Pd-Catalyzed borylative polycyclization of enediynes to alkylboronates

Article abstract of DOI:10.1002/chem.201001124

Pd-catalyzed bicyclization of 1-ene-6,11-diynes with bis(pinacolato)diboron smoothly affords synthetically useful homoallylic alkylboronates under mild conditions, avoiding the use of highly nucleophilic or basic reagents. One Ci￡B bond and two new Ci￡C b

Full text of DOI:10.1002/chem.201001124

DOI: 10.1002/chem.201001124
Pd-Catalyzed Borylative Polycyclization of Enediynes to Alkylboronates
Juan Marco-Martꢀnez, Elena BuÇuel, Ruth Lꢁpez-Durꢂn, and Diego J. Cꢂrdenas*[a]
Dedicated to Professor Josꢀ Barluenga on the occasion of his 70th birthday
Abstract: Pd-catalyzed bicyclization of
1-ene-6,11-diynes with bis(pinacolato)-
diboron smoothly affords synthetically
The obtained products suggest a cas-
cade reaction in which the last step is
the transmetalation of bis(pinacolato)-
diboron, this being faster than a possi-
ble b-hydride elimination process. The
reaction is general and has been ap-
plied to enediynes with different sub-
stituents on the alkene unit, the bridg-
ing groups, and the alkyne moiety. The
bicyclized alkylboronates thus obtained
can be functionalized by oxidation to
alcohols, formation of trifluoroborate
salts, or by Suzuki coupling reactions.
useful
homoallylic
alkylboronates
under mild conditions, avoiding the use
of highly nucleophilic or basic reagents.
À
À
One C B bond and two new C C
bonds are created, and two new stereo-
genic centers are stereospecifically
formed in a single tandem operation.
Keywords: boranes
·
boron
·
catalysts
methods
· palladium · synthetic
1,2-diols.[7] C H activation of alkanes is a promising alterna-
tive for the preparation of primary alkylboronates.[8]
Our research group has developed a novel reaction for
the formation of alkyl (homoallylic) boronates from enynes
by a formal 1,7-hydroboration with concomitant carbocycli-
zation.[9] Moreover, this methodology has recently been ex-
tended to the borylative cyclization of allenynes and enal-
lenes,[10] and even to polyunsaturated compounds such as 6-
ene-1,11-diynes, leading to bicyclic allylboronates.[11]
In order to extend the borylative polycyclization process
to other substrates with the aim of obtaining complex alkyl-
boronates, we have studied this reaction with 1-ene-6,11-
diynes. In this article, we wish to report the stereoselective
formation of bicyclic homoallylic boronates by a Pd-cata-
lyzed cascade reaction with bis(pinacolato)diboron, as well
as applications of these derivatives as synthetically useful in-
termediates.
À
Introduction
Transition metal-catalyzed cyclization reactions of polyunsa-
turated acyclic compounds allow the construction of more
complex organic structures by using tandem intramolecular
trapping agents (polycycloisomerization)[1] or even intermo-
lecular partners (polycyclohydrosilylation).[2] Moreover,
these processes usually proceed with high levels of atom
economy and selectivity.
On the other hand, the development of innovative meth-
odologies for the synthesis of organoboron derivatives is
particularly useful, since these reagents are important pre-
cursors for the preparation of more elaborate compounds by
further functionalization, and they have the advantages of
low toxicity and high functional group compatibility. In
recent years, alkylboronates and alkyltrifluoroborates have
become increasingly important intermediates for synthetic
purposes,[3,4] since they can be used as nucleophilic partners
in Suzuki cross-coupling[5] and other C C bond-forming re-
À
actions. Alkylboronates are usually synthesized by the hy-
droboration of alkenes or by reaction of main-group organo-
metallic derivatives with borate esters.[6] 1,2-Diborylated al-
kanes can be prepared by the diboration of C=C bonds, and
have recently been used for the enantioselective synthesis of
Results and Discussion
When bis
ACHTUNGTREN(NGNU malonate)-tethered 1-ene-6,11-diyne 1a was sub-
jected to reaction with bis(pinacolato)diboron in the pres-
ence of [PdACTHNUGTRENUNG(OAc)2] and MeOH in toluene, alkylboronate 2a
was formed in moderate to good yields (Scheme 1).[12]
À
This cascade reaction provides two C C bonds and one
À
C B bond in a single stereoselective operation. With the
[a] Dr. J. Marco-Martꢀnez, Dr. E. BuÇuel, R. Lꢁpez-Durꢂn,
Prof. Dr. D. J. Cꢂrdenas
aim of exploring the scope of the process, the reaction was
extended to a large number of related substrates, including
those with various modifications at the different moieties of
the enediyne, such as substituents on the double bond, var-
iations in the substitution and nature of the bridging groups,
and different substituents on the alkyne moiety (Figure 1).
Enediynes 1b–e, having different substitution patterns on
the alkene fragment, were reacted under optimized boryla-
Departamento de Quꢀmica Orgꢂnica (Mꢁdulo 01)
Facultad de Ciencias, Universidad Autꢁnoma de Madrid
Av. Francisco Tomꢂs y Valiente 7
28049 Cantoblanco, Madrid (Spain)
Fax : (+34)914973966
E-mail: diego.cardenas@uam.es
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201001124.
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Chem. Eur. J. 2011, 17, 2734 – 2741

FULL PAPER
the new stereogenic centers was
determined by comparison with
the products previously ob-
tained by the borylative cycliza-
tion of 1,6-enynes,[9] according
to the structural similarity of
the second cycle formed.
Scheme 1. Pd-catalyzed bicyclization/borylation of 1-ene-6,11-diyne 1a.
Figure 1. Possible modifications of the enediyne structure.
Scheme 2. Relative stereochemistry and demonstration of the stereospe-
cificity.
tive polycyclization conditions to give the corresponding al-
kylboronates 2b–e in good yields (Table 1). In the case of al-
lylic ester substitution (entries 1 and 2), yields were similar
to that in the case of 2a.[13] On the other hand, formation of
alkylboronates 2d and 2e from enediynes 1d and 1e, in
which b-hydrogen elimination cannot take place, afforded
the highest yields (81% and 80%, respectively).
These results allowed us to outline a possible mechanistic
pathway (Scheme 3). Thus, the reaction probably takes
place by formation of a Pd–hydride complex, followed by
hydropalladation of the terminal alkyne, rather than by re-
action with the internal linker triple bond. Next, 1,2-inser-
tion of the inner triple bond in the alkenylpalladium inter-
mediate B would result in the first cyclization to afford the
new alkenylpalladium intermediate C. Then, the alkenyl–Pd
bond in C carbometallates the pendant double bond to give
Table 1. Alkylboronates from substituted alkene derivatives.
Substrate
t [h]
Product
Yield
[%]
the alkylpalladium intermediate
D (Scheme 3). Finally,
methoxide-promoted transmetalation with bis(pinacolato)di-
boron and subsequent reductive elimination would lead to
the final alkylboronate. The higher yields observed for 1d
and 1e suggest that intermediate D may partially decom-
pose by b-hydrogen elimination, although this is a minor
process, in accord with results previously obtained for the
cyclization of simple enynes.[9]
It is worth noting that, regardless of the presence of b-hy-
drogens susceptible to elimination from the alkylpalladium
intermediate D, there may be some stabilization due to co-
ordination of the Pd by the diene moiety (Scheme 3). There-
fore, the transmetalation process is faster than the possible
b-hydrogen elimination. In fact, b-elimination products have
rarely been detected and isolated.
