Asymmetric desymmetrization of saturated and unsaturated meso-1,2-diols

TETRAHEDRON

Pergamon

Tetrahedron 56 (2000) 10141±10151

Asymmetric Desymmetrization of Saturated and Unsaturated

meso-1,2-Diols

*

Hiromichi Fujioka, Yasushi Nagatomi, Naoyuki Kotoku, Hidetoshi Kitagawa and Yasuyuki Kita

*

Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan

Received 27 November 1999; accepted 27 January 2000

AbstractÐAn asymmetric desymmetrization of saturated and unsaturated cyclic and acyclic meso-1,2-diols has been developed from the

ene acetals, prepared from the norbornene carboxyaldehyde and meso-1,2-diols. The intramolecular haloetheri®cation of the ene acetals as a

key step afforded 8-membered acetals in a stereoselective manner just by the reaction of norbornene ole®n even when the ene acetals from

unsaturated meso-1,2-diols having ole®ns in the same molecule were used. Subsequent reductive elimination, followed by protecting the

hydroxy group and transacetalization, gave optically active 1,2-diol derivatives and the starting ene acetals in good yields. q 2000 Elsevier

Introduction

to use a chiral aldehyde, chiral methyl norbornene aldehyde,

as a chiral carbonyl compound and succeeded in discrimi-

nation of saturated and unsaturated not only cyclic meso-

1,2-diols but also acyclic ones.^3,4We present here the details

of these studies.

Enantiodifferentiation of the s-symmetric diols (including

meso-diols) is an important area in organic synthesis. Many

methodologies have been developed so far. They are widely

divided into two groups. One is the group using enzymes as

a tool.¹The other is the group using chemical methods.²The

chemical enantiodifferentiation of diols is also divided into

three categories: (1) desymmetrization by the stereo-

selective cleavage of the acetals derived from s-symmetric

diols and chiral carbonyl compounds,^2a±i(2) direct desym-

metrization of s-symmetric diols with a chiral reagent,^2j±n

and (3) direct desymmetrization of s-symmetric diols in the

presence of chiral sources.^2o±sAmong these three method-

ologies, method (1) using chiral carbonyl compounds seems

to be most reliable at this time, because the products

obtained by cleavage of the acetal still have chiral unit

and this chiral unit can help to purify the product in an

optically pure state, when they are obtained in highly

optically active but not optically pure forms (Eq. (1)).

Concept

Recently, we have developed a new asymmetric synthesis of

optically active 1,4- and 1,5-diols, where intramolecular

haloetheri®cation of chiral ene acetals, prepared from C₂-

symmetric optically active diols and optically nonactive ene

aldehydes, is characterized as a crucial step. The reactions

of the ene acetals proceed via oxonium ion intermediates

(Eq. (2)).⁵This ®nding suggested us that if a large energy

difference existed among the possible intermediates formed

from the ene acetal derived from the proper chiral non-

racemic ene aldehyde and symmetric meso-diol, the

reaction may proceed through the most stable intermediate,

resulting in the discrimination of the two oxygen atoms of

the meso-diol (Eq. (3)).

ꢀ1

Several methodologies using chiral carbonyl compounds

such as menthon, b-ketosulfoxide compounds, and so on

have been developed so far. However, the desymmetrization

of acyclic meso-1,2-diols still remains a problem. We chose

ꢀ2

Keywords: asymmetric desymmetrization; meso-1,2-diol; norbornene alde-

hyde; intramolecular haloetheri®cation; ene acetal.

* Corresponding authors. Tel.: 181-6-6879-8225; fax: 181-6-6879-8229.

PII: S0040-4020(00)00859-0

10142

H. Fujioka et al. / Tetrahedron 56 (2000) 10141±10151

Scheme 1.

Preparation of ene acetals from meso-1,2-diols

Ene acetals were prepared stereospeci®cally in good yields

in every case from meso-1,2-diols 2 and 1 in the presence of

a

catalytic amount of prydinium p-toluenesulfonate

(PPTS). p-TsOH or d-camphorsulfonic acid as an acid

catalyst in place of PPTS decreased the stereoselectivity

of acetalization. The stereochemistries of the acetals were

determined by NOE experiments. It has been reported that

®ve-membered acetalization tends to give the acetals with

cis-orientation via anti-transoid oxonium ion inter-

mediates.⁷In our cases, the bulkiness of the norbornene

aldehyde skeleton realized such high stereospeci®city. It is

worthy noting that even the reaction of acyclic 2,5-

dimethyl-3,4-hexanediol 2h, which is supposed to be dis-

advantageous in the formation of the acetal structure

because of the repulsion between the two substituents,

proceeds without any problem (Table 1).

ꢀ3

Result and Discussion

As a chiral non-racemic auxiliary, we chose methyl nor-

bornene aldehyde 1. Our desymmetrization reaction cycle

is depicted in Scheme 1. The cycle consists of four steps: (1)

intramolecular haloetheri®cation of the ene acetal (step a),

(2) dehaloetheri®cation (step b), (3) protection of the

alcohol (step c), then (4) transacetalization with meso-1,2-

diol (step d). This is very useful because transacetalization

gives the optically active meso-1,2-diol derivatives with the

starting ene acetals. This means the cycle works repeatedly

once after obtaining the starting ene acetals. We selected

(1R,2R,3S,4S)-3-methyl-5-norbornene-2-carboxaldehyde 1

as a chiral norbornene aldehyde for the following four

reasons: (1) 1 is easily prepared by asymmetric Diels±

Alder reaction,⁶(2) acetalization would proceed stereo-

selectively to give the cis-isomer,⁷(3) a newly produced

chiral center (correspond to p center in oxonium ion inter-

mediate of Eq. (3)) would be formed stereospeci®cally in

the haloetheri®cation because both of the aldehyde and the

double bond are ®xed, and most importantly (4) sterically

rigid forms of the oxonium ion intermediates would be

expected to create a large energy difference. We chose

methyl norbornene aldehyde instead of norbornene alde-

hyde itself. One reason is point 1 above and another reason

is to avoid the possibility of epimerization of the aldehyde

during the reactions.

Intramolecular bromoetheri®cation in Scheme 1 (step a)

This step is the most crucial step in our desymmetrization

reaction cycle. We then investigated the reactivity and

stereochemistry of this reaction using two acetals 9a,b

derived from meso-1,2-cyclopentanediol or meso-2,3-buta-

nediol and commercially available racemic norbornene

aldehyde 8. Intramolecular haloetheri®cation with 2 equiv.

of NBS in the presence of 5 equiv. of MeOH proceeded in

good yields in the presence of 2 equiv. of g-collidine to give

the products 10a and 10b as a single isomer, respectively.

As shown from the conformations of the intermediates, a

large steric repulsion not only between the substituents and

the bicyclo[2.2.1]heptane skeleton but also between the 1,3-

dioxolane skeleton and the bicyclo[2.2.1]heptane skeleton is

observed in endo isomer whereas such repulsion is not

observed in exo isomer. X-Ray analysis of compound 10b

revealed its structure, and the reaction proceeded via the

expected preferable exo-intermediates followed by S_N2

attack of MeOH (Scheme 2).

We then examined the intramolecular haloetheri®cation of

optically pure ene acetals 4a±h from saturated meso-1,2-

diols under the same reaction condition as described

H. Fujioka et al. / Tetrahedron 56 (2000) 10141±10151

10143

Scheme 2.

comparison of its speci®c rotation [116.68 (c 1.03,

CHCl₃)] with the reported value [116.58 (c 1.10,

CHCl₃)]⁸and the X-ray crystallographic structure of 10b.

The absolute stereochemistries of other compounds 5b±h

were tentatively determined by assuming the same sense of

diastereoselection as observed in 5a and also by mechanistic

consideration (Scheme 3).

Scheme 3.

As mentioned above, our asymmetric desymmetrization

was based on an intramolecular haloetheri®cation reaction

and worked very well. We next examined to apply this

method to the ene acetals 4i±l from unsaturated meso-1,2-

diols 2i±l having ole®ns in the same molecule, although

the bromoetheri®cation reaction of the ene acetals from

above. Reactions for all ene acetals 4a±h proceeded

smoothly and gave 8-membered acetals 5a±h. Yields of

all 8-membered acetals 5a±h are shown in Table 2. The

absolute stereochemistry of 5a was determined by con-

version to the optically active 3a described below and

Scheme 4.

Scheme 5.

10144

H. Fujioka et al. / Tetrahedron 56 (2000) 10141±10151

Scheme 6.

unsaturated diols is anticipated to cause competition

between the intra- vs intermolecular route (Scheme 4).

the most preferable conformation of the two oxygen

atoms is trans-orientation because of repulsion between

the bulky norbornane skeleton and the benzyl ether.

MgBr₂cannot then coordinate with two oxygen atoms in

13 (Scheme 6).

In every case, strong kinetic control was observed, and the

desired products 5i±l by intramolecular reaction were

obtained in extremely high yields. High selectivity in

these bromoetheri®cation reactions must be due to prefer-

ence for the intramolecular reaction vs the intermolecular

one in addition to the high reactivity of norbornene ole®n to

the bromonium ion. It is noteworthy that high selectivity

was observed even in compound 4l. In this case, because

the distance between the norbornene ole®n and the acetal

oxygen is the same as that between the diol ole®n and the

acetal oxygen and both ole®ns are under same situation for

the intramolecular version, in other words each reaction

proceeds via a 5-membered transition state, compound 4l

was expected to proceed by two types of intramolecular

haloetheri®cation reaction, one with a norbornene ole®n

and the other with a diol ole®n. This high reactivity of the

ole®n of the norbornene skeleton toward the bromonium ion

is suited to our desymmerization method (Scheme 5).

