Stereocontrolled palladium-catalysed umpolung allylation of aldehydes with allyl acetates

Article abstract of DOI:10.1016/j.tet.2010.04.133

In the present work the stereocontrolled palladium-catalysed umpolung allylation of aldehydes is described. Allyl acetates are in situ transformed into the corresponding allyl boronates, which directly react with aldehydes. The question of stereocontrol is raised by employing (a) chiral boronating agents (reagent control) and by (b) utilising chiral aldehydes (substrate control). These studies reveal that the approach based on substrate control is superior to the former one with respect to yields and stereoselectivity. Remarkably, this umpolung protocol often yields the 4,5-syn products in high selectivity, which is unprecedented for direct crotylations.

Full text of DOI:10.1016/j.tet.2010.04.133

Tetrahedron 66 (2010) 6450e6456
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Stereocontrolled palladium-catalysed umpolung allylation of aldehydes with
allyl acetates
*
Monika Vogt, Sascha Ceylan, Andreas Kirschning
€
Institut für Organische Chemie and Zentrum für Biomolekulare Wirkstoffe (BMWZ), Leibniz Universitat Hannover, Schneiderberg 1B, D-30167 Hannover, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
In the present work the stereocontrolled palladium-catalysed umpolung allylation of aldehydes is
described. Allyl acetates are in situ transformed into the corresponding allyl boronates, which directly
react with aldehydes. The question of stereocontrol is raised by employing (a) chiral boronating agents
(reagent control) and by (b) utilising chiral aldehydes (substrate control). These studies reveal that the
approach based on substrate control is superior to the former one with respect to yields and stereo-
selectivity. Remarkably, this umpolung protocol often yields the 4,5-syn products in high selectivity,
which is unprecedented for direct crotylations.
Received 25 February 2010
Received in revised form 20 April 2010
Accepted 29 April 2010
Available online 6 May 2010
Keywords:
Aldehydes
Allylation
Catalysis
Ó 2010 Elsevier Ltd. All rights reserved.
Palladium
Umpolung
1. Introduction
et al.4 They showed that the latent reactivity of the palladium allyl
complex 2 can be reversed from electrophilic to nucleophilic in
Trost and Tsuji pioneered the Pd(0)-catalysed asymmetric allylic
alkylation of malonic esters and other nucleophiles (Nuꢀ)
(1/2/3; Scheme 1), which has become one of the most studied
CeC-bond-forming reactions in current asymmetric catalysis.1,2
In 1987, Brown and co-workers3 published the first example of
Nu
the presence of dialkylzinc or trialkylboron species. In situ for-
mation of allylcopper and allyliridium species has recently been
added in elegant works mainly by the group of Krische to the list
of organometallic nucleophiles.5 Importantly, Szabó and co-
workers disclosed an efficient one-pot electrophilic allylation
procedure (1/4/5) applying palladiumepincer complexes and
diboranes 6.6
+
R
Nu
R
*
The resulting umpolung reactions represent a complementary
reaction to the existing allylation methodologies. In fact, it re-
sembles the nucleophilic allylation of aldehydes (Eþ) developed by
Hoffmann, Roush and others, except that the allylborane/boronate
is formed in situ from an electrophilic allyl precursor 1.7d To date,
there have been a few enantioselective examples of the dialkylzinc-
mediated umpolung allylation (2/5) reported in the literature,
namely by Zanoni, Zhou, and Feringa,7 while the Szabó approach
has not been tested in asymmetric allylations for constructing
complex fragments of natural products.8 One noteworthy feature of
this umpolung reaction is the exclusive generation of the branched
product 5b due to formation of the sterically less hindered allyl
boronate 4 (Scheme 1).4 Thus, a terminal double bond and two new
stereogenic centers are formed, which makes the transformation
highly attractive for natural product synthesis, namely polyketides.
Here, we disclose different strategies to control the relative and
absolute configuration of the newly formed stereogenic centers
during the palladium-catalysed umpolung with in situ generation
of allyl boronates 4.
3a
3b
Nu
Pd
Pd(0)
X
R
X
R
2
1:
X= OAc, OC(O)OR
Et2Zn or
R3B, E
R2B-BR2 (6)
Pd(0)
E
*
Pd(0)
+
R
E
R
BR2
R
E
5a
5b
4
Scheme 1. Pd(0)-catalysed electrophilic and nucleophilic allylations.
an umpolung allylation which was studied in detail by Tamaru
* Corresponding author. E-mail address: andreas.kirschning@oci.uni-hannover.
de (A. Kirschning).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.04.133

M. Vogt et al. / Tetrahedron 66 (2010) 6450e6456
6451
Table 2
2. Results and discussion
Asymmetric allylation using chiral diboronates 12 and 13a
One major advantage of this one-pot procedure stems from the
fact that isolation of the labile boronate intermediates can be
avoided. Preliminary optimisation studies were carried out based
on known procedures5 using aldehyde 7, cinnamyl acetate 8, and
diboronate 10 as a model system (Table 1). In addition to different
catalytic systems, the catalyst loading and reaction times were
modified. Pd2dba3 (10 mol %) or Pd(allyl)2Cl2 in DMSO were found
to be the best combinations (entries 4 and 5).9 Other palladium
sources either gave reduced yields of allylation products (entries 3,
5, and 7) or were completely inefficient (entries 1, 2, and 6). Overall,
DMSO turned out to be the most suitable solvent, which is in ac-
cordance with Szabó’s report.6 The relative configuration of 9 was
determined after conducting a short synthetic sequence, which
comprises ozonolysis, reduction, and acetonide protection of the
intermediate 1,3-diol.10a In all cases the anti-product (rac)-9 was
formed, which strongly indicates that pinacolallyl boronate 11 must
be the reactive intermediate.
Entry
Boronate
Yieldb [%] (ee)
1
2
3
4
12 (D
)
41 (40)
39 (37)
60 (21)
50 (19)
12 (L)
13 (þ)
13 (ꢀ)
a
All reactions were carried out in degassed DMSO with 1.2 equiv of boronate 12
or 13, 1.0 equiv of 7, 1.2 equiv of 8, 10 mol % of Pd2(dba)3, 40 ꢁC, 20 h.
b
In view of this umpolung mechanism, stereocontrol can either
be achieved by chiral allyl boronates11 or by the substrate itself
(chiral aldehydes) or by both control elements (double stereo-
Isolated yield; ees were determined by chiral GC (Hydrodex-
column, 50 m, 0.25 mm).
b PM capillary
studied the reaction of substituted allyl boronates (like in-
termediate 11) to a-chiral aldehydes and determined the resulting
4,5-stereochemistry.12 (E)-Crotylboronates afforded the anti,anti
and the anti,syn adducts that originate from different facial ap-
proaches of the reagent to the aldehyde. In the present study we
Table 1
Optimisation of the model reactiona
chose a-siloxy-substituted aldehydes 17 and 18 as well as 2-phe-
nylpropanal 19 as chiral substrates for the palladium-catalysed
umpolung allylation with acetates 8 and (rac)-14, respectively
(Table 3). All reactions proceeded with moderate to good yields and
with remarkably high 3,4-anti-4,5-syn selectivities. The 4,5-ste-
reochemistry of coupling products 20 and 24 was determined by
comparison with 1H NMR data reported in the literature.13,14 The
configuration of 22 was determined after transformation into the
corresponding six-membered acetal.15 For all other products 21, 23,
and 25 it is assumed that the addition proceeds with the same
diastereocontrol as determined for adducts 20, 22, and 24 listed in
entries 1, 3, and 5 (Table 3).
