Construction of quaternary carbon centers by a base-catalyzed enantioselective aldol reaction and related reactions of trimethoxysilyl enol ethers

DOI: 10.1016/j.tet.2012.03.096

Source and publish data:

Tetrahedron p. 4210 - 4224 (2012)

Update date:2022-09-26

Topics:

Authors:

Ichibakase, Tomonori

Kaneko, Tetsuya

Orito, Yuya

Kotani, Shunsuke

Nakajima, Makoto

Read Full Text PDF DownLoad Join now for total 90,000,000 free articles

Article abstract of DOI:10.1016/j.tet.2012.03.096

The aldol reactions of trimethoxysilyl enol ethers catalyzed by lithium binaphtholate were found to be powerful tools for the construction of quaternary asymmetric carbon centers. The stereoselectivities were greatly affected by the presence of water. Trimethoxysilyl enol ether derived from a cyclic ketone, such as cyclohexanone, was used as a substrate to obtain the anti-adduct preferentially under anhydrous conditions; by contrast, the syn-adduct was preferentially obtained under aqueous conditions with high stereoselectivity. The aldol-Tishchenko reaction of a trimethoxysilyl enol ether derived from acyclic ketones proceeded to give monoacyl 1,3-diol derivatives in high enantioselectivities.

Full text of DOI:10.1016/j.tet.2012.03.096

Tetrahedron 68 (2012) 4210e4224

Contents lists available at SciVerse ScienceDirect

Tetrahedron

journal homepage: w ww.elsevier.com/locate/tet

Construction of quaternary carbon centers by a base-catalyzed enantioselective

aldol reaction and related reactions of trimethoxysilyl enol ethers

Tomonori Ichibakase ^a, Tetsuya Kaneko ^a, Yuya Orito ^a, Shunsuke Kotani ^b, Makoto Nakajima ^a

^aGraduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan

^bPriority Organization for Innovation and Excellence, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan

a r t i c l e i n f o

a b s t r a c t

Article history:

The aldol reactions of trimethoxysilyl enol ethers catalyzed by lithium binaphtholate were found to be

powerful tools for the construction of quaternary asymmetric carbon centers. The stereoselectivities

were greatly affected by the presence of water. Trimethoxysilyl enol ether derived from a cyclic ketone,

such as cyclohexanone, was used as a substrate to obtain the anti-adduct preferentially under anhydrous

conditions; by contrast, the syn-adduct was preferentially obtained under aqueous conditions with high

stereoselectivity. The aldol-Tishchenko reaction of a trimethoxysilyl enol ether derived from acyclic

ketones proceeded to give monoacyl 1,3-diol derivatives in high enantioselectivities.

Received 25 February 2012

Received in revised form 21 March 2012

Accepted 23 March 2012

Available online 29 March 2012

Keywords:

Aldol reaction

Aldol-Tishchenko reaction

Lithium binaphtholate

Trimethoxysilyl enol ether

1. Introduction

oxides¹²as Lewis bases; however, aldol reactions of trichlorosilyl

enol ether are not widely utilized in organic synthesis because

Quaternary asymmetric centers are found in a variety of organic

compounds, including many natural and bioactive products. The

efﬁcient construction of asymmetric quaternary carbon stereo-

centers is a fascinating topic in organic chemistry.^1,2Many exam-

ples of DielseAlder reactions³or Michael additions^2h,4have

achieved the stereoselective formation of quaternary carbon cen-

ters; however, few examples of aldol reactions⁵for the construction

of asymmetric quaternary centers have been reported.^6,7Retro-

aldol reactions readily proceed under acidic or basic conditions

because aldol products with quaternary carbon atoms are sterically

congested, thereby decreasing the stereoselectivity and chemical

yield of the products.

trichlorosilyl enol ethers are extremely sensitive to water. We

previously reported a lithium binaphtholate-catalyzed¹³asym-

metric aldol reaction of trimethoxysilyl enol ethers,^14,15which are

more stable than trichlorosilyl enol ethers. Herein, we describe the

enantioselective formation of quaternary carbon stereocenters

utilizing base-catalyzed aldol reactions of trimethoxysilyl enol

ethers.¹⁶

2. Results and discussion

2.1. Development of a new method for the preparation of

trimethoxysilyl enol ethers

The development of enantioselective aldol reactions has been

led by Lewis acid-catalyzed reactions of trimethylsilyl enol ethers

with carbonyl compounds, the so-called Mukaiyama aldol re-

action.⁸Recently, Lewis base-catalyzed asymmetric aldol reactions⁹

have attracted considerable attention because Lewis base-catalyzed

aldol reactions of a trichlorosilyl enol ether give the syn-adduct

from the Z-enol ether and the anti-adduct from the E-enol ether via

cyclic transition state structures involving hypervalent silicates.¹⁰

We previously described asymmetric aldol reactions of tri-

chlorosilyl enol ethers catalyzed by chiral N-oxides¹¹or phosphine

In a previous report, trimethoxysilyl enol ethers were prepared

by reacting enolates with chlorotrimethoxysilane, or by reacting

a,b-unsaturated ketones with trimethoxysilane in the presence of

Rh(I) catalyst (Fig. 1).¹⁴However, the preparation of chloro-

trimethoxysilane in high purity was troublesome, whereas the

OSi(OMe)₃

LDA

(MeO)₃SiCl

(MeO)₃SiH

Rh(PPh₃)₃Cl

neat, reflux

THF, -78 °C

* Corresponding author. Tel.: þ81 96 371 4680; fax: þ81 96 362 7692; e-mail

address: nakajima@gpo.kumamoto-u.ac.jp (M. Nakajima).

Fig. 1. Previous synthetic method for obtaining trimethoxysilyl enol ethers.

doi:10.1016/j.tet.2012.03.096

T. Ichibakase et al. / Tetrahedron 68 (2012) 4210e4224

4211

latter method was applicable to the synthesis of limited silyl enol

ethers.

ketones in high yields and in high purity.¹⁷The present facile and

versatile method provides access to trimethoxysilyl enol ethers

with high purity. Other trimethoxysilyl enol ethers 1iek were

prepared using a Rh-catalyzed conjugated reduction in the pres-

ence of trimethoxysilane.

Therefore, we began to explore a practical and convenient

method for preparing trimethoxysilyl enol ethers (Fig. 2). As an

alterative silylating reagent, we focused on trimethoxysilyl tri-

ﬂate.¹⁸Trimethoxysilyl triﬂate is a readily available silicon source

with high purity, prepared by mixing allyltrimethoxysilane and

triﬂic acid in dichloromethane. The prepared solution of trime-

thoxysilyl triﬂate was directly added dropwise to a solution of cy-

clohexane and triethylamine at 0 ^ꢀC. The reaction proceeded

smoothly to furnish the corresponding trimethoxysilyl enol ether

1a in high yield. We next applied this protocol to the silylation of 2-

methylcyclohexanone, and trimethoxysilyl enol ethers were

obtained as regioisomers, the thermodynamically stable trime-

thoxysilyl enol ether 1b, and the kinetic product, trimethoxysilyl

enol ether 1b⁰(1b/1b⁰¼60:40). To obtain 1b as a single isomer, we

screened reaction conditions and found that the use of tetra-n-

butylammonium iodide as an additive in chloroform under reﬂux

conditions improved the regioselectivity to give the desired tri-

methoxysilyl enol ethers 1b (1b/1b⁰¼>99:1). This procedure yiel-

ded the trimethoxysilyl enol ethers 1ceh from the corresponding

2.2. Construction of quaternary asymmetric centers by base-

catalyzed aldol reaction

2.2.1. Under anhydrous conditions. With the desired silyl enol

ethers in hand, we carried out the aldol reaction of the trime-

thoxysilyl enol ether 1b and the benzaldehyde 2a in the presence of

the dilithium salt of 3,3⁰-dibromobinaphthol (3e, 10 mol %) at

ꢁ23 ^ꢀC, according to our procedure described previously (Fig. 3).¹⁴

The reaction proceeded smoothly, and the aqueous work-up with

KF/KH₂PO₄and silica gel column chromatography gave the mixture

of syn-4ba and anti-4ba [96% yield, syn/anti¼1:27, 81% ee (anti)].¹⁹

in situ generation of (MeO)₃SiOTf

(MeO)₃Si

TfOH (1.5 eq)

(MeO)₃SiOTf

Et₃N

OSi(OMe)₃

Fig. 3. Aldol reactions of trimethoxysilyl enol ether 1b with 2a.

Surprisingly, we found that the chemical yields and stereo-

selectivities of the product 4ba were not reproducible across mul-

tiple experiments due to the retro-aldol reaction during the

aqueous work-up (HCl or KF/KH₂PO₄) and silica gel column chro-

matography. A screen of quenching conditions revealed that the use

of an aqueous solution of potassium ﬂuoride and formic acid (KF/

HCOOH) minimized the occurrence of the retro-aldol reaction. We

also found that careful addition of acetic acid to the eluent sup-

pressed the retro-aldol reaction during the silica gel column

chromatography step, which isolated the aldol product 4ba; how-

ever, to facilitate manipulation, the crude product was directly

benzoylated with benzoyl chloride and isolated as the benzoate 5ba

to improve the accuracy of data collection (Fig. 4). Improvements in

these isolation methods (quenching method and derivatization)

increased both the yield and the stereoselectivity of the aldol

products and secured reproducible results.

(MeO)₃SiOTf

OSi(OMe)₃

Et₃N, additive

>99

1b'

without Bu₄NI

with Bu₄NI

OSi(OMe)₃

The relative stereochemistry (syn and anti) was assigned by

comparison with the NMR data in the literature.²⁰Although the

absolute conﬁgurations were not determined, we conﬁrmed that

both syn-4ba and anti-4ba had the same absolute conﬁguration at

the benzylic position upon oxidation of syn-4ba and anti-4ba to

6ba (Fig. 5).

(MeO)₃SiH

Rh(PPh₃)₃Cl

OSi(OMe)₃

Next, we screened the substituents at the 3,3⁰-positions of the

catalyst 3 (Table 1). The unsubstituted binaphthol 3a and the

methyl substituted binaphtholate 3b gave lower stereoselectivities

(entries 1 and 2). The phenyl substituted binaphtholate 3c im-

proved the enantioselectivity but decreased the reactivity (entry 3).

Among the halogen-substituted binaphtholates, 3def, containing

chloro or bromo groups, gave better yields and selectivities (entries

4 and 5). Lowering the reaction temperature to ꢁ45 ^ꢀC with

dilithium binaphtholate 3d as a catalyst improved the enantiose-

lectivities, although the reaction times were extended.

OSi(OMe)₃

Fig. 2. Synthesis of the trimethoxysilyl enol ethers 1.

4212

T. Ichibakase et al. / Tetrahedron 68 (2012) 4210e4224

Table 2

(R)-3e

Aldol reaction of various trimethoxysilyl enol ethers 1

OSi(OMe)₃

+ PhCHO

(10 mol %)

1) 2a (1.0 eq)

THF

(R)-3d (10 mol %)

OBz

OSi(OMe)₃

OBz

quenched with

KF/HCOOH

THF, –45 °C, 3 h

2) benzoylation

not isolated

OBz

1 (1.5 eq)

syn-5

anti-5

OBz

BzCl, DMAP

CH₂Cl₂

Entry

1^c

Silyl enol ether

Product

Yield, %

syn/anti^a

ee,^b% (anti)

4aa^d

5ba

1:3.8

1:49

1:10

1:1.8

1:1.2

2.4:1

syn-5ba

anti-5ba

5ca

Fig. 4. Practical isolation of aldol adducts.

5da^e

5ea^e,f

5fa^f

Determined by NMR.

Determined by HPLC.

ꢁ23 ^ꢀC, 0.5 h.

PCC

CH₂Cl₂

PCC

CH₂Cl₂

Isolated as the aldol adduct.

(–)-anti-4ba

(+)-6ba

(+)-syn-4ba

We oxidized the hydroxyketones 4da and 4ea (aldol adducts before benzoyla-

tion) into the diketones (6da and 6ea) and conﬁrmed that both syn and anti adducts

had the same absolute conﬁguration at the benzylic position (see Experimental

section).

Fig. 5. Relationship between the relative conﬁgurations of the aldol adducts 4ba.

The relative conﬁgurations were determined by X-ray analyses of anti-5ea and

syn-4fa.

Table 1

Screening of the catalysts 3

Table 3

Aldol reaction of various aldehydes 2

OLi

RCHO, 2

(R)-3d (10 mol %)

OSi(OMe)₃

OBz

THF, –45 ˚C, 3 h

1) 3 (10 mol %)

2) benzoylation

OSi(OMe)₃

+ PhCHO

OBz

THF

1b (1.5 eq)

syn-5

anti-5

2) BzCl, DMAP

CH₂Cl₂, 0°C

Entry

Aldehyde, R

Ph (2a)

Product

Yield, %

syn/anti^a

ee,^b% (anti)

syn-5ba

anti-5ba

5ba

1:40

1:14

1:10

1:8.2

1:2.7

1:>50

1:20

1:2.4

1:5.3

4-MeOC₆H₄(2b)

4-CF₃C₆H₄(2c)

4-NO₂C₆H₄(2d)

1-Naphthyl (2e)

2-Naphthyl (2f)

(E)-PhCH]CH (2g)

PhCH₂CH₂(2h)

5bb

5bc

5bd

5be

5bf

5bg

5bh

Entry

X (3)

Temp, ^ꢀC

ꢁ23

Time, h

Yield, %

syn/anti^a

ee,^b% (anti)

H (3a)

Me (3b)

Ph (3c)

Cl (3d)

Br (3e)

I (3f)

0.5

1:17

1:8.7

1:26

1:38

1:27

1:21

1:49

ꢁ23

ꢁ45

8^c

9^c,d

Cl (3d)

Determined by NMR.

Determined by HPLC.

Determined by ¹H NMR.

Determined by HPLC.

ꢁ23 ^ꢀC, 3 h.

Using (R)-3e as a catalyst.

With optimized reaction conditions in hand, we carried out the

aldol reactions of trimethoxysilyl enol ethers 1aef and benzalde-

hyde (2a) (Table 2). The diastereo- and enantioselectivities were

dramatically increased in the reaction of the a-methyl substituted

benzaldehyde derivatives, p-anisaldehyde (2b) bearing an electron-

donating group slightly increased the enantioselectivity (entry 2).

On the other hand, introduction of electron-withdrawing groups

decreased the activity and stereoselectivity (entries 3 and 4). The

reaction of p-nitrobenzaldehyde (2d) yielded a particularly reduced

enantioselectivity (entry 4). The sterically hindered 1-

naphthaldehyde (2e) gave a low diastereoselectivity, whereas 2-

naphthaldehyde (2f) afforded results similar to benzaldehyde

(entries 5 and 6). The reaction of trans-cinnamaldehyde (2g),

a conjugated aldehyde, gave the best result (98% yield, syn/

anti¼1:20, 90% ee) (entry 7). The observed anti-selectivity was the

highest yet reported for the construction of quaternary carbon

centers in an enantioselective aldol reaction.²¹The aliphatic alde-

hydes 2h and 2i were less reactive, and the observed selectivities

were moderate (entries 8 and 9); however, the reaction of hydro-

cinnamaldehyde (2h) in the presence of the catalyst 3e at ꢁ23 ^ꢀC

improved the enantioselectivity to 85% ee (entry 9). As shown in

trimethoxysilyl enol ether 1b compared with the reaction of the

trimethoxysilyl enol ether 1a derived from cyclohexanone (entry 1

vs 2). The trimethoxysilyl enol ether 1c bearing an ethyl group also

gave good results; however the stereoselectivity was slightly re-

duced (entry 3). Trimethoxysilyl enol ether 1d derived from 2-

methylcyclopentanone gave a good enantioselectivity but the syn/

anti ratio (diastereoselectivity) was extremely reduced (entry 4).

Both the diastereo- and enantioselectivities of the reaction of 1e

were reduced (entry 5). Unexpectedly, the syn-adduct was pre-

dominantly produced from the trimethoxysilyl enol ether 1f de-

rived from 2-methylindanone, and the stereoselectivities were

modest (entry 6).

Next, we investigated the aldol reactions of trimethoxysilyl enol

ether 1b with various aldehydes 2aeh (Table 3). Among the

T. Ichibakase et al. / Tetrahedron 68 (2012) 4210e4224

4213

Table 4

Screening of the catalysts 3

Table 3, the anti-adduct was predominantly formed from the cyclic

E-enol ether 1b without exception. These results suggested that the

aldol reaction proceeded via a chair-like six-membered transition

state, although the details remain unclear.

PhCHO, 2a

catalyst, 3

H₂O (1.5 eq)

THF, –23 °C, 0.5 h

2) benzoylation

OSi(OMe)₃

OBz

2.2.2. Under aqueous conditions. We previously demonstrated that

the presence of water in the reaction medium greatly affects the

stereoselectivity in an aldol reaction of trimethoxysilyl enol

ehters.^14bFor example, the aldol reaction of 1a under anhydrous

conditions predominantly produced the anti-adduct with a mod-

erate enantioselectivity. By contrast, the syn-adduct was pre-

dominantly obtained under aqueous conditions and the

enantioselectivity of the syn-adduct was considerably better

(Fig. 6). Therefore, we investigated the aldol reaction of the tri-

methoxysilyl enol ether 1b and benzaldehyde (2a) in the presence

of water (1.5 equiv) as an additive. As expected, the syn-adduct was

preferentially obtained, and the enantioselectivity was greatly en-

hanced (Fig. 7).

syn-5ba

anti-5ba

1b (1.5 eq)

Entry

X (3)

H (3a)

Yield, %

syn/anti^a

ee,^b% (syn, anti)

1:1.6

1:1.1

1:3.1

2.3:1

1.5:1

56, 7

65, 1

24, 3

81, 1

70, 4

Me (3b)

Ph (3c)

Cl (3d)

Br (3e)

Determined by NMR.

Determined by HPLC.

(R)-3e (10 mol %)

OSi(OMe)₃

+ PhCHO

Table 5

Aldol reaction of various silyl enol ethers 1

with or without H₂O

THF, –23 °C, 0.5 h

PhCHO, 2a

(R)-3d (10 mol %)

H₂O (1.5 eq)

THF

4aa

OBz

OSi(OMe)₃

OBz

without H₂O

97% yield, syn:anti = 1 : 3.7

8 % ee (syn), 51% ee (anti)

with H₂O (1.5 eq) 94% yield, syn:anti = 3.1 : 1

80% ee (syn), 50% ee (anti)

2) benzoylation

1 (1.5 eq)

syn-5

anti-5

Fig. 6. Effect of water on the aldol reaction of 1a and 2a.

