Enantioselective synthesis of nonracemic geminal silylboronates by Pt-catalyzed hydrosilylation

Article abstract of DOI:10.1021/acscatal.8b00221

A Pt-catalyzed enantioselective hydrosilylation of alkenylboronates is described. This reaction occurs with high regio- and enantioselectivity, providing a convenient route to chiral nonracemic geminal silylboronates. These compounds are useful reagents in stereoselective synthesis.

Full text of DOI:10.1021/acscatal.8b00221

Subscriber access provided by - Access paid by the | UCSB Libraries
Letter
Enantioselective Synthesis of Nonracemic Geminal
Silylboronates by Pt-Catalyzed Hydrosilylation
Adam A. Szymaniak, Chenlong Zhang, John Ryan Coombs, and James P. Morken
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b00221 • Publication Date (Web): 23 Feb 2018
Downloaded from http://pubs.acs.org on February 23, 2018
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
ACS Catalysis is published by the American Chemical Society. 1155 Sixteenth Street
N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 6
ACS Catalysis
1
2
3
4
5
6
7
8
9
Enantioselective Synthesis of Nonracemic Geminal Silylboronates by
Pt-Catalyzed Hydrosilylation
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Adam A. Szymaniak, Chenlong Zhang, John R. Coombs, James P. Morken*
Department of Chemistry, Merkert Chemistry Center, Boston College,
Chestnut Hill, Massachusetts 02467
ABSTRACT: A Ptꢀcatalyzed enantioselective hydrosilylation of alkenylboronates is described. This reaction occurs with high
regioꢀ and enantioselectivity, providing a convenient route to chiral nonꢀracemic geminal silylboronates. These compounds are
useful reagents in stereoselective synthesis. Keywords: Hydrosilylation, Silicon, Boron, Catalysis, Asymmetric
Scheme 1. Utility and Previous Catalytic Syntheses of Nonraꢀ
cemic Geminal Dimetallic Reagents
Geminal bimetallic reagents are endowed with distinctive reꢀ
activity patterns that allow them to engage in an array of comꢀ
plexityꢀgenerating processes. While bimetallic reagents based
on Zn, Cr, and Cu species have received steady attention over
the past 20ꢀ30 years1, recent studies have focused intensely on
the synthesis and utility of geminal bis(boronates) in both
catalytic and nonꢀcatalytic processes.2 In this regard, the utiliꢀ
ty of symmetric geminal bimetallic reagents (A, Scheme 1) in
stereoselective catalysis requires the agency of a catalyst that
can not only effect chemical transformation, but can also disꢀ
criminate the enantiotopic metal groups of the substrate.3 Alꢀ
ternatively, nonracemic, nonꢀsymmetrical geminal dimetallic
reagents (B, Scheme 1) might engage in a broader array of
both catalytic and nonꢀcatalytic bond constructions wherein
the unique reactivity of each CꢀM group can be employed to
allow differential functionalization of the stereogenic carbon
atom. In spite of the significant synthetic utility of nonꢀ
symmetric dimetallic reagents, there are few methods availaꢀ
ble for their catalytic enantioselective preparation. While Hall
and Yun established catalytic4 methods that provide access to
On the basis of our studies on platinumꢀcatalyzed diboration
of alkenyl boronates8 we were prompted to consider the proꢀ
nonꢀsymmetric geminal bis(boronates) (i.e. Scheme 1, B,
M1=B(pin); M2=B(dan)), we considered that nonracemic gemꢀ
spects for an aligned Ptꢀcatalyzed hydrosilylation of this subꢀ
strate class.9 This approach to silylboronate synthesis would
inal bis(metallates) bearing different metal centers might proꢀ
vide the most diverse reactivity.5 In this connection, pioneerꢀ
have the attractive feature of accommodating a broad array of
ing studies by Hoveyda and coworkers6 (Scheme 1, eq. 1)
alkenyl substituents while avoiding the use of diboron and
silylboron reagents. Of note, successful development of this
process could rely on wellꢀprecedented "hydrideꢀfirst" inserꢀ
tion10 where production of a stable αꢀborylꢀorganoplatinum
intermediate might dictate reaction regiocontrol.
established an efficient catalytic synthesis of nonracemic gemꢀ
inal silylboronates utilizing copperꢀboron addition to substitutꢀ
ed styrenyl silanes. To provide enantiomericallyꢀenriched
nonꢀfunctionalized geminal silylboronates Lan, Liu and coꢀ
workers7 introduced a copperꢀcatalyzed aldehyde diboration
followed by deoxygenative gemꢀsilylation (Scheme 1, eq. 2).
