A chiral (alkoxy)methyl-substituted silicon group as an auxiliary for the stereoselective cuprate addition to α,β-unsaturated ketones: Synthesis of (-)-(R)-phenyl 2-phenylpropyl ketone

Tetrahedron: Asymmetr), Vol 8. No. 10, pp 1587-1603, 1997

Printed in Great Britain

) Pergamon

~

PII: S0957-4166(97)00134-1

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A chiral (alkoxy)methyl-substituted silicon group as an auxiliary for

the stereoselective cuprate addition to et,13-unsaturated ketones:

synthesis of ( -)-(R)-phenyl 2.phenylpropyl ketone

Svetoslav Bratovanov t and Stefan Bienz *

Organisch-chemisches lnstitut, Universitat Ztirich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland

Abstract: The [(benzyloxy)methyl](tert-butyl)methylsilyl group was used as the chiral

auxiliary to effect highly diastereoselective conjugate additions of organocuprates to

enones. Thus, reaction of several R2CuLi with ct-silylated cx,13-unsaturated ketones

afforded the respective addition products with rr-face selectivities of up to 99%.

Starting with an optically active substrate, enantiomerically enriched (-)-(R)-phenyl 2-

phenylpropyl ketone was prepared with virtually no loss of chiral information in a reaction

sequence involving cuprate addition, hydrolysis, and removal of the silicon group. (~) 1997

Elsevier Science Ltd

Introduction

The conjugate addition of organocuprates and other organometallics to tx,~-unsaturated ketones

and carboxylic acid derivatives is widely used in organic synthesis for the preparation of specifically

substituted carbonyl and carboxyl compounds. 1,2 In connection with the increasing importance of

synthetic access to products of stereochemical integrity, the quest for stereoselective variations of

this reaction started already some years ago. So far, a number of stereoselective transformations have

been elaborated, including enantioselective processes that make use of chiral auxiliaries such as,

e.g., chiral sulfoxides3-5 or chiral alkoxy6,7 or aikylamino/amido8-1° groups. Whereas 1,4-additions

to chiral ester and amide derivatives of ct,13-unsaturated carboxylic acids proceed often with high

degrees of diastereoselectivity, the stereochemical success of reactions with or-auxiliary-substituted

tx,13-unsaturated ketones, particularly in the cases of acyclic enone systems, has yet remained rather

modest. 3

In this paper we present the use of the chiral silicon group A as the stereochemical director for

reactions of organocuprates with 0t,13-unsaturated ketones. The group A has already provided high

diastereoselectivities in chelate controlled 1,2-additions to acylsilanes11,12 and, as shown below, proved

equally potent as chiral auxiliary for stereoselective 1,4-additions.

BnO---~ /~,

..Si

t-Bu

x

Me

A

Results and discussion

The model compounds of the type 5a,b and the chiral ot-silyl-substituted tx, 13-unsaturated ketones of

the type 6a,b used for this study have been prepared in a straightforward manner from the corresponding

chlorosilanes 1 and 2 via the allylic alcohols of the type 3a,b and 4a,b (Scheme 1). The syntheses of

the latter compounds has been described before. 13 Oxidation of the alcohols (E)-3a,b and (E)-4a,b

*

f

Corresponding author. Email: sbienz@oci.unizh.ch

Part of the Ph.D. thesis of S. Bratovanov, University of Zurich, 1997.

1587

1588

S. BRATOVANOV and S. B I E N Z

with Jones reagent14 and of the alcohols (Z)-3a,b and (Z)-4a15 with MnO2 afforded the respective

isomerically pure (x,13-unsaturated ketones 5a,b and 6a,b in high yields. The use of milder oxidation

conditions for the preparation of the (Z)-configured compounds 5a,b and 6a was neccessary because

the reaction of the respective precursors, e.g., (Z)-4a, with CrO3 provided substantial amounts of

over-oxidized (x,13-epoxyketones, e.g., 7a. The reason for this peculiar behavior of the silyl-substituted

(Z)-configured allyl alcohols is not known.

HO

~__..

O

R~

?,

CrO3 or

MnO2

IR, ~,_ -

I

Ph

R2

t-Bu--Si--CI

J' J.-

t-Bu -- Si--'(~,

/ e

P

t-Bu-- Si---(,.

/ e ~'~,,, ~

I

Me

~ " R2

R1 = Me:

1

R2

= Me

(E)- and (z)-3a R2 = Me

(E)- and (z)-3b R2 = Ph

(E)- and (z)-Sa

R2 = Ph

(E)- and (Z)-Sb

R1 = B n O C H 2 : 2

R2 = Me

R2= Ph

(E)- and (z)-4a R2 = Me

(E)- and (z)-6a

(E~-6b

(E)-4b R2

= Ph

c o,

t - B u - - ~ - ~~e

(z)-4a

=

t-Bu--~lM~e-M~OO

7a

+ (z)-6a

S c h e m e 1.

The structures of the compounds 5 and 6, particularly their double bond geometries, were ascertained

by correlation with precursor molecules. Additionally, the vinylic protons show absorptions in the 1H-

NMR spectra characteristically different for the (E)- and (Z)-configured enones, the chemical shifts

being moved towards lower fields for the latter compounds. Sound evidence for the assigned double

bond geometries arose also from the values of 3j(29Si,IH)-coupling constants determined for the

vicinal couplings of the vinylic Si- and H nuclei with the novel ACT-J-NMR experiment: 16 the (Z)-

configured compounds displayed 3j(29Si, IH)trans_values of 13-15 Hz, the (E)-configured analogs

3j(29Si, I H)cis-values of 7-8 Hz. These values are characteristic for 3j(29Si, lH)-coupling constants

of vinylsilanes of the given substitution patterns.17

Cuprate additions to (x-silylated ~x, 13-unsaturated ketones were initially tested and optimized with the

achiral model compounds 5a,b. Best results were obtained when the enones of the type 5 were treated

at low temperature with the respective lithium diorganylcuprates, and when the resulting enolates were

trapped as the silyl enol ethers (E)- or (Z)-8 (Scheme 2, Table 1). Hydrolysis with aqueous H2SO4

in acetone provided the epimeric c(-silylated ketones 10/10', which gave the desilylated ketone 12a

(R2, R3=Me, Ph) upon treatment with TBAF in MeCN.

It was imperative to capture the initially formed cuprate addition products as enol ethers: direct

hydrolytic workup led to the formation of substantial amounts of oxidized silicon-free side products.

The addition of N,N,N',N'-tetramethylethylendiamine (TMEDA) to the enolate/TMSCl solution was

neccessary to ensure complete silylation.

The reactions of the enones (E)-5b and (Z)-5a,b with approximately 1.5 equivalents of organocu-

prates and TMSC1 to afford the silyl enoi ethers of the type 8 were highly stereoselective: starting from

the (E)-configured substrate (E)-5b, the respective (E)-configured enol ether 8 was obtained as the

major product, and departing from the (Z)-configured starting materials (Z)-5a,b, the (Z)-configured

products of the type 8 were formed with high preference18 (Table 1). The selectivities probably reflect

the preferred conformations of the starting materials, being most probably s-cis for (E)-5a,b and s-trans

1589

A chiral (alkoxy)methyl-substituted

group

O

1) R32CuLi

TMSO

R1 ~ p h

t-Bu-- Si.--(,,

Et20/-80°C

R' / / ~ - p h

^{t - B u -}I^-~^{S i}R^{- . ~}2

="

IMe ~"~R2

2) -80TMSC0I/'TM°CEDAto

Me H'~R;

(E)- or (z).5a,b

(E)- or (z)6a,b

(E)- and (Z)-8

(E)- and (z)-9a-e

I

HCI / H20

Acetone

O

R3~R2ph

TBAF / MeCN

,i

71 O~.--Ph

t-Bu-- S i - - - . (

.

"eX-S

12a-e

10

11a-e

For R1, R2, R3, double bond configuration, and diastereoselectivities see the Table.

Scheme 2.

for (Z)-Sa,b;19 they are not considered to be the direct consequence of the double bond geometries of

the enones. This assumption is important in connection with the interpretation of the stereoselectivities

found in the cuprate additions performed with the chiral silicon compounds of the type 6. Among the

chiral starting materials 6a,b, the ketones (E)-6a and (Z)-6a delivered the respective addition products

(SiR*,S*,Z)-9a-c and (SiR*,R*,Z)-9a-c with high stereoselectivities, not only in respect to the newly

formed stereogenic center at C(3) but also concerning the double bond configuration of the enol

ether. The selectivities anent chiral induction of the reactions with the (Z)-configured compound were

virtually complete whereas those of the transformations of the (E)-configured analog were slightly

lower, though still satisfactory. The selectivities attained in the preparation of compounds of the type

9 starting from the phenyl-substituted (E)-6b, however, were disappointingly poor in all respects.

The high rr-face selectivities of the cuprate additions to the enones (E)- and (Z)-6a were attributed

to intermediary chelate-structures of the type 13a (Scheme 3). It is assumed that such species are

attacked by the copper reagents from the least hindered site, opposite to the ten-butyl group. This

gives rise to (Z)-enolates of the type 14, which are subsequently trapped by the silylating agent. In

the case of (Z)-6a, the respective stereochemically crucial intermediate (Z)-13a should be formed

particularly facile since negligible steric constraints are introduced into the structure. This is not the

case with (E)-6a, where AI,3 strain arises when the enone is forced from the preferred s-cis into the

s-trans conformation. Therefore, it might be assumed that (E)-6a will not exclusively react via the

highly organized intermediary (E)-13a, and this would thus account for the lower selectivities found

with (E)-6a as the starting material. The still prominent diastereoselectivities obtained in the cuprate

additions to (E)-6a show, however, that the AI,3 strain in complex (E)-13a is not too high and can

be mostly overcome by the returns of free energy attained by the formation of the chelate. With

increasing size of a vinylic substituent positioned cis to the benzoyl group in compounds of the type

(E)-6, though, increasing AI,3 strain is introduced into a derived chelate structure of the type (E)-13.

As a result, chelates of the type (E)-13 should become less favorable and the stereoselectivities of

conjugate additions must be expected to decrease. The poor stereochemical results of the reactions of

organocuprates with (E)-6b, having the rather large phenyl group positioned cis to the benzoyl moiety,

are in fact attributed to this effect.

That chelate intermediates of the type 13 might be important for the stereochemical course of the

1590

S. BRATOVANOV and S. B I E N Z

Table 1. Organocuprate additions to enones of the type 5 and 6, hydrolysis, and desilylation

~.

0

~ >

~.~

~"E

c

,-"

o o

~

.

--

.

2=_

. ~ =

- ~

. = ' o

.

~

:=

~

~;

.~

o

~

O

=

.

~

1

~

o

~

"~.~

,

,~'~

~

•

~:~

.

.k

° =

.-, ,~ ~ ~ ~

. - . -

.

o ~

~

QC

~

= ~^{. - .}=^-~ ' :

~

aC

~

~ 1 > , =~

_

~ "

0

~

0 " ~

E o . = . °

-

~LZ

:E :E :E

~

==

~

.

