Remarkably efficient enantioselective titanium(IV)-(R)-H 8-BINOLate catalyst for arylations to aldehydes by triaryl(tetrahydrofuran)aluminum reagents

Article abstract of DOI:10.1021/ja062080y

Novel asymmetric triarylaluminum AlAr₃(THF) additions to aldehydes catalyzed by 10 mol % of the titanium(IV) complex of (R)-H₈-BINOL ligand are reported. The catalytic system is extremely efficient with reactions completing within 10 min. The system applies to the most diversified aldehydes to date, and more than 20 aldehydes were examined to afford diarylmethanols having an electron-donating or an electron-withdrawing group at the 2-, 3-, or 4-position on the aryl moiety, linear or branched 1-aryl aliphatic alcohols, aryl furyl methanols, 1-aryl allylic alcohols, and, especially, 1-aryl propargylic alcohols in excellent enantioselectivities of ≥90% ee, except for the case of 1-naphthyl addition to benzaldehyde. Noteworthily, diarylmethanols in both R- and S-configurations can be obtained. Copyright

Full text of DOI:10.1021/ja062080y

Published on Web 11/01/2006
Remarkably Efficient Enantioselective Titanium(IV)-(R)-H8-BINOLate Catalyst
for Arylations to Aldehydes by Triaryl(tetrahydrofuran)aluminum Reagents
Kuo-Hui Wu and Han-Mou Gau*
Department of Chemistry, National Chung-Hsing UniVersity, Taichung, Taiwan 402
Received April 1, 2006; E-mail: hmgau@dragon.nchu.edu.tw
Organozinc is one of the most widely used reagents in the past
decade for asymmetric C-C bond formation reactions due to its
mild and controllable characteristics for inducing high enantiose-
lectivity.1 Recently, chiral diaryl alcohols,2 propargyl alcohols,3 and
allyl alcohols4 are increasingly demanded as intermediates for
important bio-active compounds.5 For asymmetric aryl additions
to aldehydes, the catalytic reaction was first reported by Seebach
and co-worker, employing a highly reactive PhTi(O-i-Pr)3 reagent
at -78 °C.6 After the works of direct ZnPh2 addition by Fu et al.,7
considerable progresses in arylation reactions were developed.8 To
improve stereoselectivities, an addition of ZnEt2 to the catalytic
system was first discovered by Pu and co-worker,9 and it was later
found by Bolm and co-workers that the quantity of the expensive
ZnPh2 can be reduced to 0.65 equiv.10 Bolm and co-worker further
developed arylzinc reagents from reactions of dialkylzinc and
arylboronic acids.11 This study extends the scope of phenylation to
arylation reactions, and several catalytic systems5d,12 were reported
to induce excellent stereoselectivities, including systems using other
arylboron reagents.13 In the most recent papers, Pu and co-workers
reported direct ZnPh2 additions to both aromatic and aliphatic
aldehydes, employing a modified H8-BINOL ligand,14 and Walsh
and co-worker reported in situ-formed arylzinc reagents from
reactions of aryllithiums and ZnCl2 for asymmetric arylations to
aldehydes.15
In contrast, organoaluminum reagents are excellent nucleophiles
for organic reactions due to their higher reactivity and a greater
Lewis acidity of the metal center.16 Moreover, the industrial bulk
aluminum alkyls or hydrides insert into unsaturated C-C bonds,17
and aluminum reagents can even deprotonate a hydrogen from sp
or sp2 carbons16h,18 to furnish diversified organoaluminum reagents
for further reactions. Additional advantages include low toxicities
and considerable stabilities for preservation under inert atmosphere
or even in air.19 Nevertheless, their applications to asymmetric
catalysis are still limited. The first asymmetric catalytic application
of organoaluminum reagents was developed by Chan and co-
workers involving triethylaluminum additions to aldehydes20 fol-
lowed by methylation reactions by Carreira et al.21 and Woodward
et al.,19 and ethylation or allylation reactions by Alexakis et al.22
and by us.23 In addition, asymmetric alkynylation reactions to a
cyclic enone were demonstrated by Corey and co-worker.24
We here report novel asymmetric additions of easily prepared
triaryl(tetrahydrofuran)aluminum AlAr3(THF)25 to aldehydes cata-
lyzed by a titanium(IV) complex of (R)-H8-BINOL. Optimizations
of reaction conditions were conducted on 2-chlorobenzaldehyde and
catalyst precursor [Ti{(R)-H8-BINOLate}(O-i-Pr)2]x (1)26 (eq 1).
