Stereospecific Nickel-Catalyzed Borylation of Secondary Benzyl Pivalates

Article abstract of DOI:10.1055/s-0036-1590962

A stereoselective nickel-catalyzed direct borylation of enantioenriched secondary benzyl pivalates is described. This methodology is characterized by an intriguing cooperativity of simple nickel and copper salts to promote the targeted C-B bond formation under mild reaction conditions. Unlike classical S _N 2-type processes, this protocol occurs with a neat retention of configuration, resulting in synthetically versatile benzyl boronic esters with excellent stereochemical fidelity.

Full text of DOI:10.1055/s-0036-1590962

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
© Georg Thieme Verlag Stuttgart · New York
2017, 28, A–E
cluster
A
en
R. Martin-Montero et al.
Cluster
Synlett
Stereospecific Nickel-Catalyzed Borylation of Secondary Benzyl
Pivalates
R. Martin-Monteroa
T. Krolikowskia
C. Zaratea
B2nep2
OPiv
R2
Bnep
R2
Ni/Cu catalyst
R1
R1
Excellent yield & broad scope
Synergistic Ni/Cu catalysis
Mild reaction conditions
R. Manzanoa
R. Martin*a,b
0
0
0
0
0-
0
0
1
7-
2
9
0
3-
9
7
9
retention of configuration
15 examples
up to 87% yield
a Institute of Chemical Research of Catalonia (ICIQ), Av. Paisos
Catalans 16, 43007, Tarragona, Spain
rmartinromo@iciq.es
b Catalan Institution for Research and Advanced Studies (ICREA),
Passseig Lluis Companys, 23, 08010, Barcelona, Spain
Published as part of the Cluster C–O Activation
Received: 01.08.2017
Accepted after revision: 26.10.2017
Published online: 08.11.2017
Although the employment of chiral ligands has become
routine in enantioselective C–C bond-forming reactions,3
an attractive alternative in these endeavours consists of the
implementation of stereospecific coupling reactions.4 In
these rather appealing scenarios, the reaction outcome is
dictated by the stereochemistry of the starting precursor,
thus avoiding the need for sophisticated, oftentimes expen-
sive, ancillary chiral ligands. Illustrative examples are the
elegant protocols described by Jarvo5 or Watson6 that make
use of enantioenriched benzyl C–O electrophiles to promote
a variety of stereospecific C–C bond-forming reactions with
well-defined organometallic reagents, allowing to reliably
transfer the stereochemical information in the starting pre-
cursors with high fidelity. Despite the advances realized,
stereoselective C–O bond-cleavage reactions remain pre-
dominantly confined to C–C bond formations (Scheme 1,
path b).5,6 In sharp contrast, the paucity of stereoselective
C–heteroatom bond-forming reactions of C–O electrophiles
other than particularly activated organic sulfonates is cer-
tainly striking,7 a rather surprising observation if one takes
into consideration the prevalence of C–heteroatom bonds in
pharmaceuticals.8 A remarkable step forward has recently
been described by Tobisu and Chatani,9 in which 2-pyridyl
benzyl ethers can be used for such purposes via chelation
control. However, the stereoselective C–heteroatom bond
formation of benzyl esters still remains elusive. Prompted
by our ongoing interest in C–O bond functionalization10 and
by the versatility of organoboranes as synthons in organic
synthesis,11 we wondered whether a stereospecific boryla-
tion of enantioenriched benzyl pivalates could be imple-
mented (Scheme 2). Herein, we present our investigations
towards this goal, demonstrating the synergy of Ni and Cu
catalysts for promoting a stereoretentive borylation event
of benzyl pivalates under mild conditions, constituting the
first example of a stereospecific C–heteroatom bond forma-
tion of readily accessible organic ester derivatives.
DOI: 10.1055/s-0036-1590962; Art ID: st-2017-s0603-c
Abstract A stereoselective nickel-catalyzed direct borylation of enan-
tioenriched secondary benzyl pivalates is described. This methodology
is characterized by an intriguing cooperativity of simple nickel and cop-
per salts to promote the targeted C–B bond formation under mild reac-
tion conditions. Unlike classical SN2-type processes, this protocol occurs
with a neat retention of configuration, resulting in synthetically versa-
tile benzyl boronic esters with excellent stereochemical fidelity.
