Asymmetric Rh(I)-catalyzed addition of MIDA boronates to N-Tert -butanesulfinyl aldimines: Development and comparison to trifluoroborates

Article abstract of DOI:10.1021/jo100318s

The Rh(I)-catalyzed addition of alkenyl and aryl MIDA boronates to N-tert-butanesulfinyl aromatic and aliphatic imines proceeds in good yields (up to 99%) and with very high selectivity (98:2 to >99:1). In comparison to trifluoroborates, higher yields and

Full text of DOI:10.1021/jo100318s

pubs.acs.org/joc
However, the efficiency of these additions is often limited
Asymmetric Rh(I)-Catalyzed Addition of MIDA
Boronates to N-tert-Butanesulfinyl Aldimines:
Development and Comparison to Trifluoroborates
due to competitive decomposition of the boron reagents. The
same conditions, namely heat, water, and transition-metal
catalysts, that promote the addition of boron reagents also
accelerate their decomposition via pathways such as proto-
deboronation, oxidation, and/or polymerization.5 There-
fore, overcoming these undesired processes has posed a
particular challenge.6
Katrien Brak and Jonathan A. Ellman*
Department of Chemistry, University of California,
Berkeley, California 94720
While boronic acids are highly versatile coupling reagents,7
their limited stability and incompatibility with many synthetic
reagents have resulted in the development of several impor-
tant surrogates. Potassium trifluoroborates,8 and even more
recently N-methyliminodiacetic acid (MIDA) boronates,9
have emerged as particularly attractive alternative organo-
boron coupling partners.10,11 These boron reagents exhibit
exceptional benchtop stability, are easy to synthesize and
isolate, and are compatible with many synthetic reagents.
Furthermore, MIDA boronates are stable to silica gel chro-
matography, allowing for expanded utility in the synthesis of
complex organoboron building blocks.12
jellman@berkeley.edu
Received February 19, 2010
MIDA boronates are inert to many of the common path-
ways of decomposition; however, they are also unreactive
toward transmetalation.13 Burke and co-workers have ele-
gantly demonstrated that cross-coupling of unstable boronic
The Rh(I)-catalyzed addition of alkenyl and aryl MIDA
boronates to N-tert-butanesulfinyl aromatic and aliphatic
imines proceeds in good yields (up to 99%) and with very
high selectivity(98:2to>99:1).Incomparisontotrifluoro-
borates, higher yields and selectivities are observed for the
addition to N-tert-butanesulfinyl aromatic imines. This
new method expands upon the versatility of the Rh(I)-
catalyzed addition of boron reagents to imines, thereby
further enabling the synthesis of chiral R-branched amines.
(5) Protodeboronation of boronic acids occurs under protic conditions
and has been shown to proceed via general acid catalysis: (a) Kuivila, H. G.;
Nahabedian, K. V. J. Am. Chem. Soc. 1961, 83, 2159. Protonation of
Ar-Rh(I) species occurs under acidic conditions: (b) Keim, W. J. J. Organo-
met. Chem. 1968, 14, 179. (c) Boyd, S. E.; Field, L. D.; Hambley, T. W.;
Partridge, M. G. Organometallics 1993, 12, 1720. Lower molecular weight
alkenylboronic acids, such as vinyl and propenylboronic acids, readily
polymerize: (d) Matteson, D. S. J. Am. Chem. Soc. 1960, 82, 4228.
(6) Improved yields have been achieved by the following: (I) Using a large
excess of boronic acid: (a) Takaya, Y.; Ogasawara, M.; Hayashi, T.; Sakai,
M.; Miyaura, N. J. Am. Chem. Soc. 1998, 120, 5579. (II) Slow addition of the
boronic acid: (b) Reference 3c.
(7) Hall, D. G. Boronic Acids; Wiley-VCH: Weinheim, Germany, 2005.