~

A chiral (alkoxy)methyl-substituted silicon group

1591

"

. Li..o

q

Bno,'Li~Q

BnO"

\k_

/

,nOh O p,

~Bu,,,,Si~

L

Ph

_ _

L

~ -'ph .CUR3 z~ J

t-BUMS'-R

LMe

H

R3

(E)-/(Z)-6a R2= Me

(E)-Sb R2= Ph

(~3-/(z)-13a Rz= Me

_

14

(E)-13b R2 = Ph

Scheme 3.

cuprate additions to (E)-6a and (Z)-6a is supported by the fact that exclusively the (Z)-configured

enol ethers 9a-c were formed. Evidently, and contradictory to the reactions with the achiral model

compounds (E)-5a,b and (Z)-5a,b, a s-trans intermediate is involved not only in the transformation of

the (Z)- but also of the (E)-configured 6a. This seems not to be the case in the transformation of (E)-

6b: since mixtures of four compounds were obtained after its treatment with cuprates and silylation,

it must be assumed that the increased steric strain resulting from a conformational change from the

s-cis to the s-trans form of (E)-6b could only partially be overcome. Reduced stereoselectivities were

notably also obtained when the cuprate additions to any of the compounds of the type 6 were performed

in the presence of a donating additive (like, e.g., TMEDA or THF) that can compete as a ligand for

complexation of the cations with the substrate and thus will disfavor the formation of the chelates of

the type 13.

The stereochemistry of the cuprate additions follows the course that is anticipated on the basis of

the above mentioned 'chelate model'. This is secured by the result obtained from a reaction sequence

starting with optically active substrate (+)-(R,E)-6a. Enantiomerically enriched (+)-(R,E)-6a (96_+2%

ee) was prepared from acetylsilane (-)-(R)-15 (96_+2% ee)2°'21 by a procedure described earlier.13

The compound was treated with Ph2CuLi and led, after direct hydrolysis of the intermediary silyl enol

ether (SiR,3S,Z)-9a, in high yields to the respective mixtures of epimeric ketones (SiR,3S)-lla/lla'

(Scheme 4). Desilylation, which was performed likewise with the racemic ketones of the type 11

and 11' (giving racemic 12a--e, Scheme 2, Table 1), was effected by treatment of (SiR,3S)-lla/lla'

with TBAF in MeCN. The compound obtained this way in 83% overall yield (from (+)-(R,E)-6b)

and in 94_+2% ee was found to be (-)-(R)-phenyl 2-phenylpropyl ketone ((-)-(R)-12a), as assigned

on the basis of its spectroscopic and chiroptic properties.22 The configuration of the chiral center of

(-)-(R)-12a, thus, corresponds to an attack of the cuprate to the Re-side of the rr-system.

BnO.

"1

°

t-Bu,,.,,Si-~(~

Me Me

(+)-(R,~-6a

(-)-(,R)-15

(96+2% ee)

~

95%

0

TBAF / MeCN

87%

H + M~ePh

Ph

k-Mo

H

Ph

(siR,3s~-I 1 a

(-)-(R)-12a

(94-+2% ee)

Scheme 4.

1592

s. BRATOVANOV and S. BIENZ

The formation of (-)-(R)-12a from (+)-(R,E)-6a does at this instance not only support the above

proposed chelate model for the stereoselective conjugate cuprate addition to chiral c~-silyl-substituted

cx,13-unsaturated ketones, but the synthesis of an acyclic 13-chiral ketone in an enantiomeric excess

of 94_+2% by means of an auxiliary-assisted diastereoselective cuprate addition represents also one

of the best examples of such a process. Thus, we have shown that the chiral silicon group A can

efficiently be used as a stereochemical director in 'chelate-controlled' conjugate addition reactions.

Experimental

General remarks

Unless otherwise stated: all org. solvents were distilled prior to use. For the reactions, THF and Et20

were dried over Na in presence of diphenylketyl; CH2CI2 was dried over molecular sieves (3 A). All

reactions were carried out under an Ar atmosphere. Soln. of salts and acids for workup procedures were

prepared in deionized H20. Extracts were dried (MgSO4) and evaporated in vacuo. Chromatography:

silica gel (SiO2) Merck 60 (40-63 pm). M.p.: Mettler FP-5/FP-52. IR (neat): Perkin-Elmer 781; data

in cm -1. UV/VIS (CHC13): Perkin Elmer 555; ~kmax in nm (lg ~). IH-NMR: at 300 MHz in CDCi3;

Bruker AC-300 or Bruker ARX-300; 8 in ppm rel. to CHC13 (=7.26 ppm); J in Hz. 13C-NMR: at 75.6

MHz in CDCI3; Bruker ARX-300; ~ in ppm rel. to CDCI3 (=77.0 ppm); multiplicities from DEPT

experiments. 29Si-NMR: at 119.2 MHz in CDCI3; Bruker ARX-600; 8 in ppm rel. to SiMe4 (=0.00

ppm). 19F-NMR: at 564.5 MHz in CDCI3; Bruker ARX-600; 6 in ppm rel. to CC13F (=0.00 ppm).

CI-MS (chemical ionization mass spectrometry) with NH3 as the reactant gas; Finnigan SSQ 700 or

Varian MAT 90; base peak and quasi-molecular ions only; data in rrdz.

1. Oxidation of the allylic alcohols of the type 3 and 4

1.1. General procedures

A: To a soln. of the respective allylic alcohol in acetone (0.1 M) was added dropwise Jones reagent14

until the color of the mixture remained persistently brown. It was diluted with H20, neutralized with

sat. aq. NaHCO3 soln., extracted with Et20, and chromatographed (SIO2, hexane/EtOAc 25:1). B: To a

soln. of the respective allylic alcohol in CH2C12 (0.1 M) was added MnO2 (5 eq.), and the mixture was

refluxed for 2 h. It was filtered, the solvent was evaporated, and the crude product chromatographed

(SIO2, hexane/EtOAc 25:1).

1.2. (E)- l-[(tert-But),l)dimethylsilyl]prop- 1-enyl phenyl ketone (E)-Sa

According to 1.1, procedure A: (E)-3a13 (232 mg, 0.89 mmol) was converted to (E)-5a (201 mg,

0.77 mmol, 87%). IR: 3080w, 3060w, 3020w, 2959s, 2920s, 2880s, 2850s, 1655s, 1595s, 1575s,

1470m, 1460m, 1445s, 1410m, 1390m, 1370m, 1360m, 1345s, 1310w, 1245s, 1225s, l170s, 1125w,

1070w, 1030m, 1015s, 1005m, 970w, 935w, 870m, 835s, 820s, 805s, 785m, 765s, 740m, 710s, 690s.

UV/VIS: 242 (3.98). IH-NMR: 7.94-7.45 (m, 5 arom. H); 6.25 (q, J=6.7, HC=); 1.63 (d, J=6.7,

MeC=); 0.91 (s, t-Bu); 0.05 (s, Me2Si). 13C-NMR: 202.3 (s, C=O); 145.3 (s, SIC=); 140.1 (d, HC=);

137.6 (s, arom. C); 133.1 (d, arom. C); 129.4, 128.8 (2d, 2×2 arom. C); 27.7 (q, Me3C); 18.3 (q,

MeCH); 18.0 (s, Me3C); -5.5 (q, MeSi). CI-MS: 261 [M+H]÷.

1.3. (Z)-l-[(tert-But),l)dimethylsilyl]prop-l-enyl phenyl ketone (Z)-5a

According to 1.1, procedure B: (Z)-3a13 (394 mg, 1.50 mmol) was converted to (Z)-5a (370 mg,

1.42 mmol, 95%). IR: 3070w, 3050w, 3020w, 2950s, 2920s, 2890s, 2850s, 1650s, 1595s, 1575m,

1465m, 1460m, 1445s, 1405m, 1390m, 1370m, 1340w, 1310m, 1250s, 1175m, 1155w, 1130w, 1070w,

1050m, 1035w, 1020m, 1005m, 955w, 935w, 905w, 870w, 835s, 825s, 800s, 760s, 740w, 730w, 705s.

UV/VIS: 245 (4.02). IH-NMR: 7.82-7.39 (m, 5 arom. H); 6.57 (q, J=6.6, HC=); 1.99 (d, J=6.6,

MeC=); 1.01 (s, t-Bu); 0.17 (s, Me2Si). 13C-NMR: 201.5 (s, C=O); 147.7 (d, HC=); 143.1 (s, SIC=);

138.2 (s, arom. C); 132.2 (d, arom. C); 129.9, 128.1 (2d, 2×2 arom. C); 27.2 (q, Me3C); 18.8 (q,

MeCH); 18.5 (s, Me3C); -3.6 (q, MeSi). CI-MS: 261 [M+H]÷.

1593

Achiral (alkoxy)methyl-substituted silicon group

1.4. (E)- l-[(tert-Butyl)dimethylsilyl]- 2-phenylethenyl phenyl ketone (E)-Sb

According to 1.1, procedure A: (E)-3b13 (113 mg, 0.35 mmol) was converted to (E)-Sb (98 rag, 0.30

mmol, 87%). IR: 3080w, 3050m, 3020m, 2950s, 2930s, 2890m, 2880m, 2850s, 1700m, 1650s, 1595m,

1580m, 1490w, 1465m, 1469m, 1445m, 1410w, 1390m, 1360m, 1315m, 1280w, 1265m, 1250m, 1230s,

1200m, 1175m, 1070w, 1045m, 1005m, 935m, 925m, 900m, 880m, 835s, 820s, 710s. UV/VIS: 247

(4.30). IH-NMR: 7.81-7.04 (m, 10 arom. H); 6.98 (s, HC=); 0.91 (s, t-Bu); 0.07 (s, Me2Si). 13C-

NMR: 202.1 (s, C=O); 145.2 (s, atom. C); 141.3 (d, HC=); 138.6 (s, SIC=); 136.3 (s, arom. C); 132.8

(d, arom. C); 129.1, 128.7 (2d, 2x2 arom. C); 128.3, 128.2 (2d, 2x2 arom. C); 128.1 (d, arom. C);

26.7 (q, Me3C), 18.1 (s, Me3C); -5.7 (q, Me2Si). CI-MS: 323 [M+H]+.

1.5. (Z)-l-[(tert-Butyl)dimethylsilyl]-2-phenylethenyl phenyl ketone (Z)-Sb

According to 1.1, procedure B: (Z)-3b13 (220 rag, 0.68 mmol) was converted to (Z)-Sb (187 mg,

0.58 mmol, 86%). IR: 3080w, 3060m, 3020w, 2950s, 2930s, 2890m, 2850s, 1655s, 1595m, 1580m,

1485m, 1470m, 1460m, 1445m, 1405w, 1390w, 1360w, 1310m, 1250s, 1235s, 1205w, 1175m, 1160w,

1115w, 1060m, 1025m, 1005w, 1000w,935w,910m, 870w, 835s, 820s,790w,760s, 750s,735m, 700s.

UV/VIS: 245 (4.20). 1H-NMR: 7.78-7.11 (m, 10 arom. H); 7.33 (s, HC=); 0.69 (s, t-Bu); -0.27 (s,

Me2Si). 13C-NMR: 201.7 (s, C=O); 149.6 (d, HC=); 145.2 (s, atom. C); 138.1 (s, SIC=); 137.7 (s,

arom. C); 132.6 (d, arom. C); 130.1, 128.3 (2d, 2x2 arom. C); 128.2 (d, arom. C); 127.9, 127.8 (2d,

2x2 arom. C); 27.6 (q, Me3C); 18.1 (s, Me3C); -2.8 (q, Me2Si). CI-MS: 323 [M+H]÷.