Key words borylation, nickel, cooperativity, stereoselective, C–O
bonds
In recent years, C–O electrophiles have received consid-
erable attention as counterparts in a myriad of metal-cata-
lyzed cross-coupling reactions.1 Such interest primarily
arises from the lack of toxicity and readily accessibility of
alcohols, as well as the possibility of implementing orthog-
onal techniques in the presence of organic halide partners,
thus becoming powerful synthetic alternatives for building
up molecular complexity. Despite the wealth of literature
data when forging C–C bonds,1 the design of enantioselec-
tive cross-coupling reactions via functionalization of C–O
electrophiles other than particularly activated organic sul-
fonates such as aryl triflates or tosylates is still in its infancy
(Scheme 1, paths b vs a).2
O
R
catalyst
catalyst
O
R1
R2
H
achiral ligand
chiral entity
electrophile
+
X
X
path a
path b
X
ample
precedents
limited
precedents
X = C, NR
X = C, NR
nucleophile
Scheme 1 Cross-coupling reactions of ester derivatives via C–O cleavage
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

B
R. Martin-Montero et al.
Cluster
Synlett
ed, an intimate interplay of all reaction parameters was
critical for success (Table 1, entries 2–7). For instance, while
the presence of CsF or CuF2 was not absolutely required,
their inclusion led to improved yields and enantioselectivi-
ties (Table 1, entries 11 and 12).14 The latter is particularly
noteworthy, indicating that nickel and copper salts might
cooperatively promote the targeted C–O bond cleavage/C–B
bond formation in high yields and excellent stereochemical
fidelity under mild reaction conditions.15 As expected, the
nature of the ligand exerted a profound influence on the re-
action outcome, with PCy3 providing the best results (Table
1, entries 2–5). Note, however, that a slight increase on the
catalyst loading of PCy3 had a deleterious effect, obtaining
2a in lower yields (Table 1, entry 8). Intriguingly, no reac-
tion took place in the absence of ligand (Table 1, entry 14)
whereas lower reactivity was found when using more steri-
cally encumbered B2pin2 as the boron source. Control ex-
periments in the absence of Ni(COD)2 revealed that no bor-
ylation occurred, recovering quantitatively 1a in 99% ee (Ta-
ble 1, entry 17).
OPiv
R2
B2nep2
Bnep
R2
Ni/Cu catalyst
R1
R1
synergistic Ni/Cu catalysis
retention of configuration
mild & broad scope
high stereochemical
fidelity
Scheme 2 Ni/Cu-catalyzed stereospecific borylation of benzyl ester
derivatives
We began our study by evaluating the borylation reac-
tion of 1a (99% ee) with B2nep2 (B2nep2 =5,5,5′,5′-te-
tramethyl-2,2′-bi-1,3,2-dioxaborinane). After a systematic
optimization of the reaction conditions,12 we found that a
cocktail containing Ni(COD)2 (7.5 mol%), PCy3 (7.5 mol%),
CuF2 (30 mol%), and CsF (30 mol%) provided the best results
at 50 °C, affording 2a in 95% yield and 95% ees (Table 1, en-
try 1).13 HPLC analysis revealed that the borylation event
occurred with a neat retention of configuration. As expect-
Table 1 Screening of the Reaction Conditionsa
B2nep2 (1.5 equiv)
Ni(COD)2 (7.5 mol%)
PCy3 (7.5 mol%)
OPiv
Me
Bnep
Bolstered by these initial results, we next turned our at-
tention to study the generality of our stereoselective bory-
lation via C–O bond cleavage of benzyl ester derivatives
(Scheme 3). As shown, a host of differently substituted en-
antioenriched benzyl pivalates, easily within reach from the
corresponding benzyl alcohols obtained via Corey–Bakshi–
Shibata (CBS) reduction,16 delivered the targeted com-
pounds in good yields and enantioselectivities. The reaction
worked equally well regardless of whether electron-rich
(2b) or electron-poor substituents were included on the
aryl backbone (2c). Unfortunately, the employment of quin-
oline (2e) or phenanthrene analogues (2f) resulted in a
markedly loss of enantiomeric excess; while the former
might suggest competitive binding of the nitrogen atom to
the metal center, the loss of fidelity in the latter can tenta-
tively be ascribed to racemization of the enantioenriched
oxidative addition species by bimolecular mechanisms with
exogeneous low-valent Ni(0)Ln.5e Substrates possessing ali-
phatic side chains other than methyl groups resulted in
lower enantioselectivities (2h–m). These observations sug-
gest that transmetalation might be hampered by the pres-
ence of larger alkyl side chains, setting the basis for the low
yields are tentatively attributed to parasitic β-hydride elim-
ination events that might erode the chiral integrity by sub-
sequent migratory insertion. In line with this notion, non-
negligible amounts of homobenzyl borylation were ob-
served in the crude reaction mixtures. Unfortunately, non-
π-extended aryl pivalates were not suited as substrates for
the targeted borylation event.17
Me
CuF2 (30 mol%), CsF (30 mol%)
PhMe, 50 °C
1a (99% ee)
2a
Entry
Deviation from standard conditions
2a (%)b
ees (%)c
1
none
95
2
95
n.d.