(8) For recent reviews on trifluoroborates, see: Molander, G. A.; Ellis,
N. M. Acc. Chem. Res. 2007, 40, 275. Stefani, H. A.; Cella, R.; Vieira, A. S.
Tetrahedron 2007, 63, 3623. Darses, S.; Genet, J.-P. Chem. Rev. 2008, 108,
288. Molander, G. A.; Canturk, B. Angew. Chem., Int. Ed. 2009, 48, 9240.
(9) For a review on MIDA boronates, see: Gillis, E. P.; Burke, M. D.
Aldrichim. Acta 2009, 42, 17.
The development of efficient and practical methods for
the asymmetric synthesis of chiral, R-branched amines is of
great importance due to the ubiquitous nature of this motif
in pharmaceutical agents and natural products.1 The Rh(I)-
catalyzed addition of boron reagents to activated imines
has emerged as a general, functional-group tolerant method
for the asymmetric synthesis of R-branched amines.2-4
(10) For reviews that compare trifluoroborates, MIDA boronates, and
1,8-diaminonaphthalene boronates, see: (a) Tobisu, M.; Chatani, N. Angew.
Chem., Int. Ed. 2009, 48, 3565. (b) Molander, G. A.; Canturk, B. Angew.
Chem., Int. Ed. 2009, 48, 9240.
(11) For select examples of other alternative organoboron coupling
partners see the following: (I) Sterically bulky boronic esters: (a) Lightfoot,
A. P.; Twiddle, S. J. R.; Whiting, A. Synlett 2005, 3, 529. (b) Yang, D. X.;
Colletti, S. L.; Wu, K.; Song, M.; Li, G. Y.; Shen, H. C. Org. Lett. 2009, 11,
381. (c) Takaya, Y.; Ogasawara, M.; Hayashi, T. Tetrahedron Lett. 1998, 39,
8479. (II) Boroximes: (d) Kerins, F.; O’Shea, D. F. J. Org. Chem. 2002, 67,
4968. (e) Hayashi, T.; Ishigedani, M. J. Am. Chem. Soc. 2000, 122, 976.
(f) Kuriyama, M.; Soeta, T.; Hao, X.; Chen, Q.; Tomioka, K. J. Am. Chem.
Soc. 2004, 126, 8128. (III) Tetraarylborates: (g) Noguchi, H.; Hojo, K.;
Suginome, M. J. Am. Chem. Soc. 2007, 129, 758. (IV) Trialkoxyborate salts:
(h) Takaya, Y.; Ogasawara, M.; Hayashi, T. Tetrahedron Lett. 1999, 40,
6957. (i) Yamamoto, Y.; Takizawa, M.; Yu, X.-Q.; Miyaura, N. Angew.
Chem., Int. Ed. 2008, 47, 928. (V) Trihydroxyborate salts: (j) Cammidge,
A. N.; Goddard, V. H. M.; Gopee, H.; Harrison, N. L.; Hughes, D. L.;
Schubert, C. J.; Sutton, B. M.; Watts, G. L.; Whitehead, A. J. Org. Lett. 2006,
8, 4071. (VI) Diethanolamine adducts: (k) Gravel, M.; Thompson, K. A.;
Zak, M.; Berube, C.; Hall, D. G. J. Org. Chem. 2002, 67, 3. (l) Bonin, H.;
Delbrayelle, D.; Demonchaux, P.; Gras, E. Chem. Comm. 2010. DOI: 10.1039/
b926547n. (VII) 1,8-diaminonaphthalene adduct: (m) Noguchi, H.; Hojo, K.;
Suginome, M. J. Am. Chem. Soc. 2007, 129, 758.
(1) Breuer, M.; Ditrich, K.; Habicher, T.; Hauer, B.; Kesseler, M.;
Sturmer, R.; Zelinski, T. Angew. Chem., Int. Ed. 2004, 43, 788.
(2) The first report of a Rh(I)-catalyzed addition of arylboronic acids to
imines: Ueda, M.; Saito, A.; Miyaura, N. Synlett 2000, 11, 1637.
(3) Asymmetric Rh(I)-catalyzed arylboron additions to imines:
(a) Kuriyama, M.; Soeta, T.; Hao, X.; Chen, Q.; Tomioka, K. J. Am. Chem.
