Chiral biscarboline N,N′-dioxide derivatives: Highly enantioselective addition of allyltrichlorosilane to aldehydes

Article abstract of DOI:10.1002/adsc.201100592

The allylation of aromatic and aliphatic aldehydes with allyltrichlorosilanes has been catalyzed with a new Lewis base organocatalyst, 1,1′-biscarboline N,N′-dioxide with high enantioselectivities of up to 99% for 4-methoxybenzaldehyde and 97% ee for cycl

Full text of DOI:10.1002/adsc.201100592

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DOI: 10.1002/adsc.201100592
Chiral Biscarboline N,N’-Dioxide Derivatives: Highly
Enantioselective Addition of Allyltrichlorosilane to Aldehydes
Bing Bai,a,b Lan Shen,a,b Jie Ren,a and Hua Jie Zhua,c,*
a
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese
Academic of Sciences, Lanhei Road 132#, Kunming 650204, Peopleꢀs Republic of China
Fax : (+86)-871-521-6179; e-mail: hjzhu@mail.kib.ac.cn
Graduate School of CAS, Beijing 100049, Peopleꢀs Republic of China
College of Life Science, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education,
b
c
Hebei University, Baoding 071002, Peopleꢀs Republic of China
Received: July 27, 2011; Revised: August 29, 2011; Published online: February 9, 2012
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201100592.
Abstract: The allylation of aromatic and aliphatic
aldehydes with allyltrichlorosilanes has been cata-
lyzed with a new Lewis base organocatalyst, 1,1’-
biscarboline N,N’-dioxide with high enantioselectiv-
ities of up to 99% for 4-methoxybenzaldehyde and
97% ee for cycloformaldehyde, respectively. In
total, 13 heteroaryl and aliphatic aldehydes were
tested.
tioselectivity in the addition of aromatic aldehydes
with allylboronic acid pinacol ester. The N!O-con-
taining catalysts, 5[7a] and 6,[6a] had high enantioselec-
tivities in the additions of aromatic aldehydes with al-
lyltrichlorosilanes but poor selectivities in the addi-
tion of aliphatic aldehydes. Herein, we report a series
of axially chiral 1,1’-biscarboline N,N’-dioxide deriva-
tives as the catalysts used in allylation. High enantio-
selectivity (up to 99% ee for benzaldehyde addition
and up to 97% ee for cycloformaldehyde) were re-
corded, respectively, when 1 mol% of catalyst was
used.
Keywords: allylation; asymmetric catalysis; 1,1’-bis-
carboline N,N’-dioxides; organocatalysts
Asymmetric additions of aldehydes with allyltrialkyl-
silanes[1] has been one of the most efficient methods
to form homoallylic alcohols catalyzed by chiral
Lewis or Brønsted acids,[2] especially using some bi-
naphthyl derivatives.[3] Chiral phosphoramides, forma-
mides or N-oxide derivatives possessing strong elec-
tron-donating properties also play important roles in
the additions.[4–5] Since Nakajimaꢀs reports that axially
chiral 2,2’-bipyridine N,N’-dioxides were effective as
catalysts for the asymmetric allylation,[6] the class of
2,2’-bipyridine N,N’-dioxide derivatives has attracted
considerable attention in the groups of Hayashi,[7]
Malkov,[8] Dennmark,[9] Kotora,[10] and others.[11] Most
of the axially chiral N,N’-dioxide derivatives reported
were analogues of biquinolines and/or bipyridines.
It is found that only the catalysts that chelated with
a metallic ion, for example, Ti complexes, 1,[12] and
2,[13] gave high enantioselectivities in the additions of
both aromatic and aliphatic aldehydes with strongly
toxic allyltributyltin (Figure 1). Catalysts 3[14] and 4[15]
exhibited high enantioselectivities in additions of ali-
phatic aldehydes. However, 4 did not show high enan- Figure 1. Previously reported, effective catalysts.
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Chiral Biscarboline N,N’-Dioxide Derivatives: Highly Enantioselective Addition of Allyltrichlorosilane
Scheme 1. Synthesis of axially chiral catalysts 13.