While this latter route is effective, yields are often modest and
it requires the use of both a BꢀB and a BꢀSi bonded reagent.
Herein, we describe a catalytic enantioselective hydrosilylaꢀ
tion of readily accessible alkenyl boronates. Importantly, this
process applies to a broad range of substrates and can be teleꢀ
scoped directly from alkyne precursors in a tandem hydroboraꢀ
tion/hydrosilylation format. For this reason, and because it
employs simple silanes and boranes as reagents, the process
described herein represents a powerful, scalable route to imꢀ
portant synthetic intermediates.
To initiate studies, reaction conditions and catalysts similar to
those employed for the diboration of alkenyl boronates were
employed, but the diboron reagent was replaced with a silane.
Specifically, Pt(dba)3, phosphonite ligand L1, and dimeꢀ
thylphenylsilane were employed in the reaction and found to
furnish the hydrosilylation product with complete conversion
and high regioselectivity (> 20:1 rr), but only modest enantioꢀ
control (Table 1, entry 1). Use of less sterically encumbered
xylylꢀsubstituted phosphonite L2 (Table 1, entry 2) showed a
notable increase in enantioselectivity. Further increases in
enanioselectivity were obtained by employing pyrrolidineꢀ
ACS Paragon Plus Environment

ACS Catalysis
derived phosphoramidite ligands L3-L4 (Table 1, entries 3ꢀ4).
Page 2 of 6
In addition to dimethylphenylsilane, benzyldimethylsilane11
(17) and diphenylmethylsilane (18) also show high reactivity
and moderate to good enantioselectivity. Product 18 highꢀ
lights the ability of the method to be applied to pharmaceutiꢀ
callyꢀrelevant problems: after oxidation of the phenyl groups
this compound would furnish silaneꢀdiol motifs that are often
utilized as tetrahedral intermediate bioisosteres.12 It is worth
noting that more substituted alkenyl boronates (→19) are not
reactive under these conditions.
1
2
3
4
5
6
7
8
With this class of ligands, selectivity is still optimal with meꢀ
taꢀsubstituted arenes on the TADDOL backbone and, of those
substituents, 3,5ꢀdialkoxysubstituted ligands L6ꢀL7 (Table 1,
entries 6ꢀ7) were consistently most effective. (see Supporting
Information for full ligand optimization). Analysis of the reꢀ
action temperature (Table 1, entry 8 vs. entry 4) showed an
increase of enantioselectivity at room temperature, and varyꢀ
ing the metalꢀligand ratios (Table 1, entries 9ꢀ10) were found
to be either less selective or efficient. After further analysis of
reaction conditions (Table 1, entries 11ꢀ17), it was concluded
that MTBE as the solvent and L7 as the ligand were optimal
conditions to explore the generality of the reaction.
9
Table 2. Scope of PtꢀCatalyzed Enantioselective Hydrosilylaꢀ
tion[a]
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 1. Catalyst Studies in Alkenyl Boronate Hydrosilylation
entry
1
2
3
4
5
6
7
8
R=
ligand
L1
L2
L3
L4
L5
L6
L7
solvent
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
temp (°C) yield (%)a
erb
ꢀCH2CH2Ph
ꢀCH2CH2Ph
ꢀCH2CH2Ph
ꢀCH2CH2Ph
ꢀCH2CH2Ph
ꢀCH2CH2Ph
ꢀCH2CH2Ph
ꢀCH2CH2Ph
ꢀCH2CH2Ph
ꢀCH2CH2Ph
ꢀCH2CH2Ph
70
70
70
70
70
70
70
r.t.
r.t.
r.t.
r.t.
95
96
96
99
99
87
80
14
71
<5
93
62:38
85:15
86:14
88:12
72:38
8:92c
90:10
93:7
L4
9
10
11
L4d
L4e
L6
91:9
n/d
94:6
12
13
14
15
16
17
ꢀCH2CH2Ph
ꢀCH2CH2Ph
ꢀCH2CH2Ph
ꢀnꢀbutyl
ꢀnꢀbutyl
ꢀnꢀbutyl
L6
L6
L6
L7
L7
L7
MTBE
toluene
cyclohexane
cyclohexane
THF
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
89
94
99
73
88
99
6:94c
7:93c
6:94c
95:5
95:5
95:5
MTBE
[a] Yields determined by NMR analysis with comparison to an internal standꢀ
ard. [b] Enantiomer ratios (er) determined by SFC analysis of the correspondꢀ
ing silyl alcohol [c] Reaction carried out using entꢀL6. [d] Reaction carried out
using 3 mol% Pt(dba)3, 3.2 mol% ligand. [e] Reaction carried out using 3
mol% Pt(dba)3, 12 mol% ligand.