and 1.25 equiv of Ti(O-i-Pr)4 afforded the product in 100% yield
in 12 h with the best enantioselectivity of 93% ee (Table 1, entry
1). Under the optimized conditions but without the catalyst
precursor, we surprisingly found that the background reaction
afforded the racemic product in 73% yield in 10 min (entry 2),
suggesting that the catalytic reaction should be complete within
10 min. Indeed, the catalytic reaction gave the product in 98% yield
with a comparable enantioselectivity of 92% ee in 10 min (entry
3), and in 5 min, the product was obtained in 86% yield with 90%
ee (entry 4). In 1 min, the reaction afforded the product in 43%
yield with 88% ee (entry 5). Catalytic reactions with lower catalyst
loading at 5 and 2.5 mol % were then examined to give the product
in 96 and 95% yields with enantioselectivities of 90 and 86% ee
(entries 6 and 7), respectively.
To elucidate roles of AlPh3(THF) and Ti(O-i-Pr)4 in the reaction,
an immediate formation of a bimetallic complex 2 was obtained
from mixing equal molar equivalents of the two reagents. The
catalytic phenyl addition using reagent 2 gave the product in the
same 93% ee. To clarify how the complex 2 transfers the phenyl
group, a stoichiometric reaction of 1, 2-chlorobenzaldehyde, and
PhTi(O-i-Pr)3 was examined to afford the product in 96% ee,
suggesting that the complex 2 probably transfers the PhTi(O-i-Pr)3
moiety to the Ti-H8-BINOLate complex to give an active bimetallic
species 3 having a structure similar to structures of bimetallic
titanium complexes of H8-BINOL26 and of N-sulfonylated â-amino
alcohol.27
Generalities of the catalytic system in a reaction time of 10 min
were examined on a variety of aldehydes (eq 2), and results are
listed in Table 2.
The catalytic system applies to aromatic aldehydes with an electron-
donating or an electron-withdrawing substituent at the 2-, 3-, or
4-position to give chiral diarylmethanols in excellent isolated yields,
and excellent enantioselectivities ranged from 92 to 97% ee (entries
1-10). For 1- or 2-naphthylaldehyde, 96 and 94% ee (entries 11
and 12) were obtained, respectively. The catalyst works equally
well for both linear and branched aliphatic aldehydes and for poly-
functional aldehydes, such as 2-furylaldehyde and vinyl aldehydes
with enantioselectivities ranging from 91 to 99% ee (entries 13-
18). Additions to poly-functional carbonyls are important reactions
It was found that the reaction employing 1.2 equiv of AlPh3(THF)
9
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J. AM. CHEM. SOC. 2006, 128, 14808-14809
10.1021/ja062080y CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Optimizations of Asymmetric Phenyl Addition of
AlPh3(THF) to 2-Chlorobenzaldehyde Catalyzed by the In
Situ-Formed 1/Ti(O-i-Pr)4 Systemsa
In summary, novel asymmetric aryl additions of AlAr3(THF) to
aldehydes catalyzed by the Ti(IV) catalyst of (R)-H8-BINOL are
reported. Important features demonstrated in this study include an
easy processing relative to previous studied systems, both easily
prepared simple and substituted arylaluminum reagents used to
afford chiral alcohols in excellent enantioselectivities, and the
catalytic system applying to the most diversified aldehydes to date.