(2) Debromoetheri®cation of 8-membered acetal in

Scheme 1 (step b). The above results suggested that the

coordination of MgBr₂to two oxygen atoms, one of which

is the debromoetheri®ed oxygen, is essential for the success

of debromoetheri®cation. We then studied reductive

debromoetheri®cation of 8-membered acetals 5a±l using

15 equiv. of Zn in the presence of additive, 6 equiv. of

MgBr₂´Et₂O for 5a±h or 6 equiv. of ZnCl₂for 5i±l, in

DMA (Scheme 7). The effects of the additives on the

saturated diols (MgBr₂) and the unsaturated ones (ZnCl₂)

are different to each other. The reason for this result is not

clear at this time. Anyway, debromoetheri®cation of every

8-membered acetals proceeded smoothly to give the

corresponding acetal alcohols 6a±l in high yields. It is

noteworthy that the debromoetheri®cation reaction works

well even towards acetal 5k which has two acid labile allylic

ether moieties. Yields are shown in Table 2.

Reductive debromoetheri®cation

This step was examined in two ways, (1) debromoetheri®-

cation of bromobenzyl ether, and (2) debromoetheri®cation

of an 8-membered mixed acetal. Method (2) was found to be

effective for our purpose.

(1) Debromoetheri®cation of bromobenzyl ether. For

reductive debromoetheri®cation, we ®rst examined the

reductive debromination of bromobenzyl ether 11, prepared

from 8-membered acetal 5b by transacetalization with

meso-1,2-cyclopentanediol 2b and protection of the

hydroxy group as a benzyl ether. After several disappointing

trials, we succeeded in reductive debromoetheri®cation of

11 using 15 equiv. of Zn and 6 equiv. of MgBr₂´Et₂O in

DMA to give the optically pure benzyl ether 12 along

with the ene acetal 4b. However, this condition failed in

the debromoetheri®cation of the corresponding compound

13 from 5e. The differences between the two reactions might

be rationalized by the coordination of MgBr₂, which aids the

debromoetheri®cation. That is, MgBr₂can coordinate with

two oxygen atoms in 11, because two oxygen atoms are

®xed cis-orientation in 11. However, in acyclic case 13,

Scheme 7.

Protection of alcohol in Scheme 1 (step c)

Protection of the hydroxy group of 6a±l as a benzyl ether by

Scheme 8.

H. Fujioka et al. / Tetrahedron 56 (2000) 10141±10151

10145

Scheme 9.

usual way proceeded well to give benzyl ether 7a±l

(Scheme 8). Yields are shown in Table 2.

Procedure for the preparation of aldehyde 1

To a solution of LiAlH₄(1.73 g, 6.6 mmol) in THF

(10.0 mL) was added (4S)-3-((3⁰R,4⁰R,5⁰S,6⁰S)-5⁰-methyl-

bicyclo[2.2.1]heptene-4⁰-carbonyl)-4-(1-methylethyl)-2-

oxazolidinone (499 mg, 13.1 mmol) in THF (3.0 mL) at 08C

under a nitrogen atmosphere. After stirring at 08C for 1 h,

AcOEt, MeOH, and aqueous NH₄Cl were successively

added to the reaction mixture. The resulting solution was

extracted with AcOEt. The extract was washed with brine,

dried over MgSO₄and concentrated in vacuo. The residue

was puri®ed by SiO₂column chromatography with hexane-

AcOEt (5/1) as an eluent to give (1R,2R,3S,4S)-3-methyl-5-

norbornene-2-methanol (875 mg, 97%) in a pure state,

whose structure was determined by the ¹H NMR spectrum:

¹H NMR d 6.22 (dd, 1H, J3.3, 5.6 Hz), 5.98 (dd, 1H,

J2.8, 5.6 Hz), 3.45±3.27 (m, 2H), 2.86 (brs, 1H), 2.38

(brs, 1H), 2.46±2.25 (m, 1H), 1.52±1.42 (m, 2H), 1.12 (d,

3H, J6.6 Hz). Thus obtained (1R,2R,3S,4S)-3-methyl-5-

norbornene-2-methanol (101 mg, 0.7 mmol) in CH₂Cl₂

(3.6 mL) was added to a solution of oxalyl chloride

(0.14 mL, 1.6 mmol) and DMSO (0.23 mL, 3.2 mmol) in

CH₂Cl₂(3.6 mL) at 2788C under a nitrogen atmosphere.

After stirring at 2788C for 1 h, Et₃N (0.50 mL, 3.5 mmol)

was added to the solution, and the temperature was allowed

to rise to rt, then aqueous NH₄Cl was added to the reaction

mixture. The resulting solution was extracted with Et₂O.

The extract was washed with brine, dried over MgSO₄and

concentrated in vacuo. The residue was puri®ed by SiO₂

column chromatography with pentane-Et₂O (25/1) as an

eluent to give (1R,2R,3S,4S)-3-methyl-5-norbornene-2-

carboxaldehyde 1 (73 mg, 73%). Compound 1 is fairly

Transacetalization with meso-1,2-diols in Scheme 1

(step d)

Transacetalization with one equiv. of meso-diols 2a±l in the

presence of a catalytic amount of PPTS afforded the

optically active 3a±l in good yields. At the same time, the

ene acetals 4a±l (Scheme 9) were produced stereo-

speci®cally in good yields. Yields are shown in Table 2.

Use of other protecting groups except benzyl ether

The advantage of this method was also proved by the proper

choice of a protective group. For example, in the case of the

diol 2g having a benzyl group, a silyl or acyl group can also

be used as a protective group. Thus 6h was converted to

silyl, acyl and para-methoxybenzyl compounds 15A⁹,B,C

in good yields without any problem (Scheme 10).

Scheme 10. a For 14A: TBDPSCl, imidazole, DMF (86%); For 14B:

(PhCO)₂O, pyr (99%); For 14C: p-MeOC₆H₄CH₂Br, NaH, DMF (86%).

b 2h (1 eq.), cat. PPTS, C₆H₆, rt {15A (91%), 4h (96%); 15B (89%), 4h

(87%); 15C (97%), 4h (90%)}.

1

volatile and its structure was determined by H NMR and

IR spectra:^{10 1}H NMR d 9.37 (d, 1H, J3.3 Hz), 6.29 (dd,

1H, J3.1, 5.6 Hz), 6.05 (dd, 1H, J2.6, 5.6 Hz), 3.13 (brs,

1H), 2.56 (brs, 1H), 2.35±2.30 (m, 1H), 1.85±1.79 (m, 1H),

1.59±1.45 (m, 2H), 1.17 (d, 3H, J6.9 Hz); IR (KBr) 1721,

Conclusion

720 cm²¹

.

We have developed a new asymmetrization method for satu-

rated and unsaturated meso-1,2-diols. Characteristic points

of the method are (i) asymmetrization with extremely highly

enantiomeric excess, (ii) wide applicability not only to

cyclic saturated and unsaturated meso-1,2-diols but also to

acyclic saturated and unsaturated ones, and (iii) high ef®-

ciency through out the asymmetrization reaction cycle.

General procedure for the acetalization of 1 with meso-

diol 2 in Table 1

To a solution of meso-diol 2 (1 mmol) and norbornene

aldehyde 1 (1 mmol) in toluene (10 mL) was added a

catalytic amount of pyridinium p-toluenesulfonate at rt

under a nitrogen atmosphere. After being stirred for over

12 h, the reaction mixture was quenched with saturated

aqueous NaHCO₃. The solution was extracted with

AcOEt. The organic phase was washed with brine, dried

over MgSO₄and concentrated in vacuo. The residue

was puri®ed by SiO₂column chromatography with

hexane-AcOEt as an eluent to give 4 in yields shown

in Table 1.

Experimental

NMR spectra were measured on 270 MHz and 500 MHz

spectrometers with CDCl₃as a solvent and with SiMe₄as

an internal standard. All solvents were dried and distilled

according to standard procedure.

10146

H. Fujioka et al. / Tetrahedron 56 (2000) 10141±10151

Table 1. Acetalization of 1 with meso-diol (2)

Entry

meso-Diol 2

Product

Yield of 4 (%)

1

2

3

4

2a: R±(CH₂)₄₂

4a

4b

4c

4d

93

99

96

99

2b: R±(CH₂)₃₂

2c: R±(CH₂)₆₂

2d: R±CH₂OCH₂₂

5

6

7

8

2e: RCH₃

4e

4f

4g

4h

99

91

83

2f: Rn-Pr

2g: RCH₂OBn

2h: Ri-Pr

9

10

2i: R±CH₂CHvCHCH₂₂

4i

4j

86

2j: R±(CH₂)₂CHvCH(CH₂)₂₂

11

12

2k: R±CHvCH₂

4k

4l

84

81

2l: R±(CH₂)₂CHvCH₂

General procedure for the intramolecular halo-

etheri®cation reaction of 4 (from 4 to 5)

Calcd for C₁₈H₂₉BrO₃: 372.1301 (M¹), 374.1294 (M¹12).

Found: 372.1300 (M¹), 374.1280 (M¹12).

5d. ¹H NMR d 4.91 (d, 1H, J7.9 Hz), 4.36±3.70 (m, 8H),

3.35 (s, 3H), 2.68±2.65 (m, 1H), 2.11 (brs, 1H), 1.92±1.46

(m, 4H), 1.03 (d, 3H, J6.9 Hz); ¹³C NMR d 107.84, 87.73,

79.08, 78.80, 71.84, 63.45, 59.00, 55.15, 53.71, 52.78,

48.20, 40.70, 32.81, 21.15; Anal. Calcd for C₁₄H₂₁BrO₄:

C, 50.46; H, 6.35; Br, 23.98. Found: C, 50.39; H, 6.23;

Br, 23.73.