To survey the scope of the alkenyl boronate hydrosilylation,
Pt(dba)3 and ligand L7 were preꢀcomplexed for 15 minutes at
80°C, cooled to room temperature, and then used as catalyst
for a room temperature reaction between the alkenyl boronate
and silane. As noted in Table 2, good yields and enantioselecꢀ
tivities were obtained for many substrates. Various alkyl subꢀ
stituents can be tolerated (1, 2, 3), however βꢀbranched groups
result in diminished reactivity and enantioselectivity (4, 5, 6).
Relocating the steric bulk further from the alkene reestablishes
high reactivity and enantioselectivity (7). The platinumꢀ
catalyzed hydrosilylation can tolerate various functional
groups such as alkyl halides (8, 9), protected alcohols (10),
and heterocycles (15, 16). Notably, the hydrosilylation is seꢀ
lective towards alkenyl boronates over terminal alkenes (11)
and ketones (14), with only trace alkene hydrosilylation obꢀ
served. Ester functional groups in various positions (12, 13,
14) are tolerated, but it is worth noting that for 12, the regioiꢀ
someric hydrosilylation product was formed in equal amount.
[a] See text and Supporting Information for experimental details. Both the
isolated yield and the enantiomer ratio (er) represent the average value for two
experiments. [b] Reaction run using L6. [c] Reaction conducted at 70°C. [d]
Reaction run using HSiMe2Bn and entꢀL6. [e] Reaction run using HSiPh2Me
and entꢀL6.
As mentioned above, the synthesis of geminal bis(metallates)
bearing different metal groups can allow for diverse functionꢀ
alization by taking advantage of the increased reactivity of
boron relative to silicon in 1,2ꢀmetallate rearrangements.13 As
depicted in Figure 1 (eq. A), direct oxidation and amination14
of the organoboronate provided the silyl alcohol (20) and silyl
amine (21) products with retention of configuration. These
types of products have been shown to be useful as chiral auxilꢀ
iaries15 and as amino acid bioisoteres16, respectively. A modiꢀ
fied procedure for the Matteson homologation17 afforded the
vicinal silyl boronate 22 with good yield, a compound that
itself might be used in further coupling reactions. To highlight
ACS Paragon Plus Environment

Page 3 of 6
ACS Catalysis
this feature and demonstrate the reactivity differences of the
ble yield and selectivity as smaller scale reactions conducted
in the glove box.
1
2
3
4
5
6
7
8
metal groups, vicinal silylboronate 22 was subjected to aminaꢀ
tion to afford vicinal silyl amine 23 (eq. B), and a modified
TamaoꢀFleming oxidation18 resulted in the formation of oxaꢀ
zolidinone 24 after cyclization on the –Boc group. The twoꢀ
step sequence towards 24 occurred in good yield and 98%
enantiospecificity.
Preliminary investigations into crossꢀ
coupling using Pd and Cu catalysis showed no reactivity of these
more substituted geminal silylboronates towards crossꢀcoupling.19
Figure 3. Gramꢀscale, dryꢀboxꢀfree enantioselective platiꢀ
numꢀcatalyzed hydrosilylation.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Although the mechanism of platinumꢀcatalyzed hydrosilylaꢀ
tion has been extensively studied,10 alkenyl boronates are
unique substrates for this reaction and probing the mechanism
was of interest. To probe this insertion mode, deuterodimeꢀ
thylphenylsilane21 was synthesized and employed in the reacꢀ
tion. As depicted in Figure 4, the enantioselective platinumꢀ
catalyzed deuterosilylation resulted in a single product diaꢀ
stereomer in high enantioselectivity. Analysis of the reaction
product by NMR (see Supporting Information for details)
showed no deuterium scrambling, which supports the hypotheꢀ
sis that olefin insertion into a platinum hydride forms a stabiꢀ
lized αꢀborylꢀorganoplatinum intermediate, and this feature
governs the regiocontrol of the hydrosilylation.
