Rhodium-Catalyzed Addition of Alkyltrifluoroborate Salts to Imines

Article abstract of DOI:10.1002/adsc.201500295

An efficient rhodium-catalyzed addition of potassium alkyltrifluoroborate salts to imines is presented. In this reaction, secondary alkyltrifluoroborate salts were coupled with N-sulfonylimines in the presence of bis[(1,5-cyclooctadiene)(hydroxy)rhodium] {[Rh(OH)(cod)]₂} in good yields under mild reaction conditions, and the γ-amino ester products could be converted to β,γ-substituted lactams via cyclization. It was shown that the addition of enantiomerically enriched substrates to imines proceeded with excellent enantiospecificity and stereoretention without β-hydride elimination.

Full text of DOI:10.1002/adsc.201500295

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DOI: 10.1002/adsc.201500295
Rhodium-Catalyzed Addition of Alkyltrifluoroborate Salts to
Imines
Sumin Lee,a Woo Lim Lee,a and Jaesook Yuna,*
a
Department of Chemistry and Institute of Basic Science, Sungkyunkwan University, Suwon 440-746, Korea
Fax: (+82)-31-290-7075; e-mail: jaesook@skku.edu
Received: March 25, 2015; Revised: May 12, 2015; Published online: July 14, 2015
Dedicated to Prof. Stephen L. Buchwald on the occasion of his 60th birthday.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500295.
Abstract: An efficient rhodium-catalyzed addition
of potassium alkyltrifluoroborate salts to imines is
presented. In this reaction, secondary alkyltrifluoro-
borate salts were coupled with N-sulfonylimines in
the presence of bis[(1,5-cyclooctadiene)(hydroxy)-
rhodium] {[Rh(OH)(cod)]2} in good yields under
mild reaction conditions, and the g-amino ester
products could be converted to b,g-substituted lac-
tams via cyclization. It was shown that the addition
of enantiomerically enriched substrates to imines
proceeded with excellent enantiospecificity and
stereoretention without b-hydride elimination.
The Rh-catalyzed addition of organoboronic acid
and organoboronate reagents to activated imines for
the synthesis of amines has been extensively studied.[5]
However, the use of alkylboron compounds in addi-
tion reactions to imines, to the best of our knowledge,
has not been reported. We herein report the rhodium-
catalyzed addition of alkyltrifluoroborate salts to
imines.
We began our study by investigating reactions of
various imines with simple potassium benzyltrifluoro-
borate salt (1) using [Rh(OH)(cod)]2 as catalyst (see
the Supporting information for details; Table S1).
Among the imines screened, reactions of N-sulfonyl-
imines, such as N-tosyl- and N-nosylimine with 1 gave
the desired addition products in only moderate yields,
while N-sulfinylimines[6] and N-diphenylphosphinoyli-
mines[6a] were not efficient coupling partners. There-
fore, we next surveyed reactions of secondary benzyl-
ic boronic ester 2a or trifluoroborate salt 3a with N-
Keywords: addition; enantiospecificity; imines; lac-
tams; rhodium
The rhodium-catalyzed 1,4-addition and 1,2-addition sulfonylimines under various reaction conditions with
of organoboron compounds to electrophiles has been the expectation of a more rapid transmetalation
established as a reliable tool for carbon-carbon bond (Table 1). Boronate ester 2a was easily prepared fol-
formation since the initial reports from Miyaura and lowing a protocol developed for b-borylation of a,b-
co-workers.[1] While excellent results using boronic unsaturated carbonyl compounds,[7] and the corre-
acids or potassium organotrifluoroborates have been sponding trifluoroborate salt 3a was prepared by
reported in addition reactions,[2] most of the existing treatment of 2a with KHF2.[8] Reactions of 3a with to-
methods have employed aryl- or alkenylboron deriva- sylimine 4a derived from p-CNC6H4CHO gave addi-
2
À
tives that have C(sp ) B bonds. In contrast, the use of tion products in good yields using the [Rh(OH)(cod)]2
transition metal catalysis with alkylboron derivatives catalyst at 458C with an appropriate amount
is rare due to challenges such as side reactions result- (60 equiv.) of water (entry 5 vs. entries 4 and 6). At
ing from slow transmetalation and b-hydride elimina- higher temperatures with less water (entries 1 and 2)
tion. Overcoming these obstacles, Aggarwal and co- or with polar solvents such as DMF (entry 3), the re-
workers reported the first stereospecific 1,2-addition action was not as effective. Using pinacolboronate 2a
of potassium alkyltrifluoroborate salts to aldehydes.[3] directly in the presence of KHF2, as had been used
Our group also recently reported a stereoretentive ad- previously in the addition to aldehydes,[4] was not effi-
dition of chiral alkyl pinacolboronates bearing a b- cient (entry 7). Finally, it was found that the reaction
carbonyl group to aldehydes to produce g-butyrolac- proceeded equally well without the phosphine ligand,
tones.[4]
and these conditions were deemed optimal (entry 8).