Entry Silyl enol ether Product Conditions

Yield, % syn/anti^aee,^b% (syn)

5ba

5ca

5da

5ea

5fa

ꢁ23 ^ꢀC, 0.5 h 72

2.3:1

2.5:1

2.3:1

1.5:1

1:5.0

6.7:1

ꢁ45 ^ꢀC, 3 h

1) (R)-3e (10 mol %)

ꢁ23 ^ꢀC, 0.5 h 52

OSi(OMe)₃

OBz

with or without H₂O

PhCHO THF, –23 °C, 0.5 h

2) benzoylation

ꢁ45 ^ꢀC, 3 h

ꢁ78 ^ꢀC, 6 h

Determined by NMR.

Determined by HPLC.

5ba

without H₂O

97% yield, syn : anti = 1 : 27

36% ee (syn), 84% ee (anti)

Table 6

Aldol reaction of various aldehydes 2

with H₂O (1.5 eq) 73% yield, syn : anti = 1.5 : 1

70% ee (syn), 1% ee (anti)

1) (R)-3d (10 mol %)

H₂O (1.5 eq)

THF, –78 °C

Fig. 7. Effect of water on the aldol reaction of 1b and 2a.

OSi(OMe)₃

RCHO

OBz

2) benzoylation

We again screened the substituents at the 3,3⁰-positions in

binaphthol under aqueous condition (Table 4). Introduction of hy-

drogen, methyl, or phenyl groups in place of a halogen atom at the

3,3⁰-positions decreased the enantioselectivity.

The catalyst 3d was used to investigate the aldol reaction of

various trimethoxysilyl enol ethers (Table 5). The reaction of the

silyl enol ether 1b at ꢁ45 ^ꢀC increased the enantioselectivity to 87%

ee but the chemical yield decreased (entry 2). Trimethoxysilyl enol

1f (1.5 eq)

syn-5

Entry

Product Time, h Yield, % syn/anti^aee,^b% (syn)

Ph (2a)

(E)-PhCH]CH (2g) 5fg

PhCH₂CH₂(2h)

c-Hex (2i)

Me (2j)

5fa

6.7:1

13:1

10:1

>50:1

12:1

5fh

5ﬁ^c

5fj

ether 1c derived from 2-ethylcyclohexanone gave

a stereo-

selectivity similar to that of 1b (entry 3). Trimethoxysilyl enol

ethers 1d and 1e were highly reactive, and the reactions proceeded

at ꢁ45 ^ꢀC (entries 4 and 5). The enol ether 1e derived from meth-

yltetralone gave the anti-adduct preferentially, although the reason

for this preference was not clear. The trimethoxysilyl enol ether 1f

derived from 2-methylindanone also provided a high reactivity;

therefore, the reaction temperature was decreased to ꢁ78 ^ꢀC to

afford a high enantioselectivity (94% ee, entry 6).

Determined by NMR.

Determined by HPLC.

Absolute conﬁguration was determined by X-ray crystallography; see the main

text.

adducts were preferentially obtained without exception. Cinna-

maldehyde (2g), a linear conjugated aldehyde, gave result similar to

those obtained from benzaldehyde (2a). Although the aliphatic al-

dehydes 2hej required longer reaction times, the stereoselectivities

were excellent (entries 3e5). Cyclohexanecarboxaldehyde (2i)

The aldol reactions of various aldehydes with the trimethoxysilyl

enol ether 1f were next investigated (Table 6). In all cases, the syn-

4214

T. Ichibakase et al. / Tetrahedron 68 (2012) 4210e4224

Table 7

Screening of the catalysts 3

particularly gave an extremely high syn/anti ratio with good

enantioselectivity.

In a parallel experiment, the hydroxyketone 4ﬁ derived from the

silyl enol ether 1f and cyclohexanecarboxaldehyde (2i) reacted with

(S)-camphorsulfonyl chloride to afford 7ﬁ, which was recrystallized

from hexane and diethyl ether to give suitable crystals for X-ray

analysis. X-ray analysis revealed that the absolute conﬁguration of

the hydroxyketone 4ﬁ was determined to be (1⁰S,2R) (Fig. 8).

OLi

OH O Ph

OSi(OMe)₃

(R)-3 (10 mol %)

PhCHO

THF, -45

C, 24 h

8ia

(2.5 eq)

Entry

Yield,^a

ee,^b

S O

H (3a)

Me (3b)

Ph (3c)

Cl (3d)

Br (3e)

Isolated yield.

Determined by HPLC.

7fi

using 3,3⁰-diphenylbinaphthol. In the above aldol reaction, the

halogen-substituted catalyst appeared to give good selectivity,

whereas the diphenylbinaphthol derivative (3c) afforded a high

reactivity and selectivity in the aldol-Tishchenko reaction (entry 3).

Next, we investigated the effects of temperature on the 3c-

catalyzed reaction (Table 8). Mild conditions gave the diol 8il in

good yields and selectivity (entry 1). Lowering the temperature

further improved the selectivity, and the best enantioselectivity

was obtained at ꢁ23 ^ꢀC (entry 4). Reactions at lower temperatures

gave decreased yields and selectivities (entries 5 and 6).

Fig. 8. Determination of the absolute conﬁguration of 7ﬁ.

2.3. Base-catalyzed aldol-Tishcheko reaction of

trimethoxysilyl enol ethers

The trimethoxysilyl enol ether 1i derived from iso-

butyrophenone was used as a substrate under anhydrous condi-

tions. Surprisingly, the reaction afforded a monobenzoyl 1,3-diol

8ia (33% yield, 75% ee) accompanied by the aldol adduct 5ia (33%

yield, 33% ee). This product was an aldol-Tishchenko product

formed by acetalization followed by a 1,5-hydride shift (Fig. 9).²²

Table 8

Effects of reaction temperature

(R)-3c

OH O Ph

OSi(OMe)₃

PhCHO, 2a

(10 mol %)

PhCHO

1i (1.5 eq)

(R)-3d (10 mol %)

THF

THF, -45 °C, 24 h

OH O Ph

Ph Ph

8ia

(2.5 eq)

Entry

Temp, ^ꢀ

Time, h

Yield,^a

ee,^b

5ia

33% yield, 33% ee

8ia

ꢁ18

ꢁ23

ꢁ45

ꢁ78

33% yield, 75% ee

OM O Ph

PhCHO

1,5-hydride shift

Isolated yield.

Determined by HPLC.

5ia'

M: H, Li, Si(OMe)₃

8ia'

With the optimized reaction conditions in hand, we performed

the aldol-Tishchenko reaction of various trimethoxysilyl enol

ethers 1 with benzaldehyde (2a) (Table 9). The acyl-transferred by-

products 9 were often observed in the aldol-Tishchenko reac-

tion.^22e25In fact, in the reaction of the enol ether 1j derived from

the isobutyraldehyde and aldehyde 2a yielded considerable

amounts of the acyl-transferred product 9ja (50% yield, 91% ee)

with the same enantioselectivity as that of 8ja (20% yield, 91% ee)

(entry 2). The reactions of the enol ethers 1g and 1h with bulky

substituents required higher temperatures, and the selectivities

were reduced (entries 3 and 4). The trimethoxysilyl enol ether 1k

with a geometric isomer gave nearly identical results, regardless of

the geometric ratio (entries 5 and 6).

Fig. 9. Base-catalyzed aldol-Tishcheko reaction.

The enantioselective aldol-Tishchenko reaction has recently

attracted interest because it forms a monoacyl-protected 1,3-diol

from carbonyl equivalents.^22e24The 1,3-anti conﬁguration of the

product could be explained based on the cyclic transition state of

the hydride shift.²⁵

Using a 2.5 mol equiv benzaldehyde (2a), we screened sub-

stituents on the catalyst for the enantioselective aldol-Tishchenko

reaction (Table 7). The enantioselectivity was affected by the sub-

stituents at the 3,3⁰-positions, and the best results were obtained

T. Ichibakase et al. / Tetrahedron 68 (2012) 4210e4224

4215

Table 9

Aldol-Tishchenko reaction of various trimethoxysilyl enol ethers 1

OSi(OMe)₃

R³

OH O Ph

(R)-3c (10 mol %)

PhCHO

R¹

THF

R²R³

R²

(2.5 eq)

3-O-ester

1-O-ester

Entry

Silyl enol ether

Conditions

Yield,^a

ee,^b

3-O-Ester (8)

1-O-Ester (9)

1i (R¹¼Ph, R²¼R³¼Me)

1j (R¹¼H, R²¼R³¼Me)

ꢁ23 ^ꢀC, 6 h

ꢁ23 ^ꢀC, 24 h

rt, 24 h

92 (8ia)

20 (8ja)

70 (8ga)

10 (8ha)

82 (8ka)

79 (8ka)

50 (9ja)

1g (R¹¼Ph, R², R³¼e(CH₂)₅e)

1h (R¹¼ⁱPr, R²¼R³¼Me)

rt, 24 h

66 (9ha)

16 (9ka)

1k (R¹¼Ph, R², R³¼Et, Me) (E/Z¼5.3:1)

1k (R¹¼Ph, R², R³¼Et, Me) (E/Z¼1.2:1)

ꢁ23 ^ꢀC, 6 h

Isolated yield.

Determined by HPLC.

The monoacylated products 8ka and 9ka are the derivatives of

examined (Table 10). p-Anisaldehyde, with an electron-donating

group, gave a high enantioselectivity, although the reactivity was

slightly low (entry 2). On the other hand, p-bromobenzaldehyde 2l,

with an electron-withdrawing group, gave result similar to those of

benzaldehyde (2a) (entry 3). Cinnamaldehyde (2g), a linear con-

jugated aldehyde, provided a high enantioselectivity but with

a signiﬁcant decrease in the chemical yield (entry 4). The reaction

of hydrocinnamaldehyde (2h), a linear aliphatic aldehyde, provided

a reduced enantioselectivity and chemical yield (entry 5). Cyclo-

hexanecarboxaldehyde (2i) also gave the corresponding products

in good yields but with low enantioselectivities (entry 6).

symmetric diol; therefore, we could not determine whether 8ka

and 9ka were the original aldol-Tishchenko products or acyl-

transferred adducts (Table 9, entries 1 and 3). This question was

addressed by reacting the enol ether 1k with 4-tolualdehyde (2k)

to obtain a set of two diastereomers (Fig. 10). At this stage, the di-

astereomers could not be identiﬁed as either a set of 8kk and 9kk

(diastereomers of the aldol-Tishchenko reaction), or a set of 8kk

and 10kk (isomers of the acyl-transferred adducts). In the former

case (8kk and 9kk), the products obtained after deacylation were

related to the diastereomers 11kk and 12kk. On the other hand,

deacylation of 8kk and 10kk produced a single 1,3-diol (11kk). We

next methanolyzed two diastereomers to yield two types of diols.

These results suggested that the original diastereomeric mixture in

the aldol-Tishchenko reaction comprised 8kk and 9kk, and the acyl

group was not transferred in the reaction of enol ether 1k with

aldehyde 2a or 2b.

Table 10

Aldol-Tishchenko reaction of various aldehydes 2

The enantioselective aldol-Tishchenko reactions of the trime-

thoxysilyl enol ether 1i with various aldehydes 2 were next

OSi(OMe)₃

OH O

(R)-3c (10 mol %)

THF, -23 °C

RCHO

OSi(OMe)₃

(2.5 eq)

(R)-3c (10 mol %)

ArCHO

Entry

Time, h

Product

Yield,^a

ee,^b

THF, -23 °C, 24 h

Ph (2a)

8ia

8ib

8il

8ig

8ih

8ii

1k (E/Z=5.3/1)

4-MeOC₆H₄(2b)

4-BrC₆H₄(2l)

(E)-PhCH]CH (2g)

PhCH₂CH₂(2h)

c-Hex (2i)

Ar = 4-MeC₆H₄

OH O Ar

OH O Ar Ar

Isolated yield.

Me Et

Determined by HPLC.

Me Et

Et Me

8kk

9kk

10kk

82% yield, 8kk:9kk = 6.5:1

The reaction mechanism was investigated by carrying out the

methanolysis

aldol-Tishchenko reaction of benzaldehyde (2a) with the silylated

aldol adducts 13 or the aldol adduct 14 (Fig. 11). No Tishchenko

adduct was obtained in the reaction of the silylated aldol adduct 13

with benzaldehyde (2a), whereas the aldol adduct 14 provided the

corresponding 1,3-diol derivative 8ja in high yield and enantiose-

lectivity. These results suggested that not the silylated aldol prod-

uct, but the lithiated adduct, was the active species during the

aldol-Tishchenko reaction. In addition, despite the investigation

of the racemate 14, the observed yield and selectivity of 8ja were

OH OH

Me Et

11kk

Me Et

11kk

Et Me

12kk

92% ee

diastereomer

Fig. 10. Determination of the mechanism of generating the diastereomers.

4216

T. Ichibakase et al. / Tetrahedron 68 (2012) 4210e4224

4. Experimental section

OH O Ph

Ph Ph

PhCHO 2a (1.5 eq)

( )-3a (10 mol %)

THF, -45 °C, 24 h

OSi(OMe)₃

4.1. General

¹H and ¹³C NMR spectra were measured in CDCl₃with JEOL AL-

300 (¹H, 300 MHz; ¹³C, 75 MHz) or JNM-ECX400 (¹H, 400 MHz; ¹³C,

100 MHz) spectrometers. Tetramethylsilane (TMS) (

8ja

no reaction

¼0 ppm) and

CDCl₃

(

¼77.0 ppm) were served as internal standards for ¹H and

¹³C NMR, respectively. Infrared spectra were recorded on JEOL JIR

6500-W. Mass spectra were measured with JEOL JMS-DX303HF

mass spectrometer. Optical rotations were recorded on JASCO P-

1010 polarimeter. High-pressure liquid chromatography (HPLC)

was performed on JASCO P-980 and UV-1575. Thin-layer chroma-

tography (TLC) analysis was carried out using Merck silica gel

plates. Visualization was accomplished with UV light, phospho-

molybdic acid, and/or anisaldehyde. Column chromatography was

performed using Kanto Chemical Silica Gel 60N (spherical, neutral,

PhCHO 2a (1.5 eq)

(R)-3c (10 mol %)

THF, -45 °C, 24 h

OH O Ph

8ja

87% yield, 88% ee

Fig. 11. Tishchenko reaction of the aldol adduct and benzaldehyde.

63e210 mm).

extremely high. This observation indicated that the aldol reaction

and acetalization processes in the reaction media were reversible.

Therefore, the enantioselectivity of the present reaction may be

controlled via the stability of the transition state of the hydride shift

(Fig. 12).^22e25The transition state B may be more stable than C,

which preferentially afforded (ꢁ)-8ja.

In enantioselective aldol reactions, the optical rotation data

were not collected for minor diastereomers, because the quantities

of the isolated minor isomers were less than few milligrams in

many cases.

4.2. Preparation of trimethoxysilyl enol ethers

OSi(OMe)₃

4.2.1. 2-Methyl-1-(trimethoxysilyloxy)cyclohexene (1b). Silylation of

ketone with trimethoxysilyl triﬂate with TBAI (procedure A): under an

Ar atmosphere, triﬂic acid (6.75 g, 45 mmol,1.5 equiv) was added to

a solution of allyltrimethoxysilane (7.30 g, 45 mmol, 1.5 equiv) in

CHCl₃(15 mL) at 0 ^ꢀC, and the mixture was stirred for 30 min at the

same temperature. The resulting pale yellow solution was trans-

ferred by cannula to a mixture of 2-methylcyclohexanone (3.6 mL,

30 mmol), triethylamine (8.35 mL, 60 mmol, 2.0 equiv), and tetra-

n-butylammonium iodide (11.1 g, 30 mmol, 1.0 equiv) in CHCl₃

(50 mL). The resulting mixture was heated to reﬂux for 3 h. After

cooling to rt, the solvent was evaporated in vacuo. The residue was

extracted with hexane (100 mLꢂ2) and dried on Na₂SO₄. Puriﬁca-

tion with distillation (77e78 ^ꢀC/4 mmHg) yielded 1b (5.1 g, 73%) as

a colorless oil. Bp: 77e78 ^ꢀC/4 mmHg. ¹H NMR (CDCl₃, 300 MHz):

OSi(OMe)₃

PhCHO

OLi

catalyst

PhCHO

OLi

PhCHO

1.53e1.69 (m, 7H), 1.94e1.98 (m, 2H), 2.12e2.16 (m, 2H), 3.63 (s,

9H). ¹³C NMR (CDCl₃, 75 MHz):

15.7, 22.8, 23.6, 29.1, 30.1, 51.3,

112.0, 141.5. IR (neat):

2929, 2842, 1695 cm^ꢁ1. LR-EIMS: 232 (M^þ),

major

217. HR-EIMS: calcd for C₁₀H₂₀O₄Si 232.1131, found 232.1125.

4.2.2. 2-Ethyl-1-(trimethoxysilyloxy)cyclohexene (1c). Procedure A:

a colorless oil. Bp: 102 ^ꢀC/6 mmHg. ¹H NMR (CDCl₃, 300 MHz):

0.96 (t, 3H, J¼7.8 Hz), 1.54e1.58 (m, 2H), 1.64e1.70 (m, 2H),

1.95e2.10 (m, 2H), 2.12e2.19 (m, 4H), 3.61 (s, 9H). ¹³C NMR (CDCl₃,

100 MHz): 12.0, 22.79, 22.81, 23.5, 27.1, 29.1, 51.1, 117.5, 141.0. IR

(neat):

2933, 2842,1687 cm^ꢁ1. LR-EIMS: 246 (M^þ). HR-EIMS: calcd

minor

L,L = binaphtholate

Fig. 12. Plausible reaction mechanism of the aldol-Tishchenko reaction.

for C₁₁H₂₂O₄Si 246.1287, found 246.1271.

4.2.3. 2-Methyl-1-(trimethoxysilyloxy)cyclopentene (1d). Procedure

A: a colorless oil. Bp: 72 ^ꢀC/8 mmHg. ¹H NMR (CDCl₃, 300 MHz):

3. Conclusion

1.60 (s, 3H), 1.79e1.85 (m, 2H), 2.19e2.22 (m, 2H), 2.36e2.41 (m,

We demonstrated that the aldol reaction of trimethoxysilyl enol

ethers catalyzed by lithium binaphtholate provides a powerful tool

for constructing quaternary asymmetric carbon centers. The ster-

eoselectivities were greatly affected by the presence of water in the

reaction mixture. The cyclic trimethoxysilyl enol ether was used as

a substrate to preferentially obtain the anti-adduct under anhy-

drous conditions; the syn-adduct was preferentially obtained under

aqueous conditions, though there are some exceptions. The tri-

methoxysilyl enol ether derived from the acyclic ketones reacted

according to the aldol-Tishchenko reaction to give the monoacyl

1,3-diol derivatives in high enantioselectivities.