The synthetic route to biscarboline N,N’-dioxide de- configuration for chiral compounds, especially for
rivatives is illustrated in Scheme 1. The Pictet–Spen- rigid chiral compounds.[16] Conformational searches
gler reaction was employed firstly to form tetrahydro- for 13a were performed using MMFF94S force field,
carboline 8. l-Tryptophan methyl ester and glyoxal the stable conformations were then optimized at the
were not used as starting materials since the product B3LYP/6-31G(d) level. Only the lower energy confor-
1,1’-bistetrahydrocarboline cannot be obtained in any mations with the relative energy from 0–2.5 kcalmolꢀ1
conditions. Carboline 9 which is derived from the ary- were used in OR computations at the B3LYP/6-311+
lation of 8 using trichloroisocyanuric acid was hydro- +GACTHUNTGRNEUNG(2d,p) level. Boltzmann statistics were then used
lyzed in the presence of p-toluenesulfonic acid to give for whole conformational OR computations. (S)-13a
aldehyde 10, the latter underwent another Pictet– had the OR magnitudes of ꢀ941.5. It was found that
Spengler condensation to form epimer 11. 1,1’-Biscar- one enantiomer of 13a had the OR values of +750.0
boline 12 was obtained through indole N-methylation (c 0.27, CHCl3). Thus, (+)-13a was assigned as the (R)
of the arylated 11 in the presence of sodium hydride configuration. Similarly, (+)-13b to (+)-13d were as-
as a base. Oxidation of the 1,1’-bicarboline 12 afford- signed as (R) too based on the positive OR magni-
ed dioxide 13 (48%) and monoxide (37%) along with tudes.[17]
traces of the unreacted 12 (<5%). The racemates 13
The addition of allyltrichlorosilane 15 to benzalde-
were resolved into enantiomers by using HPLC with hyde (14) was carried out in the presence of (+)-13
a Chiralpak IC column. The reduction of 13a using near ꢀ808C for 16 h.The effect of solvents, such as
lithium aluminum hydride afforded 13b, and acetyla- toluene, THF, EtOAc, acetonitrile and dichlorome-
tion and benzoylation of 13b produced the corre- thane on the addition reactions was investigated. The
sponding 13c and 13d, respectively.
former three solvents led to enantioselectivities from
The absolute configuration of ligand 13a was identi- 85–90% but poor conversion (about 10%). Only
fied based on the experimental optical rotation (OR) CH2Cl2 exhibited good conversion (100%) and high
values relative to the one that was calculated using enantioselectivity. Thus, CH2Cl2 was used in the addi-
density functional theory (DFT). The DFT method tion reactions. Enantioselectivity as high as 95% ee
has been widely used for OR computations, by which was recorded when 5% of catalyst was used. The high
the OR values were calculated to determine absolute enantioselectivity (up to 95% ee) was retained when
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Table 1. Enantioselectivities in the addition of allyltrichloro-
Table 2. Asymmetric allylation to aldehydes catalyzed by
(R)-(+)-13a.[a]
silane to benzaldehyde.[a]
Entry R
Yield[b]
[%]
ee[c]
[%]
Configuration[d]
Entry
Cat.* (mol%)
Conversion [%][b]
ee [%][c]
1
2
3
4
5
6
(+)-13a (10)
(+)-13a (1)
(+)-13a (0.1)
(+)-13b (5)
(+)-13c (5)
(+)-13d (5)
100
100
26
100
100
100
95 (S)
95 (S)
95 (S)
60 (S)
77 (S)
79 (S)
1
2
3
4
5
6
7
8
Ph
88
95
99
97
97
95
97
95
97
96
97
(S)
(S)
(S)
(S)
(S)
(S)
(S)
(S)
(S)
(R)[e]
4-MeO-C6H4 75
3-Cl-C6H4
4-Cl-C6H4
3-F-C6H4
4-F-C6H4
4-Me-C6H4
74
77
71
76
74
[a]
Reaction conditions: 14 (0.5 mmol), 15 (0.6 mmol),
(+)-13 (0.1–10 mol%).
Estimated by recovering unreacted PhCHO.
2-thiophenyl 83
9
10
1-naphthyl
2,6-di-Cl-
C6Hs
82
87
[b]
[c]
By HPLC using chiral column.
