A Convergent Method for the Synthesis of Highly Enantiomerically Enriched Cyclic Silanes with Silicon-Centered Chirality

FEATURE ARTICLE

2725

A Convergent Method for the Synthesis of Highly Enantiomerically Enriched

Cyclic Silanes with Silicon-Centered Chirality

C

hira

l

Cyclic

S

ilanes artin Oestreich,* Ulrike K. Schmid, Gertrud Auer, Manfred Keller¹

Institut für Organische Chemie und Biochemie, Albert-Ludwigs-Universität, Albertstrasse 21, 79104 Freiburg im Breisgau, Germany

Fax +49(761)2036100; E-mail: martin.oestreich@orgmail.chemie.uni-freiburg.de

Received 22 July 2003; revised 25 July 2003

Sommer benefitted from his classical and exceptionally

Abstract: A preparatively straightforward methodology has been

practical multi-gram preparation of the monofunctional-

developed which allows the assembly of silicon-containing car-

bocycles as mixtures of diastereomers with silicon as the sole center

of stereogenic information. One-step construction of the chiral cy-

ized silane 1 (Figure 1) which provides literally any nec-

essary quantity in enantiopure form.^6,7

clic silanes is realized by reaction of equimolar amounts of a dibro-

mide and a chirally modified dichlorosilane under Barbier

conditions giving access to several monofunctionalized 1-sila-

Ph

Si

α-Np

1,2,3,4-tetrahydronaphthalenes and a corresponding phenanthrene

derivative. Facile large scale syntheses of 3-(2-bromoaryl)propyl

bromides as well as dichlorosilanes have been elaborated. This

highly convergent methodology relies on the novel (–)-menthyl-

oxy-substituted dichlorosilanes, which have the chiral auxiliary for

the subsequent optical resolution installed. These enantiopure

dichlorosilanes are useful building blocks for a general and modular

Me

X

1

X

2

(X = functional group)

Figure 1

one-step approach to silanes with silicon-centered chirality since Since silane 1 and congeners thereof in which silicon is

this strategy avoids the linear sequences reported in literature. The

the sole center of chirality are so readily available, a cou-

optical resolution has been exemplarily optimized for the 1-phenyl-

ple of research groups have examined potential synthetic

1-sila-1,2,3,4-tetrahydronaphthalene derivative and the absolute

applications of these reagents for efficient chirality trans-

configuration has been established by X-ray crystallography. The

fer from silicon to carbon.⁸Though, asymmetric induction

chiral auxiliary is stereospecifically displaced by simple reduction

was almost without exception⁹low as exemplified by the

providing the highly enantioenriched silane (er = 98:2) which is

enantiospecifically chlorinated as verified by a Walden inversion at

allylation^10a(1, X = CH₂CH = CH₂) of acetals and by the

silicon.

reduction^10b(1, X = H) of alkyl aryl ketones.¹¹These

moderate findings have been rationalized with the nature

of silanes of type 1 where asymmetric induction originates

in the steric difference between a phenyl (Ph) and an -

naphthyl ( -Np) group. Consequently, efforts for the re-

finement of the above reactions would have demanded the

enantioselective synthesis of several novel chiral silanes

with a significantly modified constitution. The task of

producing a variety of these compounds appears to be the

dilemma that is still preventing the quest for stereoselec-

tive silicon to carbon chirality transfer reactions⁸involv-

ing silanes with silicon-centered chirality.

Key words: Grignard reactions, cyclizations, enantiomeric resolu-

tion, heterocycles, silicon

Introduction

It is a logical consequence that the successful establish-

ment of novel reagents in organic chemistry correlates

with the ease of its accessibility and – consequently –

availability. It is probably due to this, that there exists a

scarcity of synthetic applications of non-racemic silanes,

which incorporate an asymmetrically substituted silicon

atom.^2,3

The practicability of synthesizing 1 relies on the facile

optical resolution of the corresponding diastereomeric

(–)-menthyl ethers by crystallization whereby the high

crystallinity of 1 [X = (–)-menthyloxy] is attributed to the

presence of the -naphthyl ( -Np) group. Combining

(–)-menthyloxy and -naphthyl ( -Np) as substituents at

silicon has only been successfully verified for a handful of

derivatives whereas crystallization proved to be tedious if

not impossible for most substrates.¹²Alternatively, enzy-

matic methods have been developed to circumvent diffi-

culties with crystallization.¹³However, Bienz has

introduced a bioreduction to the preparation of optically

active silanes, which have been solely employed as chiral

auxiliaries in several diastereoselective transformations.¹⁴

The apparent absence of such silicon derivatives in organ-

ic synthesis appears particularly interesting in view of the

pioneering research by Sommer⁴and Corriu,⁵respectively

documented in a series of seminal publications. These el-

egant investigations have illuminated the stereochemical

course of a considerable number of reactions at a stereo-

genic silicon center and permit prediction of the degree of

stereospecifity at silicon of these transformations.^3,4Ulti-

mately, this extensive research programme initiated by

SYNTHESIS 2003, No. 17, pp 2725–2739

x

x.

x

.

2

0

3

Advanced online publication: 21.11.2003

DOI: 10.1055/s-2003-42477; Art ID: Z10903SS

In order to avoid capricious separation of diasteromeric si-

lanes, Jung introduced an optically pure cyclic silane with

2726

M. Oestreich et al.

FEATURE ARTICLE

a binaphthalene backbone without silicon-centered chiral- monofunctionalized 1-sila-1,2,3,4-tetrahydro-naphtha-

ity but with the silicon in a chiral environment.¹⁵Probing lenes. In contrast to all known methods,^4–7our novel

this reagent for the reduction of alkyl aryl ketones resulted methodology discloses the assembly of silicon-containing

only in marginal improvement^10bof the enantiomeric ra- carbocycles and the incorporation of a chiral auxiliary for

tios achieved with 1 (X = H).

the subsequent optical resolution in a single synthetic

step. With the convergence of our strategy we have estab-

lished a modular approach to chiral cyclic silanes.

We have perceived that the stereoselective preparation of

silicon-containing compounds in which silicon is the sole

center of stereochemical information has not been satisfy-

ingly tackled. Consequently, we have started a research

programme directed towards the flexible synthesis of nov-

el highly enantioenriched monofunctionalized cyclic si-

lanes and projected synthetic applications thereof. The

requirements for our target structure have been identified

as incorporation of silicon into a carbocycle and avoid-

ance of reactive sites apart from the silicon center itself

which are met by silanes with a 1-sila-1,2,3,4-tetrahy-

dronaphthalene core A (Scheme 1).¹⁶

Results and Discussion

General Strategy

The construction of achiral 1-sila-1,2,3,4-tetrahydro-

naphthalenes has been the subject of several independent

studies.^19–21As outlined in Scheme 1, we were initially

planning on adopting the general procedure introduced by

Gilman in which a pre-formed dihalide-derived (B) di-

Grignard reagent²²is reacted with an alkyl aryl dichlorosi-

lane (C, X = Bn).^21,23

In this article, we report our investigations towards the de-

velopment of a highly convergent construction of several

Biographical Sketches

Martin Oestreich (middle) was born Wilhelms-Universität Münster in fellowship (1999–2001) as well as an

in Pforzheim/Germany in 1971. He 1999. After two postdoctoral years Emmy Noether ‘Nachwuchsgruppe’

studied chemistry at the Heinrich- with Larry E. Overman at the Univer- (2001–2005) by the Deutsche For-

Heine-Universität

UMIST in Manchester/UK, and the the

Düsseldorf, sity of California, Irvine, he moved to schungsgemeinschaft. His research

Albert-Ludwigs-Universität interests involve the chemistry of or-

Philipps-Universität Marburg where Freiburg and initiated an independent ganosilicon compounds with an

he obtained his diploma under the di- research program. He was awarded a asymmetrically substituted silicon

rection of Paul Knochel in 1996. He Kekulé fellowship (1997–1999) by center and palladium-catalysis in to-

completed his doctoral degree with the Fonds der Chemischen Industrie tal synthesis.

Dieter Hoppe at the Westfälische and an Emmy Noether postdoctoral

Ulrike Schmid (left) was born in diploma in 2003 working in the labo- (TH) under the direction of Stefan

Speyer/Germany in 1978. She stud- ratory of Martin Oestreich. After her Bräse.

ied chemistry at the Albert-Ludwigs- graduation, she has continued her

Universität Freiburg and received her studies at the Universität Karlsruhe

Gertrud Auer (right) was born in the University of Glasgow/UK. After Universität Freiburg where she is

Merzig/Germany in 1978. She stud- obtaining her diploma under the di- currently working towards her doc-

ied chemistry at the Universität Kai- rection of Bernhard Witulski in 2002, toral degree under the direction of

serslautern and spent a semester at she moved to the Albert-Ludwigs- Martin Oestreich.

Synthesis 2003, No. 17, 2725–2739 © Thieme Stuttgart · New York

FEATURE ARTICLE

Chiral Cyclic Silanes

2727

benzylic bromination of 2-bromotoluene (11) with NBS

(11 12), carbon chain elongation of 12 by two carbons

was successfully effected utilizing Meyers metalated

2,4,4-trimethyl-2-oxazoline (13).²⁶Hydrolysis of the ox-

azoline under acidic conditions, reduction of the interme-

diate carboxylic acid, and final conversion of the crude

primary alcohol to the corresponding alkyl bromide pro-

vided dibromide 3 in 49% overall yield (Scheme 3).²⁷

Cl

Si

R

+

X

*

Si

Br Br

R

X

A

B

C

(R = alkyl or aryl)

X = Bn (placeholder for subsequent installation of chiral auxiliary)

X = OR* (direct installation of chiral auxiliary)

Br

a

b-e

Scheme 1 One-step assembly of 1-sila-1,2,3,4-tetrahydronaphtha-

lenes and -phenanthrenes.

82%

49%

(4 steps)

Br

Br Br

3

11

12

Treatment of 3-(2-bromophenyl)propyl bromide (3) with

magnesium at ambient temperature cleanly formed the

corresponding di-Grignard reagent 4²⁴which was subse-

quently reacted with benzyldichlorophenylsilane (5) pro-

viding the desired silicon-containing ring 6 in 85% yield

(Scheme 2). Reductive cleavage of the benzyl group (6 →

7) and in situ etherification with methanol (7 → 9) pro-

ceeded smoothly (Scheme 2).²⁵Unfortunately, all at-

tempts to install a sterically more demanding alcohol such

as (–)-menthol [(–)-8] as a chiral auxiliary have failed (7

→ 10).

Scheme 3 Reagents and conditions: a) NBS, DBPO, CCl₄, ; b) n-

BuLi, 13, THF, –78 °C; 12, THF, –78 °C r.t.; c) 3 N HCl, 100 °C;

d) LiAlH₄, Et₂O, ; e) PBr₃, 100 °C.

Analogously, another dibromide 14 was synthesized

whereby the starting material, 2-bromo-1-methylnaphtha-

lene (17), is particularly difficult to access in larger quan-

tities. For that purpose, we modified the reported

procedure²⁸and were able to make 17 in two steps from

1-indanone (15) in moderate yet reproducible yield

(Scheme 4). According to the reaction sequence opti-

mized for the preparation of 3 (Scheme 3), the final five

steps (17 → 18 → 14) afforded 14 in yields similar to

those obtained for 3.

a

b

Si

Ph Bn

85%

Mg

MgBr₂

Br Br

3

4

6

a

b

O

68%

38%

(73%

(30% of 15

Br

c

conversion)

15

reisolated)

16

17

Si

Ph OR

80% (for 9)

<5% (for 10)

Ph

H

7

9 (R = Me)

10 (R = (−)-Menthyl)

c

d-g

37%

Br

76%

(90%

conversion)

Scheme 2 Reagents and conditions: a) Mg, THF, r.t.; b) benzyldi-

chlorophenylsilane (5), THF, r.t.

menthol [(–)-8], PhMe, r.t.

(4 steps)

Br

Br Br

; c) H₂, Pd/C, MeOH or (–)-

18

14

Scheme 4 Reagents and conditions: a) MeLi, Et₂O, ; b) CHBr₃, t-

BuOK, Et₂O, r.t.; c) NBS, DBPO, CCl₄, ; d) n-BuLi, 2,4,4-trime-

This discouraging observation led us to consider an alter-

native, even more convergent route to access substrates

such as A [X = (–)-menthyloxy] (Scheme 1). We envis-

aged the direct electrophilic substitution of the di-Grig-

thyl-2-oxazoline (13), THF, –78 °C; 18, THF, –78 °C

r.t.; e) 3 N

HCl, 100 °C; f) LiAlH₄, Et₂O, ; g) PBr₃, 100 °C.

Preparation of Chiral Dichlorosilanes

nard reagents derived from

B with enantiopure

dichlorosilanes C [X = (–)-menthyloxy] that have the

chiral auxiliary already installed. At that time, we were

well aware that a possible side-reaction could be the dis-

placement of the (–)-menthyloxy residue in C rather than

the two chloride substituents.

The synthesis of the enantiopure dichlorosilanes (–)-19

emerged as extremely facile, by maintaining an etheral so-

lution of the chiral auxiliary (–)-menthol [(–)-8) or (–)-8-

phenylmenthol (–)-21]²⁹and the appropriate trichlorosi-

lane 20³⁰in the presence of urea for a couple of hours at

r.t. (Equation 1).³¹Subsequent fractional high vacuum

distillation provided multi-gram quantities of (–)-19 ei-

ther as viscous oils or colorless solids in yields ranging

from 40–68%.