2H), 3.62 (s, 9H). ¹³C NMR (CDCl₃, 75 MHz):

11.4, 19.5, 32.7, 33.5,

51.5, 113.3, 144.4. IR (neat):

2946, 2844, 1699 cm^ꢁ1. LR-EIMS: 203

((M-Me)^þ), 187. HR-EIMS: calcd for C₈H₁₅O₄Si 203.0740, found

203.0718.

4.2.4. 2-Methyl-1-(trimethoxysilyloxy)-3,4-dihydronaphthalene (1e).

Silylation of ketone with trimethoxysilyl triﬂate without TBAI (procedure

B): under an Ar atmosphere, triﬂic acid (6.75 g, 45 mmol, 1.5 equiv)

was added to a solution of allyltrimethoxysilane (7.30 g, 45 mmol,

1.5 equiv) in CH₂Cl₂(15 mL) at 0 ^ꢀC, and the mixture was stirred for

30 min at the same temperature. The resulting pale yellow solution

T. Ichibakase et al. / Tetrahedron 68 (2012) 4210e4224

4217

was transferred by cannula to a mixture of 2-methyl-1-tetralone

(4.8 g, 30 mmol), triethylamine (8.35 mL, 60 mmol, 2.0 equiv) in

CH₂Cl₂(50 mL). The mixture was stirred for 3 h. After warming to rt,

the solvent was evaporated in vacuo. The residue was extracted with

hexane (100 mLꢂ2) and dried on Na₂SO₄. Puriﬁcation with distilla-

tion yielded 1e (5.4 g, 64%) as a colorless oil. Bp: 131 ^ꢀC/5 mmHg. ¹H

Z),1.83 (s, 3H, E), 1.97 (q, 2H, J¼7.4 Hz, E), 2.31 (q, 2H, J¼7.4 Hz, Z), 3.40

(s, 9H, E and Z), 7.23e7.38 (m, 5H, E and Z). ¹³C NMR (CDCl₃,

100 MHz):

d 11.9, 13.1, 14.5, 16.8, 24.3, 26.2, 51.0, 118.9, 119.1, 127.2,

127.4, 127.6, 127.8, 128.8, 129.0, 138.0, 138.1, 141.3, 142.0. IR (neat):

1678, 1093 cm^ꢁ1. LR-EIMS: 282 (M^þ), 267, 235. HR-EIMS: calcd for

C₁₄H₂₂O₄Si 282.1287, found 282.1291.

NMR (CDCl₃, 400 MHz):

1.90 (s, 3H), 2.29 (t, 2H, J¼7.8 Hz), 2.76 (t,

2H, J¼7.8 Hz), 3.60 (s, 9H), 7.05e7.12 (m, 2H), 7.19 (dt, 1H, J¼1.8,

7.8 Hz), 7.45 (d, 1H, J¼7.8 Hz). ¹³C NMR (CDCl₃, 100 MHz):

d 16.7, 27.9,

29.1, 51.4, 117.1, 121.0, 126.1, 126.3, 126.6, 133.2, 135.6, 140.7. IR (neat):

4.3. Construction of quaternary asymmetric centers using

base-catalyzed aldol reaction under anhydrous condition

2942, 2842, 1654, cm^ꢁ1. LR-EIMS: 280 (M^þ), 265. HR-EIMS: calcd for

C₁₄H₂₀O₄Si 280.1131, found 280.1127.

4.3.1. 2-(Hydroxyphenylmethyl)-2-methylcyclohexanone

(4ba).²⁰Typical procedure for the aldol reaction under anhydrous con-

dition: under an Ar atmosphere, n-BuLi (0.094 mmol, 20 mol %) in

hexane (0.21 M, 0.45 mL) was added to a solution of (R)-3,3⁰-dichlor-

obinaphthol (16.8 mg, 0.047 mmol,10 mol %) inTHFat ꢁ45 ^ꢀC, and the

mixture was stirred for 5 min. Then a solution benzaldehyde 2a inTHF

(1.0 M, 0.47 mL, 0.47 mmol) and silyl enol ether 1b (0.71 mmol,

1.5 equiv) were successively added to the above mixture. After 3 h, the

reaction was quenched with KF/HCOOH aq (1.5 M KF, 3.0 M HCOOH,

2 mL) and the mixture was stirred for 2 h at rt. The aqueous layer was

extracted with AcOEt and the combined organic layers were succes-

sively washed with satd NaHCO₃(3 mL) and brine (3 mL). Drying over

Na₂SO₄and evaporating the solvent gave the crude product, which

was puriﬁed by silica gel column chromatography (SiO₂9.0 g, CH₂Cl₂/

hexane/AcOH 80:10:1, then CH₂Cl₂/AcOEt/AcOH 160:1:1, then

100:10:1) to afford the corresponding product as an oil (98 mg, 96%

yield, syn/anti 1:27). The enantiomeric excess was determined to be

81% (anti) and 39% (syn) bychiral HPLC [Daicel Chiralcel OD-H, hexane/

IPA¼19:1, 1.0 mL/min]: t_R10.6 min (syn-minor),16.9 min (anti-major),

4.2.5. 2-Methyl-1-(trimethoxysilyloxy)-3H-indene (1f). Procedure A:

colorless oil. Bp: 147e148 ^ꢀC/4.5 mmHg. ¹H NMR (CDCl₃,

400 MHz):

d 2.06 (s, 3H), 3.20 (s, 2H), 3.67 (s, 9H), 7.14 (dt, 1H,

J₁¼0.9, 7.3 Hz), 7.25e7.37 (m, 3H). ¹³C NMR (CDCl₃, 100 MHz):

d 11.9,

38.6, 51.7, 117.2, 120.3, 123.5, 124.3, 126.2, 140.6, 141.8, 145.6. IR

(neat):

2945, 2845, 1641, 1608 cm^ꢁ1. LR-FABMS: 289 (MþNa^þ),

267 (MþH^þ), 266 (M^þ), 251, 235. HR-FABMS: calcd for C₁₃H₁₈O₄Si

266.0974, found 266.1011.

4.2.6. [Cyclohexylidene(trimethoxysilyloxy)methyl]benzene

(1g). Procedure A: a colorless oil. Bp: 160e163 ^ꢀC/4.5 mmHg. ¹H

NMR (CDCl₃, 400 MHz):

2.41e2.44 (m, 2H), 3.39 (s, 9H), 7.21e7.37 (m, 5H). ¹³C NMR (CDCl₃,

100 MHz): 26.5, 27.1, 27.2, 27.8, 29.7, 50.9, 121.2, 127.2, 127.6, 128.9,

137.7, 139.3. IR (neat):

2923, 1664, 1080 cm^ꢁ1. LR-EIMS: 308 (M^þ),

d 1.43e1.65 (m, 6H), 2.05e2.08 (m, 2H),

276. HR-EIMS: calcd for C₁₆H₂₄O₄Si 308.1444, found 308.1385.

4.2.7. 2,4-Dimethyl-3-(trimethoxysilyloxy)-2-pentene (1h). Procedure

B: a colorless oil. Bp: 79 ^ꢀC/6 mmHg. ¹H NMR (CDCl₃, 400 MHz):

18.5 min (syn-major), 23.8 min (anti-minor).

1.04 (d, 6H, J¼6.9 Hz), 1.63 (s, 3H), 1.66 (s, 3H), 2.85 (hept, 1H,

anti-4ba:²⁰colorless oil. [

]

ꢁ40.2 (c 1.63, CHCl₃), 81% ee. ¹H

J¼6.9 Hz), 3.62 (s, 9H). ¹³C NMR (CDCl₃, 100 MHz):

17.7, 18.6, 19.8,

NMR (CDCl₃, 400 MHz): d 1.18 (s, 3H), 1.24e1.29 (m, 1H), 1.51e1.74

29.1, 51.5, 108.3, 147.5. IR (neat):

1678, 1082 cm^ꢁ1. LR-EIMS: 234

(m, 4H), 2.00e2.04 (m, 1H), 2.37e2.43 (m, 1H), 2.57e2.65 (m, 1H),

3.94 (d, 1H, J¼2.1 Hz), 4.97 (d, 1H, J¼2.1 Hz), 7.2e7.4 (m, 5H).

(M^þ), 219, 202. HR-EIMS: calcd for C₁₀H₂₂O₄Si 234.1287, found

234.1233.

syn-4ba:²⁰colorless oil. ¹H NMR (CDCl₃, 400 MHz)

d 1.07 (s, 3H),

1.35e1.41 (m, 1H), 1.63e1.77 (m, 3H), 1.98e2.20 (m, 2H), 2.34e2.40

(m, 1H), 2.55e2.63 (m, 1H), 3.06 (d, 1H, J¼4.0 Hz), 5.08 (d, 1H,

J¼4.0 Hz), 7.2e7.4 (m, 5H).

4.2.8. 2-Methyl-1-phenyl-1-(trimethoxysilyloxy)-1-propene (1i). Red-

uctive silylation of

a,b-unsaturated ketone with trimethoxysilane (pro-

cedure C): to an orange solution of Rh(PPh₃)₃Cl (17.2 mg, 19

mmol,

0.025 mol %) in 1-phenyl-2-methyl-2-penten-1-one (10.9 g, 74

mmol) was added trimethoxysilane (11.7 g, 97 mmol,1.3 equiv) under

an Ar atmosphere at rt. After heating at 90 ^ꢀC for 30 min, the reaction

mixture was cooled to rt. Ice-cooled satd NaHCO₃(15 mL) was added

and the mixture was vigorously stirred. After removing the cloudy

material by Celite ﬁltration and washing with hexane, the combined

organic layer was washed with brine, dried over Na₂SO₄, and evapo-

ratedtogivethecrudeproductasapaleyellowoil. Distillationinvacuo

gave the silyl enol ether 1i as a colorless oil (9.7 g, 49%). Bp:

4.3.2. anti-2-[(Benzoyloxy)phenylmethyl]-2-methylcyclohexanone

(5ba). Typical procedure for the preparation of benzoylated aldol

adduct: under an Ar atmosphere, n-BuLi (0.094 mmol, 20 mol %) in

hexane (0.21 M, 0.45 mL) was added to a solution of (R)-3,3⁰-

dichlorobinaphthol (16.8 mg, 0.047 mmol, 10 mol %) in THF at

ꢁ45 ^ꢀC, and the mixture was stirred for 5 min. Then a solution al-

dehyde in THF (1.0 M, 0.47 mL, 0.47 mmol) and silyl enol ether 1

(0.71 mmol, 1.5 equiv) were successively added to the above mix-

ture. After 3 h, the reaction was quenched with KF/HCOOH aq

(1.5 M KF, 3.0 M HCOOH, 2 mL) and the mixture was stirred for 2 h

at rt. The aqueous layer was extracted with AcOEt and the com-

bined organic layers were successively washed with satd NaHCO₃

(3 mL) and brine (3 mL). Drying over Na₂SO₄and evaporating the

solvent gave the crude product, which was dissolved in CH₂Cl₂

(2 mL). Benzoyl chloride (0.11 mL, 0.94 mmol, 2.0 equiv) and a so-

lution of DMAP (287 mg, 2.35 mmol, 5.0 equiv) in CH₂Cl₂(2 mL)

were added to the mixture at 0 ^ꢀC. After stirring for 1 h, 10% HCl aq

(5 mL) was added to the mixture and the entire mixture was

extracted with AcOEt (20 mLꢂ3). The organic layer was washed

with brine and dried over Na₂SO₄. After evaporating the solvent,

the residue was puriﬁed by silica gel column chromatography (SiO₂

9.0 g, CH₂Cl₂/hexane¼1:4 then 1:1) to afford the corresponding

benzoylated product 5ba as a colorless oil (143 mg, 94% yield, syn/

anti 1:49, anti 87% ee). The enantiomeric excess was determined to

be 87% (anti) and 54% (syn) by chiral HPLC [Daicel Chiralpak AD-H,

124e125 ^ꢀC/6 mmHg.¹H NMR (CDCl₃, 400 MHz):

3H), 3.40 (s,9H), 7.19e7.26 (m,1H), 7.28e7.39(m, 4H).¹³CNMR(CDCl₃,

100 MHz): 17.8, 19.9, 51.1, 113.7, 127.5, 127.9, 129.1, 138.1, 142.0. IR

(neat):

1686, 1092 cm^ꢁ1. LR-EIMS 268 (M^þ), 236. HR-EIMS: calcd for

d 1.64 (s, 3H),1.86(s,

C₁₃H₂₀O₄Si 268.1131, found 268.1120.

4.2.9. 2-Methyl-1-(trimethoxysilyloxy)-1-propene (1j). Procedure C:

a colorless oil. Bp: 90e91 ^ꢀC/6 mmHg. ¹H NMR (CDCl₃, 400 MHz):

1.55 (d, 3H, J¼1.4 Hz), 1.64 (s, 3H,), 3.62 (s, 9H), 6.15 (q, 1H,

J¼1.4 Hz). ¹³C NMR (CDCl₃, 100 MHz):

d 14.5, 19.0, 51.3, 114.9, 131.5.

IR (neat): n

1687, 1097 cm^ꢁ1. LR-EIMS: 192 (M^þ), 177, 160. HR-EIMS:

calcd for C₇H₁₆O₄Si 192.0818, found 192.0806.

4.2.10. 2-Methyl-1-phenyl-1-(trimethoxysilyloxy)-1-butene

(1k).

Procedure C: a colorless oil. Bp: 126e127 ^ꢀC/6 mmHg. ¹H NMR (CDCl₃,

400 MHz): 0.98 (t, 3H, J¼7.4 Hz, E), 1.09 (t, 3H, J¼7.4 Hz, Z), 1.61 (s, 3H,

4218

T. Ichibakase et al. / Tetrahedron 68 (2012) 4210e4224

hexane/IPA¼7:2, 1.0 mL/min]: t_R13.2 min (anti-minor), 15.8 min

[Daicel Chiralcel OD-H, hexane/IPA¼49:1, 1.0 mL/min]: t_R19.0 min

(syn-major), 32.0 min (syn-minor).

(syn-major), 16.9 min (anti-major), 26.2 min (syn-minor).

anti-5ba: a colorless needle. [

]

þ102.2 (c 1.09, CHCl₃), 87%

anti-4da:²⁰a colorless oil. [

]

²⁸þ49.1 (c 0.10, CHCl₃), 62% ee. ¹H

ee. Mp: 99e102 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

1.16 (s, 3H),

NMR (CDCl₃, 400 MHz): d 1.06 (s, 3H), 1.41e1.47 (m, 1H), 1.76e2.02

1.38e1.50 (m, 1H), 1.70e1.88 (m, 3H), 2.02e2.20 (m, 2H),

2.35e2.44 (m, 1H), 2.63e2.71 (m, 1H), 6.61 (s, 1H), 7.2e7.5 (m, 7H),

7.5e7.6 (m, 1H), 8.01 (d, 2H, J¼8.0 Hz). ¹³C NMR (CDCl₃, 100 MHz):

(m, 3H), 2.19e2.28 (m, 1H), 2.40e2.48 (m, 1H), 4.10 (s, 1H), 4.81 (s,

1H), 7.26e7.36 (m, 5H).

syn-4da:²⁰a colorless oil. [

²⁸ꢁ2.74 (c 0.10, CHCl₃), 31% ee. ¹H

18.3, 21.2, 28.0, 37.0, 38.9, 53.1, 77.1, 127.7, 128.2, 128.3, 128.6,

NMR (CDCl₃, 400 MHz): d 0.88 (s, 3H), 1.40e1.45 (m, 1H), 1.72e1.97

129.8, 130.0, 133.3, 136.5, 165.4, 212.9. IR (KBr):

1724, 1722 cm^ꢁ1

(m, 2H), 2.17e2.50 (m, 3H), 4.84 (d, 1H, J¼4.0 Hz,), 7.26e7.36 (m,

LR-EIMS: 322 (M^þ), 216, 105, 77. HR-EIMS: calcd for C₂₁H₂₂O₃

322.1569, found 322.1538.

5H).

4.3.7. (þ)-2-Benzoyl-2-methylcyclopentanone (6da).²⁶Following

the procedure for the oxidation of aldol adduct with PCC, the 1,3-

diketone 6da was obtained from anti-4da (62% ee) as a colorless

oil (33 mg, 58% yield). The enantiomeric excess was determined to

4.3.3. (þ)-2-Benzoyl-2-methylcyclohexanone (6ba).²⁶Oxidation of

aldol adduct with PCC: under an Ar atmosphere, a solution of

(ꢁ)-anti-4ba (61 mg, 0.28 mmol, 81% ee), pyridinium chlor-

ochromate (100 mg, 1.4 mmol, 5 equiv) and Celite in CH₂Cl₂

(8 mL) was stirred for 12 h. The reaction mixture was ﬁltrated

through Celite and then evaporated to give the crude product,

which was puriﬁed by silica gel column chromatography (SiO₂

9.0 g, hexane/AcOEt¼9:1) to afford the corresponding 1,3-

diketone 6ba as a colorless oil (48 mg, 79% yield). The enantio-

meric excess was determined to be 75% by chiral HPLC [Daicel

be 62% by chiral HPLC [Daicel Chiralcel OJ-H, hexane/IPA¼9:1,

1.0 mL/min]: t_R13.5 min (minor), 16.1 min (major). [

]

þ25.4 (c

0.56, CHCl₃), 62% ee. ¹H NMR (CDCl₃, 400 MHz):

d 1.49 (s, 3H),

1.85e2.13 (m, 3H), 2.34e2.50 (m, 2H), 2.76e2.91 (m, 1H), 7.41e7.53

(m, 3H), 7.83 (d, 2H, J¼6.8 Hz).

4.3.8. (ꢁ)-2-Benzoyl-2-methylcyclopentanone (6da).²⁶Following

the procedure for the oxidation of aldol adduct with PCC, the 1,3-

diketone 6da was obtained from syn-4da (31% ee) as a colorless

oil (20 mg, 36% yield). The enantiomeric excess was determined to

Chiralcel OJ-H, hexane/IPA¼300:1, 1.0 mL/min]: t_R12.5 min (mi-

nor), 14.8 min (major). [

NMR (CDCl₃, 400 MHz):

]

þ169.2 (c 1.31, CHCl₃), 75% ee. ¹H

1.40e1.49 (m, 4H), 1.67e1.84 (m, 3H),

2.00e2.16 (m, 2H), 2.40e2.43 (m, 1H), 2.80e2.84 (m, 1H),

7.38e7.85 (m, 5H).

Following the procedure for the oxidation of aldol adduct with

PCC, the 1,3-diketone 6ba was obtained from (þ)-syn-4ba (61 mg,

85% ee) as a colorless oil (49 mg, 80% yield). The enantiomeric ex-

cess was determined to be 78% by chiral HPLC [Daicel Chiralcel OJ-

be 25% by chiral HPLC [Daicel Chiralcel OJ-H, hexane/IPA¼9:1,

1.0 mL/min]: t_R13.5 min (major), 16.1 min (minor). [

ꢁ9.71 (c

1.02, CHCl₃), 25% ee.