Soc. 2004, 126, 8128. (b) Tokunaga, N.; Otomaru, Y.; Okamoto, K.;
Ueyama, K.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126,
13584. (c) Weix, D. J.; Shi, Y.; Ellman, J. A. J. Am. Chem. Soc. 2005, 127,
1092. (d) Bolshan, Y.; Batey, R. A. Org. Lett. 2005, 7, 1481. (e) Jagt, R. B. C.;
Toullec, P. Y.; Geerdink, D.; de Vries, J. G.; Feringa, B. L.; Minnaard, A. J.
Angew. Chem., Int. Ed. 2006, 45, 2789. (f) Duan, H.-F.; Jia, Y.-X.; Wang,
L.-X.; Zhou, Q.-L. Org. Lett. 2006, 8, 2567. (g) Wang, Z.-Q.; Feng, C.-G.;
Xu, M.-H.; Lin, G.-Q. J. Am. Chem. Soc. 2007, 129, 5336. (h) Nakagawa, H.;
Rech, J. C.; Sindelar, R. W.; Ellman, J. A. Org. Lett. 2007, 9, 5155.
(i) Trincado, M.; Ellman, J. A. Angew. Chem., Int. Ed. 2008, 47, 5623.
(4) Asymmetric Rh(I)-catalyzed alkenylboron additions to imines: Brak,
K.; Ellman, J. A. J. Am. Chem. Soc. 2009, 131, 3850.
(12) Gillis, E. P.; Burke, M. D. J. Am. Chem. Soc. 2008, 130, 14084.
(13) Gillis, E. P.; Burke, M. B. J. Am. Chem. Soc. 2007, 129, 6716.
DOI: 10.1021/jo100318s
r
Published on Web 04/13/2010
J. Org. Chem. 2010, 75, 3147–3150 3147
2010 American Chemical Society

Brak and Ellman
JOCNote
TABLE 1. Optimization of Reaction Conditions
TABLE 2. Scope in N-Sulfinyl Imine with Alkenyl Boron Reagents
entry
M
base
solvent system
yield (%)a,b
1
2
3
4
5
6
BF3K
NEt3
NEt3
K3PO4
K3PO4
K3PO4
K3PO4
H2O/DMF (3:2)
H2O/DMF (3:2)
H2O/DMF (3:2)
H2O/dioxane (3:2)
H2O/dioxane (1:5)
H2O/dioxane (3:2)
53
17
61
86
60
21
BMIDA
BMIDA
BMIDA
BMIDA
B(OH)2
aReaction conditions: 1 equiv of 2a, 2 equiv of 1a or 4a or 5a, 2.5 mol
% of [Rh(OH)(cod)]2, 5.0 mol % of 1,2-bis(diphenylphosphino)benzene
(dppbenz), 2 equiv of NEt3 or K3PO4, 0.125 M in 2:3 H2O/cosolvent,
60 °C, 20 h. bYields were determined by 1H NMR relative to an external
standard.
acids, via the in situ, rate-controlled hydrolysis of MIDA
boronates, is a general solution for the Suzuki-Miyaura
reaction.14 The slow release of boronic acids from MIDA
boronates maintains minimal amounts of free boronic acid
throughout the reaction, which results in improved effi-
ciency. Taking advantage of the hydrolytic stability of
N-tert-butanesulfinyl aromatic imines, we disclose herein
the first application of MIDA boronates in the Rh(I)-
catalyzed addition to imines.
We previously reported the Rh(I)-catalyzed addition
of alkenyltrifluoroborates to both aromatic and aliphatic
N-tert-butanesulfinyl imines.4 Even though trifluoroborates
were found to be significantly more effective than the corres-
ponding boronic acids, limitations still arose due to compe-
titive decomposition of the boron reagent. For example,
the addition of pentenyltrifluoroborate 1a to electron-rich
N-sulfinyl imine 2a proceeded only in moderate yield (eq 1).