1.6. (+_)-(E)- and ( +)-(R,E)- 1- {[(Benzyloxy)methyl](tert-bu~l)methylsilyl}prop- l-enyl phenyl ketone

(E)-6a and (+)-(R,E)-6a

According to 1.1, procedure A: (E)-4a13 (440 mg, 1.20 mmol) or (R,E)-(-)-4a (320 mg, 0.87

mmol) was converted to (E)-6e (430 mg, 1.17 mmol, 98%) or (R,E)-(+)-6a (295 mg, 0.81 mmol,

93%). [CX]D23=13.0 (C=1.7, THF), for (+)-(R,E)-6a. IR: 3080w, 3060w, 3020w, 2950s, 2920s, 2880m,

2850s, 1660s, 1590m, 1575m, 1490w, 1460m, 1445m, 1410w, 1390w, 1375m, 1360m, 1345m, 1310w,

1265m, 1250m, 1230s, l170m, l105m, 1095m, 1070m, 1030m, 1015m, 1000m, 980m, 935m, 900w,

865m, 825s, 810m, 780m, 765m, 735m, 720m, 695s. UV/VIS: 245 (4.03). lH-NMR: 7.85-7.12 (m, 10

arom. H); 6.25 (q, J=6.8, HC=); 4.22 (s, PhCH20); 3.19 (s, SiCH20); 1.51 (d, J=6.8, MeC=); 0.86

(s, t-Bu); 0.01 (s, MeSi). 13C-NMR: 201.5 (s, C=O); 142.6 (s, arom. C); 141.1 (d, HC=); 138.7 (s,

SIC=); 137.4 (s, arom. C); 132.8 (d, arom. C); 129.2, 128.4 (2d, 2x2 arom. C); 128.1,127.4 (2d, 2x2

arom. C); 127.2 (d, arom. C); 77.0 (t, PhCH20); 60.5 (t, SiCH20); 27.0 (q, Me3C); 18.1 (q, MeC=);

17.7 (s, Me3C); -8.5 (q, MeSi). CI-MS: 367 [M+H]÷.

1.7. (Z)- l-{(Benzyloxy)methyl](tert-butyl)methylsilyl}prop- 1-enyl phenyl ketone (Z)-6a

According to 1.1, procedure B: (Z)-4a13 (300 rag, 0.82 mmol) was converted to (Z)-6a (291 mg,

0.80 mmoi, 97%). IR: 3080w, 3060m, 3020m, 2950s, 2920s, 2890m, 2850s, 2810m, 1725w, 1700m,

1650s, 1595m, 1575m, 1490w, 1470m, 1460m, 1445m, 1390m, 1375m, 1360m, 1345w, 1310m, 1250s,

1200w, 1175m, 1155w, 1130w, 1105m, 1090m, 1070s, 1055m, 1035w, 1025m, 1005w, 975w, 935w,

905m, 879w, 830s, 825s, 805m, 770m, 760s, 735s, 705s. UV/VIS: 243 (4.09). IH-NMR: 7.69-7.02

(m, 10 arom. H); 6.53 (q, J=7.1, HC=); 4.20 (s, PhCH20); 3.31, 3.25 (AB, JAB=12.6, SiCH20); 1.89

(d, J=7.1, MeC=); 0.94 (s, t-Bu); 0.19 (s, MeSi). 13C-NMR: 201.3 (s, C=O); 149.6 (d, HC=); 141.5

(s, arom. C); 138.7 (s, SIC=); 138.3 (s, arom. C); 131.9 (d, arom. C); 129.9, 128.0 (2d, 2x2 arom.

C); 127.9, 127.4 (2d, 2x2 arom. C); 127.1 (d, arom. C); 77.1 (t, PhCH20); 61.3 (t, SiCH20); 27.7

(q, Me3C); 18.9 (q, MeCH); 18.5 (s, Me3C); -6.2 (q, MeSi). CI-MS: 367 [M+H]+.

1.8. (E)- l -[[(Benzyloxy)methyl](tert-butyl)methylsilyl}-2-phenylethenyl phen yl ketone (E )-6b

According to 1.1, procedure A: (E)-4b13 (400 mg, 0.93 mmol) was converted to (E)-6b (380 mg,

0.89 mmol, 95%). IR: 3080w, 3060m, 3020m, 2950s, 2930s, 2880m, 2850s, 2810m, 1700m, 1650s,

1594

s. BRATOVANOV and S. BIENZ

1595m, 1580m, 1570m, 1490w, 1470m, 1460m, 1445m, 1390w, 1380m, 1360m, 1310w, 1280w, 1250m,

1225s, 1200rn, l170m, 1155w, l105m, 1090rn, 1070m, 1050m, 1020m, 1005w, 980w, 940w, 930w,

900w, 880w, 825m, 780m, 765m, 745m, 735m, 695s. UV/VIS: 247 (4.25). IH-NMR: 7.86-7.05 (m,

15 arom. H); 7.05 (s, HC=); 4.32 (s, PhCH20); 3.38, 3.33 (AB, JAB =13.1, SiCH20); 0.99 (s, t-Bu);

0.13 (s, MeSi). 13C-NMR: 201.9 (s, C=O); 142.8 (s, arom. C); 142.4 (d, HC=); 138.6 (s, SIC=);

136.6, 136.3 (2s, 2 arom. C); 132.7, 129.2, 128.9, 128.2, 128.1,127.4, 127.2 (7d, 15 arom. C); 77.1 (t,

PhCH20); 60.4 (t, SiCH20); 27.1 (q, Me3C); 18.2 (s, Me3C); -8.5 (q, MeSi). CI-MS: 429 [M+H]+.

2. Preparation of the cuprates

2.1. Ph2CuLi, Bu2CuLi, and Me2CuLi

The respective organolithium reagent (2 eq., commercial) was added to a suspension of CuI (20

mg/ml) in Et20 at -50°C. The temperature was slowly raised to 0°C (30 min), and stirring was

continued for an additional 2 h.

2.2. Et2CuLi

t-BuLi (1 eq., 1.7 M in hexane) was added dropwise to a soln. of EtI in Et20 (0.3=0.4 M) at -78°C.

The temperature was slowly raised to 23°C and stirring was continued for 2 h. The resulting soln. was

dropwise added at - 5 0 ° C to a suspension of CuI (0.5 eq., 20 mg/ml) in Et20, the temperature was

slowly raised to 0°C (30 min), and stirring was continued for an additional 2 h.

3. Cuprate additions to the silylated enones of the type 5 and 6

3.1. General procedure

To a soln. of cuprate reagent (5-10 M in Et20) at - 8 0 ° C were subsequently added TMSCI (2 eq.)

and the respective ketone (0.2-0.5 eq.). The temperature was raised to 0°C over a period of 30 min.,

and the mixture was stirred for 1 h. TMEDA (2 ml) was added and stirring continued for an additional

30 min. It was quenched with sat. aq. NH4CI soln. at 0°C, extracted with Et20, and chromatographed

(SIO2, hexane/CH2Cl2 5:1).

3.2. (E)- and (Z)-2-{ (tert-Bu~'l)dimethylsilyl}- 1-( trimethylsilox3")- 1,3-diphenylbut- l-ene (E)-8 and (Z)-

8

According to 3.1, (E)-Sa (150 mg, 0.58 mmol) was reacted with Ph2CuLi (4.18 mmol) and TMSCI

(1 ml, 8.36 mmol) to give an inseparable mixture of (E)-8 and (Z)-8 (180 mg, 76%, (E)-8/(Z)-8=2:l

determined by I H-NMR). Likewise, (Z)-Sa (90 mg, 0.35 mmol) gave with Ph2CuLi (0.69 mmol) and

TMSCI (0.1 ml, 0.79 mmol) (Z)-8 (129 mg, 0.3 ! mmol, 91%); (E)-Sb ( 150 mg, 0.47 mmol) gave with

Me2CuLi (0.56 mmol) and TMSCI (0.14 ml, 0.94 mmol) (E)-8 (180 mg, 0.44 mmol, 93%); (Z)-Sb

(100 mg, 0.31 mmol) gave with Me2CuLi (0.46 mmol) and TMSCI (0.1 mi, 0.80 mmol) a mixture of

(E)-8 and (Z)-8 (82 mg, 0.20 mmol, 64%, (E)-8/(Z)-8=l:6); (Z)-Sb (112 mg, 0.35 mmol) gave with

Me2CuLi (2.00 mmol) and TMSC! (0.55 ml, 4.38 mmol) a mixture of (E)-8 and (Z)-8 (i 10 mg, 0.27

mmol, 77%, (E)-8/(Z)-8=1:2).

Data of (E)-8 (colorless oil). IR: 3080w, 3050w, 3020w, 2950s, 2920s, 2870s, 2850s, 1610m,

1585s, 1485m, 1460m, 1440m, 1405w, 1385w, 1375w, 1365w, 1355w, 1325w, 1305w, 1260s, 1250s,

1190w, 1135s, 1110m, 1095m, 1070w, 1055w, 1030w, 1005w, 990w, 935w, 920w, 885m, 850s, 840s,

820s, 810s, 785m, 775s, 765s, 725m, 700s. IH-NMR: 7.48-7.12 (m, 10 atom. H), 3.64 (q, J=7.0,

Ph(Me)CH); 1.69 (d, J=7.0, Ph(Me)CH); 0.92 (s, t-Bu); -0.37, - 0 . 4 2 (2s, Me2Si); - 0 . 4 4 (s, Me3Si).

1H, IH-NOE: irrad, at -0.44, responsive signals at 7.48-7.47, 7.30-7.12, and 3.64. 13C-NMR: 157.5

(s, PhC=); 146.6, 139.5 (2s, 2 arom. C); 129.8, 127.3, 126.9, 126.8, 126.4, 123.9 (6d, 10 arom. C);

115.7 (s, SIC=); 38.4 (d, Ph(Me)CH); 27.1 (q, Me3C); 18.5 (q, Ph(Me)CH); 18.1 (s, Me3C); 0.0 (q,

Me3Si); -4.5, -4.9 (2q, Me2Si). CI-MS: 411 [M+H]÷.

Data of (Z)-8 (colorless oil). IH-NMR: 7.61-7.12 (m, 10 arom. H); 3.53 (q, J=7.2, Ph(Me)CH);

1.33 (d, J=7.2, Ph(Me)CH); 0.95 (s, t-Bu); 0.16 (s, MeSi); - 0 . 0 7 (s, Me3Si); - 0 . 4 4 (s, MeSi). IH,IH-

1595

Achiral (alkoxy)methyl-substituted silicon group

NOE: irrad, at -0.07, responsive signals at 0.95, 0.16, and -0.44. 13C-NMR: 158.0 (s, PhC=); 145.5,

138.1 (2s, 2 arom. C); 127.4, 126.8, 126.5, 126.4, 125.9, 125.8 (6d, 10 arom. C); 117.3 (s, SIC=);

38.1 (d, Pb(Me)CH); 27.4 (q, Me3C); 18.3 (q, Ph(Me)CH); 17.4 (s, Me3C); 0.0 (q, Me3Si); -3.1,

-3.6 (2q, Me2Si). CI-MS: 411 [M+H]+.