4.3.9. anti-2-[(Benzoyloxy)phenylmethyl]-2-methyl-1-tetralone

(5ea). The enantiomeric excess was determined to be 42% (anti)

and 6% (syn) by chiral HPLC [Daicel Chiralpak AD-H, hexane/

IPA¼19:1, 1.0 mL/min]: t_R23.4 min (syn-minor), 27.7 min (anti-

H, hexane/IPA¼300:1, 1.0 mL/min]: t_R12.5 min (minor), 14.8 min

(major). [

þ169.3 (c 0.56 CHCl₃) 78% ee.

major), 37.9 min (anti-minor), 60.6 min (syn-major).

4.3.4. anti-2-[(Benzoyloxy)phenylmethyl]-2-ethylcyclohexanone

(5ca). The enantiomeric excess was determined to be 79% (anti)

and 54% (syn) by chiral HPLC [Daicel Chiralpak AD-H, hexane/

IPA¼19:1, 1.0 mL/min]: t_R10.3 min (anti-minor), 12.3 min (anti-

anti-5ea: a colorless prism. [

]

þ42.2 (c 1.05, CHCl₃), 42% ee.

Mp: 129e131 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

d 1.39 (s, 3H),

2.11e2.19 (m, 2H), 2.99e3.10 (m, 2H), 6.66 (s, 1H), 7.15e7.31 (m,

5H), 7.37e7.60 (m, 6H), 8.00e8.15 (m, 3H). ¹³C NMR (CDCl₃,

major), 17.1 min (syn-major), 38.9 min (syn-minor).

100 MHz):

20.0, 25.3, 30.1, 49.9, 78.3, 126.8, 127.8, 127.9, 128.1,

anti-5ca: a colorless needle. [

þ39.2 (c 0.96, CHCl₃) 79% ee.

128.4, 128.6, 129.6, 130.2, 131.7, 133.1, 133.3, 137.5, 142.6, 165.3,

Mp: 102e105 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

0.84 (t, 3H,

199.4. IR (KBr): n

1700, 1681, 1598, 1581 cm^ꢁ1. LR-FABMS: 393

J¼7.4 Hz), 1.54e1.93 (m, 7H), 2.03e2.12 (m, 1H), 2.32e2.47 (m,

(MþNa^þ), 105. HR-FABMS: calcd for C₂₅H₂₂O₃Na 393.1467, found

393.1469. Crystallographic data (excluding structure factors) for

this structure have been deposited with the Cambridge Crystallo-

graphic Data Centre as supplementary publication number CCDC

868918.

2H), 6.65 (s, 1H), 7.23e7.32 (m, 3H), 7.40e7.47 (m, 4H), 7.54e7.58

(m, 1H), 8.05e8.07 (m, 2H). ¹³C NMR (CDCl₃, 100 MHz):

8.3, 20.7,

25.3, 26.0, 31.4, 39.5, 56.3, 76.3, 127.77, 127.84, 128.1, 128.4, 129.6,

130.0, 133.1, 137.3, 165.2, 211.4. IR (KBr):

1716 cm^ꢁ1. LR-FABMS:

359 (MþNa^þ), 105. HR-FABMS: calcd for C₂₂H₂₄O₃Na 359.1624,

found 359.1628.

4.3.10. 2-(Hydroxyphenylmethyl)-2-methyl-1-tetralone

(4ea).^7a,bThe enantiomeric excess was determined to be 7% (anti)

and 34% (syn) by chiral HPLC [Daicel Chiralcel OD-3, hexane/

IPA¼19:1, 0.5 mL/min]: t_R26.9 min (anti-minor), 33.1 min (anti-

4.3.5. anti-2-[(Benzoyloxy)phenylmethyl]-2-methylcyclopentanone

(5da). The enantiomeric excess was determined to be 83% (anti)

and 16% (syn) by chiral HPLC [Daicel Chiralpak AD-H, hexane/

IPA¼29:1, 1.0 mL/min]: t_R18.4 min (anti-minor), 26.1 min (anti-

major), 29.3 min (syn-minor), 50.8 min (syn-major).

major), 35.6 min (syn-major), 53.7 min (syn-minor).

anti-4ea:^7a,ba colorless oil. [

]

ꢁ6.9 (c 1.02, CHCl₃), 7% ee. ¹H

NMR (CDCl₃, 400 MHz):

1.16 (s, 3H), 1.61 (dt, 1H, J¼3.6, 13.3 Hz),

anti-5da: a colorless needle. [

]

²²þ72.3 (c 1.02, CHCl₃), 83% ee.

2.42 (dt,1H, J¼5.0, 13.3 Hz), 2.86e3.00 (m, 2H),14 (br s,1H), 5.23 (d,

1H, J¼4.6 Hz), 7.20e7.36 (m, 7H), 7.48 (dt, 1H, J¼1.4, 7.3 Hz), 8.09 (d,

1H, J¼7.3 Hz).

Mp: 84e86 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

d 1.22 (s, 3H), 1.55e2.02

(m, 4H), 2.20e2.32 (m, 2H), 6.21 (s, 1H), 7.25e7.63 (m, 8H), 8.09 (m,

2H). ¹³C NMR (CDCl₃, 100 MHz):

18.8, 20.9, 32.2, 38.6, 53.4, 78.5,

syn-4ea:^7a,ba colorless oil. [

]

¹⁶ꢁ14.2 (c 1.46, CHCl₃), 34% ee. ¹H

127.4, 128.1, 128.3, 128.6, 129.8, 130.2, 133.3, 137.6, 165.4, 220.2. IR

NMR (CDCl₃, 400 MHz):

1.27 (s, 3H), 1.47 (ddd, 1H, J¼3.7, 5.0,

(KBr):

1735, 1710 cm^ꢁ1. LR-FABMS: 331 (MþNa)^þ, 105. HR-FABMS:

13.3 Hz),1.97 (dt,1H, J¼5.0,13.3 Hz), 2.81e3.04 (m, 2H), 4.88 (s,1H),

calcd for C₂₀H₂₀O₃Na 331.1310, found 331.1317.

5.03 (s, 1H), 7.21e7.52 (m, 8H), 8.06 (d, 1H, J¼1.6 Hz).

4.3.6. anti-2-(Hydroxyphenylmethyl)-2-methylcyclopentanone

(4da).²⁰The enantiomeric excess was determined to be 62% (anti)

and 31% (syn) by chiral HPLC [Daicel Chiralcel OD-H, hexane/

IPA¼29:1, 1.0 mL/min]: t_R13.4 min (anti-major), 14.5 (anti-minor);

4.3.11. (þ)-2-Benzoyl-2-methy-1-tetralone (6ea).²⁷Following the

procedure for the oxidation of aldol adduct with PCC, the 1,3-

diketone 6ea was obtained from anti-4ea (7% ee) as a colorless oil

(56 mg, 76% yield). The enantiomeric excess was determined to be

T. Ichibakase et al. / Tetrahedron 68 (2012) 4210e4224

4219

6% by chiral HPLC [Daicel Chiralcel OJ-H, hexane/IPA¼9:1, 1.0 mL/

(m, 1H), 1.67e1.85 (m, 3H), 2.01e2.14 (m, 2H), 2.35e2.43 (m, 1H),

2.60e2.72 (m, 1H), 3.78 (s, 3H), 6.56 (s, 1H), 6.85e6.88 (m, 2H),

7.30e7.55 (m, 5H), 8.01e8.03 (m, 2H). ¹³C NMR (CDCl₃, 100 MHz):

min]: t_R20.3 min (minor), 36.0 min (major). [

]

þ1.03 (c 0.38,

CHCl₃), 6% ee. ¹H NMR (CDCl₃, 400 MHz):

1.63 (s, 3H), 2.02 (dt, 1H,

J¼5.5, 13.7 Hz), 2.83e2.90 (m, 1H), 3.05e3.13 (m, 2H), 7.26e7.35 (m,

4H), 7.45 (t, 1H, J¼7.3 Hz), 7.5e7.53 (m, 1H), 7.73 (d, 2H, J¼7.8 Hz),

8.06 (d, 1H, J¼6.8 Hz).

d 18.3, 21.2, 27.9, 37.0, 38.9, 53.3, 55.3, 76.7, 113.9, 128.6, 128.9, 129.8,

130.0, 133.3, 159.5, 165.4, 213.2. IR (KBr):

1714 cm^ꢁ1. LR-FABMS:

375 (MþNa^þ), 231, 105. HR-FABMS: calcd for C₂₂H₂₄O₄Na

375.1573, found 375.1582.

4.3.12. (ꢁ)-2-Benzoyl-2-methy-1-tetralone (6ea).²⁷Following the

procedure for the oxidation of aldol adduct with PCC, the 1,3-

diketone 6ea was obtained from syn-4ea (34% ee) as a colorless

oil (52 mg, 70% yield). The enantiomeric excess was determined to

syn-5bb: a colorless prism. Mp: 135e137 ^ꢀC. ¹H NMR (CDCl₃,

400 MHz):

d 1.08 (s, 3H), 1.60e1.98 (m, 5H), 2.27e2.39 (m, 1H),

2.50e2.55 (m, 2H), 3.76 (s, 3H), 6.43 (s, 1H), 6.80e6.83 (m, 2H),

7.22e7.25 (m, 2H), 7.41e7.45 (m, 2H), 7.53e7.57 (m,1H), 8.03 (d, 2H,

be 32% by chiral HPLC [Daicel Chiralcel OJ-H, hexane/IPA¼9:1,

J¼6.8 Hz). ¹³C NMR (CDCl₃, 100 MHz):

d 20.7, 20.8, 26.5, 33.3, 39.6,

52.9, 55.3, 77.0, 113.5, 128.5, 128.9, 129.1, 129.7, 130.5, 133.0, 159.3,

1.0 mL/min]: t_R20.3 min (major), 36.0 min (minor). [

0.46, CHCl₃), 32% ee.

ꢁ3.40 (c

165.1, 212.5. IR (KBr):

1720, 1705 cm^ꢁ1. LR-FABMS: 375 (MþNa^þ),

231, 105. HR-FABMS: calcd for C₂₂H₂₄O₄Na 375.1573, found

375.1596.

4.3.13. anti-2-[(Benzoyloxy)phenylmethyl]-2-methyl-1-indanone

(5fa). The enantiomeric excess was determined to be 42% (anti)

and 31% (syn) by chiral HPLC [Daicel Chiralpak AD-H, hexane/

IPA¼4:1, 1.0 mL/min]: t_R15.9 min (anti-minor), 18.0 min (syn-mi-

4.3.16. 2-[(Benzoyloxy)(p-triﬂuoromethylphenyl) methyl]-2-

methylcyclohexanone (5bc). The enantiomeric excess was de-

termined to be 52% (anti) and 27% (syn) by chiral HPLC [Daicel

Chiralpak AD-H, hexane/IPA¼9:1, 1.0 mL/min]: t_R7.3 min (anti-

minor), 12.1 min (anti-major), 17.9 min (syn-minor), 24.1 min (syn-

nor), 19.8 min (anti-major), 54.5 min (syn-major).

anti-5fa: a colorless prism. [

þ50.4 (c 0.76, CHCl₃), 42% ee.

Mp: 132e133 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

d 1.45 (s, 3H), 2.97 (d,

1H, J¼17.4 Hz), 3.62 (d, 1H, J¼17.4 Hz), 6.37 (s, 1H), 7.10e7.19 (m,

3H), 7.25e7.35 (m, 4H), 7.43e7.50 (m, 3H), 7.55e7.59 (m, 1H), 7.68

(d, 1H, J¼7.8 Hz, AreH), 8.03 (dd, 2H, J¼1.4, 8.2 Hz, AreH). ¹³C NMR

major).

anti-5bc: a colorless prism. [

]

þ54.6 (c 0.95, CHCl₃), 52% ee.

Mp: 131e134 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

d 1.19 (s, 3H),1.46e1.58

(CDCl₃, 100 MHz):

22.6, 37.1, 54.1, 79.9, 124.3, 126.4, 127.2, 127.5,

(m, 1H), 1.75e1.88 (m, 3H), 1.95e2.10 (m, 2H), 2.38e2.49 (m, 1H),

2.55e2.64 (m, 1H), 6.60 (s, 1H), 7.43e7.60 (m, 8H), 8.01 (d, 2H,

128.1, 128.6, 129.8, 130.1, 133.3, 135.1, 136.2, 137.1, 152.5, 165.4, 207.7.

IR (KBr):

1714, 1713 cm^ꢁ1. LR-FABMS: 379 (MþNa^þ), 357 (MþH^þ),

J¼7.3 Hz). ¹³C NMR (CDCl₃, 100 MHz):

d 18.5, 21.1, 27.7, 36.4, 38.8,

235, 105. HR-FABMS: calcd for C₂₄H₂₁O₃Na 379.1310, found

379.1332.

52.9, 76.6, 123.9 (q, J¼270.8 Hz), 125.1 (q, J¼2.9 Hz), 128.1, 128.6,

129.6, 129.8, 130.3 (q, J¼32.4 Hz), 133.5, 140.8, 165.3, 212.1. IR (KBr):

1727, 1706 cm^ꢁ1. LR-FABMS: 413 (MþNa)^þ, 105. HR-FABMS: calcd

4.3.14. syn-2-(Hydroxyphenylmethyl)-2-methyl-1-indanone

(4fa).²⁸Under an Ar atmosphere, H₂O in THF (2.8 M, 0.26 mL,

0.71 mmol, 1.5 equiv) and n-BuLi (0.094 mmol, 20 mol %) in hexane

(0.21 M, 0.45 mL) were added to a solution of (ꢃ)-binaphthol

(13.5 mg, 0.047 mmol, 10 mol %) in THF at ꢁ23 ^ꢀC, and the mixture

was stirred for 5 min. Then a solution benzaldehyde 2a in THF

(1.0 M, 0.47 mL, 0.47 mmol) and silyl enol ether 1e (0.71 mmol,

1.5 equiv) were successively added to the above mixture. After 3 h,

the reaction was quenched with KF/HCOOH aq (1.5 M KF, 3.0 M

HCOOH, 2 mL) and the mixture was stirred for 2 h at rt. The

aqueous layer was extracted with AcOEt and the combined organic

layers were successively washed with satd NaHCO₃(3 mL) and

brine (3 mL). Drying over Na₂SO₄and evaporating the solvent gave

the crude product, which was puriﬁed by silica gel column chro-

matography (SiO₂9.0 g, CH₂Cl₂/hexane 8:1, then CH₂Cl₂/AcOEt

160:1, then 10:1) and crystallized from hexane/AcOEt to give syn-

4fa (38 mg, 32% yield). Mp: 105e106 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

for C₂₂H₂₁O₃F₃Na 413.1341, found 413.1346.

syn-5bc: a colorless prism. Mp: 132e135 ^ꢀC. ¹H NMR (CDCl₃,

400 MHz):

2.51e2.57 (m, 2H), 6.51 (s, 1H), 7.44e7.60 (m, 7H), 8.02 (m, 2H). ¹³C

NMR (CDCl₃, 100 MHz): 20.7, 20.8, 26.4, 33.0, 39.3, 52.5, 76.8,

124.0 (q, J¼270.8 Hz), 125.0 (q, J¼3.8 Hz), 128.1, 128.6, 129.7, 130.0,

d 1.10 (s, 3H), 1.61e2.04 (m, 5H), 2.30e2.42 (m, 1H),

130.2 (q, J¼32.4 Hz), 133.3, 141.3, 165.0, 211.7. IR (KBr):

n 1722,

1706 cm^ꢁ1

LR-FABMS: 413 (MþNa^þ). HR-FABMS: calcd for

C₂₂H₂₁O₃F₃Na 413.1341, found 413.1347.

4 . 3 .17 . 2 - [ ( B e n z o y l o x y ) ( p - n i t r o p h e n y l ) m e t h y l ] - 2 -

methylcyclohexanone (5bd). The enantiomeric excess was de-

termined to be 6% (anti) and 4% (syn) by chiral HPLC [Daicel Chir-

alpak AD-H, hexane/IPA¼9:1, 1.0 mL/min]: t_R19.6 min (anti-minor),

23.6 min (syn-major), 36.6 min (anti-major), 64.5 min (syn-minor).

anti-5bd: a viscous colorless oil. [

þ10.1 (c 0.99, CHCl₃), 6%

ee. ¹H NMR (CDCl₃, 400 MHz):

1.21 (s, 3H), 1.55e2.08 (m, 6H),

1.09 (s, 3H), 2.27 (d, 1H, J¼4.1 Hz), 2.52 (d, 1H, J¼17.0 Hz), 3.71 (d,

1H, J¼17.0 Hz), 5.14 (d, 1H, J¼4.1 Hz), 7.30e7.43 (m, 7H), 7.56e7.63

(m, 1H), 7.78e7.82 (m, 1H). ¹³C NMR (CDCl₃, 100 MHz):

22.9, 35.0,

54.6, 77.2, 124.2, 126.6, 127.2, 127.3, 127.9, 128.1, 135.0, 135.7, 141.0,

2.42e2.60 (m, 2H), 6.59 (s, 1H), 7.41e7.62 (m, 5H), 8.01 (d, 2H,

J¼7.3 Hz), 8.19 (d, 2H, J¼8.7 Hz). ¹³C NMR (CDCl₃, 100 MHz):

d 18.9,

21.0, 27.5, 36.1, 38.8, 52.9, 76.6, 123.4, 128.6, 128.7, 129.4, 129.8,

133.7, 144.3, 147.7, 165.3, 211.8. IR (KBr):

1722, 1712 cm^ꢁ1. LR-

153.6, 211.0. IR (CHCl₃):

3604, 1709 cm^ꢁ1

LR-FABMS: 275

FABMS: 390 (MþNa^þ), 176, 149. HR-FABMS: calcd for

C₂₁H₂₁NO₅Na 390.1318, found 390.1322.

(MþNa^þ), 235. HR-FABMS: calcd for C₁₇H₁₆O₂Na 275.1048, found

275.1054.Crystallographic data (excluding structure factors) for this

structure have been deposited with the Cambridge Crystallographic

Data Centre as supplementary publication number CCDC 868917.

syn-5bd: a colorless prism. Mp: 136e138 ^ꢀC. ¹H NMR (CDCl₃,

400 MHz):

d 1.13 (s, 3H), 1.57e2.07 (m, 5H), 2.28e2.41 (m, 1H),

2.47e2.63 (m, 2H), 6.51 (s, 1H), 7.40e7.62 (m, 5H), 8.02 (d, 2H,

J¼8.7 Hz), 8.16 (d, 2H, J¼8.7 Hz). ¹³C NMR (CDCl₃, 100 MHz):

d 20.7,

4. 3.15. 2-[(Benzoyloxy )(p-methoxyphenyl)methyl]-2-

methylcyclohexanone (5bb). The enantiomeric excess was de-

termined to be 81% (anti) and 78% (syn) by chiral HPLC [Daicel

Chiralpak AD-H, hexane/IPA¼6:1, 1.0 mL/min]: t_R11.1 min (anti-

minor), 15.7 min (anti-major), 24.0 min (syn-minor), 28.5 min (syn-

20.8, 26.4, 33.1, 39.2, 52.4, 76.7, 123.3, 128.6, 128.7, 129.7, 130.3,

133.5, 144.8, 147.7, 165.0, 211.4. IR (KBr):

1724, 1706 cm^ꢁ1. LR-

FABMS: 390 (MþNa^þ). HR-FABMS: calcd for C₂₁H₂₁NO₅Na

390.1318, found 390.1334.

major).