Figure 1. a: Direct transformation of silylboronate to chiral
silyl alcohol, silyl amine, and vicinal silylboronate. b: Teleꢀ
scope sequence from vicinal silylboronate to oxazolidinone by
amination and oxidation.
Figure 4. Regioselectivity of the deuteriosilylation of a vinyl
boronate under Ptꢀphosphoramidite catalysis.
To probe the utility and robustness of the hydrosilylation, a
oneꢀpot procedure starting from 3ꢀphenylꢀ1ꢀpropyne was conꢀ
ducted as shown in Figure 2. In this experiment, dicyclohexꢀ
ylborane–catalyzed hydroboration of 3ꢀphenylꢀ1ꢀpropyne,20
followed by platinumꢀcatalyzed hydrosilylation in toluene and,
lastly, in situ amination afforded the silylamine 21 in good
yield and enantioselectivity. This procedure highlights the
utility of the enantioselective platinumꢀcatalyzed hydrosilylaꢀ
tion for the practical synthesis of compounds of significance
for the pharmaceutical industry, and the insensitivity of the
reaction towards different solvents.
In conclusion, we have demonstrated the ability of a platinum
complex to catalyze the hydrosilylation of alkenyl boronates
with high regioꢀ and enantioselectivity.
The geminal
silylboronate products are shown to be versatile synthetic
building blocks by divergent functionalization of the Si and B
groups. Further studies on the hydrosilylation of other
systems are ongoing.
πꢀ
ASSOCIATED CONTENT
Supporting Information
Supporting Information (procedures, characterization, spectral
data) is available. The Supporting Information is available free of
charge on the ACS Publications website.
Figure 2. Singleꢀflask sequential catalytic alkyne hydroboraꢀ
tion/hydrosilylation/amination for the synthesis of silylamine
20 from 3ꢀphenylꢀ1ꢀpropyne.
To further examine the practical utility of this method for
largeꢀscale dryꢀbox free synthesis, the reaction in Figure 3 was
conducted. As depicted, the metal and ligand were weighed in
the open atmosphere, then the flask purged with nitrogen,
heated to 80°C for 15 minutes, cooled, and the alkenyl boroꢀ
nate and silane introduced for reaction at room temperature.
Notably, the catalyst loading could be reduced to oneꢀpercent
and the solvent volume reduced while maintaining high reacꢀ
tivity and enantioselectivity. This experiment gave comparaꢀ
ACS Paragon Plus Environment

ACS Catalysis
Page 4 of 6
(7) Wang, L.; Zhang, T.; Sun, W.; He, Z.; Xia, C.; Lan, Y.; Liu, C.
AUTHOR INFORMATION
C–O Functionalization of αꢀOxyboronates: A Deoxygenative gemꢀ
Diborylation and gemꢀSilylborylation of Aldehydes and Ketones. J.
Am. Chem. Soc. 2017, 139, 5257ꢀ5264.
1
2
Corresponding Author
*Eꢀmail: morken@bc.edu
3
4
5
6
7
8
9
(8) Coombs, J. R.; Zhang, L.; Morken, J. P. Enantiomerically Enꢀ
riched Tris(boronates): Readily Accessible Conjunctive Reagents for
Asymmetric Synthesis. J. Am. Chem. Soc. 2014, 136, 16140ꢀ16143.
(9) For other Ptꢀcatalyzed asymmetric hydrosilation of alkenes,
see: (a) Yamamoto, K.; Hayashi, T.; Kumada, M. Asymmetric homoꢀ
geneous hydrosilylation with platinum(II) complexes of chiral phosꢀ
phines. J. Am. Chem. Soc. 1971, 93, 5301ꢀ5302. (b) Yamamoto, K.;
Hayashi, T.; Zembayashi, M.; Kumada, M. Catalytic asymmetric
hydrosilylation of olefins: I. Chiral phosphineꢀplatinum(II) complexes
as hydrosilylation catalysts. J. Organomet. Chem. 1976, 118, 161ꢀ
181. For asymmetric hydrosilation of ketones, see: (c) Yamamoto, K.;
Hayashi, T.; Kumada, M. Asymmetric hydrosilylation of ketones
catalyzed by chiral phosphine—platinum(II) complexes. J. Organ-
omet. Chem. 1972, 46, C65ꢀC67. (d) Hayashi, T.; Yamamoto, K.;
Kumada, M. Catalytic asymmetric hydrosilylation of ketones: I. Chiꢀ
ral phosphineꢀplatinum(II) complexꢀcatalyzed hydrosilylation. J.
