Allylation and highly diastereoselective syn or anti crotylation of N-toluenesulfonylimines using potassium allyl- and crotyltrifluoroborates

Article abstract of DOI:10.1039/b403759f

Air and moisture stable potassium allyl- and crotyltrifluoroborates undergo addition to N-sulfonyl and N-sulfinyl aldimines in the presence of Lewis acids, to provide the corresponding homoallylic amines in high yields and excellent diastereoselectivity.

Full text of DOI:10.1039/b403759f

Allylation and highly diastereoselective syn or anti crotylation of
N-toluenesulfonylimines using potassium allyl- and crotyltrifluoroborates
Sze-Wan Li and Robert A. Batey*
Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6, Canada.
E-mail: rbatey@chem.utoronto.ca; Fax: +1(416) 978-5059; Tel: +1(416) 978-5059
Received (in Corvallis, OR, USA) 11th March 2004, Accepted 6th April 2004
First published as an Advance Article on the web 11th May 2004
Air and moisture stable potassium allyl- and crotyltrifluorobor-
ates undergo addition to N-sulfonyl and N-sulfinyl aldimines in
the presence of Lewis acids, to provide the corresponding
homoallylic amines in high yields and excellent diaster-
eoselectivity.
manner, giving homoallylic amines in high isolated yields (Table
1). The reaction conditions are mild and even enolizable imines
such as 2e react in good yield (Table 1, entry 5). Reaction of the salt
1a does not occur in the absence of a Lewis acid catalyst even at
elevated temperatures. This feature distinguishes the reactivity of 1
from most allyl boron compounds, which do not require such
activation.
Homoallylic amines are important synthetic targets, particularly as
intermediates for alkaloid syntheses. One of the most general
strategies for their formation is the addition of organometallic
reagents toward imines.1 However, the allylation and diaster-
eospecific crotylation of imines and their derivatives has been less
successful than the well-established analogous addition of allyl-
and crotylorganometallics to carbonyl compounds,2 because of the
poor electrophilicity of imines and the tendency of enolizable
imines to undergo deprotonation rather than addition.3 Examples of
diastereoselective allylations and crotylations of CNN bonds,
include the use of B, Si, Zn, and Sn reagents.4 Several recent
strategies have emerged to allow enantioselective allylations and
crotylations, including chiral base assisted addition of trichloroallyl
and crotylsilanes to hydrazones,5 Pd catalyzed addition of trimethy-
lallylsilanes6 and stannanes7 to imines, and the addition of chiral
allylboranes to N-silylimines.8 We now report a general solution to
the allylation and diastereoselective crotylation of imines, as well
as an auxiliary based approach for the synthesis of chiral
homoallylamines, using conveniently handled air and water stable
boron reagents.
We have recently shown that potassium allyl- and crotyltri-
fluoroborates 1a–c add to carbonyl compounds either under Lewis
acid catalysis9 or in biphasic and aqueous media.10 A significant
advantage of these species are their air and water stability, and in
the case of 1b–c their configurational stability. Preliminary studies
on the addition of 1a–c to simple imines, such as PhCHNNPh, led
to disappointing results with the formation of the corresponding
homoallylic alcohols, occurring as a result of in situ hydrolysis of
the imines. To overcome this problem we evaluated the use of more
stable imine derivatives, such as N-tosylimines, which were found
to be sufficiently electrophilic to undergo allylation and highly
diastereoselective crotylation using potassium ally/crotyltrifluor-
oborates in the presence of a Lewis acid (Scheme 1). Initial
attempts at the addition of 1 equiv. potassium allyltrifluoroborate
1a to N-tosylimine 2a using 1 equiv. BF3·OEt2 yielded the desired
adduct in moderate yield (i.e. 50%) after prolonged reaction times.
However, with 2 equiv. of 1a, allylation proceeded with full
conversion in 2 days. The transformation can also be achieved in
comparable yield using a catalytic amount of BF3·OEt2 (10 mol%).
Alkyl, aryl and heterocyclic sulfonylimines were allylated in this
Crotylation of aliphatic, aromatic, and heterocyclic N-tosyli-
mines using potassium (Z)- and (E)-crotyltrifluoroborate and the
developed conditions was found to work equally well with either
stoichiometric or catalytic amounts of BF3·OEt2, leading to
products 4 and 5, respectively, in high yields and with excellent
diastereoselectivities (Table 2). The use of (Z)-crotyltrifluoroborate
1b led to the preferential formation of anti homoallylic amines 4,
whereas the (E)-crotyltrifluoroborate 1c afforded the syn products
5. The relative stereochemistry of adducts 4c and 5c were
determined by comparison of 1H NMR spectra to reported authentic
compounds.11,12 These observations are consistent with the inter-
mediacy of allylboron difluoride, formed in situ by Lewis acid
promoted removal of fluoride from salt 1, and addition via a
Table 1 Allylation of N-toluenesulfonylimines 2 by potassium allyltri-
fluoroborate 1a (R1 and R2 = H) under Lewis acid catalysis
Homoallylic
amine
Entry
R3
Yielda(%)
1
2
3
4
5
6
7
Ph
3a
3b
3c
3d
3e
3f
92
99
96
91
78
88b
96
4-ClC6H4
2-furanyl
Chx
nBu
tBu
4-MeOC6H4
3g
a Isolated yields. b 1 equiv. of BF3·OEt2 was used.
Table 2 Crotylations of N-toluenesulfonylimines 2 by potassium (Z)- and
(E)-crotyltrifluoroborate 1b/c under Lewis acid catalysisa
Homo-
allylic
amine
Yieldb
(%)
Entry
R1
R2
R3
Syn:antic
1
2
3
4
5
6
7
8
9
Me
H
Me
H
Me
H
Me
H
Me
H
Me
H
H
Me
H
Me
H
Me
H
Me
H
Me
H
Ph
Ph
4a
5a
4b
5b
4c
5c
4d
5d
4e
5e
4f
94
92
99
99
99
98
97
98
63
99
90
54
3 :97
91 : 9
< 2: : 98
96 : 4
4 : 96
95 : 5
< 2 : 98
> 98: : 2
< 2 : 98
> 98 : 2
< 2 : 98
3 : 1
4-ClC6H4
4-ClC6H4
2-furanyl
2-furanyl
Chx
Chx
nBu
nBu
tBu
10
11
12
Scheme 1 Allylation and crotylation of N-toluenesulfonylimines 2 with
potassium allyl- and crotyltrifluoroborates 1 using a catalytic amount of
BF3·OEt2 (10 mol%).
Me
tBu
5f
a BF3·OEt2 (10 mol%). b Isolated yields. c Detemined by 1H NMR.
1382
C h e m . C o m m u n . , 2 0 0 4 , 1 3 8 2 – 1 3 8 3
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

