Functionalisation of tetraalkylsilanes derived from C-H activation; Towards annulations of diterpenoids

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Journal of Organometallic Chemistry 601 (2000) 172–190

Functionalisation of tetraalkylsilanes derived from CꢀH activation;

towards annulations of diterpenoids

Paul W.R. Harris, Clifton E.F. Rickard, Paul D. Woodgate *

Department of Chemistry, The Uni6ersity of Auckland, Pri6ate Bag 92019, Auckland, New Zealand

Received 9 December 1999; received in revised form 15 January 2000

Abstract

Vinyl trialkylsilanes are efﬁcient substrates for use in the ortho alkylation of aromatic ketones catalysed by zerovalent ruthenium

complexes, giving, e.g. (2-trimethylsilylethyl)acetophenones. Methods for the selective desilylation–functionalisation of such

tetraalkylsilanes are investigated. Some diterpenoid tetraalkylsilanes derived from the ruthenium-catalysed insertion of

vinyltrimethylsilane have been functionalised by benzylic bromination of an ArCH CH SiMe fragment with NaBrO –Na S O

5

2

3

2

(

optimally), leading to a 1,2-dibromoethyl derivative. Further transformations culminated in the overall conversion of

ArCH CH SiMe into ArCOCH . Attempted aldol coupling of the resulting 1,4-diketone provoked skeletal reorganisation. A

2

3

tetraalkylsilane was converted into a silanol (ArCH CH SiMe OH) by the action of aluminium chloride and water, but further

2

reserved.

Keywords: Ruthenium catalysis; Aromatic ketones; Tetraalkylsilane; Bromination/desilylation; Oxidation

1

. Introduction

tronegative substituent [4,5], the reactivity of tetraalkyl-

silanes, in which the silicon is generally regarded as

‘unactivated’, has received much less attention. We now

disclose our efforts to extend the possibilities inherent

in the ruthenium-catalysed ortho alkylation procedure,

by exploring the chemistry of the silicon centre. Thus,

We [1,2] and others [3] have reported previously on

the ruthenium-catalysed coupling of an ortho CꢀH

bond of an aromatic ketone with vinyltrimethylsilane,

resulting in high yields of ortho alkylated (2-trimethylsi-

lylethyl) products. This catalysed CꢀH activation pro-

cess offers a straightforward entry into a range of

ortho-substituted acetophenones (or analogues), useful

as relays in the synthesis of metal-free polyfunctional

organic molecules. Such applications, however, will

usually require the substitution of a trialkylsilyl moiety

in the newly introduced side chain by a typical organic

functional group. In particular, the adducts arising

from incorporation of vinyltrimethylsilane require mod-

iﬁcation by displacement of a trimethylsilyl group, in

order to yield compounds suitable for construction of

further rings, either carbocyclic or heterocyclic. While

many methods are known for the functionalisation of a

carbonꢀsilicon bond when the silicon carries an elec-

adducts of ketones containing an ArCH CH SiMe

2 2 3

moiety are elaborated into precursors suitable for the

potential construction of tetracyclic compounds derived

from podocarpic acid.

2

. Results and discussion

2.1. Brominati6e desilylation of 7-oxopodocarpanes

Since b-ketosilanes and related moieties are known

[

6,7] to be synthons for the formation of an enolate (or

related) ion, initial studies on functionalisation of the

2-trimethylsilylethyl) substituent were directed towards

(

oxidation of its benzylic methylene group. However,

repeated attempts to convert the benzylic methylene at

C(14) of the 7-oxo diterpenoid 1 into a ketone, using

*

Corresponding author. Tel.: +64-9-3737599; fax: +64-9-

3737422.

E-mail address: p.woodgate@auckland.ac.nz (P.D. Woodgate)

either CrO –HOAc or DDQ, were unproductive. This

3

PII: S 0 0 2 2 - 3 2 8 X ( 0 0 ) 0 0 0 5 9 - 0

P.W.R. Harris et al. / Journal of Organometallic Chemistry 601 (2000) 172–190

173

was presumed to reﬂect electron withdrawal by the

carbonyl group already present in ring B. Moderating

3, but also other products. Attempted modiﬁcation of

the 7-ketone in 1 as either a 1,3-dioxolane or as a

dimethyl acetal using a variety of conditions was unsuc-

cessful. Consequently, further investigations into ben-

zylic oxidations as a route to the functionalisation of

tetraalkylsilanes via derived b-ketosilanes were not

undertaken.

this effect by reduction (NaBH ; 85%) of the 7-ketone,

4

followed by attempted protection (Ac O–Py; or TB-

2

DMSCl, or TBDMSOTf) of the resulting alcohol(s)

6

resulted only in elimination to give the D alkene 2.

In another approach, it was expected that benzylic

bromination of ArCH CH SiMe would yield a b-bro-

2

3

mosilane which would undergo rapid b-elimination of

Me SiBr [12,13]. However, treatment of 1 with NBS

3

(

1.3 molar equivalents) in reﬂuxing carbon tetrachloride

for 16 h gave only the 6a-bromo-7-ketone 4. The

1

conﬁguration at C(6) was assigned from the H-NMR

spectrum (J_H₍₅₎_ꢀ_H₍₆₎=6.6 Hz) [14] and was supported

by X-ray crystallographic analysis of the related com-

pound 30 (see Section 2.7). It was apparent that more

than one molar equivalent of NBS was required to

ensure bromination of the C(14) side chain also. In-

deed, addition of six equivalents of NBS portionwise

(

one equivalent at 2 h intervals) to a reﬂuxing solution

However, as the styrene 2 is less electron poor than the

of 1 and then reﬂuxing overnight resulted in total

conversion of the starting material. The 6a-bromo-14-

7-ketone 1, oxidation of 2 could occur at the benzylic

position of the side chain to yield the desired b-ketosi-

lane. In the event, treatment of 2 with PCC (ﬁve molar

(

1,2-dibromoethyl)-7-oxo diterpenoid (5, 27%) was iso-

lated as an inseparable mixture (1:1.02), epimeric at the

newly created stereocentre in the side chain. In the

equivalents) absorbed on Celite in reﬂuxing benzene for

5

1

8 h resulted in oxidation in ring B, giving the D -en-7-

1

one 3 (51%). The a,b-unsaturated ketone moiety in 3

was clearly evident in the H- (H(6), 6.47 ppm) and

C-NMR spectra (CO, 185.8 ppm), and in the IR

H-NMR spectrum the signal due to the benzylic

1

BrꢀCꢀH was a doublet of doublets (J=9.2, 6.0 Hz) at

5.93 ppm in one stereoisomer, and a triplet (J=6.9 Hz)

at 5.99 ppm in its epimer. Separate chemical shifts were

also observed for H(6eq), for H(11) and for H(13).

Accurate measurement of the peak at highest m/z in the

mass spectrum was consistent with the formula

C H O Br , indicating that rapid loss of HBr oc-

curred before the molecular ion could be detected.

Microanalytical data was, however, in accord with for-

mulation of the product as the tribromide. Compound

1

3

−

1

spectrum (1653 cm ). Conversion of 2 into 3 requires

oxidation of an allylic CꢀH bond or an allylic alcohol,

which are well-known processes [8,9]. Rearrangement is

known to occur during oxidation of an allylic tertiary

alcohol to an enone [10], and Nicolaou has reported

that PCC in reﬂuxing benzene can cleanly oxidise an

21

25

4

2

allylic CH to the a,b-unsaturated ketone [11]. Inclu-

2

sion of NaOAc in the oxidising medium for 2 resulted

in not only a slower reaction and a lower yield (28%) of

5

is proposed to form from 4 by initial radical bromina-

tion at the benzylic position followed by rapid elimina-

tion of Me SiBr to yield a styrene, which then

3

undergoes electrophilic addition of bromine (Scheme 1).

Although functionalisation of the tetraalkylsilane

had been achieved, this approach requires that the C(6)

bromide would have to be removed eventually. There-

fore the C(7) ketone was removed in order to avoid

initial bromination at C(6) via the enol. The required

C(7) methylene compound 8 was synthesised from the

epimeric alcohols 6/7 by either ionic hydrogenation

(

CF COOH–Et SiH; 96%) or heterogeneous catalysed

3 3

hydrogenation (H –PdꢀC–HOAc; 75%). However, re-

2

action of 8 with excess NBS under the conditions

described above gave a complicated mixture (TLC,

1

H-NMR). In order to simplify this mixture it was

Scheme 1.

reﬂuxed with DBU to effect elimination.

174

P.W.R. Harris et al. / Journal of Organometallic Chemistry 601 (2000) 172–190

Table 1

Brominations of 1 in the presence of (PhCO) O and an added base

2

Run

NBS (equivalents)

Base (equivalents)

Solvent

C H

Time (h)

Yields (%) 5/11

1

2

3

4

6

12

9

6

K CO /4.5

24

21

8

23

12

5

19/12 ^a

23/15

12/13

18

23/33

2

3

6

K CO /12

C H

2

3

6

K CO /12

C H

2

3

6

b

4

K CO /9

C H

2

3

6

5

6

7

8

K CO /9

CCl₄

C H

2

3

NaHCO /6

28

3

6

KOH/6

DBU/6.5

No reaction

Mixture

6

a

C(6) monobromide 4 also isolated (28%).

Reaction using C(6) monobromide 4.

b

yield (46%), and under milder conditions (room temper-

ature, short time) relative to the reactions using NBS–

(

PhCO) O.

2

Two other methods for selective bromination/desilyl-

ation were also investigated. For simple benzene deriva-

tives which contain electron-withdrawing substituents,

bromination in an alkyl side chain can be accomplished

readily using ceric ammonium nitrate (CAN)–KBr in

HOAc at 80°C [17]. However, application of this

method to the 7-oxo diterpenoid 1 resulted in dibromi-

nation only, at C(6) and C(13), to give 13. Ishii and

co-workers have recently reported [18] that either ben-

zylic or ring bromination of alkylbenzenes can be

achieved using NaBrO –NaHSO , in either a two-

While bromination–elimination in the side chain had

taken place as desired, leading to the vinyl bromides 9

5

and 10 (1:1), a D -7-N-succinimidoyl unit had also been

incorporated. The changes in ring B occur presumably

via radical bromination at C(7) followed by loss of HBr

to give a C(6)ꢀC(7) double bond. Addition of NBS (cf.

3

[

15]) to this double bond followed by elimination of

phase or a homogeneous solvent system.

5

HBr yields the D -7-N-succinimidoyl alkene. NBS is

known to be able to introduce double bonds into a

molecule via bromination–dehydrobromination. For

example, Ogawa and co-workers [16] have reported that

some dihydrobenzofuran derivatives can be trans-

formed into benzofurans in a one-pot sequence using

NBS in the presence of K CO and dibenzoyl peroxide

For the alkylbenzenes studied by these workers, the use

of EtOAc as the organic solvent favoured bromination

in the alkyl side chain. Therefore, 1 was treated with an

excess of NaBrO –Na S O in EtOAc–H O. Unexpect-

2

3,

as initiator. Application of this procedure to 14-(2-

trimethylsilylethyl)-7-oxo diterpenoid (1) would be ex-

pected to promote the elimination of two molecules of

HBr from the intermediate tribromide 5; the results

from bromination of 1 with NBS in the presence of

various bases are given in Table 1. Use of the Ogawa

conditions (run 1) afforded 5 in only 19% yield, lower

than that when base was absent. A more polar com-

pound (C H Br O ) was also isolated (12%), and was

3

2

5

2

edly, however, the 6,13-dibromide 13 was the sole

product isolated (66%). Presumably, preferential elec-

trophilic arene bromination at C(13) inhibits bromina-

tion in the C(14) side chain. Changing the organic

solvent to hexane yielded, on one occasion, the desired

tribromide 5 in 66% yield after only 20 min, but

unfortunately this outcome could not be reproduced.

After much experimentation the conditions required to

induce brominative desilylation of 1 to give tribromide

5 consistently were established to be: (i) 12 molar

equivalents of sodium bromate; (ii) 12 molar equiva-

lents of sodium metabisulﬁte (reputable source); (iii) 3:1

2

1

22

3

5

assigned as 6-bromo-14-(2,2-dibromoethan-1-oyl)-D -7-

ketone (11). The structure of this a,a-dibromoketone

was conﬁrmed by reductive removal of the two bromine

atoms in the side chain by treatment with Zn–HOAc,

to give the acetophenone derivative 12 (COCH , l_H

3

2.52 ppm). As an alternative to either benzoyl peroxide

or AIBN, visible light can also promote the radical

sequence resulting in benzylic bromination of alkylben-

zenes. Pleasingly, treatment of 1 with NBS (six equiva-

lents) in CCl₄for 90 min under irradiation with a

tungsten lamp gave the tribromide 5 in much improved

hexane–H O (v/v) as solvents; (iv) addition of the

2

sodium metabisulﬁte as quickly as possible to the mix-

ture of diterpenoid and sodium bromate. As reaction of

1 using the Ishii method was quite exothermic, in one

variation Na S O was added at 0°C and the mixture

2

5

P.W.R. Harris et al. / Journal of Organometallic Chemistry 601 (2000) 172–190

175

was allowed to warm to room temperature; under these

conditions, however, only arene bromination occurred

to give the 13-bromo derivative 14 (78%).

a-bromo ketone 17 with Zn (two equivalents)–HOAc

[21] at room temperature [22] for 2 h resulted in quanti-

tative and selective reduction of the C(6) halogen to

give the 14(1-bromoethenyl) derivative 15. Although

this vinyl bromide did not hydrolyse during exposure to

2.2. Further transformations of the desilylated

tribromide 5

either silica gel in THF–H O, or to HCl (50%

2

aqueous), the 14-acetyl-7-oxo diterpenoid 18 was

formed in good yield overall (59%, three steps from 1)

Since modiﬁcation of the Ishii conditions had permit-

ted efﬁcient brominative desilylation of the 14-(2-

using Hg(OCOCF ) –CF COOH–HCOOH.

3 2 3

trimethylsilylethyl) diterpenoid

1

to give the

In contrast, four products were obtained from reac-

tion of the tribromide 5 with DBU (three equivalents)

in benzene at room temperature for 2 h, followed by

treatment of the crude mixture with Zn–HOAc and

14-(1,2-dibromoethyl) derivative 5, routes for conver-

sion of this intermediate into compound(s) suitable for

construction of an additional ring were sought. The

then with Hg(OCOCF ) –CF COOH–HCOOH. The

1,4-diketone 18 was regarded as such a compound.

3 2

3

1

4-ethyl-7-ketone 19 (11%) arises from the styrene 20

Clearly, reactions of 5 would mainly involve familiar

chemistry of the carbonꢀbromine bond, such as reduc-

tion, or elimination or substitution. In an exploratory

experiment, treatment of a mixture (3:2) of 6a-bromo-

(

8%). The carbonyl group at C(7) in 20 promotes

conjugate attack of zinc at the terminal methylene

group in 19 to yield a 14-(ethylzinc) species, which

undergoes protonolysis to the alkane; similar reduction

of a remote conjugated double bond has been reported

recently [23]. In turn, 20 results from reductive debrom-

ination of some 6a-bromide remaining after reaction of

5 with DBU. Formation of the 13-mercurated com-

pound 21 was unexpected since this had not occurred

during previous Hg(II)-catalysed hydrolyses of the vinyl

bromide, although mercuration is known to be facili-

tated by electron-donating groups on an aromatic ring

1

4-(2-trimethylsilylethyl)-7-oxo-diterpenoid (4) and its

4-(1,2-dibromoethyl) congener 5 with DBU (ﬁve

equivalents) in reﬂuxing benzene for 22 h returned the

debrominated ketone 1 (68%, based on 4) [19,20] and

5

its D derivative 3 (18%). The corresponding vinyl

5

bromides 15 (15%, based on 5) and its D derivative 16

(

46%), which result from elimination of HBr from the

side chain of 5, were also formed. Interestingly, these

4(1-bromoethenyl) compounds 15 and 16 have formed

1

[24].

by elimination in the opposite regiochemical sense to

vinyl bromides 9 and 10.

Since terminal alkenes are excellent synthons for the

preparation of methyl ketones [25], an alternative route

for the synthesis of the 1,4-diketone 18 involves conver-

sion of the tribromide 5 into the styrene 20, and then a

Wacker-type oxidation [26]. Thus, treatment of the

In contrast to the outcome under reﬂux, treatment of

the 6a-bromo-14-(2-trimethylsilylethyl)-7-oxo diter-

penoid 4 with either DBU or Et N at room temperature

3

for two days did not result in either reductive debromi-

nation or elimination. It therefore appeared that selec-

tive elimination in the side chain of 5 could be achieved

by controlling both the reaction temperature and time.