3.3. (SiR*,R*,E)-, (SiR*,S*,E)-, (SiR*,R*,Z)-, and (SiR*,S*,Z)-2-{[(benzylox¥)methyl](tert-butyl)-

methylsilyl}-l-(trimethylsiloxy)-l,3-diphenylbut-l-ene (SiR *,R*,E)-9a, (SiR *,S*,E)-ga, (SiR *,R*,Z)-

9a, and (SiR *,S*,Z)-9a

According to 3.1, (E)-6a (100 rag, 0.27 mmol) was reacted with PhzCuLi (1.64 mmol) and TMSCI

(0.4 ml, 3.17 mmol); (Z)-6a (70 mg, 0.19 mmol) with PhzCuLi (0.77 mmol) and TMSC1 (0.3 ml, 2.37

mmol); and (E)-6b (80 mg, 0.19 mmol) with Me2CuLi (0.37 retool) and TMSC1 (0.1 ml, 0.88 retool);

to give inseparable mixtures of (SiR*,R*,E)-9a, (SiR*,S*,E)-9a, (SiR*,R*,Z)-9a, and (SiR*,S*,Z)-9a

of the compositions and in the yields given in Table 1. (Data of (SiR*,R*,E)-9a, (SiR*,S*,E)-9a not

given, since these compounds arose only as components in the mixture of all four compounds of the

type 9a.)

Data of (SiR*,R*,Z)-9a (from (Z)-6a, slightly contaminated with (SiR*,S*,Z)-9a): IR: 3080w,

3060w, 3020w, 2960s, 2930s, 2890s, 2850s, 1605m, 1485s, 1460m, 1455m, 1440m, 1410w, 1390w,

1375w, 1360w, 1265s, 1250s, 1200w, 1195w, 1115s, 1080s, 1070s, 1050w, 1035w, 1025m, 1020m,

1000w, 975w, 960m, 935m, 920w, 905m, 870s, 840s. 825s, 785m, 775m, 760s, 745s, 735s, 700s. IH-

NMR: 7.75-7.08 (m, 15 arom. H); 4.58, 4.52 (AB, JAB=12.2, PhCH20); 3.58 (q, J=7.2, Me(Ph)CH);

3.56, 3.50 (AB, JAB=12.5, SiCH20); 1.41 (d, J=7.2, Me(Ph)CH); 1.08 (s, t-Bu); -0.05 (s, MeSi);

-0.38 (s, Me3Si). IH,IH-NOE: irrad, at -0.38, responsive signals at 775-7.08, 4.58, 4.52, 3.56,

3.50, 1.08, and -0.05. 13C-NMR: 158.5 (s, PhC=); 145.2, 138.2, 137.7 (3s, 3 arom. C); 128.1, 127.4,

126.6, 126.5, 126.3, 126.1, 125.9, 125.7, 123.7 (9d, 15 arom. C); 115.5 (s, SIC=); 75.6 (t, PhCH20);

61.9 (t, SiCH20); 37.7 (d, Me(Ph)CH); 27.6 (q, Me3C); 18.3 (q, Me(Ph)CH); 17.4 (s, Me3C); 0.0 (q,

Me3Si); -7.2 (q, MeSi). CI-MS: 517 [M+H]+.

Data of (SiR*,S*,Z)-9a (from (E)-6a, slightly contaminated with (SiR*,R*,Z)-9a): IR: 3080w,

3050w, 3020m, 2960s, 2920s, 2880s, 2850s, 2810w, 1605m, 1585s, 1485m, 1455m, 1410w, 1390w,

1375w, 1360w, 1265s, 1250s, 1200w, l140w, 1115s, 1085s, 1070s, 1055w, 1040w, 1025m, 1020m,

1000w, 980w, 960m, 935w, 920w, 910m, 870s, 840s, 835s, 805m, 785m, 775m, 750s, 735s, 700s.

IH-NMR: 7.33-7.10 (m, 15 arom. H); 4.20 (s, PhCH20); 3.54-3.47 (m, Me(Ph)CH); 2.84, 2.78 (AB,

JAB=I2.7, SiCH20); 1.33 (d, J=7.2, Me(Ph)CH); 0.97 (s, t-Bu); 0.18 (s, MeSi); -0.11 (s, Me3Si).

IH,IH-NOE: irrad, at -0.11, responsive signals at 7.33-7.10, 2.78, 2.84, 0.97, and 0.18. 13C-NMR:

158.3 (s, PhC=); 145.1, 138.1, 137.7 (3s, 3 arom. C); 128.1, 127.7, 126.8, 126.7, 126.5, 126.3,

126.1, 126.0, 123.8 (9d, 15 arom. C); 116.6 (s, SIC=); 75.4 (t, PhCH20); 61.8 (t, SiCH20); 37.9 (d,

Me(Ph)CH); 27.5 (q, Me3C); 18.0 (q, Me(Ph)CH); 17.5 (s, Me3C); 0.0 (q, Me3Si); -6.6 (q, MeSi).

CI-MS: 517 [M+H]+.

3.4. (SiR *,R*,Z)- and (SiR *,S *,Z)-2-[[(Benzyloo')methyl](tert-but3~l)methylsilyl}-3-methyl-l-(tri -

methylsiloxy)- l-phenylpent- l-ene (SIR*, R*, z)-gb and (SIR*, S*,z)-gb

According to 3.1, (E)-6a (100 rag, 0.37 mmol) was reacted with EtzCuLi (1.64 mmol) and TMSC!

(0.9 ml, 7.04 mmol); and (Z)-6a (100 mg, 0.27 mmol) with EtzCuLi (1.10 mmol) and TMSCI (0.6 ml,

4.80 mmol); to give inseparable mixtures of (SiR*,R*,Z)-9b and (SiR*,S*,Z)-9b in the yields given

in Table 1.

Data of (SiR*,R*,Z)-9b (from (Z)-6a, slightly contaminated with (SiR*,S*,Z)-9b): IR: 3060w,

3030w, 2960s, 2920s, 2890s, 2950s, 2810w, 1605m, 1575s, 1485m, 1460m, 1440m, 1410w, 1390w,

1375m, 1360w, 1310w, 1265s, 1250s, 1200w, l170w, l140w, I I00s, 1035w, 1025m, 1010w, 1000w,

980m, 965w, 950w, 920w, 905w, 875s, 840s, 825s, 785s, 760m, 735s, 700s. |H-NMR: 7.37-7.15 (m,

10 arom. H); 4.56, 4.50 (AB, JAB=I2.2, PhCH20); 3.56, 3.43 (AB, JAB=12.7, SiCH20); 1.99-1.96 (m,

1596

S. 13RATOVANOV and S. BIENZ

Et(Me)CH); 1.38-1.21, 1.09-1.06 (2m, MeCH2); 1.05 (s, t-Bu); 0.89 (d, J=7. l, Et(Me)CH); 0.72 (t,

J=7.4, MeCH2); 0.32 (s, MeSi); - 0 . 1 8 (s, Me3Si). IH, JH-NOE: irrad, at -0.18, responsive signals at

7.37-7.15, 4.56, 4.50, 3.56, 3.43, 1.05, and 0.32; irrad, at 1.05, responsive signals at 7.37-7.15, 4.56,

4.50, 3.56, 3.43, 0.32, and -0.18. 13C-NMR: 157.2 (s, PhC--); 138.5, 138.3 (2s, 2 arom. C); 128.3

(d, arom. C); 126.8, 126.5 (2d, 2x2 arom, C); 126.4 (d, atom. C); 126.1, 125.7 (2d, 2x2 arom. C);

116.4 (s, SIC=); 75.6 (t, PhCH20); 62.3 (t, SiCH20); 36.5 (d, Et(Me)CH); 28.7 (t, MeCH2); 27.4

(q, Me3C); 19.9 (q, Et(Me)CH); 17.7 (s, Me3C); 11.9 (q, MeCH2); 0.0 (q, Me3Si); -6.2 (q, MeSi).

CI-MS: 469 [M+H]+.

Data of (SiR*,S*,Z)-9b (from (Z)-6a, slightly contaminated with (SiR*,R*,Z)-9b): IR: 3060w,

3020m, 2950s, 2920s, 2890s, 2850s, 2810m, 1610m. 1570s, 1485m, 1460m, 1440m, 1410w, 1390w,

1375m, 1365m, 1310w, 1265s, 1250s, 1200w, l170w, l140w, 1100s, 1070s, 1025m, 1010w, 1000w,

985m, 950w, 920w, 905w, 875s, 840s, 825s, 780s, 760m, 735s, 700s. IH-NMR: 7.36-7.14 (m, 10

arom. H); 4.54, 4.48 (AB, JAB=I2.2, PhCH20); 3.51, 3.40 (AB, JAB=I2.7, SiCH20); 1.98-1.94

(m, Et(Me)CH); 1.35-1.13 (m, MeCH2); 1.04 (s, t-Bu); 0.87 (d, J=7.1, Et(Me)CH); 0.71 (t, J=7.4,

MeCH2); 0.31 (s, MeSi); - 0 . 1 9 (s, Me3Si). IH, IH-NOE: irrad, at -0.19, responsive signals at

7.36-7.14, 4.54, 4.48, 3.51, 3.40, 1.04, and 0.31. 13C-NMR: 157.3 (s, PhC=); 138.5, 138.2 (2s, 2

arom. C); 128.4 (d, arom. C); 126.8, 126.5 (2d, 2x2 arom. C); 126.4 (d, arom. C); 126.1, 125.7 (2d,

2x2 arom. C); i l 6 . 7 (s, SIC=); 75.6 (t, PhCH20); 62.4 (t, SiCH20); 36.5 (d, Et(Me)CH); 28.5 (t,

MeCH2); 27.3 (q, Me3C); 19.9 (q, Et(Me)CH); 17.6 (s, Me3C); 11.9 (q, MeCH2); 0.0 (q, Me3Si);

-6.3 (q, MeSi). CI-MS: 469 [M+H]+.

3.5. (SiR*,R*,Z)- and (SiR*,S*,Z)-2-{[(Benzylox3.')methyl](tert-bub, l)methylsilyl}-3-methyl-l-(tri-

methylsilo©,)- 1-phenylhept- l-ene (SIR*, R*, Z)-9c and (SIR*, S*,Z)-9c

According to 3.1, (E)-6a (100 rag, 0.27 retool) was reacted with Bu2CuLi (0.81 mmol) and TMSCI

(0.25 ml, 1.97 mmol); and (Z)-6a (104 rag, 0.28 mmol) with Bu2CuLi (0.57 retool) and TMSCI (0.2

ml, 1.34 retool); to give inseparable mixtures of (SiR*,R*,Z)-9c and (SiR*,S*,Z)-9c in the yields given

in Table 1.

Data of (SiR*,R*,Z)-9e: IR: 3060w, 3030w, 2950s, 2920s, 2850s, 2810w, 1605w, 1580s, 1485m,

1460m, 1440m, 1410w, 1390w, 1375m, 1360w, 1265s, 1250s, 1200w, 1135w, l l00s, 1070s, 1025m,

1010w, 1000w, 980w, 920w, 900m, 890m, 860s, 849s, 830s, 785s, 760m, 730m, 700s. IH-NMR:

7.39-7.12 (m, 10 arom. H); 4.55, 4.50 (AB, JAB=I2.2, PhCH20); 3.54, 3.41 (AB, JAB=12.6, SiCH20);

2.35-1.99 (m, Bu(Me)CH); 1.43-1.02 (m, Me(CH2)3); 1.03 (s, t-Bu); 0.87 (d, J=7.1, Bu(Me)CH);

0.79 (t, J=6.8, MeCH2); 0.30 (s, MeSi); - 0 . 2 0 (s, Me3Si). IH, IH-NOE: irrad, at -0.20, responsive

signals at 7.39-7.12, 4.55, 4.50, 3.54, 3.41, 1.03. and 0.30. 13C-NMR: 157.0 (s, PhC=); 138.4, 138.3

(2s, 2 arom. C); 128.3 (d, arom. C); 126.8, 126.5 (2d, 2x2 arom. C); 126.4 (d, arom. C); 126.1,125.7

(2d, 2x2 arom. C); 116.7 (s, SIC=); 75.6 (t, PhCH20); 62.3 (t, SiCH20); 35.7 (t, PrCH2); 34.7 (d,

Me(Bu)CH); 29.3 (t, ETCH2); 27.4 (q, Me3C); 21.5 (t, MeCH2); 20.2 (q, Bu(Me)CH); 17.6 (s, Me3C);

12.8 (q, MeCH2); 0.0 (q, Me3Si); -6.1 (q, MeSi). CI-MS: 497 [M+H]+.