92
78
–
2
IPr·HCl as the ligand
PCy2Ph as the ligand
dcpe as the ligand
PiPr3 as the ligand
THF as solvent
3
90
62
0
4
5
6
54
47
40
21
0
88
91
91
77
–
7
Dioxane as solvent
using PCy3 (20 mol%)
AgF in lieu of CsF
8
9
10
11
12
13
14
15
16
17
CuBr2 in lieu of CsF
in the absence of CuF2
in the absence of CsF
no CuF2, no CsF
84
75
56
0
93
92
93
–
in the absence of PCy3
no CsF, with CuF2 (1 equiv)
no CuF2, with CsF (1 equiv)
no Ni(COD)2
84
73
0
86
85
–
a Reaction conditions: 1a (0.20 mmol), B2nep2 (0.30 mmol), Ni(COD)2 (7.5
mol%), PCy3 (7.5 mol%), CuF2 (30 mol%), CsF (30 mol%) in PhMe, 50 °C.
b GC yields using decane as internal standard.
c Calculated by HPLC of the corresponding oxidized alcohol due to the in-
herent instability of 2a.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

C
R. Martin-Montero et al.
Cluster
Synlett
arenes, a recurrent limitation found in a myriad of catalytic
C–O bond-functionalization technologies.19,20 Consistent
with a SN2′ oxidative addition by attack of the Ni(0)Ln at the
ortho position, we found that benzyl pivalates containing
ortho substituents (1n,o) failed to provide the targeted ben-
zyl boronate intermediates. In these cases, a site selectivity
switch en route to linear boronic esters 2n and 2o was ob-
tained (Scheme 4, bottom). The formation of these products
likely arises from a sequence consisting of a β-hydride elim-
ination followed by a migratory insertion prior to a final C–
B bond-forming reaction that takes place selectively at the
periphery to avoid the clash with the proximal ortho sub-
stituent on the arene.
B2nep2 (1.5 equiv)
Ni(COD)2 (7.5 mol%)
PCy3 (7.5 mol%)
OPiv
Bnep
R2
R2
R1
R1
CuF2 (30 mol%)
CsF (30 mol%)
1a–m
Bnep
Me
2a–m
PhMe, 50 °C
Bnep
Me
Bnep
Me
MeO2C
MeO
2a (87%)
95% ees (99% ee)
2b (80%)
98% ees (87% ee)
2c (85%)
92% ees (92% ee)
Bnep
Me
Bnep
Me
Bnep
Me
stereoretentive oxidative addition
tBu
F
N
O
Cy3P
OPiv
2d (80%)
88% ees (74% ee)
2e (72%)
57% ees (77% ee)
2fc (75%)
75% ees (90% ee)
OPiv
R2 Ni(0)Ln
Ni
O
Cy3P Ni
R1
R2
R2
Bnep
Et
R1
R1
Bnep
Bnep
I
Et
Me
SN2’-oxidative
addition
stereoretentive
MeO
2gd (73%)
89% ees (98% ee)
2he (80%)
89% ees (94% ee)
2ie (55%)
81% ees (85% ee)
selectivity switch with ortho-substituted benzyl pivalates
OMe OPiv
OMe
Bnep
Bnep
nBu
Me
Bnep
Bnep
nPr
MeO
1n
2n (60%)
Bnep
Ni(COD)2/PCy3
B2nep2, CuF2,
CsF, PhMe, 50 °C
Et
R = nBu, 2kf (61%); 72% ees (81% ee)
R = iBu, 2lf (51%); 89% ees (92% ee)
2md (51%)
87% ees (74% ee)
2j (70%)
83% ees (91% ee)
Me
OPiv
OMe
OMe
Scheme 3 Stereospecific nickel-catalyzed borylation of benzyl piva-
lates.a,b a As Table 1 (entry 1). b Isolated yields, with enantiomeric ex-
cesses of starting precursors in parentheses. c Ni(COD)2(10 mol%), PCy3
(20 mol%), CsF (1 equiv). d Ni(COD)2 (10 mol%), PCy3 (10 mol%), CuF2
(50 mol%), CsF (50 mol%), 55 °C. e Ni(COD)2 (5 mol%), PCy3 (5 mol%),
No CuF2, CsF (50 mol%). f Ni(COD)2 (10 mol%), PCy3 (10 mol%).