To a solution of 4 (1 mmol), g-collidine (2 equiv.) and

MeOH (5 equiv.) in CH₃CN (10 mL) was added N-bromo-

succinimide (2 equiv.) at 2408C under

a nitrogen

atmosphere. The mixture was allowed to warm to rt under

stirring. Completion of the reaction was examined by TLC.

The solution was quenched with saturated aqueous

NaHCO₃, then extracted with AcOEt. The organic phase

was washed with brine, dried over MgSO₄and concentrated

in vacuo. The residue was puri®ed by SiO₂column chroma-

tography with hexane-AcOEt as an eluent to give 5 in yields

shown in Table 2.

5e. ¹H NMR d 4.72 (d, 1H, J7.6 Hz), 4.43±4.37 (m, 1H),

4.00±3.80 (m, 2H), 3.71 (t, 1H, J2.8 Hz), 3.34 (s, 3H),

2.60±2.50 (m, 1H), 2.12 (brs, 1H), 1.90±1.40 (m, 4H), 1.25

(d, 3H, J6.9 Hz), 1.12 (d, 3H, J6.6 Hz,), 1.02 (d, 3H,

J6.9 Hz); ¹³C NMR d 111.61, 85.77, 79.84, 76.44, 59.28,

54.79, 53.75, 52.27, 48.57, 42.03, 32.56, 21.15, 15.96,

10.16; HRMS m/z Calcd for C₁₄H₂₃BrO₃: 319.0868 (M¹),

321.0867 (M¹12). Found: 319.0864 (M¹), 321.0844

(M¹12)

5a. ¹H NMR d 4.72 (d, 1H, J7.9 Hz), 4.42±4.39 (m, 1H),

3.81±3.70 (m, 3H), 3.34 (s, 3H), 2.69 (brs, 1H), 2.11 (brs,

1H), 2.11±1.42 (m, 12H), 1.03 (d, 3H, J6.9 Hz); ¹³C NMR

d 111.93, 85.90, 59.71, 53.69, 52.36, 48.97, 42.07, 32.74,

30.42, 25.05, 24.85, 21.19, 20.63; Anal. Calcd for

C₁₆H₂₅BrO₃: C, 55.66; H, 7.03; Br, 23.14. Found: C,

55.25; H, 7.01; Br, 23.40.

5f. ¹H NMR d 4.74 (d, 1H, J8.3 Hz), 4.37 (brs, 1H), 3.71±

3.69 (m, 3H), 3.39 (s, 3H), 2.55 (brs, 1H), 2.13 (brs, 1H),

1.91±1.29 (m, 12H), 1.02 (d, 3H, J6.9 Hz), 0.98 (d, 3H,

J6.3 Hz), 0.93 (d, 3H, J6.9 Hz); ¹³C NMR d 111.91,

85.82, 84.22, 80.41, 59.12, 55.53, 53.77, 52.15, 48.16,

42.12, 34.13, 32.47, 26.65, 21.42, 21.13, 20.04, 14.18,

14.13; Anal. Calcd for C₁₈H₃₁BrO₃: C, 57.60; H, 8.32; Br,

21.29. Found: C, 57.41; H, 8.08; Br, 21.28.

5b. ¹H NMR d 4.86 (d, 1H, J7.9 Hz), 4.35 (m, 1H), 4.02

(m, 2H), 3.75 (m, 1H), 3.35 (s, 3H), 2.61 (brs, 1H), 2.12 (brs,

1H), 1.95±1.45 (m, 10H), 1.03 (d, 3H, J6.9 Hz); ¹³C NMR

d 108.48, 86.94, 59.50, 53.87, 52.92, 48.48, 41.08, 32.80,

31.59, 28.48, 23.74, 22.66, 19.97, 14.18, 14.09; Anal. Calcd

for C₁₅H₂₃BrO₃: C, 54.38; H, 7.00; Br, 24.12. Found: C,

54.18; H, 6.72; Br, 24.01.

5g. ¹H NMR d 7.36±7.28 (m, 10H), 4.71 (d, 1H, J7.9 Hz),

4.63±4.37 (m, 6H), 4.20±4.03 (m, 2H), 3.89±3.42 (m, 4H),

3.40 (s, 3H), 2.35 (2.36±2.33, 1H), 2.09 (brs, 1H), 1.78±

1.26 (m, 4H), 1.00 (d, 3H, J6.9 Hz); ¹³C NMR d 137.90,

137.38, 128.48, 128.39, 128.18, 127.92, 127.67, 127.57,

111.97, 85.86, 82.14, 76.44, 73.48, 73.12, 69.38, 65.59,

59.09, 55.22, 53.68, 52.31, 48.27, 41.91, 32.53, 21.15;

5c. ¹H NMR d 4.67 (d, 1H, J7.9 Hz), 4.44 (brs, 1H), 4.19±

4.10 (m, 1H), 3.74±3.67 (m, 1H), 3.33 (s, 3H), 2.39 (brs,

1H), 2.13 (brs, 1H), 2.03±1.22 (m, 16H), 1.00 (d, 3H,

J6.9 Hz); ¹³C NMR d 111.57, 85.73, 84.33, 80.00,

58.96, 54.90, 54.07, 51.84, 47.32, 42.19, 32.13, 27.91,

27.28, 26.65, 24.51, 23.22, 21.93, 21.12; HRMS m/z

H. Fujioka et al. / Tetrahedron 56 (2000) 10141±10151

10147

Table 2. Reaction cycle for asymmetrization. Yields of the products 5, 6, 7,

3, and 4 in every step of our asymmetric desymmerization, whose proce-

dures were mentioned previously, are summarized. The optical purity of

3a±l was determined by HPLC analysis (Chiralpak AD)

Anal. Calcd for C₂₈H₃₅BrO₅: C, 63.28; H, 6.64; Br, 15.03.

Found: C, 63.07; H, 6.51; Br, 14.88.

5h. ¹H NMR d 4.67 (d, 1H, J7.9 Hz), 4.39 (brs, 1H), 3.85±

3.60 (m, 2H), 3.36 (s, 3H), 3.19 (brs, 1H), 2.60 (brs, 1H),

2.18 (brs, 1H), 2.01±1.45 (m, 8H), 1.17±0.81 (m, 15H); ¹³C

NMR d 107.15, 82.98, 80.41, 77.20, 55.20, 54.79, 53.71,

52.53, 47.26, 42.93, 32.02, 28.18, 27.66, 22.18, 21.33,

21.03, 19.36, 14.81; FAB-HRMS m/z Calcd for

C₁₈H₃₁BrO₃: 374.1497 (M¹). Found 374.1486 (M¹).

Entry

Substr

Yield (%)

ee of 3^a(%)

5

6

7

3

4

1

2

3

4

5

6

7

8

4a

4b

4c

4d

4e

4f

4g

4h

4i

99

86

95

89

87

90

87

97

92

91

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5i. ¹H NMR d 5.62±5.51 (m, 2H), 4.70 (d, 1H, J7.6 Hz),

4.43 (m, 1H), 4.09 (m, 1H), 3.91 (m, 1H), 3.73 (t, 1H,

J2.8 Hz), 3.35 (s, 3H), 2.71±2.30 (m, 5H), 2.21 (brs,

1H), 1.93±1.47 (m, 4H), 1.04 (d, 3H, J6.9 Hz); ¹³C

NMR d 123.32, 122.91, 112.74, 86.20, 78.51, 74.59,

59.39, 54.83, 53.59, 52.02, 49.18, 42.34, 32.81, 31.04,

23.29, 21.17; Anal. Calcd for C₁₆H₂₃BrO₃: C, 55.99; H,

6.75; Br, 23.28. Found: C, 55.78; H, 6.59; Br, 23.16.

$99

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4j

4k

4l

^aDetermined by HPLC analysis (Chiralpak AD).

1

5j. H NMR d 5.49 (m, 2H), 4.69 (d, 1H, J8.1 Hz), 4.41

(brs, 1H), 4.25 (m, 1H), 3.77 (m, 1H), 3.69 (m, 1H), 3.35 (s,

3H), 2.78±2.42 (m, 4H), 2.22±1.85 (m, 7H), 1.72 (m, 1H),

1.57±1.45 (m, 2H), 1.03 (d, 3H, J8.9 Hz); ¹³C NMR d

130.82, 124.13, 112.78, 86.49, 86.38, 77.65, 59.46, 54.95,

53.75, 52.08, 48.34, 42.28, 32.46, 28.81, 27.46, 22.93,

22.63, 21.13; Anal. Calcd for C₁₈H₂₇BrO₃: C, 58.22; H,

7.33; Br, 21.52. Found: C, 58.02; H, 7.13; Br, 21.71.

are rather labile and tend to give 4. Then their structures

were ascertained by ¹H NMR, ¹³C NMR, and IR.

6a. ¹H NMR d 6.24 (dd, 1H, J3.1, 5.8 Hz), 6.00 (dd, 1H,

J2.8, 5.8 Hz), 3.99 (d, 1H, J8.4 Hz), 3.84±3.58 (m, 2H),

3.32 (s, 3H), 2.80 (brs, 1H), 2.39 (brs, 1H), 2.29 (brs, 1H),

1.94±1.19 (m, 12H), 1.14 (d, 3H, J6.2 Hz); ¹³C NMR d

138.74, 132.83, 106.58, 76.12, 68.43, 52.17, 50.82, 48.90,

46.11, 44.85, 36.50, 30.44, 27.87, 23.24, 21.13, 20.29.

