alkynes without the electronic bias exerted by a polar
functionality at the propargylic position10 or that found
in conjugated 1-aryl-1-alkynes9,11 or 1,3-enynes.9b,12 There-
fore, methods for the highly regiocontrolled hydroboration
of unbiased internal dialkyl alkynes are actively sought after.
terminal alkynes, including the two regiochemically com-
plementary formal hydroboration products of unbiased
internal alkynes.
At the outset of our work, propargyl sulfide 1 was
chosen as a model substrate for CuI-catalyzed B2(pin)2-
borylation17,18 under typical conditions (see Supporting
Information (SI) for ligand effects). This study showed
that both reactivity and regiocontrol were impacted by
ligand structure.19 The use of P(t-Bu)320 was essential for
effective R-regiocontrol and high catalytic activity. The
combination of CuCl (10 mol %), NaOtBu (15 mol %),
and P(t-Bu)3 (12 mol %) provided R-2 as the only detected
product in 76% yield after 2 h (Scheme 2).21
Scheme 1. Regiocontrolled Borylation of Terminal Alkyl
Alkynes
Scheme 2. Cu-Catalyzed R-Selective Borylation of Sulfide 1
To address this challenge, we envisaged the use of
terminal alkynes with a removable propargyl directing
group13 which could promote an R-regiocontrolled bor-
ylation while also serve as a handle for further elaboration
via subsequent allylic alkylation. Along this line, Walsh14
has reported on the chemoselective TsujiÀTrost substitu-
tion of allylic acetates with an embedded vinyl boronate
moiety. The development of a Cu-catalyzed allylic alkyla-
tion of similar substrates with Grignard reagents would
nicely complement Pd-catalysis, enabling the direct intro-
duction of nonstabilized alkyl, alkenyl, or aryl groups.
However, this reactivity is hampered by impediments such
as the transmetalation from alkenyl-Bpin to alkenyl-Cu
species15 or the formation of boron-ate complexes.16 In
fact, Hall found that (pin)BÀC bonds were unsuitable for
Cu-catalyzed conjugate additions of Grignard reagents.16
We hypothesized that addressing the chemical compat-
ibility of the Bpin moiety with Grignard reagents under Cu
catalysis would offer a practical indirect solution to access
formal hydroboration products of unbiased terminal
and internal alkynes. Herein, we describe the successful
execution of a borylation/allylic alkylation strategy
which relies on the use of a propargylic 2-PySO2 group
as an efficient regiodirector in the first step and a practical
stereocontroller in the second. This approach enables the
access to di- and trisubstituted vinyl boronates from simple
The regiocontrolling ability of the functionality at the
propargylic position (FG) was next assessed (see selected
results in Table 1; full results in Table S2 of the SI).
Uniformly excellent R-regiocontrol (generally R/β =
>98:<2) and high reactivity were observed for a variety
of S-, O-, and N-functional groups with different steric and
electronic properties. Notably, sulfones 3 and 4 (bearing a
coordinating 2-PySO2 group)22 were amenable to the
reaction conditions (Table 1, entries 1 and 2). Propargyl
alcohol 5, the challenging propargyl acetate 6,23 and the
N-Boc propargylamine 7 delivered the corresponding vinyl
(17) For reviews on asymmetric CuI-catalyzed borylation of conju-
ꢀ
gated alkenes, see: (a) Schiffner, J. A.; Muther, K.; Oestreich, M. Angew.
Chem., Int. Ed. 2010, 49, 1194. (b) Mantilli, L.; Mazet, C. ChemCatChem
2010, 2, 501. See also: (c) Lee, J. C. H.; McDonald, R.; Hall, D. G. Nat.