1
2
1b
1c
22
23
2b: R=H, R’=H,
R’’=CH2OAc
2c: R=H, R’=H,
R’’=CH2OBz
2d: R=Me, R’=H, R’’=H
2e: R=Me, R’=Ph, R’’=H
66
70
3
4
1d
1e
4
3.5
81
80
Moreover, with the aim of studying the stereospecificity
of the process, the E isomers of 1b and 1c were prepared.
Thus, when the reaction was carried out with (E)-1b and
(E)-1c the corresponding diastereomers of 2b and 2c were
obtained (2b’ and 2c’, respectively; Scheme 2). Isolated
yields of 2b’ and 2c’ were lower due to decomposition
during the purification process. Elimination of the boronate
with the b-ester group readily takes place, affording bicyclic
triene 3 as a by-product.[14] The relative stereochemistry of
In order to analyze the effect on the reaction outcome of
a combination of two different tethers, several such sub-
strates were tested. Thus, compounds 1 f–h, in which the
diyne moiety contains a non-malonate tether, were prepared
and reacted under the cyclization conditions to afford the
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2735

D. J. Cꢂrdenas et al.
place or it was so slow that it
led to low yields as a result of
the facile decomposition of the
palladium intermediates.
The results in Tables 2 and 3
are consistent with those ob-
tained previously for the bory-
lative cyclization of 1,6-enynes,
with non-malonate tethers lead-
ing to lower yields.[9] Most
probably, as in the case of
simple enynes,
a
weaker
Ingold–Thorpe effect[15] has a
negative influence on the cycli-
zation involving the non-malo-
nate tether moiety.[16] Taking
advantage of the high proclivity
Scheme 3. Proposed mechanistic pathway.
for cyclization of the enyne
Table 2. Alkylboronates from derivatives with non-malonate-tethered
diyne moieties.
moiety containing the malonate tether, we tried to extend
the scope of the process. Thus, reaction of enediyne 4 led to
a bicyclic compound with five- and six-membered rings (5)
in high yield (78%) (Scheme 4).[17]
Substrate
t [h]
Product
Yield [%]
1
2
3
1 f
1g
1h
18
22
5
2 f: Z=NTs
2g: Z=O
2h: Z=CH2
44
14
30[a]
[a] Calculated yield based on NMR.
Scheme 4. Synthesis of bicyclic alkylboronate 5 containing two differently
sized rings.
corresponding alkylboronates 2 f–h in moderate to low
yields (Table 2).
However, enediynes containing a non-malonate tether in
the enyne moiety (1i–l) led to higher yields in all cases (2i–
l) (Table 3).
Crystals of alkylboronate 5 suitable for X-ray diffraction
analysis were obtained by slow evaporation of the solvent
from a solution in hexane. The structure clearly showed the
double bond connecting the five- and six-membered rings
(Figure 2).
Table 3. Alkylboronates from derivatives with non-malonate-tethered
enyne moieties.
Substitution on the external alkyne provided a third class
of suitable substrates to be tested under the polycyclization
conditions. Several enediynes of this type were prepared
and in all cases afforded mixtures of inseparable products.
A possible explanation of this fact is potential competition
Substrate
t [h]
Product
Yield [%]
1
2
3
4
1i
1j
1k
1l
15
2i: Z=NTs
2j: Z=O
2k: Z=CH2
51
14.5
3.5
24
41
64[a]
54
2l: Z=CACTHNUGRTNEUNG(SO2Ph)2
[a] Calculated yield based on NMR.
These results suggest that the limiting step during the re-
action course is actually the first cyclization, that is, the cyc-
lization involving the diyne fragment. Therefore, when the
cyclization of the diyne moiety was facilitated, the second
one was quickly completed. Conversely, when the first cycli-
zation failed or was disfavored, the second one did not take
Figure 2. X-ray diffraction structure of alkylboronate 5.
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Alkylboronate Synthesis by Tandem Borylative Polycyclization
FULL PAPER
3
À
between the two alkynes for insertion into the Pd–hydride
species. Whereas in the case of one terminal alkyne and one
linker alkyne the insertion takes place regioselectively at the
terminal triple bond, when both moieties are internal al-
kynes, thus having similar reactivity, they compete to afford
different products.[18] However, one of the internal ene-
diynes (6) afforded a mixture of two compounds that could
be partially separated (Scheme 5).
testing a variety of conditions. It is well known that C
G
B bond formation in this type of coupling is still challengin-
g.[3a] An efficient approach for achieving this objective is the
conversion of alkylboronates into the corresponding trifluor-
oborate salts. These salts have been shown to be valuable
partners in Suzuki coupling reactions with a large number of
electrophiles, regardless of the hybridization of the carbon
involved in the reaction.[4a,b] Thus, alkylboronate 2a in ace-
tonitrile solution was transformed into the trifluoroborate
salt by reaction with a saturated aqueous solution of KHF2
at room temperature.[21] Trifluoroborate salt 10 was obtained
as a white solid in good yield (80%) after successive washes
with diethyl ether (Scheme 7).
Scheme 5. Synthesis of two isomers from an internal enediyne.
Thus, phenyl derivative 6 reacted under the cyclization
conditions to afford two different alkylboronates in almost
equimolar amounts (7/8 60:40) in 65% overall yield (as cal-
culated by NMR), and work-up of the mixture afforded
each compound in 12% yield. One of them was identified
as the expected alkylboronate 7 and the other was identified
as allylboronate 8.[19]
With the aim of taking advantage of the synthetic possibil-
ities offered by these new bicyclic alkylboronates and en-
hancing the importance of the borylative bicyclization, some
functionalization methods, such as oxidation to alcohols and
Scheme 7. Formation of bicyclic alkyltrifluoroborate salts.
According to previously reported conditions for Suzuki
couplings,[22,23] trifluoroborate salt 10 was coupled with aryl
chlorides bearing either electron-withdrawing or electron-
donating substituents, such as p-chlorobenzonitrile and p-
chloroanisole, respectively. The coupled products (11 and
12) were obtained in moderate to good yields (Scheme 8).
À
C C bond-forming reactions by
Suzuki coupling, were investi-
gated.
To this end, alkylboronate 2a
was transformed under alkaline
aqueous conditions, in the pres-
ence of a large excess of hydro-
gen peroxide (33% w/v).[20]
Thereby, the corresponding pri-
mary alcohol 9 was obtained in
high yield (95%) after an easy
purification by column chroma-
tography
on
silica
gel
(Scheme 6).
We were unable to couple
the homoallylic boronates with
aryl electrophiles in the pres-
ence of Pd catalysts, in spite of
Scheme 8. Suzuki couplings of trifluoroborate salt 10.
