Highly enantioselective catalytic ketone allylation with Sn(CH2CH=CH2)4/RSn(CH2CH=CH 2)3 mixtures (R = Et, Bu)

Article abstract of DOI:10.1055/s-2002-19323

In the presence of the monothiobinaphthol (MTB) ligand aryl ketones are allylated by mixtures of Sn(CH₂CH=CH₂)4/ RSn(CH₂CH=CH₂)₃ (R = Et, Bu) in high e.e. The presence of water suppresses racemic back

Full text of DOI:10.1055/s-2002-19323

LETTER
43
Highly Enantioselective Catalytic Ketone Allylation with Sn(CH2CH=CH2)4/
RSn(CH2CH=CH2)3 Mixtures (R = Et, Bu)
Enantioselective
K
n
etone
A
llyla
t
tion
w
i
h
thSn(CH2CHo=CH
)
2 4/RSnn(CH 2
C
H=CH
y
)
Mixtures Cunningham, Simon Woodward*
2
School of Chemistry, The University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom
Fax +44(115)9513564; E-mail: simon.woodward@nottingham.ac.uk
Received 19 September 2001
20 mol% (Ra)-2
O
Abstract: In the presence of the monothiobinaphthol (MTB) ligand
aryl ketones are allylated by mixtures of Sn(CH2CH=CH2)4/
RSn(CH2CH=CH2)3 (R = Et, Bu) in high e.e. The presence of water
suppresses racemic background allylation.
OH
Me
Ar
Sn(CH2CH=CH2)4
RSn(CH2CH=CH2)3
Me
Ar
(R)-3
1
R = Et, Bu
Key words: tin, asymmetric catalysis, ketones, allylation, thiols
SH
OH
Ar = Ph, 4-BrPh,
3-BrPh, 4-NO2Ph,
4-MePh, 4-ClPh,
2-C10H7
While numerous methods exist for catalytic enantioselec-
tive aldehyde allylation the equivalent chemistry for
prochiral ketones is quiet underrepresented.1,2 Including
stoichiometric reagents, few systems have been reported
that yield enantioselectivities of >80% for the ketones
RC(=O)Me.3–8 We report here a mechanistically interest-
ing system for the allylation of aryl ketones 1 (Scheme)
using mixtures of allylstannanes as the terminal allyl
source. Tin-promoted carbonyl allylation is normally ef-
(Ra)-2
Scheme
as the reaction conversion increased the enantioselecti-
vity fell. This type of behaviour is common in asymmet-
ric carbonyl allylation using organotin reagents.1
Young has proposed that tin alkoxide products
Sn(OMe)n(CH2CH=CH2)4-n (mainly n = 4), formed in re-
actions carried out in methanol, using Sn(CH2CH=CH2)4
lead to autocatalysis.15 Similar behaviour, but involving
product alkoxides, appears to be a common achiral back-
ground reaction in our ‘dry’ system and the catalysts de-
scribed by Tagliavini1 and Maruoka.2 If this behaviour is
not “switched off” then the e.e. of the alcohols 3 is com-
promised as the reaction proceeds to completion. Fortu-
nately we noticed that, for our mixed allyl systems, the
presence of small amounts of water inhibits these back-
ground reactions.16 We are unaware of such an effect be-
ing noted before. The stereoselectivity of the ‘wet’ system
can be marginally impaired compared to the ‘dry’ catalyst
but the e.e. value is independent of the reaction conver-
sion, even at reduced catalyst loadings (Table). If the ke-
tone, solvent, or stannane mixture has not been rigorously
dried an inadvertent water effect often results impairing
the procedure’s apparent reproducibility. Additionally, if
too much water is present in the reaction mixture both the
chemical yield and e.e. also suffer. For these reasons we
recommend rigorous drying of all the reaction compo-
nents so that the amounts of water present can be accurate-
ly quantified. Under these conditions the process is
completely robust.
fected
by
either
Sn(CH2CH=CH2)4
or
Bu3SnCH2CH=CH2. Alternative tin allylating sources are
rarely employed and, to the best of our knowledge, the use
of mixtures of organometallics has never been reported.
When the literature preparation9 of Sn(CH2CH=CH2)4, is
carried out using aged air-oxidised magnesium (to prepare
the intermediate allyl Grignard in the presence of EtBr)
the final product is appreciably contaminated by
EtSn(CH2CH=CH2)3 (0.15–0.30 mol fraction).10 As a
matter of course we tested this mixture in the allylation of
acetophenone (1a R1 = Ph) in the presence of monothiobi-
naphthol 211 (20 mol%) as a chiral promoter (Scheme). To
our delight this mixture showed potent efficacy: 3a was
formed in 67% e.e., in good yield, after 16 h at ambient
temperature. Very surprisingly, reactions of the pure com-
ponents alone were rather ineffective [e.e. values at 16 h:
Sn(CH2CH=CH2)4: 31% e.e.; RSn(CH2CH=CH2)3 26%
e.e. (R = Et), 11% e.e. (R = Bu)]. The most efficient ke-
tone allylation source is obtained from mixtures prepared
by combining pure Sn(CH2CH=CH2)4 (0.7 mol fraction)9
and pure RSn(CH2CH=CH2)3 (0.3 mol fraction; R = Et,12
Bu13).14 For technical simplicity the butyl compound is
preferred, as it is easily prepared from commercially
available BuSnCl3.
Reaction of the ethyl mixture, under anhydrous condi-
tions, with a range of aryl ketones 1 afforded the allylated
products 3 in very high e.e. after 1 hour (Table). However,
Compared to the predictable behaviour shown by aryl ke-
tones, aliphatic ketones gave complex results depending
on the substrate. For example, reaction of cyclohexyl me-
thyl ketone 4 (Figure) with the ‘dry’ EtSn(CH2CH=CH2)3/
Sn(CH2CH=CH2)4 system led to a time dependent e.e. At
low conversions only negligible e.e. values were realised
Synthesis 2002, No. 1, 28 12 2001. Article Identifier:
1437-2096,E;2002,0,01,0043,0044,ftx,en;D22301ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