Data of (SiR*,S*,Z)-9e: IR: 3060w, 3020w, 2950s, 2920s, 2890s, 2850s, 1605w, 1580s, 1485w,

1460m, 1440m, 1410w, 1385w, 1375m, 1360w, 1310w, 1265s, 1250s, 1135w, l l00s, 1070s, 1025m,

1010w, 1000w, 980w, 920w, 905m, 890m, 860s, 840s, 825s, 780s, 760m, 730s, 600s. IH-NMR:

7.32-7.10 (m, 10 atom. H); 4.50, 4.45 (AB, JAB=6. I, PhCH20); 3.48, 3.36 (AB, JAB=I2.7, SiCH20);

2.03-1.99 (m, Bu(Me)CH); 1.27-1.02 (m, Me(CH2)3); 1.01 (s, t-Bu); 0.84 (d, J=7.1, Bu(Me)CH);

0.76 (t, J=6.9, MeCH2); 0.27 (s, MeSi); - 0 . 1 5 (s, Me3Si). IH, IH-NOE: irrad, at -0.15, responsive

signals at 7.32-7.10, 4.50, 4.45, 3.48, 3.36, 1.01, and 0.27. 13C-NMR: 157.1 (s, PhC=); 138.5, 138.2

(2s, 2 arom. C); 128.3 (d, arom. C); 126.8, 126.5 (2d, 2x2 arom. C); 126.4 (d, arom. C); 126.1,

125.7 (2d, 2x2 arom. C); 116.9 (s, SIC=); 75.6 (t, PhCH20); 62.4 (t, SiCH20); 35.5 (t, PrCH2); 34.6

(d, Bu(Me)CH); 29.5 (t, ETCH2); 27.3 (q, Me3C); 21.4 (t, MeCH2); 20.3 (d, Bu(Me)CH); 17.6 (s,

(Me)3C); 12.8 (q, MeCH2); 0.0 (q, Me3Si); -6.2 (q, MeSi). CI-MS: 497 [M+H]+.

1597

A chiral (alkoxy)methyl-substituted silicon group

3.6. (SiR*,R*,E)-, (SiR*,S*,E)-, (SiR*,R*,Z)-, and (SiR*,S*,Z)-2-{[(Benzyloo')methyl](tert-butyl)-

methylsilyl}-1-(trimethylsiloxy)- 1,3-diphenylpent- I -ene (SiR *, R*, E)-gd, (SiR*, S *,E)-gd, (SiR *, R*, Z)-

9d, and (SiR*,S*,Z)-gd

According to 3.1, (E)-6b (80 mg, 0.19 mmol) was reacted with Et2CuLi (0.62 mmol) and TMSC1

(0.1 ml, 0.88 mmol) to give (SiR*,R*,E)-9d, (SiR*,S*,E)-9d, (SiR*,R*,Z)-9d, and (SiR*,S*,Z)-9d (91

mg, 0.17 mmol, 89%) as an inseparable mixture. 1H-NMR: rather complex; indicates the presence of

the title structures. Structural proof is given with the derived products of the type lid.

3.7. (SiR *,R *,E)-, (SiR *,S *,E)-, (SiR *,R*,Z)-, and (SiR *,S *,Z)-2-{[(Benzyloxy)methyl](tert-butyl)-

methylsilyl}- 1-(trimethylsiloxy)- 1,3-diphenylhept- l-ene SIR*, R*, E)-9e, (SIR*, S *,E)-ge, (SIR*, R *,Z)-

9e, and (SiR*,S*,Z)-9e

According to 3.1, (E)-6b (80 mg, 0.19 retool) was reacted with Bu2CuLi (0.37 mmol) and TMSCI

(0.1 ml, 0.88 mmol) to give (SiR*,R*,E)-9e, (SiR*,S*,E)-9e, (SiR*,R*,Z)-9e, and (SiR*,S*,Z)-9e (63

mg, 0.11 mmol, 59%) as an inseparable mixture. I H-NMR: rather complex; indicates the presence of

the title structures. Structural proof is given with the derived products of the type lie.

4. Hydrolysis of the enol ethers of the ~'pe 8 and 9

4.1. General procedure

To a soln. of the respective silyl enol ether in acetone (approx. 0.1 M) was added conc. H2SO4 (2-3

drops to 1.5 ml). The mixture was diluted with H20, neutralized with aq. NaHCO3 soln., extracted

with Et20, and chromatographed (SiO2, hexane/EtOAc 25:1).

4.2. (1-[(tert-Butyl)dimethylsilyl]-2-phenylpropyl phenyl ketones 10 and 10'

According to 4.1, compounds of the type 8 gave equal amounts of the epimeric compounds 10 (first

eluting) and 10' (second eluting) as colorless oils in 66-71% yield. The relative configurations of the

stereogenic centers could not be elaborated.

Data of 10 (colorless oil): IR: 3080w, 3060w, 3020m, 2950s, 2920s, 2890m, 2880m, 2850s, 1655s,

1595m, 1575m, 1490m, 1460m, 1445m, 1410w, 1390w, 1360w, 1350m, 1330m, 1305w, 1285s, 1275s,

1250m, 1215rn, 1205m, 1180m, 1155w, l140w, 1070m, 1025w, 1015w, 1000s, 990s, 930w, 905w,

895w, 835s, 820s, 805s, 770m, 760s, 745s, 720m, 700s, 690s. IH-NMR: 7.82-7.15 (m, 10 arom.

H); 3.78 (d, J=8.2, SiCH); 3.56-3.46 (m, Me(Ph)CH); 1.36 (d, J=6.8, Me(Ph)CH); 0.67 (s, t-Bu)

-0.07, -0.17 (2s, Me2Si). 13C-NMR: 203.8 (s, C=O); 147.2, 130.2, (2s, 2 arom. C); 132.2, 128.4,

128.3, 127.4, 126.3 (5d, 10 arom. C); 45.2 (d, SiCH); 41.3 (d, Me(Ph)CH); 27.0 (q, Me3C); 22.4 (q,

Me(Ph)CH); 17.9 (s, Me3C); -5.2, -5.4 (2q, Me2Si). CI-MS: 339 [M+H]+.

Data of 10' (colorless crystals): M.p. 116-118°C (from oil). IR (CHC13): 3080w, 3060w, 3020w,

2969s, 2930s, 2890m, 2880m, 2850s, 1660s, 1595m, 1580m, 1490w, 1460m, 1450m, 1445m, 1410w,

1390w, 1375w, 1360m, 1330s, 1280s, 1260s, l190m, l180m, l120m, 1090s, 1015s, 1000s, 985m,

935w, 900m, 830s, 700s. IH-NMR: 7.69-6.97 (m, 10 arom. H); 3.80 (d, J=l 1.2, SiCH); 3.63-3.53 (m,

Me(Ph)CH); 1.43 (d, J=7.0, Me(Ph)CH); 0.94 (s, t-Bu) 0.20, - 0 . 0 4 (2s, Me2Si). 13C-NMR: 203.3

(s, C=O); 147.7, 139.4, (2s, 2 arom. C); 132.0, 128.1, 128.0, 126.9, 125.7 (5d, 10 arom. C); 46.8 (d,

SiCH); 40.9 (d, Me(Ph)CH); 27.5 (q, Me3C); 24.0 (q, Me(Ph)CH); 18.2 (s, Me3C); -3.7, -5.0 (2q,

Me2Si). CI-MS: 339 [M+H]÷.

4.3. (SiR *,3R *)- and (SiR*,3S*)-l-{[(Benzyloxy)methyl](tert-butyl)methylsilyl}-2-phenylpropyl phe-

nyl ketones (SiR*,3R*)-lla, (SiR*,3S*)-lla, (SiR*,3R*)-lla', and (SiR*,3S*)-lla'

According to 4.1, compounds of the type 9a gave inseparable mixtures of epimeric compounds

(SiR*,3R*)-llaI(SiR*,3S*)-lla (first eluting) and of (SiR*,3S*)-lla'/(SiR*,3S*)-lla' (second elu-

ting) as colorless oils. Yields, diastereomeric ratios, and diastereomeric excesses (in respect to the

stereogenic centers at silicon and C(3)), see Table 1. Likewise, (-)-(SiR,3S)-lla (296 mg, 0.67 mmol,

1598

S. BRATOVANOV and S. BIENZ

84%) and (+)-(SiR,3S)-lla' (38 mg, 0.09 mmol, 11%) were obtained from (+)-(SiR,S,Z)-6a (290 mg,

0.79 mmol) by reaction with Ph2CuLi (6 eq.) according to 3.1 and direct hydrolysis accordin~ to 4.1.

Data of (SiR*,3R*)-lla (from (Z)-6a, slightly contaminated with (SiR*,3S*)-lla): IR: 3080w,

3060w, 3020m, 2960s, 2920s, 2880m, 2750s, 2710w, 1655s, 1595m, 1525m, 1490m, 1460m, 1445s,

1390w, 1380m, 1360m, 1350m, 1325m, 1010w, 1285m, 1265s, 1250s, 1220s, 1205s, l180m, 1155w,

1090s, 1070s, 1025m, 1020s, 1000m, 990m, 935w, 905w, 820s, 800m, 660s, 645s, 635s, 700s. IH-

NMR: 7.87-7.16 (m, 15 atom. H); 4.11, 4.05 (AB, Ja8=ll.9, PhCH20); 3.99 (d, J=7.9, SiCH);

3.63-3.50 (m, Me(Ph)CH); 3.14, 2.95 (AB, JAB=I2.9, SiCH20); 1.37 (d, J=6.9, Me(Ph)CH); 0.82 (s,

t-Bu); 0.13 (s, MeSi). 13C-NMR: 203.6 (s, C=O); 147.0, 140.0, 138.8 (3s, 3 arom. C); 132.1, 128.4,

128.3, 128.1, 127.9, 127.3, 127.0, 126.3 (Sd, 15 arom. C); 76.7 (t, PhCH20); 61.0 (t, SiCH20); 43.6

(d, SiCH); 40.9 (d, Me(Ph)CH); 27.5 (q, Me3C); 22.2 (q, Me(Pb)CH); 18.1 (s, Me3C); -8.3 (q, MeSi).

CI-MS: 445 [M+H]÷.