Preparation of Dibromides

The large scale synthesis of 3-(2-bromophenyl)propyl

bromide (3) was accomplished in five steps with only two

distillations for purification in good overall yield. After

Synthesis 2003, No. 17, 2725–2739 © Thieme Stuttgart · New York

2728

M. Oestreich et al.

FEATURE ARTICLE

(−)-8 or (−)-21

Cl

Si

R O

Cl

urea

Si

R O

Si

Et₂O, rt

R Cl

+

40% (for (−)-19a)

63% (for (−)-19b)

49% (for (−)-19c)

68% (for (−)-19d)

Br Br

3 or 14

20a (R = Me)

20b (R = Ph)

20c (R = α-Np)

R'

(−)-19

(−)-19a (R = Me, R' = H)

(−)-19b (R = Ph, R' = H)

(−)-19c (R = α-Np, R' = H)

(−)-19d (R = Ph, R' = Ph)

see Table 1

for details

a

Equation 1

Stereoselective Synthesis of Cyclic Silanes

Si

R O

+

Si

R O

Having accomplished operable multi-gram syntheses of

building blocks B and C [X = (–)-menthyloxy] we under-

took orientating experiments for the assembly of 1-sila-

1,2,3,4-tetrahydronaphthalenes A (Scheme 1). These pri-

mary studies clarified that pre-formation of the di-Grig-

nard reagent from 3, addition of a dichlorosilane (–)-19

results in the formation of only trace amounts (!) of de-

sired products of the general structure A [X = (–)-menth-

H

R'

(SiS*)-22 (from 3)

(SiS*)-24 (from 14)

(SiR*)-22 (from 3)

(SiR*)-24 (from 14)

Scheme 5 Reagents and conditions: a) Mg, THF, . Descriptors for

the configuration at silicon may be subject to change in dependence

on the priority rules of the CIP system. See Table 1 and the experi-

mental section for details.

yloxy] contrasting our findings for the cyclization 4

6

(Scheme 2).

Interestingly, flash chromatography on silica gel using hy-

drocarbons as solvents because of the low polarity of the

reaction products furnished silanes 22 only in poor isolat-

ed yields. Extensive investigations revealed a correlation

between the yield and the contact time of the crude mate-

rial with silica gel.³⁴We also observed that the suscepti-

bility to decomposition of silanes 22 is dependent on the

steric bulk around the silicon center ( -Np > Ph > Me)

with (SiRS)-22c being most unstable. However, when pu-

rified by flash chromatography on silica gel utilizing sol-

vent mixtures even with a small proportion of a polar

solvent, the isolated products were contaminated with by-

products but yields had not deteriorated. Rapid filtration

of gram quantities over a relatively small pad of silica gel

provided (SiRS)-22b but not (SiRS)-22c in sufficient puri-

ty. It should be noted that these impurities do not hamper

the subsequent crystallization of (SiRS)-22b!

The so-called Barbier reaction is sometimes a competitive

alternative to the more versatile Grignard reaction.³²Sev-

eral modifications of the Barbier reaction are described in

the literature and they all have in situ rather than pre-for-

mation of an organomagnesium species in common.³³

We decided to deploy a variant where an equimolar mix-

ture of dibromide 3 and a chiral dichlorosilane (–)-19 in

THF is added portionwise to an excess of thermally and

mechanically activated magnesium turnings in THF at re-

flux. Fortunately, analysis of the crude product by TLC

indicated the formation of a major product – supposedly

1

22 – which was also validated by H NMR spectroscopy

showing a diagnostic doublet at ca. 0.40 ppm and ca. 0.60

ppm for each diastereomer (Scheme 5, Table 1).

Table 1 One-Step Synthesis of Chiral Functionalized Cylic Silanes under Barbier Conditions

Entry

Dibromide

Dichlorosilane

( )-19a

R

Cyclic silane

22a

dr^a

Yield (%)^b

1

2

3

4

5

3

Me

Ph

H

50:50

55:45

58:42

23

( )-19b

H

22b

31/60^c

32

3

( )-19c

-Np

H

22c

3

( )-19d

Ph

22d

60:40

37

d

14

( )-19d

24d

16

^aThe diastereomeric ratio (dr) was determined from the ¹H NMR spectra of the crude products by integration of baseline separated doublets of

the diastereomers at ca. 0.40 ppm and ca. 0.60 ppm (see Experimental Section for assignment of signals).

^bIsolated yield after reversed phase flash chromatography of analytically pure product. All compounds gave correct elemental analyses.

^cIsolated yield (ca. 95% purity) after rapid flash filtration on silica gel.

^dNo baseline separation of signals of diastereomers.

Synthesis 2003, No. 17, 2725–2739 © Thieme Stuttgart · New York

FEATURE ARTICLE

Chiral Cyclic Silanes

2729

In order to overcome these problems, we decided to at-

tempt small-scale purification by preparative flash chro-

matography on reversed phase silica gel using MeCN–

H₂O solvent mixtures. We were pleased to find that we

were able to isolate the analytically pure target molecules

22 in approximately 30% yield as mixtures of diastereo-

mers (Table 1, entries 1–4). Analogously, we implement-

ed the large-scale separation, which allowed the

purification of up to 10 grams of crude material.³⁵

The yields are acceptable bearing in mind that a dinucleo-

phile and a trielectrophile are present in the reaction mix-

ture with the chloride and (–)-menthyloxy substituents at

silicon functioning as potential leaving groups. The ten-

dency of the (–)-menthyloxy substituent to act as a leav-

ing-group, might even be amplified by the steric

hindrance around the silicon center in 22. This speculation

is supported by isolation and structural characterization

(Figure 2) of by-product 23a formed in the reaction of 3

and (–)-19a (Scheme 6). Due to the small substituent

(R = Me) up to three (–)-menthyloxy groups can be ar-

ranged around the silicon center; the corresponding com-

pounds 23b–d bearing larger substituents (R = Ph and

-Np) were not observed. It should be noted that these re-

actions produce stoichiometric amounts (2 equiv) of mag-

nesium halides, which might also displace an alkoxide at

silicon under the forcing conditions of the Barbier reac-

tion. The liberated alkoxide itself might in turn substitute

a halide group; if this process occurs even twice, the tri-

menthoxy derivative 23a is formed (Scheme 6).

Figure 2 Crystal structure of 23a.

Optical Resolution

As mentioned in the introductory part of this article, sep-

aration of diastereomeric silanes by crystallization is a

challenging task. Nevertheless, our synthetic approach to

chiral silanes also relies on crystallizing one diastereomer

subsequent to the convergent one-step construction of the

cyclic silane with the chiral auxiliary installed. Admitted-

ly, crystallization needed quite a bit of optimization and

practice as exemplified and demonstrated for the optical

resolution of (SiRS)-22b (Equation 2).

Overall, the preparation of the 1-sila-1,2,3,4-tetrahy-

dronaphthalenes (Scheme 5) is practical in the case of the

1-aryl-substituted derivatives 22b–d (Table 1, entries 2–

4). The assembly of the 1-sila-1,2,3,4-tetrahydrophenan-

threne 24d was somewhat less efficient (Scheme 5,

Table 1, entry 5).

*

Si

Ph O

pentane

−78 °C

H

60%

(based on one

diastereomer after

two recrystallizations)

(SiRS)-22b

dr = 55:45

(SiS)-22b

dr > 96:4

Cl

Si

Me O

+

Equation 2

Br Br

3

(−)-19a

However, if the solution of the diastereomeric silanes

(SiRS)-22b is set at a fixed concentration (see experimen-

tal part for details), crystallization is feasible on any scale

(milligram up to gram quantities). The relative and abso-

lute configuration of the highly diastereoenriched silane

(SiS)-22b was unambiguously confirmed by an X-ray

crystal structure analysis (Figure 3).

23% for 22a

~15% for 23a

a

+

*

Si

O

Me O

Si

Me

O

H

Stereospecific Reduction and Chlorination

The stereospecifity of the reduction of the silicon–oxygen

bond using alanes and aluminum hydrides were thorough-

ly examined by Sommer.^4,5,36These reactions proceeded

highly enantiospecifically with retention of configuration

at the silicon center. We were able to confirm the predict-

ed high stereospecifity, reduction of our substrate with

(SiRS)-22a

23a

Scheme 6 Reagents and conditions: a) Mg, THF,

.

Synthesis 2003, No. 17, 2725–2739 © Thieme Stuttgart · New York

2730

M. Oestreich et al.

FEATURE ARTICLE

There is a gradual change of the stereochemistry from in-

version to retention when angle strain at silicon is in-

creased. An angle [(C_aryl–Si–C_alkyl)] of 105.6° – as

measured for (SiRS)-25c – indicates that in comparison to

the acyclic silane 1 (109.3°), retention is already slightly

more favored than inversion. These insights might also

apply to the related substrate (SiR)-25b, which has been

synthesized in enantiomerically enriched form.

Figure 3 Crystal structure of (SiS)-22b.

Figure 4 Crystal Structure of (SiRS)-25c.

DIBAL in CH₂Cl₂afforded (SiR)-25b in 89% yield as a

colorless liquid [Equation 3, (SiS)-22b → (SiR)-25b].

Chlorination of (SiR)-25b (er 97:3) with chlorine afforded

(SiS)-26b quantitatively with high enantiospecifity

(Scheme 7). The absolute configuration of (SiS)-26b was

unambigously assigned as S by reduction with LiAlH₄,

which proceeds with inversion of configuration at sili-

con.^7aCombining both transformations, the resulting

Walden cycle furnished (SiS)-25b with inverted absolute

configuration with an enantiomeric ratio of 6:94.

Si

Ph O

DIBAL

Si

CH₂Cl₂

−78 °C → r.t.

H

Ph

H

(SiR)-25b

89%

er = 98:2

(100%

retention)

(SiS)-22b

dr > 96:4

a

b

Equation 3

Si

Ph H

Si

Ph Cl

Si

Ph H

99%

55%

(100%

retention)

(94%

inversion)

(SiR)-25b

er = 97:3

(SiS)-26b

er = 97:3

(SiS)-25b

er = 6:94

The diastereomeric ratio (dr > 96:4) of the silyl ether

(SiS)-22b determined from the ¹H NMR spectra is in ac-

cordance with the enantiomeric ratio (er 98:2) of (SiR)-

25b measured by HPLC (see Experimental Part for de-

tails). The absolute configuration of (SiR)-25b was de-

duced from its precursor (SiS)-22b based on the strong

literature precedence suggesting a stereoretentive mecha-

nism for the reduction.

Scheme 7 Reagents and conditions: a) Cl₂, CCl₄, r.t.; b) LiAlH₄,

Et₂O, 0 °C r.t.

Conclusion

In summary, we have reported the facile synthesis of four

chirally modified dichlorosilanes (–)-19a–d which were

incorporated into cyclic silanes 22/24 by reaction with

3-(2-bromoaryl)propyl bromides 3/14 under Barbier con-

ditions. The resulting cyclization products are generated

as diastereomeric mixtures (dr 50:50 up to 60:40), which

are separable by crystallization as exemplified for com-

pound (SiS)-22b (x-ray). The chiral auxiliary is stereospe-

cifically removed by a simple reduction affording the title

compound (SiR)-25b in excellent yield.

The slightly diastereomerically enriched (SiRS)-22c

(dr 58:42) with the sterically more demanding -naphthyl

( -Np) substituent has also been reduced furnishing the

almost racemic silane (SiRS)-25c (er = 54:46) in 36%

yield.

Although we were not pursuing the chemistry of this sub-

strate any further, we were able to crystallize (SiRS)-25c

(Figure 4).³⁷The structural characterization of (SiRS)-25c

is indeed of some relevance since it allows determination

of the bond angle of both endocyclic carbons and silicon

[(C_aryl–Si–C_alkyl)]. This angle value correlates with the an-

gle strain at silicon and has been shown by Corriu and co-

workers to govern the stereochemical outcome of nucleo-

(or electrophilic) displacements at the silicon center.⁵

We think that this one-step assembly of chiral cyclic si-

lanes demonstrates the usefulness of (–)-19 as a chiral sil-

icon source. Variation of the dibromide reagent would

allow a modular approach to an enormous repertory of tai-

Synthesis 2003, No. 17, 2725–2739 © Thieme Stuttgart · New York

FEATURE ARTICLE

Chiral Cyclic Silanes

2731

(200 mL). To this soln, benzylmagnesium chloride (191 mL, 1.0

equiv, 1.045 M in Et₂O) was added dropwise at r.t. The reaction

mixture was maintained at this temperature for 38 h. In order to pre-

cipitate most of the magnesium salts, the solvent was distilled off

under vigorous stirring and the residue was suspended in pentane

(150 mL). The resulting slurry was filtered using Schlenk tech-

niques and the filter cake was washed with pentane (3 × 25 mL).

The soln was concentrated under reduced pressure and transferred

to a smaller Schlenk flask. Distillation (98 °C at 7.0 × 10^–1mbar)

provided compound 5 (35.2 g, 66%)⁴⁰as a colorless liquid. This par-

ticular dichlorosilane cannot be obtained in analytically pure form

since it is contaminated with minor amounts of dihydrostilbene re-

sulting from the preparation of the benzylic Grignard reagent.

lor-made cyclic silanes. With this novel flexible access at

hand, several reactions involving chiral silanes need to be

(re-)investigated. Further improvements to the synthesis

of enantiomerically enriched cyclic silanes and synthetic

applications thereof are currently under investigation in

our laboratory.

Reagents obtained from commercial suppliers were used without

further purification unless otherwise noted. All reactions were per-

formed in flame-dried glassware under a static pressure of argon.