We extended these studies to complex aldehydes 26, 28, and 30
that are typical examples for preparing natural product backbones
(Scheme 2). Except for the aldehyde 30, which is relevant for the
total synthesis of ansamycin antibiotics16 such as geldanamycin, the
allylations proceeded in good yield and for product 29 with ex-
cellent 4,5-syn selectivity. The absolute configuration of the sec-
ondary alcohol in 27 was determined by Mosher ester analysis.17
The configuration of the new stereogenic centers in 29 was de-
termined by analysis of the corresponding six-membered acetal.10b
Based on steric as well as electronic considerations Roush and
co-workers provided a detailed analysis of why (E)-crotylboronates
Entry
Pd(0)
Solvent
Yieldb [%]
1
2
3
4
5
6
7
8
Pd(OAc)2, PPh3
Pd(PPh3)4
Pd(OAc)2
Pd2(dba)3
Pd2(allyl)2Cl2
PeppsiÔ
Pd(CH3CN)2Cl2
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
Toluene
DMF
0
0
46
75
70
0
38
12
14
45
0
9
10
11
12
MeCN
CH2Cl2
THF
Pd2(dba)3
Pd2(dba)3
0
a
All reactions were carried out using 1.2 equiv of boronate 10, 1.0 equiv of 7,
1.2 equiv of 8, 10 mol % of catalyst, 40 ꢁC, 20 h.
b
Isolated yield; dr>20:1 (determined by 1H NMR spectroscopy and according to
favor the formation of 4,5-anti adducts in reactions with a-chiral
Ref. 10).
aldehydes.12b From a steric point of view transition states (TS) II and
III (Fig. 1) should play a dominant role for generating 4,5-anti ad-
ducts, while FelkineAnh transition state I should be made re-
sponsible for yielding 4,5-syn adducts.
differentiation). Initial studies with enantiopure diboronates 12
resulted in low yields and only moderate ee. When diboronate 13
was employed, the isolated yields improved but the ees dropped
(Table 2).
Both, Hoffmann and Roush12 noted that
a-alkoxy-substituted
One possible rationale for these results may be associated with
the reaction temperature since the formation of allyl boronate 4
requires elevated temperatures whereas the allylation should give
better stereocontrol at lower temperatures. The low melting point
of DMSO (18 ꢁC) prevents from carrying out a two-step procedure
at lower temperature. However, similar experiments were con-
ducted with MeCN, which did not give improved results.
As these preliminary results were unsatisfactory, we turned our
attention to a substrate-controlled procedure, which relies on
aldehydes show a moderate anti-selectivity in the reaction with
(E)-crotylboronates. Therefore, it can be assumed that also the
electronic properties of the aldehyde influence diastereofacial
selectivity. Thus, favorable electronic activation by the Cornforth-
type TS II was additionally made responsible for the increased
anti-selectivity. However, the reversed 4,5-syn selectivity for
(E)-crotylboronate intermediates observed in this communication
for the palladium-catalysed umpolung allylation is unprecedented.
Remarkably, both types of
a-chiral aldehydes, a-oxy aldehydes as
a
-chiral aldehydes (Table 3). Hoffmann and Roush have extensively
well as 2-phenylpropanal preferentially gave the 4,5-syn adducts.

6452
M. Vogt et al. / Tetrahedron 66 (2010) 6450e6456
Table 3
OAc
Me
OPMB
Substrate-controlled stereoselective allylation using chiral aldehydes 17e19a
OPMB
14
OH
O
TBSO
57% (1.5:1)
TBSO
Me Me Me
Me Me
27
26
OAc
Me
TBSO
OH
14
TBSO
O
60% (12:1)
Me Me Me
Me Me
28
29
b
Entry
1
Acetate
Aldehyde
Major product
Yield [%] (dr)
73 (10:1)
TBDPSO
NHBoc
O
OAc
NHBoc
OH
TBDPSO
Me
14
33% (1:1)
Me
30
OMe
Me
31
Me
OMe
Scheme 2. Palladium-catalysed umpolung allylation with complex aldehydes.
2
3
4
5
80 (5:1)
65 (7:1)
60c
Me Me
Me Me
O
Me
Me
Me
O
B
Me
Me
Me
Me
O
B
Me
O
Me
R3SiO
H
R1
H
R3SiO
R1
B
O
O
O
O
O
R1
Me
OSiR3
H
Me
I
II
III
Cornforth type TS
Felkin-Anh type TS
Felkin-Anh type TS
4,5-syn
4,5-anti
4,5-anti
Figure 1. Relevant transition states IeIII.
54 (5:1)
(entries 2e4). When a combination of Pd complex, DMSO, and
boronate 10 was added the crotylation proceeded in excellent yield
but again without any stereochemical preference (entry 5). Finally,
we added boronate Lewis acids, which could be expected to be
6
58c
Table 4
Comparison of Hoffmann’s and Roush’s allylation protocol with the Pd-catalysed
umpolung
a
All reactions were carried out in degassed DMSO with 1.2 equiv of boronate 10,
1.0 equiv of aldehyde, 1.2 equiv of acetate, 10 mol % of Pd2(dba)3, 40 ꢁC, 20 h.
b
Isolated yield; major syn-diastereomer depicted; ratios determined by 1H NMR
Entry
1
Aldehyde
Conditions
Yield [%]
dr (syn:anti)
spectroscopy.
c
The 4,5-anti-diastereomer could not be detected.
Hoffmanna,d
97
79
1:1.1
3:1
Pd-catalysedb umpolung
These results are difficult to rationalise as one would expect the
same principal ZimmermanneTraxler transition state for all three
procedures. Therefore, we repeated Hoffmann’s and Roush’s ex-
periments in our laboratories. We particularly added aldehydes 32
and 33 (entries 1 and 3) to the list of aldehydes because these have
been studied by both groups before.12b,14 We could reproduce their
results with respect to yields and selectivities (Table 4). In all cases,
the one-pot umpolung protocol gave increased 4,5-syn selectivities,
Hoffmanna
Roushc
Quant
97
73
1:1
1.3:1
10:1
2
3
Pd-catalysed
umpolungb
Roushc
50
58
1:1
1.3:1
Pd-catalysed
umpolungb
very pronounced for a-siloxy aldehyde 17 (entry 2).
