Open-chain remote stereocontrol using allylgermanes

Tetrahedron 70 (2014) 7253e7267

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Tetrahedron

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Open-chain remote stereocontrol using allylgermanes

*

Eric J. Thomas , Anna P. Weston

School of Chemistry, University of Manchester, Manchester M13 9PL, UK

a r t i c l e i n f o

a b s t r a c t

Alk-2-enyl(trialkyl- and -triaryl)germanes are transmetallated by tin(IV) halides at ꢀ78 ^ꢁC with 15 min

being sufﬁcient for the transmetallation to proceed effectively to completion. Alk-2-enyl(trialkyl)ger-

manes are transmetallated by both tin(IV) chloride and tin(IV) bromide under these conditions, but the

corresponding triphenylgermanes are only transmetallated using tin(IV) chloride. These observations led

to procedures for reactions of 5-substituted-pent-2-enyl- and -hex-2-enyl-germanes with aldehydes that

proceed with useful levels of 1,5- and 1,6-stereocontrol in favour of the (Z)-1,5-anti- and (Z)-1,6-syn-

alkenols, respectively. Slightly improved stereoselectivities were obtained using (Z)-alk-2-enylgermanes.

The reaction of (Z)-6-hydroxyhept-2-enyl(triethyl)germane with benzaldehyde when promoted using

tin(IV) bromide gave a 3-ethenyl-6-methyl-2-phenyltetrahydropyran rather than the expected homo-

allylic alcohol.

Article history:

Received 26 April 2014

Received in revised form 11 June 2014

Accepted 13 June 2014

Available online 25 June 2014

Keywords:

Allylgermane

Remote stereocontrol

Transmetallation

Stereoselective synthesis

Alcohol synthesis

1. Introduction

Chiral alk-2-enylstannanes with heteroatom containing func-

tionality are transmetallated stereoselectively by tin(IV) halides

to generate alk-1-en-3-yltin trihalides that react with aldehydes

with useful remote stereocontrol to give (Z)-alkenols.¹For ex-

ample,

transmetallation

of

5-benzyloxy-4-methylpent-2-

enyl(tributyl)stannane 1 with tin(IV) chloride generates the

(pent-1-en-3-yl)tin trichloride 2 that reacts with aldehydes to

give the (Z)-1,5-anti-alkenols 4 typically with >96:4 1,5-anti/1,5-

syn stereoselectivity possibly via the six-membered, chair-like,

transition structure 3. Slightly better stereoselectivity is observed

using tin(IV) bromide to effect the transmetallation, whereas

transmetallation using bismuth(III) iodide results in comple-

mentary stereocontrol in favour of the corresponding (E)-1,5-

anti-alkenols.²

These reactions have been used in synthesis³but it was rec-

ognised that it would be useful to carry them out without

employing organotin reagents that are toxic and which lead to the

formation of tributyltin containing side-products. Allylsilanes are

transmetallated by tin(IV) chloride but, in our hands, trans-

metallation of the pent-2-enylsilanes 5 [R¹¼Me, Ph, also (Z)-iso-

mers] was relatively slow taking 1e2 h at ꢀ78 ^ꢁC in comparison to

transmetallation of the pent-2-enylstannane 1 that was complete

in less than 5 min. This led to the formation of (Z)-alkenols with

aldehydes but with reduced overall 1,5-stereocontrol, 1,5-anti-4/

1,5-syn-6 ca. 75:25.⁴This loss of stereoselectivity was attributed

to a slow equilibration of the intermediate allyltin trichlorides.

Using the pentenylstannane 1, the high stereoselectivity of the

fast transmetallation is due to kinetic control, but under the

conditions required for the transmetallation of the allylsilanes,

the initially formed pent-1-en-3-yltin trichloride 2 has time to

equilibrate with its 3-epimer 7 so leading to less useful overall 1,5-

stereoselectivity.⁵

* Corresponding author. E-mail address: e.j.thomas@manchester.ac.uk (E.J.