After careful evaluation of the reaction conditions, it was
found that the alkenylation reaction ceases after 1 h even
though a significant quantity of the hydrolytically stable
N-tert-butanesulfinyl imine was still present. Interestingly,
the addition of another 2 equiv of the trifluoroborate after
1 h resulted in higher yields. This suggested that over a period
of 1 h, the Rh(I)-catalyst remained active while significant
consumption of the trifluoroborate had occurred through a
combination of addition and decomposition.
aReactions were performed with 2 equiv of NEt3 in 0.125 M H2O/
DMF (3:2). bReactions were performed with 2 equiv of K3PO4 in 0.125
M H2O/dioxane (3:2). cThe diastereoselectivity was the same for M =
BF3K and BMIDA and was determined by HPLC on unpurified
samples with comparison to authentic diastereomers.17 dReactions were
set up in a fumehood using Schlenk technique. eReactions were per-
formed with 1.2 equiv of boron reagent.
from MIDA boronates (Table 1). The optimal conditions
for the Rh(I)-catalyzed addition of trifluoroborates, which
utilize triethylamine as the base, were not effective for MIDA
boronates (entry 2). It is known that K3PO4 in 1:5 H2O/
dioxane promotes the continuous release of boronic acids
over approximately 3 h.14 Fortunately, K3PO4 was pre-
viously established to be a compatible base for the Rh(I)-
catalyzed addition of trifluoroborates4 and proved to be
competent for MIDA boronates as well (entry 3). While
dioxane is a poor cosolvent for the trifluoroborate-mediated
transformation, it resulted in higher yields for the MIDA
boronate (entry 4). Similarly to the trifluoroborates, it was
important to maintain the heterogeneous reaction condi-
tions by having a solvent system composed of a minimum of
60% water (entry 5).15 We also confirmed that the slow
release of boronic acids is much more effective than simply
using 2 equiv of boronic acid in the Rh-catalyzed alkenyla-
tion reaction (entry 6).
(15) Under the optimal reaction conditions (0.125 M in D2O/dioxane-d8
(3:2), 2 equiv of K3PO4, 60 °C), MIDA boronate 4a was observed by 1H
NMR to slowly hydrolyze over 3 h.
(16) An isolated example of ligand-free Rh(I)-catalyzed addition of
phenyltrifluoroborate to N-tert-butanesulfinyl 4-trifluoromethylbenzaldi-
mine in 61% yield and 96:4 dr has been reported, see ref 3d.
(17) Authentic diastereomer mixtures were prepared according to the
following: Brak, K.; Barrett, K. T.; Ellman, J. A. J. Org. Chem. 2009, 74,
3606.
While sequential addition of more trifluoroborate resulted
in improved yields, we sought to develop a more efficient and
practical process. We envisioned that higher yields could
potentially be achieved via the slow release of boronic acids
(14) Knapp, D. M.; Gillis, E. P.; Burke, M. D. J. Am. Chem. Soc. 2009,
131, 6961.
3148 J. Org. Chem. Vol. 75, No. 9, 2010

Brak and Ellman
JOCNote
TABLE 3. Scope in Alkenyl Organoboron Reagent
TABLE 4. Additions of Aryl Boron Reagents to N-Sulfinyl Imines
aIsolated yield after chromatography. bDiastereoselectivity was deter-
mined by HPLC on unpurified samples with comparison to authentic
diastereomers.17 cReactions were performed with 2 equiv of NEt3 in 0.125
M H2O/DMF (3:2). dReactions were performed with 2 equiv of K3PO4 in
0.125 M H2O/dioxane (3:2).
increased alkene substitution resulted in moderate decreases
in yield for the trifluoroborates, the MIDA boronates main-
tained excellent yields (entries 2 and 3).
aReactions were performed with 2 equiv of NEt3 in 0.125 M H2O/
DMF (3:2). bReactions were performed with 2 equiv of K3PO4 in
0.125 M H2O/dioxane (3:2). cDiastereoselectivity was the same for
M = BF3K and BMIDA and was determined by HPLC on unpurified
samples with comparison to authentic diastereomers.17
We were also interested in examining how the electronics
of the boron coupling partner affect the efficiency of the
reaction. The alkenylation was found to be strongly influ-
enced by electronics with the additions of electron-deficient
trifluoroborates proceeding in lower yield (entries 4 and 5).