Hoffmanna,d
Roushc
53
88
54
3:1
3:1
5:1
Having confirmed the unprecedented high 4,5-syn selectivity
we finally focused on the parameters and selected additives that
are relevant for the umpolung protocol and studied their influence
on the stereochemical outcome of the classical Hoffmann crotyla-
4
Pd-catalysed
umpolungb
Hoffmann conditions14: 1.0 equiv of the aldehyde and 1.0 equiv of (E)-crotyl
a
tion using chiral a-siloxy aldehyde 17 (Table 5). This aldehyde had
pinacol boronate 34 were stirred for 3 days at rt (neat).
b
Palladium-catalysed umpolung: for details refer to Table 3 and the Experimental
provided selectivities in the range of 5:1 to 10:1 in the umpolung
protocol. However, this aldehyde reacted under Hoffmann condi-
tions with boronate 34 without stereochemical preference (entry
1). No stereochemical change took place when the Pd source was
added or DMSO was used as solvent except that the yield dropped
section.
c
Roush conditions12b: 1.2 equiv of the aldehyde were dissolved in dry CH2Cl2
under nitrogen atmosphere and cooled to ꢀ78 ꢁC. Then 1.0 equiv of (E)-crotyl
pinacol boronate 34 was added and the reaction was stirred over night at ꢀ78 ꢁC.
d
Literature value.14

M. Vogt et al. / Tetrahedron 66 (2010) 6450e6456
6453
Table 5
on a Bruker DPX-400 (400 MHz and 100 MHz). Compounds 7, 8, 10,
Influence of additives on the stereochemical outcome of crotylating aldehyde 17
with boronate 34
L-12, and (ꢀ)-13 are commercially available. Compounds 26, 28, and
30 were prepared according to literature procedures.19
4.2. Preparation of allyl acetates and aldehydes
4.2.1. (rac)-3-Butene-2-methylacetate (14)20. 3-Butene-2-ol (5.0 g,
69.3 mmol, 1.0 equiv) was dissolved in dry CH2Cl2 (157 ml) under
a nitrogen atmosphere and cooled to 0 ꢁC. Dry pyridine (5.4 mL,
76.3 mmol, 1.1 equiv) was added and then acetyl chloride (6.0 mL,
74.1 mmol, 1.07 equiv) was added dropwise. After 90 min the re-
action was hydrolysed with water (40 mL). The organic phase was
washed with brine and water, dried (Na2SO4), and concentrated in
vacuo. As a result, 7.8 g (68.3 mmol, 99%) of the product were
obtained as a pale yellow oil.
Entry
Additives or modified conditions
Yield [%]
dr (syn/anti)
1
2
3
4
5
None (Hoffmann conditions)
Pd2dba3 (10 mol %)
DMSO
Quantitative
79
47
49
1:1
1:1
1.3:1
1:1
40 ꢁ
C
1H NMR (400 MHz, CDCl3)
d
: 5.82 (ddd, J¼17.2, 10.6, 6.2 Hz, 1H,
10 (1.2. equiv), Pd2dba3 (10 mol %),
Quantitative
1:1
DMSO, 40 ꢁC
H-3), 5.32 (dq, J¼6.6, 6.2 Hz, 1H, H-2), 5.22 (d, J¼17.2 Hz, 1H, H-4a),
5.12 (d, J¼10.6 Hz, 1H, H-4b), 2.04 (s, 3H, COMe), 1.29 (d, J¼6.6 Hz,
3H, H-1); 13C NMR (100 MHz, CDCl3)
d: 170.4 (q, CO), 137.8 (t, C-3),
6
7
(1.2 equiv)
80
66
1.7:1
1:1
115.8 (s, C-4), 71.0 (t, C-2), 21.4 (p, C-1), 20.0 (p, COMe).
Pinacol borane (1.2 equiv)
4.2.2. (2S)-(tert-Butyldiphenylsiloxy)-propanal
(17). (2S)-(tert-
Butyldiphenylsiloxy)-N-methoxy-N-methyl-propionamid21 (30 mg,
0.081 mmol, 1.0 equiv) was dissolved in dry THF (0.6 mL) under
a nitrogen atmosphere and cooled to ꢀ78 ꢁC. DIBAL-H (0.4 mL,
0.404 mmol, 1.0 M in hexane, 5.0 equiv) was added dropwise over
5 min and the mixture was stirred for 30 min at ꢀ78 ꢁC. The
reaction was hydrolysed by addition of ethyl acetate (0.1 mL) and
diluted with a solution of KeNaetartrate (10%, aq) and CH2Cl2. The
aqueous phase was extracted with CH2Cl2 and the combined
organic extracts were dried (MgSO4). After removal of the solvent
aldehyde 17 was obtained quantitatively as a colorless oil and
directly submitted to the umpolung reaction.
byproducts from the umpolung protocol. However, only a minor
effect toward 4,5-syn selectivity was encountered, far away from
the 10:1 ratio observed in the Pd-catalysed umpolung (entry 1,
Table 3).
At this stage, we have to encounter doubt whether the transition
state or the course of the umpolung reaction is identical with those
for the direct crotylation developed by Roush and Hoffmann, re-
spectively. As none of the altered reaction conditions had a pro-
found influence on the selectivity further studies are necessary to
unravel the mechanistic details of the palladium-catalysed umpo-
lung reaction.
4.2.3. (R)-(tert-Butyldiphenylsiloxy)-phenyl-acetaldehyde (18). Al-
dehyde 18 (0.16 mmol) was prepared from the corresponding
Weinreb amide according to the procedure described for aldehyde
17. It was obtained in quantitative yield (60 mg, 0.16 mmol) as
a colorless oil.
3. Conclusion
In summary, we disclosed the stereochemical outcome of the
palladium-catalysed umpolung allylation of aldehydes with allyl
acetates. This protocol has several beneficial features compared to
classical crotylations such as the possibility of the in situ generation
of allyl boronates and the option of employing racemic allyl ace-
tates.18 Remarkably, an unprecedented high 4,5-syn selectivity was
found for selected chiral aldehydes. In conclusion, the umpolung
procedure can become a promising tool for the stereoselective
synthesis of complex structural fragments that are present in many
polyketides. Investigations on improved catalytic conditions and
the extension of this one-pot umpolung methodology on more
elaborated allyl acetates and aldehydes that would allow to merge
large polyketide fragments are currently under way in our
laboratories.
4.2.4. (2R)-Phenyl-propionaldehyde
(40 mg, 294 mol, 1.0 equiv) was dissolved in dry CH2Cl2 (30 mL)
under nitrogen atmosphere and cooled to 0 ꢁC. Then NaHCO3
(19). (2R)-Phenyl-propanol
m
(30 mg, 353
(149 mg, 353
m
mol, 1.2 equiv) and DesseMartin-periodinane
mmol, 1.2 equiv) were added and the reaction was
stirred for 1 h at room temperature. The reaction was hydrolysed by
addition of a 1:1 mixture of Na2S2O3 (satd, aq) and NaHCO3 (satd,
aq). The aqueous phase was extracted with CH2Cl2 and the com-
bined organic extracts were washed with NaHCO3 (aq) and dried
(MgSO4). After removal of the solvent 32 mg (235 mmol, 80%) of the
product were obtained as a colorless oil, which was directly sub-
mitted to the umpolung reaction.