Thomas).

http://dx.doi.org/10.1016/j.tet.2014.06.053

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E.J. Thomas, A.P. Weston / Tetrahedron 70 (2014) 7253e7267

products were obtained with increasing amounts of branched

products indicative of incomplete transmetallation.⁸To a certain

extent, this could be mitigated by using higher concentrations, with

useful yields and stereoselectivities being obtained in some cases

with transmetallation times as low as 7e8 min. However, a trans-

metallation time of 15 min proved reliable in terms of yield and

stereoselectivity and was adopted for the standard procedure.

The stereoselectivity obtained in the reaction between the (E,Z)-

pent-2-enylgermane 9 and benzaldehyde, 96:4, was similar to the

stereocontrol observed for the reaction of the pent-2-enylstannane

1 with benzaldehyde¹and so reactions of the germane (E,Z)-9 with

other aldehydes were investigated, see Table 2.

Allylgermanes are more reactive towards electrophilic attack

than allylsilanes, but less reactive than the corresponding

allylstannanes. It was therefore of interest to study trans-

metallation of allylgermanes with tin(IV) halides to see whether

useful levels of 1,5-stereocontrol in reactions with aldehydes

reminiscent of those obtained using allylstannanes could be

achieved.⁶

Table 2

Reactions of (ꢂ)-(E,Z)-pent-2-enylgermane 9 with aldehydes

Aldehyde (R)

Products^a

Yield^b(%)

1,5-syn/1,5-anti^c

Ph

4a, 6a

4b, 6b

4c, 6c

4d, 6d

4e, 6e

4f, 6f

4g, 6g

4h, 6h

4i, 6i

58 (77)

66 (78)

(67)

69

56

(34)

42

88

(86)

(67)

96:4

99:1

98:2

96:4

99:1

98:2

93:7

94:6

97:3

95:5

2. Results and discussion

(CH₃)₂CH

CH₃(CH₂)₂

BnOCH₂

4-ClC₆H₄

3-ClC₆H₄

4-MeOC₆H₄

4-NO₂C₆H₄

(E)-CH₃CH]CH

(E)-PhCH]CH

2.1. 1,5-Stereocontrol using pent-2-enylgermanes

The racemic pent-2-enyl chloride 8 was prepared from the

corresponding alcohol¹and coupled with triphenylgermanium

bromide under Barbier conditions⁷to give the pent-2-

enyl(triphenyl)germane 9 as a mixture of (E)- and (Z)-isomers.

Tin(IV) halide promoted reactions of this mixture of germanes with

benzaldehyde were carried out at ꢀ78 ^ꢁC to establish the inﬂuence

of the time allowed for transmetallation of the pentenylgermane on

the overall 1,5-stereoselectivity, see Scheme 1 and Table 1. It was

found that if the aldehyde was added to the reaction mixture

45 min after the tin(IV) chloride had been added to the germane,

the (Z)-hex-3-enols 4a and 6a were formed (80% isolated) in a ratio

of 82:18. However, if the transmetallation time was reduced to

15 min, the yield was more or less the same (77%), but the overall

4j, 6j

a

Products were identiﬁed by comparison with samples prepared earlier.¹

Using a 1.1 mol ratio of aldehyde/germane. For the reactions in parenthesis,

b

3 equiv of aldehyde were used. Transmetallation times were 15 min.

c

Estimated by integration of the doublets attributed to the methyl or benzyl

substituents in the ¹H NMR spectra of 4 or the corresponding 4-nitrobenzoates 10

and 11.

Products 4a,b,e and g, were known compounds.¹The other

products were identiﬁed by analogy, their (Z)-alkene geometry

being conﬁrmed by vinylic coupling constants of ca. 10 Hz in all

cases. Product ratios were estimated by ¹H NMR using the methyl

or benzyl peaks. For the products prepared from 2-methylpropanal,

butanal, 2-benzyloxyacetaldehyde, 4-chlorobenzaldehyde and 4-

nitrobenzaldehyde, the ¹H NMR spectra of the 4-nitrobenzoate

esters 10 obtained by direct esteriﬁcation were compared with

those prepared with inversion of conﬁguration using a Mitsunobu

procedure, see Scheme 2 (and Experimental section). The inverted

esters 11b and 11c were also saponiﬁed to prepare the 1,5-syn-al-

cohols 6b and 6c. This work conﬁrmed that the 1,5-anti- and 1,5-

syn-epimers could be distinguished by ¹H NMR and established

which of the minor peaks in the ¹H NMR spectra of the products

from the reactions of the pent-2-enylgermane 9 were due to the

1,5-syn-isomers 6.

