A catalytic asymmetric approach to C1-chiral 3-methylene-indan-1-ols

Article abstract of DOI:10.1016/j.tet.2011.12.040

A sequential (R)-BINAP·Ag^IF (2,2′- bis(diphenylphosphino)-1,1′-binaphthyl) (6-10 mol %), and (Ph ₃P)₂Pd^IICl₂ (bis(triphenylphosphine) palladium(II) dichloride) (2 mol %) catalyzed asymmetric Sakurai-H

Full text of DOI:10.1016/j.tet.2011.12.040

Tetrahedron 68 (2012) 1988e1991
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A catalytic asymmetric approach to C1-chiral 3-methylene-indan-1-ols
*
Roya Mirabdolbaghi, Travis Dudding
Department of Chemistry, Brock University, 500 Glenridge Avenue, St. Catharines, Ontario, Canada L2S 3A1
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 October 2011
Received in revised form 15 December 2011
Accepted 15 December 2011
Available online 21 December 2011
A
sequential (R)-BINAP$AgIF (2,20-bis(diphenylphosphino)-1,10-binaphthyl) (6e10 mol %), and
(Ph3P)2PdIICl2 (bis(triphenylphosphine)palladium(II) dichloride) (2 mol %) catalyzed asymmetric Sakur-
aieHosomieYamamoto allylation/MizorokieHeck reaction that affords C1-chiral 3-methylene-indan-1-
ols with enantiomeric excess (ee) up to 80% is reported. Notably, this protocol allows for the use of
various o-substituted benzaldehydes and allyltrimethoxysilane. It was also discovered that the presence
of electron-rich groups had no effect on the enantioselectivity of the reaction, whereas electron-
withdrawing groups lead to erosion in product ee.
Keywords:
Asymmetric allylation
Heck reaction
Crown Copyright Ó 2012 Published by Elsevier Ltd. All rights reserved.
Sakurai reaction
(R)-BINAP
Sequential catalysis
1. Introduction
After acceptance of this work it was brought to our attention that
€
Schutte et. al. have reported both a racemic and, most recently, an
Both the Lewis acid-catalyzed SakuraieHosomi allylation and
palladium-catalyzed MizorokieHeck cross-coupling reactions rep-
resent two of the most powerful and widely utilized CeC bond
forming reactions in the field of synthesis at this time. Moreover,
with the ever increasing demand for highly-optically enriched
materials, such as agrochemicals and chiral pharmaceuticals, it is
noteworthy that asymmetric versions of the Heck and Sakurai re-
actions have also been developed.
enantioselective palladium-catalyzed domino Sakurai-type allyl-
stannylation-Heck reaction sequence.14 Although, of mention is that
several tandem reactions involving a Sakurai reaction are known.6 It
is also noteworthy, that the chiral indanol products of this procedure
are key substructures within a number of biologically active com-
pounds. For instance, the A and B rings of Anisatin, a biologically
active component of fruit obtained from the Japanese star anise, are
derived from a chiral indanol template. Recent syntheses of Anisatin
have hinged upon the use of a chiral indanols.7 Moreover, in 2006
Smithet al. disclosed the use of a cyclic carbamate substituted indane
motif as a side chain of HIV-1 protease inhibitors.8 Likewise, alkyli-
dene indanes have been employed in diversity oriented synthesis
(DOS) as published by Kesavan et al. in 2007.9 Chiral indanols have
also been used to prepare dopamine reuptake blockers for the
treatment of cocaine abuse.10
As for the above advancements, the (R)- and (S)-BINAP$AgIF
catalyzed asymmetric SakuraieHosomieYamamoto allylation re-
action is considered by many as being one of the most effective
means for preparing chiral homoallylic alcohols.1 It is also note-
worthy that a number of other synthetically useful procedures for
carrying out the catalytic enantioselective allylation of carbonyls
have been reported, including those by Demark, Schaus, and
Keck.2e4 Likewise, the asymmetric MizorokieHeck reaction has
been well studied over the last three decades and notably several
methodologies for constructing chiral quaternary centers have
been developed.5
Accordingly, we were attracted by the potential development of
an annulative AgIF and PdIICl2-catalyzed asymmetric Sakur-
aieHosomi/MizorokieHeck reaction sequence for the synthesis of
enantioenriched C1-chiral 3-methylene-indan-1-ol products 3a
(Scheme 1). At this time we are unaware of a previous catalytic
asymmetric SakuraieHosomi/MizorokieHeck reaction sequence.