4.2.5. (2S,
5R)-5-(tert-Butyldimethylsiloxy)-7-(4-methoxy-benzy-
mol) was
4. Experimental
4.1. General
loxy)-2,4-dimethyl-hept-3-enal (26). Aldehyde 26 (49
m
prepared by DesseMartin oxidation from the corresponding alco-
hol according to the procedure described for aldehyde 19 and was
directly submitted to the umpolung reaction. The aldehyde was
All experiments were performed under a nitrogen atmosphere
in oven-dried glassware. Anhydrous THF was obtained by distilla-
tion from sodium and benzophenone. All other chemicals and
solvents were purchased from Acros, SigmaeAldrich, and ABCR.
HRMS data were obtained on a Micromass LCT electrospray ion-
isation spectrometer. 1H NMR and 13C NMR spectra were recorded
obtained in quantitative yield (20 mg, 49 mmol) as a colorless oil.
4.2.6. (2R,
enal (28). Aldehyde 28 (269
3R)-3-(tert-Butyldimethylsiloxy)-2,4-dimethyl-pent-4-
mol) was prepared by reduction with
m
DIBAL-H from the corresponding Weinreb amide as a colorless oil
according to the procedure described for aldehyde 17 and was

6454
M. Vogt et al. / Tetrahedron 66 (2010) 6450e6456
t
directly submitted to the umpolung reaction. The aldehyde was
obtained in quantitative yield (65 mg, 269 mol) as a colorless oil.
19.5 (q, SitBu), 17.6 (p, C-1); HRMS [Mꢀ Bu]þ calcd for C19H23O2Si:
m
311.1462, found 311.1465.
4.2.7. (2S,
nylsiloxy)-phenyl]-4-methyl-2-methoxy-1-pentanal (30). Aldehyde
30 (26 mol) was prepared by DesseMartin oxidation from the
4R)-5-[tert-Butoxycarbonylamino-3-(tert-butyldiphe-
4.4.3. (2S, 3S, 4S)-2-(tert-Butyldiphenylsiloxy)-4-phenyl-5-hexen-3-
ol (21). Compound 21 was prepared according to procedure A and
was obtained in 80% yield as a colorless oil (dr 5:1). The di-
astereoisomers could not be separated. 1H NMR (400 MHz, CDCl3)
m
corresponding alcohol according to the procedure described for al-
dehyde 19 and was directly submitted to the umpolung reaction. It
d: 7.64e7.56 (m, 4H, SiPh), 7.47e7.32 (m, 6H, SiPh), 7.15e7.11 (m, 3H,
was obtained in quantitativeyield (15 mg, 26
m
mol) as a colorless oil.
Ph), 6.81e6.79 (m, 2H, Ph), 6.03 (ddd, J¼17.1, 8.1, 8.0 Hz, 1H, H-5),
4.98 (dd, J¼17.1, 8.0 Hz, 2H, H-6), 3.86 (ddd, J¼9.0, 2.9, 1.4 Hz, 1H, H-
3), 3.58 (dq, J¼6.4, 2.9 Hz, 1H, H-2), 3.18 (dd, J¼9.0, 8.1 Hz, 1H, H-4),
2.54 (d, J¼1.4 Hz, 1H, OH), 1.04 (br s, 12H, H-1 and SitBu); 13C NMR
4.3. General procedure for the palladium-catalysed
umpolung
(100 MHz, CDCl3) d: 140.2 (q, Ph), 139.9 (t, C-5), 135.9 (t, SiPh), 135.9
(t, SiPh),133.9 (q, SiPh),133.6 (q, SiPh),129.9 (t, SiPh),129.7 (t, SiPh),
128.7 (t, Ph), 127.9 (t, SiPh), 127.8 (t, Ph), 127.6 (t, SiPh), 126.5 (t, Ph),
116.1 (s, C-6), 76.8 (t, C-3), 70.1 (t, C-2), 52.6 (t, C-4), 27.2 (p, SitBu),
19.2 (q, SitBu), 15.5 (p, C-1); HRMS [MþNa]þ calcd for
C28H34O2SiNa: 453.2226, found 453.2218.
Procedure A: Pd2(dba)3echloroform adduct (29 mg, 28.8 mmol,
0.1 equiv) was dissolved in degassed DMSO (3 mL) under a nitrogen
atmosphere. The aldehyde (288 mol, 1.0 equiv) and the allyl ace-
tate (346 mol, 1.2 equiv) were added and the reaction mixture was
stirred for 10 min at room temperature. After addition of bis
(pinacol)boronate 10 (88 mg, 346 mol, 1.2 equiv) the reaction was
m
m
4.4.4. (1R, 2R, 3R)-1-(tert-Butyldiphenylsiloxy)-3-methyl-1-phenyl-
pent-4-en-2-ol (22). Compound 22 was prepared according to
procedure A and was obtained in 65% yield as a pale yellow oil (dr
m
warmed to 40 ꢁC and stirred for 20 h. The reaction was hydrolysed
with water (3 mL). After stirring for 1 h at room temperature, the
mixture was extracted with diethylether. The combined extracts
were dried (MgSO4) and concentrated in vacuo. The residue was
purified by flash chromatography.22
7:1). [
a
]
D
ꢀ43.5 (c 2.3, CH2Cl2); 1H NMR (400 MHz, CDCl3)
d:
20
7.63e7.07 (m, 15H, Ph), 5.76 (ddd, J¼17.0, 10.2, 9.2 Hz, 1H, H-4), 4.91
(d, J¼11.0 Hz, 1H, H-5a), 4.78 (d, J¼17.9 Hz, 1H, H-5b), 4.54 (d,
J¼8.1 Hz, 1H, H-1), 3.66 (ddd, J¼8.1, 2.5 Hz, 1H, H-2), 2.81 (br s, 1H,
OH), 1.87 (ddq, J¼9.2, 6.7 Hz, 1H, H-3), 1.01 (s, 9H, SitBu), 0.96 (d,
Procedure B: Pd2(dba)3echloroform adduct (29 mg, 28.8
0.1 equiv) was dissolved in degassed DMSO (3 mL) under a nitrogen
atmosphere. The allyl acetate (346 mol, 1.2 equiv) was added and
the reaction mixture was stirred for 10 min at room temperature.