4.3.18. 2-[(Benzoyloxy)(1-naphthyl)methyl]-2-methylcyclohexanone

(5be). The enantiomeric excess was determined to be 80% (anti)

and 14% (syn) by chiral HPLC [Daicel Chiralpak AD-H, hexane/

anti-5bb: a colorless prism. [

]

þ80.8 (c 0.98, CHCl₃), 81% ee.

Mp: 86e88 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

d 1.16 (s, 3H), 1.39e1.49

4220

T. Ichibakase et al. / Tetrahedron 68 (2012) 4210e4224

IPA¼19:1, 1.0 mL/min]: t_R49.0 min (anti-minor), 52.2 min (anti-

major), 61.4 min (syn-minor), 88.7 min (syn-major).

227, 105. HR-FABMS: calcd for

371.1639.

C₂₃H₂₄O₃Na 371.1623, found

anti-5be: a colorless prism. [

²⁰þ193.4 (c 1.22, CHCl₃), 80% ee.

Mp: 47e49 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

1.21e1.35 (m, 2H), 1.38

4.3.21. 2-[1-(Benzoyloxy)-3-phenylpropyl]-2-methylcyclohexanone

(5bh). The enantiomeric excess was determined to be 85% (anti)

and 70% (syn) by chiral HPLC [Daicel Chiralpak AD-H, hexane/

IPA¼19:1, 1.0 mL/min]: t_R9.7 min (syn-major), 14.4 min (anti-ma-

(s, 3H), 1.66e2.02 (m, 5H), 2.54e2.58 (m, 2H), 7.32e7.67 (m, 8H),

7.76e7.90 (m, 2H), 7.97e8.08 (m, 2H), 8.42 (d, 1H, J¼8.0 Hz). ¹³C

NMR (CDCl₃,100 MHz): d 18.9, 21.5, 27.9, 37.2, 39.4, 53.6, 73.2,124.0,

125.7, 126.4, 127.0, 127.8, 128.5, 129.0, 129.1, 129.8, 132.0, 133.2,

jor), 16.3 min (syn-minor), 19.6 min (anti-minor).

133.4, 165.5, 213.0. IR (KBr):

1716 cm^ꢁ1. LR-FABMS: 395 (MþNa^þ),

anti-5bh: a colorless prism. [

]

þ21.9 (c 1.06, CHCl₃), 85% ee.

251, 105. HR-FABMS: calcd for C₂₅H₂₄O₃Na 395.1623, found

395.1626.

Mp: 75e78 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

d 1.18 (s, 3H), 1.57e1.77

(m, 4H), 1.82e2.05 (m, 4H), 2.27e2.39 (m, 1H), 2.58e2.73 (m, 3H),

5,85 (m, 1H), 7.14e7.28 (m, 5H), 7.39e7.46 (m, 2H), 7.54e7.61 (m,

syn-5be: a colorless prism. Mp: 56e58 ^ꢀC. ¹H NMR (CDCl₃,

400 MHz)

0.98 (s, 3H), 1.68e1.95 (m, 5H), 2.03e2.08 (m, 1H),

1H), 8.02 (d, 2H, J¼8.6 Hz). ¹³C NMR (CDCl₃, 100 MHz):

d 19.0, 20.7,

2.45e2.60 (m, 2H), 7.38e7.58 (m, 8H), 7.78 (d,1H, J¼8.2 Hz), 7.83 (d,

27.2, 32.1, 32.8, 36.0, 38.9, 52.9, 76.2, 126.2, 128.5, 129.9, 130.1, 133.2,

1H, J¼7.3 Hz), 8.01e8.03 (m, 2H), 8.40 (d, 1H, J¼8.2 Hz). ¹³C NMR

141.6, 166.4, 213.5. IR (KBr)

2939, 1712 cm^ꢁ1LR-FABMS: 351

(CDCl₃, 100 MHz):

20.6, 21.6, 25.7, 31.4, 38.9, 53.0, 72.5, 123.8,

(MþH^þ). HR-FABMS: calcd for C₂₃H₂₇O₃351.1960, found 351.1994.

124.7, 125.5, 125.7, 126.3, 128.3, 128.6, 128.8, 129.5, 130.4, 132.1,

syn-5bh: a viscous colorless oil. ¹H NMR (CDCl₃, 400 MHz):

132.8, 133.4, 133.5, 164.9, 212.4. IR (KBr):

1722 cm^ꢁ1. LR-FABMS:

d 1.19 (s, 3H), 1.42e1.51 (m, 1H), 1.54e1.78 (m, 3H), 1.86e2.18 (m,

395 (MþNa^þ). HR-FABMS: calcd for C₂₅H₂₄O₃Na 395.1623, found

5H), 2.28e2.38 (m, 1H), 2.56e2.75 (m, 2H), 5.80 (dd, 1H, J¼10.5,

395.1628.

1.4 Hz), 7.12e7.26 (m, 5H), 7.42e7.51 (m, 2H), 7.56e7.62 (m, 1H),

8.04e8.12 (m, 2H). ¹³C NMR (CDCl₃, 100 MHz):

17.6, 20.8, 28.0,

4.3.19. 2-[(Benzoyloxy)(2-naphthyl)methyl]-2-methylcyclohexanone

(5bf). The enantiomeric excess was determined to be 87% (anti)

and 23% (syn) by chiral HPLC [Daicel Chiralpak AD-H, hexane/

IPA¼9:1, 1.0 mL/min]: t_R14.7 min (anti-minor), 18.4 min (anti-ma-

jor), 22.9 min (syn), 39.0 min (syn).

32.6, 37.0, 39.9, 53.9, 73.7, 126.1, 128.4, 128.58, 128.61, 129.9, 130.0,

133.3, 141.3, 166.3, 213.5. IR (KBr):

2933, 1716, 1714 cm^ꢁ1. LR-

FABMS: 373 (MþNa^þ). HR-FABMS: calcd for C₂₃H₂₆O₃Na 373.1780,

found 373.1788.

anti-5bf: a colorless prism. [

]

²⁰þ140.3 (c 1.02, CHCl₃), 87% ee.

4.4. Construction of quaternary asymmetric centers using

base-catalyzed aldol reaction under aqueous condition

Mp 115e118 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

1.24 (s, 3H), 1.45e1.57

(m, 1H), 1.68e1.96 (m, 3H), 2.01e2.24 (m, 2H), 2.40e2.52 (m, 1H),

2.64e2.76 (m, 1H), 6.78 (s, 1H), 7.41e7.62 (m, 6H), 7.76e7.89 (m,

4.4.1. syn-2-[(Benzoyloxy)phenylmethyl]-2-methylcyclohexanone

(5ba). Typical procedure for the aldol reaction under aqueous con-

dition: under an Ar atmosphere, H₂O in THF (2.8 M, 0.26 mL,

0.71 mmol, 1.5 equiv) and n-BuLi (0.094 mmol, 20 mol %) in hexane

(0.21 M, 0.45 mL) were added to a solution of (R)-3,3⁰-dichlor-

obinaphthol (16.8 mg, 0.047 mmol, 10 mol %) in THF at ꢁ23 ^ꢀC, and

the mixture was stirred for 5 min. Then a solution aldehyde 2a in

THF (1.0 M, 0.47 mL, 0.47 mmol) and silyl enol ether 1b (0.71 mmol,

1.5 equiv) were successively added to the above mixture. After 3 h,

the reaction was quenched with KF/HCOOH aq (1.5 M KF, 3.0 M

HCOOH, 2 mL) and the mixture was stirred for 2 h at rt. The

aqueous layer was extracted with AcOEt and the combined organic

layers were successively washed with satd NaHCO₃(3 mL) and

brine (3 mL). Drying over Na₂SO₄and evaporating the solvent gave

the crude product, which was dissolved in CH₂Cl₂(2 mL). Benzoyl

chloride (0.11 mL, 0.94 mmol, 2.0 equiv) and a solution of DMAP

(287 mg, 2.35 mmol, 5.0 equiv) in CH₂Cl₂(2 mL) were added to the

mixture at 0 ^ꢀC. After stirring for 1 h, 10% HCl aq (5 mL) was added

to the mixture and the entire mixture was extracted with AcOEt

(20 mLꢂ3). The organic layer was washed with brine and dried over

Na₂SO₄. After evaporating the solvent, the residue was puriﬁed by

silica gel column chromatography (SiO₂9.0 g, CH₂Cl₂/hexane¼1:4

then 1:1) to afford the corresponding benzoylated product 5ba as

a colorless oil (109 mg, 72% yield, syn/anti 2.3:1). The enantiomeric

excess was determined to be 81% (syn) and 1% (anti) by chiral HPLC

[Daicel Chiralpak AD-H, hexane/IPA¼7:2, 1.0 mL/min]: t_R13.4 min

(anti-minor), 16.2 min (syn-major), 17.2 min (anti-major), 27.1 min

4H), 8.05e8.14 (m, 2H). ¹³C NMR (CDCl₃, 100 MHz):

18.5, 21.3,

28.0, 37.0, 38.9, 53.4, 77.4, 125.4, 126.4, 127.0, 127.8, 127.9, 128.2,

128.6, 129.9, 130.0, 132.9, 133.2, 133.4, 134.2, 165.5, 212.9. IR (KBr):

1724, 1709 cm^ꢁ1. LR-FABMS: 395 (MþNa^þ), 251, 105. HR-FABMS:

calcd for C₂₅H₂₄O₃Na 395.1623, found 395.1624.

syn-5bf: a colorless prism. Mp: 151e153 ^ꢀC. ¹H NMR (CDCl₃,

400 MHz): d 1.14 (s, 3H), 1.63e2.05 (m, 5H), 2.37e2.59 (m, 3H), 6.64

(s, 1H), 7.42e7.58 (m, 5H, Ar-H), 7.75e7.85 (m, 4H), 8.06 (d, 2H,

J¼6.7 Hz). ¹³C NMR (CDCl₃, 100 MHz):

d 20.8, 21.0, 26.4, 33.2, 39.5,

52.9, 77.8, 125.6, 126.19, 126.23, 127.0, 127.7, 128.2, 128.5, 129.7,

130.4, 132.9, 133.1, 134.6, 165.1, 212.3. IR (KBr):

n 1724, 1704,

1600 cm^ꢁ1LR-FABMS: 395 (MþNa^þ), 105. HR-FABMS: calcd for

C₂₅H₂₄O₃Na 395.1623, found 395.1620.

4 . 3 . 2 0 . 2 - [ 1 - ( B e n z o yl o x y ) - 3 - p h e n yl - 2 - p r o p e n yl ] - 2 -

methylcyclohexanone (5bg). The enantiomeric excess was de-

termined to be 90% (anti) and 42% (syn) by chiral HPLC [Daicel

Chiralpak AD-H, hexane/IPA¼19:1, 1.0 mL/min]: t_R15.4 min (anti-

major), 17.2 min (syn-major), 21.1 min (anti-minor), 26.9 min (syn-

minor).

anti-5bg: a colorless prism. [

]

þ91.8 (c 0.97, CHCl₃), 90% ee.

Mp: 76e78 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

d 1.30 (s, 3H), 1.58e2.07

(m, 6H), 2.35e2.43 (m, 1H), 2.58e2.67 (m, 1H), 6.18e6.30 (m, 2H),

6.77 (d, 1H, J¼15.6 Hz), 7.23e7.57 (m, 8H), 8.01 (d, 2H, J¼7.3 Hz). ¹³C

NMR (CDCl₃, 100 MHz): d 18.8, 20.9, 27.6, 36.6, 38.9, 52.7, 77.3, 123.1,

126.8,127.2,128.3,128.5,128.7,128.8,129.8,130.1,133.2,135.1,136.1,

165.6, 213.0. IR (KBr):

1706, 1600 cm^ꢁ1. LR-FABMS: 371 (MþNa^þ),

(syn-minor).

227, 105. HR-FABMS: calcd for C₂₃H₂₄O₃Na 371.1623, found

371.1634.

syn-5ba: a colorless needle. [

]

ꢁ90.4 (c 1.08, CHCl₃), 81% ee.

Mp: 115e117 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

d 1.09 (s, 3H), 1.55e1.79

syn-5bg: a colorless prism. Mp: 141e144 ^ꢀC. ¹H NMR (CDCl₃,

(m, 2H), 1.80e2.03 (m, 3H), 2.32e2.40 (m, 1H), 2.45e2.58 (m, 2H),

6.49 (s, 1H), 7.22e7.35 (m, 5H), 7.42e7.46 (m, 2H), 7.54e7.58 (m,

400 MHz):

d 1.25 (s, 3H), 1.66e1.82 (m, 2H), 1.85e1.95 (m, 3H),

2.10e2.22 (m, 1H), 2.40e2.52 (m, 2H), 6.14e6.23 (m, 2H), 6.70 (dd,

1H), 8.04 (d, 2H, J¼6.9 Hz). ¹³C NMR (CDCl₃, 100 MHz):

d 20.76,

1H, J¼5.5, 20 Hz), 7.16e7.60 (m, 8H), 8.05 (d, 2H, J¼7.4 Hz). ¹³C

20.79, 26.5, 33.2, 39.5, 52.8, 77.5, 127.7, 128.0, 128.5, 129.7, 130.4,

NMR (CDCl₃, 100 MHz):

19.6, 20.9, 27.1, 35.0, 39.7, 53.0, 76.0,

133.1, 137.1, 165.0, 212.3. IR (KBr): n

1722, 1704 cm^ꢁ1. LR-EIMS: 322

123.2, 126.8, 128.2, 128.5, 128.6, 129.7, 130.3, 133.2, 134.8, 136.2,

(M^þ), 216, 105, 77. HR-EIMS: calcd for C₂₁H₂₂O₃322.1569, found

322.1547.

165.4, 212.4. IR (KBr):

1714, 1270 cm^ꢁ1. LR-FABMS: 371 (MþNa^þ),

T. Ichibakase et al. / Tetrahedron 68 (2012) 4210e4224

4221

4.4.2. syn-2-[(Benzoyloxy)phenylmethyl]-2-ethylcyclohexanone

(5ca). The enantiomeric excess was determined to be 79% (syn) and

19% (anti) by chiral HPLC [Daicel Chiralpak AD-H, hexane/IPA¼19:1,

1.0 mL/min]: t_R10.3 min (anti-minor), 12.3 min (anti-major),

17.1 min (syn-major), 38.9 min (syn-minor).

6.73 (d, 1H, J¼16.0 Hz), 7.19e7.29 (m, 5H), 7.34e7.43 (m, 4H),

7.49e7.53 (m, 1H), 7.58 (dt, 1H, J¼0.9, 7.6 Hz), 7.81e7.82 (m, 3H). ¹³

NMR (CDCl₃, 100 MHz):

d 21.9, 38.4, 53.0, 79.8, 123.4, 124.4, 126.5,

126.9, 127.7, 128.11, 128.5, 128.6, 129.7, 130.1, 133.2, 135.1, 135.2,

136.2, 136.5, 152.8, 165.6, 207.9. IR (neat):

1709, 1259 cm^ꢁ1. LR-

syn-5ca: a colorless needle. [

²²ꢁ116.6 (c 1.05, CHCl₃), 75% ee.

FABMS: 405 (MþNa^þ), 261, 105. HR-FABMS: calcd for C₂₆H₂₂O₃Na

Mp: 165e168 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

0.89 (t, 3H, J¼7.6 Hz),

405.1467, found 405.1492.

1.25e1.34 (m, 1H), 1.69e1.91 (m, 5H), 1.99e2.02 (m, 1H), 2.33e2.47

syn-5fg: a colorless needle. [

þ17.0 (c 1.03, CHCl₃), 93% ee.

(m, 3H), 6.56 (s, 1H), 7.24e7.56 (m, 8H), 8.01 (d, 1H, J¼7.2 Hz). ¹³C

Mp: 155e166 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz)

d 1.31 (s, 3H), 2.97 (d,

NMR (CDCl₃, 100 MHz):

8.4, 20.8, 25.7, 26.0, 30.9, 40.2, 55.8, 75.7,

1H, J¼17.0 Hz), 3.72 (d, 1H, J¼17.0 Hz), 5.91 (dd, 1H, J¼7.8, 0.9 Hz),

6.27 (dd, 1H, J¼16.0, 7.8 Hz), 6.85 (d, 1H, J¼16.0), 7.21e7.44 (m, 9H),

7.55e7.59 (m, 3H), 7.66 (dt, 1H, J¼0.9, 7.6 Hz), 7.74 (d, 1H, J¼7.8 Hz).

127.6, 127.91, 127.92, 128.3, 129.5, 130.5, 132.8, 137.1, 164.9, 211.1. IR

(KBr):

1724, 1702 cm^ꢁ1. LR-EIMS: 336 (M^þ), 105, 77. HR-EIMS:

calcd for C₂₂H₂₄O₃336.1725, found 336.1701.

¹³C NMR (CDCl₃, 100 MHz):

d 21.5, 36.7, 52.9, 78.8, 123.4, 124.6,

126.6, 126.9, 127.7, 128.28, 128.34, 128.7, 129.5, 130.1, 132.9, 135.2,

4.4.3. syn-2-[(Benzoyloxy)phenylmethyl]-2-methylcyclopentanone

(5da). The enantiomeric excess was determined to be 75% (syn)

and 42% (anti) by chiral HPLC [Daicel Chiralpak AD-H, hexane/

IPA¼29:1, 1.0 mL/min]: t_R18.4 min (anti-minor), 26.1 min (anti-

major), 29.3 min (syn-major), 50.8 min (syn-minor).

135.8, 136.0, 136.1, 152.9, 164.9, 208.2. IR (neat): n .

1713, 1705 cm^ꢁ1

LR-FABMS: 405 (MþNa^þ), 261, 55 (bp). HR-FABMS: calcd for

C₂₆H₂₂O₃Na 405.1467, found 405.1476.