Scheme 1. Synthesis of C1-chiral 3-methylene-indan-1-ols derivatives via a sequential
(R)-BINAP$AgIF catalyzed allylation/(Ph3P)2PdIICl2 Heck alkenylation reaction.
The hypothesis at the outset of this work was that a sequential, or
possiblyconcurrent, pairof catalytic reactioncyclesakintothatshown
in Scheme 2 would provide routine accesses to optically enriched
products, such as 3aef. As for the mechanistic elements of this
* Corresponding author. Tel.: þ1 905 688 5550x3405; fax: þ1 905 682 9020;
e-mail address: tdudding@brocku.ca (T. Dudding).
0040-4020/$ e see front matter Crown Copyright Ó 2012 Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.12.040

R. Mirabdolbaghi, T. Dudding / Tetrahedron 68 (2012) 1988e1991
1989
reaction. This last point is noteworthy as the precise mechanism for
the asymmetric (R)- or (S)-BINAP$AgIF SakuraieHosomieYamamoto
allylation reaction is poorly understood at this time.
TS1 possesses four energetically favorable binding interactions,
which reduce to (1) a bifurcated mode (Modes 1 and 2) of aldehyde
activation, (2) a conformational reinforcing aldehyde based CeH/F
interaction (Mode 3), and (3) an aryl CeX/Ag (X¼Cl, Br, I) agostic
interactionorAg/halogencoordination(Mode4)(Fig.1). Basedupon
this model it is surmised that the greater level of enantioselectivity
found with increasing o-aryl halogen size originates from the better
donoreacceptor coordinating ability of larger halogens with silver
(i.e., mode 4). The strengthening of this CeX/Ag interaction with
growing halogen size results in better (re)-stereofacial selectivity in
the following order I>Br>Cl, as a result of increasing transition state
stabilization. It is presumed that other non-stereoselective modes of
addition do not appreciably benefit from this interaction.
In summary, we have reported a dual metal-catalyzed meth-
odology for the synthesis of enantioenriched C1-chiral 3-
methylene-indan-1-ols (eeꢀ80%) that hinges upon the sequential
use of a Yamamoto’s asymmetric SakuraieHosomi allylation re-
action and a MizorokieHeck reaction. Notably, this procedure
benefits from the use of various o-substituted arylaldehydes,
allyltrimethoxysilane, and catalytic amounts of (R)-BINAP$AgIF
(6e10 mol %) and (Ph3P)2PdIICl2 (2 mol %). Ongoing efforts in our
group are focusing upon the extension of this approach for the
construction of C1-chiral 3-methylene-indan-1-ols into an opera-
tionally simpler concurrent tandem catalytic (CTC) process. The
development of a sequential tandem catalyzed (STC), solid support,
variant of this reaction is currently under investigation.
Scheme 2. Proposed catalytic cycle for formation of C1-chiral 3-methylene-indan-1-ols.
catalytic event, Cycle 1 corresponds to a SakuraieHosomieYamamoto
allylation that establishes C1-chirality via the formation of homoallylic
alcohol 2a. In Cycle 2 2a undergoes a 5-exo-trig ring closing Mizor-
okieHeck reaction to afford enantioenriched 3a.