After addition of bis(pinacol)boronate (88 mg, 346 mol, 1.2 equiv)
the reaction was warmed to 40 ꢁC. After stirring for 15 min the
aldehyde (288 mol, 1.0 equiv) was added and the reaction mixture
mmol,
J¼6.7 Hz, 3H, Me); 13C NMR (100 MHz, CDCl3)
d: 140.9 (q, Ph), 139.1
m
(t, C-4),136.1 (t, Ph),135.9 (t, Ph),133.7 (q, Ph),133.0 (q, Ph),129.8 (t,
Ph), 129.6 (t, Ph), 128.1 (t, Ph), 127.8 (t, Ph), 127.7 (t, Ph), 115.6 (s, C-
5), 80.7 (t, C-2), 79.7 (t, C-1), 38.8 (t, C-3), 27.1 (p, SitBu), 19.5 (q,
SitBu), 18.8 (p, Me); HRMS [MþNa]þ calcd for C28H34O2SiNa:
453.2226, found 453.2237.
m
m
was stirred at 40 ꢁC for 20 h. The reaction was hydrolysed with
water (3 mL). After stirring for 1 h at room temperature, the mix-
ture was extracted with ether. The combined extracts were dried
(MgSO4) and concentrated in vacuo. The residue was purified by
flash chromatography.21
4.4.5. (1R, 2R, 3S)-1-(tert-Butyldiphenylsiloxy)-1,3-diphenyl-pent-4-
en-2-ol (23). Compound 23 was prepared according to procedure A
and was obtained in 60% yield as a colorless oil (only one di-
astereoisomer could be detected). [
a
]
20 ꢀ21.3 (c 1.0, CH2Cl2); 1H NMR
D
(400 MHz, CDCl3)
d: 7.64e7.62 (m, 2H, Ph), 7.45e7.30 (m, 6H, Ph),
7.21e7.14 (m, 8H, Ph), 7.08e7.05 (m, 4H, Ph), 6.17 (ddd, J¼17.3, 9.8,
9.4 Hz, 1H, H-4), 5.08 (dd, J¼9.8, 1.5 Hz, 1H, H-5a), 4.87 (dd, J¼17.3,
1.5 Hz, 1H, H-5b), 4.61 (d, J¼7.9 Hz, 1H, H-1), 4.07e4.03 (m, 1H, H-2),
3.03 (dd, J¼9.4, 3.1 Hz,1H, H-3), 3.00 (d, J¼3.1 Hz,1H, OH),1.00 (s, 9H,
4.4. Analytical data of the coupling products
4.4.1. (rac)-1-Cyclohexyl-2-phenylbut-3-en-1ol (9). Compound
was prepared as a colorless oil according to procedure A and was
obtained in 75% yield. 1H NMR (400 MHz, CDCl3)
: 7.32e7.18 (m,
5H, Ph), 6.13 (ddd, J¼19.7, 17.0, 8.9 Hz, 1H, H-3), 5.20 (dd, J¼10.7,
1.7 Hz, 1H, H-4a), 5.17 (ddd, J¼17.0, 1.7, 0.7 Hz, 1H, H-4b), 3.58e3.53
(m, 1H, H-1), 3.44 (dd, J¼8.9, 7.1 Hz, 1H, H-2), 1.83e1.81 (m, 1H, Cy),
1.70e1.57 (m, 4H, Cy), 1.26e1.05 (m, 6H, Cy); 13C NMR (100 MHz,
9
SitBu); 13C NMR (100 MHz, CDCl3)
d: 143.1 (q, Ph), 141.1 (q, Ph), 136.9
d
(t, C-4), 136.4 (t, Ph), 136.2 (t, Ph), 133.8 (q, Ph), 133.1 (q, Ph), 130.1 (t,
Ph), 129.9 (t, Ph), 128.6 (t, Ph), 128.5 (t, Ph), 128.3 (t, Ph), 128.2 (t, Ph),
128.1 (t, Ph),127.9 (t, Ph),127.6 (t, Ph),126.6 (t, Ph),117.8 (s, C-5), 79.5
(t, C-2), 78.1 (t, C-1), 50.8 (t, C-3), 27.3 (p, SitBu),19.7 (q, SitBu); HRMS
[MþNa]þ calcd for C33H36O2Si1Na: 515.2392, found 515.2382.
CDCl3) d: 142.2 (t, C-3), 138.6 (q, Ph), 128.9 (t, Ph),128.0 (t, Ph),126.7
(t, Ph), 117.8 (s, C-4), 78.2 (t, C-1), 53.8 (t, C-2), 39.7 (t, Cy), 30.3 (s,
Cy), 26.7 (s, Cy), 26.6 (s, Cy), 26.5 (s, Cy), 26.1 (s, Cy); HRMS
[MþNa]þ calcd for C16H22ONa: 253.1568, found 253.1564.
4.4.6. (2R, 3R, 4R)-2-Phenyl-4-methyl-hex-5-en-3-ol (24). Com-
pound 24 was prepared according to procedure A and was obtained
in 54% yield as a pale yellow oil (dr 5:1). [
a
]
20 þ22.5 (c 1, CH2Cl2); 1H
D
NMR (400 MHz, CDCl3)
d
: 7.43e7.39 (m, 1H, Ph), 7.35e7.29 (m, 2H,
4.4.2. (2S, 3S, 4S)-2-(tert-Butyldiphenylsiloxy)-4-methyl-5-hexen-3-
Ph), 7.23e7.19 (m, 2H, Ph), 5.83 (ddd, J¼17.4, 11.0, 7.2 Hz, 1H, H-5),
5.13 (d, J¼11.0 Hz, 1H, H-6a), 5.04 (d, J¼17.4 Hz, 1H, H-6b), 3.50 (dd,
J¼6.1, 6.1 Hz, 1H, H-3), 2.85 (dq, J¼7.0, 6.1 Hz, 1H, H-2), 2.20 (ddq,
J¼7.2, 6.8, 6.1 Hz, 1H, H-4), 1.51 (d, J¼5.4 Hz, 1H, OH), 1.32 (d,
J¼7.0 Hz, 3H, H-1), 1.05 (d, J¼6.8 Hz, 3H, Me); 13C NMR (100 MHz,
ol (20). Compound 20 was prepared according to procedure A and
was obtained in 73% yield as a pale yellow oil (dr 10:1). [
a
]
20 ꢀ5.6 (c
D
1.0, CH2Cl2); 1H NMR (400 MHz, CDCl3)
d: 7.70e7.68 (m, 4H, Ph),
7.45e7.35 (m, 6H, Ph), 5.80 (ddd, J¼16.5, 10.3, 7.5 Hz, 1H, H-5), 4.96
(d, J¼10.3 Hz, 1H, H-6a), 4.93 (d, J¼16.5 Hz, 1H, H-6b), 3.85 (dq,
J¼6.0, 5.5 Hz, 1H, H-2), 3.20 (ddd, J¼5.9, 5.5, 4.7 Hz, 1H, H-3), 2.51
(d, J¼4.7 Hz, 1H, OH), 2.29 (ddq, J¼7.5, 6.9, 5.9 Hz, 1H, H-4), 1.06 (s,
CDCl3) d: 145.1 (q, Ph), 139.5 (t, C-5), 128.6 (t, Ph), 127.8 (t, Ph), 126.4
(t, Ph), 116.6 (s, C-6), 79.4 (t, C-3), 43.2 (t, C-2), 40.6 (t, C-4), 17.4 (p,
C-1),16.4 (p, Me); HRMS [MþH]þ calcd for C13H19O: 191.1430, found
191.0863.