Chem. 2011, 3, 894. (d) Kobayashi, S.; Xu, P.; Endo, T.; Ueno, M.;
Kitanosono, T. Angew. Chem., Int. Ed. 2012, 51, 12763. For the
ꢀ
ꢀ
application to R,β-unsaturated sulfones: (e) Lopez-Moure, A.; Gomez
ꢀ
Arrayas, R.; Carretero, J. C. Chem. Commun. 2011, 47, 6701. For Cu-
catalyzed borylation of allenes: (f) Meng, F.; Jung, B.; Haeffner, F.;
Hoveyda, A. H. Org. Lett. 2013, 15, 1414. For Cu-catalyzed borylation
of vinyl silanes: (g) Meng, F.; Jang, H.; Hoveyda, A. H. Chem.;Eur. J.
2013, 19, 3204.
(18) Other Cu-catalyzed B2(pin)2-borylation of internal alkynes:
(a) Yoshida, H.; Kawashima, S.; Takemoto, Y.; Okada, K.; Ohshita,
J.; Takaki, K. Angew. Chem., Int. Ed. 2012, 51, 235. Cu-catalyzed
B2(pin)2-borylation of allenes: (b) Yuan, W.; Ma, S. Adv. Synth. Catal.
2012, 354, 1867. Fe-catalyzed hydroboration: (c) Haberberger, M.;
Enthaler, S. Chem.;Asian J. 2012, 8, 50. Cu-catalyzed borylation of
ꢁ
ꢀ
acetylenic esters: (d) Lipshutz, B. H.; Boskovic, Z. V.; Aue, D. H. Angew.
Chem., Int. Ed. 2008, 47, 10183. (e) Jung, H.-Y.; Feng, X.; Kim, H.; Yun,
J. Tetrahedron 2012, 68, 3444.
(11) (a) Kim, H. R.; Jung, I. G.; Yoo, K.; Jang, K.; Lee, E. S.; Yun, J.;
Son, S. U. Chem. Commun. 2010, 46, 758. (b) Ryung, H.; Yun, J. Chem.
Commun. 2011, 47, 2943. For Cu-catalyzed carboboration of unsym-
metrical aryl-substituted internal alkynes: (c) Zhang, L.; Cheng, J.;
Carry, B.; Hou, Z. J. Am. Chem. Soc. 2012, 134, 14314.
(12) Sasaki, Y.; Horita, Y.; Zhong, C.; Sawamura, M.; Ito, H. Angew.
Chem., Int. Ed. 2011, 50, 2778.
(13) For a review on removable directing groups in catalysis, see:
Rousseau, G.; Breit, B. Angew. Chem., Int. Ed. 2011, 50, 2450.
(14) Hussain, M. M.; Walsh, P. J. Angew. Chem., Int. Ed. 2010, 49,
1834.
(19) No reaction was observed in the absence of the CuI catalyst,
whereas very low conversion and complete β-regioselectivity were
observed in the absence of ligand.
(20) An identical result was obtained when the air-stable (t-Bu3P
3
HBF4) was used (increasing the amount of NaOtBu to 27 mol %).
(21) For thorough mechanistic studies accounting for the origin of
the R-selectivity, see ref 4a. See SI for a mechanistic discussion.
(22) For the Cu-coordinating capability of the 2-pyridylsulfonyl
ꢀ
ꢀ
group, see: Esquivias, J.; Gomez Arrayas, R.; Carretero, J. C. Angew.
(15) For transmetallation from boron to copper in alkenyl boronates
to give alkenyl-Cu species: Jung, B.; Hoveyda, A. H. J. Am. Chem. Soc.
2012, 134, 1490 and references cited therein. See also ref 1e.
(16) Lee, J. C. H.; Hall, D. G. J. Am. Chem. Soc. 2010, 132, 5544.
Chem., Int. Ed. 2007, 46, 9257.
(23) The Cu-catalyzed B2(pin)2-borylation of propargylic carbonates
was found to give allenyl boronates: Ito, H.; Sasaki, Y.; Sawamura, M.
J. Am. Chem. Soc. 2008, 130, 15774.
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