Directed RhI-Catalyzed Asymmetric Hydroboration of Prochiral 1-Arylcycloprop-2-Ene-1-Carboxylic Acid Derivatives

Article abstract of DOI:10.1002/chem.201704443

A full account on rhodium-catalyzed asymmetric, directed hydroboration of functionalized prochiral cyclopropenes affording enantiomerically enriched cyclopropylboronates is reported. The scope and limitations of two alternate directing groups, ester and carboxamide, are evaluated. It was found that hydroboration of esters appeared to be more sensitive to substitution in the aromatic ring of the substrates. Specifically, ortho-halogens were detrimental for diastereo- and enantioselectivity, possibly because of additional coordination with rhodium. In contrast, more Lewis-basic amide directing groups allowed for stronger chelation to the transition metal, leading to consistently high diastereo- and enantioselectivity in hydroboration across a broader range of substrates.

Full text of DOI:10.1002/chem.201704443

A Journal of
Accepted Article
Title: Directed Rh(I)-Catalyzed Asymmetric Hydroboration of Prochiral
1-Arylcycloprop-2-ene-1-carboxylic Acid Derivatives
Authors: Andrew Edwards, Michael Rubin, and Marina Rubina
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201704443
Link to VoR: http://dx.doi.org/10.1002/chem.201704443
Supported by

10.1002/chem.201704443
Chemistry - A European Journal
FULL PAPER
Directed Rh(I)-Catalyzed Asymmetric Hydroboration of Prochiral
1-Arylcycloprop-2-ene-1-carboxylic Acid Derivatives
Andrew Edwards,[a] Marina Rubina,[a,b] and Michael Rubin*[a,c]
Abstract A full account on rhodium-catalyzed asymmetric, directed
hydroboration of functionalized prochiral cyclopropenes affording
Results and Discussion
enantiomerically enriched cyclopropylboronates is reported.
The
scope and limitations of two alternate directing groups, ester and
carboxamide, are evaluated. It was found that hydroboration of
esters appeared to be more sensitive to substitution in the aromatic
ring of the substrates. Specifically, ortho-halogens were detrimental
for diastereo- and enantioselectivity, potentially, due to additional
coordination with rhodium. In contrast, more Lewis-basic amide
directing groups allowed for stronger chelation to the transition metal,
leading to consistently high diastereo- and enantioselectivity in
hydroboration across a broader range of substrates.
Cyclopropylboronic acid derivatives are primarily employed as
stable, but reactive surrogates of cyclopropyl nucleophile.
Cyclopropylboronates are normally obtained via a reaction of
trialkylborates with cyclopropylmetal derivatives,[ 14 ] 1,3-cycliz-
ation of acyclic boronate precursors,[15] or [1+2]-cycloaddition of
carbenoid species to vinylboronates.[16] There are only a handful
of examples exploiting non-catalyzed hydroboration of the
smallest cyclic olefins to obtain these useful synthons.[17] Two
reports, succeeding our communication,[13] were published
independently by the Tian and Lin, and Tortosa groups,
showcasing copper-catalyzed formal hydroboration of cyclo-
propenes 1.[18] This reaction was reported as a non-directed
process, in which the facial selectivity was governed by a steric
effect to install the boronate moiety trans to the largest
substituent RL (Scheme 1). This was in contrast to our Rh-
catalyzed methodology that utilized a directing group (DG,
typically an ester function) in substrate 3, to furnish sterically
hindered cis-substituted cyclopropyl boronates 4 (Scheme 1). A
strong directing effect was also required, although not sufficient,
to obtain high degrees of enantioselectivity in this reaction.13
Introduction
Chiral cyclopropanes are found in a variety of natural prod-
ucts[1,2] and medicinal agents,[3] and are also highly sought-after
synthons and ligands for organic synthesis[4] and asymmetric
catalysis.[5] Such scaffolds are typically assembled via diastere-
oselective 1,3-ring closures[6] or asymmetric cyclopropanation
reactions.[ 7 , 8 ] Another less established, but potent method
involves a chemo- and diastereoselective installation of additi-
onal substituents into a pre-formed chiral or prochiral cycloprop-
ane.[9] The strain release-driven addition of different entities to
cyclopropenes has emerged as a unique tool that allows for
assembly of chiral cyclopropane scaffolds with complementary
substitution patterns.[10] Several research groups contributed
their work to the development of synthetic methodologies
exploiting ring-retentive, metal-catalyzed[11] and organocatalytic12
stereoselective additions of various reagents to cyclopropenes
en route to chiral cyclopropanes. We previously communicated
a first example of the carboxylate-directed asymmetric Rh-
catalyzed hydroboration of prochiral 3,3-disubstituted cycloprop-
enes to produce enantiomerically enriched cyclopropylboronic
esters.[13] Herein, we demonstrate the use of a carboxamide
function as an alternative, superior directing group and provide
insight into the origins of diastereo- and enantioselectivity of this
transformation.
RL
RS
RL
RS
Bpin
Cu(I)L* (cat.)
B2pin2
[Ref. 18]
1
3
2
4
R
DG
R
DG
Bpin
Rh(I)L* (cat.)
HBpin
[Ref. 13] and
this work
Scheme 1.
We have recently reported an improved protocol for catalytic
cyclopropenation of trimethylsilylacetylene,[19] which streamlined
access to esters 3 (DG = CO2Me). This allowed us to perform
an in-depth study of the asymmetric hydroboration reaction with
respect to substrate scope and limitations. Previously, we have
shown a single example of a 1-aryl-substituted ester (methyl 1-
phenylcycloprop-2-ene-1-carboxylate 3a) employed in this
transformation.[13] This result was now reproduced by treating
cyclopropene 3a with pinacolborane (Bpin) in the presence of
rhodium catalyst and (R)-BINAP (Method A, Table 1, entry 1). 1-
Naphthylcyclopropene carboxylate (3b, entry 2) was slightly less
efficient than the benchmark example in terms of selectivity
(Method B). All cyclopropenes possessing para-substituted
phenyl groups (3c-e) at C-1 provided the corresponding
cyclopropylboronates 4c-e with similar diastereo- and
enantioselectivity (entries 3-5). The stereochemical outcome in
[a]
Department of Chemistry
University of Kansas,
1251 Wescoe Hall Drive, Lawrence, Kansas 66045, USA
E-mail: mrubin@ku.edu
[b]
[c]
Peoples’ Friendship University of Russia, 6 Miklukho-Maklaya St.,
Moscow 117198, Russian Federation
Department of Chemistry
North Caucasus Federal University
1a Pushkin St., Stavropol 355009, Russian Federation
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
1
This article is protected by copyright. All rights reserved.

10.1002/chem.201704443
Chemistry - A European Journal
FULL PAPER
Table 1. Catalytic Asymmetric Hydroboration of 1-Arylcycloprop-2-ene-1-carboxylates 3
[Rh(COD)Cl]2 (3 mol%)
(R)-BINAP (6 mol%)
R
CO2Me
R
(S) CO2Me
R
(S) CO2Me
(R)
+
(S)
HBpin (1.0 equiv.)
THF (1.0 M) at RT
Bpin
Bpin
3
4
5
major
minor
er[c]
3
R
4
yield, %[a]
dr (4:5)[b]
99:1
97:3
99:1
98:2
98:2
85:15
96:4
89:11
54:46
[α]D20 (c)[d]
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
3f
3g
3h
3i
Ph
4a
4b
4c
4d
4e
4f
4g
4h
4i
99 (A)
99 (B)
94 (A)
80 (A)
89 (B)
90 (B)
75 (B)
91 (B)
55(85) (A)
99:1
97:3
98:2
96:4
97:3
99:1
96:4
97:3
90:10
88:12
90:10
68:32
83:17
93:7
83:17
94:6
-57.9 (4.07)
-40.6 (2.27)
-62.4 (2.30)
-40.6 (0.90)
-51.9 (1.17)
-35.5 (1.30)
-39.1 (1.33)
-53.5 (1.20)
-49.2 (0.77)
1-naphthyl
4-MeC6H4
4-FC6H4
4-BrC6H4
3-BrC6H4
3-CF3C6H4
2-ClC6H4
2,3-F2C6H3
10
3j
2,4-F2C6H3
4j
60(87) (B)
57:43
-48.5 (0.87)
11
12
13
14
3k
3l
3m
3n
2-Cl-4-FC6H3
2-Cl-4,5-F2C6H2
2,4-Cl2C6H3
4k
4l
4m
4n
92 (B)
83 (B)
83 (B)
81 (B)
94:6
-47.8 (2.37)
-38.7 (1.43)
-54.5 (1.63)
-38.2 (1.67)
75:25
84:16
97:3
2-Br-4-FC6H3
[a] Isolated yield of purified products (NMR yields are provided in parentheses for compounds 4i and 4j). Methods (A) and (B) correspond to addition of
cyclopropene as neat oil or as a solution in THF, respectively. [b] Diastereomeric ratios were determined by 1H NMR or HPLC analyses of crude
reaction mixtures. [c] Enantiomeric ratios were determined by chiral HPLC analyses of purified products (see Experimental Part for details) [d]
Concentrations are provided in g/100 mL of dichloromethane.
XOC
Ar
Ar
Bpin
XOC
Bpin
4, X = OMe
7, X = NR2
5, X = OMe
8, X = NR2
Bpin
Ph
Ph
Ph
Ph
Bpin
P
P
Ph
Ph
Ph
Ph
RE
Rh
S
P
P
Rh
S
O
Y
X
X
EWG
Y
RE
O
EWG
12
15
MI
MI
Bpin
Cycle I
Ph
Ph
Ph
Ph
Cycle II
Ph
Ph
Ph
Bpin
P
P
Rh
O
P
S
P
S
Ph
Ph
Ph
Ph
Rh
Ph
H
P
P
Rh
Ar
COX
H
Y
9
X
X
EWG
11
Y
3, X = OMe
6, X = NR2
O
EWG
14
S
S
Ph
Ph
Ph
Ph
Ph
Ph
Ph
OA
HBpin
P
P
P
P
S
OA
HBpin
Rh
Rh
Ph
S
Y
X
O
X
O
EWG
EWG
10
Y
13
Scheme 2. Proposed mechanism for directed asymmetric hydroboration of cyclopropenes. Structure of the ligand chiral backbone is omitted for clarity and
substituted with a curved dashed line.
hydroboration of meta-substituted substrates was not that
straightforward. Thus, facial selectivity in the reaction of meta-
trifluoromethyl-substituted derivative (3f) was very high (entry 7),
while meta-bromosubstituted boronate 4f was obtained as a
2
This article is protected by copyright. All rights reserved.