9H, SitBu), 1.01 (d, J¼6.0 Hz, 3H, H-1), 0.97 (d, J¼6.9 Hz, 3H, Me); 13
C
NMR (100 MHz, CDCl3) d: 140.3 (t, C-5), 136.0 (t, Ph), 136.0 (t, Ph),
135.4 (q, Ph), 134.3 (q, Ph), 129.9 (t, Ph), 127.8 (t, Ph), 115.0 (s, C-6),
4.4.7. (2R, 3R, 3R)-2,4-Diphenyl-hex-5-en-3-ol (25). Compound 25
was prepared according to procedure A and was obtained in 58%
79.5 (t, C-3), 71.1 (t, C-2), 40.5 (t, C-4), 27.2 (p, SitBu), 20.1 (p, Me),

M. Vogt et al. / Tetrahedron 66 (2010) 6450e6456
6455
yield as a pale yellow oil (only one diastereomer could be detected).
Caromat.), 135.6 (t, Caromat.), 133.1 (q, Caromat.), 133.0 (q, Caromat.), 133.0
[
a]
20 þ14.6 (c 1, CH2Cl2); 1H NMR (400 MHz, CDCl3)
d: 7.48e7.18 (m,
(q, Caromat.), 129.9 (t, Caromat.), 129.9 (t, Caromat.), 129.9 (t, Caromat.),
129.9 (t, Caromat.), 127.8 (t, Caromat.), 127.8 (t, Caromat.), 127.8 (t, Car-
omat.), 115.5 (s, C-1), 115.5 (s, C-1), 115.4 (t, Caromat.), 115.3 (t, Caromat.),
D
10H, Ph), 6.17 (ddd, J¼17.6, 9.9, 9.2 Hz, 1H, H-5), 5.22 (dd, J¼9.9,
1.7 Hz,1H, H-6a), 5.09 (d, J¼17.6 Hz,1H, H-6b), 3.99e3.94 (m,1H, H-
3), 3.32 (dd, J¼9.2, 6.8 Hz, 1H, H-4), 2.78e2.71 (m, 1H, H-2), 1.75 (d,
J¼3.4 Hz, 1H, OH), 1.30 (d, J¼7.2 Hz, 3H, H-1); 13C NMR (100 MHz,
t
112.3 (t, Caromat.), 112.2 (t, Caromat.), 107.6 (t, Caromat.), 80.4 (q, Bu),
79.9 (t, C-5), 79.8 (t, C-5), 76.1 (t, C-4), 73.8 (t, C-4), 57.6 (p, OMe),
57.2 (p, OMe), 44.6 (s, C-8), 44.3 (s, C-8), 40.7 (t, C-3), 39.8 (t, C-3),
37.2 (s, C-6), 35.3 (s, C-6), 31.3 (t, C-7), 30.9 (t, C-7), 28.4 (p, tBu), 26.6
(p, SitBu), 19.7 (p, C-10), 19.5 (q, SitBu), 18.7 (p, C-10), 17.7 (p, C-9),
16.2 (p, C-9); HRMS [MþH]þ calcd for C38H54NO5Si: 632.3771,
found 632.3770.
CDCl3) d: 145.4 (q, Ph),142.5 (q, Ph),138.1 (t, C-5),129.2 (t, Ph),128.8
(t, Ph), 128.2 (t, Ph), 128.1 (t, Ph), 127.0 (t, Ph), 126.7 (t, Ph), 118.3 (p,
C-6), 78.8 (t, C-3), 54.1 (t, C-4), 42.2 (t, C-2), 15.3 (p, C-1); HRMS
[MþH]þ calcd for C18H21O: 253.1587, found 253.1570.
4.4.8. (3S, 4S, 5S, 8R)-8-(tert-Butyldimethylsiloxy)-10-(4-methoxy-
benzyloxy)-3,5,7-trimethyl-deca-1,6-dien-4-ol (27). Compound 27
4.5. General procedure for the Hoffmann procedure14
was prepared according to procedure B and was obtained in 57%
20
yield as a yellow oil (dr 1.5:1). [
(400 MHz, CDCl3)
a
]
D
ꢀ4.3 (c 0.3, CH2Cl2); 1H NMR
(E)-Crotyl pinacol boronate 34 (30
the aldehyde (138 mol, 1.0 equiv) were mixed in a flask and stirred
for 3 days at room temperature. The reaction was hydrolysed with
triethanolamine (19 L, 138 mol, 1.0 equiv) and diluted with pe-
troleum ether and CH2Cl2 (1 mL, 1:1). After stirring for 1 day the
solvents were evaporated and the residue was purified by flash
chromatography.
mL, 138 mmol, 1.0 equiv) and
d
: 7.26e7.24 (m, 2H, Ph), 6.88e6.86 (m, 2H, Ph),
m
5.79 (ddd, J¼17.2, 10.3, 7.2 Hz, 1H, H-2), 5.20 (d, J¼9.8 Hz, 1H, H-6),
5.09 (dd, J¼17.2, 10.3 Hz, 2H, H-1), 4.42 (d, J¼11.4 Hz, 1H, CH2PMB),
4.36 (d, J¼11.4 Hz, 1H, CH2PMB), 4.13 (dd, J¼7.3, 5.6 Hz, 1H, H-8),
3.80 (s, 3H, OMe), 3.49e3.38 (m, 2H, H-10), 3.19e3.15 (m, 1H, H-4),
2.46 (ddq, J¼9.8, 6.9, 6.6 Hz, 1H, H-5), 2.36 (ddq, J¼7.2, 7.1, 4.4 Hz,
1H, H-3), 1.80e1.70 (m, 2H, H-9), 1.55 (s, 3H, Me), 1.38 (d, J¼6.1 Hz,
1H, OH), 1.06 (d, J¼7.0 Hz, 3H, Me), 0.94 (d, J¼6.4 Hz, 3H, Me), 0.87
(s, 9H, SitBu), 0.02 (s, 3H, SiMe), ꢀ0.01 (s, 3H, SiMe); 13C NMR
m
m
Analytical data for the product of the reaction of aldehyde 32
with boronate 34 can be found in Ref. 14.
(100 MHz, CDCl3) d: 159.2 (q, Caromat.), 139.4 (t, C-2), 137.3 (q, C-7),
4.6. General procedure for the Roush procedure
130.8 (q, Caromat.),129.4 (t, Caromat.), 128.1 (t, C-6),116.5 (s, C-1),113.8
(t, Caromat.), 79.2 (t, C-4), 75.1 (t, C-8), 72.8 (s, CH2PMB), 67.1 (s, C-10),
55.4 (p, OMe), 40.8 (t, C-5), 36.8 (s, C-9), 36.0 (t, C-3), 25.9 (p, SitBu),
18.3 (q, SitBu), 17.4 (p, Me), 16.2 (p, Me), 11.7 (p, Me), ꢀ4.4 (p, SiMe),
ꢀ4.9 (p, SiMe); HRMS [MþNa]þ calcd for C27H46O4SiNa: 485.3063,
found 485.3052.