5k. ¹H NMR d 6.00±5.86 (m, 1H), 5.60±5.07 (m, 5H), 4.74

(d, 1H, J7.9 Hz), 4.26±4.17 (m, 3H), 3.66 (t, 1H,

J2.8 Hz), 3.27 (s, 3H), 2.40 (brs, 1H), 2.06 (brs, 1H),

1.83±1.40 (m, 4H), 0.97 (d, 3H, J7.3 Hz); ¹³C NMR d

133.5, 130.9, 124.9, 116.4, 111.7, 86.1, 84.2, 82.1, 58.9,

54.8, 54.0, 52.3, 48.2, 42.0, 32.6, 21.2; Anal. Calcd for

C₁₆H₂₃BrO₃: C, 55.99; H, 6.75; Br, 23.28. Found: C,

55.90; H, 6.65; Br, 22.89.

6b. ¹H NMR d 6.24 (dd, 1H, J3.1, 5.8 Hz), 6.00 (dd, 1H,

J2.8, 5.8 Hz), 4.03±3.91 (m, 3H), 3.34 (s, 3H), 2.81 (brs,

1H), 2.51 (brs, 1H), 2.50 (brs, 1H), 1.91±1.18 (m, 10H),

1.13 (d, 3H, J5.9 Hz).

6c. ¹H NMR d 6.24 (dd, 1H, J3.1, 5.6 Hz), 6.00 (dd, 1H,

J2.6, 5.6 Hz), 3.97 (d, 1H, J9.2 Hz), 3.84±3.76 (m, 2H),

3.33 (s, 3H), 2.70 (brs, 1H), 2.65 (d, 1H, J2.6 Hz), 2.39

(brs, 1H), 1.91±1.20 (m, 16H), 1.14 (d, 3H, J 6.3 Hz); ¹³C

NMR d 138.81, 132.83, 106.68, 77.97, 71.18, 52.18, 50.82,

48.91, 44.83, 36.60, 29.18, 28.55, 26.99, 26.13, 25.30,

21.99, 21.17.

5l. ¹H NMR d 5.86± 5.75 (m, 2H), 5.13± 4.98 (m, 4H), 4.74

(d, 1H, J8.1 Hz), 4.39 (brs, 1H), 3.79± 3.70 (m, 3H), 3.40

(s, 3H), 2.55 (brs, 1H), 2.30± 1.43 (m, 13H), 1.03 (d, 3H,

J6.8 Hz); ¹³C NMR d 137.7, 137.3, 115.7, 115.2, 111.9,

86.0, 83.5, 79.4, 58.9, 55.6, 53.7, 52.1, 48.1, 42.1, 32.5,

31.9, 31.1, 30.8, 23.7, 21.1; FAB-MS m/z 399 (M¹);

FAB-HRMS Calcd for C₂₀H₃₂O₃Br: 399.1495 (M¹).

Found: 399.1523 (M¹).

6d. ¹H NMR d 6.25 (dd, 1H, J3.1, 6.1 Hz), 5.99 (dd, 1H,

J2.7, 6.1 Hz), 4.27±3.75 (m, 6H), 3.97 (d, 1H,

J9.16 Hz), 3.34 (s, 3H), 2.79 (d, 1H, J3.05 Hz), 2.76

(brs, 1H), 2.41 (brs, 1H), 1.87±1.83 (m, 1H), 1.53±1.41

(m, 2H), 1.26±1.19 (m, 1H), 1.14 (d, 3H, J6.7 Hz); ¹³C

NMR d 138.83, 132.78, 108.57, 74.25, 73.55, 70.53, 70.17,

53.86, 51.14, 48.68, 46.02, 44.62, 36.62, 21.15.

General procedure for the elimination reaction of 5

(from 5 to 6)

To a solution of 5 (1 mmol) in N,N-dimethylacetamide

(10 mL) was added MgBr₂´Et₂O (6 equiv.) for 5a±h and

ZnCl₂(6 equiv.) for 5i±l under a nitrogen atmosphere.

After stirring for 30 min at 608C, Zn powder (15 equiv.)

was added to the reaction mixture. The resulting mixture

was stirred at 758C for about 12 h. After completion of the

reaction checked by TLC, AcOEt was added to the solution,

then ®ltered with celite for removal of precipitate. The

organic phase was washed with brine, dried over MgSO₄

and concentrated in vacuo. The residue was puri®ed by

SiO₂column chromatography with hexane-AcOEt as an

eluent to give 6 in yields shown in Table 2. Compounds 6

6e. ¹H NMR d 6.24 (dd, 1H, J3.1, 5.6 Hz), 5.99 (dd, 1H,

J2.6, 5.6 Hz), 3.98 (d, 1H, J9.2 Hz), 3.87±3.82 (m, 1H),

3.70±3.66 (m, 1H), 3.33 (s, 3H), 2.80 (brs, 1H), 2.39 (brs,

1H), 2.29 (d, 1H, J2.3 Hz), 1.94±1.20 (m, 4H), 1.19±1.11

(m, 9H); ¹³C NMR d 138.80, 132.83, 106.94, 75.87, 69.04,

52.33, 50.84, 48.91, 46.09, 44.82, 36.53, 21.15, 17.45,

14.68.

1

6f. H NMR d 6.25 (dd, 1H, J3.3, 5.6 Hz), 6.00 (dd, 1H,

J2.6, 5.6 Hz), 3.99 (d, 1H, J9.2 Hz), 3.70±3.66 (m, 1H),

3.62±3.56 (m, 1H), 3.36 (s, 3H), 2.80 (brs, 1H), 2.39 (brs,

10148

H. Fujioka et al. / Tetrahedron 56 (2000) 10141±10151

1H), 2.31 (d, 1H, J4.3 Hz), 1.95±1.20 (m, 12H), 1.14 (d,

3H, J6.3 Hz), 0.95 (t, 3H, J6.9 Hz), 0.94 (t, 3H,

J7.1 Hz).

for 24 h at rt, then quenched with MeOH and H₂O. The

resulting solution was extracted with AcOEt. The organic

phase was washed with brine, dried over MgSO₄and

concentrated in vacuo. The residue was puri®ed by SiO₂

column chromatography with hexane-AcOEt as an eluent

to give 7 in yields shown in Table 2.

1

6g. H NMR 7.27±7.18 (m, 10H), 6.12 (dd, 1H, J3.1,

5.8 Hz), 5.88 (dd, 1H, J2.8, 5.8 Hz), 4.54±4.40 (m, 4H),

4.03±3.98 (m, 1H), 3.92 (d, 1H, J9.2 Hz), 3.73±3.54 (m,

5H), 3.22 (s, 3H), 2.75 (d, 1H, J4.6), 2.70 (brs, 1H), 2.29

(brs, 1H), 1.80±1.77 (m, 1H), 1.41±1.11 (m, 3H), 1.04 (d,

3H, J6.3 Hz); ¹³C NMR d 138.42, 137.99, 137.92, 133.33,

128.39, 128.34, 127.80, 127.73, 127.66, 108.19, 76.05,

73.46, 73.42, 71.00, 70.96, 70.12, 52.67, 51.04, 48.91,

45.88, 44.76, 36.28, 21.13.

7a. ¹H NMR d 7.29±7.18 (m, 5H), 6.02 (brs, 1H), 5.92 (brs,

1H), 4.52 (s, 2H), 4.05 (d, 1H, J9.1 Hz), 3.73 (brs, 1H),

3.42 (brs, 1H), 3.23 (s, 3H), 2.81 (brs, 1H), 2.27 (brs, 1H),

1.86±1.08 (m, 12H,), 1.06 (d, 3H, J6.7 Hz); ¹³C NMR d

137.63, 134.12, 128.37, 128.16, 127.75, 127.60, 127.42,

127.19, 106.99, 78.19, 73.86, 72.09, 70.33, 51.30, 50.68,

49.11, 45.73, 45.02, 36.26, 29.71, 27.41, 22.21, 21.15;

FAB-HRMS m/z Calcd for C₂₃H₃₂O₃: 356.2351 (M¹).

Found: 356.2315 (M¹).

6h. ¹H NMR d 6.26 (dd, 1H, J3.0, 5.6 Hz), 6.00 (dd, 1H,

J2.6, 5.6 Hz), 3.99 (d, 1H, J8.6 Hz), 3.48 (dd, 1H,

J2.6, 3.6 Hz), 3.38 (s, 3H), 3.35 (dd, 1H, J1.7,

3.6 Hz), 2.81 (brs, 1H), 2.39 (brs, 1H), 2.23 (d, 1H,

J2.0 Hz), 2.02±1.20 (m, 8H), 1.17±0.78 (m, 15H); ¹³C

NMR d 138.78, 132.92, 105.32, 79.21, 76.82, 53.73,

51.45, 49.06, 46.22, 45.00, 36.41, 30.10, 27.73, 21.71,

21.22, 19.95, 18.83, 17.74.

1

7b. H NMR d 7.38±7.31 (m, 5H), 6.12 (dd, 1H, J2.9,

5.1 Hz), 5.98 (dd, 1H, J2.6, 5.1 Hz), 4.61 (s, 2H), 4.05 (d,

1H, J9.4 Hz), 4.00±3.99 (m, 1H), 3.78±3.77 (m, 1H), 3.29

(s, 3H), 2.86 (brs, 1H), 2.35 (brs, 1H), 1.86±1.19 (m,

10H)1.12 (d, 3H, J6.6 Hz); ¹³C NMR d 137.81, 134.00,

128.21, 127.66, 127.33, 107.31, 80.58, 76.41, 71.14, 52.08,

50.71, 48.99, 45.77, 44.87, 36.46, 28.99, 27.32, 21.21,

18.92; HRMS m/z Calcd for C₂₂H₃₀O₃: 342.2190 (M¹),

343.2240 (M¹11). Found 342.2195 (M¹), 343.2228

(M¹11).