10.1002/chem.201704443
Chemistry - A European Journal
FULL PAPER
mixture with a notable amount of diastereomeric product 5f
(entry 6). The enantioselectivity of hydroboration in both cases
remained high.
Rh(III)-complex 11, which undergoes subsequent stereo-
chemistry defining, irreversible migratory insertion producing
chiral cyclopropyl rhodium(III) complex 12. Finally, reductive
elimination affords cis-cyclopropyl boronate 4 and regenerates
the catalytically active species 9 (Cycle I). It is believed that
catalytic Cycle II (Scheme 2) may account for poor facial
selectivity observed in hydroboration of several ortho-halogen-
ated substrates. The complementary complex 13 produced via
η2-coordination of the aromatic ring to the metal must experience
a significant back-donation component, since it is most efficiently
realized for more electron-deficient aryl rings. Furthermore,
fluorophilic interaction[21] could play an important role in stabiliz-
ation of such complexes with ortho-fluorosubstituted aryl rings.
Subsequent steps, including oxidative addition into B-H bond to
ortho-Halogenated 1-arylcyclopropene carboxylates were
generally less selective than para- and meta-analogs (entries 8-
14). All difluoro-substituted substrates, particularly those
possessing a fluorine atom in the 2-position, afforded lower
yields and poor diastereomeric ratios, with an average er near
9:1 for the main diastereomer (entries 9, 10, and 12). The lowest
enantioselectivity for the major product was obtained for
cyclopropenes 3k and 3m, both bearing an ortho-chlorophenyl
group at C-1 and an additional halogen in the 4-position (entries
11 and 13). For all fluoro-substituted analogs, the placement of
fluorine in any position other than para- (entries 4, 11, 14)
resulted in deterioration of diastereoselectivity (entries 9, 10, 12). form Rh(III)-complex 14, followed by syn-specific concerted
Based on the observations described above, we propose
the following mechanistic rationale (Scheme 2). The catalytic
cycle begins with coordination of cyclopropene 3 to chiral
rhodium(I) species 9, which can be achieved in two different
ways, leading to complementary facial selectivity. In the prefer-
red pathway, coordination of the cyclopropene double bond with
simultaneous chelation through the carbonyl moiety would
produce cationic η2-species 1020 (Scheme 2, Cycle I). Oxidative
addition of rhodium into the H-B bond of pinacolborane provides
hydrorhodation of cyclopropene and reductive elimination,
affords trans-cyclopropyl boronate 5 (Scheme 2, Cycle II).
An important implication of the proposed mechanistic
rationale was
a
potential possibility to address poor
diastereoselectivity by employing a directing group capable of
stronger binding to the transition metal. Such modification would
help shift the equilibrium between species 10 and 13 towards
the former and deter the catalytic Cycle II (Scheme 2).
Table 2. Preparation of 1-arylcycloprop-2-ene-1-carboxamides 6
O
R1 CO2H
R1 CO2Me
NaOH (aq)
MeOH/THF
1. (COCl)2
2. R2R3NH
R1
NR2R3
SiMe3
(18)
6
17
16
16
R1
17
Yield, %[a]
88 [23]
91 [23]
95
96
92
88
84
94
86 [23]
82 [23]
84
93
97
R2
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
R3
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Bn
i-Pr
6
Yield, %[a]
89 [23]
92 [23]
86
78
89
84
93
85
85 [23]
83 [23]
89
94
82
76 [23]
59 [23]
83 [23]
95 [23]
88 [23]
80 [23]
83 [23]
85 [23]
81 [23]
77 [23]
92 [23]
95 [22][b]
1
2
3
4
5
6
7
8
16a
16b
16с
16d
16e
16g
16h
16i
16j
16k
16l
16m
16n
16a
Ph
17a
17b
17с
17d
17e
17g
17h
17i
6a
6b
6c
6d
6e
6g
6h
6i
6j
6k
6l
6m
6n
6o
6p
6q
6r
1-Naphthyl
4-MeC6H4
4-FC6H4
4-BrC6H4
3-CF3C6H4
2-ClC6H4
2,3-F2C6H3
2,4-F2C6H3
2-Cl-4-FC6H3
2-Cl-4,5-FC6H2
2,4-Cl2C6H3
2-Br-4-FC6H3
Ph
9
17j
17k
17l
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
17m
17n
17a
17a
17a
17a
17a
17a
17a
17a
17a
17a
17a
Et
Bn
i-Pr
-(CH2)5-
-(CH2)2O(CH2)2-
Me
i-Pr
Me
Bu
c-C7H13
2-FuCH2
CH2CH=CH2
Et
Bn
Bn
OMe
H
H
H
6s
6t
6u
6v
6w
6x
6y
6z
H
Et
Me
[a] Isolated yields of purified products. References for previously reported compounds are given in brackets. Experimental details for preparation of
newly synthesized compounds are provided in the Supporting Information section. [b] Prepared via a base-assisted 1,2-elimination of 2-bromo-N,N-
diethyl-1-methylcyclopropanecarboxamide.
3
This article is protected by copyright. All rights reserved.

10.1002/chem.201704443
Chemistry - A European Journal
FULL PAPER
Table 3. Optimization of the chiral phosphine ligand for asymmetric hydroboration of carboxamide 6a
NEt2
O
NEt2
(R) O
NEt2
[Rh(COD)Cl]2 (3 mol%)
chiral ligand (6 mol%)
(S)
(S)
Ph
Ph
Ph
O
+
(S)
HBpin (1.0 equiv.)
THF (1.0 M) at RT
Bpin
Bpin
6a
7a
8a
Ligand (CAS Number)
(R)-BINAP (76189-55-4)
(R)-BINAP
(R)-BINAP
(R)-BINAP
(R)-Tol-BINAP (99646-28-3)
(R)-DM-BINAP (137219-86-4)
(R,R)-Norphos (71042-55-2)
(S)-Phanephos (192463-40-4)
(S)-BINAPINE (528854-26-4)
(R)-BINAM-P (74974-14-4)
(S,S)-Chiraphos (64896-28-2)
(S,S)-Me-Duphos (136735-95-0)
(R,R,S,S)-Duanphos (528814-26-8)
Taniaphos SL-T001-1 (1003012-96-1)
Josiphos SL-J008-1 (166172-63-0)
Price[a]
Time[b]
30 min
4 h
Yield, %[c]
66
77
81
97
89
90
96
86
99
81
99
80
73
27
55
dr (7:8 ratio)[d]
>98:2
er[e]
ND
ND
ND
1
2
3
4
5
6
7
8
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
97:3
>98:2
98:2
>98:2
95:5
4 h
72.60
76.80
18 h
30 min
4 h
2 h
1 h
30 min
8 h
30 min
2 h
18 h
42 h
42 h
96:4
97:3
98:2
97:3
98:2
>99:1
34:66
3:97
82:18
81:19
ND
252.07
1322.78
432.49
1113.36
387.70
175.71
159.92
417.65
484.05
556.33
9
10
11
12
13
14
15
93:7
7:93
[a] Relative prices for ligands are given in USD/mmol, as listed in Sigma-Aldrich on-line product catalog for the United States, as of summer 2017. [b]
Time required for the reactions to achieve maximum conversion. [c] NMR yields measured for crude reaction mixtures using p-xylene as the internal
standard. [d] Measured by NMR or HPLC of crude mixtures. Notation >98:2 indicates that minor isomer 8a could not be observed by these methods.
[e] Enantiomeric ratios (1S,2R)-7a:(1R:2S)-7a were determined by chiral HPLC analyses of crude mixtures.
Table 4. Catalytic Asymmetric hydroboration of 1-arylcycloprop-2-ene-1-carboxamides 6
R3 R2
N
R3 R2
R3 R2
[Rh(COD)Cl]2 (3 mol%)
N
N
R1
R1 (S)
R1 (S)
(R)-BINAP (6 mol%)
O
(R) O
Bpin
O
(S)
+
HBpin (1.0 equiv.)
THF (1.0 M) at RT
Bpin
6
7
8
major
minor
6
R1
R2
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Bn
i-Pr
R3
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Bn
i-Pr
7
yield, %[a]
dr (7:8)[b]
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
97:3
er[c]
[α]D20 (c)[d]
1
2
3
4
5
6
7
8
6a
6b
6c
6d
6e
6g
6h
6i
6j
6k
6l
6m
6n
6o
6p
6q
6r
Ph
7a
7b
7c
7d
7e
7g
7h
7i
7j
7k
7l
7m
7n
7o
7p
7q
7r
92
88
92
88
85
87
96
91
96
85
91
98
98
98
83
69
48
73
82
68
81
94
34
58
96:4
95:5
91:9
90:10
87:13
92:8
88:12
92:8
96:4
97:3
97:3
98:2
95:5
97:3
83:17
98:2
96:4
96:4
92:8
95:5
92:8
91:9
94:6
94:6
94:6
92:8
+43.2 (1.13)
+151.8 (1.87)
+44.6 (1.30)
+38.8 (1.53)
+21.3 (1.60)[e]
+9.6 (1.10)[e]
+140.6 (2.23)[e]
+103.5 (1.30)
+104.6 (1.90)
+139.1 (1.67)
+121.8 (2.30)[e]
+132.1 (2.43)[e]
+105.2 (2.77)[e]
+9.7 (0.90)
+52.0 (1.33)
+7.8 (0.73)
-59.2 (0.83)
-8.8 (1.83)
+33.1 (1.47)
-64.6 (0.73)
-30.6 (1.10)
-23.8 (1.23)
-35.8 (0.57)
-35.7 (0.37)
1-Naphthyl
4-MeC6H4
4-FC6H4
4-BrC6H4
3-CF3C6H4
2-ClC6H4
2,3-F2C6H3
2,4-F2C6H3
2-Cl-4-FC6H3
2-Cl-4,5-FC6H2
2,4-Cl2C6H3
2-Br-4-FC6H3
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
9
10
11
12
13
14
15
16
17
18
19
20
21
22
22
24
-(CH2)5-
-(CH2)2O(CH2)2-
Me
i-Pr
Me
Bu
6s
6t
Bn
Bn
OMe
H
H
H
7s
7t
6u
6v
6w
6x
6y[f]
7u
7v
7w
7x
7y
>98:2
>98:2
>98:2
>98:2 (E)
>98:2 (Z)
>98:2
c-C7H13
2-FuCH2
CH=CHMe
Ph
Ph
H
E:Z = 1:2
92
25
6z
Me
Et
Et
7z
+49.5 (0.80)[e]
[a] Isolated yields of purified products. [b] Diastereomeric ratios were determined by 1H NMR or HPLC analyses of crude reaction mixtures. [c]
Enantiomeric ratios were determined by chiral HPLC analyses of purified products (see Experimental Part for details) [d] Concentrations are provided in
g/100 mL of dichloromethane. [e] Measured in chloroform. [f] N-allylamide (R2 = allyl) was used as starting material in this reaction.
4
This article is protected by copyright. All rights reserved.