(E)-Crotyl pinacol boronate 34 (66 mL, 320 mmol, 1.0 equiv) was
dissolved in dry CH2Cl2 under an argon atmosphere and cooled to
ꢀ78 ꢁC. The aldehyde (384
mmol, 1.2 equiv) was added and stirring
was continued at ꢀ78 ꢁC for 2 h. The mixture was allowed to warm
to room temperature over night and was hydrolysed with H2O
(1 mL). The aqueous phase was extracted with ethyl acetate and the
combined organic phases were dried (MgSO4) and concentrated in
vacuo. The residue was purified by flash chromatography.
Analytical data for the product of the reaction of aldehyde 33
with boronate 34 can be found in Ref. 12b.
4.4.9. (3R, 4R, 5S, 6R)-6-(tert-Butyl-dimethyl-siloxy)-3,5,7-trimethyl-
octa-1,7-dien-4-ol (29). Compound 29 was prepared according to
procedure A and was obtained in 60% yield as a colorless oil (dr
20
12:1). [
a
]
ꢀ4.1 (c 1.6, CH2Cl2); 1H NMR (400 MHz, CDCl3)
d: 5.72
D
(ddd, J¼17.1, 9.6, 9.3 Hz, 1H, H-2), 5.11 (d, J¼17.1 Hz, 1H, H-1a), 5.09
(d, J¼9.67 Hz, 1H, H-1b), 4.93 (s, 1H, H-8a), 4.87 (s, 1H, H-8b), 4.07
(d, J¼7.9 Hz, 1H, H-6), 3.22 (d, J¼7.9 Hz, 1H, H-4), 2.90 (br s, 1H, OH),
2.29e2.23 (m, 1H, H-3), 1.77e1.73 (m, 1H, H-5), 1.66 (s, 3H,
4.7. General procedure for mechanistic investigation
experiments (Table 5)
H2CCCH3), 0.94e0.90 (m, 15H, 2ꢂ CH3, SitBu), 0.07 (s, 6H, SiMe); 13
C
(E)-Crotyl pinacol boronate 34 (42
(2S)-(tert-butyldiphenylsiloxy)-propanal 17 (60 mg, 192
m
L, 192
m
mol, 1.0 equiv) and
mol,
NMR (100 MHz, CDCl3) d: 146.1 (q, C-7), 142.1 (t, C-2), 116.1 (s, C-1),
m
113.2 (s, C-8), 80.3 (t, C-7), 75.0 (t, C-4), 42.5 (t, C-5), 38.0 (t, C-3),
26.1 (p, SitBu), 18.4 (q, SitBu), 17.5 (p, C-7), 16.7 (p, C-5), 8.1 (p, C-3),
ꢀ4.4 (p, SiMe), ꢀ4.9 (p, SiMe); HRMS [MþNa]þ calcd for
C17H34O2SiNa: 321.2226, found 321.2226.
1.0 equiv) were mixed in a flask. Then the particular additive was
added (amounts given in Table 5) and the reaction mixture was
stirred for 3 days at room temperature. The reaction was hydro-
lysed with triethanolamine (19 mL, 138 mmol, 1.0 equiv) and diluted
with petroleum ether and CH2Cl2 (1 mL,1:1). After stirring for 1 day
the solvents were evaporated and the residue was purified by flash
chromatography.
When DMSO was added the hydrolysed reaction mixture was
submitted to usual aqueous workup before it was purified by flash
chromatography.
4.4.10. (2S,
4R)-5-[tert-Butoxycarbonylamino-3-(tert-butyldiphe-
nylsiloxy)-phenyl]-4-hydroxy-5-methoxy-3,7-dimethyl-oct-2-en
(31). Compound 31 was prepared according to procedure B and
was obtained in 33% yield as a yellow oil (dr 1:1). The di-
astereoisomers could not be separated. 1H NMR (400 MHz, CDCl3)
d: 7.71e7.68 (m, 7H, SiPh), 7.43e7.33 (m, 11H, SiPh), 6.81 (s, 1H, Ph),
6.77 (s,1H, Ph), 6.66 (s,1H, Ph), 6.63 (s,1H, Ph), 6.25 (s, 2H, NH), 6.15
(s, 1H, Ph), 6.14 (s, 1H, Ph), 5.90e5.75 (m, 2H, H-2), 5.12e4.93 (m,
4H, H-1), 3.53 (dd, J¼7.8, 3.7 Hz, 1H, H-4), 3.30 (s, 3H, OMe), 3.27 (s,
3H, OMe), 3.23e3.20 (m, 2H, H-4 and H-5a), 3.18e3.12 (m, 1H, H-
5b), 2.43 (dd, J¼13.3, 5.8 Hz, 1H, H-8a), 2.34 (dd, J¼13.3, 6.1 Hz, 1H,
H-8a), 2.28e2.17 (m, 2H, H-3), 2.14e2.05 (m, 2H, H-8b), 1.76e1.72
(m, 1H, H-7), 1.67e1.62 (m, 1H, H-7), 1.60e1.58 (m, 1H, H-6a), 1.53
(s, 15H, tBu), 1.47e1.44 (m, 1H, H-6a), 1.37e1.10 (m, 2H, H-6b), 1.07
(s, 15H, 2ꢂSitBu), 1.04 (d, J¼6.8 Hz, 3H, H-9), 0.94 (d, J¼6.8 Hz, 3H,
H-9), 0.69 (d, J¼6.4 Hz, 3H, H-10), 0.63 (d, J¼6.8 Hz, 3H, H-10); 13C
Acknowledgements
The work was funded by the Fonds der Chemischen Industrie.
Supplementary data
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2010.04.133.
References and notes
NMR (100 MHz, CDCl3) d: 155.9 (q, NCO), 155.9 (q, NCO), 152.6 (q,
Caromat.), 143.0 (q, Caromat.), 142.9 (q, Caromat.), 141.3 (t, C-2), 140.1 (t,
C-2), 139.1 (q, Caromat.), 139.0 (q, Caromat.), 135.6 (t, Caromat.), 135.6 (t,
1. (a) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921e2944; (b) Review
Trost, B. M. J. Org. Chem 2004, 69, 5813e5873.

6456
M. Vogt et al. / Tetrahedron 66 (2010) 6450e6456
2. Tsuji, J. Pure Appl. Chem 1982, 54, 197e206.
11. Earlier studies by Szabó and co-workers revealed similar moderate enantiose-
lectivities: Sebelius, S.; Szabó, K. J. Eur. J. Org. Chem. 2005, 2539e2547.
12. (a) Hoffmann, R. W.; Weidmann, U. Chem. Ber. 1985, 3966e3979; (b) Roush, W.
R.; Adam, M. A.; Walts, A. E.; Harris, D. J. J. Am. Chem. Soc. 1986, 108, 3422e3434.
13. The minor anti, anti-diastereomer of 20 was converted into the corresponding
diacetate.
3. Brown, H. C.; Bhat, K. S.; Randad, R. S. J. Org. Chem. 1987, 52, 3702e3704.
4. (a) Kimura, M.; Shimizu, M.; Shibata, K.; Tazoe, M.; Tamaru, Y. Angew. Chem., Int.