Organomet. Chem. 1976, 112, 253ꢀ262.
(10) (a) Chalk, A. J.; Harrod, J. F. Homogeneous Catalysis. II. The
Mechanism of the Hydrosilation of Olefins Catalyzed by Group VIII
Metal Complexes. J. Am. Chem. Soc. 1965, 87, 16ꢀ21. (b) Chalk, A.
J.; Harrod, J. F. Dicobalt Octacarbonyl as a Catalyst for Hydrosilation
of Olefins. J. Am. Chem. Soc. 1965, 87, 1133ꢀ1133. (c) Taylor, R. B.;
Roy, A. K. The First Alkene−Platinum−Silyl Complexes: Lifting the
Hydrosilation Mechanism Shroud with LongꢀLived Precatalytic Inꢀ
termediates and True Pt Catalysts. J. Am. Chem. Soc. 2002, 124,
9510ꢀ9524. (d) Taige, M. A.; Ahrens, S.; Strassner, T. Platinum(II)ꢀ
bisꢀ(Nꢀheterocyclic carbene) complexes: synthesis, structure and
catalytic activity in the hydrosilylation of alkenes. J. Organomet.
Chem. 2011, 696, 2918ꢀ2927. (e) Meister, T. K.; Riener, K.; Gigler,
P.; Stohrer, J.; Herrmann, W. A.; Kuhn, F. E. Platinum Catalysis
Revisited—Unraveling Principles of Catalytic Olefin Hydrosilylation.
ACS Catal. 2016, 6, 1274ꢀ1284.
(11) For the utility of BnMe2Siꢀ group in crossꢀcoupling, see: (a)
Machacek, M. R.; Ball, Z. T.; Trost, B. M. RutheniumꢀCatalyzed
Vinylsilane Synthesis and CrossꢀCoupling as a Selective Approach to
Alkenes: Benzyldimethylsilyl as a Robust Vinylmetal Functionality.
Org. Lett. 2003, 5, 1895ꢀ1898. (b) Tymonko, S. A.; Denmark, S. E.
Sequential CrossꢀCoupling of 1,4ꢀBissilylbutadienes: Synthesis of
Unsymmetrical 1,4ꢀDisubstituted 1,3ꢀButadienes. J. Am. Chem. Soc.
2005, 127, 8004ꢀ8005. (c) Nakao, Y.; Hiyama, T. Siliconꢀbased crossꢀ
coupling reaction: an environmentally benign version. Chem. Soc.
Rev. 2011, 40, 4893ꢀ4901.
(12) (a) Nielsen, L.; Skrydstrup, T. Sequential C−Si Bond Forꢀ
mations from Diphenylsilane: Application to Silanediol Peptide
Isostere Precursors. J. Am. Chem. Soc. 2008, 130, 13145ꢀ13151. (b)
Min, G. K.; Hernandez, D.; Skrydstrup T. Efficient Routes to Carꢀ
bon–Silicon Bond Formation for the Synthesis of SiliconꢀContaining
Peptides and Azasilaheterocycles. Acc. Chem. Res. 2013, 46, 457ꢀ470.
(13) Millan, A.; Grigol Martinez, P. D.; Aggarwal, V. K. Stereꢀ
ocontrolled Synthesis of Polypropionate Fragments based on a Buildꢀ
ing Block Assembly Strategy using LithiationꢀBorylation Methodoloꢀ
gies. Chem. Eur. J. 2017, 24, 730ꢀ735.
ORCID
James P. Morken: 0000ꢀ0002ꢀ9123ꢀ9791
Author Contributions
The manuscript was written through contributions of all authors.
Notes
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This work was supported by the NIH (GMꢀ59417).
REFERENCES
(1) Marek, I.; Normant, J. ꢀF. Synthesis and Reactivity of sp3ꢀ
Geminated Organodimetallics. Chem. Rev. 1996, 96, 3241ꢀ3268.
(2) (a) Xu, L.; Zhang, S.; Li, P. Boronꢀselective reactions as powerꢀ
ful tools for modular synthesis of diverse complex molecules. Chem.
Soc. Rev. 2015, 44, 8848ꢀ8858. (b) Rygus, J. P. G.; Crudden, C. M.