With this mechanistic proposal in mind, a one-pot concurrent
tandem catalysis (CTC) reaction using 2-chlorobenzaldehyde (1a)
(1.0 equiv), allyltrimethoxysilane (1.8 equiv), and (R)-BINAP$AgIF
(6e10 mol %) and (Ph3P)2PdIICl2 (2 mol %) in MeOH was attempted
that only afforded an intractable mixture of products.11
Nevertheless, we felt confident that our envisioned reaction
sequence could be achieved. As such, a subsequent reaction uti-
lizing sequential tandem catalysis (STC) conditions afforded the
targeted C1-chiral indanol product 3a with moderate ee¼68% in
45% yield (Table 1, entry 1).
2. Experimental
2.1. General
Materials were obtained from commercial suppliers (Sigmae
Aldrich)and were used without further purification. DMF (dime-
thylformamide) was distilled under reduced pressure. All reactions
were performed under an inert atmosphere. Reactions were mon-
itored by thin layer chromatography (TLC) using TLC silica gel 60
F254, EMD Merck. Flash column chromatography was performed
over Silicycle ultrapure silica gel (230e400 mesh). NMR spectra
were obtained with a Bruker DPX-300 (1H 300 MHz, 13C 75.5 MHz)
Having found this to be the optimal set of reaction conditions we
then set out to explore the substrate scope of this reaction. The
more sterically demanding and electron-deficient substrate o-
bromodobenzaldehyde (1b) resulted in the formation of 2b in
slightly higher ee than 2a (Table 1, entry 2 vs 1). This result was
unexpected, as in general, marked erosion in enantioselectivity is
observed when o-substituted arylaldehyde are used in catalytic
asymmetric allylations.12 The sterically more demanding o-iodo-
benzaldehyde substrate 1c was then reacted, which afforded the
desired indanol 3a with even higher ee (Table 1, entry 3). In order to
explore this trend further we tested the sterically demanding o-
trifluromethylsulfonylated substrate 1d. Under these reaction
conditions no reaction occurred and only starting material and
decomposition products were obtained (Table 1, entry 4). Further
exploration of the reaction scope demonstrated that electron-rich
2-bromo-5-methoxyaldehdye 1e afforded 3e of comparable ee to
3a (Table 1, entry 5). In contrast, the use of the electron-deficient 2-
bromo-5-fluoroaldehdye 1f resulted in a dramatic decrease in
product ee (Table 1, entry 6).
in CDCl3. The chemical shifts are reported as d values (ppm) relative
to tetramethylsilane. Enantiomeric excess were measured on an
Agilent 1100 series high pressure liquid chromatography (HPLC)
with (OD-H) column. Mass spectra were obtained on an MSI/Kratos
concept IS Mass spectrometer.
2.2. Synthesis
The typical procedure for the asymmetric allylation of an alde-
hyde with allyltrimethoxysilane and (R)-BINAP$AgF as catalyst.
2.2.1. Synthesis of (R)-1-(2-bromophenyl)-3-buten-1-ol, 2b (Table 1,
entry 2). A mixture of AgF (32.9 mg, 0.26 mmol) and (R)-BINAP$AgF
(99.6 mg, 0.16 mmol) was dissolved in anhydrous methanol (3 ml)
under nitrogen atmosphere with exclusion of direct light, and it
was stirred at room temperature for 10 min. To the resulting so-
lution were added dropwise 2-bromobenzaldehyde (264
mL,
2.6 mmol) and allyltrimethoxysilane (791
m
L, 4.7 mmol) at ꢁ20 ꢂC.