Scheme 1. Preparation of (ꢂ)-(E,Z)-5-benzyloxy-4-methylpent-2-enyl(triphenyl)ger-

mane 9 and its reactions with benzaldehyde. Reagents and conditions: i, Ph₃GeBr, Mg,

THF, 30 min, heat to 45 ^ꢁC, 4 h [85%, (E)/(Z)¼55:45]; ii, SnCl₄, DCM, ꢀ78 ^ꢁC, then

PhCHO, ꢀ78 ^ꢁC, 45 min (77e83% see Table).

Table 1

Effect of transmetallation time on 1,5-stereoselectivity

Transmetallation time (min)

Yield^a(%)

4a/6a^b

45

30

15

80

83

77

82:18

88:12

94:6

a

A 3-fold excess of benzaldehyde was used. Yields are based on the allylgermane.

Both products are known. The ratios of the products were estimated by in-

b

tegration of the doublets due to the 4-Me peaks in ¹H NMR spectra.

stereoselectivity was signiﬁcantly better being 96:4 in favour of the

1,5-anti-epimer 4a. With a transmetallation time of 30 min, the 1,5-

stereoselectivity was 88:12. If the transmetallation time was re-

duced signiﬁcantly below 15 min, lower yields of the required

Scheme 2. Preparation of the 4-nitrobenzoates 10 and 11 and the 1,5-syn-alcohols 6.

Reagents and conditions: i, 4-nitrobenzoyl chloride, DMAP (cat.), Et₃N, THF, 0 ^ꢁC to rt

(10b, 59%; 10c, 44%; 10d, 66%; 10e, 67%; 10h, 85%); ii, DIAD, 4-nitrobenzoic acid, Ph₃P,

THF, 0 ^ꢁC, 7 h (11b, 54%; 11c, 57%; 11d, 68%; 11e, 62%; 11h, 79%), iii, NaOH, MeOH, rt, 2 h

(6b, 60%; 6c, 92%).

E.J. Thomas, A.P. Weston / Tetrahedron 70 (2014) 7253e7267

7255

In all cases useful stereoselectivities in favour of the (Z)-1,5-anti-

products 4 were obtained. The yields were generally good but were

not optimised and so the modest yields obtained for 3-chloro- and

4-methoxy-benzaldehydes may not be deﬁnitive.

During the studies of reactions of the pent-2-enylstannane 1, the

inﬂuence of the geometry of the stannane on the overall stereo-

selectivity of reactions with aldehydes was not investigated, most

results being obtained using mixtures of (E)- and (Z)-stannanes in

which the (E)-isomer was the major component, typically 70:30.

However, in the present work, since the pent-2-enylgermanes

could be prepared as single geometrical isomers, it was decided

to investigate the inﬂuence of pent-2-enylgermane geometry on

the overall stereoselectivity.

Allylic acetates are known to react with lithium bis(-

triethylgermyl)cuprate to give the corresponding allylgermanes.¹⁰

Thus the (E)- and (Z)-pent-2-enyl acetates (E)-12 and (Z)-12 were

prepared from the corresponding alcohols.^1,11,12Initial studies were

directed towards the preparation of the (E)- and (Z)-pent-2-

enyl(triphenyl)germanes using lithium bis(triphenylgermyl)cup-

rate following the literature procedure for triethylgermanes. The

required products (E)- and (Z)-9 were obtained but only in modest

yields. However, with the bis(triethylgermyl)cuprate, although the

(E)-pent-2-enyl(triethyl)germane (E)-13 was obtained again in only

a modest yield, an excellent yield (96%) of the (Z)-pent-2-

enyl(triethyl)germane (Z)-13 was achieved, see Scheme 3.