Data of (SiR*,3R*)-lla' (from (Z)-6a, slightly contaminated with (SiR*,3S*)-lla'): IR: 3080w,

3060m, 3020m, 2960s, 2930s, 2880s, 2850s, 2810w, 1660s, 1595m, 1575m, 1490m, 1465m, 1455s,

1445s, 1404w, 1390w, 1380m, 1360m, 1325m, 1280m, 1260s, 1210m, 1190m, 1180m, 1155m, 1090s,

1070s, 1025m, 1015m, 1000m, 985w, 935w, 905m, 830s, 805m, 785m, 760s, 700s. 1H-NMR: 7.94-6.94

(m, 15 arom. H); 4.31 (s, PhCH20); 3.89 (d, J=l 1.1, SiCH); 3.71-3.60 (m, Me(Ph)CH); 3.32, 3.22

(AB, JAB=I2.9, SiCH20); 1.45 (d, J=7.0, Me(Ph)CH); 0.97 (s, t-Bu); 0.12 (s, MeSi). 13C-NMR: 203.3

(s, C=O); 147.5, 139.2, 138.6 (3s, 3 arom. C); 131.9, 128.2, 128.1, 128.0, 127.5, 127.3, 127.0, 125.8

(Sd, 15 arom. C); 77.0 (t, PhCH20); 61.0 (t, SiCH20); 46.3 (d, SiCH); 41.0 (d, Me(Ph)CH); 27.8 (q,

Me3C); 23.7 (q, Me(Ph)CH); 18.7 (s, Me3C); -6.4 (q, MeSi). CI-MS: 445 [M+H]+.

Data of (-)-(SiR,3S)-lla (from (R,E)-6a, slightly contaminated with (SiR,3R)-Ila): [cx]D23= - 13.8

(c=l.0, THF). IR: 3080w, 3060m, 3020m, 2960s, 2930s, 2880s, 2850s, 2810m, 1660s, 1595m, 1575m,

1490m, 1460m, 1450s, 1445s, 1430w, 1390w, 1380m, 1360m, 1350m, 1330m, 1310w, 1285m, 1265s,

1250s, 1205s, l180m, 1155w, 1090m, 1070s, 1025m, 1000s, 995s, 935w, 905m, 825s, 805s, 780m,

760s, 750s, 735s, 700s. IH-NMR: 7.87-7.11 (m, 15 arom. H); 4.24, 4.18 (AB, JAB=I 1.9, PhCH20);

4.01 (d, J=8.5, SiCH); 3.66-3.56 (m, Me(Ph)CH); 2.97, 2.64 (AB, JAB=I2.8, SiCH20); 1.33 (d, J=6.9,

Me(Ph)CH); 0.76 (s, t-Bu) 0.13 (s, MeSi). 13C-NMR: 203.8 (s, C=O); 146.9, 139.9, 138.8 (3s, 3

arom. C); 132.3, 128.5, 128.3, 128.1,127.4, 127.2, 126.3 (7d, 15 arom. C); 76.9 (t, PhCH20); 60.7 (t,

SiCH20); 43.2 (d, SiCH); 41.1 (d, Me(Ph)CH); 27.5 (q, Me3C); 22.5 (q, Me(Ph)CH); 18.2 (s, Me3C);

-8.3 (q, MeSi). CI-MS: 445 [M+H]+.

Data of (+)-(SiR,3S)-lla' (from (R,E)-6a, slightly contaminated with (SiR,3R)-lla'): [cx]D23=33.6

(c=1.2, THF). IR: 3080w, 3060w, 3020m, 2960s, 2920s, 2850s, 2810w, 1725w, 1685w, 1660s, 1595m,

1580m, 1490m, 1470m, 1450s, 1445s, 1390w, 1375m, 1360m, 1325m, 1280m, 1260s, 1210m, 1190m,

1180m, 1155w, 1090s, 1070s, 1025m, 1015m, 1000m, 985m, 935w, 900w, 830s, 800m, 790m, 760s,

735s, 700s. I H-NMR: 7.69-6.91 (m, 15 arom. H); 4.29, 4.23 (AB, JAB=11.8, PhCH20); 3.94 (d, J= 11.2,

SiCH) 3.66-3.55 (m, Me(Ph)CH); 3.30, 3.13 (AB, JAB=12.8, SiCH20); 1.44 (d, J=6.8, Me(Ph)CH);

1.04 (s, t-Bu); 0.11 (s, MeSi). 13C-NMR: 203.0 (s, C=O); 147.3, 139.2, 138.6 (3s, 3 atom. C); 131.8,

128.0, 127.9, 127.8, 127.4, 127.1,127.0, 126.0 (8d, 15 arom. C); 76.9 (t, PhCH20); 61.7 (t, SiCH20);

45.6 (d, SiCH); 41.1 (d, Me(Ph)CH); 28.0 (q, Me3C); 23.7 (q, Me(Ph)CH); 18.6 (s, Me3C); -7.5 (q,

MeSi). CI-MS: 445 [M+H]+.

ketones (SiR*,3R*)-llb, (siR*,3s*)-llb, (siR*,3R*)-11b', and (SiR*,3S*)-11b'

According to 4.1, compounds of the type 9b gave inseparable mixtures of (SiR*,3R*)-llb,

(SiR*,3S*)-llb, (SiR*,3R*)-llb', and (SiR*,3S*)-llb' as colorless oils. Yields, diastereomeric ratios,

and diastereomeric excesses (in respect to the stereogenic centers at silicon and C(3)), see Table 1.

Data of mixture (SiR*,3R*)-llb/(SiR*,3R*)-llb' (from (Z)-6a, slightly contaminated with

(SiR*,3S*)-llb/(SiR*,3S*)-llb'): IR: 3080w, 3060m, 3030m, 2960s, 2930s, 2850s, 2810m, 1730w,

Achiral (alkoxy)methyl-substituted silicon group

1599

1660s, 1595m, 1575m, 1490w, 1460s, 1445s, 1430m, 1410w, 1390m, 1380m, 1360m, 1320m, 1300w,

1280m, 1255s, 1210s, 1205s, 1180m, 1155m, 1095s, 1070s, 1035m, 1000m, 990m, 935w, 905m, 825s,

805s, 780m, 735s, 700s. IH-NMR (major two isomers): 7.87-7.83, 7.43-7.04 (2m, 10 atom. H);

4.23, 4.05, 4.01 (s and AB, JAB=12.2, PhCH20); 3.62, 3.44 (2d, J=5.6, 7.9, SiCH); 3.19, 3.11, 3.14,

2.89 (2AB, JAB=12.9, 12.9, SiCH20); 2.23-2.10, 2.07-1.98 (2m, Et(Me)CH); 1.55-1.39, 1.20-1.05

(2m, MeCH2); 1.00, 0.99 (2d, J=6.8, 6.8, Et(Me)CH); 0.91, 0.81 (2s, t-Bu); 0.81, 0.72 (2t, J=7.8,

7.4, MeCH2); 0.03, 0.00 (2s, MeSi). 13C-NMR (major two isomers): 204.0, 203.5 (2s, C=-O); 140.1,

139.9, 138.8, 138.7 (4s, 2 arom. C); 132.2, 132.1, 128.4, 128.3, 128.2, 128.1, 128.0, 127.5, 127.2,

127.0 (10d, 10 arom. C); 77.9, 76.8 (2t, PhCH20); 61.6, 61.1 (2t, SiCH20); 44.0, 41.3 (2d, SiCH);

36.4, 36.2 (2d, Et(Me)CH); 31.1, 29.2 (2t, MeCH2); 27.7 (q, Me3C); 20.1, 18.6 (2q, MeCH); 18.4,

18.2 (2s, Me3C); 12.2, 11.7 (2q, MeCH2); -6.8, -8.3 (2q, MeSi). 29Si-NMR: 4.92, 4.26, 4.25, 3.87

(ratio 3:38:58:1). CI-MS: 397 [M+H]+.

Data of mixture (SiR*,3S*)-llb/(SiR*,3S*)-Ilb' (from (E)-6a, slightly contaminated with

(SiR*,3R*)-llb/(SiR*,3R*)-Ilb'): IR: 3080w, 3060m, 3020m, 2960s, 2920s, 2850s, 2810m, 1660s,

1595m, 1575m, 1490w, 1460s, 1445s, 1430m, 1390m, 1380m, 1360m, 1320m, 1275m, 1250s, 1210s,

l180m, 1155w, l105m, 1090m, 1070s, 1025m, 1000m, 990m, 935w, 905m, 825m, 805m, 780m,

730s, 700s. IH-NMR (major two compounds): 7.93-7.90, 7.51-7.11 (2m, 10 arom. H); 4.36, 4.17,

4.12 (s and AB, JAB=12.0, PhCH20); 3.61, 3.58 (2d, J=6.0, 7.7, SiCH); 3.31, 3.23, 3.23, 3.02 (2AB,

JaB=13.0, 13.0, SiCH20); 2.25-2.09 (m, Et(Me)CH); 1.70-1.50 1.30-1.12 (2m, MeCH2); 1.05 1.03

(2d, J=6.7, 6.7, Et(Me)CH); 0.97, 0.87 (2s, t-Bu); 0.89, 0.81 (2t, J=5.9, 7.3, MeCH2); 0.08, 0.07 (2s,

MeSi). 13C-NMR (major two compounds): 203.9, 203.6 (2s, C=O); 140.1, 139.9, 138.8, 138.7 (4s,

2 arom. C); 132.2, 132.1, 128.3, 128.2, 128.1, 128.0, 128.5, 127.3, 127.0 (9d, 10 arom. C); 77.1,

76.8 (2t, PhCH20); 61.7, 61.0 (2t, SiCH20); 43.4, 42.1 (2d, SiCH); 36.2 (d, Et(Me)CH); 31.0, 28.8

(2t, MeCH2); 27.9, 27.7 (2q, Me3C); 20.1, 18.7 (2q, MeCH); 18.4, 18.3 (2s, Me3C); 12.1, 11.7 (2q,

MeCH2); -7.3, -7.9 (2q, MeSi). 29Si-NMR: 4.92, 4.26, 4.25, 3.87 (ratio 59:5:5:31). CI-MS: 397

[M+H] +.

4.5. (SiR*,3R*)- and (SiR*,3S *)-l-{[(Benzylox).,)methyl](tert-buo, l)methylsilyl}-2-methylhexyl phenyl

ketones (SiR*,3R*)-llc, (SiR*,3S*)-llc, (SiR*,3R*)-11c', and (SiR*,3S*)-11c'

According to 4.1, compounds of the type 9c gave inseparable mixtures of (SiR*,3R*)-llc,

(SiR*,3S*)-Ilc, (SiR*,3R*)-llc', and (SiR*,3S*)-llc' as colorless oils. Yields, diastereomeric ratios,

and diastereomeric excesses (in respect to the stereogenic centers at silicon and C(3)), see Table 1.