Heating under reﬂux, and for a relatively short time,

was essential. Thus, reﬂuxing the tribromide 5 with

DBU (three equivalents) in benzene for 1–2 h afforded

the 6a-bromo-14(1-bromoethenyl) derivative 17 as the

sole product, and in quantitative yield. Retention of the

1

4-(2-trimethylsilylethyl)-7-ketone 1 with NaBrO₃–

Na S O (12 equivalents each) followed by reaction of

2

5

the crude product with Zn–HOAc gave 20 (58%). The

results from attempted conversion of this styrene into a

methyl ketone are given in Table 2. The Wacker oxida-

tion of alkenes to ketones is usually accomplished with

a catalytic amount of palladium(II) and a re-oxidant

such as copper(II) chloride. In the present case, how-

ever, even an excess of PdCl (6.5 equivalents, run 1) in

2

6

5

a-bromide was evident by a doublet (J=6.17 Hz) at

DMF–water gave only a trace of the methyl ketone

1

.69 ppm in the H-NMR spectrum, while the terminal

1

(

H-NMR), together with unidentiﬁed components.

methylene group in 17 was characterised by doublets

J=1.8 Hz) at 5.73 and 5.86 ppm. Stirring the crude

Mercury(II) acetate in combination with PdCl₂is

known to promote the efﬁcient oxidation of a terminal

alkene to a methyl ketone [27], but treatment of the

(

Table 2

Oxidations of the alkene 20

styrene 20 with Hg(OAc) (one equivalent) for 10 min

2

followed by the addition of PdCl₂(one equivalent)

returned mostly starting material (run 2). An alterna-

tive procedure was to isolate the hydration product

before addition of an oxidising agent (run 3). Thus,

hydroxymercuration of the alkene followed by reduc-

tive demercuration with NaBH gave a mixture of the

7

of which gave the 1,4-diketone 18 (26% from 20).

Run Conditions

Result

1

2

PdCl –DMF–H O (4 h)

Ketone (trace)

2

Hg(OAc) –THF–H O (10 min); PdCl

2

(4 h)

4

3

Hg(OAc) –THF–H O (30 min);

Ketone (26%)

2

b-14(1j-hydroxyethyl) epimeric diols, Jones’ oxidation

NaBH –NaOH(aq.); Jones

4

176

P.W.R. Harris et al. / Journal of Organometallic Chemistry 601 (2000) 172–190

Clearly, the desired bromination/desilylation in the

C(14) side chain of 22 had not occurred, and instead

generation of a carbocation at C(7) was favoured. On

the basis that carbocation formation might be disfa-

voured by moderating electron donation from the sub-

stituent para to C(7), the C(12)-acetate 26 was

synthesised (96%) from the C(12)ꢀTBDMS ether 22.

However, treatment of 26 with NaBrO –Na S O (12

3

2

5

equivalents each) in 3:1 hexane–water for 30 min also

resulted in reaction at C(7), to give a 7-bromo deriva-

tive which eliminated HBr during silica gel chromatog-

raphy to afford the alkene 27 (68%). Extending the

reaction time to 4 h resulted in bromination not only at

C(7) but also of the C(13) acetyl group. That is, while

an acetate at C(12) had prevented secondary formation

of the 6,7-bromohydrins, initial bromination was still

favoured at C(7) rather than in the 14(2-trimethylsi-

lylethyl) side chain. The C(7) methylene group in 22

was therefore converted into the C(7) ketone. Since

TBDMS derivatives are known to cleave under oxidis-

Fig. 1. The atomic arrangement in 30.

2

.3. Attempted brominati6e desilylation of 13-acetyl

analogues

Since a sequence for the conversion of ArCH CH -

2

^Sⁱ^M^e3 ⁱⁿ^t^o^A^r^C^O^C^H3 in 14-(2-trimethylsilylethyl)-7-

oxo diterpenoid (1) had been established, the route was

attempted on related compounds containing a 13-acetyl

group, the aim being to generate a 1,4-diketone which

might allow cyclopentaannulation across C(13)/C(14),

leading to steroidal analogues with an aromatic ring C.

Thus, 13-acetyl-12-(((1,1-dimethylethyl)dimethylsilyl)-

oxy)-14-(2-trimethylsilylethyl) diterpenoid (22) was

treated with NaBrO –Na S O (six equivalents each) in

ing conditions (I –MeOH [29], CAN [30]) to give a

2

phenol, which could lead to oxidation of the arene ring,

the silyl ether at C(12) in 22 was ﬁrst transformed into

the methyl ether 28 using TBAF–MeI [31]. Treatment

of 28 with CAN then gave the desired 13-acetyl-7-ke-

tone 29 (45%). Based on our previous work it was

expected that exposure of 29 to NaBrO –Na S O

3

2

5

hexane–water for 30 min (optimum conditions for for-

mation of 5 from 1). Although three products were

formed, none had undergone desilylation/bromination

3

2

5

would effect bromination initially at C(6), and then in

the C(14) side chain. In the event, treatment of 29 for

1 h with NaBrO –Na S O (12 equivalents each) in

6

in the C(14) side chain. Instead, the D -alkene 23 (30%)

3

2

5

and a mixture of the derived cis bromohydrins 24 and

7:2 hexane–water gave only monobromination, at

C(6) (93%). The stereochemistry of monobromide 30

was conﬁrmed as 6a by single-crystal X-ray diffraction

analysis (Fig. 1). These studies established that in con-

trast to the 7-oxo analogue 1, the 13-acetyl-14(2-tri-

methylsilylethyl) diterpenoid 22 was not a suitable sub-

strate for brominative desilylation.

2

5 were isolated. The regiochemistry of addition of

HOBr to the alkene was determined by correlations in

the 2D-NMR spectra, and the stereochemistry was

deduced from relative J values. The cis stereochemistry

was unexpected as trans bromohydrins are usually

formed under these conditions [28]. Isolation of 24 and

6

2

5 suggests that the D alkene 23 reacts with elec-

2.4. Attempted annulation of 18 by aldol coupling

trophilic bromine to yield a mixture of 6a-bromo and

b-bromo open C(7) carbocations stabilised by the

6

In the expectation that a bulky base would favour

p-methoxyphenyl ring. Water then approaches from the

same face (internal delivery?) as the bromine atom,

leading to the stereoisomeric cis adducts.

deprotonation at the more accessible acetyl group, the

,4-diketone 18 was reﬂuxed in THF with potassium

1

t-butoxide for 16 h, but no reaction occurred. Similarly,

reﬂuxing 18 with 10% KOH in methanol for 15 h

returned only the starting diketone. The use of either

LDA at −78°C or NaH in reﬂuxing THF for 3 h also

did not effect the aldol transformation. Since aldol

reactions between two ketones are invariably easily

reversible [32], the product of cyclopentaannulation

may not be stable. Guthrie has reported [33] that

self-condensation of acetophenone is endothermic

−

1

(

computed DG, +22.5 kJ mol ), indicating that the

annulation required in the present work might be

difﬁcult. Should the aldol form, however, then loss of

water to form the conjugated ketone should be rapid

−

1

(

exothermic, −13.3 kJ mol ).

P.W.R. Harris et al. / Journal of Organometallic Chemistry 601 (2000) 172–190

177

Since base did not promote aldol cyclisation in 18,

attention was turned to the use of an acidic catalyst.

The skeletal reorganisation required to form 31 is

proposed to occur via methyl migration in a stabilised

allylic cation, itself formed by a 1,3-hydride shift [34–

36] from H(5a) to C(7) followed by loss of water

(Scheme 2).

Reﬂuxing the 1,4-diketone with ZnCl (one equivalent)

2

in either benzene or toluene for 24 h returned starting

,

material, while p-TsOH/4 A sieves in reﬂuxing toluene

for 5 h gave a product whose spectroscopic data were

not consistent with an aldol. Prominent peaks at m/z 43

2.5. Lewis acid-promoted clea6age of the

carbonꢀsilicon bond in 1

and (M-43) in the mass spectrum indicated that COCH

3

−

1

was still present, as did absorption at 1685 cm

in the

−

1

^I^R^s^p^e^c^t^r^u^m⁽^c^f^.^eⁿ^oⁿ^e^,^wmax expected 1650 cm ).

After extensive 2D-NMR analysis the structure was

Reports of the functionalisation of a carbonꢀsilicon

bond when the silicon contains only alkyl groups and is

therefore regarded as unactivated are limited to electro-

chemical or photochemical methods [5] and to the use

of electrophilic species such as BCl₃, GaCl₃,

Tl(OCOCF ) , HgCl₂, Hg(NO₃)₂, [(C H )PtCl ] ,

1

proposed to be 31. The H-NMR spectrum of 31

conﬁrmed the presence of two quaternary methyl

groups, and of COMe, 19-OMe and 12-OMe. The

signals due to the protons of ring A were multiplets

3

2

4

2 2

(

1.86–1.73 and 2.30–2.36 ppm) that integrated for only

H PtCl ·6H O [37] or [PhTl(crown ether)][Otf] [38],

2

6

2

four hydrogens, and there were ﬁve aromatic/vinyl pro-

tons evident. Two of these were clearly H(11) and

H(13) (d, J=2.6 Hz). Doublets at 6.86 and 6.48 ppm

were mutually coupled (J=10.3 Hz), indicating an

isolated double bond. The remaining hydrogen bound

each of which shows varying degrees of efﬁciency and

selectivity. In the present work, oxidative cleavage of a

siliconꢀmethyl bond occurred during treatment of 12-

methoxy-14-(2-trimethylsilylethyl)-7-ketone (1) with

AlCl (ﬁve equivalents) in reﬂuxing CH Cl [39]. The

3

2

1

to sp carbon gave a multiplet at 6.05 ppm; the H

COSY spectrum showed coupling with the multiplet at

expected phenol 32, which was isolated in only 4%

yield, gave the correct accurate measurement for the

molecular ion in the mass spectrum, and expulsion of

2.30–2.36 ppm, and therefore the latter hydrogens were

allylic. Hence ring A contained a double bond. The

SiMe occurred to yield a strong fragment ion at m/z

1

3

C-NMR spectrum revealed that there were only two

3

29. Accurate measurement of the molecular ion of the

CH groups present, and that C(5) was quaternary. A

2

major product, the polar silanol 33 (89%), revealed that

an extra oxygen atom was present, and the base peak in

the spectrum (in contrast to that of 32) was due to loss

3

methyl group was placed at C(5) because J coupling

from H(7) was detected, and also because of the signiﬁ-

cant upﬁeld shift (19.9 ppm) of the signal due to C(18).

1

of water. The H-NMR spectrum of 33 conﬁrmed that

one methyl group had been lost from silicon. This

transformation represents important methodology for

the functionalisation of tetraalkylsilanes, since the reac-

tion is high yielding with minimum formation of by-

products. Transfer of a methyl group from silicon to

aluminium is proposed to be concomitant with transfer

of a chlorine atom from the metal centre to the silicon

[40]; the resulting trialkylchlorosilane reacts with water

to yield the silanol (Scheme 3).

The ketone at C(7) is crucial to conversion of the

tetraalkylsilane into the silanol by the Lewis acid. Thus,

treatment of methyl 12-methoxy-14-(2-trimethylsi-

lylethyl)podocarpa-8,11,13-trien-19-oate (8) with AlCl₃

(

ﬁve equivalents) in reﬂuxing CH Cl for 24 h did not

2 2

lead to any silanols or disiloxanes. Instead, loss of the

4-(2-trimethylsilylethyl) side chain occurred (13%), as

did cleavage of the CH ꢀSiMe bond to give the 14-

1

2

3

ethyl derivative (52%; GC–MS), disproportionation of

which afforded the 14-methyl (14%) and 14-propyl

Scheme 2.

Scheme 3.

(

11%) congeners. The 13-acetyl-12-hydroxy-14-(2-

trimethylsilylethyl)-7-ketone 38 (12%) was also isolated

−

1

[w_m_a_x1726 (ester), 1704 and 1681 cm

(CꢁO ketone)].

This diketone probably arises from alkylation of a

phenol at C(13) by either an ethyl or ethylsilyl group

which oxidises to the acetyl group on exposure to air.

178

P.W.R. Harris et al. / Journal of Organometallic Chemistry 601 (2000) 172–190

The fact that cleavage of ArCH CH SiMe to

starting material, while BH ·DMS (four equivalents)

2

3

ArCH CH SiMe OH by AlCl is promoted by the pres-

resulted in both deoxygenation of the ketone and inter-

molecular reaction to give the disiloxane 40 (34%).

Deoxygenation also occurred with CF COOH–Et SiH,

2

3

ence of the C(7) ketone in 1 reﬂects a combination of

factors. The electron-withdrawing effect of the carbonyl

group will inhibit dealkylation via carbocation interme-

diates (cf. 8). Perhaps more signiﬁcantly, coordination

of aluminium chloride to the ketone oxygen may serve

to deliver the chlorine atom to silicon.

3

concomitant with triethylsilylation at C(12) to give 41

(24%). Since we have shown in related work that oxida-

tion of a siliconꢀcarbon bond in the 14-(2-trimethylsi-

lylethyl) side chain results also in Baeyer–Villiger

oxidation of a C(7) ketone [43], these results are note-

worthy as ketone deoxygenation provides a way of

avoiding the undesired lactone formation. In the con-

text of the present work, however, cleavage of a sili-

conꢀethyl carbon bond in the diterpenoid silanol could

not be induced.

2

.6. In6estigation of carbonꢀsilicon clea6age in silanol

33

There have been few reports of cleavage of the

carbonꢀsilicon bond in silanols, although they are likely

intermediates in the oxidation reaction [41]. In the

current investigation, treatment of 12-hydroxy-14(2-hy-

droxydimethylsilylethyl) (33) with an excess of H O –

2.7. X-ray crystal structure of 30

2

KF–NaHCO at either reﬂux or room temperature was

3

Data were collected on a Siemens SMART area detec-

unproductive. The ﬁrst step during oxidation of a car-

bonꢀsilicon bond under these conditions is usually co-

ordination of ﬂuoride to create a hypervalent silicon

species. It appeared likely that trialkylsilanol 33, which

already has a hydroxy group on silicon, was too elec-

tron-rich for this nucleophilic step to occur. Since an

acetate group on silicon would attenuate electron dona-

tion and might therefore allow such attack, the silanol

tor diffractometer using 0.3° frames and proﬁle ﬁtting.

Lorentz, polarisation and absorption corrections [44]

were applied and equivalent reﬂections averaged to give

173 unique data. Unit cell parameters were obtained

by a least-squares ﬁt to all data with I\10|(I). The

6

structure was solved by direct methods [45] and reﬁned

2

by full-matrix least-squares on F [46]. Hydrogen atoms

were placed geometrically and reﬁned with a riding

model, including free rotation for methyl groups, with

thermal parameter 20% (50% for methyl groups)

^g^r^e^a^t^e^r^t^h^aⁿ^Uiso of the carrier atom. All non-hydrogen

atoms were reﬁned with anisotropic thermal parame-

^t^e^r^s^.^R^e^ﬁⁿ^e^m^eⁿ^t^c^oⁿ^v^e^r^g^e^d^t^o^R1 (observed data)

3

3 was stirred with an excess of Ac O in pyridine

2

containing a catalytic amount of DMAP. However,

only the phenol was esteriﬁed, giving the 12-acetate 39.

Acylation of a silanol is known to be difﬁcult, even

when an excess of acetic anhydride is used [42]. Acetyl

chloride, which is more reactive than acetic anhydride,

also gave 39 (63%). Treatment of the 12-acetoxy tri-

alkylsilanol 39 with H O (24 equivalents) and KF–

0

.0476. Crystal data and reﬁnement parameters are

given in Table 3 and the structure is shown in Fig. 1,

which shows the absolute conﬁguration.

2

NaHCO in THF–MeOH at 60°C returned starting

3

material after 18 h, while m-CPBA (three or 12 equiva-

lents)–KF in DMF [42] at either room temperature or

2.8. Summary

90°C gave either no reaction or a complicated mixture

(

in which oxidation had not occurred). Since cyclic

alkoxysilanes usually undergo oxidative cleavage more

readily than straight chain analogues, an alternative

strategy was proposed, involving reduction of a 7-ke-

tone to an alcohol followed by intramolecular capture

by the 14-ethylsilanol prior to exposure to H O . In the

These investigations have shown that the tetraalkylsi-

lanes readily available from the ruthenium-catalysed

ortho alkylation of some diterpenoid ketones with

vinyltrimethylsilane can undergo brominative desilyla-

tion. The resulting silicon-free compounds have been

used to explore routes for annulation of ring C aro-

matic diterpenoids.