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Sumin Lee et al.
Table 1. Optimization of the addition reaction.[a]
Entry
Catalyst
Temperature [8C]
Solvent/H2O (equiv.)
Yield [%][b]
1
2
3
4
[Rh(OH)(cod)]2/dppbz[c]
RhCl(cod)2/dppbz
80
80
55
55
45
45
45
45
toluene/H2O (40)
toluene/H2O (40)
DMF/H2O (70)
toluene/H2O (70)
toluene/H2O (60)
toluene/H2O (10)
toluene/H2O (60)
toluene/H2O (60)
45
40
[Rh(OH)(cod)]2/dppbz
[Rh(OH)(cod)]2/dppbz
[Rh(OH)(cod)]2/dppbz
[Rh(OH)(cod)]2/dppbz
[Rh(OH)(cod)]2[/gd] ppbz
[Rh(OH)(cod)]2
N.R.[d]
60
5
68 (1:1.1)[e]
N.R.[d]
45
6
7[f]
8
70 (1:1.3)[e]
[a]
2.5 mol% Rh catalyst, 5 mol% ligand, 3a, and 1.2 equiv. of 4a relative to 3a were used.
Isolated yield of a mixture of diastereomers.
1,2-Bis(diphenylphosphino)benzene.
[b]
[c]
[d]
[e]
[f]
No significant product formation.
Diastereomeric ratio of 5a-syn and 5a-anti determined by H NMR analysis of the crude mixture.
1
2a and 1.2 equiv. of KHF2 were used.
No phosphine ligand was used.
[g]
Table 2. Rhodium-catalyzed addition of b-carbonyl trifluoroborate salts 3 to imines.
Entry
3
Imines Ar2
P[a]
Yield of 5 [%][b] (dr)[c]
Yield of 6 [%][d] (dr)[c]
1
2
3
4
5
6
7
8
3a
3a
3a
3a
3a
3a
3a
3a
3b
3b
3b
3c
4-CNC6H4
4-NO2C6H4
4-MeO2CC6H4
4-CF3C6H4
Ph
tosyl (4a)
tosyl (4b)
tosyl (4c)
tosyl (4d)
tosyl (4e)
tosyl (4f)
nosyl (4g)
nosyl (4h)
tosyl (4b)
tosyl (4d)
nosyl (4i)
tosyl (4b)
– (5a)
– (5b)
62 (1:1.1)
71 (1:1)
–
–
–
–
60 (1:1.2)
–
92
79[f]
–
84 (5c) (1:1.7)
68 (5d) (1:1.5)
54 (5e) (1:1.4)
N.R.[e] (5f)
64 (5g)
42 (5h) (1.7:1)
90 (5i) (1:1)
85 (5j) (1:1)
63 (5k) (1.5:1)
52 (5l) (1:1.5)
4-MeOC6H4
Ph
2-CH3C6H4
4-NO2C6H4
4-CF3C6H4
4-MeOC6H4
4-NO2C6H4
9
10
11
12
–
[a]
tosyl=p-toluenesulfonyl, nosyl=p-nitrophenylsulfonyl.
Isolated yield of 5-syn and 5-anti.
[b]
[c]
[d]
[e]
[f]
The diasteromeric ratio (dr) was determined by 1H NMR analysis.
Isolated yield of 6-cis and 6-trans over 3 steps.
No reaction.
Yield of 6j from 5j.
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Rhodium-Catalyzed Addition of Alkyltrifluoroborate Salts to Imines
Scheme 1. Enantiospecifity of the imine addition.
Table 3. 1,2-Addition of secondary benzyltrifluoroborate salts 7 to imines.
Entry
Substrate (7) Ar1
Imine (4)
Yield of 8 [%][a] (dr)[b]
1
2
3
4
Ph (7a)
4-MeOC6H4 (7b)
7b
7b
4e
4b
4d
4g
67 (1:2) (8a)
83 (1:1.5) (8b)
75 (1:2) (8c)
61 (1:1.7) (8d)
[a]
Isolated yield of 8.
[b]
The diasteromeric ratio (dr) was determined by 1H NMR analysis.
The optimized reaction conditions were applied to is noteworthy that nosyl derivatives of simple phenyl
combinations of a range of organotrifluoroborate salts (4g), sterically encumbered o-tolyl (4h), and electron-
(3) and N-sulfonylimines (4) with several electronical- donating p-methoxylphenyl (4i) substrates participat-
ly and sterically different aryl groups to examine the ed in the reaction to give improved yields of the addi-
scope of the reaction (Table 2). Addition products (5) tion products (entries 7, 8, and 11).