10.1002/chem.201704443
Chemistry - A European Journal
FULL PAPER
Our previous experience with alkali metal-assisted nucleophilic
additions to cyclopropenes directed by a carboxamide function
at C-3[ 23 ] prompted us to probe this directing group in the
transition metal-catalyzed hydroboration. Substrates required
for this investigation, prochiral 1-arylcycloprop-2-ene-1-carbox-
amides 6, are now easily available from acyl chlorides generated
in situ from the corresponding 1-arylcycloprop-2-ene-1-
carboxylic acids 17.[24] The acids, in turn, can be prepared by
hydrolysis of esters 16[19,25] accompanied by desilylation of the
cyclopropene double bond. This two-step protocol was
employed for preparation of N,N-diethylcycloprop-2-ene-1-
carboxamides 6a-n, bearing various aryl substituents at C-1
(Table 2, entries 1-13). Also, employing 1-phenylcycloprop-2-
ene-1-carboxylic acid 17a and different amines 18, we have
synthesized a series of secondary (6v-y, entries 21-24) and
tertiary amides 6o-t (entries 14-19), including Weinreb amide 6u
(entry 20).[23]
atom in N,N-diisopropylamide 6p lowered the overall yield of
product 7p, as well as the enantioselectivity, although cis-
diastereoselectivity remained high (entry 15). Likewise,
hydroboration of amide 6t bearing an isopropyl and a benzyl
group at nitrogen atom displayed, but less dramatic, reduction of
enantioselectivity 7t (entry 19). An attempt to employ derivatives
To test the efficiency of cyclopropene carboxamides in the
directed asymmetric hydroboration we subjected compound 6a
to standard reaction conditions with pinacolborane in the
presence of [Rh(COD)Cl]2 (3 mol%) and chiral diphosphine
ligand (6 mol%). A series of chiral ligands were screened, which
have previously demonstrated promising results in the reaction
with esters.[13] Our main goal for this optimization was to
maximize conversion and the enantioselectivity, as high
diastereoselectivity has been routinely observed in reactions of
carboxamides.
Striving to develop an economically-viable
method, we also took into consideration the relative cost of chiral
diphosphine ligands. Our results showed that the most
affordable (R)-BINAP was superior or on par with many of the
more expensive ligands tested (Table 3). (R,R)-Norphos and
(S)-BINAPINE outperformed (R)-BINAP (Table 3, entries 7, 9),
but were cost-prohibitive for the preparative method
development. Furthermore, the reactivity and selectivity of
(R,R)-Norphos and (S,S)-Chiraphos appeared to be specific to
substrate 6a. Reactions with other cyclopropenes provided
variable selectivities in the presence of these ligands, while
hydroboration catalyzed by (R)-BINAP complex afforded
consistently good results for all carboxamides tested (Table 4).
Indeed, all N,N-diethylamides 6b-h derived from cycloprop-2-
enecarboxylic acids bearing various mono-substituted aryl
groups at C-1, reacted smoothly affording (+)-(1S,2R)-boronates
7b-h (Table 4, entries 2-7) in high yields as single diastereomers,
although optical purity of the products was generally somewhat
lower than that of the corresponding ester analogs 4b-h (Table 1,
entries 2-8). However, amides 6i-n displayed greater diastereo-
and enantioselectivity (Table 4, entries 8-13), as compared to
parent poly-halogenated arylcyclopropyl esters 3i-n (Table 1,
entries 9-14).
Figure 1. ORTEP drawing of (1S,2R)-(+)-N,N-Dibenzyl-1-phenyl-2-(4,4,5,5-
tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopropane-1-carboxamide (7o) showing
50% probability amplitude displacement ellipsoids.
Bpin
Bpin
Ph
Ph
P
H
P
P
P
Rh
O
Ph
Rh
O
Ph
H
vs
X
X
R
11
18
R
Bpin
Bpin
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
P
P
P
P
Rh
Rh
S
S
O
O
X
X
12
R
R
19
With these results in hand, we examined the compatibility
of this reaction with various substituents at the nitrogen atom in
the amide moiety. In spite of increased steric hindrance around
the directing group, N,N-dibenzylamide 6o afforded the
corresponding cis-cyclopropyl boronate 7o very selectively
(Table 3, entry 14). The relative and absolute configuration of
this product was unambiguously assigned by X-ray crystal-
lography (Figure 1). An excessive steric hindrance at nitrogen
(R) Ar
Ar
(S)
(R)
(S)
ent-4, X = OMe
ent-7, X = NR2
4, X = OMe
7, X = NR2
COX
Bpin
XOC
Bpin
Figure 2. Proposed rationale for the origins of enantioselectivity in the Rh-
catalyzed hydroboration of cyclopropenyl esters and amides.
5
This article is protected by copyright. All rights reserved.

10.1002/chem.201704443
Chemistry - A European Journal
FULL PAPER
of cyclic amines (6q,r) led to a notable decrease of chemical
yield; however, provided consistently high diastereo- and enanti-
opurity of the resulting boronates 7q,r (entries 16, 17). Finally,
Weinreb amide 6u, amenable for subsequent functionalization,26
reacted smoothly to provide cis-boronate 7u (entry 20).
Hydroboration of secondary amides bearing either a primary
(6v) or a secondary (6w) alkyl group at nitrogen atom proved
very efficient and highly selective (entries 21-22). N-(furan-2-
ylmethyl)-substituted analog 7x was also obtained very
selectively, although chemical yield in this reaction was rather
poor (entry 22). Interestingly, hydroboration of allylamide 6y
was accompanied by the Rh-catalyzed 1,2-migration of the
double bond to afford a thermodynamically more stable N-prop-
2-enyl amide 7y as a mixture of E- and Z-isomers (entry 24).
We have also evaluated the catalytic hydroboration of 3-methyl-
cyclopropene-3-carboxamide 6z. The corresponding boronate
7z was obtained in high yield and reasonably high enantio-
selectivity, as a sole diastereomer (entry 25).
The observed enantioselectivity can be attributed to the
predominant formation of the octahedral Rh(III)-complex 11 with
a left-handed chelation of cyclopropenyl carboxylate (or carbox-
amide) (Figure 2). This orientation, as opposed to the alternate
arrangement in complex 18, allows for minimal steric interaction
between the phenyl rings of the ligand and the substrate, leading
to the formation of cyclopropylrhodium complex 12 and,
ultimately, products 4 and 7 (Figure 2).
with BH3 complexes and alkylboranes, affording racemic cyclo-
propylboranes[27] or products of their thermal rearrangements.[28]
We also examined the possibility to employ catecholborane as a
hydroborating agent in the Rh(I)-catalyzed reaction of cyclo-
propene 6a. Fast and complete conversion of the starting
material was observed, however, the obtained cyclopropyl-
boronates 21 were hydrolytically unstable and readily decom-
posed during isolation attempts.
Ar
CO2Me
Ar
DIBAL
Et2O
OH
3a: Ar = Ph
3i: Ar = 2,3-F2C6H3
3j: Ar = 2,4-F2C6H3
22a: Ar = Ph: 79% [Ref. 28]
22i: Ar = 2,3-F2C6H3: 80%
22j: Ar = 2,4-F2C6H3: 79% [Ref. 28]
Ar
Rh(I)-(R)-BINAP (cat.)
OH
HBPin
23a: Ar = Ph: 51%
23j: Ar = 2,4-F2C6H3: 49%
Scheme 4.
22a: Ar = Ph
22i: Ar = 2,3-F2C6H3
Ar
OH
22j: Ar = 2,4-F2C6H3
MOMCl
Et3N/CH2Cl2
Ac2O
Py
TBSCl
Et3N/CH2Cl2
NEt2
NEt2
NEt2
O
Ph
Ph
Ph
+
O
B
O
B
Rh(I)-(R)-BINAP
Ph
Ph
Ar
9-BBN
OAc
OMOM
OTBS
6a
trans-20
cis-20
24a
25a
26a: Ar = Ph, 95%
26i: Ar = 2,3-F2C6H3, 92%
26j: Ar = 2,4-F2C6H3, 90%
dr (trans:cis) 70:30 (87:13 in the absence of catalyst),
er 50:50 (trans), 73:50 (cis)
combined yield 59% (63% in the absence of catalyst)
Rh(I)-(R)-BINAP
HBPin
NEt2
Rh(I)-(R)-BINAP
Rh(I)-(R)-BINAP
Ph
O
HBPin
HBPin
Rh(I)-(R)-BINAP
decomposition
O
B
HBcat
Ph
Ph
Ar
O
OMOM
OAc
OTBS
21
PinB
PinB
PinB
Scheme 3.
27a: 81%
dr 98:2, er 68:32
28a: 83%
dr 96:4, er 79:21
29a: Ar = Ph, 83%,
dr 92:8, er 80:20
29i: Ar = 2,3-F2C6H3, 72%,
dr 71:29, er 82:18
A
scale up hydroboration using standard reaction
conditions and 2 mmols of 6a was also performed to obtain
product 7a in excellent yield (96%) and high diastereo- and
enantioselectivity (dr >99:1, er 94:6). We also tested the
possibility to employ different hydroborating agents in this
transformation. Hydroboration or 6a with 9-BBN carried out in
the presence of Rh(I) complex with chiral BINAP ligand afforded
a mixture of racemic cyclopropropylboranes trans-20 (major
product, resulting from non-directed process) and partially
enriched cis-20 (minor product) (Scheme 3). Very similar
diastereoselectivity and yield were obtained upon hydroboration
of 6a with 9-BBN in the absence of Rh-catalyst, which suggests
significant contribution of a background, non-catalytic hydro-
boration process. This observation is in accord with numerous
literature reports on non-catalyzed reactions of cyclopropenes
(81:19 for minor)
29j: Ar = 2,4-F2C6H3, 79%,
dr 67:33, er 82:18
(73:27 for minor)
Scheme 5.
On an earlier submission of this manuscript, a reviewer
suggested the possibility to flip the diastereoselectivity of the
reaction by accentuating the “ortho-fluoro” effect described
above. To test this idea, we synthesized cyclopropenes 22, 24-
26, bearing weakly-directing[29] alkoxymethyl substituents. We
first probed alcohols 22a and 22j, obtained by reduction of the
corresponding esters 3a and 3j with DIBAL.[30] The hydroxy-
methyl group appeared to be incompatible with the reaction
6
This article is protected by copyright. All rights reserved.