2

event, treatment of the 7-ketone 33 with NaBH (six

equivalents) in ethanol at either r.t. or reﬂux gave only

4

P.W.R. Harris et al. / Journal of Organometallic Chemistry 601 (2000) 172–190

179

Table 3

(

SiꢀC). l_H0.082, s, 9H, SiMe ; 0.8–0.87, m, 2H, 14-

3

Data collection and processing parameters for 30

CH CH SiMe ; 0.87, s, 3H, H(20); 1.14, td, J=13.5,

2

3

.9 Hz, 1H, H(3ax); 1.34, s, 3H, H(18); 1.60, td, J=

Formula

C H BrO Si

26 37 5

Molecular weight

Temperature (K)

537.56

203

0.71073

13.5, 4.1 Hz, 1H, H(1ax); 1.73, dp, J=13.5, 4.3, 1H,

H(2eq); 1.95, qt, J=13.9, 3.6 Hz, 1H, H(2ax); 2.21 bd,

J=12.4 Hz, 1H, H(1eq); 2.34, t, J=2.84 Hz, 1H, H(5);

Wavelength (A

,

)

Crystal system

Space group

Orthorhombic

2

.36, bd, 1H, H(3eq); 2.62–2.70, m, 2H, 14-

P2 2 2

1

1 1

a (A

,

)

8.3704(1)

14.3873(2)

22.6929(1)

2732.85(5)

4

CH CH SiMe ; 3.71, s, 3H, 19-OMe; 3.82, s, 3H, 12-

2

3

b (A

,

OMe; 6.44, dd, J=10.1, 2.44 Hz, 1H, H(6); 6.58, d,

J=2.52 Hz, 1H, H(13); 6.63, dd, J=10.1, 3.1 Hz, 1H,

H(7); 6.68, d, J=2.52 Hz, 1H, H(11). l_C−1.89,

c (A

V (A

,

³)

,

Z

D_c_a_l_c(g cm⁻3₎

SiMe ; 18.8, 14-CH CH SiMe ; 19.05, C(20); 19.7,

1.307

3 2 2 3

F(000)

1128

1.580

C(2); 27.6, 14-CH CH SiMe ; 27.7, C(18); 36.3, C(1);

2 2 3

v (mm⁻¹)

3

1

7.2, C(3); 38.4, C(10); 43.4, C(4); 50.8, C(5); 51.4,

9-OMe; 55.0, 12-OMe; 106.9, C(11); 110.6, C(13);

Crystal size (mm)

q Range (°)

0.64×0.35×0.22

1.7–27.5

−105h510, 05k518,

2

Index ranges

121.2, C(6); 122.9, C(8); 127.3, C(7); 142.2, C(14);

0

5l529

148.7, C(9); 158.2, C(12); 177.5, C(19). m/z 400 (100,

Reﬂections collected

Independent reﬂections

A (min/max)

25 771

6173 [R_i_n_t=0.0368]

0.431, 0.722

+

M ), 73 (55, SiMe ). Found: M , 400.2416. Calc. for

3

C H O Si: M, 400.2434.

24

36

3

2

o

2 2

c

Function minimised

Data/restraints/parameters

Goodness of ﬁt on F²

Flack parameter

R₁(observed data)

wR₂(all data)

Sw(F −F )

6173/0/306

1.026

0.014(9)

0.0476

0.1402

3

7

.2. Methyl 12-methoxy-14-(2-trimethylsilylethyl)-

-oxopodocarpa-5,8,11,13-tetraen-19-oate (3)

Difference map (min/max)

1.78 and −0.30

To a solution of methyl 12-methoxy-14-(2-trime-

−

3

(

e A

,

)

thylsilylethyl)podocarpa-6,8,11,13-tetraen-19-oate

(2,

2

2 2

c

R =SꢀꢀF ꢀ−ꢀF ꢀꢀ/SꢀF ꢀ

wR ={S[w(F −F ) ]/

1

o

c

o

2

o

2 1/2

1

06 mg, 0.265 mmol) in benzene (15 ml) was added a

2

S[w(F ) ]}

o

homogenized mixture of PCC (0.284 g, 1.325 mmol)

and Celite (1 g). The mixture was stirred and reﬂuxed

for 18 h and then ether was added. Filtration through a

short pad of Celite–MgSO followed by solvent re-

4

3

. Experimental

moval and ﬂash chromatography (silica gel, 3:1 hex-

anes–ether) gave methyl 12-methoxy-14-(2-trimethyl-

silylethyl) - 7 - oxopodocarpa - 5,8,11,13 - tetraen - 19-

oate (3, 51%, 56 mg) as an orange oil. w_m_a_x1731 (CꢁO

For general experimental details see Ref. [2].

ester), 1653 (CꢁO enone), 1600 (CꢁC), 1290, 1246, 861,

3

.1. Methyl 12-methoxy-14-(2-trimethylsilylethyl)-

−1

8

2

35 cm

(SiꢀC). l_H0.1, s, 9H, SiMe ; 0.78–0.85, m,

3

podocarpa-6,8,11,13-tetraen-19-oate (2)

H, 14-CH CH SiMe ; 1.22, td, J=13.6, 4.2 Hz, 1H,

2

3

H(3ax); 1.29, s, 3H, H(20); 1.47, s, 3H, H(18); 1.52, td,

J=13.5, 4.1 Hz, 1H, H(1ax); 1.69–1.73, m, 1H,

H(2eq); 2.11, qt, J=13.8, 3.6 Hz, 1H, H(2ax); 2.32, bd,

J=13.2 Hz, 1H, H(1eq); 2.51, bd, J=13.3, 1H,

H(3eq); 3.0–3.23, m, 2H, 14-CH CH SiMe ; 3.63, s,

To a stirred solution of methyl 12-methoxy-14-(2-

trimethylsilylethyl) - 7 - oxopodocarpa-8,11,13-trien-19-

oate (1, 154 mg, 0.370 mmol) in ethanol (3 ml) was

added NaBH (41 mg, 1.11 mmol). After 11 h saturated

4

2

3

aqueous ammonium chloride was added, and the

product was extracted with dichloromethane. The com-

bined extracts were dried and the solvent removed in

vacuo to give a colourless oil (135 mg, 87%). This was

dissolved in dichloromethane (2 ml), and acetic anhy-

dride (0.121 ml, 1.29 mmol) and pyridine (0.103 ml,

3

6

1

H, 19-OMe; 3.87, s, 3H, 12-OMe; 6.47, s, 1H, H(6);

.72, d, J=2.48 Hz, 1H, H(11); 6.84, d, J=2.48 Hz,

^H^,^H⁽¹³⁾^.^lC −1.76, SiMe ; 18.9, 14-CH CH SiMe ;

3

2

3

9.3, C(2); 27.0, C(20); 28.4, C(18); 30.7, 14-

CH CH SiMe ; 37.0, C(3); 40.4, C(1); 42.4, C(10); 47.3,

2

3

C(4); 51.9, 19-OMe; 55.1, 12-OMe; 109.0, C(13); 114.4,

C(11); 121.2, C(8); 128.2, C(6); 151.4, C(14); 156.8,

C(9); 161.0, C(5); 161.9, C(12); 175.7, C(19); 185.8,

1

.29 mmol) were added. After stirring overnight the

mixture was poured into ice and extracted with

dichloromethane. Work-up gave methyl 12-methoxy-

+

1

4-(2-trimethylsilylethyl)podocarpa-6,8,11,13-tetraen-

9-oate (2, 106 mg, 81%) as a colourless oil. w_m_a_x1727

C(7). m/z 414 (70, M ), 399 (50, M−15), 341 (70,

+

M−SiMe ), 73 (100, SiMe ). Found: M , 414.2210.

3

−

1

(

CꢁO ester), 1600, 1464 (CꢁC), 1247, 861, 835 cm

Calc. for C H O Si: M, 414.2226.

24 34 4

180

P.W.R. Harris et al. / Journal of Organometallic Chemistry 601 (2000) 172–190

3

.3. Methyl 6h-bromo-12-methoxy-14-(2-trimethyl-

both isomers; 2.38, bd, J=13.5 Hz, 1H, H(3eq) both

isomers; 2.46, t, J=6.2 Hz, 1H, H(5) both isomers;

silylethyl)-7-oxopodocarpa-8,11,13-trien-19-oate (4)

3

.74, s, 3H, 19-OMe both isomers; 3.92, s, 3H, 12-OMe

Methyl 12-methoxy-14-(2-trimethylsilylethyl)-7-oxo-

podocarpa-8,11,13-trien-19-oate (1, 0.122 g, 0.293

mmol), N-bromosuccinimide (0.067 g, 0.380 mmol) and

benzoyl peroxide (0.014 g, 0.058 mmol) were reﬂuxed in

both isomers; 4.02–4.14, m, 2H, 14-CH(Br)CH Br both

2

isomers; 5.77, d, J=6.45 Hz, H(6ax) major; 5.78, d,

J=6.45 Hz, H(6eq) minor; 5.93, dd, J=9.2, 6.0 Hz,

1H, 14-C(Br)H major; 5.99, t, J=6.9 Hz, 1H, 14-

C(Br)H minor; 6.86, d, J=1.76 Hz, 1H, H(11) major;

6.88;, d, J=1.76 Hz, 1H, H(11) minor; 7.09, d, J=1.76

Hz, 1H, H(13) major; 7.22, d, J=1.76 Hz, 1H, H(13)

CCl (4 ml) for 16 h. The cooled mixture was ﬁltered

4

and the residue washed with CCl . Flash chromatogra-

4

phy (silica gel, benzene) gave methyl 6a-bromo-12-

methoxy-14-(2-trimethylsilylethyl)-7-oxopodocarpa-8,-

minor. l 19.2, C(2) both isomers; 23.6, C(20) minor;

C

1

8

1,13-trien-19-oate (4, 59%, 86 mg) as a brown oil. w_m_a_x

23.6, C(20) major; 28.6, C(18) both isomers; 34.7, 14-

727 (CꢁO ester), 1682 (CꢁO ketone), 1596 (CꢁC), 861,

CH(Br)CH Br major; 36.8, 14-CH(Br)CH Br minor;

2

−

1

35 cm

(SiꢀC). l_H0.04, s, 9H, SiMe ; 0.88, s, 3H,

37.24, C(1) minor; 37.28, C(1) major; 37.8, C(3) both

isomers; 39.1, C(10) both isomers; 44.8, 14-PhC(H)Br

major; 45.2, C(4) both isomers; 46.7, 14-PhC(H)Br

minor; 50.0, C(6) minor; 50.15, C(6) major; 51.9, 19-

OMe both isomers; 55.4, 12-OMe both isomers; 56.8,

C(5) minor; 56.9, C(5) major; 109.7, C(11) both iso-

mers; 110.9, C(13) major; 112.5, C(13) minor; 123.4,

C(8) both isomers; 141.4, C(14) minor; 142.1, C(14)

major; 153.5, C(9) minor; 153.7, C(9) major; 162.7,

C(12) minor; 162.9, C(12) major; 176.5, C(19) both

isomers; 192.4, C(7) major; 192.6, C(7) minor. m/z

3

H(20); 0.83–0.92, m, 2H, 14-CH CH SiMe ; 1.19, td,

2

3

J=13.4, 3.7 Hz, 1H, H(3ax); 1.53, s, 3H, H(18); 1.70–

.78, m, 2H, H(2eq) and H(1ax); 1.93, qt, J=14.0, 3.3

Hz, 1H, H(2ax); 2.12. bd, J=12.3 Hz, 1H, H(1eq);

1

2

1

.37, bd, J=13.6 Hz, 1H, H(3eq); 2.43, dd, J=6.52,

H, H(5); 2.74, td, J=13.2, 4.8 Hz, 1H, 14-

CHCH SiMe ; 2.96, td, J=13.4, 4.4 Hz, 1H, 14-

CHCH SiMe ; 3.73, s, 3H, 19-OMe; 3.87, s, 3H,

2

3

2

3

1

2-OMe; 5.72, d, J=6.56 Hz, H(6ax); 6.69, d, J=2.4

Hz, 1H, H(11); 6.73, d, J=2.32 Hz, 1H, H(13). l_C

1.87, SiMe ; 18.3, C(2); 19.4, 14-CH CH SiMe ;

+

−

499/501/503 (2, M ). Found: M 501.0084. Calc. for

3

2

3

,

79

81

23.6, C(20); 27.5, 14-CH CH SiMe ; 28.6, C(18); 37.3,

C H Br BrO : M, 501.0099. Found: C, 42.3; H, 4.2.

21 25 4

2

3

C(1); 37.9, C(3); 39.0, C(10); 45.2, C(4); 51.0, C(6);

Anal. Calc. for C H O Br : C, 43.3; H, 4.3%.

21 26 4 3

5

1

1.5, 19-OMe; 55.2, 12-OMe; 57.1, C(5); 106.6, C(11);

12.4, C(13); 123.4, C(8); 149.9, C(14); 153.7, C(9);

62.4, C(12); 176.2, C(19); 192.7, C(7). m/z 494/496 (5,

3.5. Reduction of methyl 12-methoxy-14-

(2-trimethylsilylethyl)-7-oxopodocarpa-8,11,13-

trien-19-oate (1)

+

M ), 415 (100, M−Br), 73 (60, SiMe ). Found: M ,

3

494.1473. Calc. for C H BrO Si: M, 496.1468.

24 35 4

3

.4. Methyl 6h-bromo-14-(1,2-dibromoethyl)-12-

Sodium borohydride (216 mg, 5.84 mmol) was added

to a stirred solution of methyl 12-methoxy-14-(2-

trimethylsilylethyl)-7-oxopodocarpa-8,11,13-trien-19-

oate (1, 0.81 mg, 1.94 mmol) in methanol (10 ml). After

12 h sodium borohydride (one equivalent) was added

and the mixture was stirred for 3 h. Saturated aqueous

ammonium chloride was added and the mixture was

extracted with dichloromethane. Flash chromatography

(silica gel, 3:1 hexanes–ether) gave the crude alcohols

(0.688 g, 85%). A portion of the crude material was

subjected to PLC (4:1 hexanes–ether) to give (i) methyl

7a-hydroxy-12-methoxy-14-(2-trimethylsilylethyl)podo-

carpa-8,11,13-trien-19-oate (7) as white ﬂakes, m.p.

111–113°C. w_m_a_x3429 (OH), 1728 (CꢁO ester), 1600

methoxy-7-oxopodocarpa-8,11,13-trien-19-oate (5)

To suspension of methyl 12-methoxy-14-(2-

a

trimethylsilylethyl)-7-oxopodocarpa-8,11,13-trien-19-

oate (1, 95 mg, 0.228 mmol) in hexane (4 ml) and

sodium bromate (206 mg, 1.37 mmol) in water (1 ml)

was added sodium metabisulﬁte (260 mg, 1.37 mmol) in

water (1 ml) over 10 min. After 20 min ether was added

and the yellow organic layer was separated, washed

with saturated aqueous sodium thiosulfate solution (re-

sulting in a colourless organic layer) and dried

(

MgSO ). Flash chromatography (silica gel, 4:1 hex-

4

anes–ether) yielded methyl 6a-bromo-14-(1,2-dibro-

moethyl)-12-methoxy-7-oxopodocarpa-8,11,13-trien-19-

oate (5, 87 mg, 66%) as a colourless oil [mixture (1.02:1)

of diastereoisomers]. w_m_a_x1727, 1716 (CꢁO ester), 1687,

−

1

(CꢁC), 1247, 861, 837 cm

(SiꢀC). l_H0.082, s, 9H,

SiMe ; 0.82–0.94, m, 2H, 14-CH CH SiMe ; 0.98, s,

3

2

3

3H, H(20); 1.16, td, J=13.6, 4.2 Hz, 1H, H(3ax); 1.30,

s, 3H, H(18); 1.44, td, J=13.3, 4.1 Hz, 1H, H(1ax);

1.64–1.69, m, 1H, H(2eq); 1.94–2.05, m, 2H, H(5),

H(2ax); 2.16, td, J=11.4, 3.4 Hz, 1H, H(6ax); 2.23, bd,

J=12.8 Hz, 1H, H(1eq); 2.31–2.34, m, 2H, H(3eq),

H(6eq); 2.70, dddd, J=13.4, 12.2, 5.9 Hz, 1H, 14-

CHCH SiMe ; 2.85, dddd, J=13.4, 12.2, 5.9 Hz, 1H,

−

1

1682 (CꢁO ketone), 1596, 1463 (CꢁC), 737 cm . l_H

0.89, s, 3H, H(20) major; 0.90, s, 3H, H(20) minor;

1.20, td, J=13.6, 2.6 Hz, 1H, H(3ax) both isomers;

1.54, s, 3H, H(18) both isomers; 1.70–1.81, m, 2H,

H(2eq), H(1ax) both isomers; 1.91, qd, J=13.5, 2.9 Hz,

H, H(2ax) both isomers; 2.13–2.16. m, 2H, H(1eq)

1

2

3

P.W.R. Harris et al. / Journal of Organometallic Chemistry 601 (2000) 172–190

181

1

4-CHCH SiMe ; 3.67, s, 3H, 19-OMe; 3.80, s, 3H,

2-OMe; 4.99, t, J=2.91 Hz, 1H, H(7eq); 6.69, s, 2H,

H(7ax) obscured; 2.88, dd, J=16.5, 4.2 Hz, 1H,

H(7eq); 3.72, s, 3H, 19-OMe; 3.82, s, 3H, 12-OMe;

6.68, d, J=2.4 Hz, 1H, H(13); 6.74, d, J=2.4 Hz, 1H,

H(11). l −1.81, SiMe ; 17.0, 14-CH CH SiMe ; 20.0,

2

3

H(11), H(13). l_C−1.91, SiMe₃; 19.3, 14-

CH CH SiMe ; 19.9, C(2); 21.9, C(20); 26.0, 14-

2

3

C

3

2

3

CH CH SiMe ; 28.2, C(18); 30.3, C(6); 37.3, C(3);

C(2); 20.9, C(6); 22.8, C(20); 27.2, 14-CH CH SiMe ;

2

3

2 2 3

3

1

9.15, C(10); 39.24, C(1); 43.4, C(4); 45.2, C(5); 51.2,

9-OMe; 55.0, 12-OMe; 64.6, C(7); 108.4, C(11); 112.1,

28.0, C(7); 28.4, C(18); 37.5, C(3); 38.8, C(10); 39.8,

C(1); 43.9, C(4); 51.1, 19-OMe; 52.4, C(5); 55.0, 12-

OMe; 108.5, C(11); 111.0, C(13); 125.8, C(8); 144.3,

C(13); 125.7, C(8); 146.9, C(14); 150.3, C(9); 159.2,

C(12); 177.9, C(19). m/z 418 (10, M ), 400 (100, M−

H O), 73 (65, SiMe ). Found: M , 418.2519. Calc. for

C H O Si: M, 418.2539; and (ii) methyl 7b-hydroxy-

1

+

C(14); 149.5, C(9); 157.5, C(12); 177.8, C(19). m/z 402

+

2

3

(100, M ), 327 (25, M−75), 73 (60, SiMe ). Found:

3

+

2

4

38

4

M , 402.2584. Calc. for C H O Si: M, 402.2590.