In particular, by using the electrophile p-chlorobenzo-
nitrile, the coupled product 11 was obtained in 67% yield
after 6 h under the optimized conditions. However, under
similar conditions, the reaction with the electron-donor-
substituted p-chloroanisole afforded the corresponding
coupled product 12 in lower yield (<50%) accompanied
by a small amount of an inseparable and unidentified im-
purity.
Scheme 6. Formation of alcohols from bicyclic alkylboronates.
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2737

D. J. Cꢂrdenas et al.
3,3,3’,3’-tetracarboxylate (2b): Following the general procedure for bory-
lative polycyclization, 2b was obtained after 22 h in 66% yield as a color-
less oil (hexane/EtOAc 5:1 to 3:1). 1H NMR (300 MHz, CDCl3): d=5.13
(s, 1H), 5.10 (s, 1H), 4.22 (dd, J=11.1, 5.5 Hz, 1H), 4.05 (dd, J=10.8,
9.8 Hz, 1H), 3.73 (s, 3H), 3.71 (s, 6H), 3.70 (s, 3H), 3.30 (m, 1H), 3.22–
2.77 (m, 6H), 2.70 (ddd, J=13.4, 8.4, 1.3 Hz, 1H), 2.27 (q, J=4.8 Hz,
1H), 2.15 (dd, J=13.2, 8.0 Hz, 1H), 2.02 (s, 3H), 1.19 ppm (s, 12H);
13C NMR (75 MHz, CDCl3, DEPT-135): d=172.3 (C), 172.1 (C), 172.0
(C), 171.9 (C), 171.3 (C), 143.9 (C), 140.5 (C), 128.7 (C), 110.3 (CH2),
83.6 (C), 65.1 (CH2), 58.8 (C), 57.3 (C), 53.0 (CH3), 52.9 (CH3), 52.8
(CH3), 43.8 (CH2), 41.8 (CH2), 41.4 (CH2), 38.8 (CH2), 38.5 (CH), 25.4
(CH-B, HMQC), 25.0 (CH3), 24.9 (CH3), 21.1 ppm (CH3); HRMS
(ESI+): m/z: calcd for C29H41BO12Na: 615.2583 [M+Na]+; found:
615.2577.
Conclusion
We have developed a cascade borylative bicyclization pro-
cess for a broadly applicable stereoselective synthesis of bi-
cyclic homoallylic alkylboronates under mild conditions.
À
À
One C B bond and two new C C bonds are formed, and
even two new asymmetric centers can be stereospecifically
obtained. The reaction tolerates the presence of b-hydro-
gens, avoids the use of highly nucleophilic and basic re-
agents, and is compatible with a wide variety of functional
groups. Moreover, some functionalizations of these deriva-
tives have been carried out, such as the transformation into
alcohols, the synthesis of alkyltrifluoroborate salts, and the
AHCTUNGTERG(NNUN rac)-Tetramethyl (1Z,5R)-5-[(1S)-2-(acetyloxy)-1-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)ethyl]-5’-methylene-1,1’-bi(cyclopentylidene)-
3,3,3’,3’-tetracarboxylate (2b’): Following the general procedure for bory-
lative polycyclization, 2b’ was obtained after 6 h in 30% yield as a color-
less oil (hexane/EtOAc 4:1 to 2:1) as a diastereomer of 2b. This com-
À
formation of C C coupling products by Suzuki reaction.
1
pound was difficult to purify since it partially decomposed to 3. H NMR
(300 MHz, CDCl3): d=5.15 (s, 1H), 5.09 (s, 1H), 4.21 (dd, J=11.1,
6.4 Hz, 1H), 4.03 (dd, J=11.1, 7.2 Hz, 1H), 3.74 (s, 3H), 3.71 (s, 9H),
3.41 (m, 1H), 3.13–2.93 (m, 4H), 2.86 (d, J=15.1 Hz, 2H), 2.65 (dd, J=
13.6, 9.1 Hz, 1H), 2.22 (m, 2H), 1.98 (s, 3H), 1.21 (s, 6H), 1.20 ppm (s,
6H); HRMS (ESI+): m/z: calcd for C29H41BO12Na: 615.2583 [M+Na]+;
found: 615.2571.
Experimental Section
General methods: Commercially available reagents were used without
additional purification. For the borylative cyclization reactions, toluene
(SDS, anhydrous, analytical grade) was dried by standing over activated
4 ꢄ molecular sieves for several days prior to use. Anhydrous MeOH
(SDS, anhydrous, analytical grade) was also stored over 4 ꢄ molecular
sieves. Bis(pinacolato)diboron (Aldrich) was used as received and stored
under Ar at 48C. Silica gel 60 (0.40–0.063 mm), purchased from SDS, was
used for column chromatography. Reagents were weighed in air, but re-
actions were performed under Ar. Subsequent work-up was performed in
air. NMR spectra were recorded at 238C on a Bruker AC-300 spectrome-
ter (300 MHz for 1H; 75 MHz for 13C) from samples in deuterated chloro-
form, taking the solvent signals at 7.26 ppm in 1H NMR and 77.2 ppm in
13C NMR as internal standards. Coupling constants (J) are reported in
Hz and chemical shifts (d) in ppm. In the case of molecules containing
boron, the chemical shift of the a-carbon to the boron was determined
by HMQC experiments since no signal from this carbon is seen in the
13C NMR spectrum due to the quadrupole moment of the boron nucleus.
Mass spectra (FAB, EI, and electrospray) were recorded on a GCT Wal-
ters spectrometer coupled to an Agilent 6890N gas chromatograph. Melt-
ing points were determined using a Gallenkamp apparatus.
AHCTUNGTERG(NNUN rac)-Tetramethyl (1Z,5R)-5-[(1R)-2-(benzoyloxy)-1-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)ethyl]-5’-methylene-1,1’-bi(cyclopentylidene)-
3,3,3’,3’-tetracarboxylate (2c): Following the general procedure for bory-
lative polycyclization, 2c was obtained after 23 h in 70% yield as a sticky
colorless oil (hexane/EtOAc 3:1). 1H NMR (300 MHz, CDCl3): d=8.02
(d, J=7.6 Hz, 2H), 7.54 (t, J=7.5 Hz, 1H), 7.42 (t, J=7.5 Hz, 2H), 5.16
(s, 1H), 5.12 (s, 1H), 4.47 (dd, J=11.1, 5.1 Hz, 1H), 4.33 (dd, J=10.6,
9.6 Hz, 1H), 3.74 (s, 3H), 3.72 (s, 3H), 3.71 (s, 3H), 3.69 (s, 3H), 3.44 (m,
1H), 3.25–2.72 (m, 7H), 2.44 (q, J=4.8 Hz, 1H), 2.25 (dd, J=13.3,
7.9 Hz, 1H), 1.19 ppm (s, 12H); 13C NMR (75 MHz, CDCl3, DEPT-135):
d=172.3 (C), 172.1 (C), 172.0 (C), 171.9 (C), 166.8 (C), 143.9 (C), 140.5
(C), 132.9 (CH), 130.6 (C), 129.7 (CH), 128.8 (C), 128.4 (CH), 110.5
(CH2), 83.6 (C), 65.7 (CH2), 58.8 (C), 57.3 (C), 53.0 (CH3), 52.9 (CH3),
52.8 (CH3), 43.8 (CH2), 41.8 (CH2), 41.4 (CH2), 38.9 (CH2), 38.7 (CH),
25.5 (CH-B, HMQC), 25.1 (CH3), 25.0 ppm (CH3); HRMS (ESI+): m/z:
calcd for C34H43BO12Na: 677.2739 [M+Na]+; found: 677.2731.