Liquids were transferred with syringes or double-ended needles and

all solvents were dried and distilled prior to use following standard

procedures. Solvents (cyclohexane, t-butylmethylether (TBME),

and EtOAc) for extractions and chromatography were distilled be-

fore use. Analytical thin-layer chromatography was performed on

silica gel SIL G-25 glass plates, flash chromatography on silica gel

(40–63 m, 230–400 mesh, ASTM), and reversed-phase flash chro-

matography on reversed-phase silica gel (polygoprep, 100-50, C18)

using the indicated solvents – all stationary phases were obtained

from Macherey-Nagel/Germany. High vacuum distillations (10^–5

mbar) were performed using standard glassware and an Edwards

turbo molecular pump. ¹H and ¹³C NMR spectra were recorded in

CDCl₃on Bruker AM 400 and DRX 500 instruments. Analytical

HPLC analysis on a chiral stationary phase using a Daicel Chiralcel

OD-H column (n-heptane–i-PrOH solvent mixtures) provided base-

line resolution of enantiomers.³⁸

IR (film): 3060 (m), 3029 (m), 2894 (w), 2360 (w), 1600 (m), 1494

(s), 1453 (m), 1430 (s), 1396 (w), 1336 (w), 1306 (w), 1211 (s),

1166 (m), 1118 (s), 1059 (m), 1030 (w), 998 (w), 907 (w), 819 (m),

769 (s), 739 (s), 696 (s) cm^–1.

¹H NMR (500 MHz, CDCl₃): = 2.86 (s, 2 H), 7.09 (d, J = 7.7 Hz,

2 H), 7.17–7.21 (m, 1 H), 7.22–7.27 (m, 2 H), 7.43 (dd, J = 7.5, 7.5

Hz, 2 H), 7.52 (dddd, J = 7.4, 7.4, 1.3, 1.3 Hz, 1 H), 7.64 (dd,

J = 8.0, 1.3 Hz, 2 H) (contaminated with traces of dihydrostilbene).

¹³C NMR (125 MHz, CDCl₃): = 30.4, 125.9, 128.3, 128.5, 129.3,

131.6, 131.8, 133.8, 133.9 (contaminated with traces of dihydrostil-

bene).

LRMS (EI): m/z = 266/268 [M⁺], 175/177 [(M – Bn)⁺], 91 [Bn⁺], 77

[Ph⁺].

HRMS (EI): m/z calcd for C₁₃H₁₂Cl₂Si, 266.00854; found,

266.00848.

1-Bromo-2-(3-bromopropyl)benzene (3)

Compound 3 was prepared following the four-step sequence de-

scribed for 14. A soln of 2,4,4-trimethyl-2-oxazoline (13) (9.40 mL,

73.1 mmol) and THF (70 mL) was treated with n-BuLi (60.0 mL,

84.0 mmol, 1.15 equiv, 1.4 M in hexane) at –78 °C. Addition of 1-

bromo-2-(bromomethyl)benzene (12) (20.0 g, 80.0 mmol, 1.14

equiv) and THF (30 mL) was followed by the usual work-up after

18 h. The residue was hydrolyzed with 3 N HCl (64 mL) affording

the crude carboxylic acid which was used in the next step without

further purification. The subsequent reduction was conducted using

LiAlH₄(4.90 g, 129 mmol, 1.5 equiv) and Et₂O (130 mL). To this

suspension, a soln of the carboxylic acid (19.7 g, 86.0 mmol) and

Et₂O (86 mL) was added dropwise. The reaction was terminated as

described after 18 h. Final bromination of the crude primary alcohol

(15.8 g, 73.5 mmol) was achieved employing PBr₃(5.20 mL, 54.7

mmol, 0.75 equiv) to which the alcohol was added over a period of

1.5 h and then maintained for 3 h at 100 °C. Usual work-up fur-

nished the crude primary bromide. Distillation (103–106 °C at 7.0

× 10^–1mbar)³⁹provided dibromide 3 (10.1 g, 49% over four steps)

as a colorless, slightly cloudy liquid.

1-Benzyl-1-phenyl-1-sila-1,2,3,4-tetrahydronaphthalene (6)

A three-necked 250 mL flask equipped with a reflux condenser, a

pressure-equalizing dropping funnel, and a magnetic stir bar was

charged with magnesium turnings (1.01 g, 41.4 mmol, 2.50 equiv).

After flame-drying the flask under argon, the magnesium turnings

were vigorously stirred for several hours. To the thermally and me-

chanically activated magnesium turnings was added THF (5 mL).

Subsequently, a soln of 1-bromo-2-(3-bromopropyl)benzene (3)

(4.60 g, 16.5 mmol) and THF (70 mL) was added dropwise with the

internal temperature kept below 40 °C. After complete addition, the

reaction mixture was maintained at r.t. for 15 h. The resulting green

soln was transferred via cannula to a soln of benzyldichlorophenyl-

silane (5) (3.29 g, 12.4 mmol, 0.75 equiv) and THF (10 mL). After

heating at reflux for 2.5 h and cooling back to r.t., the reaction mix-

ture was poured into sat. aq NH₄Cl (50 mL). The aq phase was ex-

tracted with TBME (3 × 150 mL) and the combined organic layers

were back-extracted with H₂O (50 mL). Drying (MgSO₄), filtration,

removal of the volatiles under reduced pressure, and purification of

the crude product by flash chromatography on silica gel (cyclohex-

ane–Et₃N, 50:1) provided the title compound 6 (3.32 g, 85%) as a

colorless solid.

IR (film): 3060 (m), 3025 (w), 2959 (m), 2862 (w), 1918 (vw), 1566

(w), 1494 (w), 1470 (s), 1438 (s), 1352 (vw), 1271 (m), 1239 (s),

1206 (w), 1024 (s), 962 (w), 852 (w), 810 (w), 751 (s), 699 (m), 658

(m) cm^–1.

¹H NMR (500 MHz, CDCl₃): = 2.18 (tt, J = 7.1, 7.1 Hz, 2 H), 2.90

(t, J = 7.4 Hz, 2 H), 3.42 (t, J = 6.7 Hz, 2 H), 7.08 (ddd, J = 7.9, 6.6,

2.8 Hz, 1 H), 7.25 (m, 2 H), 7.54 (d, J = 7.7 Hz, 1 H).

Mp 61 °C (cyclohexane); R_f0.42 (cyclohexane).

IR (film): 3059 (m), 3027 (m), 3000 (m), 2932 (s), 2859 (m), 2371

(w), 2325 (w), 1597 (m), 1493 (m), 1425 (m), 1411 (w), 1271 (vw),

1212 (w), 1153 (m), 1112 (m), 1076 (w), 977 (w) cm^–1.

¹H NMR (500 MHz, CDCl₃): = 1.10 (dd, J = 6.8, 6.8 Hz, 2 H),

1.68–1.76 (m, 1 H), 1.81–1.89 (m, 1 H), 2.56 (ddd, J = 16.9, 9.0, 3.1

Hz, 1 H), 2.61 (d, J = 13.8 Hz, 1 H), 2.67 (d, J = 13.9 Hz, 1 H), 2.71

(ddd, J = 16.2, 8.2, 3.0 Hz, 1 H), 6.89 (d, J = 7.0 Hz, 2 H), 7.05 (dd,

J = 7.4, 7.4 Hz, 1 H), 7.08–7.15 (m, 3 H), 7.22 (dd, J = 7.4, 7.4 Hz,

1 H), 7.30 (ddd, J = 7.6, 7.6, 1.5 Hz, 1 H), 7.32–7.40 (m, 3 H), 7.48–

7.55 (m, 3 H).

¹³C NMR (125 MHz, CDCl₃): = 32.5, 33.0, 34.5, 124.5, 127.5,

128.0, 130.6, 133.0, 140.0.

LRMS (CI/isobutene): m/z = 276/278/280 [M⁺], 197/199 [(M –

Br)⁺].

HRMS (EI): m/z calcd for C₉H₁₀Br₂, 275.91492; found, 275.91473.

Benzyldichlorophenylsilane (5)

¹³C NMR (125 MHz, CDCl₃): = 10.2, 22.4, 24.4, 35.2, 124.3,

125.4, 127.9, 128.2, 128.7, 128.8, 129.3, 131.2, 134.7, 135.5, 137.1,

138.9, 149.8.

A three-necked 1 L flask equipped with a pressure-equalizing drop-

ping funnel, reflux condenser, and a magnetic stirring bar was

charged with PhSiCl₃(20b) (32.0 mL, 200 mmol) dissolved in Et₂O

Synthesis 2003, No. 17, 2725–2739 © Thieme Stuttgart · New York

2732

M. Oestreich et al.

FEATURE ARTICLE

LRMS (EI): m/z = 314 [M⁺], 223 [(M – Bn)⁺].

¹³C NMR (125 MHz, CDCl₃): = 31.2, 32.4, 33.7, 122.9, 124.0,

126.0, 127.2, 128.3, 128.9, 130.2, 132.8, 132.9, 136.0.

Anal. Calcd for C₂₂H₂₂Si (314.50): C, 84.02; H, 7.05. Found: C,

83.86; H, 7.13.

LRMS (EI): m/z = 326/328/330 [M⁺], 219/221 [(M – C₂H₄,Br)⁺],

168 [(M – Br₂)⁺].

2-Bromo-1-(3-bromopropyl)naphthalene (14); Typical Proce-

dure for the Carbon Chain Elongation (Four Steps)

Anal. Calcd for C₁₃H₁₂Br₂(328.04): C, 47.60; H, 3.69. Found: C,

47.98; H, 3.75.

In a 50 mL Schlenk flask equipped with a pressure-equalizing drop-

ping funnel and a magnetic stirring bar n-BuLi (5.9 mL, 8.2 mmol,

1.15 equiv, 1.4 M in hexane) was added dropwise to a soln of 2,4,4-

trimethyl-2-oxazoline (13) (0.91 mL, 7.09 mmol) and THF (10 mL)

at –78 °C. At this temperature, a soln of 2-bromo-1-(bromometh-

yl)naphthalene (18) (2.33 g, 7.77 mmol, 1.10 equiv) and THF (10

mL) was slowly added. After the additon was completed, the reac-

tion mixture was allowed to return to r.t. and was stirred for a further

16 h. The reaction mixture was poured into cold water (15 mL) and

the aq phase was acidified with concd HCl (pH 3–4). After separa-

tion of the organic phase, the aq layer was extracted with TBME (3

× 25 mL) followed by EtOAc (3 × 25 mL), then carefully neutral-

ized with aq 40% NaOH and again extracted with TBME (3 × 25

mL). The combined organic extracts were dried over MgSO₄, fil-

tered, and the solvents were removed under reduced pressure. The

residue was used without any further purification in the following

step. This crude product was dissolved in 3 N HCl (25 mL) in a one-

necked 50 mL flask equipped with a reflux condenser and a magnet-

ic stir bar. The reaction mixture was heated at reflux for 2 h and was

then allowed to cool to r.t. TBME (25 mL) was added, the organic

layer was separated, and the aq phase was extracted with TBME (3

× 25 mL) and EtOAc (3 × 25 mL). The combined organic phases

were dried (MgSO₄), filtered, and the volatiles were removed in

vacuo affording the crude carboxylic acid (1.88 g), which was used

without further purification. A three-necked 100 mL flask equipped

with a pressure-equalizing dropping funnel, a reflux condenser, and

magnetic stir bar was charged with LiAlH₄(381 mg, 10.1 mmol,

1.50 equiv), which was suspended in Et₂O (12 mL). A soln of the

crude acid (1.88 g, 6.74 mmol) and Et₂O (8.5 mL) was added drop-

wise under cooling with an ice–H₂O bath. Afterwards, the reaction

mixture was heated at reflux for 20 h followed by cooling to 0 °C

using an ice–H₂O bath. H₂O (5 mL) and aq 10% H₂SO₄(15 mL)

were added portionwise, the organic layer was separated, and the aq

phase was extracted with TBME (4 × 25 mL). The organic phases

were combined, dried (MgSO₄), filtered, and the solvents were

evaporated under reduced pressure yielding the crude alcohol (1.57

g). Finally, a one-necked 50 mL flask equipped with a reflux con-

denser and a magnetic stir bar was charged with PBr₃(0.4 mL, 4.4

mmol, 0.75 equiv). The alcohol (1.57 g, 5.92 mmol) was added

dropwise under ice-cooling. The resulting reaction mixture was ini-

tially heated at reflux for 3 h and then maintained for a further 16 h

at r.t. The reaction mixture was diluted with CH₂Cl₂(25 mL),

cooled to 0 °C, and hydrolyzed by extremely careful addition of

H₂O (5 mL). The organic layer was separated and the aq phase was

extracted with CH₂Cl₂(3 × 25 mL). Drying of the combined organic

phases over MgSO₄, filtration, removal of the solvent in vacuo, and

purification by flash chromatography on silica gel (cyclohexane)

provided dibromide 14 (0.88 g, 37% over four steps) as a colorless

oil.

2-Bromo-1-methylnaphthalene (17)

Modifying the reported preparation of 17,²⁸a one-necked 250 mL

flask equipped with a septum and magnetic stir bar was charged

with t-BuOK (7.52 g, 63.6 mmol, 1.05 equiv, 95% purity) and Et₂O

(90 mL). To this suspension 3-methyl-1H-indene (16) (7.83 g, 60.6

mmol) was added dropwise and the flask was pre-cooled with a wa-

ter bath. Freshly distilled CHBr₃(5.2 mL, 60 mmol, 0.99 equiv) was

slowly added and the reaction mixture was maintained for 16 h at

r.t. After addition of H₂O (30 mL), the aq phase was extracted with

TBME (5 × 10 mL). The combined organic layers were dried over

MgSO₄, filtered, and concentrated under reduced pressure. The

brownish residue was treated with EtOH (135 mL) and KOH (1.78

g, 31.7 mmol, 0.53 equiv) and heated for 2 h at reflux. The volatiles

were removed in vacuo; the crude product was loaded onto silica gel

(5 g) and pre-purified by flash chromatography on silica gel (cyclo-

hexane). Distillation under oil pump vacuum (85 °C at 7.0 × 10^–1

mbar) provided naphthalene 17 (3.72 g, 28% and 38%, respectively

based on reisolated starting material) as a colorless solid along with

unreacted starting material 16 (2.08 g, 27%).