24 38 3

2-methoxy-14-(2-trimethylsilylethyl)podocarpa-8,11,-

³^-^t^rⁱ^eⁿ^-¹⁹^-^o^a^t^e⁽⁶⁾^a^s^a^c^o^l^o^u^r^l^e^s^s^oⁱ^l^.^wmax 3510 (OH),

3.7. Bromination of methyl 12-methoxy-14-

2-trimethylsilylethyl)podocarpa-8,11,13-trien-19-oate

(8)

−

1

725 (CꢁO ester), 1600 (CꢁC), 1246, 861, 836 cm

(

1

SiꢀC). l_H0.073, s, 9H, SiMe ; 0.80–0.97, m, 2H,

3

4-CH CH SiMe ; 1.05, td, J=13.6, 4.2 Hz, 1H,

2 2 3

H(3ax); 1.17, s, 3H, H(20); 1.30, s, 3H, H(18), H(1ax)

obscured; 1.46, dd, J=13.2, 1.7 Hz, 1H, H(5); 1.59–

Methyl 12-methoxy-14-(2-trimethylsilylethyl)podo-

carpa-8,11,13-trien-19-oate (8, 222 mg, 0.55 mol), N-

bromosuccinimide (589 mg, 3.31) and benzoyl peroxide

13 mg, 0.055 mmol) were reﬂuxed in carbon tetrachlo-

ride (15 ml) for 3.5 h. The mixture was cooled to room

temperature and the ﬁltrate washed with carbon tetra-

chloride. The solvent was removed to afford an oil (448

mg), which was dissolved in benzene (10 ml). DBU (250

mg, 1.65 mmol) was added and the mixture reﬂuxed for

2 h. Work-up and ﬂash chromatography (silica gel, 4:1

benzene–ether) gave a mixture of compounds. PLC

1:1 benzene–ether) on 46 mg of this mixture gave (i)

1.64, m, 1H, H(2eq); 1.93–2.04, m, 2H, H(6ax), H(2ax);

2.19, bd, J=13.4 Hz, 1H, H(3eq); 2.31–2.34, bd, J=

13.4 Hz, 1H, H(1eq); 2.72, dddd, J=13.4, 13.6, 7.6, 1.6

(

Hz, 1H, H(6eq); 2.76–2.90, m, 2H, 14-CH CH SiMe ;

2

3

3.70, s, 3H, 19-OMe; 3.81, s, 3H, 12-OMe; 4.98, bs, 1H,

H(7ax); 6.66, d, J=2.8 Hz, 1H, H(11); 6.71, d, J=2.80

Hz, 1H, H(13). l_C−1.85, SiMe₃; 18.8, 14-

CH CH SiMe ; 19.9, C(2); 22.0, C(20); 27.4, 14-

2

3

1

CH CH SiMe ; 28.2, C(18); 32.4, C(6); 37.3, C(3); 39.2,

2

3

C(10); 40.3, C(1); 43.6, C(4); 49.4, C(5); 51.3, 19-OMe;

(

5

1

5.0, 12-OMe; 68.7, C(7); 108.1, C(11); 112.5, C(13);

methyl 12-methoxy-14-(Z-2-bromoethenyl)-7a-succin-

imidoylpodocarpa-5,8,11,13-tetraen-19-oate (10, 8 mg)

27.7, C(8); 147.5, C(14); 150.9, C(9); 158.7, C(12);

+

77.4, C(19). m/z 418 (5, M ), 400 (100, M−H O), 73

2

^a^s^g^o^l^d^eⁿ^r^o^d^s^,^m^.^p^.¹⁵⁵^–¹⁵⁶^°^C^.^wmax 1722 (CꢁO ester),

+

(

30, ^Sⁱ^M^e3⁾^.Found: M , 418.2519. Calc. for

−1

1

704 (CꢁO amide), 1595 (CꢁC), 1080 cm

(CꢀO). l_H

C H O Si: M, 418.2539.

2

4

38

4

.18, td, J=13.2, 4.1 Hz, 1H, H(3ax); 1.24, s, 3H,

H(20); 1.34, s, 3H, H(18); 1.66–1.69, m, 1H, H(2eq);

1

2

.92, td, J=12.2, 5.6 Hz, 1H, H(1ax); 2.05–2.19, m,

H, H(2ax), H(1eq); 2.40, bd, J=10.9 Hz, 1H, H(3eq);

.42–2.55, bs, 4H, CH CH ; 3.63, s, 3H, 19-OMe; 3.82,

3

.6. Methyl 12-methoxy-14-(2-trimethylsilylethyl)-

podocarpa-8,11,13-trien-19-oate (8)

2

s, 3H, 12-OMe; 5.53, d, J=3.64 Hz, 1H, H(6); 5.97, d,

J=3.60 Hz, 1H, H(7eq); 6.45, d, J=13.6, Hz, 1H,

Triﬂuoroacetic acid (142 mg, 1.24 mmol) was added

to a stirred solution of the alcohols (6/7, 104 mg, 0.248

mmol) and triethylsilane (434 mg, 3.73 mmol), in

dichloromethane (3 ml). After 2 min solid sodium

hydrogencarbonate was added and the product was

extracted with dichloromethane. The combined extracts

1

4-C(H)ꢁC(H)Br; 6.65, d, J=2.56 Hz, 1H, H(13); 6.92,

d, J=2.56 Hz, 1H, H(11); 7.12, d, J=13.6, Hz, 1H,

⁴^-^C⁽^H⁾^ꢁ^C⁽^H⁾^B^r^.^lC 19.5, C(2); 27.4, 27.7, C(18),

C(20); 28.0, CH CH ; 37.0, C(3); 39.4, C(1); 40.0,

1

2

C(10); 46.1, C(7); 46.9, C(4); 51.7, 19-OMe; 55.0, 12-

OMe; 106.7, 14-C(H)ꢁC(H)Br; 110.7, C(13); 111.0,

C(11); 117.2, C(6); 118.9, C(8); 134.9, C(14); 137.2,

were dried (MgSO ) and the solvent removed to give

4

methyl 12 - methoxy - 14 - (2 - trimethylsilylethyl)podo-

carpa-8,11,13-trien-19-oate (8, 96 mg, 96%) as yellow

chunks, m.p. 85–88°C. w_m_a_x1726 (CꢁO ester), 1603,

1

4-C(H)ꢁC(H)Br; 144.7, C(5); 148.5, C(9); 158.9, C(12);

+

−

1

75.0, CꢁO amide; 177.0, C(19). m/z 501/503 (58, M ),

1

466 (CꢁC), 1246 (SiꢀC), 1144, 860, 836 cm

(SiꢀC).

+

l_H0.115, s, 9H, SiMe ; 0.83–0.87, m, 2H, 14-

424/426 (100, M−77). Found: M , 501.1151. Calc. for

C H28BrNO : M, 501.1149; and (ii) methyl 12-

3

79

CH CH SiMe ; 1.10, s, 3H, H(18); 1.12, td, J=13.5,

25 5

2

3

4

1

.2 Hz, 1H, H(3ax); 1.32, s, 3H, H(20); 1.41, td, J=

3.3, 4.0 Hz, 1H, H(1ax); 1.55, d, J=11.1 Hz, 1H,

methoxy - 14 - (Z - 2 - bromoethenyl) - 7b - succinimidoyl-

podocarpa-5,8,11,13-tetraen-19-oate (9, 8 mg) as a

brown oil. w_m_a_x1722 (CꢁO ester), 1704 (CꢁO amide),

H(5); 1.66, bdp, J=15.4, 3.0 Hz, 1H, H(2eq); 1.92–

.10, m, 2H, H(6ax), H(2ax); 2.26–2.33, m, 3H, H(3eq),

H(1eq), H(6eq); 2.53–2.58, m, 2H, 14-CH CH SiMe ,

−

1

2

1595 (CꢁC), 1080 cm

(CꢀO). l_H1.15, td, J=13.6,

4.2 Hz, 1H, H(3ax); 1.37, s, 3H, H(18); 1.42, s, 3H,

2

3

182

P.W.R. Harris et al. / Journal of Organometallic Chemistry 601 (2000) 172–190

H(20); 1.49, td, J=13.0, 4.2 Hz, 1H, H(1ax); 1.63–

3.9. Reduction of methyl 6-bromo-14-

1

2

.68, m, 1H, H(2eq); 2.08–2.22, m, 2H, H(2ax), H(1eq);

.39, bd, J=13.0 Hz, 1H, H(3eq); 2.50–2.80, bs, 4H,

(2,2-dibromoethan-1-oyl)-12-methoxy-7-oxopodocarpa-

5,8,11,13-tetraen-19-oate (11) with Zn–acetic acid

CH CH ; 3.62, s, 3H, 19-OMe; 3.82, s, 3H, 12-OMe;

2

Methyl 6-bromo-14-(2,2-dibromoethan-1-oyl)-12-

methoxy-7-oxopodocarpa-5,8,11,13-tetraen-19-oate (11,

1 mg, 0.103 mmol) and zinc (0.026 g, 0.412 mmol)

were stirred in acetic acid (3 ml) for 16 h.

Dichloromethane was then added and mixture washed

with brine, sodium hydrogencarbonate and dried.

Work-up and PLC (2:1 hexanes–ethyl acetate) gave

5.66, d, J=4.76 Hz, 1H, H(6); 5.17, d, J=4.76 Hz, 1H,

H(7ax); 6.46, d, J=13.6, Hz, 1H, 14-C(H)ꢁC(H)Br;

6

1

.66, d, J=2.56 Hz, 1H, H(13); 6.91, d, J=2.56 Hz,

H, H(11); 7.12, d, J=13.6, Hz, 1H, 14-C(H)ꢁC(H)Br.

l 19.4, C(2); 25.4, C(20); 27.3, C(18); 27.9, CH CH ;

C

2

36.8, C(3); 40.0, C(10); 41.2, C(1); 46.0, C(7); 46.7,

C(4); 51.2, 19-OMe; 55.1, 12-OMe; 107.1, 14-

C(H)ꢁC(H)Br; 110.4, C(13); 111.9, C(11); 116.9, C(6);

methyl

14-acetyl-6-bromo-12-methoxy-7-oxopodo-

carpa-5,8,11,13-tetraen-19-oate (12, 10 mg, 22%) as

1

18.6, C(8); 136.0, C(14); 136.7, 14-C(H)ꢁC(H)Br;

needles, m.p. 246–249°C. w_m_a_x1732, (CꢁO ester), 1701,

46.0, C(5); 149.4, C(9); 158.9, C(12); 176.8, C(19);

−1

(

CꢁO ketone), 1651 (CꢁO enone), 1585 cm . l 1.65,

H

+

amide CꢁO not detected. m/z 501/503 (58, M ), 424/

s, 3H, H(20); 1.69, s, 3H, H(18); 1.80–1.89, m, 2H,

H(1), H(3); 1.99–2.18, m, 2H, H(2); 2.44–2.50, m, 2H,

H(1), H(3); 2.52, s, 3H, 14-COMe; 3.74, s, 3H, 19-

OMe; 3.91, s, 3H, 12-OMe; 6.69, d, J=2.3 Hz, 1H,

+

426 (100, M−77). Found: M , 501.1151. Calc. for

79

28

C H BrNO : M, 501.1149.

2

5

H(13); 7.02, d, J=2.30 Hz, 1H, H(11). l 14.3, C(2);

C

3

(

1

.8. Bromination of methyl 12-methoxy-14-

2-trimethylsilylethyl)-7-oxopodocarpa-8,11,13-trien-

9-oate (1) with NBS and K CO

2

1

2

1.8, C(20); 28.8, C(3) or C(1); 30.4, C(3) or C(1); 30.7,

4-COMe; 31.4 H(18); 44.8, C(10); 51.4, C(4); 52.8,

9-OMe; 55.6, 12-OMe; 109.9, C(13); 111.1, C(11);

18.8, C(8); 125.1, C(6); 147.3, C(14); 154.1, C(9);

63.2, C(12); 164.3, C(5); 175.6, C(19); 176.8, C(7);

2

3

Methyl 12-methoxy-14-(2-trimethylsilylethyl)-7-oxo-

podocarpa-8,11,13-trien-19-oate (1, 0.184 g, 0.442

mmol), N-bromosuccinimide (0.272 g, 2.65 mmol),

potassium carbonate (0.366 g, 2.65 mmol) and benzoyl

peroxide (20 mg) were reﬂuxed in carbon tetrachloride

+

04.5, 14-COMe. m/z 434/436 (6, M ), 341 (30, M−

+

CH Br), 189 (100). Found: M , 436.0712. Calc. for

2

81

C H BrO : M, 436.0708.

21

23

5

(

8 ml) under a nitrogen atmosphere for 8 h. The

3.10. Methyl 6h,13-dibromo-12-methoxy-14-

(2-trimethylsilylethyl)-7-oxopodocarpa-8,11,13-trien-

19-oate (13)

reaction mixture was ﬁltered and the ﬁltrate washed

with carbon tetrachloride. The solvent was removed

from the ﬁltrate and the residue ﬂash chromatographed

(

silica gel, 4:1, 3:1 hexanes–ethyl acetate) to give (i)

starting material (5 mg, 3%); (ii) methyl 6a-bromo-14-

1,2-dibromoethyl)-12-methoxy-7-oxopodocarpa-8,11,-

3-trien-19-oate (5, 59 mg, 23%); and (iii) methyl 6-

A solution of sodium metabisulﬁte (1.06 g, 5.6 mmol)

in water (4 ml) was added to a stirred suspension of

methyl 12-methoxy-14-(2-trimethylsilylethyl)-7-oxo-

podocarpa-8,11,13-trien-19-oate (1, 0.296 g, 0.936

mmol) in ethyl acetate (3 ml) and sodium bromate

(

1

bromo-14-(2,2-dibromoethan - 1 - oyl) - 12 - methoxy-7-

oxopodocarpa-5,8,11,13-tetraen-19-oate (11, 88 mg,

3

(

0.843 g, 5.6 mmol) in water (4 ml). A slight exotherm

was observed and the mixture became orange. After 4 h

ether was added and the organic layer was removed and

3%) as a brown oil. w_m_a_x1725, (CꢁO ester), 1714, (CꢁO

ketone), 1643 (CꢁO enone), 1582 (CꢁC), 1309, 1254,

−

1

dried (MgSO

hexanes–ether)

methoxy-14-(2-(trimethylsilyl)ethyl)-7-oxopodocarpa-

,11,13-trien-19-oate (13, 272 mg, 66%) as colourless

needles, m.p. 151–153°C. w_m_a_x1726 (CꢁO ester), 1688

). Flash chromatography (silica gel, 2:1

4

1

2

3

123 cm . l_H1.66, s, 3H, H(20); 1.69, s, 3H, H(18);

.85–1.90, m, 2H, H(1), H(3); 2.06–2.16, m, 2H, H(2);

.44–2.54, m, 2H, H(1), H(3); 3.74, s, 3H, 19-OMe;

gave methyl 6a,13-dibromo-12-

8

.93, s, 3H, 12-OMe; 6.28, s, 1H, 14-COCHBr ; 7.02, d,

2

J=2.32 Hz, 1H, H(13); 7.12, d, J=2.30 Hz, 1H,

H(11). l_C14.2, C(2); 21.6, C(20); 28.6, C(3) or C(1);

−1

(

CꢁO ketone), 1575 (CꢁC), 1222, 8611, 835 cm

SiꢀC). l 0.085, s, 9H, SiMe ; 0.86, s, 3H, H(20); 0.95,

H

3

4

1

0.3, C(3) or C(1); 31.3, H(18); 44.3, 14-COCHBr₂;

5.0, C(10); 51.5, C(4); 52.8, 19-OMe; 55.9, 12-OMe;

12.5, C(11); 115.5, C(13); 119.8, C(8); 128.8, C(6);

39.4, C(14); 154.0, C(9); 163.1, C(12); 166.0, C(5);

td, J=12.5, 4.2, 1H, 14-CH CH SiMe ; 1.0, td, J=

2

3

1

3.7, 4.4, 1H, 14-CH CH SiMe ; 1.15, td, J=13.6, 3.6

2 2 3

Hz, 1H, H(3ax); 1.49, s, 3H, H(18); 1.67–1.76, m, 2H,

H(1ax), H(2eq); 1.83–1.92, m, 1H, H(2ax); 2.13, bd,

J=12.2 Hz, 1H, H(1eq); 2.34, bd, J=13.8 Hz, 1H,

H(3eq), 2.38, d, J=6.4 Hz, 1H, H(5); 2.74, td, J=13.0,

4.6, 1H, 14-CH CH SiMe ; 3.12, td, J=13.0, 4.0, 1H,

77.0, C(19); 191.5, 14-COCHBr ; C(7) not detected.