AHCTUNGTERG(NNUN rac)-Tetramethyl (1Z,5R)-5-[(1S)-2-(benzoyloxy)-1-(4,4,5,5-tetramethyl-
General procedure for the synthesis of alkylboronates: The requisite ene-
diyne (ca. 50 mg), bis(pinacolato)diboron (1.2 equiv), and [Pd
(OAc)2]
1,3,2-dioxaborolan-2-yl)ethyl]-5’-methylene-1,1’-bi(cyclopentylidene)-
3,3,3’,3’-tetracarboxylate (2c’): Following the general procedure for bory-
lative polycyclization, 2c’ was obtained after 21 h in 25% yield as a
sticky colorless oil (hexane/EtOAc 4:1 to 2:1) as a diastereomer of 2c.
(5 mol%) were sequentially added to a 5 mL flask. After purging with
Ar, dry toluene (1 mL) and MeOH (1 equiv) were added. The mixture
was heated at 508C for the indicated time. After cooling to room temper-
ature, Celiteꢅ was added and the solvent was evaporated. Column chro-
matography (hexane/EtOAc) afforded the product. To obtain the highest
possible yield, a silica gel column of diameter 2 cm and height 8–12 cm
was used. Partial decomposition of the boronate was detected when
using longer columns or retention times, probably due to hydrolysis.
1
This compound was difficult to purify since it decomposed to 3. H NMR
(300 MHz, CDCl3): d=7.97 (d, J=8.2 Hz, 2H), 7.52 (t, J=7.4 Hz, 1H),
7.41 (t, J=7.3 Hz, 2H), 5.16 (s, 1H), 5.13 (s, 1H), 4.47 (dd, J=11.4,
5.8 Hz, 1H), 4.34 (dd, J=11.4, 7.5 Hz, 1H), 3.71 (s, 3H), 3.70 (s, 3H),
3.69 (s, 3H), 3.65 (s, 3H), 3.49 (m, 1H), 3.10–2.95 (m, 4H), 2.86 (d, J=
16.4 Hz, 1H), 2.72 (ddd, J=13.7, 8.8, 1.3 Hz, 1H), 2.68 (d, J=17.6 Hz,
1H), 2.45 (m, 1H), 2.30 (dd, J=13.7, 7.9 Hz, 1H), 1.20 ppm (s, 12H);
13C NMR (75 MHz, CDCl3, DEPT-135): d=172.1 (C), 171.8 (C), 166.6
(C), 143.6 (C), 140.3 (C), 132.9 (CH), 130.7 (C), 129.7 (CH), 128.7 (C),
128.5 (CH), 110.8 (CH2), 83.8 (C), 63.9 (CH2), 58.6 (C), 53.0 (CH3), 52.9
(CH3), 52.8 (CH3), 43.7 (CH2), 42.3 (CH2), 41.2 (CH2), 38.9 (CH), 37.1
(CH2), 25.0 (CH3), 24.9 (CH3), 23.7 ppm (CH-B, HMQC); HRMS
Tetramethyl (1Z)-5-methylene-5’-[(4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lan-2-yl)methyl]-1,1’-bi(cyclopentylidene)-3,3,3’,3’-tetracarboxylate (2a):
Following the general procedure for borylative polycyclization, 2a was
obtained after 2 h in 60% yield (71% yield when the reaction was
scaled-up to 400 mg of enediyne) as a colorless oil (hexane/EtOAc 6:1 to
4:1). 1H NMR (300 MHz, CDCl3): d=5.08 (s, 1H), 5.02 (s, 1H), 3.73 (s,
3H), 3.71 (s, 6H), 3.70 (s, 3H), 3.27–2.78 (m, 7H), 2.67 (dd, J=13.5,
8.4 Hz, 1H), 2.12 (dd, J=13.5, 4.5 Hz, 1H), 1.22 (brs, 13H), 0.71 ppm
(dd, J=16.3, 11.5 Hz, 1H); 13C NMR (75 MHz, CDCl3, DEPT-135): d=
172.7 (C), 172.5 (C), 172.0 (C), 171.9 (C), 143.8 (C), 143.2 (C), 127.3 (C),
109.7 (CH2), 83.2 (C), 58.6 (C), 57.5 (C), 53.0 (CH3), 52.9 (CH3), 43.6
(CH2), 41.8 (CH2), 40.9 (CH2), 40.8 (CH2), 36.7 (CH), 25.0 (CH3), 24.9
(CH3), 15.4 ppm (CH2-B, HMQC); HRMS (ESI+): m/z: calcd for
C26H37BO10Na: 543.2371 [M+Na]+; found: 543.2355.
AHCTUNGTRENNUNG
(ESI+): m/z: calcd for C34H43BO12Na: 677.2739 [M+Na]+; found:
677.2739.
Tetramethyl (1Z)-5-methyl-5’-methylene-5-[(4,4,5,5-tetramethyl-1,3,2-di-
oxaborolan-2-yl)methyl]-1,1’-bi(cyclopentylidene)-3,3,3’,3’-tetracarboxy-
late (2d): Following the general procedure for borylative polycyclization,
2d was obtained after 4 h in 81% yield as a white solid (hexane/EtOAc
3:1 to 2.5:1). M.p. 105–1088C; 1H NMR (300 MHz, CDCl3): d=5.15 (s,
1H), 5.12 (s, 1H), 3.74 (s, 3H), 3.72 (s, 6H), 3.71 (s, 3H), 3.16–2.77 (m,
6H), 2.67 (d, J=13.5 Hz, 1H), 2.40 (dd, J=13.5, 1.3 Hz, 1H), 1.33 (m,
ACHTUNGTRENNUNG
2738
www.chemeurj.org
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 2734 – 2741

Alkylboronate Synthesis by Tandem Borylative Polycyclization
FULL PAPER
2H), 1.23 (s, 3H), 1.20 (s, 6H), 1.19 ppm (s, 6H); 13C NMR (75 MHz,
CDCl3, DEPT-135): d=173.0 (C), 172.8 (C), 172.2 (C), 172.1 (C), 145.4
(C), 143.7 (C), 128.4 (C), 112.6 (CH2), 83.0 (C), 57.8 (C), 56.5 (C), 53.0
(CH3), 52.9 (CH3), 50.6 (CH2), 44.1 (CH2), 44.0 (C), 42.7 (CH2), 41.4
(CH2), 28.3 (CH3), 25.1 (CH3), 24.9 (CH3), 22.2 ppm (CH2-B, HMQC);
HRMS (ESI+): m/z: calcd for C27H39BO10Na: 557.2528 [M+Na]+;
found: 557.2527.