1

6i. H NMR d 6.25 (dd, 1H, J5.8, 3.1 Hz), 6.01 (dd, 1H,

J5.6, 2.6 Hz), 5.60 (m, 2H), 3.94 (m, 3H), 3.33 (s, 3H),

2.81 (brs, 1H), 2.36 (m, 6H), 1.92 (m, 1H), 1.44 (m, 2H),

1.22 (m, 1H), 1.13 (d, 3H, J5.9 Hz); ¹³C NMR d 138.78,

132.85, 124.04, 123.70, 106.78, 73.19, 67.17, 52.63, 50.66,

48.90, 46.04, 44.78, 36.66, 31.66, 28.75, 21.13.

1

7c. H NMR d 7.37±7.26 (m, 5H), 6.11 (dd, 1H, J3.0,

5.6 Hz), 6.00 (dd, 1H, J2.6, 5.6 Hz), 4.59±4.56 (m, 2H),

4.10 (d, 1H, J9.2 Hz), 3.95±3.91 (m, 1H), 3.64±3.61 (m,

1H), 3.31 (s, 3H), 2.86 (brs, 1H), 2.34 (brs, 1H), 2.11±1.18

(m, 16H), 1.13 (d, 3H, J6.6 Hz); ¹³C NMR d 137.77,

134.05, 128.40, 128.18, 127.78, 127.62, 127.49, 127.19,

107.46, 80.67, 77.00, 71.02, 51.38, 50.84, 49.13, 45.77,

45.00, 36.23, 30.75, 29.13, 27.24, 26.72, 23.33, 22.68,

21.15; FAB-HRMS m/z Calcd for C₂₅H₃₆O₃: 384.2720

(M¹). Found 384.2728 (M¹).

1

6j. H NMR d 6.24 (dd, 1H, J5.8, 3.1 Hz), 6.00 (dd, 1H,

J5.6, 2.6 Hz), 5.63 (m, 2H), 3.96±3.85 (m, 3H), 3.33 (s,

3H), 2.82 (brs, 1H), 2.58 (m, 2H), 2.38 (brs, 1H), 2.20 (d,

1H, J4.6 Hz), 2.10±1.37 (m, 9H), 1.20 (m, 1H), 1.13 (d,

3H, J6.3 Hz); ¹³C NMR d 138.69, 132.99, 130.01, 128.99,

107.67, 79.48, 73.78, 52.54, 50.95, 48.95, 46.04, 44.85,

36.48, 32.17, 30.19, 23.24, 22.61, 21.15.

6k. ¹H NMR d 6.24 (dd, 1H, J3.1, 5.6 Hz), 5.99 (dd, 1H,

J3.0, 5.6 Hz), 5.93±5.82 (m, 2H), 5.39±5.21 (m, 4H),

4.23±4.10 (m, 2H), 3.97 (d, 1H, J9.2 Hz), 3.30 (s, 3H),

2.82 (brs, 1H), 2.57 (d, 1H, J5.0 Hz), 2.39 (brs, 1H), 1.95±

1.86 (m, 1H), 1.53±1.17 (m, 3H), 1.13 (d, 1H, J5.6 Hz);

¹³C NMR d 138.71, 136.17, 135.08, 132.94, 118.08, 116.73,

107.64, 80.29, 74.41, 54.00, 51.25, 48.74, 45.99, 44.55,

36.68, 21.19.

1

7d. H NMR d 7.39±7.27 (m, 5H), 6.16 (dd, 1H, J3.3,

5.6 Hz), 5.96 (dd, 1H, J2.6, 5.6 Hz), 4.67 (d, 2H,

J6.6 Hz), 4.25±3.83 (m, 7H), 3.29 (s, 3H), 2.82 (brs,

1H), 2.37 (brs, 1H), 1.89±1.18 (m, 4H), 1.13 (d, 3H,

J5.9 Hz); ¹³C NMR d 138.11, 137.93, 133.60, 128.37,

127.84, 127.75, 107.75, 77.77, 73.60, 72.04, 70.41, 70.10,

52.65, 50.62, 48.90, 45.75, 44.71, 36.46, 21.15; HRMS m/z

Calcd for C₂₁H₂₈O₄: 344.1991 (M¹), 345.2038 (M¹11).

Found: 344.1987 (M¹), 345.2021 (M¹11).

1

6l. H NMR d 6.26 (dd, 1H, J3.1, 5.8 Hz), 5.99 (dd, 1H,

J2.8, 5.8 Hz), 5.89± 5.77 (m, 2H), 5.10±4.96 (m, 4H),

3.98 (d, 1H, J9.0 Hz), 3.71±3.59 (m, 2H), 3.36 (s, 3H),

2.80 (brs, 1H), 2.38±2.09 (m, 6H), 1.93 (m, 1H), 1.73±1.22

(m, 7H), 1.15 (d, 3H, J6.3 Hz); ¹³C NMR d 138.68,

138.22, 138.08, 132.48, 114.79, 114.53, 106.28, 78.07,

70.99, 53.46, 50.88, 48.87, 46.05, 44.75, 36.50, 30.72,

30.36, 30.10, 28.58, 21.16.

1

7e. H NMR d 7.34±7.31 (m, 5H), 6.20±6.10 (m, 1H),

6.03±5.95 (m, 1H), 4.60 (s, 2H), 4.05 (d, 1H, J9.2 Hz),

3.77±3.74 (m, 1H), 3.50±3.47 (m, 1H), 3.32 (s, 3H), 2.86

(brs, 1H), 2.35 (brs, 1H), 1.23 (d, 3H, J6.1 Hz), 1.22 (d,

3H, J6.1 Hz), 1.13 (d, 3H, J6.7 Hz); ¹³C NMR d 138.06,

133.76, 128.27, 127.53, 127.35, 107.85, 78.42, 75.53, 71.02,

51.68, 51.09, 49.08, 45.86, 44.96, 36.23, 21.17, 17.33,

15.29; FAB-HRMS m/z Calcd for C₂₁H₃₀O₃: 330.2195

(M¹). Found: 330.2182 (M¹).

General procedure for the benzylation reaction of 6

(from 6 to 7)

1

7f. H NMR d 7.38±7.29 (m, 5H), 6.12 (dd, 1H, J3.0,

A solution of 6 (1 mmol) and NaH (60% oil suspension,

3 equiv.) in THF-DMF (v/v4/1, 10 mL) was stirred for

30 min at rt under a nitrogen atmosphere. BnBr (3 equiv.)

was added to the solution. The reaction mixture was stirred

5.8 Hz), 6.06 (dd, 1H, J2.6, 5.8 Hz), 4.57 (s, 2H), 4.11

(d, 1H, J9.2 Hz), 3.81±3.73 (m, 1H), 3.43±3.35 (m,

1H), 3.35 (s, 3H), 2.87 (brs, 1H), 2.34 (brs, 1H), 1.95±

H. Fujioka et al. / Tetrahedron 56 (2000) 10141±10151

10149

1.10 (m, 12H), 1.14 (d, 3H, J6.3 Hz), 1.00±0.80 (m, 6H);

¹³C NMR d137.90, 128.21, 127.78, 127.67, 127.64, 124.26,

109.87, 85.72, 78.01, 77.20, 56.57, 52.90, 52.89, 51.63,

49.13, 45.05, 32.81, 29.69, 24.46, 21.08, 19.61, 14.31;

FAB-HRMS m/z Calcd for C₂₅H₃₈O₃: 386.2820 (M¹).

Found 386.2830 (M¹).

1H), 3.43±3.35 (m, 4H), 2.86 (brs, 1H), 2.34±2.10 (m, 5H),

1.86±1.12 (m, 11H); ¹³C NMR d 138.7, 138.6, 138.3, 137.9,

134.0, 129.0, 128.8, 127.8, 127.46, 114.86, 114.69, 107.89,

80.91, 76.07, 71.90, 53.26, 51.73, 49.11, 45.78, 45.06, 36.1,

33.6, 30.9, 30.4, 30.4, 29.2, 21.3; FAB-MS m/z 433

(M¹1Na); FAB-HRMS Calcd for C₂₇H₃₈O₃Na: 433.2697

(M¹1Na). Found: 433.2708 (M¹1Na).

1

7g. H NMR d 7.34±7.23 (m, 15H), 6.13 (dd, 1H, J3.0,

5.6 Hz), 5.95 (dd, 1H, J2.6, 5.6 Hz), 4.73±4.50 (m, 6H),

4.05±3.65 (m, 6H), 3.29 (s, 3H), 2.76 (brs, 1H), 2.33 (brs,

1H), 1.88±1.83 (m, 1H), 1.47±1.10 (m, 8H); ¹³C NMR d

138.71, 138.38, 138.24, 138.06, 133.64, 128.27, 128.23,

128.16, 127.67, 127.55, 127.44, 127.33, 108.30, 78.78,

76.26, 73.24, 73.21, 72.69, 70.12, 69.87, 52.02, 51.09,

48.99, 45.81, 44.82, 36.12, 21.12; Anal. Calcd for

C₃₅H₄₂O₅: C, 77.46; H, 7.80. Found: C, 77.64; H, 7.78.