11
12
PhCH=CH2
PhCH2CH2
c-C6H11
90
73
53
91
92
97
(S)
(R)
the quantity of (+)-13a was reduced to 1 mol%. It 13
(S)[f]
was fascinating that (+)-13a gave 95% enantioselec-
tivity when 0.1 mol% of (+)-13a was used although a
lower conversion (26%) was recorded when the addi-
tion was carried out for 16 h. Ligands (+)-13b,
(+)-13c and (+)-13d had low enantioselectivities
(Table 1, entries 4, 5, 6).
[a]
Reaction conditions: aldehyde (0.5 mmol), 15 (0.6 mmol),
(+)-13a (1 mol%).
Isolated yield. Some products are fairly volatile.
Determined by HPLC using a chiral column.
Determined by comparing OR data and retention times
using HPLC.
[b]
[c]
[d]
[e]
The absolute configuration was determined using two
methods: one is to refer the report (Ref.[18]), the other
one is to compute its det(D) values (Ref.[19]). The com-
puted det(D) for the (S) enantiomer was ꢀ20.9. The re-
corded optical rotation was +10.0 with the corresponding
k0 of ꢀ0.48. Thus, only (R) enantiomer has negative OR
values.
(R)-(+)-13a (1 mol%) was used in addition of other
aldehydes (Table 2). The observed % ee values for
most aldehydes additions were over 96%. Especially,
this catalyst had both strong enantioselectivity in ad-
dition to aliphatic aldehydes, for example, cyclofor-
maldehyde (97% ee) and high conversion (up to
100%). In contrast, most reported metallic ion-free
catalysts exhibited low to moderate enantioselectivi-
ties in the additions of allyltrichlorosilane to aliphatic
aldehydes.[1c,7a,8a] Enantiomer (ꢀ)-13a had the same
[f]
Determined after conversion to the 3,5-dinitrobenzoate
ester.
catalytic ability as (+)-13a as expected, including the Experimental Section
conversion (100%) and % ee values (up to 96% ee) in
the addition of benzaldehyde with allyltrichlorosilane, 1,1’-Biscarboline N,N’-Dioxide [(ꢁ)-13a]
its addition product had the opposite OR sign. The
strong enantioselective ability that 13a exhibited is
one of the best known for current catalysts.
m-Chloroperoxybenzoic acid (70%, 3 mmol) was added por-
tion-wise to a stirred solution of 12 (1 mmol) in CH2Cl2
(50 mL) at 08C, and the stirring was continued at room tem-
The general mechanism was proposed by Nakajima.
During the allylation reaction, the N-oxide functional
group possesses a notable electron-pair donor proper-
ty, and exhibits a significant nucleophilicity towards
the silicon atom.[6a] The allyl group was then trans-
ferred to the carbonyl group via a chair-like six-mem-
bered cyclic transition state.
In conclusion, a highly efficient, axially chiral 1,1’-
biscarboline N,N’-dioxide, (R)-(+)-13a, has been de-
veloped and this catalyst exhibited excellent enantio-
selectivity in the asymmetric allylation of various al-
dehydes. Studies on expanding the scope and consid-
ering the mechanism of enantioselective reactions are
in progress and will be reported in the future.
perature for further 24 h. Then the mixture was poured into
saturated aqueous NaHCO3 (50 mL) and extracted with
CH2Cl2. The combined organic layers were dried over
Na2SO4. The filtered solution was concentrated under
vacuum. The residue was purified by chromatography (silica
gel) eluting with CH2Cl2/CH3OH (80/1) to give dioxide (ꢁ)-
13a as a pale yellow solid; yield: 245 mg (48%). The racemic
mixtures of (ꢁ)-13a were resolved by HPLC on a Chiral-
pak-IC column (250ꢂ10 mm, CH2Cl2/CH3OH=40/60) and
both (+)-13a and (ꢀ)-13a were obtained in 48% and 47%
yields, respectively.
(+)-13a: [a]D: +750 (c 0.27, CHCl3); mp>3008C
(decomp.); MS-ESI: m/z=511 [M+H]+; HR-MS: m/z=
511.1608, calcd. for C28H23N4O6 [M+H]+: 511.1617; IR
(KBr): n=3440, 1738, 1598, 1436, 1392, 1284, 1242,
356
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Chiral Biscarboline N,N’-Dioxide Derivatives: Highly Enantioselective Addition of Allyltrichlorosilane
751 cmꢀ1
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1H NMR (400 MHz, CDCl3): d=3.44 (s, 3Hꢂ2,
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