1o
2o (58%)
Scheme 4 Mechanistic hypothesis
Prompted by the pivotal role of organoboron reagents as
synthetic intermediates,11 we next turned our attention to
study the prospective impact of this protocol by exploring
the reactivity of the corresponding benzyl boronic ester in-
termediates (Scheme 5). Among the different alternatives,
we found that in situ generated 2a could trigger a Suzuki–
Miyaura reaction21 with a catalytic protocol based on
Pd2(dba)3/PPh3,22 resulting in the formation of 3 in excellent
overall yield from (S)-1a, thus constituting an alternative to
existing methodologies for the preparation of enantioen-
riched diarylmethanes. Consistent with a well-precedented
stereoretentive transmetalation,18 the C–C bond formation
occurred with retention of configuration. Inspired by the
reaction conditions reported by Zweifel,23 we next won-
dered whether α-vinyl arenes could be within reach from
2a. As shown in Scheme 4 (bottom, right), this turned out to
be the case. Specifically, we found that a simple exposure of
in situ generated 2a to vinylmagnesium bromide followed
by addition of I2 and NaOMe/MeOH at –78 °C resulted in 4
in good overall yield and exquisite stereochemical fidelity.
Independently on the starting precursor utilized, the
borylation of 1a–m invariably occurred with a neat reten-
tion of configuration. This observation was corroborated by
direct comparison of the alcohols obtained by oxidation of
1a–m with authentic samples obtained by CBS reduction of
the corresponding ketone derivatives. Taking into consider-
ation that both transmetalation and reductive elimination
should proceed with stereoretention,18 our results suggest a
scenario consisting of an initial oxidative addition occurring
with retention of configuration. In line with recent litera-
ture reports,6a,5f we propose that the pivalate motif initially
binds the nickel catalyst, setting the stage for a directed SN2′
oxidative addition that generate a putative π-benzyl nick-
el(II) intermediate I (Scheme 4, top). Such observation tacit-
ly explains the considerably higher reactivity of extended
π-systems, as partial dearomatization is required en route
to the corresponding π-benzyl species I. In line with this
notion, little reactivity, if any, was found with regular
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

D
R. Martin-Montero et al.
Cluster
Synlett
(2) For selected enantioselective, rather than stereospecific, cross-
coupling reactions of C–O electrophiles other than particularly
activated organic sulfonates, see: (a) Cornella, J.; Jackson, E. P.;
Martin, R. Angew. Chem. Int. Ed. 2015, 54, 4075. (b) Oelke, A. J.;
Jianwei, S.; Fu, G. C. J. Am. Chem. Soc. 2012, 134, 2966.
(S)-1a
99% ee
B2nep2
Ni(COD)2 / PCy3
MeO
(3) Chenery, A. H.; Kadunce, N. T.; Reisman, S. E. Chem. Rev. 2015,
115, 9587.
CuF2 / CsF
PhMe, 50 °C
(4) Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds;
John Wiley and Sons: New York, 1994.
Pd2(dba)3
PPh3
MgBr
then
Me
Me
2a
ArI
(5) (a) Erickson, L. W.; Lucas, E. L.; Tollefson, E. J.; Jarvo, E. R. J. Am.
Chem. Soc. 2016, 138, 14006. (b) Konev, M. O.; Hanna, L. E.;
Jarvo, E. R. Angew. Chem. Int. Ed. 2016, 55, 6730. (c) Tollefson, E.
J.; Dawson, D. D.; Osborne, C. A.; Jarvo, E. R. J. Am. Chem. Soc.