The mixture was stirred for 4 h at this temperature, and then
treated with a mixture of 1 N HCl (13 ml) and solid KF (1.3 g) at
room temperature for 30 min. The resulting precipitate was filtered
off, dried over Na2SO4, and concentrated in vacuo. The residual
crude product was purified by column chromatography on silica gel
with ethyl acetate/hexane (1:6) as eluent to afford the chiral
As a working model we propose transition state TS1 (Fig. 1, X¼Cl,
Br, I) to account for the increase in product ee as a function of hal-
ogen size (see entries 1e3, Table 1). TS1 not only accounts for the
increase in product ee observed herein, but also offers a rational for
the enantioselectivity in the SakuraieHosomieYamamoto allylation

1990
R. Mirabdolbaghi, T. Dudding / Tetrahedron 68 (2012) 1988e1991
Table 1
Sequential (R)-BINAP$AgIF catalyzed allylationa/(Ph3P)2PdIICl2 Heck alkenylationb reaction of functionally different electrophilic aldehyde
Entry
Substrate
Step 1
Step 2
Intermediate
Yieldb (%)
T (ꢂC)
t (h)
Product
Yieldc (%)
eed (%)
1
2
2a
2b
91
100
130
48
24
0
de
1a
1b
45
68
3a
80
100
24
3a
73
75
3
4
2c
81
0
100
12
3a
64
80
1c
2d
d
d
1d
5
2e
64
100
24
76
74
1e
3e
3f
6
2f
67
100
130
48
24
0
d
40
58
1f
Reaction conditions:
a
(R)-BINAP$AgIF (6e10 mol %), MeOH, ꢁ20 ꢂC, 4 h.
b
c
(Ph3P)2PdIICl2 (2 mol %), DMF.
Yields of isolated products after flash chromatography.
Enantiomeric excess was determined by HPLC analysis (OD-H).
(d) Not applicable.
d
e
Hall reported that chiral homoallylic alcohol (R)-2b had an optical
rotation of ½a 2D5
þ50.71 (c 1.61, CHCl3). The absolute configurations
ꢃ
of the remaining chiral homoallylic alcohols (i.e., (R)-2a, (R)-2cef)
reported in the present submission were assumed to be the same as
(R)-2b.
2.2.2. (R)-1-(2-Chlorophenyl)-3-buten-1-ol, 2a (in Table 1, entry
1). 1H NMR (300 MHz, CDCl3):
d
¼2.30 (br, 1H), 2.40e2.45 (m, 1H),
2.61e2.69 (m, 1H), 5.21e5.82 (m, 3H), 5.82e5.96 (m, 1H),
7.20e7.25 (m, 3H), 7.35 (dd, J¼7.8, 1.6 Hz, 1H); 13C NMR (75.5 MHz,
CDCl3):
d
¼42.0, 69.6, 118.5, 127.0, 127.1, 128.4, 129.3, 131.7, 134.3,
141.3; MS (EI) m/z 182 (Mþ); HRMS (EI): m/z calcd for C10H11ClO
(Mþ): 182.0498; found: 182.0495; ½a 2D0
þ78.8 (c 1.9, CHCl3).
ꢃ
Fig. 1. Proposed transition state model TS1.
2.2.3. (R)-1-(2-Iodophenyl)-3-buten-1-ol, 2c (in Table 1, entry 3). 1H
NMR (300 MHz, CDCl3):
d
¼2.28e2.35 (m, 2H), 2.38e2.66 (m, 1H),
homoallylic alcohol (469 mg, 2 mmol, 80% yield) as a colorless oil.
1H NMR (300 MHz, CDCl3):
4.94 (dd, J¼8.6, 3.7 Hz, 1H), 5.19e5.26 (m, 1H), 5.87e5.93 (m, 1H),
6.70 (td, J¼7.5, 1.5 Hz, 1H), 7.37 (td, J¼7.6, 0.5 Hz, 1H), 7.54 (dd,
J¼8.1, 0.9 Hz, 1H), 7.82 (dd, J¼7.8, 0.9 Hz, 1H); 13C NMR (75.5 MHz,
d
¼2.35e2.43 (m, 1H), 2.62e2.65 (m,
2H), 5.12 (dd, J¼8.5, 3.8 Hz, 1H), 5.21e5.25 (m, 2H), 5.85e5.91 (m,
1H), 7.14 (td, J¼7.3, 1.8 Hz, 1H), 7.35 (td, J¼7.6, 1.0 Hz, 1H), 7.52e7.59
CDCl3):
d
¼42.3, 76.3, 97.5, 118.6, 127.1, 128.5, 129.2, 134.3, 139.3,
(m, 2H); 13C NMR (75.5 MHz, CDCl3):
d
¼42.1, 71.8,118.7, 121.8, 127.3,
145.6; MS (EI) m/z 274 (Mþ); HRMS (EI): m/z calcd for C10H11IO
127.7, 128.8, 132.6, 134.3, 142.7; MS (EI) m/z 226 (Mþ); HRMS (EI):
m/z calcd for C10H11BrO (79Br) (Mþ): 225.9993; found: 225.9989.