Ed. 2003, 42, 3392e3395; (b) Tamaru, Y. J. Organomet. Chem. 1999, 576,
215e231; (c) Tamaru, Y.; Tanaka, A.; Yasui, K.; Goto, S.; Tanaka, S. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 787e789; (d) Yasui, Y. G.; Yajima, T.; Taniseki, Y.; Fugami,
A.; Tamaru, Y. Tetrahedron Lett. 1993, 34, 7619e7622; (e) Qiao, X.-C.; Zhu, S.-F.;
Zhou, Q.-L. Tetrahedron: Asymmetry 2009, 20, 1254e1261; (f) Ito, H.; Okura, T.;
Matsuura, K.; Sawamura, M. Angew. Chem. 2010, 122, 570e573; Angew. Chem.,
Int. Ed. 2010, 49, 560e563.
5. (a) Itoh, J.; Han, S. B.; Krische, M. J. Angew. Chem. 2009, 121, 6431e6434; Angew.
Chem., Int. Ed. 2009, 48, 6313e6316; (b) Lu, Y.; Krische, M. J. Org. Lett. 2009, 11,
3108e3111; (c) Han, S. B.; Kim, I. S.; Krische, M. J. Chem. Commun. 2009,
7278e7287.
6. (a) Selander, N.; Kipke, A.; Sebelius, S.; Szabó, K. J. J. Am. Chem. Soc. 2007, 129,
13723e13731; (b) Sebelius, S.; Olsson, V. J.; Wallner, O. A.; Szabó, K. J. J. Am.
Chem. Soc. 2006, 128, 8150e8151.
7. Asymmetric umpolung examples: (a) Zanoni, G.; Gladiali, S.; Marchetti, A.;
Piccinini, P.; Tredici, I.; Vidari, G. Angew. Chem., Int. Ed. 2004, 43, 846e849; (b)
Zhu, S. F.; Yang, Y.; Wang, L. X.; Liu, B.; Zhou, Q. L. Org. Lett. 2005, 7, 2333e2335;
(c) Howell, G. P.; Minnaard, A. J.; Feringa, B. L. Org. Biomol. Chem. 2006, 4,
1278e1283 For a recent review on asymmetric allylations of aldehydes and
applications in synthesis, see: (d) Denmark, S. E.; Fu, J. Chem. Rev. 2003, 103,
2763e2794.
1H NMR (400 MHz, CDCl3)
d
: 5.68 (ddd, J¼17.7, 9.5, 8.5 Hz, 1H, H-5), 5.04e4.95
(m, 4H, H-6, H-3, H-2), 2.43 (dq, J¼7.1, 8.5 Hz, 1H, H-4), 2.07 (s, 3H, OAc), 2.01 (s,
3H, OAc), 1.20 (d, J¼6.4 Hz, 3H, H-1), 1.02 (d, J¼7.1 Hz, 3H, Me); [
a
]
20 ꢀ40 (c 0.2,
D
CH2Cl2) and the analytical data were identical with those reported by: Toshima,
K.; Jyojima, T.; Yamaguchi, H.; Noguchi, Y.; Yoshida, T.; Murase, H.; Nakata, M.;
Matsumura, S. J. Org. Chem. 1997, 62, 3271e3284.
14. Brinkmann, H.; Hoffmann, R. W. Chem. Ber. 1990, 2395e2401.
15. (a) Liu, H.; Nasi, R.; Jayakanthan, K.; Sim, L.; Heipel, H.; Rose, D. R.; Pinto, B. M. J.
Org. Chem. 2007, 72, 6562e6572; (b) Priepke, H. W. M.; Warriner, S. L.; Ley, S. V.
Angew. Chem., Int. Ed. Engl. 1994, 33, 2290e2292;
8. Selander, N.; Sebelius, S.; Estay, C.; Szabó, K. J. Eur. J. Org. Chem. 2006,
4085e4087.
9. Ishiyama, T.; Ahiko, T.; Miyaura, N. Tetrahedron Lett. 1996, 37, 6889e6892.
10. (a) The relative stereochemistry was determined after a three-step modifica-
tion of product 9 and analysis was carried out according to Rychnowsky et al.:
Rychnovsky, S.; Skalitzky, D. J. Tetrahedron Lett. 1990, 31, 945e948 Thus, the
anti-configuration was assigned based on the large coupling constant JH-4,
H-
¼10.8 Hz; see also Lombardo, M.; Morganti, S.; Tozzi, M.; Trombini, C. Eur. J.
5
Org. Chem. 2002, 2823e2830 who determined a J¼10.6 Hz for a related case.
1H NMR (400 MHz, CDCl3)
d: 7.41e7.39 (m, 2H, Ph), 7.36e7.30 (m, 3H, Ph), 6.00
(ddd, J¼17.2, 10.3, 9.0 Hz, 1H, H-8), 5.06 (d, J¼10.3 Hz, 1H, H-9), 4.91 (d, J¼17.
2 Hz, 1H, H-9), 4.54 (d, J¼9.8 Hz, 1H, H-6), 3.71 (dd, J¼9.8, 2.0 Hz, 1H, H-5), 3.27
(s, 3H, H-11), 3.25 (s, 3H, H-11), 1.93 (ddq, J¼9.0, 7.1, 2.0 Hz, 1H, H-7), 1.33 (s, 3H,
H-12), 1.30 (s, 3H, H-12), 1.00 (d, J¼7.1 Hz, 3H, H-10).
16. Kirschning, A.; Harmrolfs, K.; Knobloch, T. C.R. Chim. 2008, 1523e1543.
17. Dale, A. J.; Mosher, H. S. J. Am. Chem. Soc. 1973, 24, 512e519.
18. Utilisation of the corresponding allyl carbonates is also possible but resulted in
lower yields which is presumably due to the lower stability of compared to the
acetates: Mennecke, K.; Vogt, M.; Kirschning, A. Unpublished results.
19. (a) For the preparation of compound 26 see: Frenzel, T.; Brünjes, M.; Kirschn-
ing, A. Org. Lett. 2006, 8, 135e138; (b) The synthesis of compound 28 is
(b) The relative stereochemistry was determined after a two-step modification
of compound 29 and analysis was carried out according to Rychnowsky, et al.
(see Ref. 10a). Based on the 13C NMR signals of the methyl groups (
d: 30.1, 19.
€
reported in: Schoning, K.-U.; Wittenberg, R.; Kirschning, A. Synlett 1999,
1624e1626.
6 ppm) the syn configuration was assigned.
(c) A detailed procedure for the synthesis of compound 30 will be published
elsewhere.
20. Potuzak, J. S.; Moilanen, S. B. J. Am. Chem. Soc. 2005, 127, 13769e13797.
21. Paterson, I.; Wallace, D. J.; Cowden, C. J. Synthesis 1998, 639e652.
22. For removing impurities derived from dba traces the crude product was sub-
mitted to a DIBAL-H reduction before it was purified by flash chromatography.