2014, 136, 14951. (d) Harris, M. R.; Konev, M. O.; Jarvo, E. R.
J. Am. Chem. Soc. 2014, 136, 7825. (e) Yonova, I. M.; Johnson, A.
G.; Osborne, C. A.; Moore, C. E.; Morrissette, N. S.; Jarvo, E. R.
Angew. Chem. Int. Ed. 2014, 53, 2422. (f) Harris, M. R.; Hanna, L.
E.; Greene, M. A.; Moore, C. E.; Jarvo, E. R. J. Am. Chem. Soc. 2013,
135, 3303. (g) Taylor, B. L. H.; Swift, E. C.; Waetzig, J. D.; Jarvo, E.
R. J. Am. Chem. Soc. 2011, 133, 389.
(6) (a) Zhou, Q.; Cobb, K. M.; Tan, T.; Watson, M. P. J. Am. Chem. Soc.
2016, 138, 12057. (b) Zhou, Q.; Srnivas, H. D.; Zhang, S.; Watson,
M. P. J. Am. Chem. Soc. 2016, 138, 11989. (c) Srnivas, H. D.; Zhou,
Q.; Watson, M. P. Org. Lett. 2014, 16, 3596. (d) Zhou, Q.; Srinivas,
H. D.; Dasgupta, S.; Watson, M. P. J. Am. Chem. Soc. 2013, 135,
3307.
(7) For selected references, see: (a) Zarate, C.; Nakajima, M.; Martin,
R. J. Am. Chem. Soc. 2017, 139, 1191. (b) Zarate, C.; Manzano, R.;
Martin, R. J. Am. Chem. Soc. 2015, 137, 6754. (c) Zarate, C. M.;
Martin, R. J. Am. Chem. Soc. 2014, 136, 7253. (d) Tobisu, M.;
Yasutome, A.; Yamakawa, A.; Yamakawa, K.; Shimasaki, T.;
Chatani, N. Tetrahedron 2012, 68, 5157. (e) Tobisu, M.;
Shimasaki, T.; Chatani, N. Chem. Lett. 2009, 38, 710.
(8) For selected comprehensive reviews on C–heteroatom bond-
forming reactions: (a) Zhu, X.; Chiba, S. Chem. Soc. Rev. 2016, 45,
4504. (b) Surry, D. S.; Buchwald, S. L. Chem. Sci. 2011, 2, 27.
(c) Catalyzed Carbon-Heteroatom Bond-Formation; Yudin, A. K.,
Ed.; Wiley-VCH: Weinheim, 2010. (d) Hartwig, J. F. Nature 2008,
455, 314.
Ag2O, THF
60 °C
I2, NaOMe
94% ee
4 (51%)
99% ees
3 (57%)
93% ees
MeOH, –78 °C
Scheme 5 Synthetic applicability
In summary, we have developed a stereospecific nickel-
catalyzed borylation of enantioenriched benzyl pivalates
with neat retention of configuration.24 This method is char-
acterized by the cooperativity of Cu and Ni salts to effect
the targeted C–B bond-forming event with excellent stereo-
chemical fidelity by a mechanism consistent with a stereo-
retentive oxidative addition. This work constitutes the first
C–heteroatom bond formation from enantioenriched ben-
zyl ester derivatives. Current investigations are focused on
extending the scope of these reactions beyond C–B bond-
forming reactions.
Funding Information
MINECO (CTQ2015-65496-R & Severo Ochoa Excellence Accreditation
2014-2018, SEV-2013-0319) and Cellex Foundation.
)(
Acknowledgment
C. Zárate and R. Martin-Montero thank MINECO and La Caixa Founda-
tion for predoctoral fellowships.
(9) Tobisu, M.; Zhao, J.; Kinuta, H.; Furukawa, T.; Igarashi, T.;
Chatani, N. Adv. Synth. Catal. 2016, 358, 2417.
(10) Selected references: (a) ref. 2a and 7a,b. (b) Gu, Y.; Martin, R.
Angew. Chem. Int. Ed. 2017, 56, 3187. (c) Correa, A.; Martin, R.
J. Am. Chem. Soc. 2014, 136, 7253. (d) Correa, A.; León, T.;
Martin, R. J. Am. Chem. Soc. 2014, 136, 1062. (e) Alvarez-Ber-
cedo, P.; Martin, R. J. Am. Chem. Soc. 2010, 132, 17352.