Although cinnamyl MIDA boronate 4d added in signifi-
cantly higher yield than the corresponding trifluoroborate
(entry 4), the addition of the highly electron-deficient trifluoro-
methyl-substituted MIDA boronate 4e proceeded in low yield
(entry 5).18 Electron-poor boron reagents are known to be less
nucleophilic and undergo transmetalation at a slower rate in
addition to being prone to homocoupling.19
The conditions developed for the alkenylation also were
applicable to the arylation of N-tert-butanesulfinyl imines.
The Rh(I)-catalyzed addition of aryl boron reagents to both
electron deficient and rich N-sulfinyl aromatic imines 2d and
2a,20 respectively, proceeded with high selectivity and yields
for the MIDA boronates (Table 4).16 Whereas the diastereos-
electivity was found to be identical for MIDA boronates and
trifluoroborates in the alkenylation reaction, a noticeable
difference was observed in the arylation reaction with the
MIDA boronate additions proceeding with higher selectivity.
In conclusion, the slow release of boronic acids from
MIDA boronates minimizes the decomposition of the boron
reagents and enables their Rh-catalyzed addition to N-tert-
butanesulfinyl imines in very high yields and selectivities.
This practical and general method enables the asymmetric
synthesis of R-branched amines from stable and easily
Encouraged by these results, we next evaluated the
MIDA boronate slow-release method with a variety of
N-tert-butanesulfinyl imines (Table 2). For the Rh(I)-catalyzed
alkenylation of N-tert-butanesulfinyl aromatic aldimines, MIDA
boronates performed better than the trifluoroborates (entries
1-7). The Rh(I)-catalyzed addition of pentenyl MIDA boronate
to electron neutral (entries 1 and 4) and deficient (entry 5)
N-sulfinyl imines provided the corresponding allylic amines in
nearly quantitative yield and with excellent diastereoselectivities.
Notably, the most dramatic improvements in yield were achieved
for the addition to electron-rich imines (entries 6 and 7).
For N-sulfinyl imines 2 that are aliphatic, imine hydrolysis
is the major side reaction competing with the alkenylation
reaction. Consequently, this substrate class does not benefit
from the slow release of boronic acids from MIDA boro-
nates. For nonhindered aliphatic imines, MIDA boronates
resulted in the same yield as trifluoroborates (entry 8).
However, for sterically hindered aliphatic imines, the addi-
tion of the MIDA boronate resulted in a lower yield (entry 9).
It is important to note that the [Rh(OH)(cod)]2 precatalyst
and dppbenz ligand are air stable, and therefore the alkeny-
lation reactions can be set up by using standard Schlenk
techniques without requiring the use of an inert atmosphere
box (entry 2, Table 2). Moreover, the equivalents of MIDA
boronate reagent 4a could be reduced without appreciably
affecting the reaction yield (entry 3).
(18) The addition of vinyltrifluoroborate (13%) and vinyl MIDA boronate
(11%) to imine 2d proceeds in low yields. The vinyl boron reagents most likely
failed to couple efficiently due to their electron-deficient as well as unstable nature.
(19) (a) Wong, M. S.; Zhang, X. L. Tetrahedron Lett. 2001, 42, 4087.
(b) Kuivila, H. G.; Reuwer, J. F.; Mangravite, J. A. J. Am. Chem. Soc. 1964,
86, 2666.
(20) The addition of phenylboronic acid to imine 2a was reported to
proceed in 45% yield and 91:9 dr with [Rh(cod)(CH3CN)2]BF4 as the catalyst
without any phosphine ligand, 1:2 dioxane/water as solvent, and Et3N (2
equiv) as an additive, see ref 3d.