lative polycyclization, 2i was obtained after 15 h in 51% yield as a white
solid (hexane/EtOAc 4:1). M.p. 117–1208C; H NMR (300 MHz, CDCl3):
1
d=7.72 (d, J=8.1 Hz, 2H), 7.33 (d, J=8.1 Hz, 2H), 5.08 (s, 1H), 5.00 (s,
1H), 3.99 (d, J=15.2 Hz, 1H), 3.72 (s, 3H), 3.68 (s, 3H), 3.50 (d, J=
15.2 Hz, 1H), 3.37 (d, J=8.7 Hz, 1H), 3.15 (m, 1H), 3.07 (dd, J=9.0,
6.0 Hz, 1H), 2.98 (m, 2H), 2.79 (s, 2H), 2.43 (s, 3H), 1.22 (s, 12H), 1.02
(d, J=2.2 Hz, 1H), 0.99 ppm (s, 1H); 13C NMR (75 MHz, CDCl3, DEPT-
135): d=171.8 (C), 171.6 (C), 143.8 (C), 143.7 (C), 138.7 (C), 132.7 (C),
129.8 (CH), 128.2 (CH), 127.2 (C), 110.0 (CH2), 83.5 (C), 57.6 (C), 55.5
(CH2), 53.1 (CH3), 53.0 (CH3), 52.1 (CH2), 43.2 (CH2), 40.2 (CH2), 37.0
(CH), 25.0 (CH3), 21.7 (CH3), 14.7 ppm (CH2-B, HMQC); HRMS
(FAB+): m/z: calcd for C28H39BNO8S: 560.2489 [M+H]+; found:
560.2472.
ACHTUNGTRENNUNG(rac)-Tetramethyl (1Z,5R)-5-methyl-5’-methylene-5-[(R)-phenyl(4,4,5,5-
tetramethyl-1,3,2-dioxaborolan-2-yl)methyl]-1,1’-bi(cyclopentylidene)-
3,3,3’,3’-tetracarboxylate) (2e): Following the general procedure for bory-
lative polycyclization, 2e was obtained after 3.5 h in 80% yield as a col-
orless oil (hexane/EtOAc 2.5:1 to 2:1). 1H NMR (300 MHz, CDCl3): d=
7.25–7.10 (m, 5H), 5.50 (s, 1H), 5.29 (s, 1H), 3.75 (s, 3H), 3.72 (s, 3H),
3.71 (s, 3H), 3.61 (s, 3H), 3.31 (s, 1H), 3.10–2.72 (m, 7H), 2.50 (dd, J=
14.3, 2.2 Hz, 1H), 1.40 (s, 3H), 1.27 (s, 3H), 1.22 ppm (s, 3H); 13C NMR
(75 MHz, CDCl3, DEPT-135): d=172.9 (C), 172.1 (C), 172.0 (C), 145.2
(C), 143.9 (C), 139.6 (C), 131.4 (CH), 128.9 (C), 127.8 (CH), 126.0 (CH),
113.5 (CH2), 83.6 (C), 57.7 (C), 56.5 (C), 52.9 (CH3), 52.8 (CH3), 52.7
(CH3), 48.5 (C), 45.7 (CH2), 44.9 (CH2), 43.9 (CH2), 42.6 (CH2), 38.3
(CH-B, HMQC), 26.4 (CH3), 25.0 (CH3), 24.9 ppm (CH3); HRMS
Dimethyl (4E)-3-methylene-4-{4-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)methyl]dihydrofuran-3ACTHNUGTRNEUNG(2H)-ylidene}cyclopentane-1,1-dicarboxylate
(2j): Following the general procedure for borylative polycyclization, 2j
was obtained after 14.5 h in 41% yield as a colorless oil (hexane/EtOAc
5:1 to 4:1). 1H NMR (300 MHz, CDCl3): d=5.13 (s, 1H), 5.10 (s, 1H),
4.41 (d, J=14.7 Hz, 1H), 4.19 (d, J=14.7 Hz, 1H), 3.82 (d, J=3.0 Hz,
2H), 3.72 (s, 6H), 3.17 (m, 1H), 3.04 (brs, 2H), 2.83 (m, 2H), 1.23 (s,
12H), 1.10–0.99 ppm (m, 2H); 13C NMR (75 MHz, CDCl3, DEPT-135):
d=171.9 (C), 171.8 (C), 144.1 (C), 142.2 (C), 124.7 (C), 108.9 (CH2), 83.4
(C), 75.9 (CH2), 71.4 (CH2), 57.9 (C), 53.0 (CH3), 43.0 (CH2), 40.0 (CH2),
38.0 (CH), 25.0 (CH3), 24.9 (CH3), 13.7 ppm (CH2-B, HMQC); HRMS
(ESI+): m/z: calcd for C21H32BO7: 407.2235 [M+H]+; found: 407.2224.
ACHTUNGTRENNUNG
(ESI+): m/z: calcd for C33H43BO10Na: 633.2841 [M+Na]+; found:
633.2835.
Dimethyl (3E)-3-{4-methylene-1-[(4-methylphenyl)sulfonyl]pyrrolidin-3-
ylidene}-4-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl]cyclopen-
tane-1,1-dicarboxylate (2 f): Following the general procedure for boryla-
tive polycyclization, 2 f was obtained after 18 h in 44% yield as a color-
Dimethyl (1Z)-5-methylene-2’-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)methyl]-1,1’-bi(cyclopentylidene)-3,3-dicarboxylate (2k): Following the
general procedure for borylative polycyclization, 2k was obtained after
3.5 h in 64% yield (calculated by NMR) as a colorless oil (hexane/
EtOAc 10:1). 1H NMR (300 MHz, CDCl3): d=5.12 (s, 1H), 5.03 (s, 1H),
3.71 (s, 6H), 3.09 (m, 1H), 3.03 (t, J=1.8 Hz, 2H), 2.91 (m, 2H), 2.42–
2.12 (m, 2H), 1.82–1.51 (m, 4H), 1.24 (s, 6H), 1.23 (s, 6H), 1.06 (dd, J=
15.9, 2.0 Hz, 1H), 0.74 ppm (dd, J=15.9, 11.9 Hz, 1H); 13C NMR
(75 MHz, CDCl3, DEPT-135): d=172.3 (C), 172.2 (C), 148.5 (C), 144.4
(C), 125.5 (C), 108.0 (CH2), 83.2 (C), 57.6 (C), 52.9 (CH3), 43.8 (CH2),
41.0 (CH2), 37.7 (CH), 34.7 (CH2), 33.2 (CH2), 25.0 (CH3), 24.9 (CH3),
22.7 (CH2), 14.5 ppm (CH2-B, HMQC); HRMS (ESI+): m/z: calcd for
C22H33BO6Na: 427.2262 [M+Na]+; found: 427.2262.