(f) Cornella, J.; Martin, R. Org. Lett. 2013, 15, 6298. (g) Cornella,
J.; Gómez-Bengoa, E.; Martin, R. J. Am. Chem. Soc. 2013, 135,
1997.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1590962.
S
u
p
p
ortioInfgrmoaitn
S
u
p
p
ortiInfogrmoaitn
References and Notes
(11) (a) Sandford, C.; Aggarwal, V. K. Chem. Commun. 2017, 53, 5481.
(b) Hall, D. G. Boronic Acids; Wiley-VCH: Weinheim, 2005.
(12) For details, see Supporting Information.
(1) (a) Zarate, C.; Van Gemmeren, M.; Somerville, R. J.; Martin, R.
Adv. Organomet. Chem. 2016, 66, 143. (b) Tollefson, E. J.; Hanna,
L. E.; Jarvo, E. R. Acc. Chem. Res. 2015, 47, 2344. (c) Su, B.; Cao, Z.-
C.; Shi, Z.-J. Acc. Chem. Res. 2015, 48, 886. (d) Tobisu, M.;
Chatani, N. Acc. Chem. Res. 2015, 48, 1717. (e) Cornella, J.;
Zarate, C.; Martin, R. Chem. Soc. Rev. 2014, 43, 8081.
(f) Yamaguchi, J.; Muto, K.; Itami, K. Eur. J. Org. Chem. 2013, 19.
(g) Rosen, B. M.; Quasdorf, K. W.; Wilson, D. A.; Zhang, N.;
Resmerita, A.-M.; Garg, N.; Percec, V. Chem. Rev. 2011, 111,
1346.
(13) The mass balance of the reaction accounts for the formation of
2-ethylnaphthalene via protodeborylation and the correspond-
ing homobenzylboronic ester obtained from the putative oxida-
tive addition species by a β-hydride elimination/migratory
insertion prior C–B bond formation at the terminal position.
(14) The synergistic use of CuF2 and low-valent nickel species was
initially demonstrated by our group when forging C–Si bonds,
see ref. 7c. For the beneficial role of CsF in recent C–O bond-
cleavage procedures, see: Schwarzer, M. C.; Konno, R.; Hojo, T.;
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

E
R. Martin-Montero et al.
Cluster
Synlett
Ohtsuki, A.; Nakamura, K.; Yasutome, A.; Takahashi, H.;
Shimasaki, T.; Tobisu, M.; Chatani, N.; Mori, S. J. Am. Chem. Soc.
2017, 139, 10347.
(23) (a) Zweifel, G.; Arzoumanian, H.; Whitney, C. C. J. Am. Chem. Soc.
1967, 89, 3652. (b) Evans, A.; Crawford, T. C.; Thomas, R. C.;
Walker, J. A. J. Org. Chem. 1976, 41, 3947. (c) Sonawane, R. P.;
Jheengut, V.; Rabalakos, C.; Larouche-Gauthier, R.; Scott, H. K.;
Aggarwal, V. K. Angew. Chem. Int. Ed. 2011, 50, 3760.
(15) For recent examples of Ni/Cu cooperativity for effecting C–hetero-
atom bond-forming reactions, see: (a) Gou, L.; Chatupheeraphat,
A.; Rueping, M. Angew. Chem. Int. Ed. 2016, 55, 11810.
(b) Semba, K.; Ohtagaki, Y.; Nakao, Y. Org. Lett. 2016, 18, 3956.
(c) Pu, X.; Hu, J.; Zhao, Y.; Shi, Z. ACS Catal. 2016, 6, 6692.
(16) Bakshi, R. K.; Shibata, S.; Chen, C.; Singh, V. K.; Corey, E. J. J. Am.
Chem. Soc. 1987, 109, 7925.
(17) Recovered starting material was observed when employing
non-π-extended aryl pivalates.