4.4.7. 2-[1-(Benzoyloxy)-3-phenylpropyl]-2-methyl-1-indanone

(5fh). The enantiomeric excess was determined to be 96% (syn) and

69% (anti) by chiral HPLC [Daicel Chiralpak AD-HþChiralcel OD-H,

hexane/IPA¼19:1, 1.0 mL/min]: t_R27.7 min (anti-major), 30.8 min

(anti-minor), 32.9 min (syn-minor), 36.0 min (syn-major).

syn-5da: a colorless needle. [

]

²²þ12.9 (c 1.01, CHCl₃), 75% ee. Mp:

111e114 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

d 0.95 (s, 3H), 1.63e1.71 (m,

1H), 1.77e1.91 (m, 1H), 2.05e2.13 (m, 1H), 2.20e2.31 (m, 1H),

2.40e2.49 (m,1H), 2.62e2.71 (m,1H), 6.05 (s,1H), 7.25e7.60 (m, 8H),

7.95e8.02 (m, 2H). ¹³C NMR (CDCl₃, 100 MHz):

18.7, 20.4, 31.2, 38.6,

anti-5fh: a colorless oil. ¹H NMR (CDCl₃, 400 MHz):

d 1.31 (s, 3H),

53.0, 78.9, 127.5, 128.27, 128.31, 128.5, 129.6, 130.3, 133.1, 137.7, 164.8,

1.77e1.87 (m, 1H), 1.95e2.06 (m, 1H), 2.57e2.65 (m, 2H), 2.90 (d, 1H,

J¼17.4 Hz), 3.47 (d, 1H, J¼17.4 Hz), 5.62 (dd, 1H, J¼10.5, 2.3 Hz),

7.07e7.13 (m, 3H), 7.18e7.21 (m, 2H), 7.35e7.43 (m, 4H), 7.53e7.58

(m, 2H), 7.78 (d, 1H, J¼7.8 Hz), 7.91e7.94 (m, 2H). ¹³C NMR (CDCl₃,

220.3. IR (KBr):

1735, 1720, 1600, 1583 cm^ꢁ1. LR-FABMS: 331

(MþNa)^þ. HR-FABMS: calcd for C₂₀H₂₀O₃Na 331.1310, found 331.1315.

4.4.4. syn-2-[(Benzoyloxy)phenylmethyl]-2-methyl-1-tetralone

(5ea). The enantiomeric excess was determined to be 85% (syn)

and 72% (anti) by chiral HPLC [Daicel Chiralpak AD-H, hexane/

IPA¼19:1, 1.0 mL/min]: t_R23.4 min (syn-major), 27.7 min (anti-mi-

nor), 36.6 min (anti-major), 62.3 min (syn-minor).

100 MHz): d 22.4, 32.67, 32.70, 38.0, 53.2, 78.3, 124.5, 126.0, 126.6,

127.7, 128.41, 128.45, 128.5, 129.8, 130.0, 133.2, 135.3, 136.3, 141.4,

152.8, 166.4, 208.2. IR (neat):

385, 263. HR-FABMS: calcd for C₂₆H₂₄O₃Na 407.1623, found 407.1645.

1709 cm^ꢁ1. LR-FABMS: 407 (MþNa^þ),

syn-5fh: a colorless needle. [

]

þ16.1 (c 0.98, CHCl₃), 96% ee.

syn-5ea: a colorless prism. [

]

²²ꢁ88.1 (c 1.02, CHCl₃), 85% ee. Mp:

Mp: 106e107 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

d 1.31 (s, 3H),

158e160 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

1.17 (s, 3H), 1.88e1.97 (m,

1.92e2.09 (m, 1H), 2.18e2.29 (m, 1H), 2.69e2.79 (m, 2H), 2.93 (d,

1H, J¼17.4 Hz), 3.54 (d, 1H, J¼17.4 Hz), 5.62 (dd, 1H, J¼10.0, 2.8 Hz),

7.15e7.22 (m, 3H), 7.25e7.35 (m, 5H), 7.45e7.54 (m, 2H), 7.61 (dt,

1H, J¼0.9, 7.8 Hz), 7.69 (d, 1H, J¼7.8 Hz), 7.77e7.79 (m, 2H). ¹³C NMR

1H), 2.58e2.70 (m,1H), 2.96e3.17 (m, 2H), 6.57 (s,1H), 7.20e7.56 (m,

11H), 7.88 (d, 2H, J¼7.2 Hz), 8.06 (d, 1H, J¼7.0 Hz). ¹³C NMR (CDCl₃,

100 MHz):

d 19.5, 25.0, 28.8, 49.1, 78.7, 126.8, 127.6, 127.9, 128.0,

128.3,128.7,129.5,130.1,131.9,132.8,133.4,136.8,143.1,164.9,199.4.

(CDCl₃, 100 MHz): d 21.0, 32.7, 33.0, 37.6, 53.3, 77.1, 124.6, 126.1,

IR (KBr):

1726, 1673 cm^ꢁ1. LR-FABMS: 393 (MþNa^þ), 105. HR-

126.6, 127.7, 128.4, 128.5, 128.6, 129.7, 130.0, 133.0, 135.2, 135.9,

FABMS: calcd for C₂₅H₂₂O₃Na 393.1467, found 393.1474.

141.6, 152.6, 165.9, 208.2. IR (KBr): n

1720 cm^ꢁ1. LR-FABMS: 385

((MþH)^þ), 313, 263, 154, 105. HR-FABMS: calcd for C₂₆H₂₅O₃

4.4.5. syn-2-[(Benzoyloxy)phenylmethyl]-2-methyl-1-indanone

(5fa). The enantiomeric excess was determined to be 94% (syn) and

35% (anti) by chiral HPLC [Daicel Chiralpak AD-H, hexane/IPA¼4:1,

1.0 mL/min]: t_R15.9 min (anti-minor), 18.0 min (syn-major),

385.1804, found 385.1801.

4.4.8. (1⁰S,2R)-2-[(Benzoyloxy)(cyclohexyl)methyl]-2-methyl-1-

indanone (5ﬁ). The enantiomeric excess was determined to be 99%

(syn) and 86% (anti) by chiral HPLC [Daicel Chiralpak AD-H, hexane/

IPA¼19:1, 1.0 mL/min]: t_R25.6 min (syn-major), 27.0 min (anti-

major), 31.0 min (syn-minor), 33.9 min (anti-minor).

19.8 min (anti-major), 54.5 min (syn-minor).

syn-5fa: a colorless prism. [

]

ꢁ45.8 (c 1.18, CHCl₃), 94% ee.

Mp: 103e104 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

d 1.18 (s, 3H, eCH₃),

2.73 (d, 1H, J¼17.0 Hz), 3.91 (d, 1H, J¼17.0 Hz), 6.26 (s, 1H), 7.24 (t,

anti-5ﬁ: a colorless oil. ¹H NMR (CDCl₃, 400 MHz):

d 1.00e1.14

2H, J¼7.8 Hz), 7.29e7.47 (m, 7H), 7.55 (d, 1H, J¼7.8 Hz), 7.61e7.68

(m, 5H), 1.26 (s, 3H), 1.38e1.76 (m, 6H), 2.88 (d, 1H, J¼17.4 Hz), 3.56

(d, 1H, J¼17.4 Hz), 5.47 (d, 1H, J¼6.4 Hz), 7.37e7.47 (m, 4H),

7.54e7.62 (m, 2H), 7.80 (d, 1H, J¼7.8 Hz), 8.04 (dd, 2H, J¼0.9,

(m, 3H), 7.77 (d, 1H, J¼7.8 Hz). ¹³C NMR (CDCl₃, 100 MHz):

d 22.3,

36.0, 53.6, 79.8, 124.6, 126.7, 127.3, 127.7, 128.34, 128.39, 128.43,

129.5, 130.0, 133.0, 135.2,135.8, 137.5, 152.9, 164.7, 208.4. IR (neat):

8.5 Hz). ¹³C NMR (CDCl₃, 100 MHz):

d 24.2, 26.0, 26.1, 26.3, 29.0,

1716 cm^ꢁ1. LR-FABMS: 357 (MþH^þ), 235, 105. HR-FABMS: calcd for

31.5, 37.5, 40.5, 53.4, 81.5, 124.6, 126.8, 127.7, 128.5, 129.8, 130.2,

C₂₄H₂₁O₃357.1491, found 357.1510.

133.1, 135.1, 136.0, 152.4, 166.2, 208.0. IR (neat): n .

1718, 1704 cm^ꢁ1

LR-FABMS: 363 (MþH^þ), 241, 105. HR-FABMS: calcd for C₂₄H₂₇O₃

4.4.6. 2-[1-(Benzoyloxy)-3-phenyl-2-propenyl]-2-methyl-1-

indanone (5fg). The enantiomeric excess was determined to be 93%

(syn) and 79% (anti) by chiral HPLC, after hydrogenation of double

bond [Daicel Chiralpak AD-HþChiralcel OD-H, hexane/IPA¼19:1,

1.0 mL/min]: t_R27.7 min (anti-major), 30.2 min (anti-minor),

33.4 min (syn-minor), 35.3 min (syn-major).

363.1960, found 363.1972.

syn-5ﬁ: a colorless prism. [

]

²⁸þ29.1 (c 1.09, CHCl₃), 99% ee. Mp:

69e70 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

d 1.00e1.35 (m, 8H),

1.57e1.95 (m, 6H), 2.96 (d, 1H, J¼17.0 Hz), 3.70 (d, 1H, J¼17 Hz), 5.51

(d, 1H, J¼2.8 Hz), 7.20e7.28 (m, 3H), 7.35e7.42 (m, 1H), 7.45e7.56

(m, 2H), 7.62e7.66 (m, 1H), 7.67e7.72 (m, 1H). ¹³C NMR (CDCl₃,

anti-5fg: a colorless needle. Mp: 71e72 ^ꢀC. ¹H NMR (CDCl₃,

100 MHz): d 21.8, 26.1, 26.48, 26.55, 27.9, 31.9, 37.9, 39.8, 53.3, 80.0,

400 MHz):

1.39 (s, 3H), 3.02 (d, 1H, J¼17.4 Hz), 3.48 (d, 1H,

124.6, 126.5, 127.5, 128.3, 129.6, 130.1, 132.8, 135.0, 135.3, 153.0,

J¼17.4 Hz), 5.90 (dd, 1H, J¼7.8, 0.9 Hz), 6.30 (dd, 1H, J¼16.0, 7.8 Hz),

165.5, 208.8. IR (neat):

1712, 1705 cm^ꢁ1. LR-FABMS: 363 (MþH^þ),

4222

T. Ichibakase et al. / Tetrahedron 68 (2012) 4210e4224

241, 159, 105. HR-FABMS: calcd for C₂₄H₂₇O₃363.1960, found

363.1952.

procedure for the aldol-Tishchenko reaction: under an Ar atmo-

sphere, n-BuLi (0.094 mmol, 20 mol %) in hexane (0.21 M, 0.45 mL)

was added to a solution of (R)-3,3⁰-diphenylbinaphthol (20.7 mg,

0.047 mmol, 10 mol %) in THF at ꢁ23 ^ꢀC, and the mixture was stir-

red for 5 min. Then an aldehyde (1.18 mmol, 2.5 equiv) and silyl

enol ether 1 (0.47 mmol) were successively added to the above

mixture. After 6 h, the reaction was quenched with KF/HCOOH aq

(1.5 M KF, 3.0 M HCOOH, 2 mL) and the mixture was stirred for 2 h

at rt. The aqueous layer was extracted with AcOEt and the com-

bined organic layers were successively washed with satd NaHCO₃

(3 mL) and brine (3 mL). Drying over Na₂SO₄and evaporating the

solvent gave the crude product, which was puriﬁed by silica gel

column chromatography (SiO₂9.0 g, CH₂Cl₂/hexane¼1:1) to afford

the product (156 mg, 92% yield) as a colorless needle. The enan-

tiomeric excess was determined to be 88% by chiral HPLC [Daicel

4.4.9. 2-[1-(Benzoyloxy)ethyl]-2-methyl-1-indanone (5fj). The en-

antiomeric excess was determined to be 93% (syn) and 64% (anti) by

chiral HPLC [Daicel Chiralcel OD-H, hexane/IPA¼69:1, 1.0 mL/min]:

t_R15.2 min (anti-minor), 16.8 min (anti-major), 22.4 min (syn-mi-

nor), 23.9 min (syn-major).

anti-5fj: a colorless oil. ¹H NMR (CDCl₃, 400 MHz)

d 1.28 (d, 1H,

J¼6.4 Hz), 1.36 (s, 3H), 2.96 (d, 1H, J¼17.4 Hz), 3.44 (d, 1H,

J¼17.4 Hz), 5.41 (q, 1H, J¼6.4 Hz), 7.34e7.62 (m, 6H), 7.80e7.82 (m,

3H). ¹³C NMR (CDCl₃, 100 MHz):

d 15.5, 21.9, 38.0, 52.6, 75.7, 124.3,

126.4, 127.5, 128.3, 129.5, 130.2, 132.9, 135.0, 136.5, 152.9, 165.8,

208.1. IR (neat):

calcd for C₁₉H₁₈O₃Na 317.1154, found 317.1169.

1716 cm^ꢁ1. LR-FABMS: 317 (MþNa^þ). HR-FABMS:

syn-5fj: a colorless needle. [

þ33.1 (c 1.38, CHCl₃), 93% ee.

Chiralpak AD-H, hexane/IPA¼4:1, 1.0 mL/min]: t_R10.2 min (major),

Mp: 63e64 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz)

1.28 (s, 3H), 1.45 (d, 3H,

27.4 min (minor).

[

]

ꢁ30.4 (c 1.06, CHCl₃), 88% ee. Mp:

J¼6.4 Hz), 2.93 (d,1H, J¼17.0 Hz), 3.57 (d,1H, J¼17.0 Hz), 5.40 (q,1H,

J¼6.4 Hz), 7.21e7.26 (m, 2H), 7.34e7.45 (m, 2H), 7.52e7.58 (m, 3H),

7.62e7.66 (m, 1H), 7.70e7.72 (m, 1H). ¹³C NMR (CDCl₃, 100 MHz):

128e129 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

3.01 (br s,1H), 4.74 (s,1H), 6.37 (s,1H), 7.19e7.57 (m,13H), 8.11e8.13

(m, 2H). ¹³C NMR (CDCl₃, 100 MHz):

17.9, 19.2, 42.9, 76.9, 80.0,

d 0.80 (s, 3H), 0.87 (s, 3H),

15.4, 20.6, 36.6, 52.8, 74.7, 124.3, 126.4, 127.4, 128.1, 129.2, 130.2,

127.2, 127.4, 127.68, 127.71, 128.09, 128.14, 128.5, 129.6, 130.2, 133.1,

132.6, 134.9, 135.9, 152.6, 165.2, 208.3. IR (neat):

1720 cm^ꢁ1. LR-

137.9, 141.1, 166.0. IR (CHCl₃)

1720 cm^ꢁ1. LR-FABMS: 383 (MþNa^þ),

FABMS: 295 (MþH^þ), 173, 105. HR-FABMS: calcd for C₁₉H₁₉O₃

176, 105. HR-FABMS: calcd for C₂₄H₂₄O₃Na 383.1623, found

383.1627.

(MþH^þ) 295.1334, found 295.1381.

4.4.10. (1⁰S,2R)-2-{[(1S)-10-Camphorsulfonyloxy] (cyclohexyl)methyl}-

2-methyl-1-indanone (7ﬁ). Under an Ar atmosphere, H₂O in THF

(2.8 M, 0.26 mL, 0.71 mmol, 1.5 equiv) and n-BuLi (0.094 mmol,

20 mol %) in hexane (0.21 M, 0.45 mL) were added to a solution of

(R)-3,3⁰-dichlorobinaphthol 2d (16.8 mg, 0.047 mmol, 10 mol %) in

THF at ꢁ23 ^ꢀC, and the mixture was stirred for 5 min. Then a solution

cyclohexanecarboxaldehyde 2i in THF (1.0 M, 0.52 mL, 0.47 mmol)

and silyl enol ether 1f (0.71 mmol,1.5 equiv) were successively added

to the above mixture. After 3 h, the reaction was quenched with KF/

HCOOH aq (1.5 M KF, 3.0 M HCOOH, 2 mL) and the mixture was

stirred for 2 h at rt. The aqueous layer was extracted with AcOEt and

the combined organic layers were successively washed with satd

NaHCO₃(3 mL) and brine (3 mL). Drying over Na₂SO₄and evapo-

rating the solvent gave the crude product, which was dissolved in

CH₂Cl₂(2 mL). 10-S-Camphorsulfonyl chloride (354 mg, 0.94 mmol,

2.0 equiv) and a solution of DMAP (287 mg, 2.35 mmol, 5.0 equiv) in

CH₂Cl₂(2 mL) were added to the mixture at 0 ^ꢀC. After stirring for 1 h,

10% HCl aq (5 mL) was added to the mixture and the entire mixture

was extracted with AcOEt (20 mLꢂ3). The organic layer was washed

with brine and dried over Na₂SO₄. After evaporating the solvent, the

residue was puriﬁed by silica gel column chromatography (SiO₂9.0 g,

4.5.2. anti-3-Hydroxy-2,2-dimethyl-1-phenylpropyl benzoate (8ja).

The enantiomeric excess was determined to be 91% by chiral HPLC

[Daicel Chiralpak AD-H, hexane/IPA¼9:1, 1.0 mL/min]: t_R10.8 min

(major), 17.7 min (minor). A colorless oil. [

]

ꢁ43.7 (c 0.77, CHCl₃),

91% ee. ¹H NMR (CDCl₃, 400 MHz):

d 0.97 (s, 3H), 1.00 (s, 3H), 2.31 (br

s, 1H), 3.32 (d, 1H, J¼11.5 Hz), 3.53 (d, 1H, J¼11.5 Hz), 6.06 (s, 1H),

7.26e7.37 (m, 3H), 7.41e7.49 (m, 4H), 7.56e7.60 (m, 1H), 8.08e8.11

(m, 2H). ¹³C NMR (CDCl₃, 100 MHz):

d 19.5, 21.5, 40.4, 69.1, 79.4, 127.8,

127.9, 128.5, 129.7, 130.1, 133.2, 137.6, 166.2. IR (CHCl₃):

n 3506,

1718 cm^ꢁ1. LR-FABMS: 307 (MþNa^þ), 105. HR-FABMS: calcd for

C₁₈H₂₀O₃Na 307.1310, found 307.1325.

4.5.3. anti-3-Hydroxy-2,2-dimethyl-3-phenylpropyl benzoate (9ja).²⁴

The enantiomeric excess was determined to be 91% by chiral HPLC

[Daicel Chiralpak AD-H, hexane/IPA¼9:1, 1.0 mL/min]: t_R9.6 min

(major), 14.6 min (minor). A colorless prism. [

]

ꢁ23.1 (c 1.13,

CHCl₃), 91% ee. Mp: 73e74 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

d 0.97 (s,

3H), 1.04 (s, 3H), 2.38 (br s, 1H), 4.02 (d, 1H, J¼11.0 Hz), 4.43 (d, 1H,

J¼11.0 Hz), 4.69 (s, 1H), 7.25e7.48 (m, 7H), 7.56e7.60 (m, 1H),

8.04e8.06 (m, 2H).