44
A. Cunningham, S. Woodward
LETTER
Table Enantioselective Allylation of Ketones 1 by 2 (20 mol%) and
Allyltin Mixtures [1.1 Equivalents of a 70:30 mol Fraction Mix of
Sn(CH2CH=CH2)4/RSn(CH2CH=CH2)3; R = Et, Bu].
References
(1) Casolari, S.; D’Addario, D.; Tagliavini, E. Org. Lett. 1999,
1, 1061.
(2) Hanawa, H.; Kii, S.; Maruoka, K. Adv. Synth. Catal. 2001,
343, 57.
(3) (a) Titze, L. F.; Schiemann, K.; Wegner, C.; Wulf, C. Chem.
Eur. J. 1998, 4, 1862. (b) Titze, L. F.; Völkel, L.; Wulff, C.;
Weigand, B.; Bittner, C.; McGrath, P.; Johnson, K.; Schäfer,
M. Chem. Eur. J. 2001, 7, 1304.
(4) Yasuda, M.; Kitahara, N.; Fujibayashi, T.; Baba, A. Chem.
Lett. 1998, 743.
(5) Loh, T.-P.; Zhou, J.-R.; Li, X.-R. Tetrahedron Lett. 1999,
40, 9333.
(6) Soderquist, J. A.; Prasad, K. G. 220th Meeting Am. Chem.
Soc.-Abstr. Paper 2000, ORGN-508.
(7) Nakamura, M.; Hirai, A.; Sogi, M.; Nakamura, E. J. Am.
Chem. Soc. 1998, 120, 5846.
(8) Jadhav, P. K.; Bhat, K. S.; Perumal, P. T.; Brown, H. C. J.
Org. Chem. 1986, 51, 432.
‘Dry’ Methoda
‘Wet’ Methoda
1
a
a
b
c
d
e
f
Ar
Yield [%] e.e. [%]
Yield [%] e.e. [%]
Ph
40–43
–
90–92
–
>98
71b
97
86–89
84b
86
Ph
4-BrPh
3-BrPh
4-NO2Ph
4-MePh
4-ClPh
2-C10H7
51
53
–
92
85
–
>99
>98
78c
94
88
86
32
–
90
-
82
87
g
53
87
>98
84
(9) O’Brien, S.; Fishwick, M.; McDermott, B.; Wallbridge, M.
G. H.; Wright, G. A. Inorg. Synth. 1972, 13, 73.
(10) Other EtnSn(CH2CH=CH2)4-n, n = 2–4 species are also
present as very minor contaminants in these preparations.
Control reactions using d5-EtBr confirm that the ethyl group
arises from the EtBr used for magnesium activation in ref. 9.
Fresh (silver-coloured) as opposed to aged (>2 years, black-
coloured) magnesium leads only to pure Sn(CH2CH=CH2)4.
Electron microscopy in conjunction with EDS studies reveal
that the surface of aged magnesium has an appreciable
oxygen content (presumably MgO) and it appears to be this
that favours production of EtMgBr over CH2=CHCH2MgCl.
(11) (a) Blake, A. J.; Cunningham, A.; Ford, A.; Teat, S. J.;
Woodward, S. Chem. Eur. J. 2000, 6, 3586. (b) Azad, S.
M.; Bennett, S. M. W.; Brown, S. M.; Green, J.; Sinn, E.;
Topping, C. M.; Woodward, S. J. Chem. Soc., Perkin Trans.
1 1997, 687.
a Yields and e.e. values at 1 h for ‘dry’ method using R = Et mix or 16
h for ‘wet’ method using R = Bu mix; see ref. 14 for details.
b At 9 mol% 2,1.5 L water and 16 h.
c 96% yield at 43 h, e.e. unaffected.
for product 5 (Figure) but this maximised at 59% e.e. at 19
h.
With
the
‘wet’
BuSn(CH2CH=CH2)3/
Sn(CH2CH=CH2)4 system both the chemical yield and
stereoselectivity were low [28% yield of 5 after 16 h, 41%