Based upon the work of Hall et al.13 we assigned the absolute
configuration of the chiral homoallylic alcohol (R)-2b [entry 2,
a 20
þ
(M ): 273.9855; found: 273.9849; ½ ꢃD þ54.8 (c 1.6, CHCl3).
2.2.4. (R)-1-(2-Bromo-5-methoxyphenyl)-3-buten-1-ol, 2e (in Table
1, entry 5). 1H NMR (300 MHz, CDCl3):
2.62e2.68 (m, 1H), 3.83 (s, 3H), 5.04e5.08 (m, 1H), 5.19e5.25 (m,
d
¼2.37e2.39 (m, 2H),
Table 1: ½a 2D0
þ38.2 (c 3.7, CHCl3)] as (R)-configuration. Previously,
ꢃ

R. Mirabdolbaghi, T. Dudding / Tetrahedron 68 (2012) 1988e1991
1991
2H), 5.84e5.97 (m, 1H), 7.71 (dd, J¼8.9, 3.1 Hz,1H), 7.14 (d, J¼3.0 Hz,
133.0, 145.7, 148.6, 160.6; MS (EI) m/z 176 (Mþ); HRMS (EI): m/z
1H). 7.27 (d, J¼8.1 Hz, 1H); 13C NMR (75.5 MHz, CDCl3):
d¼42.0,
calcd for C11H12O2 (Mþ): 176.0837; found: 176.0835; ½a 2D0
ꢁ42.7 (c
ꢃ
55.5, 71.9, 112.0, 114.9, 118.5, 133.2, 134.3, 143.9, 145.1, 159.2; MS (EI)
0.9, CHCl3); The enantioselectivity was determined by HPLC anal-
ysis on a chiral column (OD-H, hexane/iPrOH 95:5, flow rate
1.0 mL minꢁ1) to be 74%: tminor¼11.81 min (S), tmajor¼13.56 min (R).
m/z 256 (Mþ); HRMS (EI): m/z calcd for C11H13BrO2 79Br) (Mþ):
(
256.0099; found: 256.0101; ½a D20
þ2.3 (c 2, CHCl3).
ꢃ
2.2.5. (R)-1-(2-Bromo-5-fluorophenyl) -3-buten-1-ol, 2f (in Table 1,
entry 6). 1H NMR (300 MHz, CDCl3):
2.3.3. (R)-6-Fluoro-3-methylene-2,3-dihydro-1H-inden-1-ol, 3f (in
d¼2.31e2.40 (m, 2H),
Table 1, entry 6). 1H NMR: (300 MHz, CDCl3):
d¼2.62e2.68 (m, 2H),
2.60e2.67 (m,1H), 5.02e5.07 (m,1H), 5.19e5.24 (m, 2H), 5.83e5.90
(m, 1H), 6.88 (td, J¼8.1, 3.1 Hz, 1H), 7.31 (dd, J¼9.7, 3.0 Hz, 1H). 7.47
3.14e3.22 (m, 1H), 5.05 (br, 1H), 5.19 (br, 1H), 5.43 (br, 1H),
7.02e7.13 (m, 2H), 7.45 (dd, J¼8.3, 4.9 Hz, 1H); 13C NMR (75.5 MHz,
(dd, J¼8.7, 5.3 Hz, 1H); 13C NMR (75.5 MHz, CDCl3):
d
¼42.0, 71.7,
CDCl3): d 42.9, 73.0, 103.9, 111.7, 116.3, 122.2, 136.3, 145.3, 149.1,
114.6, 116.2, 119.2, 133.9, 145.2, 145.3, 160.8, 164.1; MS (EI) m/z 244
161.9; MS (EI) m/z 164 (Mþ); HRMS (EI): m/z calcd for C10H9FO
(Mþ); HRMS (EI): m/z calcd for C10H10BrFO (79Br) (Mþ): 243.9899;
(Mþ): 164.0637; found: 164.0633; ½a 2D0
ꢁ2.9 (c 1, CHCl3); The
ꢃ
found: 243.9899; ½a D20
ꢃ
þ65.6 (c 0.7, CHCl3).