10.1002/chem.201704443
Chemistry - A European Journal
FULL PAPER
(<8 ppm residual oxygen and moisture) using a combination of glovebox
and standard Schlenk techniques. After quench the reaction mixtures
and compounds were treated on air. All the obtained materials were
moisture and oxygen stable at ambient temperatures. Representative
procedures are provided below. See Supporting Information for the full
account.
conditions, potentially, due to rapid protonolysis of the interm-
ediate cyclopropyl rhodium species. As a result, cyclopropanes
23[ 31 ] and 23j were the only products isolated from these
reactions. Next, MOM ether 24a, acetate 25a, and silyl ethers
26a,i,j were subjected to the catalytic hydroboration reaction
under the standard reaction conditions. The parent substrates
bearing an unsubstituted phenyl ring (24a, 25a, 26a) reacted
selectively cis- to the protected primary alcohol function. The
diastereoselectivity in the series 27a, 28a, 29a decreased only
slightly with increase of the protecting group size (Scheme 5). In
sharp contrast, the facial selectivity in hydroboration of ortho-
fluorinated substrates 26i,j was significantly lower (Scheme 5),
manifesting the contribution of the “ortho-fluoro” effect into
stabilization of reactive intermediates 13-15 (Scheme 2).
However, gain in thermodynamic stability appears to be
insufficient to outweigh the input of other effects (primarily the
significant sterics of the aryl ring) and allow for a complete
switch of the selectivity in the hydroboration reaction.
Hydroboration of Esters
(-)-Methyl (1S,2R)-1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborol-
an-2-yl)cyclopropanecarboxylate (4a), Typical Procedure A: A 1 mL
reaction vial was charged in a glove box with [Rh(COD)Cl]2 (7.4 mg,
0.015 mmol, 3 mol%) and (R)-BINAP (19.9 mg, 0.03 mmol, 6 mol%).
Freshly distilled anhydrous tetrahydrofuran (500 μL) was then added to
the vial via syringe and the mixture was stirred until homogenous.
Pinacol borane (73 μL, 0.50 mmol, 1.0 equiv.) was added via syringe
followed by methyl 1-phenylcycloprop-2-ene-1-carboxylate (3a)32 (87 mg,
0.50 mmol, 1.0 equiv.). The reaction was then stirred for 30 min at room
temperature. The product was purified by column chromatography on
Silica gel eluting with a mixture hexane/EtOAc (3:1). The titled compound
was obtained as pale-yellow oil, Rf 0.52. Yield 149 mg (0.493 mmol,
99%), dr >99:1, er 99:1. 1H NMR (400 MHz, CDCl3) δ 7.38 – 7.33 (m,
2H), 7.27 – 7.18 (m, 3H), 3.56 (s, 3H), 1.62 (dd, J = 8.4, 3.5 Hz, 1H), 1.30
(dd, J = 10.2, 3.5 Hz, 1H), 1.25 (s, 6H), 1.24 (s, 6H), 0.71 (dd, J = 10.2,
8.4 Hz, 1H).; 13C (126 MHz, CDCl3): δ 174.5, 140.4, 130.3 (+, 2C), 128.2
(+, 2C), 127.3 (+), 83.7 (2C), 52.5 (+), 34.5, 25.1 (+, 4C), 19.1 (-), 11.9;
FT IR (KBr, cm-1): 3052, 3026, 2978, 2949, 2932, 1718, 1435, 1410,
1391, 1371, 1313, 1292, 1215, 1198, 1167, 1144, 1107, 972, 858, 768,
752, 700, 667; HRMS (TOF ES): HRMS (TOF ES): Found 302.1685,
Conclusions
We have evaluated the scope and limitations of two alternate
directing groups, ester and carboxamide, in the metal-catalyzed,
asymmetric hydroboration of prochiral cyclopropenes. Hydro-
boration of esters appeared to be more sensitive to substitution
in the aromatic ring of the substrates. ortho-Halogens have been
particularly detrimental for diastereo- and enantioselectivity,
potentially, due to complementary coordination with rhodium.
This effect was also observed in the hydroboration of alkoxy-
methyl-substituted analogs. In contrast, a more Lewis-basic
amide directing groups allowed for stronger chelation to the
transition metal, leading to consistently high diastereo- and
enantioselectivity in hydroboration across a large variety of
substrates.
20
calculated for C17H23BO4 (M+) 302.1689 (1.3 ppm); [α]D -57.9o (c 4.07,
CH2Cl2).
(-)-Methyl (1S,2R)-1-(naphthalen-1-yl)-2-(4,4,5,5-tetramethyl-1,3,2-di-
oxaborolan-2-yl)cyclopropanecarboxylate (4b), Typical Procedure B:
A 1 mL reaction vial was charged in a glove box with [Rh(COD)Cl]2 (3.8
mg, 7.50 μmol, 3 mol%.) and (R)-BINAP (10 mg, 0.015 mmol, 6 mol%.).
Freshly distilled anhydrous tetrahydrofuran (500 μl) was then added to
the vial via syringe and the mixture was stirred until homogenous.
Pinacol borane (37.0 μL, 0.25 mmol, 1.0 equiv.) was added via syringe
followed by solution of methyl 1-(naphthalen-1-yl)cycloprop-2-ene-1-
carboxylate (3b)19 (56 mg, 0.25 mmol, 1.0 equiv.) in a minimal amount of
tetrahydrofuran (about 100 μL). The reaction mixture was stirred for 30
min at room temperature. The product was purified by column chrom-
atography on Silica gel eluting with a mixture hexane/EtOAc (3:1). The
titled compound was obtained as a colorless solid, mp 122.3-124.7 oC, Rf
0.52. Yield 87.2 mg (0.248 mmol, 99%), dr 97:3; er 97:3. 1H NMR (500
MHz, CDCl3): δ 8.29 (d, J = 8.4 Hz, 1H), 7.89 – 7.81 (m, 1H), 7.81 – 7.75
(m, 1H), 7.60 – 7.44 (m, 3H), 7.45 – 7.37 (m, 1H), 3.53 (s, 3H), 1.98 –
1.85 (m, 1H), 1.54 – 1.43 (m, 1H), 1.35 (s, 6H), 1.34 (s, 6H), 0.95 – 0.80
(m, 1H); 13C (126 MHz, CDCl3): δ 174.9, 136.9, 133.7, 133.3, 128.6 (+),
128.2 (+), 127.9 (+), 126.4 (+), 125.7 (+), 125.3 (+), 125.1 (+), 83.8 (2C),
52.6 (+), 32.1, 25.2 (+, 2C), 25.1 (+, 2C), 20.2 (-), 13.4; FT IR (KBr, cm-
1): 3045, 2976, 2949, 2930, 1717, 1437, 1414, 1391, 1312, 1288, 1223,
1202, 1165, 1144, 970, 858, 800, 779, 736, 685; HRMS (TOF ES):
HRMS (TOF ES): Found 352.1844, calculated for C21H25BO4 (M+)
352.1846 (0.6 ppm); [α]D20 -40.6o (c 2.27, CH2Cl2).
Experimental Section
General Information. NMR spectra were recorded on a 400 MHz NMR
instrument equipped with BBO probe or 500 MHz NMR instrument,
equipped with dual carbon/proton (CPDUL) cryoprobe at room
temperature. 13C NMR spectra were registered with broad ‐ band
decoupling. Signs (+) and (-) represent positive and negative intensities
of signals in 13C DEPT‐135 experiments. Column chromatography was
carried out employing silica gel with particle size 63-200 µm). Anhydrous
tetrahydrofuran was obtained by passing degassed HPLC ‐ grade
commercially available stabilizer-free solvent consecutively through two
columns with activated alumina (Innovative Technology). Anhydrous
DMSO was obtained by distilling degassed HPLC-grade solvent over
calcium hydride. Starting materials, cyclopropene esters 3a-n and 16a-n
were prepared according to our earlier published report.[19] Carboxylic
acids 17a, 17b, 17j, and 17k and carboxamides 6a,b, 6j,k, and 6o-y
were also synthesized according to the previously published
procedures.[23] Preparation of carboxylic acids 17c-e, 17g-i, and 17l-n as
well as amides 6c-e, 6g-i, 6l-n, is detailed in the Supporting Information.
All other solvents and reagents were purchased from commercial
vendors and used as received. All manipulations with transition metal
complexes and chiral ligands were conducted under inert atmosphere
Hydroboration of Amides
(1S,2R)-(+)-N,N-Diethyl-1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxa-
borolan-2-yl)cyclopropane-1-carboxamide (7a): This compound was
obtained via typical procedure B using N,N-diethyl-1-phenylcycloprop-2-
ene-1-carboxamide (6a)[24] (54 mg, 0.25 mmol, 1.0 equiv.) and allowing
reaction to stir overnight. The product was purified by column chromat-
ography eluting with a mixture hexane/EtOAc (2:1). The titled compound
7
This article is protected by copyright. All rights reserved.