e.e.]. Methyl t-butyl ketone 6 (Figure) did not participate
in reaction with the ‘wet’ system.
O
(12) Kawakam, K.; Kuivila, H. G. J. Org. Chem. 1969, 34, 1502.
(13) Gambaro, A.; Peruzzo, V.; Plazzogna, G.; Tagliavini, G. J.
Organomet. Chem. 1980, 197, 45.
OH
Me
c-Hex
Me
c-Hex
4
5
(14) Experimental Procedure: All operations were performed
under argon; toluene was distilled from sodium. A toluene
solution of MTB 2 (24 mg, 0.08 mmol in 1.0 mL) was treated
with a mixture of Sn(CH2CH=CH2)4/SnR(CH2CH=CH2)3
(0.7:0.3 mol fraction mix, 0.46 mmol total Sn content, R =
Et, Bu). For the ‘dry’ catalyst this mixture (R = Et) was
heated directly for 2 h at 52 °C. For the ‘wet’ catalyst water
(3 L, 0.16 mmol) was added to the mixture (R = Bu) prior
to the heating period. The mixtures were cooled to ambient
temperature, the ketone 1 (or 4) (0.4 mmol) added and the
mixture stirred whilst its composition was monitored by GC,
HPLC, or 1H/119Sn NMR spectroscopy. Flash
chromatography afforded the known alcohols 3 (or 5) as
essentially single products. Enantioselectivities were
determined by GC (CYCLODEX-B for 3c, oktakis(6-O-
methyl-2,3-di-O-pentyl)- -cyclodextrin for 3a, 3b, 3e, 3f, 5)
or HPLC (Chiralcel AD for 3d, Chiralcel OD for 3g).
(15) (a) Cokley, T. M.; Marshall, R. L.; McCluskey, A.; Young,
D. J. Tetrahedron Lett. 1996, 37, 1905. (b) Cokley, T. M.;
Harvey, P. J.; Marshall, R. L.; McCluskey, A.; Young, D. J.
J. Org. Chem. 1997, 62, 1961.
O
tBu
Me
6
Figure
In conclusion we have developed new catalytic systems
for the allylation of aryl ketones in high e.e. The presence
of RSn(CH2CH=CH2)3 (R = Et, Bu) components in the
terminal tetraallytin and a strong promotion effect by wa-
ter are both highly beneficial. The variation of these com-
ponents might also account for the non-reproducibility
occasionally seen in other catalytic systems using tetraal-
lytin as an allyl source. Further works on developing the
utility of this new approach and in understanding its un-
derlying mechanism are in hand.
(16) We speculate that water co-ordination to mixed allyl-
alkoxide species may limit their Lewis acidity preventing
them acting as allylation promoters. For a review of water
effects in asymmetric synthesis see: Ribe, S.; Wipf, P. Chem.
Commun. 2001, 299.
Acknowledgement
We thank EPSRC for provision of a studentship (AC) and grant GR/
R06205. We are also grateful to Mrs. Bridget K. Stein (EPSRC
Mass Spectrometry Service) for GCMS advice and to Mrs. Nicola
Bock for electron microscopy studies.
Synthesis 2002, No. 1, 43–44 ISSN 0936-5214 © Thieme Stuttgart · New York