1
less oil (hexane/EtOAc 4:1). H NMR (300 MHz, CDCl3): d=7.70 (d, J=
8.1 Hz, 2H), 7.32 (d, J=8.1 Hz, 2H), 5.06 (s, 1H), 5.04 (s, 1H), 3.94 (m,
2H), 3.88 (m, 1H), 3.82 (m, 1H), 3.74 (s, 3H), 3.69 (s, 3H), 3.13 (m, 1H),
3.07 (d, J=17.5 Hz, 1H), 2.75–2.58 (m, 2H), 2.42 (s, 3H), 2.13 (dd, J=
13.4, 4.7 Hz, 1H), 1.20 (s, 6H), 1.19 (s, 6H), 1.10 (dd, J=16.5, 2.8 Hz,
1H), 0.66 ppm (dd, J=16.5, 11.4 Hz, 1H); 13C NMR (75 MHz, CDCl3,
DEPT-135): d=172.3 (C), 172.2 (C), 143.9 (C), 143.8 (C), 140.2 (C),
133.0 (C), 129.9 (CH), 128.1 (CH), 124.5 (C), 109.3 (CH2), 83.4 (C), 58.6
(C), 55.0 (CH2), 53.3 (CH2), 53.0 (CH3), 41.6 (CH2), 40.6 (CH2), 36.8
(CH), 25.0 (CH3), 24.8 (CH3), 21.7 (CH3), 14.6 ppm (CH2-B, HMQC);
HRMS (ESI+): m/z: calcd for C28H39BNO8S: 560.2483 [M+H]+; found:
560.2486.
Dimethyl
(3E)-3-(4-methylenedihydrofuran-3(2H)-ylidene)-4-[(4,4,5,5-
Dimethyl
(1Z)-5-methylene-4’,4’-bis(phenylsulfonyl)-2’-[(4,4,5,5-tetra-
tetramethyl-1,3,2-dioxaborolan-2-yl)methyl]cyclopentane-1,1-dicarboxy-
late (2g): Following the general procedure for borylative polycyclization,
2g was obtained after 22 h in 14% yield as a colorless oil (hexane/
EtOAc, 3.5:1). 1H NMR (300 MHz, CDCl3): d=5.09 (s, 1H), 5.06 (s,
1H), 4.45 (m, 2H), 4.43–4.35 (m, 2H), 3.74 (s, 3H), 3.70 (s, 3H), 3.24 (m,
1H), 3.08 (m, 1H), 2.77–2.66 (m, 2H), 2.15 (dd, J=13.6, 4.8 Hz, 1H),
1.29 (m, 1H), 1.24 (s, 12H), 0.77 ppm (dd, J=16.3, 11.4 Hz, 1H);
13C NMR (75 MHz, CDCl3, DEPT-135): d=172.5 (C), 172.3 (C), 143.3
(C), 141.1 (C), 127.3 (C), 106.2 (CH2), 83.4 (C), 74.8 (CH2), 73.3 (CH2),
59.0 (C), 53.1 (CH3), 53.0 (CH3), 41.6 (CH2), 40.2 (CH2), 36.6 (CH), 25.0
(CH3), 24.9 (CH3), 15.2 ppm (CH2-B, HMQC); HRMS (ESI+): m/z:
calcd for C21H31BO7Na: 429.2055 [M+Na]+; found: 429.2044.
methyl-1,3,2-dioxaborolan-2-yl)methyl]-1,1’-bi(cyclopentylidene)-3,3-di-
carboxylate (2l): Following the general procedure for borylative polycyc-
lization, 2l was obtained after 24 h in 54% yield as a colorless oil
(hexane/EtOAc 3:1 to 2.5:1). 1H NMR (300 MHz, CDCl3): d=8.12 (m,
2H), 7.97 (m, 2H), 7.76–7.50 (m, 6H), 5.09 (s, 1H), 4.79 (s, 1H), 3.77 (s,
3H), 3.72 (s, 3H), 3.62 (m, 1H), 3.07–2.85 (m, 6H), 2.73 (m, 1H), 2.54
(dd, J=15.1, 6.0 Hz, 1H), 1.28 (m, 1H), 1.23 (s, 6H), 1.22 (s, 6H),
0.91 ppm (dd, J=16.0, 10.7 Hz, 1H); 13C NMR (75 MHz, CDCl3, DEPT-
135): d=171.8 (C), 143.3 (C), 140.8 (C), 137.7 (C), 136.3 (C), 134.7 (CH),
134.6 (CH), 131.4 (CH), 131.1 (CH), 129.0 (CH), 128.8 (CH), 128.0 (C),
111.1 (CH2), 92.5 (C), 83.4 (C), 57.4 (C), 53.1 (CH3), 53.0 (CH3), 43.7
(CH2), 41.1 (CH2), 39.4 (CH2), 38.4 (CH2), 37.2 (CH), 25.1 (CH3), 25.0
(CH3), 15.6 ppm (CH2-B, HMQC); HRMS (ESI+): m/z: calcd for
C34H41BO10S2Na: 707.2126 [M+Na]+; found: 707.2138.
Dimethyl (1Z)-2’-methylene-5-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)methyl]-1,1’-bi(cyclopentylidene)-3,3-dicarboxylate (2h): Following the
general procedure for borylative polycyclization, 2h was obtained after
5 h in 30% yield (calculated by NMR) as a colorless oil (hexane/EtOAc
10:1). 1H NMR (300 MHz, CDCl3): d=5.05 (s, 1H), 4.97 (s, 1H), 3.75 (s,
3H), 3.70 (s, 3H), 3.24 (m, 1H), 3.12 (d, J=16.8 Hz, 1H), 2.83 (d, J=
16.8 Hz, 1H), 2.67 (dd, J=13.4, 8.2 Hz, 1H), 2.39 (m, 2H), 2.32 (m, 2H),
2.17 (dd, J=13.2, 4.2 Hz, 1H), 1.64 (q, J=7.2 Hz, 2H), 1.29 (m, 1H),
1.23 (s, 12H), 0.74 ppm (dd, J=16.2, 11.6 Hz, 1H); 13C NMR (75 MHz,
CDCl3, DEPT-135): d=173.0 (C), 172.8 (C), 148.4 (C), 141.2 (C), 131.1
(C), 107.8 (CH2), 83.2 (C), 58.6 (C), 52.9 (CH3), 42.0 (CH2), 40.0 (CH2),
37.1 (CH2), 36.7 (CH), 33.9 (CH2), 25.1 (CH3), 24.8 (CH3), 23.0 (CH2),
15.5 ppm (CH2-B, HMQC); HRMS (ESI+): m/z: calcd for C22H34BO6:
405.2442 [M+H]+; found: 405.2438.
Tetramethyl (1Z)-5-methylene-5’-vinyl-1,1’-bi(cyclopentylidene)-3,3,3’,3’-
tetracarboxylate (3): Following the general procedure for borylative poly-
cyclization, 3 was obtained by decomposition of 2b’ and 2c’ in variable
quantities as a sticky white solid. 1H NMR (300 MHz, CDCl3): d=5.63
(ddd, J=17.2, 10.3, 5.0 Hz, 1H), 5.03 (s, 2H), 4.98 (dt, J=10.3, 1.5 Hz,
1H), 4.89 (dt, J=17.2, 1.5 Hz, 1H), 3.73 (s, 6H), 3.72 (s, 3H), 3.69 (s,
3H), 3.59 (m, 1H), 3.21 (d, J=17.3 Hz, 1H), 3.01 (m, 4H), 2.84 (d, J=
17.3 Hz, 1H), 2.62 (dd, J=13.1, 8.5 Hz, 1H), 2.39 ppm (dd, J=13.1,
2.9 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=172.4, 172.0, 171.9, 143.7,
137.4, 137.0, 130.7, 115.4, 110.5, 58.5, 57.6, 53.1, 53.0, 52.9, 45.3, 43.2, 41.0,
40.9, 40.7 ppm.