Enantiospecific and Iterative Suzuki–Miyaura CrossꢀCouplings. J.
Am. Chem. Soc. 2017, 139, 18124ꢀ18137
(3) (a) Sun, C.; Potter, B.; Morken, J. P. A Catalytic Enantiotopicꢀ
GroupꢀSelective Suzuki Reaction for the Construction of Chiral Orꢀ
ganoboronates. J. Am. Chem. Soc. 2014, 136, 6534ꢀ6537. (b) Potter,
B.; Szymaniak, A. A.; Edelstein, E. K.; Morken, J. P. Nonracemic
Allylic Boronates through EnantiotopicꢀGroupꢀSelective Crossꢀ
Coupling of Geminal Bis(boronates) and Vinyl Halides. J. Am.
Chem. Soc. 2014, 136, 17918ꢀ17921. (c) Potter, B.; Edelstein, E. K.;
Morken, J. P. Modular, Catalytic Enantioselective Construction of
Quaternary Carbon Stereocenters by Sequential CrossꢀCoupling Reꢀ
actions. Org. Lett. 2016, 18, 3286ꢀ3289. (d) Joannou, M. V.; Moyer,
B. S.; Meek, S. J. Enantioꢀ and Diastereoselective Synthesis of 1,2ꢀ
Hydroxyboronates through CuꢀCatalyzed Additions of Alkylꢀ
boronates to Aldehydes. J. Am. Chem. Soc. 2015, 137, 6176ꢀ6179. (e)
Murray, S. A.; Green, J. C.; Tailor, S. B.; Meek, S. J. Enantioꢀ and
Diastereoselective 1,2ꢀAdditions to αꢀKetoesters with Diborylmeꢀ
thane and Substituted 1,1ꢀDiborylalkanes. Angew. Chem. Int. Ed.
2016, 55, 9065ꢀ9069. (f) Shi, Y.; Hoveyda, A. H. Catalytic SN2′ꢀ and
Enantioselective Allylic Substitution with a Diborylmethane Reagent
and Application in Synthesis. Angew. Chem. Int. Ed. 2016, 55, 3455ꢀ
3458.
(4) (a) Lee, C. H.; McDonald, R.; Hall, D. G. Enantioselective
preparation and chemoselective crossꢀcoupling of 1,1ꢀdiboron comꢀ
pounds. Nat. Chem. 2011, 3, 894ꢀ899. (b) Feng, X.; Jeon, H.; Yun, J.
Regioꢀ and Enantioselective Copper(I)ꢀCatalyzed Hydroboration of
Borylalkenes: Asymmetric Synthesis of 1,1ꢀDiborylalkanes. Angew.
Chem. Int. Ed. 2013, 52, 3989ꢀ3992.
(5) For a recent nonꢀcatalytic asymmetric route to geminal silylꢀ
boronates, see: (a) Bootwicha, T.; Feilner, J. M.; Meyers, E. L.; Agꢀ
garwal, V. K. Iterative assembly line synthesis of polypropionates
with full stereocontrol. Nat. Chem. 2017, 9, 896ꢀ902. (b) Aggarwal,
V. K.; Binanzer, M.; de Ceglie, M. C.; Gallanti, M.; Glasspoole, B.
W.; Kendrick, S. J. F.; Sonawane, R. P.; VazquezꢀRomero, A.; Webꢀ
ster, M. P. Asymmetric Synthesis of Tertiary and Quaternary Allylꢀ
and Crotylsilanes via the Borylation of Lithiated Carbamates. Org.
Lett. 2011, 13, 1490ꢀ1493. (c) Barsamian, A. L.; Wu, Z.; Blakemore,
P. R. Enantioselective synthesis of αꢀphenylꢀ and αꢀ
(dimethylphenylsilyl)alkylboronic esters by ligand mediated stereoinꢀ
ductive reagentꢀcontrolled homologation using configurationally
labile carbenoids. Org. Biomol. Chem. 2015, 13, 3781ꢀ3786.