Data of mixture (SiR*,3R*)-IIc/(SiR*,3R*)-llc' (from (Z)-6a, slightly contaminated with

(SiR*,3S*)-llc/(SiR*,3S*)-llc'): IR: 3080w, 3060w, 3020w, 2950s, 2920s, 2850s, 1655s, 1595m,

1575m, 1490w, 1465m, 1445m, 1375m, 1360m, 1340w, 1325w, 1275m, 1250m, 1220m, 1210m,

1180m, 1155w, l105m, 1090m, 1070s, 1025w, 1000m, 995m, 935w, 905w, 825m, 800m, 780m,

735s, 695s. IH-NMR (major two isomers): 7.90-7.86, 7.48-7.06 (2m, 10 arom. H); 4.27, 4.06 (2s,

PhCH20); 3.64, 3.48 (2d, J=5.6, 7.6, SiCH); 3.23, 3.14, 3.14, 2.91 (2AB,JAB=12.8, 12.8, SiCH20);

2.30-2.21, 2.20-2.16 (2m, Bu(Me)CH); 1.53-1.03 (m, Me(CH2)3); 1.04, 1.02 (2d, J=4.5, 4.7,

MeCH); 0.95, 0.84 (2s, t-Bu); 0.78, 0.76 (2t, J=5.1, 4.8 MeCH2); 0.07, 0.04 (2s, MeSi). 13C-NMR

(major two isomers): 204.0, 203.6 (s, C=O); 140.2, 139.9, 138.7, 138.6 (4s, 2 arom. C); 132.2, 132.0,

128.4, 128.3, 128.2, 128.1, 128.0, 127.5, 127.2, 127.0 (10d, 10 arom. C); 77.0, 76.8 (2t, PhCH20);

61.6, 61.1 (2t, SiCH20); 44.2, 41.7 (2d, SiCH); 38.1, 36.2 (2t, PrCH2); 34.6 (d, Me(Bu)CH); 29.9,

29.7 (2t, EtCH2); 27.8, 27.7 (2q, Me3C); 22.7 (t, MeCH2); 20.7, 19.1 (2q, MeCH); 18.4, 18.2

(2s, Me3C); 14.0 (q, MeCH2); -6.8, -8.2 (2q, MeSi). 29Si-NMR: 4.93, 4.28, 4.24, 3.89 (ratio

2.5:46:48:3.5). CI-MS: 425 [M+H]+.

Data of mixture (SiR*,3S*)-llcl(SiR*,3S*)-ll¢' (from (E)-6a, slightly contaminated with

(SiR*,3R*)-llcI(SiR*,3R*)-lle'): IR: 3080w, 3060m, 3020m, 2850s, 2820s, 2790s, 2810m, 1660s,

1595m, 1575m, 1490w, 1460s, 1445s, 1375m, 1360m, 1320m, 1275m, 1250s, 1220m, 1210m, l180m,

1600

S. BRATOVANOV and S. BIENZ

1155w, 1090m, 1070s, 1025m, 1000m, 995m, 935w, 905w, 825s, 800m, 780m, 695s. IH-NMR

(major two compounds): 7.93-7.89, 7.49-7,11 (2m, 10 arom. H); 4.36, 4.16, 4.12 (s and AB, J=l 1.5,

PhCH20); 3.59, 3.57 (2d, J=6.1, 7.8, SiCH); 3.31, 3.24, 3.23, 3.02 (2AB, JAB=I2.9, 12.9, SiCH20);

2.26-2.19, (m, Bu(Me)CH); 1.55-1.19 (m, Me(CH2)3); 1.05, 1.03 (2d, J=5.7, 6.7, MeCH); 0.97,

0.88 (2s, t-Bu); 0.83, 0.81 (2t, J=6.8, 7.6, MeCH2); 0.08, 0.06 (2s, MeSi). 13C-NMR (major two

compounds): 203.9, 203.7 (s, C=O); 140.1, 140.0, 138.8, 138.7 (4s, 2 arom. C); 132.2, 132.1, 128.3,

128.24, 128.2, 128.1, 128.0, 127.5, 127.3, 127.1 (10d, 10 atom. C); 77.1, 76.8 (2t, PhCH20); 61.7,

61.0 (2t, SiCH20); 43.6, 42.3 (2d, SiCH); 38.1, 35.9 (2t, PrCH2); 34.7, 34.5 (2d, Bu(Me)CH); 29.9,

29.8 (2t, ETCH2); 27.9, 27.7 (2q, Me3C); 22.7 (t, MeCH2); 20.8, 19.2 (2q, MeCH); 18.4, 18.3 (2s,

Me3C); 14.0 (q, MeCH2); -7.3, -7.9 (2q, MeSi). 29Si-NMR: 4.93, 4.28, 4.24, 3.89 (ratio 63:5:4:28).

CI-MS: 425 [M+H]÷.

4.6. (SiR *,3R *)- and (SiR *,3S *)- l-{[(Benzylox3")methyl](tert-butvl)methylsilyl}-2-phenylbuo, l phenyl

ketones (SiR*,3R*)-lld, (SiR*,3S*)-lld, (SiR*,3R*)-IId'. and (SiR*,3S*)-lld'

According to 4.1, compounds 9d (91 mg, 0.17 mmol, 89%) gave inseparable mixtures of epimeric

(SiR*,3R*)-lld/(SiR*,3S*)-Ild (25 mg, 0.05 mmol, 32'~', first eluting, ratio 5:1, determined by 1H-

NMR) and of(SiR*,3R*)-lld'/(SiR*,3S*)-lld' (32 rag, 0.07 mmol, 41%, second eluting, ratio 1.6:1,

determined by 1H-NMR).

Data of (SiR*,3R*)-lld/(SiR*,3S*)-lld (as a mixture): IR: 3080w, 3060m, 3020m, 2980s, 2930s,

2850s, 2810m, 1660s, 1595m, 1575m, 1490m, t460m, 1450s, 1445s, 1430w, 1390w, 1375m, 1360m,

1325m, 1310w, 1290w, 1260s, 1250s, 1215m, 1200m, l lS0m, 1155w, l140w, l105m, 1090s, 1070s,

1025m, 1010m, 1000m, 985m, 960w, 935w, 905w, 860m, 830m, 800m, 780m, 755m, 740s, 700s. IH-

NMR: 7.94-7.82, 7.56-7.12 (2m, 15 arom. H); 4.20, 4.14, 4. I1,4.05 (2AB, JAB=I 1.9, 9.3, PhCH20);

4.05, 4.02 (2d, J=9.3, 10.6, SiCH); 3.35-3.25 (rn, Ph(Et)CH); 3.13, 2.97, 2.90, 2.47 (2AB, JAB=12.9,

12.8, SiCH20); 1.90-1.77, 1.70-1.57 (2m, MeCH2); 0.79, 0.75 (2s, t-Bu) 0.59, 0.57 (2t, J=5.9, 7.2

MeCH2); -0.02, -0.07 (2s, MeSi). 13C-NMR: 204.1. 204.0 (2s, C=O); 144.1, 139.9, 138.8 (3s, 3

arom. C); 132.4, 132.2, 128.6, 128.5, 128.3, 128.2, 128.1, 127.9, 127.4, 127.3, 127.2, 126.4 (12d, 15

atom. C); 76.8, 76.7 (2t, PhCH20); 61.0, 60.1 (2t, SiCH20); 48.7, 48.6 (2d, SiCH); 44.3, 43.1 (2d,

Ph(Et)CH); 29.2, 28.7 (2t, MeCH2); 27.6 (q, Me3C); 18.3, 18.1 (2s, Me3C); 12.3 (q, MeCH2); -8.4

(q, MeSi). CI-MS: 459 [M+H]+.

Data of (SiR*,3R*)-lld' and (SiR*,3S*)-lld' (as a mixture): IR: 3080m, 3060s, 3020s, 2950s,

2920s, 2850s, 2810m, 1655s, 1595m, 1575m, 1490m, 1460s, 1450s, 1430m, 1405m, 1390m, 1375m,

1360m, 1320m, 1300m, 1255s, 1215rn, 1185m, 1155m, l105m, 1090s, 1070s, 1025m, 1010m, 1000m,

975m, 930m, 920m, 900m, 845m, 835m, 800m, 780m, 765m, 735rn, 700s. IH-NMR: 7.68-7.62,

7.42-6.95 (2m, 15 arom. H); 4.33, 4.31,4.25 (s and AB, JAB=12.0, PhCH20); 4.00, 3.93 (2d, J=l 1.1,

11.0, SiCH); 3.39-3.24 (m, Ph(Et)CH); 3.34, 3.24, 3.31, 3.14 (2AB, JAB=I2.9, 12.8, SiCH20);

2.15-1.99, 1.70-1.58 (2m, MeCH2); 1.05, 0.98 (2s, t-Bu) 0.75, 0.66 (2t, J=12.3, 7.4 MeCH2); 0.10 (s,

MeSi). 13C-NMR: 203.1,202.8 (2s, C=O); 144.6, 144.4, 139.4, 138.6 (4s, 3 arom. C); 131.8, 128.6,

128.5, 128.3, 128.2, 128.1, 128.9, 127.9, 127.7, 127.5, 127.4, 127.3, 127.1, 125.7 (14d, 15 arom. C);

77.1, 76.9 (2t, PhCH20); 61.8, 61.0 (2t, SiCH20); 48.4, 48.2 (2d, SiCH); 45.9, 45.0 (2d, Ph(Et)CH);

29.7, 29.1 (2t, MeCH2); 28.1, 27.8 (q, Me3C); 18.7, 18.1 (2s, Me3C); 12.3, 12.2 (2q, MeCH2); -6.3,

-7.6 (q, MeSi). CI-MS: 459 [M+H]+.

ketones (SiR*,3R*)-Ile, (SiR*,3S*)-Ile, (SiR*,3R*)-lle', and (SiR*,3S*)-lle'

According to 4.1, compounds 9e (63 mg, 0.11 mmol, 59%) gave inseparable mixtures of epimeric

(SiR*,3R*)-IIe/(SiR*,3S*)-lle (17 mg, 0.03 mmol, 27%, first eluting, ratio 8:1, determined by IH-

NMR) and of (SiR*,3R*)-lle' and (SiR*,3S*)-lle' (36 rag, 0.07 mmol, 66%, second eluting, ratio

3:1, determined by IH-NMR).

A chiral (alkoxy)rnethyl-substituted silicon group

1601

Data of (SiR*,3R*)-lle/(SiR*,3S*)-Ile (as a mixture): IR: 3080m, 3060m, 3020m, 2950s, 2930s,

2850s, 2810m, 1665s, 1595m, 1580m, 1490m, 1465s, 1450s, 1445s, 1410w, 1390w, 1375m, 1360m,

1325m, 1300w, 1275m, 1259s, 1205m, 1185m, 1155w, l l05m, 1090s, 1070s, 1025m, 1000m, 985m,

935w, 905m, 825s, 800m, 780m, 765s, 735s, 700s. 1H-NMR (major isomer): 7.80-7.77, 7.45-7.10 (2m,

15 arom. H); 4.10, 4.03 (AB, JAB=I 1.9, PhCH20); 3.97 (d, J=8.l, SiCH); 3.35-3.28 (m, Ph(Bu)CH);

3.09, 2.94 (AB, JAB=12.9, SiCH20); 1.83-1.64 (m, PrCH2): 1.21-0.80 (m, Me(CH2)2); 0.78 (s, t-Bu)

0.71 (t, J=7.4, MeCH2); -0.08 (s, MeSi). 13C-NMR (major isomer): 203.8 (s, C=O); 144.8, 140.0,

138.8 (3s, 3 arom. C); 132.1, 128.4, 128.3, 128.2, 127.9, 127.3, 127.0, 126.4 (Sd, 15 arom. C); 76.6 (t,

PhCH20); 61.0 (t, SiCH20); 46.7 (d, SiCH); 44.0 (d, Ph(Bu)CH); 35.3 (t, PrCH2); 30.3 (t, ETCH2);

27.5 (q, Me3C); 22.4 (t, MeCH2); 15.2 (s, Me3C); 13.9 (q, MeCH2);-8.2 (q, MeSi). CI-MS: 487

[M+H] +.