The scope of the organoboron coupling partner was next
evaluated with N-sulfinyl 4-chlorobenzaldimine 2d under the
standard set of conditions (Table 3). The Rh(I)-catalyzed
alkenylation was not especially sensitive to substitution on
the alkene, with the addition of di- (entry 1), tri- (entry 2),
and tetrasubstituted (entry 3) alkenyltrifluoroborates all
proceeding in good yields and with high selectivities. While
J. Org. Chem. Vol. 75, No. 9, 2010 3149

Brak and Ellman
JOCNote
accessible N-sulfinyl imine and MIDA boronate starting
aqueous K3PO4 solution were added by cannula. The Schlenk
tube was capped, and the reaction mixture was heated in a 60 °C
oil bath with stirring for 20 h whereupon the reaction mixture
becomes biphasic with globules of starting imine/product in the
reaction medium. The reaction mixture was allowed to cool to
room temperature and diluted with EtOAc (10 mL). The organic
layer was washed with brine (10 mL), and the aqueous layer was
back-extracted with EtOAc (3 ꢀ 10 mL). The combined organic
layers were dried over Na2SO4, filtered, and concentrated under
reduced pressure. The products were isolated by silica gel chro-
matography with use of EtOAc/hexanes mixtures and were
visualized with PMA stain.
(RS)-N-((R,E)-1-(4-Methoxyphenyl)hex-2-enyl)-2-methylpro-
panesulfinamide (3a). MIDA boronate addition: The general
procedure was followed with use of sulfinyl imine 2a (59.8 mg,
0.250 mmol) and MIDA boronate 4a (113 mg, 0.500 mmol) in
2:3 dioxane:H2O (0.8:1.2 mL). The reaction mixture was stirred
for 20 h. Column chromatography (Biotage Flashþ cartridge,
12-100% EtOAc/hexanes) afforded 65.6 mg (85% yield, 99:1
dr) of 3a as a colorless oil. HPLC (silica column, hexanes:iPrOH
97:3, 1.0 mL/min, λ = 222 nm): tminor = 17.8 min, tmajor = 23.0
min. 1H NMR and HPLC data corresponded to previously
reported data.4 Trifluoroborate addition: The preparation of
sulfinamide 3a by the Rh(I)-catalyzed addition of trifluorobo-
rate 1a was previously reported.4
materials.21
Experimental Section
General Procedure for the Addition of MIDA Boronates to
N-tert-Butanesulfinyl Imines. Inert atmosphere box procedure:
Reactions were set up in an inert atmosphere box. Hydroxy-
(1,5-cyclooctadiene)rhodium(I) dimer (2.9 mg, 0.0063 mmol,
0.025 equiv) was dissolved in dioxane (0.4 mL, 0.62 M), and the
resulting mixture was added to a vial containing 1,2-bis-
(diphenylphosphino)benzene (5.6 mg, 0.013 mmol, 0.050 equiv).
The mixture of catalyst and ligand was then added to a vial
containing a stir-vane and the appropriate MIDA boronate
(0.300-0.500 mmol, 1.2-2.0 equiv). To the mixture of catalyst,
ligand, and MIDA boronate was added the appropriate sulfinyl
imine (0.250 mmol, 1.0 equiv) dissolved in dioxane (0.4 mL,
0.62 M), followed by water (1.2 mL, 0.21 M) and K3PO4 (106 mg,
0.500 mmol, 2.0 equiv). The reaction vial was capped, removed
from the inert atmosphere box, and placed in a heating block on
the benchtop with stirring. The reaction mixture was heated to
60 °C and stirred for 20 h. Upon heating and stirring, the reaction
mixture becomes biphasic with globules of starting imine/product
in the reaction medium. The reaction mixture was allowed to cool
to room temperature and diluted with EtOAc (10 mL). The
organic layer was washed with brine (10 mL), and the aqueous
layer was back-extracted with EtOAc (3 ꢀ 10 mL). The combined
organic layers were dried over Na2SO4, filtered, and concentrated
under reduced pressure. The products were isolated by silica gel