enantioselectivity was determined by HPLC analysis on a chiral
column (OD-H, hexane/iPrOH 95:5, flow rate 1.0 mL minꢁ1) to be
58%: tminor¼7.55 min (S), tmajor¼8.22 min (R).
2.3. Typical procedure for alkenylation of chiral homoallylic
alcohol with catalytic amount of (Ph3P)2PdIICl2
Acknowledgements
2.3.1. Synthesis of (R)-3-methylene-2,3-dihydro-1H-inden-1-ol, 3a
(in Table 1, entry 2). To a mixture of (R)-1-(2-bromophenyl)-3-
buten-1-ol (385.9 mg, 1.7 mmol), bis(triphenylphosphine)palladiu-
m(II) chloride (23.8 mg, 0.034 mmol), potassium carbonate
(469.9 mg, 3.4 mmol), and DMF (3 ml) were added under a nitrogen
atmosphere followed by 2 drops of hydrazine monohydrate by sy-
ringe. The mixture was heated at 100 ꢂC for 24 h. The resulting
mixture was filtered off and it was diluted with ether and washed
with water. The ether layer was dried over Na2SO4 and concentrated.
The residual crude product was purified by column chromatography
onsilica gel withpentane/ether (1:4)astheeluent toafford thechiral
(R)-3-methylene-2,3-dihydro-1H-inden-1-ol (180 mg, 1.2 mmol,
We are grateful to the Natural Sciences and Engineering Re-
search Council of Canada (NSERC) for funding of this research. We
thank Dr. Costa Metallinos and Dr. Paul Zelisko of Brock University
for use of equipment and helpful suggestions.
References and notes
1. Asakawa, K.; Matsumoto, Y.; Yamamoto, H. Angew. Chem., Int. Ed. 1999, 38,
3701e3703.
2. Denmark, S. E.; Fu, J. Chem. Rev. 2003, 103, 2763e2793.
3. Barnett, D. S.; Moquist, P. N.; Schaus, S. E. Angew. Chem., Int. Ed. 2009, 48,
8679e8682.
4. Keck, G. E.; Tarbet, K. H.; Geraci, L. S. J. Am. Chem. Soc. 1993, 115, 8467e8468.
5. Dounay, A. B.; Overman, L. E. Chem. Rev. 2003, 103, 2945e2963.
6. For select examples, see (a) Stevens, B. D.; Nelson, S. G. J. Org. Chem. 2005, 70,
4375e4379; (b) Tietze, L. F.; Rischer, M. Angew. Chem., Int. Ed. Engl. 1992, 31,
1221e1222.
73% yield) as a colorless oil. 1H NMR: (300 MHz, CDCl3):
d¼1.82 (d,
J¼7.3 Hz,1H), 2.66e2.73 (m,1H), 3.18e3.28 (m,1H), 5.12 (t, J¼1.9 Hz,
1H), 5.27e5.34 (m, 1H), 5.55 (t, J¼2.3 Hz, 1H), 7.28e7.38 (m, 2H),
7.49e7.57 (m, 2H); 13C NMR (75.5 MHz, CDCl3):
d 42.4, 73.1, 104.1,
120.6, 125.2, 128.6, 128.9, 140.2, 146.5, 147.1; MS (EI) m/z 146 (Mþ);