CH₂Cl₂/hexane¼1:4 then 1:1) to afford the corresponding product as

4.5.4. anti-{1-[(Hydroxyl)(phenyl)methyl]cyclohexyl}(phenyl)methyl

benzoate (8ga). The enantiomeric excess was determined to be 71%

by chiral HPLC [Daicel Chiralpak AD-H, hexane/IPA¼9:1, 1.0 mL/min]:

an colorless prism. [

]

þ61.0 (c 1.60, CHCl₃). Mp: 110e111 ^ꢀC. ¹H

0.70 (s, 3H), 1.07 (s, 3H),1.12e1.85 (m,17H),

NMR (CDCl₃, 400 MHz):

1.95e2.05 (m, 2H), 2.23e2.29 (m, 1H), 2.35e2.42 (m, 1H), 2.54 (d,1H,

J¼14.7 Hz), 2.92 (d, 2H, J¼14.7 Hz), 3.63 (d, 1H, J¼17.0 Hz), 5.11 (d, 1H,

J¼2.3 Hz), 7.37 (t, 1H, J¼7.3 Hz), 7.50 (d, 1H, J¼7.8 Hz), 7.64 (t, 1H,

t_R18.8 min (major), 21.3 min (minor). A colorless needle. [

]

³²ꢁ22.3

(c 1.15, CHCl₃), 71% ee. Mp: 159e160 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz)

1.07e1.70 (m, 8H), 1.75e1.95 (m, 2H), 3.42 (br s, 1H), 4.85 (s, 1H),

6.43 (s, 1H), 7.18e7.62 (m, 13H), 8.05e8.13 (m, 2H). ¹³C NMR (CDCl₃,

100 MHz): 20.7, 21.2, 25.8, 26.1, 29.3, 44.1, 77.0, 78.8, 127.3, 127.5,

J¼7.3 Hz), 7.74 (d, 1H, J¼7.8 Hz). ¹³C NMR (CDCl₃, 100 MHz):

d 19.3,

19.7, 22.1, 24.4, 25.7, 26.3, 26.4, 26.8, 27.3, 31.3, 37.1, 39.5, 42.3, 42.4,

47.7, 47.8, 53.4, 57.6, 89.5, 124.3, 126.8, 127.7, 134.5, 135.6, 153.3, 209.2,

127.6, 128.0, 128.1, 128.3, 128.7, 129.5, 130.0, 133.3, 137.3, 140.7, 164.9.

214.0. IR (CHCl₃)

1745, 1709, 1360, 1171, 769 cm^ꢁ1. LR-FABMS: 495

IR (CHCl₃):

3589, 1724 cm^ꢁ1. LR-FABMS: 423 (MþNa^þ), 105. HR-

(MþNa^þ). HR-FABMS: calcd for C₂₇H₃₆O₅SNa 495.2181, found

495.2178. Crystallographic data (excluding structure factors) for this

structure have been deposited with the Cambridge Crystallographic

Data Centre as supplementary publication number CCDC 868919.

FABMS: calcd for C₂₇H₂₈O₃Na 423.1936, found 423.1972.

4.5.5. anti-3-Hydroxy-2,2,4-trimethyl-1-phenylpentyl

benzoate

(8ha). The enantiomeric excess was determined to be 60% by chiral

HPLC [Daicel Chiralpak AD-H, hexane/IPA¼9:1, 1.0 mL/min]: t_R

4.5. Base-catalyzed aldol-Tishchenko reaction of

trimethoxysilyl enol ethers

10.2 min (major),15.2 min (minor). A colorless oil. [

]

³²ꢁ34.1 (c 1.12,

CHCl₃), 60% ee. ¹H NMR (CDCl₃, 400 MHz):

0.89 (s, 3H), 1.05 (d, 3H,

J¼6.9 Hz), 1.07 (d, 3H, J¼6.9 Hz), 1.14 (s, 3H), 1.95e2.05 (m, 1H), 2.34

4.5.1. anti-3-Hydroxy-2,2-dimethyl-1,3-diphenypropyl benzoate 3-

(br s, 1H), 3.41 (s, 1H), 6.15 (s, 1H), 7.25e7.60 (m, 8H), 8.05e8.13 (m,

Benzoyloxy-2,2-dimethyl-1,3-diphenylpropan-1-ol (8ia).²⁹Typical

2H). ¹³C NMR (CDCl₃, 100 MHz):

d 17.1, 19.3, 24.0, 28.8, 43.3, 78.2,

T. Ichibakase et al. / Tetrahedron 68 (2012) 4210e4224

4223

81.0, 127.8, 128.2, 128.5, 129.7, 130.3, 133.2, 137.9, 166.0. IR (CHCl₃):

(0.05 mmol, 11 mol %) in MeOH (0.5 M, 0.1 mL). After 3 h, the

mixture was diluted with AcOEt (20 mL), and washed with water

(5 mL). The aqueous layer was extracted twice with AcOEt

(10 mLꢂ2) and the combined organic layers were washed with

brine (10 mL) and dried over Na₂SO₄. After concentration in vacuo,

the residue was puriﬁed by column chromatography (SiO₂, hexane/

AcOEt¼4:1) to gave diol 11kk (74 mg, 81%) as a colorless oil. The

enantiomeric excess was determined to be 92% by chiral HPLC

[Daicel Chiralpak AD-H, hexane/IPA¼19:1, 1.0 mL/min]: t_R24.9 min

3514, 1720 cm^ꢁ1. LR-FABMS: 349 (MþNa^þ),105. HR-FABMS: calcd for

C₂₁H₂₆O₃Na 349.1780, found 349.1834.

4.5.6. anti-3-Hydroxy-2,2-dimethyl-1-(methylethyl)-3-phenylpropyl

benzoate (9ha). The enantiomeric excess was determined to be 60%

by chiral HPLC [Daicel Chiralpak AD-H, hexane/IPA¼9:1, 1.0 mL/

min]: t_R7.4 min (major), 14.5 min (minor). A colorless oil. [

]

³⁰þ7.6

(c 1.12, CHCl₃), 60% ee. ¹H NMR (CDCl₃, 400 MHz):

d 0.88 (s, 3H),

0.96 (s, 3H), 1.07 (d, 3H, J¼6.9 Hz), 1.09 (d, 3H, J¼6.9 Hz), 2.18e2.31

(m, 1H), 3.29 (d, 1H, J¼2.7 Hz), 4.48 (d, 1H, J¼1.8 Hz), 5.34 (d, 1H,

J¼2.7 Hz), 7.16e7.30 (m, 5H), 7.45e7.52 (m, 2H), 7.58e7.65 (m, 1H),

(major), 27.7 min (minor). [

(CDCl₃, 400 MHz):

]

¹⁸ꢁ5.1 (c 1.22, CHCl₃), 92% ee. ¹H NMR

0.64 (s, 3H), 0.87 (t, 3H, J¼7.3 Hz), 1.02e1.11 (m,

1H), 1.80e1.89 (m, 1H), 2.36 (s, 3H), 3.96 (d, 1H, J¼4.1 Hz), 4.34 (d,

8.08e8.25 (m, 2H). ¹³C NMR (CDCl₃, 100 MHz):

d 17.6, 18.2, 20.1,

1H, J¼2.3 Hz), 4.60 (d, 1H, J¼4.1 Hz), 4.62 (d, 1H, J¼2.3 Hz), 7.12 (d,

23.5, 28.9, 43.3, 77.1, 81.7, 127.1, 127.3, 128.3, 128.5, 129.8, 133.2,

2H, J¼8.2 Hz), 7.19e7.24 (m, 7H). ¹³C NMR (CDCl₃, 100 MHz):

d 7.4,

140.6, 167.4. IR (CHCl₃):

3493, 1697 cm^ꢁ1

LR-FABMS: 349

19.3, 21.1, 23.5, 43.2, 79.0, 79.3, 127.1, 127.4, 127.9, 128.0, 128.4, 137.0,

(MþNa^þ), 309,105 (bp). HR-FABMS: calcd for C₂₁H₂₆O₃Na 349.1780,

138.0, 141.1. IR (CHCl₃): n . LR-FABMS: 307

3602, 3467 cm^ꢁ1

found 349.1779.

(MþNa^þ). HR-FABMS: calcd for C₁₉H₂₄O₂Na 307.1674, found

307.1670.

4.5.7. 2-(Hydroxyphenylmethyl)-2-methyl-1-phenylbutyl benzoate

(8ka and 9ka). The enantiomeric excess was determined to be 8ka

93% and 9ka 93% by chiral HPLC [Daicel Chiralpak AD-H, hexane/

IPA¼9:1, 1.0 mL/min]: t_R13.4 min (8ka, major), 16.9 min (9ka,

Compound 12kk: the enantiomeric excess was determined to be

92% by chiral HPLC [Daicel Chiralpak AD-H, hexane/IPA¼19:1,

1.0 mL/min]: t_R23.3 min (major), 29.6 min (minor). A colorless oil.

]

¹⁹ꢁ2.8 (c 1.05, CHCl₃), 92% ee. ¹H NMR (CDCl₃, 400 MHz):

d 0.67

major), 24.9 min (8ka, minor), 82.0 min (9ka, minor).

(s, 3H), 0.90 (t, 3H, J¼7.3 Hz), 1.05e1.14 (m, 1H), 1.82e1.91 (m, 1H),

Compound 8ka: a colorless needle. [

]

ꢁ28.4 (c 1.25, CHCl₃),

2.32 (s, 3H), 3.86 (br s, 1H), 4.09 (br s, 1H), 4.63 (s, 1H), 4.67 (d, 1H,

93% ee. Mp: 96e97 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

0.84 (s, 3H),

J¼4.1 Hz), 7.06e7.36 (m, 9H). ¹³C NMR (CDCl₃, 100 MHz):

d 7.5, 19.3,

0.84 (t, 3H, J¼6.7 Hz), 1.26e1.37 (m, 1H), 1.85e1.95 (m, 1H), 3.25 (br

s, 1H), 4.80 (s, 1H), 6.18 (s, 1H), 7.15e7.35 (m, 8H), 7.42e7.51 (m, 4H),

7.53e7.60 (m, 1H), 8.05e8.10 (m, 2H). ¹³C NMR (CDCl₃, 100 MHz):

21.0, 23.7, 43.3, 79.1, 79.5, 127.4, 127.7, 127.8, 128.0, 128.2, 136.9,

138.0, 141.3. IR (CHCl₃):

n . LR-FABMS: 307

3602, 3477 cm^ꢁ1

(MþNa^þ). HR-FABMS: calcd for C₁₉H₂₄O₂Na, 307.1674, found

7.9, 19.3, 23.3, 44.6, 77.9, 80.6, 127.2, 127.5, 127.97, 128.02, 128.1,

307.1673.

128.5, 129.5, 130.0, 133.2, 137.5, 141.0, 165.2. IR (CHCl₃)

n 3591,

1724 cm^ꢁ1. LR-FABMS: 397 (MþNa^þ), 105. HR-FABMS: calcd for

4.5.10. anti-3-Hydroxy-2,2-dimethyl-1-(p-methoxyphenyl)-3-

phenylpropyl p-methoxybenzoate (8ib). The enantiomeric excess

was determined to be 95% by chiral HPLC [Daicel Chiralpak AD-H,

C₂₅H₂₆O₃Na 397.1779, found 397.1786.

Compound 9ka: a colorless needle. [

]

ꢁ24.2 (c 0.89, CHCl₃),

93% ee. Mp 139e140 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

0.92 (s, 3H),

hexane/IPA¼1L1, 1.0 mL/min]: t_R11.1 min (major), 48.5 min (mi-

1.00 (t, 3H, J¼7.4 Hz), 1.22e1.37 (m, 1H), 1.51e1.65 (m, 1H), 3.00 (br

s,1H), 4.86 (s,1H), 6.19 (s,1H), 7.22e7.31 (m, 8H), 7.38e7.42 (m, 2H),

7.45e7.51 (m, 2H), 7.55e7.60 (m, 1H), 8.12e8.15 (m, 2H). ¹³C NMR

nor). A colorless needle. [

]

ꢁ37.1 (c 1.45, CHCl₃), 95% ee. Mp:

126e127 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

d 0.79 (s, 3H), 0.84 (s, 3H),

3.21 (d, J¼3.2 Hz), 3.75 (s, 3H), 3.83 (s, 3H), 4.70 (d, J¼2.8 Hz, 1H),

(CDCl₃, 100 MHz): d 8.8, 17.5, 25.7, 45.1, 76.8, 81.3, 127.5, 127.7, 127.8,

6.29 (s, 1H), 6.84e6.89 (m, 2H), 6.94e6.99 (m, 2H), 7.2e7.5 (m, 7H),

127.93,127.95,128.03,128.6,129.7,130.2,133.2,137.8,141.1,165.5. IR

8.05e8.10 (m, 2H). ¹³C NMR (CDCl₃, 100 MHz):

18.0, 19.4, 43.1,

(CHCl₃):

3602, 1722 cm^ꢁ1. LR-FABMS: 397 (MþNa^þ), 105. HR-

55.2, 55.5, 77.5, 79.7, 113.3, 113.9, 122.7, 127.3, 127.5, 128.2, 129.4,

FABMS: calcd for C₂₅H₂₆O₃Na 397.1779, found 397.1779.

130.3, 131.8, 141.3, 159.1, 163.7, 166.0. IR (CHCl₃) n .

3493, 1709 cm^ꢁ1

LR-FABMS: 443 (MþNa^þ), 163, 135. HR-FABMS: calcd for

4.5.8. 2-(Hydroxyphenylmethyl)-2-methyl-1-(p-methylphenyl)butyl

C₂₆H₂₈O₅Na 443.1834, found 443.1823.

p-methylbenzoate (8kk and 9kk). Compound 8kk: a colorless

prism. [

(CDCl₃, 400 MHz):

]

²⁴ꢁ36.7 (c 1.39, CHCl₃), 92% ee. Mp: 116e117 ^ꢀC. ¹H NMR

4.5.11. anti-1-(p-Bromophenyl)-3-hydroxy-2,2-dimethyl-3-

phenylpropyl p-bromobenzoate (8ik). The enantiomeric excess was

determined to be 86% by chiral HPLC [Daicel Chiralpak AD-H,

0.81 (s, 3H), 0.84 (t, 3H, J¼7.3 Hz), 1.26e1.35

(m, 1H), 1.84e1.93 (m, 1H), 2.31 (s, 3H), 2.38 (s, 3H), 3.45 (br s, 1H),

4.80 (s, 1H), 6.13 (s, 1H), 7.13e7.28 (m, 9H), 7.36 (d, 2H, J¼7.8 Hz),

hexane/IPA¼1:1, 1.0 mL/min]: t_R9.3 min (major), 55.2 min (mi-

7.95 (d, 2H, J¼8.2 Hz). ¹³C NMR (CDCl₃, 100 MHz):

7.8, 19.4, 21.0,

nor). A colorless needle. [

]

ꢁ55.8 (c 1.22, CHCl₃), 86% ee. Mp:

21.5, 23.1, 44.4, 77.8, 80.5, 127.1, 127.2, 127.4, 127.8, 128.1, 128.7,

167e168 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

d 0.76 (s, 3H), 0.85 (s, 3H),

129.2, 129.5, 134.4, 137.6, 140.9, 143.9, 165.1. IR (CHCl₃):

3581,

2.79 (br s,1H), 4.72 (s,1H), 6.28 (s,1H), 7.20e7.35 (m, 7H), 7.42e7.47

1722 cm^ꢁ1. LR-FABMS: 425 (MþNa^þ), 119. HR-FABMS: calcd for

(m, 2H), 7.60e7.63 (m, 2H), 7.90e7.95 (m, 2H). ¹³C NMR (CDCl₃,

C₂₇H₃₀O₃Na 425.2093, found 425.2093.

100 MHz): d 18.0, 19.1, 42.9, 77.2, 79.6, 122.0, 127.6, 127.7, 128.2,

Compound 9kk: a colorless prism. [

ꢁ31.3 (c 0.89, CHCl₃),

128.6, 129.1, 129.9, 131.1, 131.2, 132.0, 137.1, 141.2, 165.2. IR (CHCl₃): n

92% ee. Mp: 140e141 ^ꢀC. ¹H NMR (CDCl₃, 400 MHz):

0.91 (s, 3H),

3608, 3514, 1720 cm^ꢁ1. LR-FABMS: 543, 541, 539 (MþNa^þ). HR-

0.99 (t, 3H, J¼7.4 Hz), 1.24e1.33 (m, 1H), 1.50e1.60 (m, 1H), 2.31 (s,

FABMS: calcd for C₂₄H₂₂Br₂O₃Na 538.9834, found 538.9836.

3H), 2.43 (s, 3H), 3.19 (br s, 1H), 4.84 (s, 1H), 6.12 (s, 1H), 7.11e7.31

(m, 11H), 8.00e8.02 (m, 2H). ¹³C NMR (CDCl₃, 100 MHz):

8.7, 17.4,

4.5.12. anti-(E)-5-Hydroxy-4,4-dimethyl-1,5-diphenyl-1-pentenyl 3-

O-trans-cinnamate (8ig). The enantiomeric excess was determined

to be 89% by chiral HPLC [Daicel Chiralpak AD-H, hexane/IPA¼2:1,

1.0 mL/min]: t_R10.1 min (major), 75.1 min (minor). A colorless oil.

21.1, 21.7, 25.7, 45.0, 76.9, 81.2, 127.4, 127.7, 127.8, 127.9, 128.0, 128.7,

129.3, 129.7, 134.8, 137.5, 141.1, 144.0, 165.5. IR (CHCl₃):

n 3583,

1720 cm^ꢁ1. LR-FABMS: 425 (MþNa^þ), 119. HR-FABMS: calcd for

C₂₇H₃₀O₃Na 425.2093, found 425.2109.

[

]

³³ꢁ38.6 (c 1.35, CHCl₃), 89% ee. ¹H NMR (CDCl₃, 400 MHz):

d 0.90

(s, 3H), 0.94 (s, 3H), 3.10 (br s,1H), 4.63 (s,1H), 5.84 (d,1H, J¼7.8 Hz),

6.32 (dd, 1H, J¼7.8, 16.0 Hz), 6.54 (d, 1H, J¼16.0 Hz), 6.72 (d, 1H,

J¼16.0 Hz), 7.23e7.43 (m, 13H), 7.56e7.58 (m, 2H), 7.77 (d, 1H,

4.5.9. 2-Ethyl-2-methyl-3-(p-methylphenyl)-1-phenyl-propane-1,3-

diol (11kk and 12kk). Hydrolysis of monoester: 1,3-diol monoester

8kk was dissolved in MeOH (2 mL) and treated with NaOMe

J¼16.0 Hz). ¹³C NMR (CDCl₃, 100 MHz):

d 17.6, 19.7, 42.7, 76.9, 79.2,

4224

T. Ichibakase et al. / Tetrahedron 68 (2012) 4210e4224

9. (a) Denmark, S. E.; Winter, S. B. D.; Su, X.; Wong, K.-T. J. Am. Chem. Soc. 1996, 118,

7404e7405; (b) Denmark, S. E.; Wong, K.-T.; Stavenger, R. A. J. Am. Chem. Soc.