Mp 31 °C (cyclohexane).

¹H NMR (500 MHz, CDCl₃): = 2.80 (s, 3 H), 7.45–7.57 (m, 3 H),

7.60 (d, J = 7.9 Hz, 1 H), 7.80 (d, J = 8.0 Hz, 1 H), 8.03 (d, J = 8.8

Hz, 1 H).

¹³C NMR (125 MHz, CDCl₃): = 18.8, 122.8, 124.5, 125.8, 126.8,

127.6, 128.7, 130.2, 132.5, 133.4, 133.5.

LRMS (EI): m/z = 220/222 [M⁺], 141 [(M – Br)⁺].

2-Bromo-1-(bromomethyl)naphthalene (18)

2-Bromo-1-methylnaphthalene (17) (2.51 g, 11.4 mmol) and diben-

zoylperoxide (DBPO) (28 mg, 0.1 mmol, 0.01 equiv) were dis-

solved in CCl₄(40 mL) in a one-necked 100 mL flask equipped with

a reflux condenser and a magnetic stirring bar. NBS (1.95 g, 10.9

mmol, 0.96 equiv) was added in one portion and the reaction mix-

ture was slowly heated to reflux at which it was kept for 20 h. After

cooling to r.t., FeSO₄(10 mL, 1 M in H₂O) was added and the reac-

tion mixture was vigorously stirred for 30 min. The organic phase

was dried over MgSO₄, filtered, and the filter cake was washed with

CH₂Cl₂(3 × 25 mL). The solvents were evaporated under reduced

pressure and the crude product was loaded onto silica gel (20 g). Pu-

rification by flash chromatography on silica gel (cyclohexane) pro-

vided 18 (2.33 g, 68% and 76%, respectively based on reisolated

starting material) as a pale yellow solid along with unreacted start-

ing material 17 (264 mg, 10%).

Mp 90 °C (cyclohexane); R_f0.42 (cyclohexane).

IR (cuvette): 3839 (vw), 3748 (w), 3674 (w), 3567 (vw), 3156 (m),

2986 (w), 2902 (w), 2360 (m), 2339 (m), 2255 (s), 1814 (m), 1794

(m), 1700 (w), 1651 (m), 1559 (m), 1508 (m), 1473 (m), 1383 (m),

1297 (vw), 1215 (m), 1168 (w), 1096 (m), 1048 (w), 934 (s), 895

(s), 765 (s), 693 (s), 542 (w) cm^–1.

¹H NMR (500 MHz, CDCl₃): = 5.13 (s, 2 H), 7.54 (dd, J = 7.4, 7.4

Hz, 1 H), 7.62 (d, J = 9.0 Hz, 1 H), 7.64 (ddd, J = 8.3, 7.0, 1.4 Hz,

1 H), 7.68 (d, J = 8.7 Hz, 1 H), 7.84 (d, J = 8.3 Hz, 1 H), 8.11 (d,

J = 8.7 Hz, 1 H).

R_f0.50 (cyclohexane).

IR (cuvette): 3839 (vw), 3748 (vw), 3690 (vw), 3156 (m), 3061

(vw), 2984 (w), 2903 (vw), 2361 (m), 2339 (m), 2255 (s), 1794 (m),

1700 (w), 1651 (m), 1559 (m), 1508 (m), 1472 (m), 1383 (m), 1295

(vw), 1246 (w), 1216 (w), 1167 (w), 1097 (m), 935 (s), 887 (s), 806

(m), 771 (s), 728 (s) 688 (s), 652 (s), 543 (w) cm^–1.

¹H NMR (500 MHz, CDCl₃): = 2.24 (m, 2 H), 3.41 (m, 2 H), 3.58

(t, J = 6.6 Hz, 2 H), 7.50 (ddd, J = 8.1, 6.9, 1.1 Hz, 1 H), 7.56 (ddd,

J = 8.5, 6.7, 1.6 Hz, 1 H), 7.57 (d, J = 9.0 Hz, 1 H), 7.60 (d, J = 8.9

Hz, 1 H), 7.82 (dd, J = 8.2, 1.2 Hz, 1 H), 8.08 (d, J = 8.3 Hz, 1 H).

¹³C NMR (125 MHz, CDCl₃): = 30.3, 123.8, 123.8, 126.6, 127.8,

128.9, 130.4, 130.6, 132.2, 132.3, 132.9.

Synthesis 2003, No. 17, 2725–2739 © Thieme Stuttgart · New York

FEATURE ARTICLE

Chiral Cyclic Silanes

2733

LRMS (EI): m/z = 298/300/302 [M⁺], 219/221 [(M – Br)⁺], 141 [(M

(–)-Dichloro-[(1R,2S,5R)-8-phenylmenthoxy]phenyl-silane

[(–)-19d] (Table 2, Entry 4)

– Br₂)⁺].

According to the typical procedure, a mixture of PhSiCl₃(20b)

(1.40 mL, 8.68 mmol) and urea (562 mg, 1.1 equiv) was reacted

with a soln of (–)-8-phenylmenthol [(–)-21] (2.00 g, 8.68 mmol, 1.0

equiv) and Et₂O (10 mL) in a 25 mL Schlenk flask equipped with a

magnetic stirring bar. Addition occurred over a period of 30 min and

the reaction mixture was maintained at r.t. for a further 3 h. Usual

work-up and fractional distillation (169 °C at 3 × 10^–5mbar) yielded

(–)-19d (2.42 g, 68%) as a highly viscous liquid.

Anal. Calcd for C₁₁H₈Br₂(299.99): C, 44.04; H, 2.69. Found: C,

43.95; H, 2.68.

(–)-Dichloro-(1R,2S,5R)-menthoxymethylsilane [(–)-19a] (Ta-

ble 2, Entry 1)

Following the typical procedure, in a two-necked 500 mL flask

equipped with a pressure-equalizing dropping funnel and a magnet-

ic stirring bar a mixture of MeSiCl₃(20a) (30.0 mL, 254 mmol) and

urea (16.4 g, 274 mmol, 1.1 equiv) was treated with (–)-menthol

[(–)-8] (39.4 g, 254 mmol, 1.0 equiv) in Et₂O (300 mL). The addi-

tion was completed after 1.5 h and the reaction mixture was main-

tained at r.t. for a further 3 h. Usual work-up and fractional

distillation (73 °C at 7.0 × 10^–1mbar) under reduced pressure pro-

vided dichlorosilane (–)-19a (27.4 g, 40%) as a colorless liquid.

20

[ ]_D–35.1, [ ]₅₇₈–36.3, [ ]₅₄₆–41.2, [ ]₄₃₆–66.7, [ ]₃₆₅

–101 (c 13.19, CHCl₃).

LRMS (CI/NH₃): m/z = 424/426/428 [(M + NH₄)⁺], 215 [8-Phenyl-

menthyl⁺], 119 [(2-Phenylpropyl)⁺].

Anal. Calcd for C₂₂H₂₈Cl₂OSi (407.45): C, 64.85; H, 6.93. Found:

C, 64.89; H, 6.93.

20

[ ]_D–61.4, [ ]₅₇₈–63.8, [ ]₅₄₆–72.3, [ ]₄₃₆–121, [ ]₃₆₅

–186 (c 10.04, CHCl₃).

GC-LRMS (EI): m/z = 183 [(M – C₆H₁₃)⁺].

Trichloro( -naphthyl)silane (20c)

A three-necked 500 mL flask equipped with a pressure-equalizing

dropping funnel, a reflux condenser, and a magnetic stir bar was

charged with magnesium turnings (5.00 g, 206 mmol, 1.5 equiv)

and was flame-dried in vacuo under vigorous stirring (3 times). Af-

ter back-filling with argon, Et₂O (25 mL) and benzene (25 mL) were

added followed by dropwise addition of a soln of -bromonaphtha-

lene (19.2 mL, 137 mmol), Et₂O (25 mL), and benzene (25 mL).

Ice-cooling was needed at the beginning of the Grignard reaction in

order to ensure a gentle reflux. The reaction mixture was maintained

for 30 min at ambient temperature after complete addition. The

highly viscous suspension was decanted from the excess of magne-

sium and transferred to a pressure-equalizing dropping funnel. A

second three-necked 500 mL flask equipped with the above pres-

sure-equalizing dropping funnel, a reflux condenser, and a magnetic

stir bar was charged with SiCl₄(23.5 mL, 206 mmol, 1.5 equiv).

The Grignard reagent was added dropwise and the resulting reaction

mixture was maintained for 18 h at 45 °C. The reaction mixture was

allowed to return to ambient temperature and was filtered using

Schlenk techniques. The filter cake was washed with n-pentane (3

× 20 mL) and the combined organic solvents were evaporated under

reduced pressure. The crude product was distilled (125 °C at 7.0 ×

10^–1mbar) affording 20c (16.8 g, 47%) as a colorless, highly vis-

cous liquid, which partially solidifies upon standing.

Anal. Calcd for C₁₁H₂₂Cl₂OSi (269.28): C, 49.06; H, 8.23. Found:

C, 49.16; H, 8.40.

(–)-Dichloro-(1R,2S,5R)-menthoxyphenylsilane [(–)-19b] (Ta-

ble 2, Entry 2); Typical Procedure

A three-necked 500 mL flask equipped with a pressure-equalizing

dropping funnel, a reflux condenser, and a magnetic stir bar was

charged with PhSiCl₃(20b) (40.8 mL, 254 mmol) and urea (16.4 g,

273 mmol, 1.1 equiv). At ambient temperature, a soln of (–)-men-

thol [(–)-8] (39.6 g, 254 mmol, 1.0 equiv) and Et₂O (330 mL) was

added dropwise over a period of 2 h. The reaction mixture was

maintained at this temperature for 3 h followed by filtration using

Schlenk techniques. The filter cake was washed with pentane (3 ×

50 mL) and the filtrate was concentrated in vacuo. Fractional distil-

lation of the residue once or – if necessary – twice (138 °C at 7.0 ×

10^–1mbar) provided (–)-19b (53.1 g, 63%) as a colorless liquid.

20

[ ]_D–46.8, [ ]₅₇₈–48.9, [ ]₅₄₆²⁰–55.2, [ ]₄₃₆²⁰–91.7, [ ]₃₆₅

–140 (c 13.19, CHCl₃).

LRMS (CI/NH₃): m/z = 348/350/352 [(M + NH₄)⁺], 330/332/335

[M⁺], 313/315 [(M – Cl + NH₄)⁺], 175/176/ 178 [(M – OMenthyl)⁺].

Anal. Calcd for C₁₆H₂₄Cl₂OSi (331.35): C, 58.00; H, 7.30. Found:

C, 57.81; H, 7.58.

IR (film): 3061 (m), 3009 (vw), 1591 (w), 1567 (w), 1508 (m), 1429

(w), 1367 (w), 1327 (m), 1220 (m), 1149 (m), 1027 (m), 985 (m),

830 (m), 797 (s), 773 (s), 733 (w), 673 (s), 624 (m), 579 (s) cm^–1.

¹H NMR (500 MHz, CDCl₃): = 7.53–7.62 (m, 2 H), 7.62–7.68 (m,

1 H), 7.94 (d, J = 7.7 Hz, 1 H), 8.08 (d, J = 8.0 Hz, 1 H), 8.13–8.20

(m, 1 H), 8.35–8.42 (m, 1 H).

¹³C NMR (125 MHz, CDCl₃): = 124.8, 126.7, 127.3, 127.5, 128.1,

129.5, 133.7, 134.2, 134.5, 135.6.

LRMS (CI/isobutene): m/z = 260/262/264/266 [M⁺], 129 [Np⁺].

(–)-Dichloro-(1R,2S,5R)-menthoxy( -naphthyl)silane [(–)-19c]

(Table 2, Entry 3)

-NpSiCl₃(20c) (10.0 g, 38.2 mmol) and urea (2.52 g, 42.0 mmol,

1.1 equiv) were dissolved in Et₂O (12 mL) in a two-necked 100 mL

flask equipped with a pressure-equalizing dropping funnel and a

magnetic stirring bar. According to the typical procedure, a soln of

(–)-menthol [(–)-8] (5.80 g, 38.2 mmol, 1.0 equiv) and Et₂O (20

mL) was added at ambient temperature over a period of 1 h. The re-

action mixture was stirred at this temperature for a further 3 h. Usual

work-up and fractional distillation (160–170 °C at 6 × 10^–5mbar)

provided (–)-19c (7.07 g, 49%) as a colorless liquid, which crystal-

lized upon standing in the freezer.

Anal. Calcd for C₁₀H₇Cl₃Si (261.61): C, 45.91; H, 2.70. Found: C,

45.73; H, 2.89.

(SiRS)-1-(1R,2S,5R)-Menthoxy-1-methyl-1-sila-1,2,3,4-tetra-

hydronaphthalene [(SiRS)-22a] (Table 3, Entry 1)

20

[ ]_D–22.1, [ ]₅₇₈–23.1, [ ]₅₄₆²⁰–26.1, [ ]₄₃₆²⁰–42.1, [ ]₃₆₅

–61.4 (c 10.55, CHCl₃).

Following the typical procedure, activated magnesium turnings

(300 mg, 12.5 mmol, 9.0 equiv) were treated with 1,2-dibromoet-

hane (0.05 mL, 0.58 mmol, 0.4 equiv) in THF (2.5 mL) in a 10 mL

Schlenk flask equipped with a micro reflux condenser and a mag-

netic stirring bar. An equimolar soln of 3 (386 mg, 1.39 mmol) and

(–)-19a (377 mg, 1.39 mmol, 1.0 equiv) in THF (2.5 mL) was add-

ed. The reaction mixture was heated at reflux for 15 h. Purification

of the crude product by flash chromatography on silica gel (cyclo-

hexane) provided (SiRS)-22a (100 mg, 23%) as a colorless liquid.