Dimethyl
(3Z)-3-[4,4-bis(methoxycarbonyl)-2-methylenecyclopentyl-
Dimethyl (4E)-3-methylene-4-{1-[(4-methylphenyl)sulfonyl]-4-[(4,4,5,5-
tetramethyl-1,3,2-dioxaborolan-2-yl)methyl]pyrrolidin-3-ylidene}cyclo-
pentane-1,1-dicarboxylate (2i): Following the general procedure for bory-
idene]-4-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl]cyclohex-
ane-1,1-dicarboxylate (5): Following the general procedure for borylative
polycyclization, 5 was obtained after 4 h in 78% yield as a white crystal-
Chem. Eur. J. 2011, 17, 2734 – 2741
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2739

D. J. Cꢂrdenas et al.
line solid (hexane/EtOAc 3:1). M.p. 109–1128C; 1H NMR (300 MHz,
CDCl3): d=5.18 (s, 1H), 5.07 (s, 1H), 3.73 (s, 3H), 3.71 (s, 3H), 3.70 (s,
6H), 3.40 (m, 1H), 3.24–2.85 (m, 5H), 2.55 (d, J=14.6 Hz, 1H), 2.21–
1.99 (m, 2H), 1.72–1.49 (m, 2H), 1.25 (m, 1H), 1.21 (s, 6H), 1.20 (s, 6H),
0.88 ppm (dd, J=15.5, 4.6 Hz, 1H); 13C NMR (75 MHz, CDCl3, DEPT-
135): d=172.6 (C), 172.2 (C), 171.2 (C), 144.5 (C), 137.0 (C), 129.7 (C),
110.6 (CH2), 83.2 (C), 56.7 (C), 56.6 (C), 52.9 (CH3), 52.8 (CH3), 52.5
(CH3), 43.8 (CH2), 38.8 (CH2), 32.2 (CH2), 32.0 (CH), 28.5 (CH2), 25.9
(CH2), 25.1 (CH3), 24.9 (CH3), 14.4 ppm (CH2-B, HMQC); HRMS
(ESI+): m/z: calcd for C27H40BO10: 537.2709 [M+H]+; found: 537.2720.
of alkylboronate 2a (ca. 250 mg) in acetonitrile at RT. After 3 h at RT,
the solvent was evaporated, and the remaining white residue was repeat-
edly extracted with hot acetone, and the combined extracts were filtered
to remove inorganic impurities. The solvent was completely removed
under vacuum and the white solid obtained was washed with warm Et2O
and dried under vacuum without further purification. Primary alkyltri-
fluoroborate salt 10 was obtained in 80% yield as a white solid. M.p.
115–1208C; 1H NMR (300 MHz, [D6]acetone): d=5.32 (s, 1H), 4.97 (s,
1H), 3.68 (s, 6H), 3.67 (s, 3H), 3.64 (s, 3H), 3.13–3.68 (m, 7H), 2.58 (dd,
J=13.7, 8.2 Hz, 1H), 2.31 (dd, J=13.6, 4.0 Hz, 1H), 0.60 (m, 1H),
0.02 ppm (m, 1H); 13C NMR (75 MHz, [D6]acetone, DEPT-135): d=
173.7 (C), 173.3 (C), 172.4 (C), 172.3 (C), 148.4 (C), 144.5 (C), 125.3 (C),
109.9 (CH2), 59.4 (C), 58.3 (C), 53.0 (CH3), 52.8 (CH3), 44.2 (CH2), 42.3
(CH2), 41.5 (CH2), 41.3 (CH2), 39.2 (CH), 25.0 ppm (CH2-B, HMQC);
HRMS (ESI+): m/z: calcd for C20H25BO8F3: 461.1600; found: 461.1618.
Tetramethyl (1Z,5E)-5-benzylidene-5’-[(4,4,5,5-tetramethyl-1,3,2-dioxa-
borolan-2-yl)methyl]-1,1’-bi(cyclopentylidene)-3,3,3’,3’-tetracarboxylate
(7): Following the general procedure for borylative polycyclization, 7 was
obtained after 18 h in a mixture with 8 (65% yield calculated by NMR;
7:8 (60:40)) and in 12% isolated yield as a sticky colorless oil (hexane/
EtOAc 6:1). 1H NMR (300 MHz, CDCl3): d=7.76–7.28 (m, 4H), 7.23–
7.16 (m, 1H), 6.59 (s, 1H), 3.76 (s, 3H), 3.73 (s, 3H), 3.70 (s, 3H), 3.69 (s,
3H), 3.39 (m, 1H), 3.31 (s, 2H), 3.18 (d, J=17.4 Hz, 1H), 3.03–2.87 (m,
3H), 2.72 (dd, J=13.4, 8.2 Hz, 1H), 2.15 (dd, J=13.4, 5.0 Hz, 1H), 1.35
(dd, J=16.2, 2.6 Hz, 1H), 1.22 (s, 6H), 1.21 (s, 6H), 0.80 ppm (dd, J=
16.2, 11.4 Hz, 1H); 13C NMR (75 MHz, CDCl3, DEPT-135): d=172.7 (C),
172.1 (C), 142.0 (C), 138.4 (C), 137.6 (C), 129.7 (C), 129.1 (CH), 128.3
(CH), 126.7 (CH), 126.0 (CH), 83.3 (C), 58.5 (C), 58.0 (C), 53.0 (CH3),
52.9 (CH3), 42.0 (CH2), 41.5 (CH2), 40.4 (CH2), 40.2 (CH2), 37.0 (CH),
25.1 (CH3), 24.9 (CH3), 15.8 ppm (CH2-B, HMQC); HRMS (ESI+): m/z:
calcd for C32H41BO10Na: 619.2684 [M+Na]+; found: 619.2694.
General procedure for Suzuki coupling: A reaction flask was charged
with trifluoroborate salt (ca. 50 mg), [PdACTHNUTRGENUN(G OAc)2] (5 mol%), [RuPhos]
(10 mol%), K2CO3 (3 equiv), and the requisite aryl chloride (1.2 equiv)
under Ar. Toluene and H2O (10:1) were then added and the mixture was
heated at 808C. After the indicated time, water and Et2O were added to
the resulting mixture. The aqueous layer was separated and extracted
with Et2O (3ꢆ5 mL). The combined organic fractions were dried over
anhydrous MgSO4 and filtered through anhydrous Na2SO4. The solvent
was removed under vacuum and the residue was purified by column
chromatography (hexane/EtOAc).