2

+

m/z 591/593/595/597 (7, M +H), 189 (55), 94 (100),

4

C H Br O : (M+H), 596.8956.

+

3 (80, COCH ). Found: (M +H), 596.8957. Calc. for

3

2

3

81

22

2

1

3

5

14-CH CH SiMe ; 3.71, s, 3H, 19-OMe; 3.92, s, 3H,

2 2 3

P.W.R. Harris et al. / Journal of Organometallic Chemistry 601 (2000) 172–190

183

1

2-OMe; 5.71, d, J=6.4 Hz, 1H, H(6ax); 6.70, s, 1H,

mmol) was added and reﬂuxing continued for 14 h.

Work-up and ﬂash chromatography (silica gel, benzene,

then 7:3 benzene–ether) yielded (i) methyl 12-methoxy-

14-(2-trimethylsilylethyl)-7-oxopodocarpa-8,11,13-trien-

19-oate (1, 44 mg, 41%); (ii) a mixture (7:3, 48 mg) of

H(11). l −1.92, SiMe ; 12.4, 14-CH CH SiMe ; 19.2,

C(2); 23.3, C(20); 27.6, 14-CH CH SiMe ; 28.5, C(18),

3

C(6); 51.9, 19-OMe; 56.1, 12-OMe; 57.1, C(5); 103.4,

C(11); 113.7, C(13); 125.0, C(8); 147.7, C(14); 152.1,

C

3

2

3

2

3

7.4, C(1); 37.8, C(3); 39.0, C(10); 45.4, C(4); 50.6,

methyl

12-methoxy-14-(2-trimethylsilylethyl)-7-oxo-

C(9); 176.1, C(19); 192.1, C(7). m/z 572/574/576 (5,

podocarpa-8,11,13-trien-19-oate (1) and methyl 12-

methoxy-14-(2-trimethylsilylethyl)-7-oxopodocarpa-5,-

8,11,13-tetraen-19-oate (3); and (iii) a mixture (1:2, 37

mg) of methyl 14-(1-bromoethenyl)-12-methoxy-7-oxo-

podocarpa-8,11,13-trien-19-oate (15) and methyl 14-(1-

bromoethenyl) - 12 - methoxy - 7 - oxopodocarpa-5,8,11,-

+

M ), 494/496 (80, M−Br), 73 (100, SiMe ). Found:

3

+

79

34

M , 572.0585. Calc. for C H Br O Si: M, 572.0593.

2

4

2

4

3.11. Methyl 13-bromo-12-methoxy-14-(2-trimethyl-

silylethyl)-7-oxopodocarpa-8,11,13-trien-19-oate (14)

1

3-tetraen-19-oate (16). w_m_a_x₋1729 (CꢁO ester), 1658,

1

A solution of sodium metabisulﬁte (0.926 g, 4.88

mmol) in water (4 ml) was added over 15 min to a

stirred suspension of methyl 12-methoxy-14-(2-

trimethylsilylethyl)-7-oxopodocarpa-8,11,13-trien-19-

oate (1, 0.312 g, 0.75 mmol) in hexane (8 ml) and

sodium bromate (0.0.731 g, 4.88 mmol) in water (3 ml)

at 0°C. After 5 min the cooling bath was removed and

the mixture was stirred for 3 h. Ether was added and

the organic layer was removed, washed with a dilute

solution of sodium thiosulfate and dried (MgSO₄).

Flash chromatography (silica gel, 4:1, 2:1 hexanes–

ether) gave methyl 13-bromo-12-methoxy-14-(2-

trimethylsilylethyl)-7-oxopodocarpa-8,11,13-trien-19-

oate (14, 292 mg, 78%) as a colourless oil. w_m_a_x1725

1661 (CꢁO ketone), 1589 cm

(CꢁC). l_H1.12, s, 3H,

H(20) minor; 1.15, td, J=13.7, 3.96 Hz, 1H, H(3ax)

minor; 1.25, td, J=13.6, 4.3 Hz, 1H, H(3ax) major;

1.28, s, 3H, H(18) minor; 1.32, s, 3H, H(20) major;

1.49, s, 3H, H(18) major; 1.55, td, J=13.5, 4.1 Hz, 1H,

H(1ax) both isomers; 1.71–1.78, m, 1H, H(2eq) both

isomers; 1.98–2.20, m, 1H, H(2ax) both isomers; 2.32,

dd, J=13.2, 2.8, H(5) minor, H(1eq) or H(3eq) ob-

scured (both isomers); 2.52, bd, J=13.6 Hz, 1H,

H(1eq) or H(3eq) both isomers; 2.95, dd, J=18.0, 3.7

Hz, 1H, H(6eq) minor; 3.23, dd, J=18.0, 14.3 Hz, 1H,

H(6ax) minor; 3.65, s, 3H, 19-OMe minor; 3.71, s, 3H,

19-OMe major; 3.86, s, 3H, 12-OMe minor; 3.90, s, 3H,

12-OMe major; 5.06, d, J=1.80 Hz, 1H, 14-C(Br)ꢁCH₂

(

1

0

CꢁO ester), 1672 (CꢁO ketone), 1572 (CꢁC), 1298,

minor; 5.69, d, J=1.70 Hz, 1H, 14-C(Br)ꢁCH major;

2

−

1

267, 862, 837 cm

(SiꢀC). l_H0.087, s, 9H, SiMe₃;

5.71, d, J=1.70 Hz, 1H, 14-C(Br)ꢁCH minor; 5.77, d,

2

.76–0.86, m, 2H, 14-CH CH SiMe ; 1.06, s, 3H,

J=1.70 Hz, 1H, 14-C(Br)ꢁCH major; 6.52, s, 1H,

2

3

2

H(20); 1.08, td, J=13.6, 3.9 Hz, 1H, H(3ax); 1.21, s,

H, H(18); 1.52, td, J=13.2, 4.0 Hz, 1H, H(1ax); 1.69,

dp, J=14.4, 3.2 Hz, H(2eq); 1.96, dd, J=14.0, 4.0, 1H,

H(5), H(2ax) obscured; 2.24–2.30, m, 2H, H(1eq),

H(3eq); 2.88, dd, J=17.8, 4.1 Hz, 1H, H(6eq); 3.02–

H(6) major; 6.70, d, J=2.5 Hz, 1H, H(11) or H(13)

minor; 6.79, d, J=2.56 Hz, 1H, H(11) or H(13) major;

6.93, d, J=2.56 Hz, 1H, H(11) or H(13) minor; 7.01, d,

3

J=2.56 Hz, 1H, H(11) or H(13) major. l 19.1, C(2)

C

major; 19.6, C(2) minor; 21.3, C(20) minor; 27.0, C(18)

major; 27.7, C(18) minor; 28.0, C(20) major; 36.9 ma-

3

.10, bs, 2H, 14-CH CH SiMe ; 3.22, dd, J=17.8, 14.1

2 2 3

Hz, 1H, H(6ax); 3.66, s, 3H, 19-OMe; 3.90, s, 3H,

jor, 37.2 minor, 38.1 minor, 38.8 minor all CH ; 39.2,

2

1

2

2-OMe; 6.76, s, 1H, H(11). l_C−1.87, SiMe ; 16.3,

C(10) minor; 40.2, C(1) major; 42.3, C(10) major; 43.8,

C(4) minor; 47.5, C(4) major; 49.3, C(5) minor; 51.5,

19-OMe minor; 52.0, 19-OMe major; 55.4, 12-OMe

both isomers; 111.1, 114.5, C(11), C(13) minor; 111.9,

3

4-CH CH SiMe ; 19.6, C(2); 21.3, C(20); 27.6, C(18),

2

3

8.8, 14-CH CH SiMe ; 37.2, C(3); 38.9, C(6); 39.1,

2

3

C(1); 39.4, C(10); 43.8, C(4); 49.0, C(5); 51.5, 19-OMe;

5

1

6.1, 12-OMe; 104.9, C(11); 114.5, C(13); 124.2, C(8);

115.2, C(11), C(13) major; 117.1, 14-C(Br)ꢁCH minor;

2

49.2, C(14); 156.8, C(9); 158.5, C(12); 176.2, C(19);

117.2, 14-C(Br)ꢁCH major; 120.7, 121.7, 127.4, 130.6,

2

+

98.2, C(7). m/z 494/496 (35, M ), 479/481 (100, M−

130.7, 142.8, 143.7, 155.9, 157.9, Ar-C; 161.7, C(5)

major; 162.1, C(12) major; 162.5, C(12) minor; 175.5,

C(19) major; 176.9, C(19) minor; 183.2, C(7) major;

+

5), 73 (75, SiMe ). Found: M , 496.1468. Calc. for

3

81

35

C H BrO Si: M, 496.1468.

2

4

1

96.0, C(7) minor. These compounds hydrolysed read-

3

.12. Reaction of the monobromide 4 and tribromide 5

ily on standing or during ﬂash chromatography (silica

gel, 3:1 hexanes–ethyl acetate) to give (i) methyl 14-

acetyl-12-methoxy-7-oxopodocarpa-8,11,13-trien-19-

oate (18, 7 mg) as clear needles, m.p. 135–140°C. w_m_a_x

1714 (CꢁO ester), 1696 (CꢁO ketone), 1672 (CꢁO ke-

with DBU

A mixture of methyl 6a-bromo-12-methoxy-14-(2-

trimethylsilylethyl)-7-oxopodocarpa-8,11,13-trien-19-

oate (4, 0.256 mmol), methyl 6a-bromo-14-(1,2-dibro-

moethyl)-12-methoxy-7-oxopodocarpa-8,11,13-trien-19-

oate (5, 0.144 mmol) and DBU (160 mg, 1.04 mmol)

was reﬂuxed in benzene for 8 h. DBU (106 mg, 0.7

−

1

tone), 1158 (CꢁC), 1288 cm

(CꢀO). l_H1.12, s, 3H,

H(20); 1.15, td, J=13.7, 4.0 Hz, 1H, H(3ax); 1.28, s,

3H, H(18); 1.55, td, J=13.4, 4.2 Hz, 1H, H(1ax); 1.73,

dp, J=14.4, 3.1 Hz, 1H, H(2eq); 2.05, qt, J=14.0, 3.7

184

P.W.R. Harris et al. / Journal of Organometallic Chemistry 601 (2000) 172–190

Hz, 1H, H(2ax); 2.09, dd, J=14.5, 3.4 Hz, 1H, H(5);

3.14. Reaction of tribromide 5 with DBU at r.t.

2

3

1

.34, dt, J=13.3, 3.2 Hz, 2H, H(1eq), H(3eq); 2.47, s,

H, 14-COMe; 2.95, dd, J=18.2, 3.4 Hz, H, H(6eq);

.21, dd, J=18.2, 14.4 Hz, 1H, H(6ax); 3.72, s, 3H,

9-OMe; 3.87, s, 3H, 12-OMe; 6.38, d, J=2.4 Hz, 1H,

Methyl 6a-bromo-14-(1,2-dibromoethyl)-12-methoxy-

7

-oxopodocarpa-8,11,13-trien-19-oate (5, 0.155 g, 0.261

mmol) and DBU (0.119 g, 0.785 mmol) were stirred at

r.t. in benzene (4 ml) for 2 h. Work-up gave a brown oil

0.142 g) which was dissolved in acetic acid (2 ml). An

H(13); 6.92, d, J=2.4 Hz, 1H, H(11). l_C19.5, C(2);

2

3

C(5); 51.6, 19-OMe; 55.5, 12-OMe; 108.9, C(13); 110.8,

C(11); 121.2, C(8); 147.2, C(14); 157.7, C(9); 163.8,

C(12); 176.8, C(19); 196.8, C(7); 205.4, 14-COMe. m/z

(

1.3, C(20); 27.8, C(18); 30.6, 14-COMe; 36.9, C(6);

7.3, C(3); 38.4, C(1); 38.9, C(10); 43.8, C(4); 49.7,

excess of zinc dust was added and the mixture stirred

overnight. The zinc dust was removed by ﬁltration and

potassium carbonate was added to the ﬁltrate. The

organic layer was run off and the solvent removed to

reveal a yellow oil (84 mg) which was dissolved in 3:3

triﬂuoroacetic acid–90% formic acid (6 ml, v/v) and

mercury(II) bis(triﬂuoroacetate) (0.166 g, 0.39 mmol)

was added and the reaction stirred overnight.

Dichloromethane was then added and the organic layer

removed. Work-up gave an oil (50 mg) which was

puriﬁed by PLC (4:1 hexanes–ethyl acetate, four

sweeps) to give (i) methyl 14-ethyl-12-methoxy-7-ox-

opodocarpa-8,11,13-trien-19-oate (19, 10 mg, 11%) as a

white smear. w_m_a_x1725 (CꢁO ester), 1668 (CꢁO ketone),

+

3

58 (20, M ), 343 (65, M−15), 283 (60, M−

+

HCO Me), 43 (48, COMe). Found: M , 358.1774.

Calc. for C H O : M, 358.1780; and (ii) methyl 14-

acetyl-12-methoxy-7-oxopodocarpa-5,8,11,13-tetraen-

1

2

1

26

5

9-oate (42, 13 mg) as golden chunks, m.p. 198–200°C.

−

1

^wmax 1723 (CꢁO ester), 1993 (CꢁO ketone), 1651 cm

(

^C^ꢁ^O^k^e^t^oⁿ^e⁾^.^lH 1.24, td, J=13.6, 4.4 Hz, 1H,

H(3ax); 1.33, s, 3H, H(20); 1.49, s, 3H, H(18); 1.54, td,

J=13.5, 4.1 Hz, 1H, H(1ax); 1.71–1.77, m, 1H,

H(2eq); 2.16, qt, J=14.0, 3.7 Hz, 1H, H(2ax); 2.34, bd,

J=13.3 Hz, 1H, H(1eq); 2.52, s, 3H, 14-COMe; 2.54,

m, 1H, H(3eq); 3.66, s, 3H, 19-OMe; 3.87, s, 3H,

−

1

1595 (CꢁC), 1277 cm

(CꢀO). l_H1.11, s, 3H, H(20);

1.15, td, J=13.6, 4.0 Hz, 1H, H(3ax); 1.24, t, J=7.4

Hz, 3H, 14-CH CH ; 1.27, s, 3H, H(18); 1.55, td,

2

3

1

2-OMe; 6.54, s, 1H, H(6); 6.69, d, J=2.4 Hz, 1H,

J=13.4, 4.1 Hz, 1H, H(1ax); 1.71, dp, J=14.3, 3.2 Hz,

H(2eq); 1.98–2.10, m, 2H, H(2ax), H(5); 2.29–2.33, m,

2H, H(1eq), H(3eq); 2.89, dd, J=17.8, 3.8 Hz, 1H,

H(13); 7.0, d, J=2.4 Hz, 1H, H(11). l_C19.0, C(2);

2

4

1

7.1, C(18); 27.7, C(20); 30.8, 14-COMe; 37.0, C(3);

0.1, C(1); 42.4, C(10); 47.8, C(4); 52.1, 19-OMe; 55.4,

2-OMe; 109.7, C(13); 111.6, C(11); 120.5, C(8); 125.9,

H(6eq); 3.01–3.16, m, 2H, 14-CH

1

3

CH

7.8, 14.3 Hz, 1H, H(6ax); 3.71, s, 3H, 19-OMe; 3.86, s,

H, 12-OMe; 6.67, d, J=2.6 Hz, 1H, H(13); 6.79, d,

; 3.22, dd, J=

2

3

C(6); 146.0, C(14); 155.4, C(9); 162.9, C(12); 164.8,

C(5); 175.2, C(19); 183.4, C(7); 205.4, 14-COMe. m/z

J=2.6 Hz, 1H, H(11). l 15.4, 14-CH CH ; 19.7, C(2);

C

2

3

+

21.4, C(20); 27.8, C(18), 29.1, 14-CH CH ; 37.3, C(3);

356 (25, M ), 341 (100, M−15), 281 (60, M−

2 3

+

39.1, C(6), C(1); 39.3, C(10); 43.8, C(4); 49.3, C(5);

1.5, 19-OMe; 55.1, 12-OMe; 108.1, C(11); 113.7,

HCO Me), 43 (48, COMe). Found: M , 356.1615.

Calc. for C H O : M, 356.1624.