chromatography with use of EtOAc/hexanes mixtures and were
visualized with PMA stain. Schlenk-line procedure: Reactions
were set up in a fumehood with Schlenk techniques. The appro-
priate sulfinyl imine (0.250 mmol, 1.0 equiv) was added to a 5 mL
single-necked pear-shaped flask fitted with a rubber septum,
which was subjected to three cycles of evacuation and refilling
with nitrogen gas via an inlet needle. Water (1.2 mL) and K3PO4
(106 mg, 0.500 mmol, 2.0 equiv) were added to a separate 5 mL
single-necked round-bottomed flask fitted with a rubber septum,
which was subjected to three cycles of evacuation and refilling
with nitrogen gas via an inlet needle. A 5 mL Schlenk tube equipped
with a vacuum adaptor, septum, and stir bar was charged with
hydroxy(1,5-cyclooctadiene)rhodium(I) dimer (2.9 mg, 0.0063
mmol, 0.025 equiv) and 1,2-bis(diphenylphosphino)benzene
(5.6 mg, 0.013 mmol, 0.050 equiv). After evacuating and refilling
the flask with N2 gas (3ꢀ), freshly distilled dioxane (0.3 mL) was
added by gas-tight syringe. The catalyst and ligand were stirred
under N2 atmosphere for 2 min, and then the septum was
removed and the MIDA boronate (0.500 mmol, 2.0 equiv) was
added while maintaining a strong N2 gas flow. The mixture of
catalyst, ligand, and MIDA boronate was stirred under a N2
atmosphere until the solution was homogeneous. Then the
sulfinyl imine dissolved in dioxane (0.5 mL) followed by the
(RS)-N-((R,E)-1-(Phenyl)hex-2-enyl)-2-methylpropanesulfin-
amide (3b). MIDA boronate addition (glovebox procedure): The
general inert atmosphere box procedure was followed with use of
sulfinyl imine 2b (52.3 mg, 0.250 mmol) and MIDA boronate 4a
(113 mg, 0.500 mmol) in 2:3 dioxane:H2O (0.8:1.2 mL). The
reaction mixture was stirred for 20 h. Column chromatography
(Biotage Flashþ cartridge, 12-100% EtOAc/hexanes) afforded
68.4 mg (98% yield, 99:1 dr) of 3b as a colorless oil. HPLC (silica
column, hexanes:iPrOH 98:2, 1.0 mL/min, λ = 210 nm): tminor
=
1
10.6 min, tmajor = 12.5 min. H NMR and HPLC data corres-
ponded to previously reported data.4 MIDA boronate addition
(Schlenk procedure): The general Schlenk-line procedure was
followed with use of sulfinyl imine 2b (52.3 mg, 0.250 mmol)
and MIDA boronate 4a (113 mg, 0.500 mmol) in 2:3 dioxane:H2O
(0.8:1.2 mL). The reaction mixture was stirred for 20 h. Column
chromatography (Biotage Flashþ cartridge, 12-100% EtOAc/
hexanes) afforded 64.2 mg (92% yield, 99:1 dr) of 3b as a colorless
oil. HPLC (silica column, hexanes:iPrOH 98:2, 1.0 mL/min, λ =
1
210 nm): tminor = 10.4 min, tmajor = 12.2 min. H NMR and
HPLC data corresponded to previously reported data.1 Trifluoro-
borate addition: The preparation of sulfinamide 3b by the Rh(I)-
catalyzed addition of trifluoroborate 1a was previously reported.4
Acknowledgment. This work was supported by a grant
from the National Science Foundation (CHE-0742565).
Supporting Information Available: General experimental
methods and materials, synthesis and characterization of
MIDA boronates 4, specific reaction conditions, and copies of
1H NMR and HPLC traces of sulfinamides 3. This material is
available free of charge via the Internet at http://pubs.acs.org.
(21) For the addition of an alkenyl MIDA boronate and the correspond-
ing trifluoroborate to more complex N-tert-butanesulfinyl imines in the
context of a natural product synthesis, see: Brak, K.; Ellman, J. A. Org.
Lett. DOI: 10.1021/ol100470g. Published Online: March 31, 2010.
3150 J. Org. Chem. Vol. 75, No. 9, 2010