1997, 119, 2333e2334; (c) Denmark, S. E.; Stavenger, R. A.; Wong, K.-T. J. Org.

Chem. 1998, 63, 918e919; (d) Denmark, S. E.; Stavenger, R. A.; Su, X.; Wong, K.-

T.; Nishigaichi, Y. Pure Appl. Chem. 1998, 70, 1469e1476; (e) Denmark, S. E.;

Stavenger, R. A.; Wong, K.-T. Tetrahedron 1998, 54, 10389e10402; (f) Denmark,

S. E.; Stavenger, R. A. J. Org. Chem. 1998, 63, 9524e9527; (g) Denmark, S. E.; Su,

X.; Nishigaichi, Y. J. Am. Chem. Soc. 1998, 120, 12990e12991; (h) Denmark, S. E.;

Stavenger, R. A.; Wong, K.-T.; Su, X. J. Am. Chem. Soc. 1999, 121, 4982e4991; (i)

Denmark, S. E.; Pham, S. M. Helv. Chim. Acta 2000, 83, 1846e1853; (j) Denmark,

S. E.; Stavenger, R. A. J. Am. Chem. Soc. 2000, 122, 8837e8847; (k) Denmark, S. E.;

Stavenger, R. A. Acc. Chem. Res. 2000, 33, 432e440; (l) Denmark, S. E.; Ghosh, S.

K. Angew. Chem., Int. Ed. 2001, 40, 4759e4762; (m) Denmark, S. E.; Pham, S. M. J.

Org. Chem. 2003, 68, 5045e5055.

10. (a) Rendler, S.; Oestreich, M. Synthesis 2005, 1727e1736; (b) Orito, Y.; Nakajima,

M. Synthesis 2006, 1391e1401; (c) Denmark, S. E.; Beutner, G. L. Angew. Chem.,

Int. Ed. 2008, 47, 1560e1638.

11. (a) Nakajima, M.; Yokota, T.; Saito, M.; Hashimoto, S. Tetrahedron Lett. 2004, 45,

61e64.

12. (a) Kotani, S.; Hashimoto, S.; Nakajima, M. Synlett 2006, 1116e1118; (b) Kotani,

S.; Hashimoto, S.; Nakajima, M. Tetrahedron 2007, 63, 3122e3132.

13. (a) Tanaka, K.; Ueda, T.; Ichibakase, T.; Nakajima, M. Tetrahedron Lett. 2010, 51,

2168e2169; (b) Ueda, T.; Tanaka, K.; Ichibakase, T.; Orito, Y.; Nakajima, M.

Tetrahedron 2010, 66, 7726e7731.

117.7, 124.4, 126.6, 127.3, 127.5, 128.0, 128.1, 128.2, 128.6, 128.9,

130.5, 134.3, 134.6, 136.4, 140.8, 145.7, 166.8. IR (CHCl₃) n 3491, 1709,

1172 cm^ꢁ1. LR-FABMS: 435 (MþNa^þ), 413, 131, 107. HR-FABMS:

calcd for C₂₈H₃₈O₃Na 435.1936, found 435.1966.

4.5.13. anti-1-Hydroxy-2,2-dimethyl-1,5-diphenylpentanyl 3-O-hy-

drocinnamate (8ih). The enantiomeric excess was determined to be

28% by chiral HPLC [Daicel Chiralpak AD-H, hexane/IPA¼9:1, 1.0 mL/

min]: t_R13.5 min (minor), 17.1 min (major). A colorless oil. [

]

³²þ3.9

(c1.36, CHCl₃), 28% ee.¹HNMR (CDCl₃, 400 MHz)

0.65(s, 3H), 0.78(s,

3H),1.84e1.97 (m, 2H), 2.47e2.59 (m, 2H), 2.73e2.79 (m, 2H), 3.02 (t,

2H, J¼7.4 Hz), 3.20 (d, 1H, J¼3.6 Hz), 4.21 (d, 1H, J¼4.1 Hz), 5.18 (dd,

1H, J¼4.1, 9.2 Hz), 7.13e7.30 (m, 15H). ¹³C NMR (CDCl₃, 100 MHz):

19.3, 30.9, 31.7, 33.0, 35.8, 42.1, 76.5, 78.7, 126.0, 126.5, 127.1, 127.3,

128.2,128.3,128.36,128.42,128.6,140.2,140.4,141.5,174.1. IR: (CHCl₃)

3502, 1713 cm^ꢁ1. LR-FABMS: 439 (MþNa^þ), 413, 176, 91, 23. HR-

FABMS: calcd for C₂₈H₃₂O₃Na 439.2249, found 439.2291.

4.5.14. anti-1-Cyclohexyl-3-hydroxy-2,2-dimethyl-3-phenylpropyl

cyclohexanecarboxylate (8ii). The enantiomeric excess was de-

termined to be 30% by chiral HPLC [Daicel Chiralpak AD-H, hexane/

IPA¼29:1, 1.0 mL/min]: t_R10.3 min (minor), 13.1 min (major). A

14. (a) Nakajima, M.; Orito, Y.; Ishizuka, T.; Hashimoto, S. Org. Lett. 2004, 6,

3763e3765; (b) Orito, Y.; Hashimoto, S.; Ishizuka, T.; Nakajima, M. Tetrahedron

2006, 62, 390e400.

15. For acid-catalyzed aldol reaction of trimethoxysilyl enol ethers, see: (a) Yana-

gisawa, A.; Nakatsuka, Y.; Asakawa, K.; Wadamoto, M.; Kageyama, H.; Yama-

moto, H. Synlett 2001, 69e72; (b) Yanagisawa, A.; Nakatsuka, Y.; Asakawa, K.;

Wadamoto, M.; Kageyama, H.; Yamamoto, H. Bull. Chem. Soc. Jpn. 2001,

1477e1481; (c) Wadamoto, M.; Ozasa, N.; Yanagisawa, A.; Yamamoto, H. J. Org.

Chem. 2003, 68, 5593e5601.

colorless prism. [

]

³⁰þ1.2 (c 1.03, CHCl₃), 30% ee. Mp: 87e88 ^ꢀC. ¹H

NMR (CDCl₃, 400 MHz)

d 0.76 (s, 3H), 0.88 (s, 3H), 1.05e1.43 (m,

8H), 1.45e1.90 (m, 11H), 1.95e2.05 (m, 2H), 2.39e2.49 (m, 1H), 3.25

(d, J¼2.8 Hz,1H), 4.44 (d, J¼1.8 Hz), 4.92 (q, J¼2.8 Hz,1H), 7.22e7.30

16. A part of this work was reported as a communication Ichibakase, T.; Orito, Y.;

(m, 5H). ¹³C NMR (CDCl₃, 100 MHz):

d 17.5, 20.4, 25.4, 25.5, 25.7,

Nakajima, M. Tetrahedron Lett. 2008, 49, 4427e4429.

17. Enol ether 1be1d, 1f, and 1g were prepared in chloroform under reﬂux con-

dition. Enol ethers 1e and 1h were prepared in dichloromethane at 0 ^ꢀC.

18. (a) Uhlig, W. J. Organomet. Chem. 1993, 452, 29e32; (b) Uhlig, W. Chem. Ber.

1996, 129, 733e739.

26.1, 26.4, 26.6, 28.5, 29.3, 29.4, 33.9, 38.5, 42.9, 43.7, 77.0, 81.4,

127.1, 127.3, 128.2, 140.7, 176.6. IR (CHCl₃)

3500, 1705 cm^ꢁ1. LR-

FABMS: 395 (MþNa^þ), 355, 83. HR-FABMS: calcd for C₂₄H₃₆O₃Na

19. Although syn or anti may be not truly accurate terms to indicate the stereo-

chemistry of the successive stereogenic centers including the quaternary car-

bon centers, herein we use these terms for convenience in order to discuss the

relationship of the stereochemistries between enol ethers and aldol adducts.

20. (a) Mahrwald, R.; Schetter, B. Org. Lett. 2006, 8, 281e284; (b) Schetter, B.;

Ziemer, B.; Schnakenburg, G.; Mahrwald, R. J. Org. Chem. 2008, 73, 813e819.

21. To the best of our knowledge, the best syn/anti ratio for constructing quaternary

carbon centers by an enantioselective aldol reaction reported to date is 1:6

Wang, W.; Li, H.; Wang, J. Tetrahedron Lett. 2005, 46, 5077e5079.

22. Reviews on the enantioselective aldol-Tishchenko reactions, see: (a) Mahr-

ward, R. Curr. Org. Chem. 2003, 7, 1713e1723; (b) Mlynarski, J. Eur. J. Org. Chem.

2006, 4779e4786.

23. (a) Loog, O.; Maeorg, U. Tetrahedron: Asymmetry 1999, 10, 2411e2415; (b) Mas-

carenhas, C. M.; Miller, S. P.; White, P. S.; Morken, J. P. Angew. Chem., Int. Ed. 2001, 40,

601e603;(c) Gnanadesikan, V.; Horiuchi, Y.;Ohshima, T.;Shibasaki, M. J. Am. Chem.

Soc. 2004, 126, 7782e7783; (d) Horiuchi, Y.; Gnanadesikan, V.; Ohshima, T.; Masu,

H.; Katagiri, K.; Sei, Y.; Yamaguchi, K.; Shibasaki, M. Chem.dEur. J. 2005, 11,

5195e5204; (e) Mlynarski, J.; Mitura, M. Tetrahedron Lett. 2004, 45, 7549e7552; (f)

Mlynarski, J.; Jankowska, J.; Rakiel, B. Chem. Commun. 2005, 4854e4856; (g)

Mlynarski, J.; Jankowska, J.; Rakiel, B. Tetrahedron: Asymmetry 2005,16,1521e1526;

(h) Mlynarski, J.; Rakiel, B.; Stodulski, M.; Suszczynska, A.; Frelek, J. Chem.dEur. J.

2006, 12, 8158e8167; (i) Rohr, K.; Herre, R.; Mahrwald, R. Org. Lett. 2005, 7,

4499e4501; (j) Rohr, K.; Herre, R.; Mahrwald, R. J. Org. Chem. 2009, 74, 3744e3749.

24. (a) Ichibakase, T.; Nakajima, M. Org. Lett. 2011, 13, 1579e1581; (b) Ichibakase, T.;

Nakatsu, M.; Nakajima, M. Molecules 2011, 16, 5008e5019.

25. Mechanistic studies of the aldol-Tishchenko reaction: (a) Evans, D. A.; Hoveyda,

A. H. J. Am. Chem. Soc. 1990, 112, 6447e6449; (b) Burkhardt, E. R.; Bergman, R.

G.; Heathcock, C. H. Organometallics 1990, 9, 30e44; (c) Mahrwald, R.; Cos-

tisella, B. Synthesis 1996, 1087e1089; (d) Bodnar, P. M.; Shaw, J. T.; Woerpel, K.

A. J. Org. Chem. 1997, 62, 5674e5675; (e) Abu-Hasanayn, F.; Streitwieser, A. J.

Org. Chem. 1998, 63, 2954e2960; (f) Lu, L.; Chang, H.-Y.; Fang, J.-M. J. Org. Chem.

1999, 64, 843e853; (g) Mascarenhas, C. M.; Duffey, M. O.; Liu, S.-Y.; Morken, J. P.

Org. Lett. 1999, 1, 1427e1429; (h) Markert, M.; Mahrwald, R. Synthesis 2004,

1429e1433.

26. Nishimura, Y.; Miyake, Y.; Amemiya, R.; Yamaguchi, M. Org. Lett. 2006, 8,

5077e5080.

27. Hasegawa, T.; Nishimura, M.; Kodama, Y.; Yoshioka, M. Bull. Chem. Soc. Jpn. 1990,

63, 935e937.

395.2562, found 395.2539.

References and notes

1. Herein a ‘quaternary carbon atom’ means a carbon atom singly bonded to four

other carbon atoms.

2. For reviews on the construction of quaternary asymmetric carbon, see: (a) Fuji,

K. Chem. Rev. 1993, 93, 2037e2066; (b) Corey, E. J.; Guzman-Perez, A. Angew.

Chem., Int. Ed. 1998, 37, 388e401; (c) Denissova, I.; Barriault, L. Tetrahedron

2003, 59, 10105e10146; (d) Douglas, C. J.; Overman, L. E. Pure Appl. Chem. 2004,

101, 5363e5367; (e) Peterson, E. A.; Overman, L. E. Pure Appl. Chem. 2004, 101,

11943e11948; (f) Christpher, J. D.; Overman, L. E. Proc. Natl. Acad. Sci. U.S.A.

2004, 101, 5363e5367; (g) Trost, B. M.; Jiang, C. Synthesis 2006, 369e396; (h)

Bella, M.; Gasperi, T. Synthesis 2009, 1583e1614; (i) Das, J. P.; Marek, I. Chem.

Commun. 2011, 4593e4623.

3. For reviews on DielseAlder reactions, see: (a) Shen, J.; Tan, C.-H. Org. Biomol.

Chem. 2007, 6, 3229e3236; (b) Reymond, S.; Cossy, J. Chem. Rev. 2008, 108,

5359e5406; (c) Tadano, K. Eur. J. Org. Chem. 2009, 4381e4394.

4. For reviews on Michael additions, see: (a) Christffers, J. Chem.dEur. J. 2003, 9,

4862e4867; (b) Jautze, S.; Peters, R. Synthesis 2010, 365e388.

5. For reviews on enantioselective aldol reaction, see: (a) Nelson, S. G. Tetrahedron:

€

Asymmetry 1998, 9, 357e389; (b) Groger, H.; Vogl, E. M.; Shibasaki, M. Chem.dEur.

J. 1998, 4, 1137e1141; (c) Mahrwald, R. Chem. Rev. 1999, 99, 1095e1120; (d) Ma-

chajewski, T. D.; Wong, C.-H. Angew. Chem., Int. Ed. 2000, 39, 1352e1374.

6. For recent reviews, see: Schetter, B.; Mahrwald, R. In Quaternary Stereocenters:

Challenges and Solutions for Organic Synthesis; Christoffers, J., Baro, A., Eds.;

Wiley-VCH: Weinheim, Germany, 2005; pp 51e81.

7. (a) Ando, A.; Miura, T.; Tatematsu, T.; Shioiri, T. Tetrahedron Lett. 1993, 34,

1507e1510; (b) Shioiri, T.; Bohsako, A.; Ando, A. Heterocycles 1996, 42, 93e97;

2420e2423; (d) Ishikawa, S.; Hamada, T.; Manabe, K.; Kobayashi, S. J. Am. Chem.

Soc. 2004, 126, 12236e12237; (e) Kobayashi, S.; Ogino, T.; Shimizu, H.; Ishikawa,

S.; Hamada, T.; Manabe, K. Org. Lett. 2005, 7, 4729e4731; (f) Denmark, S. E.;

Wilson, T. W.; Burk, M. T.; Heemstra, J. R. J. J. Am. Chem. Soc. 2007, 129,

14864e14865; (g) Markert, M.; Schefﬂer, U.; Mahrward, R. J. Am. Chem. Soc.

2009, 131, 16642e16643.

28. Cheon, C. H.; Yamamoto, H. Tetrahedron 2010, 66, 4257e4264.

29. Patit, M. N.; Gonnade, R. G.; Joshi, N. N. Tetrahedron 2010, 66, 5036e5041.

8. Carreira, E. M. In Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A.,

Yamamoto, H., Eds.; Springer: Berlin, 1999; Vol. 3, pp 997e1065.

Products guided by the article

Product name:C₁₀H₂₀O₄Si

Cas No:1379003-19-6

R&D Labs maybe for 1379003-19-6

Shanghai Dynamic Industrial Co.,Ltd.

website:http://www.shdynamic.com

Contact:86-021 3392 6680

Address:Room 805 Information Tower, No.1403 Minsheng Road, Pudong New Area, Shanghai 200135, P. R. China
Cerametek Materials（ShenZhen）Co., Ltd.

Contact:+86-755-2324.2554

Address:A3-#9, YongChuan Street, Suite 501
Jiangsu Seed Chem Co.,Ltd.

Contact:86-513-84128750/13773795976

Address:No.48.Youyi West Road ,Rudong Development Zone,Jiangsu Province,China
Qingdao S. H. Huanyu Imp. & Exp. Co., Ltd.

Contact:86-532-88250866

Address:Room 615, World Trade Centre Building B, Hongkong Middle Roda 6#, Qingdao, Shandong, China
Zibo Jujin Chemical Industry Co., Ltd.（Dongming Jujin Chemical Industry Co., Ltd. ）

Contact:+86-533-2975022

Address:No.99 Shanquan Road, Zhangdian District

Relevant to this article

Circular dichroism and circularly polarized luminescence triggered by self-assembly of tris(phenylisoxazolyl)benzenes possessing a perylenebisimide moiety

Doi:10.1039/c2cc31512b
(2012)
Mechanistic insight into the regioselective palladation of indole derivatives: Tetranuclear indolyl palladacycles with high C2-Pd or C3-Pd bond selectivity

Doi:10.1021/om300284t
(2012)
Synthesis of 1-aminoisoquinolines via the coinage metal cocatalyzed reaction of 2-alkynylbenzaldoximes with isocyanoacetates

Doi:10.1055/s-0034-1378654
(2014)
A comparative Study of the Decomposition of o-Alkynyl-Substituted Aryl Diazo Ketones. Synthesis of Polysubstituted β-Naphthols via Arylketene Intermediates

Doi:10.1021/jo00075a045
(1993)
IMMOBILIZED PENICILLINACYLASE: APPLICATION TO THE SYNTHESIS OF THE DIPEPTIDE ASPARTAME

Doi:10.1016/S0040-4039(00)84751-6
(1986)
The effect of thiophene ring substitution position on the properties and electrochemical behaviour of alkyne-dicobaltcarbonylthiophene complexes

Doi:10.1016/j.jorganchem.2008.08.005
(2008)

Article Doi

Construction of quaternary carbon centers by a base-catalyzed enantioselective aldol reaction and related reactions of trimethoxysilyl enol ethers

DOI: 10.1016/j.tet.2012.03.096

Source and publish data:

Authors:

Article abstract of DOI:10.1016/j.tet.2012.03.096

Full text of DOI:10.1016/j.tet.2012.03.096

Products guided by the article

R&D Labs maybe for 1379003-19-6

Relevant to this article

Hot Product