GC-LRMS (CI/isobutene): m/z = 436/438/440 [(M + isobutene)⁺],

380/382/384 [M⁺], 345/347 [(M – Cl)⁺], 242/244/246 [(M – Menth-

yl)⁺], 139 [Menthyl⁺], 128 [Np⁺].

Anal. Calcd for C₂₀H₂₆Cl₂OSi (381.41): C, 62.98; H, 6.87. Found:

C, 63.34; H, 6.91.

Synthesis 2003, No. 17, 2725–2739 © Thieme Stuttgart · New York

2734

M. Oestreich et al.

FEATURE ARTICLE

Table 2 Spectroscopic Data for Chirally Modified Dichlorosilanes (–)-19a–d

1

Entry

1

Product

IR (film) (cm

)

¹H NMR

(500 MHz, CDCl₃)

¹³C NMR

(125 MHz, CDCl₃)

( )-19a

3180 (vw), 2957 (s), 2926 (s), 2725

(vw), 1651 (vw), 1456 (s), 1405 (w),

1372 (m), 1347 (w), 1265 (s), 1238

(w), 1180 (m), 1151 (m), 1085 (s),

1003 (m), 981 (w), 938 (w), 885 (s),

833 (s), 794 (s), 742 (s)

0.77 (s, 3 H), 0.78 (d, J = 7.0 Hz, 3 H), 0.84 (dddd, 5.3, 16.0, 21.1, 22.2,

J = 12.4, 12.4, 12.4, 3.7 Hz, 1 H), 0.90 (d, J = 7.1

Hz, 3 H), 0.91 (d, J = 6.8 Hz, 3 H), 0.98 (dddd, J =

12.8, 12.8, 12.8, 3.4 Hz, 1 H), 1.11 (ddd, J =

12.2, 12.2, 10.9 Hz, 1 H), 1.24 (dddd, J = 12.7, 10.3

Hz, 3.0, 3.0 Hz, 1 H), 1.34–1.48 (m, 1 H), 1.58–

1.70 (m, 2 H), 2.04–2.16 (m, 2 H), 3.89 (ddd,

J = 10.5, 10.5, 4.5 Hz, 1 H)

23.0, 25.6, 31.7, 34.4,

44.2, 49.5, 76.0

2

( )-19b

3076 (w), 2957 (s), 2925 (s), 2870 (s), 0.82 (d, J = 6.8 Hz, 3 H), 0.84–0.93 (m, 1 H), 0.94 15.9, 21.2, 22.2, 22.9,

2724 (vw), 1959 (vw), 1890 (vw),

1819 (vw), 1593 (w), 1455 (s), 1432

(s), 1372 (m), 1347 (w), 1237 (w),

(d, J = 7.1 Hz, 3 H), 0.95 (d, J = 6.5 Hz, 3 H), 1.03 25.6, 31.7, 34.4, 44.2,

(dddd, J = 12.9, 12.9, 12.9, 3.3 Hz, 1 H), 1.23 (ddd, 49.5, 76.4, 128.3,

J = 11.8, 11.8, 11.8 Hz, 1 H), 1.36 (dddd,

131.9, 132.0, 133.7

1180 (m), 1124 (s), 1072 (s), 1053 (s), J = 10.2, 10.2, 2.9, 2.9 Hz, 1 H), 1.40–1.53 (m, 1

1001 (m), 936 (w), 880 (m), 822 (m),

806 (w), 740 (s), 713 (s), 695 (s), 620

(m)

H), 1.59–1.73 (m, 2 H), 2.15–2.27 (m, 2 H), 4.06

(ddd, J = 10.4, 10.4, 4.3 Hz, 1 H), 7.46 (dd, J = 7.3,

7.3 Hz, 2 H), 7.53 (dddd, J = 6.7, 6.7, 1.4, 1.4 Hz, 1

H), 7.78 (d, J = 6.8 Hz, 2 H)

3

( )-19c

3044 (w), 2956 (s), 2926 (s), 2869 (m), 0.82 (d, J = 6.8 Hz, 3 H), 0.83–1.00 (m, 1 H), 0.91 15.6, 21.3, 22.2, 22.8,

2723 (vw), 1590 (w), 1507 (m), 1456

(m), 1370 (m), 1347 (w), 1326 (w),

1276 (vw), 1220 (m), 1180 (w), 1150

(d, J = 7.1 Hz, 3 H), 0.95 (d, J = 6.6 Hz, 3 H), 1.04 25.5, 31.8, 34.3, 44.2,

(dddd, J = 12.9, 12.9, 12.9, 3.1 Hz, 1 H), 1.37 (ddd, 49.6, 76.8, 124.8,

J = 12.3, 12.3, 11.1 Hz, 1 H), 1.39 (dddd, J = 12.4, 126.2, 126.9, 128.0,

(m), 1071 (s), 1051 (s), 1003 (m), 987 10.1, 2.9, 2.9 Hz, 1 H), 1.43–1.54 (m, 1 H), 1.65–

128.7, 129.1, 132.9,

(m), 935 (vw), 878 (m), 818 (m), 798

(s), 774 (s), 733 (m), 672 (m)

1.73 (m, 2 H), 2.25 (ddd, J = 6.9, 6.9, 2.4 Hz, 1 H), 133.6, 135.3, 135.4

2.26–2.32 (m, 1 H), 4.17 (ddd, J = 10.5, 10.5, 4.5

Hz, 1 H), 7.50–7.57 (m, 2 H), 7.60 (ddd, J = 8.3,

7.0, 1.5 Hz, 1 H), 7.90 (d, J = 7.3 Hz, 1 H), 8.01 (d,

J = 8.3 Hz, 1 H), 8.12 (dd, J = 6.8, 1.3 Hz, 1 H),

8.40 (d, J = 8.3 Hz, 1 H)

4

( )-19d

3056 (w), 2956 (s), 2923 (s), 2871 (m), 0.71–0.86 (m, 1 H), 0.89 (d, J = 6.5 Hz, 3 H), 0.88– 22.0, 24.5, 27.2, 29.6,

1596 (w), 1495 (w), 1456 (m), 1432

(m), 1384 (w), 1372 (w), 1265 (m),

1.02 (m, 1 H), 1.28 (ddd, J = 12.3, 12.4, 10.9 Hz, 1 31.8, 34.6, 40.5, 45.4,

H), 1.31–1.37 (m, 1 H), 1.33 (s, 3 H), 1.38–1.48 (m, 53.0, 78.1, 125.2,

1191 (vw), 1125 (s), 1094 (s), 1062 (s), 1 H), 1.42 (s, 3 H), 1.48–1.56 (m, 1 H), 1.91 (ddd, 125.7, 128.0, 128.2,

974 (vw), 875 (m), 822 (m), 763 (m),

740 (s), 699 (s)

J = 12.3, 9.9, 3.3 Hz, 1 H), 2.26 (dddd, J = 12.3,

131.7, 132.0, 133.6,

4.3, 2.4, 2.4 Hz, 1 H), 4.24 (ddd, J = 10.4, 10.4, 4.3 151.2

Hz, 1 H), 7.08 (dddd, J = 7.2, 7.2, 1.3, 1.3 Hz, 1 H),

7.22 (dd, J = 7.9, 7.9 Hz, 2 H), 7.28 (dd, J = 8.4,

1.1 Hz, 2 H), 7.43 (dd, J = 7.4, 7.4 Hz, 2 H), 7.51

(dddd, J = 7.5, 7.5, 1.3, 1.3 Hz, 1 H), 7.67 (dd,

J = 8.0, 1.4 Hz, 2 H)

The diastereomeric ratio of 50:50 was determined from the ¹H NMR

spectra by integration of the baseline separated doublets at 0.57 and

0.65 ppm. MeSi(OMenthyl)₃(23a) was also isolated in varying

quantities.

cally activated magnesium was treated with a soln of 1,2-

dibromoethane (0.95 mL, 10.9 mmol, 0.4 equiv) and THF (50 mL).

The reaction mixture was heated at reflux for 10 min followed by

addition of a mixture of equimolar amounts of 1-bromo-2-(3-bro-

mopropyl)benzene (3) (7.56 g, 27.2 mmol, 1.0 equiv) and the chiral

dichloride (–)-19b (9.00 g, 27.2 mmol, 1.0 equiv) in THF (25 mL).

After maintaining the reaction mixture for a further 14 h at reflux, it

was allowed to return to ambient temperature. Diluting with cyclo-

hexane (50 mL) resulted in additional precipitation of magnesium

salts, which were filtered off and the solvents were removed under

reduced pressure; this process was repeated at least once. Rapid

flash filtration on silica gel (cyclohexane–TBME, 99:1) furnished

slightly contaminated (SiRS)-22b (6.15 g, 60%, ca. 95% purity). In

comparison, purification of the sticky residue resulting from a Bar-

bier reaction run on a 10.6 mmol scale by flash chromatography on

reversed phase silica gel (MeCN–H₂O, 9:1) provided analytically

pure (SiRS)-22b (1.23 g, 31%) as a colorless viscous oil. The dias-

tereomeric ratio of 55:45 was determined from the ¹H NMR spectra

R_f0.27 (cyclohexane).

LRMS (EI): m/z = 316 [M⁺], 301 [(M – Me)⁺].

Anal. Calcd for C₂₀H₃₂OSi (316.55): C, 75.88; H, 10.19. Found: C,

75.83; H, 10.37.

(SiRS)-1-(1R,2S,5R)-Menthoxy-1-phenyl-1-sila-1,2,3,4-tetrahy-

dronaphthalene [(SiRS)-22b]; Typical Procedure (Table 3, En-

try 2)

A 250 mL three-necked flask equipped with a reflux condenser, a

pressure-equalizing dropping funnel, an argon inlet and a magnetic

stirring bar was charged with magnesium turnings (5.95 g, 244.8

mmol, 9.0 equiv). The tube was flame-dried under vigorous stirring

at least three times. After backfilling with argon, the vigorous stir-

ring was continued for several hours. The thermally and mechani-

Synthesis 2003, No. 17, 2725–2739 © Thieme Stuttgart · New York

FEATURE ARTICLE

Chiral Cyclic Silanes

2735

by integration of the baseline separated doublets at 0.48 and 0.62

ppm.

(SiRS)-1-Phenyl-[(1R,2S,5R)-8-phenylmenthoxy]-1-sila-1,2,3,4-

tetrahydronaphthalene [(SiRS)-22d] (Table 3, Entry 6)

In accordance with the typical procedure, the magnesium turnings

(300 mg, 12.5 mmol, 9.0 equiv) were reacted with 1,2-dibromoet-

hane (0.05 mL, 0.58 mmol, 0.4 equiv) in THF (2.5 mL) in a 10 mL

Schlenk flask equipped with a micro reflux condenser and a mag-

netic stir bar. Treatment of the activated magnesium with 3 (386

mg, 1.39 mmol) and (–)-19d (570 mg, 1.39 mmol, 1.0 equiv) for 15

h at reflux was followed by the usual work-up. Purification by flash

chromatography on reversed phase silica gel (MeCN–H₂O, 9:1)

provided (SiRS)-22d (231 mg, 37%) as a colorless viscous oil. The

R_f0.34 (cyclohexane).

LRMS (CI/NH₃): m/z = 396 [(M + NH₄)⁺], 379 [M⁺], 240 [(M –

Menthyl)⁺], 223 [(M – OMenthyl)⁺].

Anal. Calcd for C₂₅H₃₄OSi (378.62): C, 79.31; H, 9.05. Found: C,

79.30; H, 9.03.

(SiS)-1-(1R,2S,5R)-Menthoxy-1-phenyl-1-sila-1,2,3,4-tetrahy-

dronaphthalene [(SiS)-22b] (Table 3, Entry 3)

1

diastereomeric ratio of 60:40 was determined from the H NMR

spectra by integration of the baseline separated doublets at 0.70 and

0.74 ppm.

A 0.5 M soln of (SiRS)-22b is kept at –78 °C for at least 24 h. De-

pending on time and purity of the diastereomeric mixture, variable

amounts of amorphus crystals were collected after decanting the

mother liquor, which is enriched in (SiR)-22b. This process was re-

peated once or twice and furnished several crops of diastereomeri-

cally enriched (SiS)-22b. The diastereomeric ratio of >96:4 was

determined from the ¹H NMR spectra by integration of the baseline

separated doublets at 0.47 and 0.60 ppm.

R_f0.30 (cyclohexane).

LRMS (CI/NH₃): m/z = 473 [(M + NH₄)⁺], 455 [M⁺], 240 [(M –

(8-Phenylmenthyl))⁺], 215 [(8-Phenylmenthyl)⁺].

Anal. Calcd for C₃₁H₃₈OSi (454.72): C, 81.88; H, 8.42. Found: C,

81.69; H, 8.77.

20

[ ]_D–45.5, [ ]₅₇₈–46.7, [ ]₅₄₆–53.9, [ ]₄₃₆–92.4, [ ]₃₆₅

–148 (c 0.33, CHCl₃).

(SiRS)-1-Phenyl-[(1R,2S,5R)-8-phenylmenthoxy]-1-sila-1,2,3,4-

tetrahydrophenanthrene [(SiRS)-24d] (Table 3, Entry 7)

Following the typical procedure, a 10 mL Schlenk flask equipped

with a micro reflux condenser and a magnetic stir bar and charged

with a suspension of magnesium turnings (264 mg, 10.9 mmol, 8.9

equiv) and THF (2.0 mL) was syringed 1,2-dibromoethane (0.04

mL, 0.49 mmol, 0.4 equiv). A mixture of dibromide 14 (401 mg,

1.22 mmol) and (–)-19d (481 mg, 1.22 mmol, 1.0 equiv) was added

in three portions at reflux and the resulting reaction mixture was

maintained at ambient temperature for 22 h. The usual work-up fur-

nished a cloudy oil. Purification by flash chromatography on re-

versed phase silica gel (MeCN–H₂O, 9:1) provided (SiRS)-24d (96

mg, 16%) was isolated as a sticky oil which solidified upon stand-

ing. The diastereomeric ratio could not be determined by ¹H NMR

spectroscopy since there were no baseline separated signals of the

diastereomers.