10.1002/chem.201704443
Chemistry - A European Journal
FULL PAPER
was obtained as a pale-yellow oil, Rf 0.37. Yield 79 mg (0.229 mmol,
92%), dr >98:2, er 96:4. 1H NMR (500 MHz, CDCl3): δ 7.33 – 7.23 (m,
4H), 7.21 – 7.13 (m, 1H), 3.50 – 3.29 (m, 2H), 3.27 – 3.14 (m, 2H), 1.65
(dd, J = 9.8, 3.9 Hz, 1H), 1.41 (dd, J = 7.5, 3.9 Hz, 1H), 1.24 (s, 6H), 1.22
(s, 6H), 1.16 (t, J = 7.1 Hz, 3H), 0.71 (t, J = 7.1 Hz, 3H), 0.65 (dd, J = 9.8,
7.5 Hz, 1H); 13C (126 MHz, CDCl3): δ 175.5, 140.1, 128.7 (+, 2C), 127.7
(+, 2C), 126.8 (+), 81.4 (2C), 43.1 (-), 42.1 (-), 36.0, 25.2 (+, 2C), 25.1 (+,
2C), 19.5 (-), 18.7, 12.6 (+), 12.6 (+); FT IR (KBr, cm-1): 3061, 2976,
2935, 2876, 1643, 1634, 1601, 1470, 1454, 1404, 1381, 1325, 1211,
1142, 1115, 953, 860, 760, 700; HRMS (TOF ES): HRMS (TOF ES):
Found 366.2214, calculated for C20H30BNO3Na (M+Na) 366.2216 (0.5
ppm); [α]D20 +43.2o (c 1.13, CH2Cl2).
ES): Found 338.2650, calculated for C22H33BNO (M+H) 338.2655 (1.5
ppm).
(1-(2,4-Difluorophenyl)cyclopropyl)methanol (23j): This compound
was obtained via under condition of typical procedure B employing (1-
(2,4-difluorophenyl)cycloprop-2-en-1-yl)methanol (22j)[30] (91.0 mg, 0.50
mmol, 1.00 equiv.). The product was purified by column chromatography
eluting with a mixture hexane:EtOAc (3:1). The titled compound was
obtained as a pale yellow oil, Rf 0.22. Yield 45.1 mg (0.244 mmol, 49%).
1H NMR (500 MHz, CDCl3): δ 7.34 – 7.27 (m, 1H), 6.90 – 6.73 (m, 2H),
3.60 (d, J = 6.1 Hz, 2H), 1.47 (t, J = 6.2 Hz, 1H), 0.92 – 0.76 (m, 4H); 13C
NMR (126 MHz, CDCl3): δ 162.6 (dd, J = 249.5, 11.8 Hz), 162.1 (dd, J =
247.7, 12.0 Hz), 133.2 (+, dd, J = 9.6, 6.0 Hz), 125.6 (dd, J = 14.1, 3.7
Hz), 111.1 (+, dd, J = 20.9, 3.6 Hz), 105.5 – 101.5 (+, m), 70.4 (-), 23.6,
10.3 (-, d, J = 1.7 Hz, 2C); 19F NMR (376 MHz, CDCl3) δ -111.5 (d, J =
7.5 Hz), -112.0 (d, J = 7.5 Hz); FT IR (KBr, cm-1): 3354, 3082, 3007,
2928, 2872, 1614, 1601, 1506, 1466, 1421, 1267, 1138, 1117, 1084,
1036, 968, 849, 816, 734; HRMS (TOF ES): HRMS (TOF ES): Found
235.0558, calculated for C11H10F2O2Na (M+Na) 235.0547 (4.7 ppm).
The same reaction was performed in the presence of cationic Rh species.
To this end (procedure C), the reaction vessel was charged [Rh(CO)Cl]2
(6.1 mg, 12 μmol, 4 mol%), AgOTf (6.6 mg, 26 μmol, 8.5 mol%), and (R)-
BINAP (15 mg, 24 μmol, 8.0 mol%). Anhydrous THF was added and the
mixture was stirred at room temperature for 30 min. Then pinacolborane
(76 mg, 0.30 mmol, 1.0 equiv.) was added, immediately followed with
N,N-diethyl-1-phenylcycloprop-2-ene-1-carboxamide (6a) (65 mg, 0.30
mmol, 1.0 equiv.). Alternatively (procedure D) the reaction vessel was
loaded with Bis(norbornadiene)rhodium(I) tetrafluoroborate (Rh(nbd)BF4,
9.0 mg, 24 μmol, 8.0 mol%), and (R)-BINAP (15 mg, 24 μmol, 8.0 mol%).
Anhydrous THF was added and the mixture was stirred at room
temperature for 30 min. Then pinacolborane (76 mg, 0.30 mmol, 1.0
equiv.) was added, immediately followed with N,N-diethyl-1-
phenylcycloprop-2-ene-1-carboxamide (6a) (65 mg, 0.30 mmol, 1.0
equiv.). The resulting reaction mixtures were stirred at room temper-
ature for 18 hr and then worked up in the same manner as described
above for procedures A and B. In both cases compound 7a was
obtained as sole product as pale-yellow oil. Yields 99 mg (0.288 mmol,
96%), dr >98:2, er 95:5 for procedure C and 95 mg (0.276 mmol, 92%),
dr >98:2, er 95:5, for procedure D, respectively. Chromatographic and
spectral properties of these samples were identical to those for material
7a described above.
(+)-2-((1R,2S)-2-((Methoxymethoxy)methyl)-2-phenylcyclopropyl)-
4,4,5,5-tetramethyl-1,3,2-dioxaborolane (27a): This compound was
obtained via typical procedure B employing (1-((methoxymethoxy)meth-
yl)cycloprop-2-en-1-yl)benzene (24a)[11a] (95.2 mg, 0.50 mmol, 1.0
equiv.), [Rh(COD)Cl]2 (14.8 mg, 0.03 μmol, 0.06 equiv.) and (R)-BINAP
(37.4 mg, 0.06 mmol, 0.12 equiv.), pinacol borane (148.0 μl, 1.0 mmol,
2.0 equiv.) and allowing reaction to stir overnight. The product was
purified by column chromatography eluting with a mixture hexane:EtOAc
(20:1). The titled compound was obtained as a colorless oil, Rf 0.31.
Yield 128.2 mg (0.402 mmol, 81%), dr: 98:2, er: 68:32 (Column IC, IPA
3%, Flow rate 1 mL/min). 1H NMR (500 MHz, CDCl3) δ 7.43 – 7.38 (m,
2H), 7.31 – 7.25 (m, 2H), 7.21 – 7.16 (m, 1H), 4.53 (s, 2H), 3.96 (d, J =
10.1 Hz, 1H), 3.70 (d, J = 10.1 Hz, 1H), 3.14 (s, 3H), 1.29 (s, 6H), 1.28 (s,
6H), 1.22 (dd, J = 9.5, 3.8 Hz, 1H), 1.12 (dd, J = 7.3, 3.8 Hz, 1H), 0.47
(dd, J = 9.5, 7.3 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 144.7, 128.9 (+,
2C), 128.1 (+, 2C), 126.3 (+), 96.3 (-), 83.4 (2C), 72.8 (-), 55.1 (+), 32.3,
25.1 (+, 2C), 24.8 (+, 2C), 17.6 (-), 7.3 (+); FT IR (KBr, cm-1): 2978, 2929,
2882, 1415, 1371, 1323, 1215, 1147, 1106, 1053, 966, 859, 700; HRMS
(TOF ES): Found 337.2322, calculated for C20H31BO2Na (M+Na)
337.2315 (2.1 ppm); [α]D20 +10.5o (c 1.04, CHCl3).
Hydroboration of Other Substrates
2-(9-Borabicyclo[3.3.1]nonan-9-yl)-N,N-diethyl-1-phenylcycloprop-
ane-1-carboxamide (20): This compound was obtained via typical
procedure B using N,N-diethyl-1-phenylcycloprop-2-ene-1-carboxamide
(6a) (108 mg, 0.50 mmol, 1.0 equiv.) and 9-borabicyclo[3.3.1]nonane
dimer (1.0 ml, 0.5M in THF, 0.50 mmol, 1.0 equiv.) and allowing reaction
to stir overnight. The product was purified by column chromatography
eluting with a mixture hexane:EtOAc (3:1). The titled compound was
obtained as a colorless solid, Rf 0.31. Yield 89.6 mg yield (0.266 mmol,
53%), dr: 70:30. 1H NMR (500 MHz, CDCl3): Major (trans): δ 7.32 – 7.27
(m, 2H), 7.26 – 7.18 (m, 3H), 3.48 (dq, J = 14.2, 7.1 Hz, 1H), 3.35 (dq, J
= 14.0, 7.1 Hz, 1H), 3.26 (dq, J = 14.4, 7.2 Hz, 1H), 3.07 (dq, J = 14.2,
7.1 Hz, 1H), 1.99 – 1.88 (m, 2H), 1.86 – 1.80 (m, 3H), 1.76 – 1.66 (m,
5H), 1.54 (s, 2H), 1.46 – 1.40 (m, 1H), 1.21 (t, J = 7.1 Hz, 3H), 1.00 –
0.93 (m, 2H), 0.73 (t, J = 7.1 Hz, 3H), 0.69 – 0.64 (m, 1H), 0.50 – 0.42 (m,
1H). Minor (cis): δ 7.31 – 7.27 (m, 2H), 7.21 – 7.17 (m, 2H), 7.11 – 7.06
(m, 1H), 3.74 – 3.38 (m, 4H), 1.95 (dd, J = 8.4, 2.8 Hz, 1H), 1.92 – 1.82
(m, 3H), 1.82 – 1.73 (m, 1H), 1.71 – 1.61 (m, 3H), 1.54 (s, 2H), 1.45 (dd,
J = 8.4, 2.7 Hz, 1H), 1.34 (t, J = 7.2 Hz, 3H), 1.26 – 1.23 (m, 1H), 1.25 (t,
J = 7.2 Hz, 3H), 1.22 – 1.16 (m, 1H), 1.13 – 1.05 (m, 1H), 0.77 – 0.71 (m,
1H), 0.71 – 0.61 (m, 1H), 0.59 – 0.53 (m, 1H); 13C NMR (126 MHz,
CDCl3): Major (trans): δ 179.8, 140.8, 129.0 (+, 2C), 128.9 (+, 2C), 126.7
(+), 44.4 (-), 43.7 (-), 36.1, 33.6 (-), 32.7 (-), 32.4 (-), 31.8 (-), 28.0 (+),
27.9 (+), 25.9 (-), 25.5 (-), 18.8 (-), 12.6 (+), 12.5(+), 12.2 (+). Minor (cis):
δ 178.9, 148.3, 129.8 (+, 2C), 127.8 (+, 2C), 124.8 (+), 44.8 (-), 43.0 (-),
33.0 (-), 32.7 (-), 32.5 (-), 31.0 (-), 27.1, 27.0 (+), 26.9 (+), 25.6 (-), 25.0
(-), 21.5 (-), 14.3 (+), 13.0 (+), 12.9 (+); FT IR (KBr, cm-1): 2978, 2914,
2869, 2835, 1600, 1488, 1314, 1212, 968, 759, 726, 700; HRMS (TOF
(-)-(1S,2R)-1-Phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
cyclopropyl)methyl acetate (28a): This compound was obtained via
typical procedure B employing (1-phenylcycloprop-2-en-1-yl)methyl acet-
ate (25a)[11a] (94.2 mg, 0.50 mmol, 1.00 equiv.) and allowing the reaction
to stir overnight. The product was purified by column chromatography
eluting with a mixture hexane:EtOAc (3:1). The titled compound was
obtained as a pale-yellow oil, Rf 0.29. Yield 130.0 mg (0.412 mmol, 83%),
dr 96:4, er 79:21 (Column IC, IPA 3%, Flow Rate 1.0mL/min). 1H NMR
(500 MHz, CDCl3): δ 7.37 – 7.32 (m, 2H), 7.30 – 7.24 (m, 2H), 7.22 –
7.17 (m, 1H), 4.51 (d, J = 11.41 Hz, 1H), 4.19 (d, J = 11.4 Hz, 1H), 1.97
(s, 3H), 1.27 (s, 6H), 1.24 (s, 6H), 1.24 – 1.19 (m, 1H), 1.15 (dd, J = 7.3,
3.9 Hz, 1H), 0.51 (dd, J = 9.6, 7.3 Hz, 1H); 13C NMR (126 MHz, CDCl3):
δ 171.1, 143.8, 129.0 (+, 2C), 128.2 (+, 2C), 126.7 (+), 83.5 (2C), 70.2 (-),
31.1, 25.1 (+, 2C), 24.6 (+, 2C), 21.2 (+), 17.9 (-), 7.3; FT IR (KBr, cm-1):
3059, 2978, 2934, 1742, 1732, 1416, 1371, 1362, 1327, 1248, 1215,
1167, 1144, 1028, 976, 858, 729, 700, 671; HRMS (TOF ES): HRMS
(TOF ES): Found 339.1745, calculated for C18H25BO4Na (M+Na)
339.1744 (0.3 ppm); [α]D20 -35.6o (c 1.25, CHCl3).
(-)-tert-Butyldimethyl(((1S,2R)-1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)cyclopropyl)methoxy)silane (29a): This compound
was obtained via typical procedure B employing tert-butyldimethyl((1-
phenylcycloprop-2-en-1-yl)methoxy)silane (26a) (130.2 mg, 0.50 mmol,
8
This article is protected by copyright. All rights reserved.