2

5

2

1

24

5

C(13); 122.8, C(8); 150.4, C(14); 158.4, C(9); 162.4,

+

C(12); 177.0, C(19); 198.8, C(7). m/z 344 (100, M ),

+

3

8

.13. Methyl 14-acetyl-12-methoxy-7-oxopodocarpa-

,11,13-trien-19-oate (18)

327 (45, M−17). Found: M , 344.1988. Calc. for

C H O : M, 344.1988; (ii) methyl 14-ethenyl-12-

21

28

4

methoxy-7-oxopodocarpa-8,11,13-trien-19-oate (20, 7

mg, 8%) as a colourless oil. w_m_a_x1724 (CꢁO ester), 1666

Methyl 6a-bromo-14-(1,2-dibromoethyl)-12-methoxy-

-oxopodocarpa-8,11,13-trien-19-oate (5, 97 mg, 0.166

−

1

(

CꢁO ketone), 1590 (CꢁC), 1281 cm

s, 3H, H(20); 1.13, td, J=13.6, 4.0 Hz, 1H, H(3ax);

.27, s, 3H, H(18); 1.54, td, J=13.4, 4.1 Hz, 1H,

(CꢀO). l 1.11,

H

7

mmol) and DBU (76 mg, 0.5 mmol) were reﬂuxed in

benzene (4 ml) for 1 h. The mixture was cooled to r.t.,

poured into a separatory funnel, washed with brine and

dried. Evaporation of the solvent yielded an oil (46 mg)

which was dissolved in acetic acid (2 ml). Zinc dust (21

mg, 0.325 mmol) was added and the mixture stirred for

1

H(1ax); 1.71, dp, J=14.3, 3.2 Hz, H(2eq); 2.03, dd,

J=13.8, 2.9 Hz, 1H, H(5), H(2ax) obscured; 2.23, dd,

J=12.6, 3.3 Hz, 2H, H(1eq), H(3eq); 2.92, dd, J=

1

5

8.0, 3.8 Hz, 1H, H(6eq); 3.21, dd, J=18.0, 14.3 Hz,

H, H(6ax); 3.71, s, 3H, 19-OMe; 3.89, s, 3H, 12-OMe;

2

h. Work-up gave an oil (49 mg) which was dissolved

.32, dd, J=10.8, 1.5 Hz, 1H, 14-C(H)ꢁCH (cis); 5.51,

2

in 1:1 triﬂuoroacetic acid–90% formic acid (4 ml, v/v).

To the stirred solution was added mercury(II) bis(triﬂ-

uoroacetate) (74 mg, 0.174 mmol) and the mixture

stirred for 24 h. Work-up followed by ﬂash chromatog-

raphy (silica gel, 2:1 hexanes–ethyl acetate) yielded

methyl 14-acetyl-12-methoxy-7-oxopodocarpa-8,11,13-

trien-19-oate (18, 34 mg, 59%, three steps).

dd, J=17.3, 1.5 Hz, 1H, 14-C(H)ꢁCH (trans); 6.87, d,

J=2.5 Hz, 1H, H(13); 6.88, d, J=2.5 Hz, 1H, H(11);

2

7

.56, dd, J=17.3, 10.8 Hz, 1H, 14-C(H)ꢁCH . l 19.7,

2

C

C(2); 21.3, C(20); 27.8, C(18); 37.3, C(3); 38.6, C(6);

38.9, C(1); 39.1, C(10); 43.8, C(4); 49.3, C(5); 51.5,

19-OMe; 55.2, 12-OMe; 110.0, C(11); 111.5, C(13);

115.1, 14-C(H)ꢁCH ; 127.4, C(8); 139.1, 14-C(H)ꢁCH ;

2

P.W.R. Harris et al. / Journal of Organometallic Chemistry 601 (2000) 172–190

185

1

43.6, C(14); 157.9, C(9); 162.6, C(12); 176.9, C(19);

and the organic layer was removed, washed with a

dilute solution of sodium thiosulfate and dried. Re-

moval of the solvent in vacuo afforded a yellow oil

which was ﬂash chromatographed (silica gel, 2:1 hex-

anes–ether) to give (i) methyl 13-acetyl-12-(((1,1-

dimethylethyl)dimethylsilyl)oxy) - 14 - (2 - trimethylsilyl-

ethyl)-podocarpa-6,8,11,13-tetraen-19-oate (23, 32 mg,

31%) as an unstable colourless oil. w_m_a_x1728 (CꢁO

+

98.8, C(7). m/z 342 (80, M ), 341 (100, M−H).

+

Found: M , 342.1833. Calc. for C H O : M,

3

carpa-8,11,13-trien-19-oate-C )mercury(II)

2

1

26

4

42.1831; (iii) (methyl 14-ethyl-12-methoxy-7-oxopodo-

13

bromide

(

21, 7 mg, 4%) as brown crystals, m.p. 156–160°C. w_m_a_x

1

724 (CꢁO ester), 1667 (CꢁO ketone), 1564 (CꢁC), 1277

−1

(

CꢀO), 1277, 1261, 1232, 1097, 1053, 736 cm . l_H

.13, s, 3H, H(20); 1.15, td, J=13.6, 3.9 Hz, 1H,

H(3ax); 1.27–1.31, m, 7H, 14-CH CH , H(18); 1.58, td,

−

1

ester), 1703 (CꢁO ketone), 1248, 861, 839 cm

(SiꢀC).

l

H

0.06, s, 9H, SiMe ; 0.21, s. 3H, SiMe; 0.22, s. 3H,

2

3

J=13.3, 4.1 Hz, 1H, H(1ax); 1.71, dt, J=14.2, 3.2 Hz,

H(2eq); 2.03, dd, J=14.2, 3.9, 1H, H(5); 2.06, qt,

J=13.9, 3.5, 1H, H(2ax); 2.30–2.35, m, 2H, H(1eq),

H(3eq); 2.91, dd, J=17.9, 4.0 Hz, 1H, H(6eq); 3.0–

SiMe; 0.72–0.82, m, 2H, 14-CH CH SiMe ; 0.84, s,

2 2 3

3H, H(20); 0.97, s, 9H, CMe ; 1.12, td, J=13.7, 4.1 Hz,

3

1H, H(3ax); 1.33, s, 3H, H(18); 1.60, td, J=12.9, 3.9

Hz, 1H, H(1ax); 1.74, dp, J=14.2, 3.1 Hz, 1H, H(2eq);

1.95, qt, J=13.8, 3.4 Hz, 1H, H(2ax); 2.10, bd, J=

12.6 Hz, 1H, H(1eq); 2.32, t, J=2.60 Hz, 1H, H(5),

H(3eq) obscured; 2.40–2.54, m, 2H, 14-CH CH SiMe ;

3

1

6

2

3

5

.15, m, 2H, 14-CH CH ; 3.24, dd, J=17.8, 14.2 Hz,

H, H(6ax); 3.72, s, 3H, 19-OMe; 3.87, s, 3H, 12-OMe;

2 3

.83, s, 1H, H(11). l_C17.0, 14-CH CH ; 19.7, C(2);

2

3

2

3

1.4, C(20); 27.7, C(18); 34.1, 14-CH CH ; 37.2, C(3);

2.49, s, 3H, 13-COMe; 3.70, s, 3H, 19-OMe; 6.47, dd,

J=10.2, 2.50 Hz, 1H, H(6); 6.55, dd, J=10.2, 3.0 Hz,

2

3

9.1, C(6), C(1); 39.8, C(10); 43.8, C(4); 49.2, C(5);

1.5, 19-OMe; 55.3, 12-OMe; 104.4, C(11); 112.8,

1H, H(7); 6.57, s, 1H, H(11). l −4.35, SiMe; −4.22,

C

C(13); 124.5, C(8); 153.3, C(14); 160.4, C(9); 163.5,

SiMe; −2.10, SiMe ; 18.0, CMe ; 19.05, H(20); 19.5,

3

+

C(12); 176.9, C(19); 198.6, C(7). m/z 624 (15, M ), 580

19.6, C(2), 14-CH CH SiMe ; 23.9, 14-CH CH SiMe ;

2 3 3 2 3 3

+

(

6

60, M−44), 341 (100, M−HgBr). Found: M ,

25.6, CMe ; 27.6, C(18); 32.8, 13-COMe; 36.3, C(3);

3

79

27

202

24.0791. Calc. for C H Br HgO : M, 624.0800; and

37.1, C(1); 38.3, C(10); 43.4, C(4); 50.4, C(5); 51.5,

19-OMe; 111.2, C(11); 121.0, C(6); 123.6, C(8); 128.3,

C(7); 131.4, C(13); 138.2, C(14); 148.8, C(9); 150.8,

C(12); 177.4, C(19); 206.3, 13-COMe. m/z 542 (10,

2

1

4

(

iv) methyl 14-acetyl-12-methoxy-7-oxopodocarpa-

8,11,13-trien-19-oate (18, 9 mg, 10%).

+

t

+

3

8

.15. Methyl 14-ethenyl-12-methoxy-7-oxopodocarpa-

,11,13-trien-19-oate (20)

M ), 485 (60, M− Bu), 73 (100, SiMe ). Found: M ,

3

542.3228. Calc. for C H O Si : M, 542.3248; and (ii) a

31

50

4

2

mixture (1:1) of methyl 13-acetyl-6a-bromo-7a-

hydroxy-12-(((1,1-dimethylethyl)dimethylsilyl)oxy)-14-

(2-trimethylsilylethyl)podo-carpa-8,11,13-trien-19-oate

(24) and methyl 13-acetyl-6b-bromo-7b-hydroxy-12-

(((1,1-dimethylethyl)dimethylsilyl)oxy)-14-(2-trimethyl-

silylethyl)podocarpa-8,11,13-trien-19-oate (25, 35 mg,

30%) as an unstable yellow foam. w_m_a_x3484 (OH), 1728

(CꢁO ester), 1704 (CꢁO ketone), 1593, 1463 (CꢁC),

To

a suspension of methyl 12-methoxy-14-(2-

trimethylsilylethyl)-7-oxopodocarpa-8,11,13-trien-19-

oate (1, 126 mg, 0.302 mmol) in hexane (10 ml) and

sodium bromate (548 mg, 3.63 mmol) in water (2 ml)

was added sodium metabisulﬁte (690 mg, 3.63 mmol) in

water (1 ml) over 1 min. After 40 min ether was added,

and usual work-up yielded an oil (228 mg) which was

dissolved in acetic acid (5 ml). Zinc dust (200 mg, 3.02

mmol) was added and the mixture was stirred at r.t. for

−

1

1249, 860, 840 cm

(SiꢀC). l_H0.06, 0.063, s, 9H,

SiMe ; 0.11, 0.13, s, 6H, SiMe ; 0.83–0.89, 2H, 14-

3

2

20 min. Flash chromatography (silica gel, 4:1 hexanes–

CH CH SiMe ; 0.97, s, 9H, CMe ; 1.15–1.19, m, 1H,

2 2 3 3

ether) gave methyl 14-ethenyl-12-methoxy-7-oxopodo-

carpa-8,11,13-trien-19-oate (20, 103 mg, 58%, two

steps).

H(3ax); 1.24, s, 3H, H(20); 1.37, s, 3H, H(18); 1.44, s,

3H, H(20); 1.55, s, 3H, H(18), H(1ax) obscured; 1.64–

1.74, m, 1H, H(2eq); 1.95–2.04, m, 1H, H(2ax); 2.12,

bd, J=12.2 Hz, 1H, H(1eq); 2.19–2.26, m, 1H, H(2ax);

2.32, d, J=6.1 Hz, 1H, H(5), H(3eq) obscured; 2.45–

2.54, m, 5H, 13-COMe, 14-CH CH SiMe ; 2.57, s, 1H,

3

1

.16. Attempted bromination of methyl

3-acetyl-12-(((1,1-dimethylethyl)dimethyl-silyl)oxy)14-

2

3

(

2-trimethylsilylethyl)podocarpa-8,11,13-trien-19-oate

22)

H(5); 2.66–2.72, m, 2H, 14-CH CH SiMe ; 3.72, 3.73 s,

2 2 3

3H, 19-OMe; 4.85, d, J=2.5 Hz, 1H, H(6eq); 5.17, d,

J=2.8 Hz, 1H, H(7ax); 5.54, s, 1H, H(7eq); 5.63, d,

J=6.1 Hz, 1H, H(6ax); 6.62, 6.70, s, 1H, H(11). l_C

−4.3, −4.27, −4.21, −3.7, SiMe ; −2.1, SiMe ;

To a stirred suspension of methyl 13-acetyl-14-(2-

trimethylsilyl)ethyl)-12-(((1,1-dimethylethyl)dimethyl-

(

2

3

silyl)oxy)podocarpa-8,11,13-trien-19-oate (22, 0.270 g,

.496 mmol) and sodium bromate (0.168 mmol, 1.13

17.9, CMe₃; 19.5, 19.9, C(2); 20.1, 20.3, 14-

CH CH SiMe ; 23.3, 23.9, 14-CH CH SiMe ; 24.3,

0

2

3

2

3

mmol) in 9:1 hexane–water (10 ml, v/v) was added a

solution of sodium metabisulﬁte (0.123 g, 1.13 mmol) in

water (1 ml) over 1 min. After 30 min ether was added

C(20); 25.5, CMe ; 28.0. 29.0, C(18); 32.62, 32.67,

13-COMe; 37.9, 38.3, C(3); 39.5, C(10); 39.9, C(1);

40.0, C(10); 43.2, C(4); 44.3, C(1); 45.0, C(4); 47.8,

3

186

P.W.R. Harris et al. / Journal of Organometallic Chemistry 601 (2000) 172–190

C(5); 50.1, C(6); 51.3, 51.6, 19-OMe; 54.6, C(6); 59.4,

C(5); 70.9, 71.9, C(7); 112.0, 114.3, C(11); 123.4, 124.6,

C(8); 132.0, 132.6, C(13); 142.3, 143.1, C(14); 149.9,

trimethylsilylethyl)podocarpa-8,11,13-trien-19-oate (26,

0.057 g, 0.120 mmol) and sodium bromate (0.217

mmol, 1.44 mmol) in 8:1 hexane–water (9 ml, v/v).

After 30 min ether was added and the organic layer was

removed. Work-up and ﬂash chromatography (silica

gel, 3:1 hexanes–ether) gave methyl 13-acetyl-12-

acetoxy-14-(2-trimethylsilylethyl)podocarpa-6,8,11,13-

tetraen-19-oate (27, 0.038 g, 68%) as brown needles,

m.p. 112–115°C. w_m_a_x1770 (CꢁO ester aromatic), 1727

(CꢁO ester aliphatic), 1704 (CꢁO ketone), 1248 (SiꢀC),

1

2

50.9, C(9); 151.9, 152.0, C(12); 176.8, 177.6, C(19);

+

06.1, 13-COMe. m/z 639/641 (5, M +H), 621/623

+

(

60, [M+H]−H O), 73 (100, SiMe ). Found: (M +

2 3

81

H), 641.2510. Calc. for C H BrO Si : (M+H),

31

52

5

2

641.2516.

3.17. Methyl 13-acetyl-12-acetoxy-14-(2-trimethyl-

−

1

silylethyl)podocarpa-8,11,13-trien-19-oate (26)

1196 (CꢀO), 861, 837 cm

(SiꢀC). l_H0.07, s, 9H,

SiMe ; 0.71–0.82, m, 2H, 14-CH CH SiMe ; 0.87, s,

3

2

3

A solution of TBAF in THF (0.745 ml, 0.744 mmol)

was added to a stirred solution of methyl 13-acetyl-12-

3H, H(20); 1.13, td, J=13.4, 3.8 Hz, 1H, H(3ax); 1.33,

s, 3H, H(18); 1.58–1.75, m, 2H, H(1ax), H(2eq); 1.94,

qt, J=13.8, 3.4 Hz, 1H, H(2ax); 2.12, bd, J=12.4 Hz,

1H, H(1eq); 2.26, s, 3H, 12-OCOMe; 2.33–2.35, m, 2H,

H(3eq), H(5); 2.42–2.61, m, 2H, 14-CH CH SiMe ;

(

((1,1-dimethylethyl)dimethylsilyl)oxy)-14-(2-trimethyl-

silylethyl)podocarpa-8,11,13-trien-19-oate (22, 0.270 g,

.496 mmol) in THF (3 ml). After 1 h ethyl acetate and

0

2

3

brine were added. Work-up yielded an oil (270 mg)

which was dissolved in pyridine (4 ml). Acetic anhy-

dride (0.101 g, 0.992 mmol) and DMAP (20 mg) were

added and the mixture was stirred overnight. Brine was

then added and the product extracted with ether.