(SiRS)-1-(1R,2S,5R)-Menthoxy-1-naphthyl-1-sila-1,2,3,4-tet-

rahydronaphthalene [(SiRS)-22c] (Table 3, Entry 5)

Magnesium turnings (300 mg, 12.5 mmol, 9.0 equiv) were activated

in a 10 mL Schlenk flask equipped with a micro reflux condenser

and a magnetic stir bar according to the typical procedure. After ad-

diton of 1,2-dibromoethane (0.05 mL, 0.58 mmol, 0.4 equiv) and

THF (2.5 mL) and heating at reflux, the magnesium was reacted

with a mixture of 3 (386 mg, 1.39 mmol) and (–)-19c (534 mg, 1.40

mmol, 1.0 equiv). Subsequent heating at reflux for 15 h was fol-

lowed by the usual work-up. Purification by flash chromatography

on reversed phase silica gel (MeCN–H₂O, 9:1). The title compound

(SiRS)-22c (192 mg, 32%) was isolated as a colorless sticky oil. On

the contrary, purification on silica gel (cyclohexane) resulted in a

substantially deteriorated yield (17 mg, 3%)! The diastereomeric

ratio of 58:42 was determined from the ¹H NMR spectra by integra-

tion of the baseline separated doublets at 0.33 and 0.65 ppm.

R_f0.57 (cyclohexane).

R_f0.32 (cyclohexane).

LRMS (EI): m/z = 504 [M⁺], 385 [(M – Cumyl)⁺], 273 [(M –

(8-Phenylmenthyloxy)⁺].

LRMS (EI): m/z = 428 [M⁺], 300 [(M – Np)⁺], 273 [(M – OMenth-

yl)⁺], 128 [Np⁺].

HRMS (EI): m/z calcd for C₃₅H₄₀OSi, 504.28484; found,

504.28488.

HRMS (EI): Calcd for C₂₉H₃₆OSi: 428.25354. Found: 428.25348.

Table 3 Spectroscopic Data for Chiral Functionalized Cyclic Silanes 22a–d and 24d

Entry

1

Product

IR (film) (cm^–1)

¹H NMR (500 MHz, CDCl₃)

¹³C NMR (125 MHz, CDCl₃)

(SiRS)-22a

3055 (w), 2997 (w), 2954 (s),

0.34 (s, 1.5 H), 0.35 (s, 1.5 H), 0.57 (d, J = 6.8

1.0, 14.2, 14.3, 15.8, 15.9,

21.4, 21.4, 22.4, 22.4, 22.8,

22.8, 22.9, 22.9, 25.2, 25.3,

31.7, 34.6, 35.4, 35.4, 45.3,

2921 (s), 2869 (s), 2721 (vw), Hz, 1.5 H), 0.65 (d, J = 7.0 Hz, 1.5 H), 0.70–

2651 (vw), 1590 (w), 1454 0.98 (m, 9 H), 1.00 (ddd, J = 12.4, 12.4, 10.4

(m), 1436 (m), 1404 (w), 1370 Hz, 0.5 H), 1.03 (ddd, J = 12.4, 12.4, 10.6 Hz,

(m), 1346 (w), 1292 (w), 1268 0.5 H), 1.03–1.19 (m, 2 H), 1.23–1.38 (m, 1 H), 45.6, 50.2, 72.9, 73.0, 125.4,

(w), 1252 (m), 1179 (w), 1141 1.52–1.64 (m, 2 H), 1.79–2.06 (m, 3 H), 2.14– 125.4, 128.5, 128.6, 129.5,

(m), 1106 (s), 1081 (s), 1053

(s), 1000 (m), 977 (m), 930

(m), 915 (w), 872 (s), 826 (s),

800 (s), 740 (s), 701 (w), 680

(w), 638 (m)

2.25 (m, 1 H), 2.72 (ddd, J = 15.9, 8.1, 2.5 Hz, 129.5, 134.0, 134.1, 134.4,

1 H), 2.78–2.87 (m, 1 H), 3.43 (ddd, J = 10.3,

10.3, 4.3 Hz, 0.5 H), 3.47 (ddd, J = 10.4, 10.4

Hz, J = 4.2 Hz, 0.5 H), 7.09 (d, J = 7.3 Hz, 1

H), 7.20 (dd, J = 7.9,7.9 Hz, 1 H), 7.26 (dd,

J = 7.4, 7.4 Hz, 1 H), 7.55 (m, 1 H)

134.4, 148.9, 149.0

2736

M. Oestreich et al.

FEATURE ARTICLE

Table 3 Spectroscopic Data for Chiral Functionalized Cyclic Silanes 22a–d and 24d (continued)

Entry

2

Product

IR (film) (cm^–1)

¹H NMR (500 MHz, CDCl₃)

¹³C NMR (125 MHz, CDCl₃)

(SiRS)-22b

3051 (m), 2999 (m), 2954 (s),

2921 (s), 2869 (s), 1590 (m),

1562 (w), 1454 (m), 1431 (s),

0.48 (d, J = 7.1 Hz, 1.5 H), 0.62 (d, J = 7.1 Hz, 13.5, 13.8, 15.7, 15.7, 21.4,

1.5 H), 0.76–0.94 (m, 2 H), 0.81 (d, J = 6.5 Hz, 21.4, 22.3, 22.4, 22.8, 22.8,

1.5 H), 0.86 (d, J = 7.1 Hz, 1.5 H), 0.87 (d,

23.0, 23.1, 25.2, 25.3, 31.7,

1402 (w), 1371 (m), 1345 (w), J = 6.5 Hz, 1.5 H), 0.91 (d, J = 7.1 Hz, 1.5 H), 31.7, 34.5, 34.6, 35.4, 35.4,

1292 (w), 1270 (m), 1236 (w), 1.05 (ddd, J = 12.2, 12.2, 10.6 Hz, 0.5 H), 1.13 45.2, 45.6, 50.3, 73.2, 73.4,

1180 (m), 1140 (s), 1112 (s),

1081 (s), 999 (m), 973 (m), 930 1.35 (m, 4 H), 1.54–1.65 (m, 2 H), 1.80–1.86

(m), 914 (w), 870 (m), 817

(m), 810 (m), 781 (m), 737 (s), 2 H), 2.28 (qqd, J = 7.0, 7.0, 2.5 Hz, 0.5 H),

(ddd, J = 12.3, 12.3, 10.7 Hz, 0.5 H), 1.14–

125.4, 125.4, 127.7, 127.8,

128.6, 128.7, 129.5, 129.5,

(m, 0.5 H), 1.89–1.95 (m, 0.5 H), 1.96–2.12 (m, 129.7, 129.7, 132.1, 132.3,

134.5, 134.6, 135.5, 135.6,

137.4, 137.5, 149.8, 149.8

700 (s), 655 (m)

2.34 (qqd, J = 7.0, 7.0, 2.6 Hz, 0.5 H), 2.80

(ddd, J = 16.1, 7.2, 3.2 Hz, 0.5 H), 2.81 (ddd,

J = 16.1,7.3, 3.7 Hz, 0.5 H), 2.89 (ddd, J = 16.3

Hz, J = 8.5, 3.9 Hz, 0.5 H), 2.90 (ddd, J = 16.3

Hz, J = 8.3 Hz, J = 4.5 Hz, 0.5 H), 3.52 (ddd,

J = 10.3, 4.5 Hz, 0.5 H), 3.55 (ddd, J = 10.4 Hz,

J = 4.4 Hz, 0.5 H), 7.15 (dd, J = 8.3, 4.0 Hz, 1

H), 7.29 (ddd, J = 7.3, 1.4 Hz, 1 H), 7.31–7.37

(m, 3 H), 7.55 (dd, J = 7.8, 1.2 Hz, 0.5 H), 7.57

(dd, J = 7.3, 1.2 Hz, 0.5 H), 7.58–7.63 (m, 2 H)

3

4

5

(SiS)-22b

(SiR)-22b

(SiRS)-22c

= 0.47 (d, J = 6.9 Hz, 3 H), 0.84 (d, J = 6.9

Hz, 3 H), 0.85 (d, J = 6.5 Hz, 3 H), 0.75–0.94

(m, 2 H), 1.11 (ddd, J = 12.3, 10.6 Hz, 1 H),

13.8, 15.7, 21.4, 22.4, 22.8,

23.1, 25.3, 31.7, 34.6, 35.5,

45.7, 50.3, 73.3, 125.4, 127.8,

1.17–1.34 (m, 4 H), 1.53–1.62 (m, 2 H), 1.87– 128.6, 129.5, 129.7, 132.2,

1.94 (m, 1 H), 1.96–2.12 (m, 2 H), 2.26 (qqd,

J = 7.0 Hz, 2.2 Hz, 1 H), 2.80 (ddd, J = 16.2

Hz, J = 7.4 Hz, J = 3.7 Hz, 1 H), 2.89 (ddd,

J = 16.2 Hz, J = 8.0 Hz, J = 3.8 Hz, 1 H), 3.51

(ddd, J = 10.4, 4.3 Hz, 1 H), 7.11–7.19 (m, 2

H), 7.28 (ddd, J = 7.5, 1.6 Hz, 1 H), 7.30–7.38

(m, 3 H), 7.53 (dd, J = 7.3 Hz, J = 1.3 Hz, 1 H),

7.57–7.62 (m, 2 H)

134.5, 135.6, 137.6, 149.9

0.60 (d, J = 7.1 Hz, 3 H), 0.79 (d, J = 6.8 Hz, 3 13.5, 15.7, 21.4, 22.3, 22.8,

H), 0.90 (d, J = 7.1 Hz, 3 H), 0.74–0.93 (m, 2

H), 1.03 (ddd, J = 12.3, 10.7 Hz, 1 H), 1.16

23.0, 25.3, 31.7, 34.6, 35.4,

45.2, 50.3, 73.4, 125.4, 127.8,

(ddd, J = 14.4, 8.7, 4.2 Hz, 1 H), 1.20–1.28 (m, 128.7, 129.5, 129.7, 132.3,

3 H), 1.53–1.60 (m, 2 H), 1.78–1.84 (m, 1 H),

1.94–2.10 (m, 2 H), 2.33 (qqd, J = 7.0, 7.0, 2.5

Hz, 1 H), 2.79 (ddd, J = 16.3, 7.7, 3.4 Hz, 1 H),

2.88 (ddd, J = 16.2, 8.6, 3.3 Hz, 1 H), 3.54

(ddd, J = 10.4, 10.4, 4.3 Hz 1 H), 7.14 (d,

J = 7.7 Hz, 1 H), 7.18 (dd, J = 6.8, 6.8 Hz, 1 H),

7.26–7.38 (m, 4 H), 7.56 (dd, J = 7.1, 1.3 Hz, 1

H), 7.57–7.60 (m, 2 H)

134.6, 135.5, 137.4, 149.8

3434 (s), 2927 (w), 2870 (w),

0.33 (d, J = 7.0 Hz, 1.2 H), 0.65 (d, J = 6.7 Hz, 14.3, 15.1, 15.7, 15.8, 21.4,

21.5, 22.3, 22.4, 22.8, 23.2,

2360 (w), 2253 (m), 2127 (w), 1.8 H), 0.72 (d, J = 6.8 Hz, 1.8 H), 0.79 (d,

1664 (m), 1054 (s), 1028 (s),

1007 (s), 824 (m), 762(m)

J = 7.1 Hz, 1.2 H), 0.89 (d, J = 6.1 Hz, 1.2 H), 23.2, 25.1, 25.3, 31.7, 31.8,

0.91 (d, J = 7.0 Hz, 1.8 H), 0.74–0.95 (m, 2 H), 34.5, 34.6, 35.4, 45.0, 45.7,

1.00 (ddd, J = 12.4, 12.4, 10.8 Hz, 0.6 H),

1.17–1.43 (m, 4.4 H), 1.50–1.64 (m, 2 H),

50.4, 50.5, 73.5, 73.9, 125.0,

125.4, 125.4, 125.5, 125.6,

1.73–1.79 (m, 1 H), 2.00–2.11 (m, 2.4 H), 2.22 125.7, 128.7, 128.8, 128.9,

(qqd, J = 7.0, 7.0, 2.3 Hz, 0.4 H), 2.40 (qqd, 128.9, 129.0, 129.8, 130.3,

J = 7.0, 7.0, 2.3 Hz, 0.6 H), 2.80–3.00 (m, 2 H), 130.3, 135.7, 135.9, 135.9

3.58 (ddd, J = 10.2, 10.2, 4.2 Hz, 0.4 H), 3.66

(ddd, J = 10.3, 10.3,4.3 Hz, 0.6 H), 7.16–7.23

(m, 2 H), 7.31–7.50 (m, 4 H), 7.56–7.68 (m, 1

H), 7.68 (dd, J = 6.8, 1.2 Hz, 0.6 H), 7.70 (dd,

J = 6.8, 1.3 Hz, 0.4 H), 7.82–7.87 (m, 2 H),

8.21–8.27 (m, 1 H)

FEATURE ARTICLE

Chiral Cyclic Silanes

2737

Table 3 Spectroscopic Data for Chiral Functionalized Cyclic Silanes 22a–d and 24d (continued)

Entry

6

Product

IR (film) (cm^–1)

¹H NMR (500 MHz, CDCl₃)

¹³C NMR (125 MHz, CDCl₃)

(SiRS)-22d

3307 (w), 3054 (m), 2999 (m), 0.64–0.84 (m, 2 H), 0.70 (d, J = 6.5 Hz, 0.6 H), 13.6, 13.9, 22.0, 22.1, 22.9,