7. Loh, T.-P.; Hu, Q.-Y. Org. Lett. 2001, 3, 279e281.
HRMS (EI): m/z calcd for C10H10O (Mþ): 146.0732; found: 146.0730;
8. Smith, A. B., III; Charnley, A. K.; Harada, H.; Beiger, J. J.; Cantin, L.-D.; Kenesky, S.;
Hirschmann, R.; Munshi, S.; Olsen, D. B.; Stahlhut, M. W.; Schleifb, W. A.; Kuo,
L. C. Bioorg. Med. Chem. Lett. 2006, 16, 859e863.
9. Kesavan, S.; Panek, J. S.; Porco, J. A., Jr. Org. Lett. 2007, 9, 5203e5206.
10. Mark Froimowitz, M.; Wu, K.-M.; Moussa, A.; Haidar, R. M.; Jurayj, J.; George, C.;
Gardner, E. J. Med. Chem. 2000, 43, 4981e4992.
½
a 20
ꢃ
ꢁ6.7 (c 0.4, CHCl3), ½a 20
ꢃ
ꢁ8.8 (c 0.5, CHCl3), ½a D20
ꢁ10.5 (c 0.5,
ꢃ
CHCl3) for intermediate 2a, 2b, and 2c, respectively. The enantiose-
lectivity was determined by HPLC analysis on a chiral column (OD-H,
hexane/iPrOH 95:5, flow rate 1.0 mL minꢁ1
) to be 68%:
11. Wasilke, J.-C.; Obrey, S. J.; Baker, R. T.; Bazan, G. C. Chem. Rev. 2005, 105,
1001e1020.
tminor¼9.33 min (S), tmajor¼10.40 min (R), 75%: tminor¼9.29 min (S),
tmajor¼10.49 min (R), 80% tminor¼9.36 min (S), tmajor¼10.43 min (R)
for intermediate 2a, 2b, and 2c, respectively.
12. As noted, the catalytic enantioselective allylation of o-substituted aldehydes
generally results in reduced product stereoselectives. This fact may be readily
appreciated by a detailed inspection of a recent review, see: (a) Yus, M.;
Gonzalez-Gomez, J. C.; Foubelo, F. Chem. Rev. 2011, 111, 7774e7854 For recent
papers, see: (b) Haddad, T. D.; Hirayama, L. C.; Singaram, B. J. Org. Chem. 2010,
75, 642e649; (c) Hrdina, R.; Valterova, I.; Hodacova, J.; Cisarova, I.; Kotora, M.
Adv. Synth. Catal. 2007, 349, 822e826.
2.3.2. (R)-6-Methoxy-3-methylene-2,3-dihydro-1H-inden-1-ol,
3e
¼1.79 (d, J¼7.9 Hz,
(in Table 1, entry 5). 1H NMR: (300 MHz, CDCl3):
d
1H), 2.65e2.72 (m, 1H), 3.19e3.27 (m, 1H), 3.83 (s, 3H), 4.98 (t,
J¼1.8 Hz, 1H), 5.22e5.28 (m, 1H), 5.37 (t, J¼2.3 Hz, 1H), 6.93 (dd,
J¼8.5, 2.3 Hz, 1H), 7.00 (d, J¼2.0 Hz, 1H), 7.45 (d, J¼8.1 Hz, 1H); 13C
13. Rauniyar, V.; Zhai, H.; Hall, D. G. J. Am. Chem. Soc. 2008, 130, 8481e8490.
ꢀ
€
€
€
14. (a) Cvengros, J.; Schutte, J.; Schlorer, N.; Neudorfl, J.; Schmalz, H.-G. Angew.
€
Chem. 2009, 121, 6264e6267; (b) Schutte, J.; Ye, S.; Schmalz, H.-G. Synlett 2011,
18, 2725e2729.
NMR (75.5 MHz, CDCl3):
d
43.0, 55.5, 73.3, 101.9, 108.6, 116.3, 121.7,