General procedure for the transacetalization reaction of

7 (from 7 to 3 and 4)

To a solution of 7 (1 mmol) and meso-diol 2 (1 mmol) in

toluene (10 mL) was added a catalytic amount of pyri-

dinium p-toluenesulfonate at rt under

a

nitrogen

atmosphere. After stirring for over 12 h, the reaction

mixture was quenched with saturated aqueous NaHCO₃.

The solution was extracted with AcOEt. The organic

phase was washed with brine, dried over MgSO₄and

concentrated in vacuo. The residue was puri®ed by SiO₂

column chromatography with hexane-AcOEt as an eluent

to give 3 and 4 in yields shown in Table 2. Ee values of 3

were determined by HPLC analysis (Chiralpak AD, hexane-

i-PrOH).

1

7h. H NMR d 7.40±7.23 (m, 5H), 6.20 (dd, 1H, J3.1,

5.8 Hz), 6.03 (dd, 1H, J2.8, 5.8 Hz), 4.84 (d, 1H,

J11.2 Hz), 4.50 (d, 1H, J11.2 Hz), 3.99 (d, 1H,

J8.6 Hz), 3.50±3.46 (m, 1H), 3.39 (s, 3H), 3.22±3.17

(m, 1H), 2.88 (brs, 1H), 2.36 (brs, 1H), 2.02±1.20 (m,

8H), 1.17±0.90 (m, 15H).; ¹³C NMR d 138.40, 133.46,

128.21, 127.57, 127.28, 107.62, 86.90, 80.74, 74.04,

55.43, 52.80, 49.06, 45.95, 44.89, 36.07, 30.37, 29.42,

21.35, 20.88, 20.76, 19.37, 18.97; Anal. Calcd for

C₁₅H₂₄O₂: C, 77.68; H, 9.91. Found: C, 77.91; H, 9.83.

3a. [a]²_D⁵116.68 (c 1.03, CHCl₃); H NMR d 7.36±7.23

1

(m, 5H), 4.63 (d, 1H, J11.5 Hz), 4.52 (d, 1H, J11.5 Hz),

3.86 (brs, 1H), 3.52±3.51 (m, 1H), 2.26 (d, 1H, J5.1 Hz),

1.83±1.26 (m, 6H); ¹³C NMR d 138.62, 128.43, 127.62,

127.55, 78.17, 70.15, 68.15, 30.42, 26.58, 22.10, 21.22;

HRMS m/z Calcd for C₁₃H₁₈O₂: 206.1299 (M¹). Found:

206.1307 (M¹).

1

7i. H NMR d 7.37±7.23 (m, 5H), 6.12 (dd, 1H, J5.6,

3.0 Hz), 6.00 (dd, 1H, J5.5, 2.8 Hz), 5.60 (s, 2H), 4.68

(d, 1H, J12.1 Hz), 4.61 (d, 1H, J12.1 Hz), 4.16 (d, 1H,

J9.3 Hz), 4.03 (m, 1H), 3.70 (m, 1H), 3.31 (s, 3H), 2.86

(brs, 1H), 2.36 (m, 5H), 1.91 (m, 1H), 1.49±1.21 (m, 3H),

1.12 (d, 3H, J6.4 Hz); ¹³C NMR d 137.86, 134.02, 128.23,

127.48, 127.33, 124.38, 124.28, 107.37, 76.07, 71.68, 70.68,

51.29, 50.57, 49.09, 45.77, 45.03, 36.30, 31.25, 28.84,

21.13; FAB-HRMS m/z Calcd for C₂₃H₃₀O₃Na: 377.2093

(M¹1Na). Found: 377.2122.

1

3b. [a]³_D⁰119.68 (c 0.86, CHCl₃); H NMR d 7.36±7.29

(m, 5H), 4.60 (d, 1H, J11.7 Hz), 4.55 (d, 1H, J11.7 Hz),

4.10 (m, 1H), 3.82 (dt, 1H, J4.3, 6.6 Hz), 2.49 (d, 1H,

J4.3 Hz), 1.88±1.47 (m, 6H); ¹³C NMR d 128.46,

127.78, 127.67, 81.38, 72.24, 71.56, 31.14, 27.89, 19.66;

HRMS m/z Calcd for C₁₂H₁₆O₂: 192.1141 (M¹), 193.1186

(M¹11). Found: 192.1150 (M¹), 193.1184 (M¹11).

1

7j. H NMR d 7.35±7.26 (m, 5H), 6.18 (dd, 1H, J5.6,

3c. [a]³_D⁰149.98 (c 0.92, CHCl₃); H NMR d 7.39±7.27

1

3.2 Hz), 5.97 (brs, 1H), 5.66 (m, 2H), 4.59 (brs, 2H), 3.96

(brs, 2H), 3.72 (brs, 1H), 3.30 (s, 3H), 2.83 (brs, 1H), 2.71

(brs, 2H), 2.36 (brs, 1H), 2.11±1.21 (m, 10H), 1.13 (d, 3H,

J6.4 Hz); ¹³C NMR d 139.16, 138.13, 133.38, 130.20,

128.27, 128.10, 127.65, 127.50, 127.07, 126.98, 82.24,

79.17, 72.09, 71.50, 51.82, 51.10, 49.16, 45.95, 44.97,

36.31, 22.09, 21.47, 21.24; FAB-HRMS m/s Calcd for

C₂₅H₃₄O₃Na: 405.2406 (M¹1Na). Found: 405.2412.

(m, 5sH), 4.63 (d, 1H, J11.9 Hz), 4.51 (d, 1H, J11.5 Hz),

3.97±3.92 (m, 1H), 3.64±3.59 (m, 1H), 2.57 (d, 1H,

J3.6 Hz), 2.03±1.40 (m, 12H); ¹³C NMR d 128.43,

127.66, 127.60, 80.88, 71.52, 70.82, 29.47, 26.81, 26.63,

25.52, 22.52; Anal. Calcd for C₁₅H₂₂O₂: C, 76.88, H, 9.46.

Found: C, 77.08; H, 9.47.

1

3d. [a]²_D⁰116.78 (c 0.18, CHCl₃); H NMR d 7.38±7.25

7k. ¹H NMR d 7.35±7.25 (m, 5H, Ph), 6.14 (dd, 1H, J3.1,

5.4 Hz), 5.95 (dd, 1H, J2.1, 6.1 Hz), 5.90±5.84 (m, 2H),

5.37±5.19 (m, 4H), 4.64 (d, 1H, J11.9 Hz), 4.44 (d, 1H,

J12.2 Hz), 4.13±4.09 (m, 1H), 4.04 (d, 1H, J9.2 Hz),

3.84±3.79 (m, 1H), 3.25 (s, 3H), 2.85 (brs, 1H), 2.34 (brs,

1H), 1.88±1.84 (m, 1H), 1.49±1.17 (m, 3H), 1.11 (d, 3H,

J5.9 Hz); ¹³C NMR d 138.04, 136.46, 135.08, 133.78,

128.21, 127.67, 127.37, 119.12, 117.17, 108.05, 83.27,

80.40, 70.33, 52.85, 51.34, 48.93, 45.81, 44.76, 36.35,

21.21.

(m, 5H), 4.60 (s, 2H), 4.26±4.22 (m, 1H), 4.06±4.03 (m,

1H), 3.89±3.86 (m, 2H), 3.79±3.72 (m, 2H), 2.85 (d, 1H,

J5.8 Hz); ¹³C NMR d 137.14, 128.61, 128.19, 127.87,

78.26, 73.44, 72.56, 70.33, 69.99; HRMS m/z Calcd for

C₁₁H₁₄O₃: 194.0931 (M¹), 195.0986 (M¹11). Found:

194.0943 (M¹), 195.0976 (M¹11).

1

3e. [a]³_D⁰123.18 (c 0.13, CHCl₃); H NMR d 7.36±7.25

(m, 5H), 4.63(d, 1H, J11.9 Hz), 4.51(d, 1H, J11.9 Hz),

3.95±3.85 (m, 1H), 3.58±3.42 (m, 1H), 2.07 (brs, 1H),

1.18±1.12 (m, 6H); ¹³C NMR d 128.43, 127.61, 127.58,

78.20, 70.71, 69.20, 17.65, 13.43; HRMS m/z Calcd for

C₁₁H₁₆O₂: 180.1130 (M¹), 181.1158 (M¹11). Found:

180.1150 (M¹), 181.1184 (M¹11).

7l. ¹H NMR d 7.37±7.25 (m, 5H), 6.11±6.05 (m, 2H), 5.88±

5.78 (m, 2H), 5.07± 4.95 (m, 4H), 4.70 (d, 1H, J11.4 Hz),

4.44 (d, 1H, J11.5 Hz), 4.09 (d, 1H, J9.2 Hz), 3.79 (m,

10150

H. Fujioka et al. / Tetrahedron 56 (2000) 10141±10151

3f. [a]³_D¹28.58 (c 0.38, CHCl₃); ¹H NMR d 7.35±7.29 (m,

5H), 4.60 (d, 2H, J11.6 Hz), 4.55 (d, 2H, J11.6 Hz),

3.95±3.80 (m, 1H), 3.42±3.26 (m, 1H), 1.98 (s, 1H),

1.62±1.27 (m, 8H), 0.96±0.88 (m, 6H); ¹³C NMR d

128.43, 127.82, 127.71, 82.14, 71.92, 71.47, 34.13, 30.84,

19.41, 19.09, 14.23, 14.14; Anal. Calcd for C₁₅H₂₄O₂: C,

76.23; H, 10.23. Found: C, 76.41; H, 10.14.