10.1002/chem.201704443
Chemistry - A European Journal
FULL PAPER
1.0 equiv.) and allowing reaction to stir overnight. The product was
purified by column chromatography eluting with a mixture hexane:EtOAc
(20:1). The titled compound was obtained as a colorless oil, Rf 0.47.
Yield 154.6 mg (0.398 mmol, 80%), dr 92:8, er 80:20 (Column IC, IPA
0.4%, Flow Rate 1.0mL/min). 1H NMR (500 MHz, CDCl3): δ 7.41 – 7.35
(m, 2H), 7.26 – 7.21 (m, 2H), 7.19 – 7.14 (m, 1H), 3.85 (d, J = 10.5 Hz,
1H), 3.74 (d, J = 10.4 Hz, 1H), 1.29 (s, 6H), 1.27 (s, 6H), 1.10 – 1.06 (m,
1H), 1.04 (dd, J = 7.1, 3.7 Hz, 1H), 0.77 (s, 9H), 0.39 (dd, J = 9.2, 7.2 Hz,
1H), -0.25 (s, 3H), -0.27 (s, 3H); 13C NMR (126 MHz, CDCl3): δ 145.0,
130.3 (+, 2C), 127.7 (+, 2C), 126.3 (+), 83.3 (2C), 68.7 (-), 35.4, 26.1 (+,
3C), 25.2 (+, 2C), 24.8 (+, 2C), 18.5, 16.4 (-), 6.1, -5.5 (+), -5.6 (+); FT
IR (KBr, cm-1): 3059, 2978, 2955, 2928, 2885, 2856, 1472, 1416, 1379,
1321, 1252, 1213, 1146, 1088, 1076, 837, 773, 700; HRMS (TOF ES):
HRMS (TOF ES): Found 411.2523, calculated for C22H37BO3SiNa
(M+Na) 411.2503 (4.9 ppm); [α]D20 -23.39 (c 1.24, CHCl3).
1.26 (s, 6H), 1.11 – 1.02 (m, 2H), 0.75 (s, 9H), 0.30 (dd, J = 9.2, 7.4 Hz,
1H), -0.24 (s, 3H), -0.27 (s, 3H). Minor (trans): δ 7.32 – 7.21 (m, 1H),
6.81 – 6.73 (m, 1H), 6.74 – 6.64 (m, 1H), 3.83 (d, J = 10.1 Hz, 1H), 3.39
(d, J = 10.1 Hz, 1H), 1.13 (dd, J = 9.5, 3.7 Hz, 1H), 1.10 (s, 6H), 1.07 (dd,
J = 7.1, 3.7 Hz, 1H), 0.96 (s, 6H), 0.79 (s, 9H), 0.43 (dd, J = 9.6, 7.0 Hz,
1H), -0.11 (s, 3H), -0.15 (s, 3H); 13C NMR (126 MHz, CDCl3): Major
(cis): δ 163.0 (dd, J = 249.5, 12.6 Hz), 162.9 (dd, J = 248.2, 12.5 Hz),
134.4 (+, dd, J = 9.5, 5.9 Hz), 127.7 (dd, J = 13.6, 3.6 Hz), 110.3 (+, dd, J
= 20.8, 3.6 Hz), 103.3 (+, t, J = 25.5 Hz), 83.4 (2C), 67.4 (-), 30.1, 26.0 (+,
3C), 25.2 (+, 2C), 24.7 (+, 2C), 18.4, 15.9 (-), 5.5 (+), -5.5 (+), -5.7 (+).
Minor (trans): δ 162.6 (dd, J = 249.2, 12.0 Hz), 162.0 (dd, J = 246.5,
12.0 Hz), 134.2 (+, dd, J = 9.8, 6.3 Hz), 125.0 (dd, J = 13.7, 3.6 Hz),
110.4 (+, dd, J = 20.6, 3.3 Hz), 103.3 (+, t, J = 25.5 Hz), 83.0 (2C), 69.1
(-), 29.4, 25.9 (+, 3C), 24.9 (+, 2C), 24.6 (+, 2C), 18.4, 14.4 (-), 4.1 (+), -
5.5 (+), -5.5 (+); 19F NMR (376 MHz, CDCl3) Major (cis): δ -111.8 (d, J =
7.4 Hz), -113.0 (d, J = 6.9 Hz). Minor (trans): δ -111.0 (d, J = 7.5 Hz), -
113.3 (d, J = 7.3 Hz); FT IR (KBr, cm-1): 2979, 2952, 2929, 2887, 2858,
1598, 1504, 1446, 1415, 1371, 1359, 1325, 1257, 1083, 968, 837, 775;
HRMS (TOF ES): HRMS (TOF ES): Found 447.2299, calculated for
C22H35BF2O3SiNa (M+Na) 447.2314 (3.4 ppm); [α]D20 Major (cis): -31.1o
(c 2.04, CHCl3) Minor (trans): -18.9o (c 1.44, CHCl3).
(-)-tert-Butyl(((1S,2R)- and (-)-tert-Butyl(((1S,2S)-1-(2,3-difluorophen-
yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopropyl)meth-
oxy)dimethylsilane (cis-29i and trans-29i):
This compound was
obtained via typical procedure employing tert-butyl((1-(2,3-
B
difluorophenyl)cycloprop-2-en-1-yl)methoxy)dimethylsilane (26i) (148.0
mg, 0.50 mmol, 1.0 equiv.) and allowing reaction to stir overnight. The
product was purified by column chromatography eluting with a mixture
hexane:EtOAc (20:1). The titled compound was obtained as a colorless
oil, Rf 0.35 (major), 0.30 (minor). Yield 152.2 mg (0.358 mmol, 72%), dr
2.5:1, dr: 2.5:1, er: Major (cis): 82:18 (Column IB, IPA 0.4%, Flow Rate
1.0mL/min) Minor (trans): 73:27 (Column IB, IPA 0.4%, Flow Rate
1.0mL/min); 1H NMR (500 MHz, CDCl3): Major (cis): δ 7.16 – 7.07 (m,
1H), 7.04 – 6.89 (m, 2H), 3.88 (d, J = 10.7 Hz, 1H), 3.71 (d, J = 10.7 Hz,
1H), 1.28 (s, 6H), 1.26 (s, 6H), 1.11 – 1.09 (m, 1H), 1.09 – 1.07 (m, 1H),
0.75 (s, 9H), 0.35 (t, J = 8.4 Hz, 1H), -0.23 (s, 3H), -0.27 (s, 3H). Minor
(trans): δ 7.10 – 7.04 (m, 1H), 7.04 – 6.91 (m, 2H), 3.86 (d, J = 10.1 Hz,
1H), 3.44 (d, J = 10.2 Hz, 1H), 1.16 (dd, J = 9.6, 3.7 Hz, 1H), 1.11 – 1.09
(m, 1H), 1.10 (s, 6H), 0.96 (s, 6H), 0.80 (s, 9H), 0.48 (dd, J = 9.6, 7.0 Hz,
1H), -0.10 (s, 3H), -0.14 (s, 3H); 13C NMR (126 MHz, CDCl3): Major
(cis): δ 150.6 (dd, J = 247.0, 12.8 Hz), 150.2 (dd, J = 248.6, 12.3 Hz),
134.2 (d, J = 10.8 Hz), 128.2 (+, t, J = 3.1 Hz), 123.0 (+, dd, J = 7.2, 4.6
Hz), 115.4 (+, d, J = 17.2 Hz), 83.4 (2C), 67.4 (-), 30.4 (d, J = 2.7 Hz),
26.0 (+, 3C), 25.2 (+, 2C), 24.7 (+, 2C), 18.4, 15.8 (-), 5.6 (+), -5.6 (+), -
5.7 (+). Minor (trans): δ 151.7 (dd, J = 249.5, 13.8 Hz), 151.6 (dd, J =
249.5, 16.4 Hz), 131.6 (d, J = 10.1 Hz), 128.1 (+, t, J = 3.2 Hz), 123.2 (+,
dd, J = 6.6, 4.9 Hz), 115.3 (+, d, J = 16.8 Hz), 83.0 (2C), 68.9 (-), 29.8,
25.9 (+, 3C), 24.9 (+, 2C), 24.5 (+, 2C), 18.4, 14.4 (-), 4.1 (+), -5.5 (+), -
5.5 (+); 19F NMR (376 MHz, CDCl3) Major (cis): δ -140.0 (d, J = 20.8
Hz), -141.2 (d, J = 20.5 Hz). Minor (trans): δ -140.3 (d, J = 21.0 Hz), -
140.5 (d, J = 20.8 Hz); FT IR (KBr, cm-1): 2978, 2956, 2929, 2885, 2857,
1372, 1324, 1255, 1213, 1146, 1090, 836, 780, 729; HRMS (TOF ES):
Found 421.2893, calculated for C24H40BF2OSi (M+H) 421.2910 (4.0
Acknowledgements
This project received financial support from the Russian
Foundation for Basic Research (Grant No. 15-03-02661) and the
Ministry of Education and Science of the Russian Federation
(Grant numbers 02.a03.21.0008 and 4.1196.2017). Support
for NMR instruments used in this project was provided by NIH
Shared Instrumentation Grant No. S10RR024664 and NSF
Major Research Instrumentation Grant No. 0329648.
Keywords: cyclopropenes • hydroboration • asymmetric
catalysis • stereoselectivity • directing effect
[1]
See, for reviews: (a) Chen, D. Y.-K.; Pouwer, R. H.; Richard, J.-A.
Chem. Soc. Rev. 2012, 41, 4631-4642; (b) Donaldson, W. A.
Tetrahedron 2001, 57, 8589-8627; (c) Fan, Y.-Y.; Gao, X.-H.; Yue, J.-M.
Sci. China Chem. 2016, 59, 1126-1141; (d) Keglevich, P.; Keglevich,
A.; Hazai, L.; Kalaus, G.; Szantay, C. Cur. Org. Chem. 2014, 18, 2037-
2042.
[2]
[3]
See, for recent examples: (a) Shim, S. Y.; Kim, J. Y.; Nam, M.; Hwang,
G.-S.; Ryu, D. H. Org. Lett. 2016, 18, 160-163; (b) Williams, J. D.;
Yazarians, J. A.; Almeyda, C. C.; Anderson, K. A.; Boyce, G. R. J. Agric.
Food Chem. 2016, 64, 4319-4326.
20
ppm); [α]D Major (cis): -30.7o (c 1.88, CHCl3), Minor (trans): -14.8o (c
See, for examples: (a) Onajole, O. K.; Vallerini, G. P.; Eaton, J. B.;
Lukas, R. J.; Brunner, D.; Caldarone, B. J.; Kozikowski, A. P. ACS
Chem. Neurosci. 2016, 7, 811-822; (b) Reddy, C. N.; Nayak, V. L.;
Mani, G. S.; Kapure, J. S.; Adiyala, P. R.; Maurya, R. A.; Kamal, A.
Bioorg. Med. Chem. Lett. 2015, 25, 4580-4586; (c) Riss, P. J.; Roesch,
0.88, CHCl3).
(-)-tert-Butyl(((1S,2R)- and (-)-tert-Butyl(((1S,2S)-1-(2,4-difluorophen-
yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopropyl)meth-
oxy)dimethylsilanes (cis-29j and trans-29j): This compound was
F.
Org. Biomol. Chem. 2008, 6, 4567-4574; (d) Unzner, T. A.;
obtained via typical procedure
B
employing tert-butyl((1-(2,4-
Grossmann, A. S.; Magauer, T. Angew. Chem., Int. Ed. 2016, 55, 9763-
9767; (e) Hopkins, C. D.; Schmitz, J. C.; Chu, E.; Wipf, P. Org. Lett.
2011, 13, 4088-4091.
difluorophenyl)cycloprop-2-en-1-yl)methoxy)dimethylsilane (26j) (148.0
mg, 0.50 mmol, 1.00 equiv.) and allowing reaction to stir overnight. The
product was purified by column chromatography eluting with a mixture
hexane:EtOAc (20:1). The titled compound was obtained as a colorless
oil, Rf 0.30 (major), 0.25 (minor). Yield 167.2 mg (0.394 mmol, 79%), dr
2:1, er: Major (cis): 82:18 (Column IB, IPA 0.2%, Flow Rate 1.0mL/min)
Minor (trans): 81:19 (Column IB, IPA 0.4%, Flow Rate 1.0mL/min). 1H
NMR (500 MHz, CDCl3): Major (cis): δ 7.35 – 7.28 (m, 1H), 6.77 – 6.67
(m, 2H), 3.84 (d, J = 10.6 Hz, 1H), 3.66 (d, J = 10.6 Hz, 1H), 1.28 (s, 6H),
[4]
See, for review: (a) Wang, L.; Tang, Y. Israel J. Chem. 2016, 56, 463-
475; See for recent examples: (b) Sanchez-Diez, E.; Vesga, D. L.;
Reyes, E.; Uria, U.; Carrillo, L.; Vicario, J. L. Org. Lett. 2016, 18, 1270-
1273; (c) Cao, B.; Mei, L.-Y.; Li, X.-G.; Shi, M. RSC Adv. 2015,
5, 92545-92548; (d) Gharpure, S. J.; Nanda, L. N.; Shukla, M. K. Org.
Lett. 2014, 16, 6424-6427.
9
This article is protected by copyright. All rights reserved.