Work-up and ﬂash chromatography (silica gel, 3:1 hex-

anes–ether) gave methyl 13-acetyl-12-acetoxy-14-(2-

2.45, s, 3H, 13-COMe; 3.71, s, 3H, 19-OMe; 6.60, s,

2H, H(6), H(7); 6.84, s, 1H, H(11). l_C−2.10, SiMe₃;

18.9, C(20); 19.4, 14-CH CH SiMe ; 19.5, C(2); 20.9,

2

3

12-OCOMe; 24.0, 14-CH CH SiMe ; 27.6, C(18); 32.2,

2

3

13-COCH ; 36.1, C(1); 37.0, C(3); 38.4, C(10); 43.2,

3

C(4); 50.2, C(5); 51.6, 19-OMe; 114.9, C(11); 120.7,

C(6); 128.2, C(8); 130.8, C(7); 132.3, C(13); 137.9,

C(14); 145.3, C(12); 148.9, C(9); 169.0, 12-OCOMe;

(

trimethylsilyl)ethyl)podocarpa - 8,11,13 - trien - 19 - oate

26, 0.224 g, 96%) as white needles, m.p. 130–133°C.

+

177.3, C(19); 203.9, 13-COMe. m/z 470 (11, M ), 428

+

w_m_a_x1769 (CꢁO ester aromatic), 1725 (CꢁO ester

(100, M−OꢁCꢁCH ), 73 (45, SiMe ). Found: M ,

2

3

aliphatic), 1703 (CꢁO ketone), 1248, 1267, 861, 836

470.2486. Calc. for C H O Si: M, 472.2486.

27

38

5

−

1

cm (SiꢀC). l 0.036, s, 9H, SiMe ; 0.64–0.81, m, 2H,

H

3

1

4

1

4-CH CH SiMe ; 1.03, s, 3H, H(20); 1.06, td, J=13.5,

.1 Hz, 1H, H(3ax); 1.27, s, 3H, H(18); 1.37, td, J=

3.5, 4.1 Hz, 1H, H(1ax); 1.49, d, J=12.0 Hz, 1H,

3.19. Methyl 13-acetyl-12-methoxy-14-(2-trimethyl-

silylethyl)podocarpa-8,11,13-trien-19-oate (28)

2

3

H(5); 1.60, bd, J=14.1, 1H, H(2eq); 1.89–2.06, m, 2H,

H(6ax), H(2ax); 2.14, bd, J=12.9 Hz, 1H, H(1eq);

A solution of TBAF (1.43 ml, 1.43 mmol) in THF (3

,

ml) that had been pre-dried over 3 A molecular sieves

2

.22–2.28, m, 5H, 12-OCOMe, H(3eq), H(6eq); 2.36–

was added to a stirred solution of methyl 13-acetyl-12-

(((1,1-dimethylethyl)dimethylsilyl)oxy)-14-(2-trimethyl-

silylethyl)podocarpa-8,11,13-trien-19-oate (22, 0.389 g,

0.715 mmol) and iodomethane (0.202 g, 1.43 mmol) in

THF (5 ml) under nitrogen. After stirring overnight the

reaction mixture was ﬁltered, poured onto brine and

extracted with ether. Work-up and ﬂash chromatogra-

phy (silica gel, 3:1 hexanes–ether) gave methyl 13-

acetyl - 12 - methoxy - 14 - (2 - trimethylsilylethyl)podo-

carpa-8,11,13-trien-19-oate (28, 0.284 g, 89%) as

colourless needles, m.p. 115–118°C. w_m_a_x1726 (CꢁO

ester), 1698 (CꢁO ketone), 1456, 1462 (CꢁC), 1247

.49, m, 2H, 14-CH CH SiMe ; 2.42, s, 3H, 13-COMe;

2

3

.59, ddd, J=16.7, 12.5, 6.3 Hz, 1H, H(7ax); 2.88, dd,

J=16.8, 4.5 Hz, 1H, H(7eq); 3.67, s, 3H, 19-OMe;

.89, s, 1H, H(11). l_C−2.10, SiMe ; 17.9, 14-

6

3

CH CH SiMe ; 19.7, C(2); 20.7, C(6); 20.9, 12-

2

3

OCOMe; 22.6, C(20); 23.9, 14-CH CH SiMe ; 28.2,

2

3

C(7); 28.3, C(18), 32.2, 13-COMe; 37.2, C(3); 38.9,

C(10); 39.4, C(1); 43.7, C(4); 51.2, 19-OMe; 51.7, C(5);

1

17.2, C(11); 131.2, C(8); 131.9, C(13); 140.4, C(14);

44.4, C(12); 150.9, C(9); 169.0, 12-OCOMe; 177.5,

+

C(19); 203.9, 13-COMe. m/z 472 (15, M ), 457 (50,

−

1

M−15), 430 (100, M−OꢁCꢁCH ), 415 (80, 430–15).

(SiꢀC), 1146 (CꢀO), 861, 835 cm

(SiꢀC). l 0.065, s,

2

H

+

Found: M , 472.2643. Calc. for C H O Si: M,

9H, SiMe ; 0.65–0.83, m, 2H, 14-CH CH SiMe ; 1.07,

2

7

40

5

3

2

3

472.2645.

s, 3H, H(20); 1.10, td, J=13.6, 4.2 Hz, 2H, H(3ax);

.30, s, 3H, H(18); 1.40, td, J=13.3, 4.1 Hz, 1H,

1

3.18. Methyl 13-acetyl-12-acetoxy-14-(2-trimethyl-

H(1ax); 1.52, dd, J=12.3, 1.4 Hz, 1H, H(5); 1.63–1.68,

silylethyl)podocarpa-6,8,11,13-tetraen-19-oate (27)

m, 1H, H(2eq); 1.88–2.09, m, 2H, H(2ax), H(6ax);

2

.22–2.32, m, 3H, H(1eq), H(3eq), H(6eq); 2.34–2.47,

A solution of sodium metabisulﬁte (0.275 g, 1.44

mmol) in water (1 ml) was added over 1 min to a stirred

suspension of methyl 13 - acetyl - 12 - acetoxy - 14 - (2-

m, 2H, 14-CH CH SiMe ; 2.48, s, 3H, 13-COMe; 2.56,

ddd, J=16.5, 12.6, 6.2 Hz, 1H, H(7ax), 2.86, dd,

J=16.5, 3.9 Hz, 1H, H(7eq); 3.68, s, 3H, 19-OMe;

2

3

P.W.R. Harris et al. / Journal of Organometallic Chemistry 601 (2000) 172–190

187

3

.78, s, 3H, 12-OMe; 6.70, s, 1H, H(11). l_C−2.1,

v/v). After 1 h ether was added and the organic layer

was removed. Work-up and ﬂash chromatography (sil-

ica gel, 3:1 hexanes–ether) gave methyl 13-acetyl-6a-

bromo-12-methoxy-14-(2-trimethylsilylethyl)-7-oxo-

podocarpa-8,11,13-trien-19-oate (30, 88 mg, 93%)

which was recrystallised from CH Cl –hexanes as

SiMe ; 18.1, 14-CH CH SiMe ; 19.9, C(2); 20.9, C(6);

3

2

3

22.6, C(20); 23.8, 14-CH CH SiMe ; 27.9, C(7); 28.3,

2 2 3

C(18); 32.6, 13-COMe; 37.3, C(3); 39.1, C(10); 39.7,

C(1); 43.8, C(4); 51.1, 19-OMe; 52.2, C(5); 55.3, 12-

OMe; 105.6, C(11); 125.6, C(8); 129.2, C(13); 140.2,

2

C(14); 150.2, C(9); 153.8, C(12); 177.7, C(19); 206.3,

golden rods, m.p. 202–205°C. w_m_a_x1730 (CꢁO ester),

+

1

3-COMe. m/z 444 (25, M ), 429 (100, M−15), 73

1704 (CꢁO ketone), 1681 (CꢁO ketone), 1584 (CꢁC),

+

−1

(

28, SiMe₃). Found: M , 444.2694. Calc. for

1267, 1246, (SiꢀC), 1208, (CꢀO), 862, 835 cm

(SiꢀC).

C H O Si: M, 444.2696.

l

0.04, s, 9H, SiMe ; 0.87, td, J=13.8, 3.8 Hz, 1H,

2

6

40

4

H

3

1

4-CH CH SiMe ; 0.89, s, 3H, H(20); 1.03, td, J=13.9,

2 2 3

3.20. Methyl 13-acetyl-12-methoxy-14-(2-trimethyl-

4.2 Hz, 1H, 14-CH CH SiMe ; 1.19, td, J=13.5, 3.6

2 2 3

silylethyl)-7-oxopodocarpa-8,11,13-trien-19-oate (29)

Hz, 1H, H(3ax); 1.52, s, 3H, H(18); 1.73–1.82, m, 2H,

H(1ax), H(2eq); 1.97, qt, J=14.2, 3.4 Hz, 1H, H(2ax);

2.14, bd, J=14.0 Hz, 1H, H(1eq); 2.29–2.46, m, 3H,

H(3eq), H(5), 14-CH CH SiMe ; 2.50, s, 3H, 13-

Ceric ammonium nitrate (0.302 g, 0.551 mmol) in

water (1 ml) was added to a stirred solution of methyl

2

3

13-acetyl-12-methoxy-14-(2-trimethylsilylethyl)podo-

COMe; 2.93, td, J=13.4, 4.0, 1H, 14-CH CH SiMe ;

2 2 3

carpa-8,11,13-trien-19-oate (28, 49 mg, 0.11 mmol) in

acetonitrile (4 ml). The mixture was stirred for 2 h and

then extracted with ethyl acetate. PLC (3:1 hexanes–

3.73, s, 3H, 19-OMe; 3.87, s, 3H, 12-OMe; 5.70, d,

J=6.5 Hz, 1H, H(6ax); 6.72, s, 1H, H(11). l_C−2.1,

SiMe ; 19.2, 14-CH CH SiMe ; 20.0, C(2); 23.4, C(20);

3

2

3

ether)

gave

methyl

13-acetyl-12-methoxy-14-(2-

24.1, 14-CH CH SiMe ; 28.6, C(18); 32.4, 13-COMe;

2 2 3

trimethylsilylethyl)-7-oxopodocarpa-8,11,13-trien-19-

oate (29, 23 mg, 45%) as a colourless oil. w_m_a_x1725

37.4, C(1); 37.9, C(3); 39.3, C(10); 45.2, C(4); 50.6,

C(6); 51.9, 19-OMe; 55.4, 12-OMe; 56.9, C(5); 102.5,

C(11); 124.2, C(8); 130.6, C(13); 144.8, C(14); 154.3,

C(9); 158.5, C(12); 176.5, C(19); 192.4, C(7); 204.6,

(

1

9

CꢁO ester), 1705 (CꢁO ketone), 1670 (CꢁO ketone),

−1

583 (CꢁC), 1267, 862, 835 cm

(SiꢀC). l_H0.066, s,

+

H, SiMe ; 0.72–0.87, m, 2H, 14-CH CH SiMe ; 1.11,

13-COMe. m/z 537/539 (40, M +H), 457 (60, [M+

3

2

3

+

s, 3H, H(20); 1.14, td, J=13.9, 4.1 Hz, 1H, H(3ax);

.26, s, 3H, H(18); 1.55, td, J=13.1, 3.9 Hz, 1H,

H]−Br), 73 (100, SiMe ). Found: (M +H), 537.1672.

3

1

Calc. for C H BrO Si: (M+H), 537.1672.

26

38

5

H(1ax);.1.73, dp, J=14.3, 3.1 Hz, 1H, H(2eq); 2.0, dd,

J=14.2, 4.0 Hz, 1H, H(5); 2.09, qt (partially obscured),

J=13.9, 3.5 Hz, 1H, H(2ax); 2.31, dt, J=13.2, 2.9 Hz,

3.22. Methyl 14-acetyl-12-methoxy-5i-methyl-10-

norpodocarpa-6,8,10,11,13-pentaen-19-oate (31)

2H, H(1eq), H(3eq); 2.48, s, 3H, 13-COMe; 2.78, td,

J=12.7, 4.5 Hz, 1H, 14-CH CH SiMe ; 2.88–2.96, m,

2

3

2

H, H(6eq), 14-CH CH SiMe ; 3.22, dd, J=17.7, 14.2

Methyl 14-acetyl-12-methoxy-7-oxopodocarpa-8,11,-

13-trien-19-oate (18, 24 mg, 0.067 mmol) and p-tolue-

nesulfonic acid (two crystals) were reﬂuxed in toluene

2

3

Hz, 1H, H(6ax); 3.68, s, 3H, 19-OMe; 3.86, s, 3H,

1

2-OMe; 6.79, s, 1H, H(11). l_C−2.0, SiMe ; 19.0,

4-CH CH SiMe ; 19.6, C(2); 21.3, C(20); 26.0, 14-

3

(4 ml) with 4 A molecular sieves for 3.5 h. More

,

2

3

CH CH SiMe ; 27.7, C(18); 32.5, 13-COMe; 37.2, C(3);

3

C(5); 51.5, 19-OMe; 55.4, 12-OMe; 104.3, C(11); 122.6,

C(8); 131.2, C(13); 146.2, C(14); 158.3, C(9); 158.9,

C(12); 176.9, C(19); 198.5, C(7); 205.1, 13-COMe. m/z

p-toluenesulfonic acid was added and reﬂuxing contin-

ued for a further 3 h. Work-up followed by ﬂash

chromatography (silica gel, 3:1 hexanes–ethyl acetate)

gave methyl 14-acetyl-12-methoxy-5b-methyl-10-nor-

podocarpa-6,8,10,11,13-pentaen-19-oate (31, 16 mg,

67%) as a colourless oil. w_m_a_x1723 (CꢁO ester), 1685

2

3

9.1, C(1); 39.3, C(6); 39.7, C(10); 43.8, C(4); 49.2,

+

4

58 (40, M ), 443 (100, M−15), 73 (31, SiMe ).

3

+

−1

Found: M , 458.2490. Calc. for C H O Si: M,

(CꢁO ketone), 1594, 1463 (CꢁC), 1203, cm (CꢀO). l_H

2

6

38

5

458.2490.

1.10, s, 3H, 5-Me; 1.32, s, 3H, H(18); 1.68–1.73, m, 2H,

H(2); 2.30–2.36, m, 2H, H(3); 2.56, s, 3H, 14-COMe;

3.75, s, 3H, 19-OMe; 3.86, s, 3H, 12-OMe; 6.05, m, 1H,

H(1); 6.48, d, J=10.3 Hz, 1H, H(6); 6.48, d, J=10.3

Hz, 1H, H(7); 6.98, d, J=2.6 Hz, 1H, H(13); 7.02, d,

3.21. Methyl 13-acetyl-6h-bromo-12-methoxy-14-

(

2-trimethylsilylethyl)-7-oxopodocarpa-8,11,13-trien-

19-oate (30)

J=2.6 Hz, 1H, H(11). l 19.9, C(18); 22.9, C(2); 23.7,

C

A solution of sodium metabisulﬁte (0.373 g, 1.96

5-Me; 26.9, C(3); 30.1, 14-COMe; 41.8, C(5); 45.7,

C(4); 51.6, 19-OMe; 55.4, 12-OMe; 112.8, C(13); 113.6,

C(11); 121.3, C(7); 122.6, C(8); 125.3, C(1); 135.0, C(6);

136.6, 136.8, Ar-C(quaternary); 138.3, C(9); 158.0,

C(12); 176.8, C(19); 202.3, 14-COMe. m/z 340 (40,

mmol) in water (1 ml) was added over 1 min to a stirred

suspension of methyl 13-acetyl-12-methoxy-14-(2-

trimethylsilylethyl)-7-oxopodocarpa-8,11,13-trien-19-

oate (29, 0.075 g, 0.103 mmol) and sodium bromate

+

(

0.294 mmol, 1.96 mmol) in 7:1 hexane–water (8 ml,

M ), 240 (100, M−100), 197 (890, 240−COMe), 43

188

P.W.R. Harris et al. / Journal of Organometallic Chemistry 601 (2000) 172–190

+

(

80, COMe). Found: M , 340.1680. Calc. for

(10, M ), 386 (100, M−18). Found: M , 404.2045.

C H O : M, 340.1675.

Calc. for C H O Si: M, 404.2019.

2

1

24

4

22 32

5

3

.24. Reaction of methyl 12-methoxy-14-(2-tri-

3

.23. Reaction of methyl-12-methoxy-14-(2-trimethyl-

methylsilylethyl)podocarpa-8,11,13-trien-19-oate (8)

^wⁱ^t^h^A^l^C^l3

silylethyl)-7-oxopodocarpa-8,11,13-trien-19-oate (1)

with AlCl₃

Methyl 12-methoxy-14-(2-trimethylsilylethyl)podo-

carpa-8,11,13-trien-19-oate (8, 142 mg, 0.35 mmol) and

aluminium chloride (235 mg, 1.76 mmol) were reﬂuxed

in dichloromethane (6 ml) for 24 h. Saturated sodium

hydrogencarbonate was added and the mixture ex-

tracted with dichloromethane, washed with brine and

Methyl-12-methoxy-14-(2-trimethylsilylethyl)-7-oxo-

podocarpa-8,11,13-trien-19-oate (1, 0.320 g, 0.79 mmol)

and aluminium chloride (0.5 g, 3.84 mmol) were

reﬂuxed in dry dichloromethane (10 ml) for 48 h.