137.97, 136.30, 135.98, 133.87, 133.41, 129.56, 129.38,

128.19, 128.09, 127.57, 127.51, 217.44, 127.31, 127.22,

108.21, 77.22, 76.30, 73.53, 72.99, 72.76, 71.38, 70.26,

52.22, 51.27, 49.04, 45.82, 44.82, 36.21, 27.05, 21.17,

19.39; FAB-HRMS m/z Calcd for C₄₄H₅₄O₅Si: 690.3734

(M¹). Found: 690.3740 (M¹).

14B. ¹H NMR d 8.17±7.19 (m, 15H), 6.17 (dd, 1H, J3.0,

5.6 Hz), 6.00 (dd, 1H, J3.0, 5.6 Hz), 5.61±5.58 (m, 1H),

4.56±3.53 (m, 4H), 4.18±3.69 (m, 7H), 3.28 (s, 3H), 2.76

(brs, 1H), 2.34 (brs, 1H), 1.89±1.84 (m, 1H), 1.47±1.18 (m,

5H), 1.11 (d, 1H, J6.6 Hz); ¹³C NMR d 165.73, 138.22,

138.04, 137.99, 134.47, 133.57, 132.90, 130.51, 130.22,

129.70, 128.82, 128.27, 127.69, 127.55, 127.51, 107.94,

74.72, 73.39, 73.39, 73.28, 73.01, 69.78, 68.16, 52.27,

50.96, 49.00, 45.90, 44.76, 36.16, 21.10, 20.97, 14.14;

HRMS m/z Calcd for C₃₅H₄₀O₆: 556.2823 (M¹). Found:

556.2824 (M¹).

1

3g. [a]³_D¹117.08 (c 0.01, CHCl₃); H NMR d 7.35±7.25

(m, 15H), 4.72±4.52 (m, 6H), 4.00±3.86 (m, 1H), 3.78±

3.75 (m, 1H), 3.71±3.59 (m, 4H), 2.59 (d, 1H, J4.9 Hz),

3.28 (dd, 1H, J3.3, 5.6 Hz), 2.05±1.87 (m, 3H), 1.04±0.90

(m, 12H); ¹³C NMR d 128.39, 128.34, 127.89, 127.82,

127.75, 127.66, 78.17, 77.22, 73.51, 73.41, 72.62, 70.98,

70.75, 70.14; Anal. Calcd for C₂₅H₂₈O₄: C, 76.50; H, 7.19.

Found: C, 76.77; H, 7.33.

3h. [a]³_D⁰22.598 (c 0.54, CHCl₃); H NMR d 7.37±7.25

1

(m, 5H), 4.60 (d, 2H, J4.3 Hz), 3.52 (dd, 1H, J4.0,

5.6 Hz), 3.28 (dd, 1H, J3.3, 5.6 Hz), 2.05±1.87 (m, 3H),

1.04±0.90 (m, 12H), ¹³C NMR d 128.36, 127.57, 84.44,

76.17, 73.60, 29.24, 28.92, 20.99, 19.73, 17.61, 17.25;

Anal. Calcd for C₂₅H₂₄O₂: C, 76.23; H, 10.23. Found: C,

75.99; H, 10.05.

1

14C. H NMR d 7.34±7.20 (m, 12H), 6.85±6.80 (m, 2H),

6.13 (dd, 1H, J3.3, 5.6 Hz), 5.95 (dd, 1H, J2.6, 5.6 Hz),

4.61±4.45 (m, 6H), 4.03 (d, 1H, J9.2, Hz), 3.92±3.80 (m,

2H), 3.79 (s, 3H), 3.74±3.65 (m, 4H), 3.29 (s, 3H), 2.76 (brs,

1H); 2.33 (brs, 1H), 1.88±1.83 (m, 1H), 1.47±1.18 (m, 5H),

1.11 (d, 1H, J6.3 Hz); ¹³C NMR d 159.15, 138.11, 133.66,

129.34, 128.27, 127.73, 127.58, 127.49, 127.46, 113.60,

108.34, 78.31, 73.23, 72.35, 70.12, 69.87, 55.24, 51.97,

51.07, 49.02, 45.82, 44.84, 36.14, 21.15; FAB-HRMS m/z

Calcd for C₃₆H₄₄O₆: 572.3138 (M¹). Found: 572.3136

(M¹).

1

3i. [a]²_D⁷145.88 (c 0.30, CHCl₃); H NMR d 7.36±7.29

(m, 5H), 5.58 (m, 2H), 4.65 (d, 1H, J12.1 Hz), 4.57 (d, 1H,

J11.9 Hz), 4.10 (brs, 1H), 3.68 (m, 1H), 2.31 (brs, 4H),

2.17 (d, 1H, J4.0 Hz); ¹³C NMR d 138.44, 128.45, 127.69,

127.58, 123.83, 123.68, 75.89, 70.37, 66.76, 31.59, 27.21;

Anal. Calcd for C₁₃H₁₆O₂: C, 76.44; H, 7.90. Found: C,

76.31; H, 8.06.

15A. [a]³_D⁰114.48 (c 0.93, CHCl₃); ¹H NMR d 7.68±7.10

(m, 20H), 4.49 (d, 1H, J11.9 Hz), 4.44 (d, 1H, J

11.9 Hz), 4.26 (d, 1H, J11.6 Hz), 4.19 (d, 1H, J

11.9 Hz), 4.00 (m, 1H), 3.94±3.89 (m, 1H), 3.65±3.56 (m,

2H), 3.47 (d, 2H, J4.3 Hz), 2.61 (d, 1H, J4.6 Hz), 1.02

(s, 9H); ¹³C NMR d 135.99, 135.80, 129.70, 129.54, 128.34,

128.19, 127.75, 127.60, 127.55, 127.42, 73.26, 73.01, 72.78,

72.26, 71.39, 71.12, 26.97, 19.41; Anal. Calcd for

C₃₄H₄₀O₄Si: C, 75.52; H, 7.46. Found: C, 75.59; H, 7.54.

3j. [a]²_D⁰25.98 (c 0.34, CHCl₃); ¹H NMR d 7.35±7.25 (m,

5H), 5.63 (m, 2H), 4.61 (d, 1H, J11.9 Hz), 4.52 (d, 1H,

J11.7 Hz), 4.06 (brs, 1H), 3.73 (dd, 1H, J8.8, 4.0 Hz),

2.60 (m, 2H), 2.08±1.71 (m, 7H); ¹³C NMR d 130.03,

129.36, 128.36, 127.49, 127.44, 82.37, 73.69, 71.32,

32.49, 28.81, 22.82, 22.25; Anal. Calcd for C₁₅H₂₀O₂: C,

77.55; H, 8.68. Found: C, 77.55; H, 8.80.

1

3k. [a]²_D⁰157.68 (c 0.93, CHCl₃); H NMR d 7.36±7.25

15B. [a]³_D⁰118.78 (c 1.79, CHCl₃); ¹H NMR d 7.91±7.09

(m, 15H), 5.21±5.15 (m, 1H), 4.48±4.36 (m, 4H), 4.11±

4.07 (m, 1H), 3.81±3.67 (m, 2H), 3.53±3.42 (m, 2H), 2.71

(brs, 1H); ¹³C NMR d 165.82, 137.81, 137.66, 133.10,

129.97, 129.78, 128.37, 127.76, 127.67, 127.60, 73.44,

73.33, 73.03, 70.68, 69.88, 68.88; Anal. Calcd for

C₂₅H₂₆O₅: C, 73.87; H, 6.45. Found: C, 73.59; H, 6.59.

(m, 5H), 5.91±5.74 (m, 2H), 5.42±5.19 (m, 4H), 4.66 (d,

1H, J11.9 Hz), 4.41 (d, 1H, J11.9 Hz), 4.23 (brs, 1H),

3.85 (dd, 1H, J4.1, 7.8 Hz), 2.28 (d, 1H, J5.3 Hz), ¹³C

NMR d 136.24, 134.21, 128.39, 127.75, 127.67, 120.14,

116.75, 83.06, 74.50, 70.33.

1

3l. [a]²_D⁰214.28C (c 1.48, CHCl₃); H NMR d 7.39±7.22

(m, 5H), 5.88±5.76 (m, 2H), 5.08±4.95 (m, 4H), 4.61 (d,

1H, J11.6 Hz), 4.53 (d, 1H, J11.4 Hz), 3.85 (m, 1H),

3.39 (m, 1H), 2.30±2.03 (m, 5H), 1.76±1.48 (m, 4H); ¹³C

NMR d 137.8, 138.8, 137.9, 128.8, 128.5, 128.3, 115.0,

81.0, 77.4, 71.5, 34.7, 33.5, 32.1, 29.7; MS (EI) m/z 260

(M¹); HRMS Calcd for C₁₇H₂₄O₂: 260.1776 (M¹). Found:

260.1776 (M¹).

15C. [a]³_D⁰118.48 (c 0.50, CHCl₃); ¹H NMR d 7.36±7.24

(m, 10H), 7.21±7.17 (m, 2H), 6.90±6.81 (m, 2H), 4.64±

4.47 (m, 6H), 3.96±3.80 (m, 1H), 3.78 (s, 3H), 3.77±3.72

(m, 1H), 3.68±3.56 (m, 4H), 2.60 (d, 1H, J5.5 Hz); ¹³C

NMR d 157.50, 138.13, 138.01, 130.40, 129.52, 128.36,

127.78, 127.71, 127.64, 113.73, 77.65, 73.46, 73.35,

72.20, 70.96, 70.73, 70.14, 55.24; Anal. Calcd for

C₂₆H₃₀O₅: C, 73.91; H, 7.16. Found: C, 73.63; H, 7.25.