2871 (s), 2724 (vw), 2119 (s), 0.74 (d, J = 6.1 Hz, 0.4 H), 1.04 (ddd, J = 12.3, 23.1, 23.6, 23.8, 27.4, 31.1,

1954 (w), 1884 (w), 1818 (w), 12.3, 10.7 Hz, 0.6 H), 1.13–1.30 (m, 4.5 H),

31.5, 31.8, 34.8, 34.8, 35.4,

1673 (w), 1592 (m), 1563 (w), 1.26 (s, 1.8 H), 1.28 (s, 1.2 H), 1.33–1.48 (m, 1 35.5, 40.9, 40.9, 46.5, 47.0,

1494 (m), 1432 (s), 1402 (w),

1368 (m), 1291 (m), 1268 (m), (m, 1.6 H), 1.86 (ddd, J = 8.8, 3.9, 2.1 Hz, 0.4

1236 (m), 1201 (m), 1111 (s),

1063 (s), 1043 (s), 1014 (m),

H), 1.41 (s, 1.2 H), 1.47 (s, 1.8 H), 1.71–1.82

53.6, 53.7, 75.4, 75.5, 125.0,

125.3, 125.4, 126.0, 126.1,

127.7, 127.7, 127.8, 127.9,

H), 1.93–2.02 (m, 1 H), 2.02–2.14 (m, 1 H),

2.74–2.86 (m, 1 H), 2.90 (ddd, J = 16.2, 9.2, 3.1 128.7, 128.8, 129.4, 129.4,

973 (m), 913 (m), 866 (s), 810 Hz, 1 H), 3.77 (ddd, J = 9.9, 9.9, 4.1 Hz, 0.4 H), 129.6, 129.6, 132.3, 132.7,

(s), 778 (m), 739 (s), 700 (s),

655 (m)

3.86 (ddd, J = 10.5, 10.5, 4.3 Hz, 0.6 H), 7.09– 134.5, 134.6, 135.7, 137.6,

7.40 (m, 11 H), 7.54 (dd, J = 7.2, 1.1 Hz,

137.9, 149.6, 149.6, 151.2,

151.7

0.6 H), 7.57–7.62 (m, 2.6 H)

7

(SiRS)-24d

3155 (w), 3056 (w), 2956 (m),

2924 (s), 2870 (m), 2361 (m),

2254 (s), 1794 (w), 1600 (w),

1558 (w), 1458 (m), 1430 (m), 0.5 H), 1.13–1.32 (m, 2.5 H), 1.23–1.31 (m, 2

1381 (m), 1170 (w), 1098 (s), H), 1.26 (s, 1.5 H), 1.26 (s, 1.5 H), 1.35–1.42

= 0.64 (d, J = 6.5 Hz, 1.5 H), 0.61–0.71 (m, 1 12.6, 13.1, 22.0, 22.1, 22.2,

H), 0.75 (d, J = 5.8 Hz, 1.5 H), 0.77–0.83 (m, 1 22.3, 23.7, 23.8, 27.4, 27.5,

H), 1.04 (ddd, J = 12.0 Hz, J = 10.8, 10.8 Hz,

30.3, 31.1, 31.6, 31.8, 31.8,

34.8, 34.8, 40.9, 46.4, 47.1,

53.7, 53.8, 75.6, 75.6, 123.7,

1062 (m), 929 (s), 903 (s), 884 (m, 1 H), 1.40 (s, 1.5 H), 1.47 (s, 1.5 H), 1.68– 125.0, 125.4, 125.4, 125.4,

(s), 810 (m), 772 (s), 736 (s),

717 (s), 652 (m)

1.83 (m, 1.5 H), 1.87–1.90 (m, 0.5 H), 2.08–

2.17 (m, 1 H), 2.18–2.28 (m, 1 H), 3.32 (dd,

J = 5.5, 4.5 Hz, 1 H), 3.32 (dd, J = ca. 5.0, 5.0

125.9, 125.9, 126.1, 126.3,

127.7, 127.7, 127.8, 127.9,

128.8, 128.9, 129.4, 129.5,

Hz, 1 H), 3.78 (ddd, J = 9.5, 9.5, 4.2, 0.5 Hz, 1 131.3, 131.4, 134.3, 134.3,

H), 3.91 (ddd, J = 9.9, 9.9, 4.2, 0.5 Hz), 1 H, 134.7, 134.7, 137.3, 137.3,

7.08 (dd, J = 7.2, 7.2 Hz, 1 H), 7.15 (d, J = 8.0 146.5, 146.6, 151.2, 151.7

Hz, 1 H), 7.19 (dd, J = 7.8, 7.8 Hz, 1 H), 7.19

(dd, J = 7.8, 7.8 Hz, 1 H), 7.25 (d, J = 8.3 Hz, 1

H), 7.29–7.40 (m, 3 H), 7.48–7.54 (m, 2 H),

7.57–7.68 (m, 4 H), 7.82 (dd, J = 7.4, 1.5 Hz, 1

H), 8.13 (dd, J = 7.5, 7.5 Hz, 1 H)

(SiR)-1-Phenyl-1-sila-1,2,3,4-tetrahydronaphthalene [(SiR)-

25b]; Typical Procedure

1406 (w), 1292 (w), 1269 (w), 1188 (vw), 1141 (m), 1115 (s), 1074

(m), 980 (m), 822 (s), 777 (m), 746 (s), 700 (s) cm^–1.

Chiral (SiS)-22b (475 mg, 1.25 mmol, dr > 96:4) was dissolved in

CH₂Cl₂(25 mL) in a 50 mL Schlenk flask equipped with a magnetic

stirring bar and the resulting soln was cooled to –78 °C. DIBAL

(1.28 mL, 1.28 mmol, 1.02 equiv, 1 M in hexane) was added and the

reaction mixture was maintained for a further 1.5 h at this tempera-

ture. Afterwards, the reaction mixture was allowed to warm to am-

bient temperature and a second equivalent of DIBAL (1.28 mL,

1.28 mmol, 1.02 equiv, 1 M in hexane) was syringed into the reac-

tion mixture. The progress of the transformation was monitored by

TLC and was terminated after almost complete conversion – ap-

pearance of by-products was detected – by the addition of acetone

(6 mL) and concd HCl (5 mL). After diluting with H₂O (20 mL), the

organic layer was separated and the aq phase was extracted with

TBME (3 × 25 mL). The combined organic phases were dried

(MgSO₄), filtered, and the volatiles were evaporated in vacuo. Puri-

fication by flash chromatography on silica gel (cyclohexane) pro-

vided the cyclic silane (SiR)-25b (249 mg, 89%, er 98:2) as a

colorless liquid. The enantiomeric ratio of 98:2 was determined

from the HPLC by integration of baseline separated peaks which

were assigned as the enantiomers.

¹H NMR (500 MHz, CDCl₃): = 1.12–1.20 (m, 1 H), 1.25–1.35 (m,

1 H), 1.96–2.10 (m, 2 H), 2.81–2.91 (m, 2 H), 4.90 (dd, J = 3.4, 3.4

Hz, 1 H), 7.16 (d, J = 7.4 Hz, 1 H), 7.17 (dd, J = 6.9, 6.9 Hz, 1 H),

7.29 (ddd, J = 7.5, 7.5 Hz, J = 1.6 Hz, 1 H), 7.33–7.41 (m, 3 H),

7.43 (dd, J = 8.0, 1.6 Hz, 1 H), 7.57 (dd, J = 7.9, 1.4 Hz, 2 H).

¹³C NMR (125 MHz, CDCl₃): = 9.6, 22.4, 35.1, 125.6, 128.0,

129.0, 129.6, 129.6, 129.6, 135.2, 135.9, 136.3, 149.5.

LRMS (EI): m/z = 224 [M⁺], 146 [(M – Ph)⁺].

Anal. Calcd for C₁₅H₁₆Si (224.37): C, 80.30; H, 7.19. Found: C,

80.18; H, 7.23.

(SiRS)-1-( -Naphthyl)-1-sila-1,2,3,4-tetrahydronaphthalene

[(SiRS)-25c]

Following the typical procedure, a soln of silyl ether (SiRS)-22c

(200 mg, 460 mol) and n-Bu₂O (4.6 mL) was treated with DIBAL

(1.41 mL, 1.41 mmol, 3.06 equiv, 1 M in hexane) at 120 °C for 100

h in a 10 mL Schlenk flask equipped with a micro condenser and a

magnetic stir bar. After the usual work-up with acetone (4 mL) and

concd HCl (2 mL), the aq phase was extracted with TBME (4 × 10

mL). Purification twice by flash chromatography on silica gel (cy-

clohexane) provided the title compound (SiRS)-25c (46 mg, 36%)

as a pale yellow solid which started to decompose at r.t. over a cou-

ple of days but proved to be stable below 0 °C. The enantiomeric ra-

tio of 54:46 was determined from the HPLC by integration of

baseline separated peaks which were assigned as the enantiomers.

R_f0.45 (cyclohexane).

HPLC (Daicel Chiracel OD-H column, column temperature 20 °C,

solvent n-heptane, flow rate 0.5 mLmin^–1): t_R15.17 min for (SiR)-

25b (major enantiomer), t_R19.13 min for (SiS)-25b (minor enanti-

omer).

20

[ ]_D–50.8, [ ]₅₇₈–53.9, [ ]₅₄₆–61.6, [ ]₄₃₆–116, [ ]₃₆₅

R_f0.53 (cyclohexane).

–205 (c 0.42, CHCl₃).

HPLC (Daicel Chiracel OD-H column, column temperature 20 °C,

IR (film): 3051 (m), 2998 (m), 2923 (s), 2854 (m), 2361 (w), 2117

(s), 1956 (vw), 1885 (vw), 1818 (vw), 1591 (w), 1473 (w), 1430 (s),

solvent n-heptane, flow rate 0.5 mLmin^–1): t_R35.24 min for (SiS*)-

2738

M. Oestreich et al.

FEATURE ARTICLE

25c (major enantiomer), t_R41.16 min for (SiR*)-25c (minor

enantiomer).

HPLC (Daicel Chiracel OD-H column, column temperature 20 °C,

solvent n-heptane, flow rate 0.5 mLmin^–1): t_R15.20 min for (SiR)-

25b (minor enantiomer), t_R18.52 min for (SiS)-25b (major enanti-

omer).

IR (film): 3854 (w), 3748 (w), 3690 (w), 3156 (w), 3058 (m), 2998

(w), 2928 (m), 2859 (w), 2360 (m), 2255 (s), 2126 (m), 1814 (w),

1794 (m), 1651 (m), 1559 (m), 1504 (m), 1472 (s), 1437 (m), 1383

(s), 1267 (w), 1218 (w), 1145 (m), 1096 (m), 987 (s), 936 (s), 883

(s), 838 (s), 753 (s), 657 (s) cm^–1.

Acknowledgment

The research was supported by the Deutsche Forschungsgemein-

schaft (Emmy Noether-Stipendium, Oe 249/2-1 and Oe 249/2-2),

the Fonds der Chemischen Industrie, and the Wissenschaftliche Ge-

sellschaft in Freiburg im Breisgau. The authors thank Ilona Hauser

for skillful technical assistance, Michael Tauchert for his excellent

contributions to the project, and Professor Dr. Reinhard Brückner

for his support. Generous donations of chemicals from Bayer, Le-

verkusen/Germany and Haarmann & Reimer, Minden/Germany are

gratefully acknowledged.

¹H NMR (500 MHz, CDCl₃): = 1.21–1.28 (m, 1 H), 1.41–1.48 (m,

1 H), 2.01–2.10 (m, 2 H), 2.86–2.98 (m, 2 H), 5.32 (dd, J = 3.4, 3.4

Hz, 1 H), 7.11–7.26 (m, 2 H), 7.33 (ddd, J = 7.7, 7.7, 1.6 Hz, 1 H),

7.41 (dd, J = 8.0, 6.8 Hz, 1 H), 7.44 (d, J = 8.6 Hz, 1 H), 7.45–7.51

(m, 2 H), 7.63 (dd, J = 6.8, 1.5 Hz, 1 H), 7.84–7.91 (m, 2 H), 8.04–

8.08 (m, 1 H).

¹³C NMR (125 MHz, CDCl₃): = 9.83, 22.6, 35.1, 125.3, 125.7,

125.7, 126.2, 127.8, 129.1, 129.7, 130.5, 136.1, 136.4.

LRMS (EI): m/z = 274 [M⁺], 146 [(M – Np)⁺].

Anal. Calcd for C₁₉H₁₈Si (274.43): C, 83.16; H, 6.61. Found: C,

83.04; H, 6.85.

References

(1) To whom inquiries about the reported crystal structure

analyses should be addressed.

(2) For a general reference see: Brook, M. A. Silicon in Organic

Organometallic and Polymer Chemistry; Wiley-

Interscience: New York, 2000.

(3) For reviews including the utilization of compounds with

chiral silicon centers see: (a) Maryanoff, C. A.; Maryanoff,

B. E. In Asymmetric Synthesis, Vol. 4; Morrison, J. D.; Scott,

J. W., Eds.; Academic Press: Orlando, 1984, 355–374.

(b) Fleming, I.; Barbero, A.; Walter, D. Chem. Rev. 1997,

97, 2063.

(SiS)-1-Chloro-1-phenyl-1-sila-1,2,3,4-tetrahydronaphthalene

[(SiS)-26b]

A sat. soln of Cl₂in CCl₄(1.0 mL) was added dropwise to a vigor-

ously stirred soln of (SiR)-25b (152 mg, 0679 mmol) and CCl₄(4.4

mL) at r.t. until a pale yellow discoloration appeared. The reaction

mixture was maintained at r.t. for 3 min and a second portion of Cl₂

in CCl₄(0.6 mL) was added. The yellow soln was purged with argon

after 1 min. Evaporation of the solvent under high vaccum provided

(SiS)-26b (174 mg, 99%) as a yellowish oil which was used without

further purification.