Zimmerman–Traxler chair-like transition state. In the reaction of
the sterically hindered sulfonylimine 1f with (E)-crotyltrifluorobor-
ate 1c significant amounts of the anti-product 5f were observed
(Table 2, entries 12). In this case some reaction via a boat-like
transition state is possible due to the destabilization of the chair-like
transition state, because of an unfavourable 1,2- axial–equatorial
interaction between the tBu group and the methyl group in 1c.3a
The success of the allyl/crotylation of N-tosylimines 2 using the
salts 1, prompted us to extend the use of allyl/crotylation reagents
to the synthesis of chiral homoallylic amines. We envisaged that
Ellman’s chiral N-tert-butanesulfinamides13 could serve as useful
precursors, having successfully been employed in diastereose-
lective additions of various organometallic reagents (e.g. Grignard
regents14 and organolithiums15). Interestingly, only allyl Grignard
reagents have been added to N-sulfinylimines14b,16 and crotylations
of these compounds have not been previously explored. Sulfinyli-
mine 6 was synthesized according to the literature procedure.17
Under the conditions developed for the allyl/crotylation of N-
tosylimines 2, the allylation of sulfinylimine 6 proceeded smoothly
to give the desired product 7 as a single diastereomer as observed
by 1H NMR (Scheme 2). The acid-labile chiral auxiliary was
readily cleaved by treatment of the product with acid. The
corresponding optically active homoallylic amine 8 was then
obtained in good yield after neutralization.8c,18
In conclusion, we have established an efficient protocol for the
synthesis of protected homoallylic amines using potassium allyl-
and crotyltrifluoroborates. These reagents offer advantages over
existing allylboron reagents, including high yielding additions and
excellent levels of diastereocontrol in the case of crotylation
reactions. An auxiliary base approach using N-tert-butanesulfina-
mides provides a convenient approach to the enantioselective
synthesis of primary homoallylic amines.
This work was supported by the Natural Sciences and Engineer-
ing Research Council of Canada (NSERC). S.-W. Li thanks the
University of Toronto for fellowship support. R.A.B. gratefully
acknowledges receipt of a Premier’s Research Excellence Award.
We thank Dr A. B. Young for mass spectrometric analysis.
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Scheme 2 Asymmetric synthesis of homoallylic amine 7 utilizing potassium
allyltrifluoroborate 1a.
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C h e m . C o m m u n . , 2 0 0 4 , 1 3 8 2 – 1 3 8 3
1383