Data of (SiR*,3R*)-lle' and (SiR*,3S*)-lle' (as a mixture): IR: 3080w, 3060m, 3020m, 2950s,

2930s, 2850s, 2810m, 1660s, 1595m, 1580m, 1490m, 1465m. 1450m, 1445m, 1390w, 1375m, 1360m,

1325m, 1300w, 1280m, 1250m, 1215m, 1200m, 1180m, 1165w, 1090m, 1070m, 1025w, 1000m, 940w,

905w, 825m, 800m, 780m, 735m, 700s. |H-NMR: 7.67-7.61, 7.41-6.94 (2m, 15 atom. H); 4.33, 4.26

(2s, PhCH20); 3.98, 3.92 (2d, J=l 1.3, 11.0, SiCH); 3.48-3.34 (m, Ph(Bu)CH); 3.34, 3.24, 3.24, 3.12

(2AB, JAB=13.0, 12.8, SiCH20); 2.06-1.95, 1.69-1.56 (2m, PrCH2); 1.31-1.10 (m, Me(CH2)2); 1.05,

0.98 (2s, t-Bu) 0.81,0.76 (2t, J=7.4, 7.2, MeCH2); 0.11,0.10 (2s, MeSi). 13C-NMR: 203.2,202.9 (2s,

C=O); 145.0, 144.8, 139.4, 138.6 (4s, 3 arom. C); 131.8, 128.2, 128.0, 127.9, 127.7, 127.6, 127.4,

127.3, 127.1, 125.7 (10d, 15 arom. C); 77.1,76.9 (2t, PhCH20); 61.9, 61.0 (2t, SiCH20); 46.7.46.5

(2d, SiCH); 46.1,45.2 (2d, Ph(Bu)CH); 36.6, 36.5 (2t, PrCH2); 29.9, 29.8 (2t, ETCH2); 28.0, 27.9 (2q,

Me3C); 22.6 (t, MeCH2); 18.6 (s, Me3C); 15.2, 14.0 (2q, MeCH2); -6.2, -7.6 (2q, MeSi). CI-MS:

487 [M+H]+.

5. Removal of the silicon groups of compounds of the t3"pe 10 and 11

5.1. General procedure

To a soln. of the respective cx-silylated ketone in CH3CN (0.1 M) was added TBAF (4 eq., 1 M

in THF). The mixture was stirred for 1 h and diluted with H20. It was extracted with Et20 and

chromatographed (SiO2, hexane/EtOAc 25:1).

5.2. (+_)- and (-)-(R)-Phenyl 2-phenylpropyl ketone (+_)-12a and (-)-(R)-12a

According to 5.1, a mixture of all racemic isomeric compounds of the type 10 ( 159 mg, 0.47 mmol)

gave (_+)- 12a (86 mg, 0.38 mmol, 82%) as a colorless oil. Likewise, a mixture of all racemic compounds

of the type 11 (170 mg, 0.38 mmol) gave (_+)-12a (75 rag, 0.33 mmol, 87%) (oil), and (-)-(SiR,3S)-I la

(170 mg, 0.38 mmol) gave (-)-(R)-12a (75 rag, 0.33 mmol, 87%) as a colorless solid. M.p.: 45-50°C

(oil for (-)-(R)-12a,22 45--48°C for (+)-(S)-12a23). [or]D23= - 12.4 (c=1.4, CC14)(- 14.8 (c=1.2, CC14)

for (-)-(R)-12a,22 +13.3 (c=2.8, CC14) for (+)-(S)-12a23). |R: 3080m, 3050m, 3020s, 2960s, 2920m,

2870m, 1685s, 1595s, 1580m, 1490m, 1445s, 1400m, 1360m, 1310m, 1270s, 1215s, 1200s, 1175m,

1155w, 1100w, 1075w, 1020m, 990s, 935w, 905w, 875w, 840w, 835w, 790w, 755s, 700s. IH-NMR:

7.98-6.96 (m, 10 arom. H); 3.55-3.42 (m, Me(Ph)CH); 3.28, 3.16 (AB ofABX, JAB=16.4, JAX=8.2,

JBX=5.7, PhCOCH2); 2.51 (d, J=6.9, MeCH). 13C-NMR: 199.0 (s, C=O); 146.5, 137.2 (2s, 2 arom.

C); 132.9, 128.5, 128.0, 126.8, 126.2 (5d, 10 arom. C); 47.0 (t, PhCOCH2); 35.5 (d, MeCH); 15.2 (q,

MeCH). CI-MS: 242 [M+NH4]+.

The enantiomeric excess of (-)-(R)-12a was determined by means of the Mosher method:24 (-)-

(R)-12a (160 rag, 0.71 mmol) was reduced with LiAIH4 (32 mg, 0.84 mmol) in Et20 (5 ml) to give two

isomeric alcohols (ratio ca. 1:1,94%), which were separated by chromatography (SiO2, hexane/EtOAc

25:1). The first eluting isomer (20 mg, 0.09 mmol) was transferred into the respective Mosher ester

(20 mg, 0.05 mmol, 61%) by treatment with (-)-(R)-ot-methoxy-o~-trifluoromethylphenylacetic acid

chloride (112 mg, 0.44 mmol) in the presence of Et3N. 19F-NMR: 71.42, 71.91 (ratio 97:3).

1602

S. BRATOVANOV and S. BIENZ

5.3. 2-Methylbuo,l phenyl ketone 12b

According to 5.1, a mixture of all compounds of the type lib (243 mg, 0.61 mmol) gave 12b

(93 mg, 0.53 mmol, 86%) as a colorless oil. IR: 3080w, 3060m, 3020w, 2960s, 2920s, 2870s, 1690s,

1595m, 1580m, 1470m, 1445s, 1405m, 1360s, 1320m, 1280m, 1260m, 1205s, 1180m, ! 155w, 1 lO0w,

1075w, 1015m, 1000m, 995w, 965w, 930w, 915w, 890w, 840w, 825w, 780w, 750s, 690s. IH-NMR:

7.78-7.24 (m, 5 arom. H); 2.76, 2.55 (AB ofABX, JAB=I 5.7, JAX=7.9, JBX=5.7, PhCOCH2); 1.96-1.85

(m, Me(Et)CH); 1.32-0.98 (m, MeCH2); 0.77 (d, J=6.7, MeCH); 0.74 (t, J=7.4, MeCH2). 13C-NMR:

200.4 (s, C=O); 137.4 (s, arom. C); 132.7 (d, arom. C); 128.4, 128.0 (2d, 2×2 arom. C); 45.5 (t,

PhCOCH2); 31.3 (d, Me(Et)CH); 29.6 (t, MeCH2): 19.4 (q, MeCH); 11.3 (q, MeCH2). CI-MS: 194

[M+NH4] +.

5.4. 2-Methylhex3'l phenyl ketone 12c

According to 5.1, a mixture of all compounds of the type llc (261 mg, 0.62 mmol) gave 12e (112

mg, 0.55 mmol, 89%) as a colorless oil. IR: 3080w, 3060w, 3020w, 2950s, 2920s, 2870s,, 2850s, 1690s,

1595m, 1580m, 1460rn, 1445s, 1405w, 1375m, 1360rn, 1315w, 1280m, 1250w, 1215m, 1190w, 1180m,

1155w, 1100w, 1070w, 1000m, 940w, 910w, 890w, 840w, 770w, 750s, 690s. IH-NMR: 7.78-7.23

(m, 5 arom. H); 2.76, 2.55 (AB of ABX, JAB--15.8, JAX=7.9, JBX=5.7, PhCOCH2); 2.00-1.93 (m,

Me(Bu)CH); 1.24-0.99 (m, Me(CH2)3); 0.77 (d, J=6.7, MeCH); 0.76-0.68 (m, MeCH2). 13C-NMR:

200.4 (s, C=O); 137.4 (s, atom. C); 132.7 (d, arom. C); 128.4, 128.0 (2d, 2x2 arom. C); 45.9 (t,

PhCOCH2); 36.8 (t, PrCH2); 29.7 (d, Me(Bu)CH); 29.2 (t, ETCH2); 22.8 (t, MeCH2); 19.9 (q, MeCH);

14.0 (q, MeCH2). CI-MS: 222 [M+NH4] +.

5.6. Phenyl 2-phenylbut3,1 ketone 12d

According to 5.1, a mixture of all compounds of the type lid (50 mg, 0.11 mmol) gave 12d (20

mg, 0.08 mmol, 77%) as a colorless oil. IR: 3080m, 3060m, 3020m, 2960s, 2920s, 2870m, 1725w,

1690s, 1595m, 1580m, 1490m, 1445s, 1405m, 1375m, 1365m, 1350m, 1330m, 1315m, 1280m, 1245m,

1210m, 1200m, 1180m, 1155w, 1100w, 1070w, 1115m, 975m, 950w, 925w, 905w, 840w, 785w, 750s,

700s. IH-NMR: 7.94-7.16 (m, 10 arom. H); 3.30-3.23 (2m, Ph(Et)CH and PhCOCH2); 1.88-1.59

(m, MeCH2); 0.82 (t, J=7.3, MeCH2). 13C-NMR: 199.1 (s, C=O); 144.6, 137.2 (2s, 2 arom. C);

132.8, 128.4, 128.3, 128.0, 127.6 (5d, 5×2 arom. C): 45.5 (t, PhCOCH2); 43.0 (d, Ph(Et)CH); 29.1

(t, MeCH2); 12.0 (q, MeCH2). CI-MS: 256 [M+NH4]+.

5. 7. Phenyl 2-phenylhe.u,l ketone 12e

According to 5.1, a mixture of all compounds of the type 1 le (50 mg, 0.10 mmol) gave 12e (20 mg,

0.08 mmol, 73%) as a colorless oil. IR: 3080m, 3050m, 3020s, 3000m, 2950s, 2920s, 2850s, 1725w,

1690s, 1595s, 1580m, 1490m, 1465m, 1445m, 1405m, 1365rn, 1350m, 1330m, 1315m, 1285m, 1270m,

1250m, 1215m, 120Om, llS0m, 1155w, l l l 0 w , 1070m, 1020m, 975m, 940w, 930w, 905w, 885w,

870w, 840w, 750s, 725m, 700s. IH-NMR: 7.95-7.15 (m, 10 arom. H); 3.38-3.31 (m, Ph(Bu)CH);

3.29-3.21 (m, PhCOCH2); 1.80-1.58 (m, PrCH2); 1.35-1.07 (m, Me(CH2)2); 0.83 (t, J=7.2, MeCH2).

13C-NMR: 198.9 (s, C=O); 144.7, 137.0 (2s, 2 arom. C); 132.5, 128.2, 128.1, 128.0, 127.2 (5d, 5×2

arom. C); 45.7 (t, PhCOCH2); 41.0 (d, Ph(Bu)CH); 35.7 (t, PrCH2); 29.3 (t, ETCH2); 22.3 (t, MeCH2);

13.6 (q, MeCH2). CI-MS: 284 [M+NH4]+.

Acknowledgements

We like to express our thanks to Prof. Dr M. Hesse who provided us with laboratory space,

equipment, and regular occasions for professional discussion, to the members of the analytic

laboratories of our institute for the measurements of the numerous spectra, and to the 'Swiss National

Science Foundation' for their generous financial support.

A chiral (alkoxy)methyl-substiluted silicon group

1603

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(Received in UK 6 March 1997)

Article Doi

A chiral (alkoxy)methyl-substituted silicon group as an auxiliary for the stereoselective cuprate addition to α,β-unsaturated ketones: Synthesis of (-)-(R)-phenyl 2-phenylpropyl ketone

DOI: 10.1016/S0957-4166(97)00134-1

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Full text of DOI:10.1016/S0957-4166(97)00134-1

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