10.1002/chem.201704443
Chemistry - A European Journal
FULL PAPER
[5]
(a) Rubina, M.; Sherrill, W. M.; Barkov, A. Yu.; Rubin, M. Beilst. J. Org.
Chem. 2014, 10, 1536-1548; (b) Rubina, M.; Sherrill, W. M.; Rubin, M.
Organometallics 2008, 27, 6393-6395; (c) Molander, G. A.; Burke, J.
P.; Carrol, P. J. J. Org. Chem. 2004, 69, 8062–8069; (d) Aviron-Violet,
P.; Colleuille, Y.; Varagnat, J. J. Mol. Catal. 1979, 5, 41–50; (e) Okada,
Y.; Minami, T.; Yamamoto, T.; Ichikawa, J. Chem. Lett. 1992, 21, 547–
550; (f) Khlebnikov, A. F.; Kozhushkov, S. I.; Yufit, D. S.; Schill, H.;
Reggelin, M.; Spohr, V.; de Meijere, A. Eur. J. Org. Chem. 2012, 1530–
1545.
[13] M. Rubina, M. Rubin, V. Gevorgyan, J. Am. Chem. Soc. 2003, 125,
7198-7199.
[14] See, for example: (a) E. S. Priestley, C. P. Decicco, Org. Lett. 2000, 2,
3095-3097; (b) S. Lohr, A. deMeijere Synlett 2001, 489-492; (c) D. J.
Wallace, C. Chen, Tetrahedron Lett. 2002, 43, 6987-6990.
[15] (a) P. Binger, R. Köster, Angew. Chem. 1962, 74, 652; (b) H. C. Brown,
S. P. Rhodes, J. Am. Chem. Soc. 1969, 91, 4306-4307; (c) D. S.
Matteson, G. D. Schauberg, J. Org. Chem. 1966, 31, 726-731.
[16] See, for example: (a) T. Imai, H. Mineta, S. Nishida, J. Org. Chem.
1990, 55, 4986-4988; (b) J. E. A. Luithle, J. Pietruszka, J. Org. Chem.
1999, 64, 8287-8297; (c) J. P. Hildebrand, S. P. Marsden, Synlett 1996,
893-894; (d) I. E. Marko, T. Kumamoto, T. Giard, Adv. Synth. Catal.
2002, 344, 1063-1067; (e) S.-M. Zhou, M.-Z. Deng, L.-J. Xia, M.-H.
Tang, Angew. Chem., Int. Ed. 1998, 37, 2845-2847.
[6]
[7]
See, for recent examples: (a) Bender, T. A.; Dabrowski, J. A.; Zhong,
H.; Gagné, M. R. Org. Lett. 2016, 18, 4120-4123; (b) Li, J.-H.; Feng,
T.-F.; Du, D.-M. J. Org. Chem. 2015, 80, 11369-11377; (c) Tollefson, E.
J.; Erickson, L. W.; Jarvo, E. R. J. Am. Chem. Soc. 2015, 137, 9760-
9763.
See, for recent examples: (a) Chanthamath, S.; Mandour, H. S. A.;
Tong, T. M. T.; Shibatomi, K.; Iwasa, S. Chem. Commun. 2016, 52,
7814-7817; (b) Meazza, M.; Ashe, M.; Shin, H. Y.; Yang, H. S.;
Mazzanti, A.; Yang, J. W.; Rios, R. J. Org. Chem. 2016, 81, 3488-
3500; (c) Su, Y.; Li, Q.-F.; Zhao, Y.-M.; Gu, P. Org. Lett. 2016, 18,
4356-4359; (d) Luo, C.; Wang, Z.; Huang, Y. Nat. Commun. 2015, 6,
10041; (e) Joshi-Pangu, A.; Cohen, R. D.; Tudge, M. T.; Chen, Y. J.
Org. Chem. 2016, 81, 3070-3075; (f) Adly, F. G.; Gardiner, M. G.;
Ghanem, A. Chem. Eur. J. 2016, 22, 3447-3461; (g) Pedroni, J.;
Cramer, N. Angew. Chem., Int. Ed. 2015, 54, 11826-11829; (h)
Hayashi, Y.; Yamazaki, T.; Nakanishi, Y.; Ono, T.; Taniguchi, T.;
Monde, K.; Uchimaru, T. Eur. J. Org. Chem. 2015, 5747-5754; (i) Ji,
K.; Zheng, Z.; Wang, Z.; Zhang, L. Angew. Chem., Int. Ed. 2015, 54,
1245-1249.
[17] For examples on non-catalytic hydroboration of cyclopropenes, see: (a)
R. Köster, S. Arora, P. Binger, Angew. Chem., Int. Ed. Engl. 1969, 8,
205-206; (b) H. E. Zimmerman, J. M. Nuss, A. W. Tantillo, J. Org.
Chem. 1988, 53, 3792-3803; (c) M. A. Rubin, M. S. Baird, I. G. Bolesov,
Russ. J. Org. Chem. 1997, 33, 900-902; (d) M. Rubina, M. Rubin,
Chem. Heterocycl. Comp. 2012, 48, 807-821.
[18] (a) A. Parra, L. Amenos, M. Guisán-Ceinos, A. Lopez, J. L. Garcia
Ruano, M. Tortosa, J. Am. Chem. Soc. 2014, 136, 15833-15836; (b) B.
Tian, Q. Liu, X. Tong, P. Tian, G-Q. Lin, Org. Chem. Front. 2014, 1,
1116-1122. For related reaction of cyclobutenes, see: (c) M. Guisán-
Ceinos, A. Parra, V. Martín-Heras, M. Tortosa, Angew. Chem. Int. Ed.
2016, 55, 1-5.
[19] A. Edwards, M. Rubin, Tetrahedron, 2015, 71, 3237-3246.
[20] We suggest formation of cationic six-coordinated 18e- Rh(III)-
complexes here, to accommodate for chelation with both chiral
diphosphine ligand and cyclopropene substrate with directing group. It
should be pointed out, that reactions carried out in the presence of
AgOTf taken as chloride-scavenger or cationic Rh(nbd)BF4 taken as
transition metal source afforded the same results, i.e. yields, dr’s and
er’s, which strongly supports this idea.
[8]
[9]
For review, see: (a) Bartoli, G.; Bencivenni, G.; Dalpozzo, R. Synthesis
2014, 46, 979-1029; (b) Pellissier, H. Tetrahedron 2008, 64, 7041-
7095; (c) Mikolajczyk, M. Pur. Appl. Chem. 2005, 77, 2091-2098; (d)
Doyle, M. P.; Protopopova, M. N. Tetrahedron, 1998, 54, 7919-7946.
N. Hoshiya, K. Takenaka, S. Shuto, J. Uenishi, Org. Lett. 2016, 18, 48-
51.
[10] See, for reviews: (a) Vicente, R. Synthesis 2016, 48, 2343-2360; (b)
Muller, D. S.; Marek, I. Chem. Soc. Rev. 2016, 45, 4552-4566; (c) Zhu,
Z.-B.; Wei, Y.; Shi, M. Chem. Soc. Rev. 2011, 40, 5534-5563; (d) Rubin,
M.; Rubina, M.; Gevorgyan, V. Chem. Rev. 2007, 107, 3117-3179; (e)
Rubin, M.; Rubina, M.; Gevorgyan, V. Synthesis 2006, 1221-1245.