Methanol was added, the mixture poured onto brine

and extracted with dichloromethane. The solvent was

removed to yield an oil (316 mg) which was puriﬁed by

ﬂash chromatography (silica gel, 1:1 hexanes–ether) to

give (i) methyl 12-hydroxy-14-(2-trimethylsilylethyl)-7-

oxopodocarpa-8,11,13-trien-19-oate (32, 13 mg, 4%) as

a colourless oil. w_m_a_x3369 (OH), 1726 (CꢁO ester), 1644

dried (MgSO ). Flash chromatography (silica gel, 3:1,

4

1

:1 hexanes–ether) gave (i) a mixture of 12-methoxy-

podocarpa-8,11,13-trien-19-oate (34, 13%) and methyl

4-alkylated [methyl (35, 14%), ethyl (36, 52%), propyl

37, 11%)]-12-methoxypodocarpa-8,11,13-trien-19-oate

1

(

−

1

(GC–MS analysis, 114 mg) which was repuriﬁed by

chromatography to give 48 mg of the above compo-

nents; and (ii) methyl 13-acetyl-12-hydroxy-14-(2-

trimethylsilylethyl)-7-oxopodocarpa-8,11,13-trien-19-

oate (38) which was repuriﬁed by ﬂash chromatography

(

CꢁO ketone), 1599 (CꢁC), 1247, 861, 831 cm (SiꢀC).

l_H0.039, s, 9H, SiMe ; 0.74–0.88, m, 2H, 14-

3

CH CH SiMe ; 1.07, s, 3H, H(20); 1.11, td, J=13.5,

2

3

1

.6 Hz, 1H, H(3ax); 1.23, s, 3H, H(18); 1.51, td, J=

3.2, 3.6 Hz, 1H, H(1ax); 1.61, bd, J=14.1, 1H,

(

1:1 hexanes–ether) to give (18 mg, 12%) of the pure

H(2eq); 1.93–2.02, m, 2H, H(2ax), H(5); 2.21–2.30, m,

H, H(3eq), H(1eq); 2.91, dd, J=17.9, 3.44 Hz, 1H,

H(6eq); 2.95–3.08, m, 2H, 14-CH CH SiMe ; 3.22, dd,

compound. w_m_a_x1726 (CꢁO ester), 1704, (CꢁO ketone),

2

−

1

(

681, (CꢁO ketone) 1583 (CꢁC) 1246, 862, 836, cm

2

3

SiꢀC). l_H0.078, s, 9H, SiMe ; 0.74, td, J=14.0, 4.5

Hz, 1H, 14-CH CH SiMe ; 0.84, td, J=13.0, 4.3 Hz,

3

J=17.8, 14.3 Hz, 1H, H(6ax); 3.68, s, 3H, 19-OMe;

2

3

6

7

.67, s, 1H, H(13); 6.63, d, J=1.60 Hz, 1H, H(11);

1

H, 14-CH CH SiMe ; 1.08, s, 3H, H(20); 1.12, td,

2 2 3

.73, bs, 1H, 12-OH. l_C−1.85, SiMe ; 18.6, 14-

3

J=13.4, 4.1 Hz, 1H, H(3ax); 1.26, s, 3H, H(18); 1.51,

td, J=13.4, 4.4, 1H, H(1ax); 1.70, dp, J=14.3, 3.1 Hz,

CH CH SiMe ; 19.7, C(2); 21.3, C(20); 27.7, C(18);

2

3

0.3, 14-CH CH SiMe ; 37.2, C(3); 38.9, C(6), C(1);

2 2 3

1

H, H(2eq); 2.01, dd, J=14.0, 4.4 Hz, 1H, H(5); 2.01,

39.2, C(10); 43.8, C(4); 49.3, C(5); 51.5, 19-OMe; 109.4,

qt (partially obscured), J=14.0, 3.5 Hz, 1H, H(2ax);

C(11); 116.0, C(13); 121.7, C(8); 152.4, C(14); 159.3,

2

1

4

1

.24, bd, J=12.8 Hz, 1H, (1eq); 2.30, bd, J=13.8 Hz,

H, H(3eq); 2.62, s, 3H, 13-COMe; 2.91, dd, J=18.0,

.3 Hz, 1H, H(6eq); 3.06, td, J=12.9, 4.3 Hz, 1H,

4-CH CH SiMe ; 3.28, dd, J=18.0, 14.4 Hz, 1H,

C(9); 160.4, C(12); 177.3, C(19); 199.9, C(7). m/z 402

+

(

100, M ), 387 (70, M−15), 329 (85, M−SiMe ).

3

+

Found: M , 402.2216. Calc. for C H O Si: M,

2

3

34

4

2

3

402.2226; and (ii) methyl 12-hydroxy-14-(2-hydroxy-

H(6ax), 14-CH CH SiMe obscured; 3.70, s, 3H, 19-

2

3

dimethylsilylethyl)-7-oxopodocarpa-8,11,13-trien-19-

^o^a^t^e⁽³³^,²⁷⁶^m^g^,⁸⁹^%⁾^a^s^a^w^hⁱ^t^e^f^o^a^m^.^wmax 3328

OMe; 6.83 s 1H, H(11); 9.42, bs, 1H, 12-OH. l_C

−1.98, SiMe ; 19.6, 14-CH CH SiMe ; 19.9, C(2);

3

2

3

(

OH), 1725 (CꢁO ester), 1643 (CꢁO ketone), 1599

2

1.2, C(20); 26.5, 14-CH CH SiMe ; 27.7, C(18); 32.7,

2 2 3

−1

CꢁC), 1252, 841 cm

⁽^Sⁱ^ꢀ^C⁾^.^lH 0.063, s, 6H,

13-COMe; 37.3, C(3); 38.7, C(6); 39.3, C(1) and C(10);

43.8, C(4); 48.7, C(5); 51.5, 19-OMe; 110.9, C(11);

SiMe OH; 0.84–0.99, m, 2H, 14-CH CH SiMe OH;

2

1

2

1

3

1

.07, s, 3H, H(20), H(3ax) obscured; 1.23, s, 3H, H(18);

.51, bt, J=13.0 Hz, 1H, H(1ax); 1.61, bd, 1H, H(2eq);

.99, dd, J=13.9, 3.5 Hz, 1H, H(5), H(2ax) obscured;

.26, m, 2H, H(3eq), H(1eq); 2.91, dd, J=17.9, 3.4 Hz,

1

25.7, C(8); 150.2, C(14); 159.4, C(9); 160.9, C(12);

76.8, C(19); 199.1, C(7); 206.6, 13-COMe. C(13) not

+

detected. m/z 444 (90, M ), 429 (85, M−15), 73 (100,

SiMe ). Found: M , 444.2327. Calc. for C H O Si:

M, 444.2332.

+

3

25 36

5

H, H(6eq); 3.02–3.17, m, 2H, 14-CH CH SiMe OH;

2

.25, dd, J=17.9, 14.3 Hz, 1H, H(6ax); 3.68, s, 3H,

9-OMe; 6.81, s, 1H, H(11); 6.85, s, 1H, H(13); 9.1, bs,

3.25. Methyl 12-acetoxy-14-(2-hydroxydimethylsilyl-

ethyl)-7-oxopodocarpa-8,11,13-trien-19-oate (39)

H, 12-OH. l_C0.38, SiMe OH; 19.8, C(2), 14-

2

CH CH SiMe OH; 21.3, C(20); 27.7, C(18); 29.7, 14-

2

CH CH SiMe OH; 37.2, C(3); 38.9, C(6), C(1); 39.1,

Methyl 12-hydroxy-14-(2-hydroxydimethylsilylethyl)-

7-oxopodocarpa-8,11,13-trien-19-oate (33, 40 mg, 0.099

mmol) was stirred with acetic anhydride (101 mg, 0.99

mmol) in pyridine (2 ml) for 2 days. The mixture was

2

C(10); 43.7, C(4); 49.2, C(5); 51.6, 19-OMe; 109.7,

C(11); 116.4, C(13); 121.4, C(8); 152.2 C(14); 159.6,

C(9); 161.3, C(12); 177.2, C(19); 200.7, C(7). m/z 404

P.W.R. Harris et al. / Journal of Organometallic Chemistry 601 (2000) 172–190

189

poured onto brine and extracted with dichloromethane.

The combined extracts were washed with 2 M HCl,

OR; 2.84, dd, J=16.4, 4.3 Hz, 2H, H(7eq); 3.68, s, 3H,

19-OMe; 5.17, s, 2H, bs, 12-OH; 6.61, d, J=2.4 Hz,

2H, H(13); 6.65, J=2.4 Hz, 2H, H(11). l_C0.17,

SiMe OR; 18.6, 14-CH CH SiMe OR; 20.0, C(2); 20.9,

dried (MgSO ) and the solvent removed to reveal an oil

4

(

40 mg) which was puriﬁed by ﬂash chromatography

silica gel, 6:1 hexanes–ethyl acetate) to give methyl

2

C(6); 22.7, C(20); 26.3, 14-CH CH SiMe OR; 28.0,

2

1

2 - acetoxy - 14 - (2 - hydroxydimethylsilylethyl) - 7 - oxo-

C(7); 28.4, C(18); 37.3, C(3); 38.7, C(10); 39.7, C(1);

43.8, C(4); 51.3, 19-OMe; 52.3, C(5); 109.7, C(11);

112.6, C(13); 125.0, C(8); 144.3, C(14); 149.8, C(9);

podocarpa-8,11,13-trien-19-oate (39, 24 mg, 53%) as a

colourless oil. w_m_a_x3437 (OH), 1768 (CꢁO ester aro-

matic), 1726 (CꢁO ester aliphatic), 1679 (CꢁO ketone),

+

153.5, C(12); 178.0, C(19). m/z 762 (16, M ), 55 (100).

−

1

+

1

593 (CꢁC), 1198 (CꢀO), 736 cm . l_H0.18, s, 6H,

Found: M , 762.4339. Calc. for C H O Si : M,

44

66

7

2

SiMe OH; 0.81–0.95, m, 2H, 14-CH CH SiMe OH

762.4347.

2

1.04, s, 3H, H(20); 1.13, td, J=13.6, 3.9 Hz, 1H,

H(3ax); 1.26, s, 3H, H(18); 1.55, td, J=13.3, 3.9 Hz,

3.27. Attempted ionic hydrogenation of methyl 12-

triethylsilyloxy-14-(2-hydroxydimethylsilylethyl)-

podocarpa-8,11,13-trien-19-oate (33)

1

5

H, H(1ax); 1.67–1.72, m, 1H, H(2eq); 2.04, dd, J=

4.2, 3.8, 1H, H(5), H(2ax) obscured; 2.24–2.31, m,

H, 12-OCOMe, H(1eq), H(3eq); 2.92, dd, J=17.8, 3.8

Hz, 1H, H(6eq); 2.98, m, 2H, 14-CH CH SiMe OH;

Methyl 12-hydroxy-14-(2-hydroxydimethylsilylethyl)-

7-oxopodocarpa-8,11,13-trien-19-oate (33, 115 mg, 284

mmol), triﬂuoroacetic acid (0.325 g, 2.84 mmol) and

triethylsilane (0.165 g, 1.54 mmol) were dissolved in

dichloromethane (3 ml) and stirred at r.t. for 20 h.

Solid sodium hydrogencarbonate and brine were added

and the organic layer was removed. The aqueous layer

was extracted with dichloromethane and the combined

extracts were washed with saturated sodium hydrogen-

2

3.26, dd, J=17.8, 14.2 Hz, H(6ax); 3.70, s, 3H, 19-

OMe; 6.91, d, J=2.20 Hz, 1H, H(13); 7.01, d, J=2.20

Hz, 1H, H(11). l_C0.22, SiMe OH; 19.6, C(2); 21.1,

2

1

2

3

2-OCOMe; 20.1, 14-CH CH SiMe OH; 21.4, C(20);

2 2 2

7.7, C(18); 29.3, 14-CH CH SiMe OH; 37.2, C(1);

2

8.9, C(3); 39.15, C(6); 39.3, C(10); 43.8, C(4); 49.2,

C(5); 51.5, 19-OMe; 115.5, C(11); 121.7, C(13); 126.7,

C(8); 151.1, C(14); 153.5 C(12); 157.7, C(9); 168.8,

1

2-OCOMe; 176.9, C(19); 199.2 C(7). m/z 446 (B1,

carbonate and dried (MgSO ). Flash chromatography

(silica gel, 3:1 hexanes–ether) gave methyl 12-triethyl-

silyloxy-14-(2-hydroxydimethylsilylethyl)podocarpa-8,-

4

+

M ), 428 (100, M−H O), 43 (98, COCH ). Found:

M , 446.2118. Calc. for C H O Si: M, 466.2125.

2

3

+

24

34

6

1

1,13-trien-19-oate (41, 35 mg, 24%) as a white foam.

3

.26. Reaction of methyl 12-hydroxy-14-(2-hydroxy-

w_m_a_x3426 (OH), 1727 (CꢁO ester), 1610 (CꢁC), 1250,

−

1

dimethylsilylethyl)-7-oxopodocarpa-8,11,13-trien-

740, 776 (SiꢀC), 1068 cm

(SiꢀO). l_H0.16, s, 6H,

19-oate (33) with BH ·DMS

SiMe OH; 0.56, q, J=8.0 Hz, 6H, SiCH CH ; 0.81–

3

2

3

0

.85, m, 2H, 14-CH CH SiMe OH; 0.97, m, 6H,

2 2 2

To a stirred solution of methyl 12-hydroxy-14-(2-hy-

SiCH CH ; 1.06, s, 3H, H(20); 1.10, td, J=13.5, 4.1,

2 3

droxydimethylsilylethyl)-7-oxopodocarpa-8,11,13-trien-

9-oate (33, 0.040 g, 0.099 mmol) was added borane-

1H, H(3ax); 1.30, s, 3H, H(18); 1.38, td, J=13.4, 4.0,

1H, H(1ax); 1.52, dd, J=12.3, 1.2 Hz, 1H, H(5); 1.63,

dp, J=14.2, 2.9 Hz, 1H, H(2eq); 1.89–2.06, m, 2H,

H(2ax), H(6ax); 2.18–2.30, m, 3H, (1eq), H(3eq),

H(6eq); 2.49–2.58, m, 3H, H(7ax), 14-CH CH SiMe -

1

dimethyl sulﬁde (0.030 g, 0.396 mmol) under an atmo-

sphere of nitrogen, causing the evolution of hydrogen.

The solution was stirred for 19 h, diluted carefully with

methanol, then brine and the organic layer removed.

The aqueous layer was extracted with dichloromethane

and the combined layers washed with brine and dried.

Removal of the solvent in vacuo afforded an oil (48

mg) which was puriﬁed by ﬂash chromatography (silica

gel, 1:1 hex-anes–ether) to give bis[2-(14-(methyl 12-hy-

droxypodocarpa-8,11,13-trien-19-oate)ethyl)dimethyl]-

disiloxane (40, 26 mg, 34%) as white ﬂakes, m.p. 160–

2

OH; 2.83, dd, J=16.6, 4.1 Hz, 1H, H(7eq); 3.69, s, 3H,

19-OMe; 6.58, d, J=2.52 Hz, 1H, H(13); 6.65, d,

J=2.52 Hz, 1H, H(11). l_C0.18, SiMe OH; 2.3,

2

SiCH CH ; 6.7, SiCH CH ; 18.4, 14-CH CH SiMe -

2

3

2

3

2

OH; 19.9, C(2); 20.9, C(6); 22.7, C(20); 26.3, 14-

CH CH SiMe OH; 28.0, C(7); 28.4, C(18); 37.4, C(3);

2

38.7, C(10); 39.7, C(1); 43.9, C(4); 51.2, 19-OMe; 52.3,

C(5); 109.6, C(11); 112.4, C(13); 125.1, C(8); 144.4,

C(14); 149.7, C(9); 153.5, C(12); 178.0, C(19). m/z 504

1

6

70°C. w_m_a_x3319 (OH), 1726 (CꢁO ester), 1456 (CꢁC),

−1

+

252 (SiꢀC), 1059 (SiꢀO), 843 cm (SiꢀC). l 0.155, s,

(90, M ), 475 (100, M−29). Found: M , 504.3114.

H

H,

SiMe OR;

0.81–0.98,

m,

4H,

14-

Calc. for C H O Si : M, 504.3091.

2

28 48

4

2

CH CH SiMe OR; 1.04, s, 6H, H(20); 1.07, td, J=

2

13.8, 3.8 Hz, 2H, H(3ax); 1.29, s, 6H, H(18); 1.36, td,

J=13.3, 4.0 Hz, 2H, H(1ax); 1.52, d, J=12.7 Hz, 1H,

H(5); 1.60–1.64, m, 2H, H(2eq); 1.89–2.04, m, 4H,

H(2ax), H(6ax); 2.17–2.29, m, 6H, H(1eq), H(3eq),

H(6eq); 2.49–2.58, m, 6H, H(7ax), 14-CH CH SiMe -

4. Supplementary material

Crystallographic data for the structure reported in

this paper have been deposited with the Cambridge

2

190

P.W.R. Harris et al. / Journal of Organometallic Chemistry 601 (2000) 172–190

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