(18) (a) Netherton, M. R.; Fu, G. C. Angew. Chem. Int. Ed. 2002, 41,
(24) (R)-1-(6-fluoronaphthalen-2-yl)ethanol (2d) – Typical Proce-
dure
A 5 mL oven-dried screw-capped test tube containing a stirring
bar was charged with the benzyl pivalate 1d (54.8 mg, 0.2
mmol). The test tube was introduced in an argon-filled glovebox
where B2nep2 (67.8 mg, 0.3 mmol, 1.5 equiv), CuF2 (6 mg, 30
mol%), CsF (9.1 mg, 30 mol%), Ni(COD)2 (304 μL, 7.5 mol%, 0.05
M in toluene), PCy3 (152 μL, 7.5 mol%, 0.1 M), and toluene (1
mL) were then added sequentially. The tube with the mixture
was taken out of the glovebox and stirred at 50 °C for 15 h. The
mixture was then allowed to warm to room temperature,
diluted with EtOAc (5 mL), and filtered through a Celite® plug,
eluting with additional EtOAc (5mL). The filtrate was concen-
trated removing the volatiles. Then the reaction was cooled to 0
°C (water/ice bath) and BHT (ca. 1 mg) was added followed by
anhydrous THF (1 mL). An ice-cold degassed mixture of 3 M
NaOH (1.2 mL) and 30% aq H2O2 (0.75 mL) was added all at once.
The reaction mixture was stirred at room temperature for 2 h.
Then, the reaction mixture was diluted with water (4 mL) and
extracted with Et2O (3 × 10 mL). The combined organic layers
were washed with brine and dried over MgSO4. The filtrate was
concentrated and purified by silica gel chromatography to give
the title product 2d (30.5 mg, 80%) as a white solid (mp 84–86
°C). The enantiomeric excess was determined to be 65% ee (88%
ees) by chiral HPLC analysis (CHIRALPAK IB, 1 mL/min, 2%
EtOH/hexane, λ = 220 nm): tR (minor) = 12.4 min, tR (major) =
3910. (b) Stille, J. K. In The Chemistry of the Metal–Carbon Bond;2Vo.
Hartley, F. R.; Patai, S., Eds.; John Wiley and Sons: New York,
1985, 625.
l
(19) For selected references limited to π-extended systems or to the
presence of ortho- or para-activating groups, see: (a) Guo, L.;
Liu, X.; Baumann, C.; Rueping, M. Angew. Chem. Int. Ed. 2016, 55,
15415. (b) Zhao, Y.; Snieckus, V. J. Am. Chem. Soc. 2014, 136,
11224. (c) Yu, D.-G.; Shi, Z.-J. Angew. Chem. Int. Ed. 2011, 50,
7097. (d) Tobisu, M.; Yamakawa, K.; Shimasaki, T.; Chatani, N.
Chem. Commun. 2011, 47, 2946. (e) Yu, D. G.; Li, B. J.; Zheng, S.
F.; Guan, B. T.; Wang, B. Q.; Shi, Z. J. Angew. Chem. Int. Ed. 2010,
49, 4566. (f) Alvarez-Bercedo, R.; Martin, R. J. Am. Chem. Soc.
2010, 132, 17352. (g) Tobisu, M.; Shimasaki, T.; Chatani, N.
Angew. Chem. Int. Ed. 2008, 47, 4866.
(20) η2-Coordination of π-extended systems to low-valent metal
complexes is known to be stronger than regular arenes due to
the partial preservation of the aromaticity: Bauer, D. J.; Krueger,
C. Inorg. Chem. 1977, 16, 884.
(21) Martin, R.; Buchwald, S. L. Acc. Chem. Res. 2008, 41, 1461.
(22) Imao, D.; Glasspole, B. W.; Laberge, V. S.; Crudden, C. M. J. Am.
Chem. Soc. 1987, 109, 4756.
13.9 min. [α]D = 43.2 (c 0.06, CHCl3).1H NMR (500 MHz,
24
CDCl3): δ = 7.83–7.76 (m, 3 H), 7.53 (dd, J = 2.0 Hz, 1 H), 7.44
(dd, J = 2.6 Hz, 1 H), 7.26 (td, J = 2.6 Hz, 1 H), 5.06 (q, J = 6.4 Hz, 1
H), 1.97 (s, 1 H, OH), 1.58 (d, J = 6.4 Hz, 3 H) ppm. 13C NMR (126
MHz, CDCl3): δ = 161.8, 159.4, 142.5, 133.6, 130.3, 127.7, 124.9,
123.8, 116.6, 110.7, 70.3, 25.2 ppm. 19F NMR (376 MHz, CDCl3):
δ = –115.1 ppm.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E