were generally obtained in good yields, and in some
The enantiospecificity (es)[12] of the addition was in-
cases, the initial products were directly transformed vestigated with the enantiomerically enriched
into the corresponding lactams (6) without isolation.[9] trifluoroborate salt (S)-3a.[7b] Reaction of (S)-3a with
In general, the diastereoselectivity of the reaction was tosyl- (4b) and nosylimine (4g) proceeded to give ad-
not high and did not vary significantly with different dition products 5b and 5g, which were subsequently
substrates.[10] With regard to the nucleophilic compo- converted to the corresponding g-lactams 6[10b,13] by
nent, potassium trifluoroborates with phenyl (3a) or cyclization (Scheme 1). Excellent enantiospecificity
electron-donating aryl groups (3b) gave products in (>99%) was obtained in both cases and complete
high yields. In comparison, a substrate with an elec- stereoretention[14] was observed in this process.
tron-withdrawing CF3 group (3c) was less efficient,
Next, we briefly examined whether the extra coor-
but was reactive enough to afford addition products dinating carbonyl group was necessary for a successful
in moderate yields. These results are similar to reports reaction. Simple trifluoroborate salts 7 were prepared
of other Rh-catalyzed additions where electron-poor by hydroboration[15] and subsequent transformation to
boron reagents are less nucleophilic and afford prod- the salts (Table 3). The conditions developed for addi-
ucts in lower yields.[11]
tion of b-carbonyl trifluoroborates were applied, and
Activated tosylimines with an electron-withdrawing the reactions with N-sulfonylimines gave the desired
substituent (4a–4d) and phenyl group (4e) were suita- products in good yields.[16]
ble substrates affording good yields of the addition
In summary, we report the first example of a metal-
products (entries 1–5), but the reaction with an imine catalyzed addition of potassium alkyltrifluoroborates
possessing a strongly electron-donating MeO group to imines using a Rh catalyst. The reaction proceeded
(4f) was not efficient (entry 6). However, this limita- well with a variety of N-tosyl- or nosylimines with al-
tion was overcome by use of nosylimine derivatives. It kyltrifluoroborate salts under mild reaction condi-
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Sumin Lee et al.
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tions, and amino ester products could subsequently
undergo cyclization to afford b,g-substituted lactams.
The addition reaction proceeded with high enantio-
specificity and stereoretention, providing a good ex-
ample of the competency of alkyl-organometallic
compounds in conjunction with transition metal catal-
ysis.
Experimental Section
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General Procedure
A mixture of [Rh(OH)(cod)]2 (2.5 mol%, 2.3 mg), potassi-
um secondary alkyltrifluoroborates (3 or 7) (0.2 mmol) and
N-sulfonylimines (4) (0.3 mmol) was dissolved in anhydrous
toluene (1.4 mL). Distilled H2O (12 mmol, 0.2 mL) was
added to the reaction mixture under a nitrogen atmosphere.
The reaction mixture was stirred at 458C and monitored by
TLC. After 24 h, the reaction mixture was extracted with
ethyl acetate (3”10 mL). The combined organic layers were
dried over Na2SO4 and concentrated. The product (5 or 8)
was purified by chromatography on silica gel or transformed
to the corresponding lactam.
[7] a) S. Mun, J.-E. Lee, J. Yun, Org. Lett. 2006, 8, 4887–
4889; b) J.-E. Lee, J. Yun, Angew. Chem. 2008, 120,
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Schrimpf, J. Org. Chem. 1995, 60, 3020–3027; b) R. A.
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[10] The relative stereochemistry of addition products 6g
was determined by comparison with NMR data report-
ed in the literature and by NOE experiments on 6k,
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b) J. Escalante, M. A. Gonzµlez-Tototzin, Tetrahedron:
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other products in Table 2 was assigned by analogy.
[11] a) K. Brak, J. A. Ellman, J. Org. Chem. 2010, 75, 3147–
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Acknowledgements
This research was supported by the Basic Science Research
Program administered through the National Research Foun-
dation of Korea (NRF) funded by the Ministry of Education,
Science, and Technology (NRF-2013R1A1A2058160).
[12] The enantiospecificity can be calculated using the equa-
tion [% es=(ee of product/ee of starting material)”
100], which indicates the degree of conservation of
enantiomeric purity over the course of the reaction:
S. E. Denmark, T. Vogler, Chem. Eur. J. 2009, 15,
11737–11745.
[13] a) S. Lesniak, R. B. Nazarski, B. Pasternak, Tetrahedron
2009, 65, 6364–6369; b) N. K. Yee, Tetrahedron Lett.
1997, 38, 5091–5094.
[14] The absolute configuration of the b-carbon of 6g was
determined as S by comparing its HPLC chromatogram
with that of 6g derived from the known compound. See
ref.[10b] and the Supporting Information for details.
[15] a) D. Noh, H. Chea, J. Ju, J. Yun, Angew. Chem. 2009,
121, 6178–6180; Angew. Chem. Int. Ed. 2009, 48, 6062–
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Chem. Asian J. 2011, 6, 1967–1969.
[16] The relative stereochemistry of addition product (8a)
was determined by comparison with NMR data report-
ed in the literature after deprotection, J. L. G. Ruano, J.
Alemµn, I. Alonso, A. Parra, V. Marcos, J. Aguirre,
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