 1a. The
NMR data obtained for 10c are identical with the literature
values.52 1H NMR (CDCl3) δ 7.39 (d, J = 7.6 Hz, 2H), 7.32 (t,
J = 7.6 Hz, 2H), 7.24 (t, J = 7.6 Hz, 1H), 6.61 (d, J = 15.5 Hz,
1H), 6.24 (dd, J = 6.5, 15.5 Hz, 1H), 5.92 (m, 1H), 5.67 (m, 1H),
4.24 (t, J = 6.5 Hz, 1H), 2.98 (m, 1H), 2.37 (m, 2H), 2.00 (m,
1H), 1.81 (m, 1H), 1.69 (br, 1H, OH); 13C NMR (CDCl3) δ
137.0, 134.0, 131.1, 131.0, 130.9, 128.7, 127.7, 126.6, 75.6, 52.5,
32.4, 24.7; HRMS (ESI) calcd for [C14H16ONa]þ m/z 223.1093,
found 223.1094.
Cyclopentenylbenzene (11a). This compound was prepared
according to method B from 1a and 8a except that barium
hydroxide (0.3 mmol, 95 mg) was used as base for the second
step coupling reaction. The NMR data obtained for 11a are
identical with the literature values.53,54 1H NMR (CDCl3) δ 7.45
Experimental Section
Method A: General Procedure for Allylation Reactions. Iri-
dium catalyst 2 (0.003 mmol, 2 mol %, 2 mg), 3a (0.15 mmol, 38
mg), and 4a (0.075 mmol, 11.4 mg) were dissolved in neat alkene
(0.2 mL). Then this reaction mixture was stirred at the tempera-
tures and times given in Table 1 (cond. 1). After cooling to room
temperature the corresponding aldehyde 7a-e (0.18 mmol) was
added to the mixture and the stirring was continued for the
allotted times and temperatures given in Table 1 (cond. 2). The
(51) Takagi, J.; Takahasi, K.; Ishiyama, T.; Miyaura, N. J. Am. Chem.
Soc. 2002, 124, 8001.
(52) Nishio, K.; Kobayashi, S. J. Org. Chem. 1994, 59, 6620.
(53) Furstner, A.; Scheiper, B.; Bonnekessel, M.; Krause, H. J. Org.
Chem. 2004, 69, 3943.
(54) Song, C.; Ma, Y.; Chai, Q.; Ma, C.; Jiang, W.; Andrus, M. B.
Tetrahedron 2005, 61, 7438.
7722 J. Org. Chem. Vol. 74, No. 20, 2009