Data for the compounds in Scheme 10

HPLC analysis data for 3a±h and 15B,C

14A. ¹H NMR d 7.72±7.07 (m, 20H), 6.14 (dd, 1H, J3.0,

5.6 Hz), 5.93 (dd, 1H, J2.6, 5.6 Hz), 4.42±3.48 (m, 11H),

3.25 (s, 3H), 2.71 (brs, 1H), 2.34 (brs, 1H), 1.84±1.19 (m,

4H, CH₂), 1.13±0.94 (m, 12H); ¹³C NMR d 138.47, 138.33,

Ee values of the optically active 3a±h shown in Table 2 and

15B,C in Scheme 10 were determined by comparison with

their racemic ones using Daicel Chiralpak AD as a chiral

H. Fujioka et al. / Tetrahedron 56 (2000) 10141±10151

10151

Compound

Conditions

Retention time (min)

(^) - 3a

(^) - 3b

(^) - 3c

(^) - 3d

(^) - 3e

(^) - 3f

(^) - 3g

(^) - 3h

(^) - 3I

(^) - 3j

(^) - 3k

(^) - 3l

(^) - 15B

(^) - 15C

Hexane/i-PrOH93/7, 0.5 mL/min ¯ow rate

Hexane/i-PrOH98/2, 0.4 mL/min ¯ow rate

Hexane/i-PrOH96/4, 0.8 mL/min ¯ow rate

Hexane/i-PrOH97/3, 0.5 mL/min ¯ow rate

Hexane/i-PrOH93/7, 0.5 mL/min ¯ow rate

Hexane/i-PrOH97/3, 0.9 mL/min ¯ow rate

Hexane/i-PrOH93/7, 0.35 mL/min ¯ow rate

Hexane/i-PrOH95/5, 1.0 mL/min ¯ow rate

Hexane/i-PrOH97/3, 0.8 mL/min ¯ow rate

Hexane/i-PrOH98/2, 0.8 mL/min ¯ow rate

Hexane/i-PrOH95/5, 1.0 mL/min ¯ow rate

Hexane/i-PrOH95/5, 0.8 mL/min ¯ow rate

Hexane/i-PrOH95/5, 1.0 mL/min ¯ow rate

14.8, 16.1; (14.8)

14.9, 16.1; (14.9)

29.5, 33.3; (34.0)

27.5, 29.5; (27.9)

20.8, 22.1; (20.8)

14.2, 15.1; (13.9)

48.6, 53.3; (54.4)

20.6, 22.3; (21.0)

11.4, 12.0; (11.5)

17.3, 18.7; (16.7)

13.8, 15.1; (14.5)

7.45, 8.13; (7.42)

54.2, 63.0; (62.4)

32.7, 41.1; (41.6)

104. (i) Harada, T.; Wada, I.; Oku, A. J. Org. Chem. 1989, 54,

2599±2605. For recent examples for desymmetrization of

s-symmetric diols with a chiral reagent, see: (j) Yamada, S.;

Katsumata, H. Chem. Lett. 1998, 995±996. (k) Appelt, A.; Willis,

A. C.; Wild, S. B. J. Chem. Soc., Chem. Commun. 1988, 938±940.

(l) Mukaiyama, T.; Tomioka, I.; Shimizu, M. Chem. Lett. 1984,

49±52. (m) Mukaiyama, T.; Tanabe, Y.; Shimizu, M. Chem. Lett.

1984, 401±404. (n) Nara, M.; Terashima, S.; Yamada, S.

Tetrahedron 1980, 36, 3161±3170. For recent examples for

desymmetrization with chiral sources, see: (o) Oriyama, T.; Imai,

K.; Hosoya, T.; Sano, T. Tetrahedron Lett. 1998, 39, 397±400.

(p) Vedejs, E.; Daugulis, O.; Diver, S. T. J. Org. Chem. 1996,

61, 430±431. (q) Ishihara, K.; Kubota, M.; Yamamoto, H. Synlett

1994, 611±614. (r) Suzuki, T.; Uozumi, Y.; Shibasaki M. J. Chem.

Soc., Chem. Commun. 1991, 1593±1595. (s) Ichikawa, J.; Asami,

M.; Mukaiyama, T. Chem. Lett. 1984, 949±952.

column (UV detector: at 259 nm for benzyl compounds

3a±3l, at 227 nm for benzoyl ester 15B, and at 275 nm for

4-methoxybenzyl ether 15C) at 248C. Retention times

shown by the optically active ones are written in the

parenthesis.

X-Ray experimental data of 10b

C₁₃H₂₁BrO₃: M 305.20, crystal size 0.40£0.40£0.30 mm³,

monoclinic, space group P21/n, a18.275 (3), b9.979 (2),

Ê

Ê ³

c7.703 (2) A, b101.33 (1), V1377.4 (4) A , Z4,

D_calc1.47 g/cm³, m (Cu, K-a) 37.83 cm²¹, R0.054,

Re¯ection used 2222.

Acknowledgements

3. Fujioka, H.; Nagatomi, Y.; Kitagawa, H.; Kita, Y. J. Am. Chem.

Soc. 1997, 119, 12016±12017.

Financial support from Monbusho (Grant-in-Aid for

Scienti®c Research on Priority Areas, No. 706: Dynamic

Control of Stereochemistry) and Promotion of Science

(No. 10671989) are gratefully acknowledged.

4. Fujioka, H.; Nagatomi, Y.; Kotoku, N.; Kitagawa, H.; Kita, Y.

Tetrahedron Lett. 1998, 39, 7309±7312.

5. For intramolecular haloetheri®cation of ene acetals, see:

(a) Fujioka, H.; Kitagawa, H.; Matsunaga, N.; Nagatomi, Y.;

Kita, Y. Tetrahedron Lett. 1996, 37, 2245±2248. (b) Fujioka, H.;

Kitagawa, H.; Nagatomi, Y.; Kita, Y. J. Org. Chem. 1996, 61,

7309±7315.

References

1. For examples, see: (a) Fadel A.; Arzel, P. Tetrahedron:

Asymmetry 1997, 8, 283±291. (b) Schoffers, E.; Golebiowski,

A.; Johnson, C. R. Tetrahedron 1996, 52, 3769±3826. (c) Theil,

F. Chem. Rev. 1995, 95, 2203±2227. (d) Ban®, L.; Guanti, G.

Synthesis 1993, 1029±1056. (e) Santaniello, E.; Ferraboschi, P.;

Grisenti, P.; Manzocchi, A. Chem. Rev. 1992, 92, 1071±1140.

6. Prepared in three steps: (i) aymmetric Diels±Alder reaction of

the commercially available N-crotonyl-(4S)-isopropyl-2-oxazoli-

dinone and cyclopentadiene according to Evans's method

(Evans, D. A.; Chapman, K. T.; Bisaha, J. J. Am. Chem. Soc.

1988, 110, 1238±1256). (ii) LiAlH₄reduction in THF at room

temperature (97%). (iii) Swern oxidation (73%).

È

(f) Bolando, W.; Frobl, C.; Lorenz, M. Synthesis 1991, 1049±1072.

7. There are some reports showing that acetalization of an

aldehyde and a cis-diol tends to form a cis-acetal as a major

product under kinetic control. For review, see: Clode, D. M.

Chem. Rev. 1979, 79, 491±513.

2. For recent examples for the stereoselective cleavage of the

acetals, see: (a) Kinugasa, M.; Harada, T.; Oku, A. J. Am. Chem.

Soc. 1997, 119, 9067. (b) Davis, A. P. Angew. Chem., Int. Ed. Engl.

1997, 36, 591±594. (c) Maezaki, N.; Sakamoto, A.; Matsumori, Y.;

Tanaka, T.; Iwata, C. Tetrahedron 1996, 52, 6527±6546.

(d) Prasad, K.; Underwood, R. L.; Repic, O. J. Org. Chem. 1996,

61, 384±385. (e) Maezaki, N.; Soejima, M.; Sakamoto, A.;

Sakamoto, I.; Matsumori, Y.; Tanaka, T.; Ishida, T.; In, Y.;

Iwata, C. Tetrahedron: Asymmetry 1996, 7, 29Y.32. (f) Maezaki,

N.; Soejima, M.; Takeda, M.; Sakamoto, A.; Tanaka, T.; Iwata, C.

J. Chem. Soc., Chem. Commun. 1994, 1345Y.1346. (g) Suemune,

H.; Watanabe, K.; Kato, K.; Sakai, K. Tetrahedron: Asymmetry

1993, 4, 1767Y.1770. (h) Harada, T.; Oku, A. Synlett 1994, 95±

8. Naemura, K.; Takeuchi, S.; Hirose, K.; Tobe, Y.; Kaneda, T.;

Sakata, Y. J. Chem. Soc., Perkin Trans. 1 1995, 213±219.

1

9. The ee value of silyl ether 15A was determined by H NMR

analysis of its acetate because 15A was decomposed under the

HPLC analysis conditions.

10. Compound

1 containing its exo-isomer is reported in

(a) Ishihara K.; Gao Q.; Yamamoto H. J. Am. Chem. Soc. 1993,

115, 10412±10413. (b) Howarth J.; Helmchen G.; Kiefer M.

Tetrahedron Lett. 1993, 34, 4095±4096.

Article Doi

Asymmetric desymmetrization of saturated and unsaturated meso-1,2-diols

DOI: 10.1016/S0040-4020(00)00859-0

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Article abstract of DOI:10.1016/S0040-4020(00)00859-0

Full text of DOI:10.1016/S0040-4020(00)00859-0

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