Tetramethyl
(1Z)-5-(4-cyanobenzyl)-5’-methylene-1,1’-bi(cyclopentyl-
idene)-3,3,3’,3’-tetracarboxylate (11): Following the general procedure for
Suzuki coupling and starting from trifluoroborate salt 10 and p-chloro-
benzonitrile, coupling product 11 was obtained after 6 h in 67% yield as
Dimethyl 3-[(E)-4,4-di(methoxycarbonyl)-2-benzylidenecyclopentyl]-4-
[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl]cyclopent-3-ene-1,1-
dicarboxylate (8): Following the general procedure for borylative poly-
cyclization, 8 was obtained after 18 h in a mixture with 7 (65% yield cal-
culated by NMR; 7/8 60:40) and in 12% isolated yield as a sticky color-
less oil (hexane/EtOAc 6:1). 1H NMR (300 MHz, CDCl3): d=7.33–7.27
(m, 4H), 7.21–7.13 (m, 1H), 6.08 (q, J=2.5 Hz, 1H), 3.74 (s, 6H), 3.72 (s,
3H), 3.70 (m, 1H), 3.65 (s, 3H), 3.43 (d, J=17.8 Hz, 1H), 3.20–3.10 (m,
2H), 3.01 (d, J=16.4 Hz, 1H), 2.92 (d, J=3.8 Hz, 2H), 2.51 (ddd, J=
12.7, 7.2, 1.6 Hz, 1H), 2.04 (t, J=12.7 Hz, 1H), 1.79 (d, J=14.9 Hz, 1H),
1.68 (d, J=14.9 Hz, 1H), 1.22 ppm (s, 12H); 13C NMR (75 MHz, CDCl3,
DEPT-135): d=172.9 (C), 172.7 (C), 172.2 (C), 141.6 (C), 138.2 (C),
133.5 (C), 130.5 (C), 128.5 (CH), 128.4 (CH), 126.3 (CH), 123.4 (CH),
83.6 (C), 59.7 (C), 57.7 (C), 53.1 (CH3), 53.0 (CH3), 52.9 (CH3), 52.8
(CH3), 45.6 (CH2), 43.8 (CH), 39.7 (CH2), 39.0 (CH2), 37.4 (CH2), 25.0
(CH3), 24.9 (CH3), 12.7 ppm (CH2-B, HMQC); HRMS (ESI+): m/z:
calcd for C32H41BO10Na: 619.2684 [M+Na]+; found: 619.2699.
1
a colorless oil (hexane/EtOAc 3:1). H NMR (300 MHz, CDCl3): d=7.58
(d, J=8.2 Hz, 2H), 7.29 (d, J=8.2 Hz, 2H), 5.20 (s, 1H), 5.16 (s, 1H),
3.76 (s, 3H), 3.75 (s, 3H), 3.74 (s, 3H), 3.70 (s, 3H), 3.36 (m, 1H), 3.17–
2.91 (m, 7H), 2.41 (d, J=14.0 Hz, 1H), 2.38 (dd, J=13.9, 5.2 Hz, 1H),
2.16 ppm (dd, J=13.9, 3.9 Hz, 1H); 13C NMR (75 MHz, CDCl3, DEPT-
135): d=172.7 (C), 172.0 (C), 171.9 (C), 171.7 (C), 145.9 (C), 144.5 (C),
140.0 (C), 132.4 (CH), 129.9 (CH), 129.4 (C), 119.1 (C), 110.3 (C), 109.6
(CH2), 58.2 (C), 57.3 (C), 53.1 (CH3), 53.0 (CH3), 43.5 (CH2), 42.2 (CH),
41.1 (CH2), 38.5 (CH2), 37.3 ppm (CH2); HRMS (ESI+): m/z: calcd for
C27H29NO8Na: 518.1785 [M+Na]+; found: 518.1770.
Tetramethyl (1Z)-5-(4-methoxybenzyl)-5’-methylene-1,1’-bi(cyclopentyl-
idene)-3,3,3’,3’-tetracarboxylate (12): Following the general procedure for
Suzuki coupling and starting from trifluoroborate salt 10 and p-chloroani-
sole, coupling product 12 was obtained after 20 h in less than 50% yield
as a colorless oil (hexane/EtOAc 5:1). 1H NMR (300 MHz, CDCl3): d=
7.09 (d, J=8.5 Hz, 2H), 6.83 (d, J=8.5 Hz, 2H), 5.24 (s, 1H), 5.19 (s,
1H), 3.78 (s, 3H), 3.77 (s, 3H), 3.75 (s, 3H), 3.74 (s, 3H), 3.69 (s, 3H),
3.30 (m, 1H), 3.14–2.80 (m, 7H), 2.43 (dd, J=13.9, 8.1 Hz, 1H), 2.23 ppm
(m, 2H); HRMS (ESI+): m/z: calcd for C27H32O9Na: 523.1938 [M+Na]+
; found: 523.1939.
General procedures for transformations to alcohols and trifluoroborate
salts:
Tetramethyl
(1Z)-5-(hydroxymethyl)-5’-methylene-1,1’-bi(cyclopentyl-
idene)-3,3,3’,3’-tetracarboxylate (9): An aqueous solution of NaOH (3m,
3 equiv) was slowly added to a solution of alkylboronate 2a (ca. 50 mg)
in THF (5 mL) at RT. The mixture was then cooled to 08C, whereupon a
solution of H2O2 (33% w/v, 30 equiv) was added dropwise and the result-
ing mixture was stirred at RT for 1.5 h. Water and Et2O were then
added, and the aqueous layer was separated and extracted with Et2O (3ꢆ
5 mL). The combined organic fractions were dried over anhydrous
MgSO4 and filtered through anhydrous Na2SO4. The solvent was re-
moved under vacuum and the residue was purified by column chromatog-
raphy (hexane/EtOAc 1:1.5). Primary alcohol 9 was obtained in 95%
Acknowledgements
We thank Cꢇsar Pastor (SIdI-UAM) for performing the X-ray studies.
We gratefully acknowledge the MEC (projects CTQ2004-02040/BQU
and CTQ2007-60494/BQU) for financial support and for an FPU fellow-
ship to J.M.M.
1
yield as a colorless oil. H NMR (300 MHz, CDCl3): d=5.16 (s, 1H), 5.09
(s, 1H), 3.74 (s, 3H), 3.72 (s, 3H), 3.71 (s, 6H), 3.66 (dd, J=11.1, 3.9 Hz,
1H), 3.46 (dd, J=11.1, 8.1 Hz, 1H), 3.31 (m, 1H), 3.08–2.86 (m, 6H),
2.59–2.45 (m, 2H), 1.79 ppm (brs, 1H); 13C NMR (75 MHz, CDCl3,
DEPT-135): d=172.8 (C), 172.3 (C), 172.0 (C), 171.7 (C), 144.0 (C),
137.1 (C), 130.3 (C), 109.7 (CH2), 62.2 (CH2), 58.3 (C), 57.3 (C), 53.1
(CH3), 53.0 (CH3), 52.9 (CH3), 44.1 (CH), 43.2 (CH2), 41.3 (CH2), 41.0
(CH2), 37.1 ppm (CH2); HRMS (ESI+): m/z: calcd for C20H27O9:
411.1649 [M+H]+; found: 411.1640.
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Chem. Eur. J. 2011, 17, 2734 – 2741

Alkylboronate Synthesis by Tandem Borylative Polycyclization
FULL PAPER
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Received: April 28, 2010
Revised: November 11, 2010
Published online: January 30, 2011
Chem. Eur. J. 2011, 17, 2734 – 2741
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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