(14) Mlynarski, S. N.; Karns, A. S.; Morken, J. P. This is a
modification of the following reference and its details will be reported
separately: Direct Stereospecific Amination of Alkyl and Aryl Pinacol
Boronates. J. Am. Chem. Soc. 2012, 134, 16449ꢀ16451.ꢀ
(15) Cossrow, J.; Rychnovsky, S. D. Optically Pure αꢀ
(Trimethylsilyl)benzyl Alcohol: A Practical Chiral Auxiliary for Oxoꢀ
carbenium Ion Reactions. Org. Lett. 2002, 4, 147ꢀ150.ꢀ
(16) (a) Reḿond, E.; Martin, C.; Martinez, J.; Cavelier, F. Siliconꢀ
Containing Amino Acids: Synthetic Aspects, Conformational Studies,
and Applications to Bioactive Peptides. Chem. Rev. 2016, 116,
11654ꢀ11684. (b) Ramesh, R.; Reddy, D. S. Quest for Novel Chemiꢀ
cal Entities through Incorporation of Silicon in Drug Scaffolds. J.
(6) Meng, F.; Jang, H.; Hoveyda, A. H. Exceptionally Eꢀ and βꢀ
Selective NHC–CuꢀCatalyzed ProtoꢀSilyl Additions to Terminal Alꢀ
kynes and Siteꢀ and Enantioselective ProtoꢀBoryl Additions to the
Resulting Vinylsilanes: Synthesis of Enantiomerically Enriched Viciꢀ
nal and Geminal Borosilanes. Chem. Eur. J. 2013, 19, 3204ꢀ3214.
Med.
Chem.
2017,
ASAP,
http://dx.doi.org/10.1021/acs.jmedchem.7b00718.
ACS Paragon Plus Environment

Page 5 of 6
ACS Catalysis
(17) (a) Mah, R. W. H.; Matteson, D. S. Neighboring Boron in Nuꢀ
Directing Modifier on the Boron Atom. Chem. Lett. 2011, 40, 916ꢀ
918. (b) Zhang, Z.ꢀ Q.; Yang, C.ꢀ T.; Liang, L.ꢀ J.; Xiao, B.; Lu, X.;
Liu, J.ꢀ H.; Sun, Y.ꢀ Y.; Marder, T. B.; Fu, Y. Copperꢀ
Catalyzed/Promoted Crossꢀcoupling of gemꢀDiborylalkanes with
Nonactivated Primary Alkyl Halides: An Alternative Route to Alkylꢀ
boronic Esters. Org. Lett. 2014, 16, 6342ꢀ6345.
(20) Shirakawa, K.; Arase, A.; Hoshi, M. Preparation of (E)ꢀ1ꢀ
Alkenylboronic Acid Pinacol Esters via Transfer of Alkenyl Group
from Boron to Boron. Synthesis, 2004, 11, 1814ꢀ1820.
(21) Takale, B. S.; Tao, S. M.; Yu, X. Q.; Feng, X. J.; Jin, T.; Bao,
M.; Yamamoto, Y. Exclusive Chemoselective Reduction of Imines in
the Coexistence of Aldehydes Using AuNPore Catalyst. Org. Lett.
2014, 16, 2558ꢀ2561.
cleophilic Displacement. J. Am. Chem. Soc. 1963, 85, 2599ꢀ2603. (b)
For effect of sodium triflate: Lovinger, G. J.; Aparece, M. D.;
Morken, J. P. PdꢀCatalyzed Conjunctive CrossꢀCoupling between
GrignardꢀDerived Boron “Ate” Complexes and C(sp2) Halides or
Triflates: NaOTf as a Grignard Activator and Halide Scavenger. J.
Am. Chem. Soc. 2017, 139, 3153ꢀ3160.
(18) (a) Smitrovich, J. H.; Woerpel, K. A. Oxidation of Sterically
Hindered Alkoxysilanes and Phenylsilanes under Basic Conditions. J.
Org. Chem. 1996, 61, 6044ꢀ6046. (b) Walleser, P.; Bruckner, R. Steꢀ
reocontrolled Synthesis of a C1–C10Building Block (“Southwestern
Moiety”) for the Unnatural Enantiomers of the Polyene Polyol Antiꢀ
biotics Filipin III and Pentamycin: A SultoneꢀForming RingꢀClosing
Metathesis for Protection of Homoallylic Alcohols. Eur. J. Org.
Chem. 2014, 15, 3210ꢀ3224.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(19) (a) Ihara, H.; Ueda, A.; Suginome, M. Rutheniumꢀcatalyzed
C–H Silylation of Methylboronic Acid Using a Removable αꢀ
ACS Paragon Plus Environment

ACS Catalysis
Page 6 of 6
GRAPHICAL ABSTRACT:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
6
ACS Paragon Plus Environment