Moreover, diarylmethanols in both R- and S-configurations can be
obtained. Most importantly, the catalytic system is extremely
efficient with the reactions completing within 10 min, and the
suppression of the background reaction is not required.
entry
1 (mol%)
time
yield (%)b
ee (%)c
1
2
3
4
5
6
7
10
12 h
100
73
98
86
43
96
95
93
10 min
10 min
5 min
1 min
10 min
10 min
10
10
10
5
92
90
88
90
86
2.5
a 2-Chlorobenzaldehyde/AlPh3(THF)/Ti(O-i-Pr)4 ) 0.5/0.6/0.625 mmol.
b Yields were based on 1H NMR spectra. c Enantioselectivities were
determined by HPLC.
Acknowledgment. Financial support under Grant Number NSC
94-2113-M-005-012 from the National Science Council of Taiwan
is appreciated.
Table 2. Asymmetric AlAr3(THF) Addition to Aldehydes Catalyzed
by the In Situ-Formed 1/Ti(O-i-Pr)4 Catalysta
Supporting Information Available: Synthesis of compounds and
HPLC analytical conditions of chiral products. This material is available
free of charge via the Internet at http://pubs.acs.org.
entry
RCHO
Ar
yield (%)b
ee (%)c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
2-ClC6H4CHO
3-ClC6H4CHO
4-ClC6H4CHO
2-MeC6H4CHO
3-MeC6H4CHO
4-MeC6H4CHO
2-(MeO)C6H4CHO
3-(MeO)C6H4CHO
4-(MeO)C6H4CHO
4-(CF3)C6H4CHO
1-naphthylaldehyde
2-naphthylaldehyde
n-BuCHO
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
93
90
92
92
96
95
96
94
96
94
90
92
90
89
70
89
95
91
93
96
88
80
87
90
52
92 (R)
94 (R)
95 (R)
96 (R)
94 (R)
95 (R)
95 (R)d
94 (R)
97 (R)
96 (R)
96 (R)
94 (R)
91 (S)
96 (S)
99 (S)
94 (R)
91 (S)d
92 (S)
95 (R)
97 (R)
94 (S)
90 (S)
93 (S)e
92 (S)
72 (S)
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i-PrCHO
t-BuCHO
2-furylaldehyde
(E)-PhCHdCHCHO
(E)-n-PrCHdCHCHO
PhCtCCHO
n-BuCtCCHO
C6H5CHO
C6H5CHO
C6H5CHO
C6H5CHO
C6H5CHO
p-tolyl
4-(MeO)C6H4
4-(TMS)C6H4
2-naphthyl
1-naphthyl
a Substrate/AlAr3(THF)/1/Ti(O-i-Pr)4 ) 0.5/0.6/0.05/0.625 mmol. b Iso-
lated yields. c Enantioselectivities were determined by HPLC using suitable
chiral column from Daicel. d Ti(O-i-Pr)4, 0.75 mmol. e The enantioselectivity
was determined after conversion the TMS product into the bromo product.
to afford corresponding alcohols as building blocks for further
reactions, and asymmetric alkynyl additions to R,â-unsaturated
aldehydes have been demonstrated in a recent paper by Trost and
co-workers.28 To our knowledge, only one example of a phenyl
addition to the acetylenyl aldehyde, TIPSCtCCHO, was reported
to afford the propargyl alcohol in 85% ee.8c Our system also applies
to phenylacetylenyl and n-butylacetylenyl aldehydes to afford
propargyl alcohols in 95 and 97% ee (entries 19 and 20). Entries
21-24 demonstrate additions of substituted aryl to afford desired
products with excellent stereoselectivities from 90 to 94% ee. The
additions of substituted aryl to benzaldehyde afforded products in
reverse S-configurations in contrast to the R-products obtained by
the phenyl addition to the substituted benzaldehydes. However, the
addition by the more hindered 1-naphthyl to benzaldehyde gave
the product in only 52% yield with 72% ee (entry 25). In entry 23,
the resulted phenyl 4-(trimethylsilyl)phenyl methanol is an important
product since the TMS substituent can be easily converted into other
functional groups such as a bromo, an iodo, or a boron dichloride
substituent for further applications.29 In this study, the product was
demonstrated to transform into the phenyl 4-bromophenyl metha-
nol.30
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