[11] For hydrometallations, see: (a) Rubina, M.; Rubin, M.; Gevorgyan, V. J.
Am. Chem. Soc. 2004, 126, 3688-3689; (b) Lou, Y.; Horikawa, M.;
Kloster, R. A.; Hawryluk, N. A.; Corey, E. J. Am. Chem. Soc. 2004, 126,
8916-8918; (c) Parra, A.; Amenos, L.; Guisan-Ceinos, M.; Lopez, A.;
Garcia Ruano, J. L.; Tortosa, M. J. Am. Chem. Soc. 2014, 136, 15833-
15836; (d) Rubin, M.; Gevorgyan, V. Synthesis 2004, 796-800; for
carbometallations, see: (e) Muller, D. S.; Marek, I. J. Am. Chem. Soc.
2015, 137, 15414-15417; (f) Simaan, M.; Delaye, P. O.; Shi, M.; Marek,
I. Angew. Chem. Int. Ed. 2015, 54, 12345-12348. (g) Didier, D.;
Delaye, P.-O.; Simaan, M.; Island, B.; Eppe, G.; Eijsberg, H.; Kleiner,
A.; Knochel, P.; Marek, I. Chem. Eur. J. 2014, 20, 1038-1048; (h)
Delaye, P.-O.; Didier, D.; Marek, I. Angew. Chem., Int. Ed. 2013, 52,
5333-5337; (i) Kramer, K.; Leong, P.; Lautens, M. Org. Lett. 2011, 13,
819-821; (j) Simaan, S.; Masarwa, A.; Zohar, E.; Stanger, A.; Bertus,
P.; Marek, I. Chem. Eur. J. 2009, 15, 8449-8464; (k) Tarwade, V.; Liu,
X.; Yan, N.; Fox, J. M. J. Am. Chem. Soc. 2009, 131, 5382-5383; for
hydroformylation, see: (l) Sherrill, W. M.; Rubin, M. J. Am. Chem. Soc.
2008, 130, 13804-13809; for hydroacylation, see: (m) Phan, D. H. T.;
Kou, K. G. M.; Dong, V. M. J. Am. Chem. Soc. 2010, 132, 16354-
16355; for benzamidation, see: (n) Semakul, N.; Jackson, K. E.; Paton,
R. S.; Rovis, T. Chem. Sci. 2017, 8, 1015-1020.
[21] For agostic interactions in transition metal complexes involving ortho-
fluorine atoms, see: (a) R. F. Munha, M. A. Antunes, L. G. Alves, L. F.
Veiros, M. D. Fryzuk, A. M. Martins, Organometallics 2010, 29, 3753-
3764. (b) L. A. Watson, D. V. Yandulov, K. G. Caulton, J. Am. Chem.
Soc. 2001, 123, 603-611. (c) R. M. Catala, D. Cruz-Garritz, P. Sosa, P.
Terreros, H. Torrens, A. Hills, D. L. Hughes, R. L. Richards, J.
Organomet. Chem. 1989, 359, 219-232.
[22] Sherrill, W. M.; Kim, R.; Rubin, M. Synthesis 2009, 1477-1484.
[23] (a) Banning, J. E.; Gentillon, J.; Ryabchuk, P. G.; Prosser, A. R.;
Rogers, A.; Edwards, A.; Holtzen, A.; Babkov, I. A.; Rubina, M.; Rubin,
M. J. Org. Chem. 2013, 78, 7601-7616. (b) Banning, J. E.; Prosser, A.
R.; Alnasleh, B. K.; Smarker, J.; Rubina, M.; Rubin, M. J. Org. Chem.
2011, 76, 3968-3986; (c) Yamanushkin, P.; Lu-Diaz, M.; Edwards, A.;
Aksenov, N. A.; Rubina, M.; Rubin, M. Org. Biomol. Chem., 2017, DOI:
10.1039/C7OB01785E.
[24] A. Edwards, M. Rubin, Org. Biomol. Chem. 2016, 14, 2883-2890.
[25] L. Liao, N. Yan, J. M. Fox, Org. Lett. 2004, 6, 4937-4939.
[26] For reviews on synthetic utility of Weinreb amies, see: (a) S.
Balasubramaniam, I. S. Aidhen, Synthesis 2008, 3707-3738. (b) V. K.
Khlestkin, D. G. Mazhukin, Cur. Org. Chem. 2003, 7, 967-993. For
cyclopropanation, employing diazo Weinreb amides, see: (c) S.
Chanthamath, H. S. A. Mandour, T. M. T. Tong, K. Shibatomi, S. Iwasa,
Chem. Commun. 2016, 52, 7814-7817. (d) H. S. A. Mandour, S.
Chanthamath, K. Shibatomi, S. Iwasa, Adv. Synth. Catal. 2017, 359,
1742-1746.
[27] (a) Köster, R.; Arora, S.; Binger, P. Angew. Chem., Int. Ed. 1969, 8,
205-206. (b) Zimmerman, H. E.; Nuss, J. M.; Tantillo, A. W. J. Org.
Chem. 1988, 53, 3792-3803. (c) Rubin, M. A.; Baird, M. S.; Bolesov, I.
G. Russ. J. Org. Chem. 1997, 33, 900-902.
[12] For organocatalytic asymmetric hydroacylation of cyclopropenes, see:
(a) Liu, F.; Bugaut, X.; Schedler, M.; Froehlich, R.; Glorius, F. Angew.
Chem., Int. Ed. 2011, 50, 12626-12630; For organocatalytic asymmetric
carbometallation, see: (b) Liu, X.; Fox, J. M. J. Am. Chem. Soc. 2006,
128, 5600-5601.
[28] Rubina, M.; Rubin, M. Chem. Heterocycl. Comp. 2012, 48, 807-821.
10
This article is protected by copyright. All rights reserved.

10.1002/chem.201704443
Chemistry - A European Journal
FULL PAPER
[29] An alkoxymethyl group has previously proven to be a rather inefficient
director in the Rh-catalyzed hydroboration in the presence of (R)-
BINAP in THF [See Ref. 13]
[30] A. Edwards, T. Bennin, M. Rubina, M. Rubin, RSC Adv. 2015, 5,
71849-71853.
[31] Bodnar, B. S.; Vogt, P. F. J. Org. Chem. 2009, 74, 2598-2600.
[32] M. Rubin, V. Gevorgyan, Synthesis 2004, 796-800.
11
This article is protected by copyright. All rights reserved.

10.1002/chem.201704443
Chemistry - A European Journal
FULL PAPER
Entry for the Table of Contents (Please choose one layout)
FULL PAPER
Andrew Edwards, Marina Rubina, and
Michael Rubin*
Page No. – Page No.
Directed Rh(I)-Catalyzed Asymmetric
Hydroboration of Prochiral 1-
Arylcycloprop-2-ene-1-carboxylic
Acid Derivatives
Directed enantioselective Rh(I)-catalyzed hydroboration of cyclopropenes
12
This article is protected by copyright. All rights reserved.