(4) (a) For an excellent monograph see: Sommer, L. H.

Stereochemistry Mechanism and Silicon; McGraw-Hill:

New York, 1965. (b) Sommer, L. H. Intra-Sci. Chem. Rep.

1973, 7, 1.

(5) For comprehensive reviews see: (a) Corriu, R. J. P.; Guerin,

C.; Moreau, J. J. E. In Topics in Stereochemistry, Vol. 15;

Eliel, E. L., Ed.; Wiley: New York, 1984, 43–198.

(b) Corriu, R. J. P.; Guerin, C. Adv. Organomet. Chem. 1982,

20, 265.

20

[ ]_D+22.4, [ ]₅₇₈+22.7, [ ]₅₄₆+22.4, [ ]₄₃₆+25.4, [ ]₃₆₅

+29.9 (c 0.33, CHCl₃).

IR (film): 3155 (w), 3072 (m), 3003 (m), 2930 (s), 2863 (m), 2360

(w), 2254 (s), 1794 (vw), 1591 (w), 1473 (m), 1432 (s), 1383 (m),

1293 (w), 1271 (w), 1142 (m), 1113 (s), 1077 (s), 974 (s), 917 (s),

907 (s), 891 (s), 782 (s), 742 (s), 724 (s) cm^–1.

¹H NMR (300 MHz, CDCl₃): = 1.40–1.47 (m, 2 H), 2.09–2.18 (m,

2 H), 2.87 (ddd, J = 16.8, 5.6, 4.7, 1 H), 2.97 (ddd, J = 16.1, 5.4, 4.7

Hz, 1 H), 7.18 (d, J = 8.2 Hz, 1 H), 7.22 (dd, J = 7.3, 7.3 Hz, 1 H),

7.35 (ddd, J = 7.3, 7.3, 1.8 Hz, 1 H), 7.39–7.48 (m, 3 H), 7.53 (dd,

J = 7.9, 1.8 Hz, 1 H), 7.67 (dd, J = 7.9, 2.1 Hz, 2 H).

(6) Sommer, L. H.; Frye, C. L.; Parker, G. A.; Michael, K. W. J.

Am. Chem. Soc. 1964, 86, 3271.

(7) (a) Cyclic substrate 2 (Figure 1) with the stereogenic silicon

being incorporated into a carbocycle was also successfully

resolved by an analogous procedure: Corriu, R. J. P.; Masse,

J. Bull. Soc. Chim. Fr. 1969, 3491. (b) The achiral 2-sila-

1,2,3,4-tetrahydronaphthalene unit is easily assembled in

high yield: Vdovin, V. M.; Nametkin, N. S.; Finkel’shtein,

E. S.; Oppengeim, V. D. Bull. Acad. Sci. USSR Div. Chem.

Sci. (Engl. Trans.) 1964, 429.

¹³C NMR (100 MHz, CDCl₃): = 15.7, 22.0, 34.7, 126.0, 128.1,

128.9, 130.2, 130.4, 130.6, 134.3, 134.5, 135.4, 149.1.

LRMS (EI): m/z = 258/260 [M⁺], 180/182 [(M – Ph)⁺].

HRMS (EI): m/z calcd for C₁₅H₁₅ClSi: 258.06315. Found:

258.06332.

(8) In principle transformations involving reagents with a

stereogenic silicon should be sharply distincted into two

classes: (a) silicon functions as the reaction center with

bonds being formed and broken at silicon whereby any

induced stereoselectivity stems from the stereogenic silicon

(formal silicon to carbon chirality transfer) and (b) an

asymmetrically substituted silicon induces chirality within a

molecule corresponding to chiral auxiliary.

(9) (a) Brook, A. G.; Duff, J. M.; Anderson, D. G. J. Am. Chem.

Soc. 1970, 92, 7567. (b) Bonini, B. F.; Mazzanti, G.; Zani,

P.; Maccagnani, G. J. Chem. Soc., Chem. Commun. 1988,

365. (c) Larson, G. L.; Cruz de Maldonado, V.; Fuentes, L.

M.; Torres, L. E. J. Org. Chem. 1988, 53, 633.

(10) (a) Hathaway, S. J.; Paquette, L. A. J. Org. Chem. 1983, 48,

3351. (b) Fry, J. L.; McAdam, M. A. Tetrahedron Lett. 1984,

25, 5859.

(SiS)-1-Phenyl-1-sila-1,2,3,4-tetrahydronaphthalene [(SiS)-

25b]

Silyl chloride (SiS)-26b (21.6 mg, 0.0834 mmol) was reacted with

LiAlH₄(6.4 mg, 0.17 mmol, 2.0 equiv) in Et₂O (1.0 mL) at 0 °C.

The reaction mixture was maintained at r.t. for 10 min and then ac-

etone (1.0 mL) and H₂O (1.0 mL) were added. The aq phase was ex-

tracted with TBME (3 × 5 mL) and the combined organic phases

were dried over MgSO₄, filtered, and the volatiles were evaporated

under reduced pressure. Purification by flash chromatography on

silica gel (cyclohexane) provided (SiS)-25b (10.2 mg, 55%, er 6:94)

as a colorless liquid. The spectral data were in full accordance with

those for (SiR)-25b.

R_f0.45 (cyclohexane).

FEATURE ARTICLE

Chiral Cyclic Silanes

2739

(11) See also: (a) Daniels, R. G.; Paquette, L. A.

Organometallics 1982, 1, 1449. (b) Larson, G. L.;

Sandoval, S.; Cartledge, F.; Fronczek, F. R.

(27) Alternatively we accessed 3 from expensive 2-bromo-

iodobenzene in a three-step sequence consisting of Heck

reaction with methyl acrylate under Jeffrey conditions (81%

yield using 18 mol% catalyst) followed by standard

reduction and bromination. For the Heck arylation see:

Vallgårda, J.; Appelberg, U.; Arvidsson, L.-E.; Hjorth, S.;

Svensson, B. E.; Hacksell, U. J. Med. Chem. 1996, 39,

1485–1493.

Organometallics 1983, 2, 810. (c) Larson, G. L.; Torres, E.

J. Organomet. Chem. 1985, 293, 19.

(12) Other chiral auxiliaries have been employed as a subsitute

for (–)-menthol [(–)-8]: (a) (+)-tartrate: Dang, H.-S.;

Roberts, B. P.; Tocher, D. A. J. Chem. Soc., Perkin Trans 1

1995, 117. (b) (–)-2-Amino-1-butanol: Jankowski, P.;

Schaumann, E.; Wicha, J.; Zarecki, A.; Adiwidjaja, G.

Tetrahedron: Asymmetry 1999, 10, 519–526. (c) (–)-Man-

delic acid: Strohmann, C.; Hörnig, J.; Auer, D. J. Chem.

Soc., Chem. Commun. 2002, 766.

(28) Lambert, J. B.; Fabricius, D. M.; Hoard, J. A. J. Org. Chem.

1979, 44, 1480.

(29) Ort, O. Org. Synth. 1987, 65, 203.

(30) MeSiCl₃(20a) and PhSiCl₃(20b) are commercially available

whereas -NpSiCl₃(20c) is prepared from SiCl₄and

-NpMgBr in 47% yield. See also: Gilkey, J. W.; Tyler, L.

J. J. Am. Chem. Soc. 1951, 73, 4982.

(13) (a) Djerourou, A.-H.; Blanco, L. Tetrahedron Lett. 1991, 32,

6325. (b) Fukui, T.; Kawamoto, T.; Tanaka, A.

Tetrahedron: Asymmetry 1994, 5, 73. (c) Huber, P.;

Bratovanov, S.; Bienz, S.; Syldatk, C.; Pietzsch, M.

Tetrahedron: Asymmetry 1996, 7, 69–78; and references

cited therein.

(31) For the synthesis of the methyl-substituted derivative

(–)-19a see: Adrianov, K. A.; Mamedov, A. A.; Volkova, L.

M.; Klabunovskii, E. I. Bull. Acad. Sci. USSR Div. Chem.

Sci. (Engl. Trans.) 1967, 1432.

(14) (a) For an account see: Bienz, S. Chimia 1997, 51, 131.

(b) For a recent application see: Trzoss, M.; Shao, J.; Bienz,

S. Tetrahedron 2002, 58, 5885.

(15) Jung, M. E.; Hogan, K. T. Tetrahedron Lett. 1988, 29, 6199.

(16) So far very few enantiomerically enriched cyclic silanes

have been reported^7,17with only 2 (Figure 1) being

accessible in reasonable amounts; however the benzylic

position has been shown to be a reactive site.¹⁸

(17) (a) Roark, D. N.; Sommer, L. H. J. Am. Chem. Soc. 1973, 95,

969. (b) Lefour, J. M.; Loupy, A. Tetrahedron 1978, 34,

2597. (c) For related work see: Dang, H.-S.; Roberts, B. P.;

Tocher, D. A. J. Chem. Soc., Perkin Trans. 1 1995, 117.

(18) Corriu, R. J. P.; Henner, B. J. L. J. Organomet. Chem. 1976,

105, 303.

(19) For intramolecular Friedel-Crafts acylations see:

(a) Barcza, S.; Hoffmann, C. W. Tetrahedron 1975, 31,

2363. (b) Pitt, C. G.; Friedman, A. E.; Rector, D.; Wani, M.

C. Tetrahedron 1975, 31, 2369.

(32) Russo, D. A. In Handbook of Grignard Reagents;

Silverman, G. S.; Rakita, P. E., Eds.; Marcel Dekker: New

York, 1996, 405–439; and references cited therein.

(33) Barbier conditions have also been successfully applied to the

one-step synthesis of silicon-containing rings. For an early

example see: Kiely, J. S.; Boudjouk, P. J. Organomet. Chem.

1979, 182, 173.

(34) As a matter of fact the phenomenon that silyl ethers are

prone to cleavage when maintained in a hydrocarbon solvent

in the presence of deactivated alumina has been reported and

applied to selective deprotection of alcohols: Feixas, J.;

Capdevilla, A.; Camps, F.; Guerrero, A. J. Chem. Soc.,

Chem. Commun. 1992, 1451.

(35) The major shortcoming of preparative reversed phase flash

chromatography is the exeptionally costly reversed phase

silica gel, which we found to be long-lasting with respect to

the number of chromatographies and the quality of the

product separation. MeCN was simply distilled at a rotary

evaporator in a fume cupboard and re-used.

(20) For an example of a failed intramolecular Friedel-Crafts

alkylation (compare ref.^7b) see: Corriu, R.; Henner, B.;

Masse, J. Bull. Soc. Chim. Fr. 1968, 3013.

(36) Sommer, L. H.; McLick, J.; Golino, C. J. J. Am. Chem. Soc.

1972, 94, 669.

(21) (a) Gilman, H.; Marrs, O. L. J. Org. Chem. 1964, 29, 3175.

(b) Gilman, H.; Marrs, O. L. J. Org. Chem. 1965, 30, 325.

(22) (a) Bickelhaupt, F. In Grignard Reagents: New

Developments; Richey, H. G., Ed.; Wiley-Interscience: New

York, 1999, 367–393. (b) Cannon, K. C.; Krow, G. R. In

Handbook of Grignard Reagents; Silverman, G. S.; Rakita,

P. E., Eds.; Marcel Dekker: New York, 1996, 497–526.

(23) For a very recent example of formation of cyclic silanes via

di-Grignard reagents see: Tacke, R.; Handmann, V. I.;

Bertermann, R.; Burschka, C.; Penka, M.; Seyfried, C.

Organometallics 2003, 22, 916–924.

(24) (a) This particular Grignard reagent has been thoroughly

examined: Freijee, F. J. M.; Schat, G.; Akkerman, O. S.;

Bickelhaupt, F. J. Organomet. Chem. 1982, 240, 217.

(b) For a detailed review see: Bickelhaupt, F. Angew. Chem.,

Int. Ed. Engl. 1987, 26, 990.

(37) Since (SiR)-25b is a light liquid wherefore the 1-sila-1,2,3,4-

tetrahydronaphthalenes 25 needed to be structurally

characterized with the (SiRS)-25c instead which is isolated

as a highly viscous oil which solidified upon standing.

(38) Crystallographic data for the structures reported in this paper

have been deposited with the Cambridge Crystallographic

Data Centre as supplementary publication no. CCDC-

208732(23a), CCDC-208733 [(SiRS)-25c], and CCDC-

208734 [(SiS)-22b]. Copies of the data can be obtained free

of charge on application to CCDC 12 Union Road

Cambridge CB21EZ UK [fax: +44(1223)336033; email:

deposit@ccdc.cam.ac.uk].

(39) For another synthesis of 1-bromo-2-(3-bromopropyl)-

benzene(3), see: Beeby, M. H.; Mann, F. G. J. Chem. Soc.

(B) 1951, 411.

(40) See also: van der Winkel, Y.; van Baar, B. L. M.; Bastiaans,

H. M. M.; Bickelhaupt, F.; Schenkel, M.; Stegmann, H. B.

Tetrahedron 1990, 46, 1009.

(25) Pitt, C. G.; Friedman, A. E.; Rector, D. H.; Wani, M. C. J.

Organomet. Chem. 1976, 121, 37.

(26) Meyers, A. I.; Temple, D. L.; Nolen, R. L.; Mihelich, E. D.

J. Org. Chem. 1974, 39, 2778.

Article Doi

A Convergent Method for the Synthesis of Highly Enantiomerically Enriched Cyclic Silanes with Silicon-Centered Chirality

DOI: 10.1055/s-2003-42477

Source and publish data:

Authors:

Article abstract of DOI:10.1055/s-2003-42477

Full text of DOI:10.1055/s-2003-42477

Products guided by the article

R&D Labs maybe for 74685-38-4

Relevant to this article

Hot Product