The reactions of the (E)- and (Z)-pent-2-enylgermanes (E)-9, (E)-

13, (Z)-9 and (Z)-13 with benzaldehyde were investigated under the

usual conditions, i.e., with 15 min for the transmetallation using

tin(IV) chloride, see Table 3. Although only qualitative data were

obtained, it did appear that the reactions using the (Z)-pent-2-

enylgermanes were more stereoselective in favour of the (Z)-1,5-

anti-product 4a, compare 90:10 and 88:12 for the (E)-germanes,

with 98:2 for both (Z)-isomers.

Tin(IV) chloride promoted reactions of the (Z)-pent-2-

enyl(triethyl)germane (Z)-13 with several aldehydes were then

investigated and the results are summarised in Table 3. In all cases

excellent stereoselectivities in favour of the (Z)-1,5-anti-alkenols 4

were obtained. Indeed, these results compare favourably to those

obtained using the pent-2-enylstannane 1.

During studies of remote stereocontrol using allylstannanes,

improved stereoselectivities were observed using tin(IV) bromide

rather than tin(IV) chloride for the transmetallation and so pro-

motion of the reaction of the pent-2-enylgermanes 9 and 13 with

benzaldehyde using tin(IV) bromide was brieﬂy investigated.

Somewhat surprisingly, it was found that unchanged pent-2-

enyl(triphenyl)germane was isolated during attempts to promote

the reactions of either the (E)- or (Z)-pent-2-enyl(triphenyl)ger-

manes (E)-9 and (Z)-9 with benzaldehyde under the usual condi-

tions (ꢀ78 ^ꢁC, 15 min transmetallation, 45 min for the reaction with

the aldehyde). However the reaction using the (Z)-pent-2-

enyl(triethyl)germane (Z)-13 was successful and gave the (Z)-1,5-

anti-product 4a in a reasonable yield (67%) and with excellent

stereoselectivity (99:1).

Tin(IV) chloride promoted reactions of 4-benzyloxypent-2-

enylstannanes with aldehydes also proceed with excellent 1,5-

stereocontrol,¹³and so it was of interest to investigate the analo-

gous reactions of the corresponding triethylgermane 15. The (E)-

isomer of this germane (E)-15 was prepared from the correspond-

ing acetate 14¹⁴using lithium bis(triethylgermyl)cuprate.

15 min were allowed for transmetallation with tin(IV) chloride at

ꢀ78 ^ꢁC before the addition of the aldehyde but only low to modest

yields of the known¹³(Z)-1,5-syn-alkenols 16 were obtained, see

Scheme 2. With benzaldehyde, the reaction proceeded with 89:11

stereoselectivity in favour of the (Z)-1,5-syn-product 16a (40%).

However, with 4-nitrobenzaldehyde and butanal, only 34% and 11%

yields of the products 16b and 16c were obtained. Using tin(IV)

bromide, only 26% of the (Z)-alkenol 16a, 90:10 stereoselectivity,

was obtained. The low yields in these reactions of the germane 15

were attributed to a competing 1,4-elimination process. In some

cases, benzyl alcohol was detected in the product mixtures sup-

porting this hypothesis (Scheme 4).

Scheme 3. Preparation of the (E)- and (Z)-pent-2-enylgermanes 9 and 13. Reagents

t

and conditions: i, R₃GeH, TMEDA, THF, BuLi, pentane, 30 min, 0 ^ꢁC, CuI, 10 min, 0 ^ꢁC,

ꢀ23 ^ꢁC, add (E)- or (Z)-12, 30 min [(E)-9, 17%; (E)-13, 29%; (Z)-9, 52%; (Z)-13, 96%).

Table 3

Reactions of the (E)- and (Z)-pent-2-enylgermane with aldehydes

Aldehyde (R)

Ph

Germane

Products^a

Yield^b(%)

1,5-syn/1,5-anti^c

(E)-9

(E)-13

(Z)-9

4a, 6a

86

63

73

98

57

74

57

84

81

85

90:10

88:12

98:2

99:1

97:3

99:1

96:4

99:1

(Z)-13

(CH₃)₂CH

CH₃(CH₂)₂

BnOCH₂

4-ClC₆H₄

4-MeOC₆H₄

4-NO₂C₆H₄

4b, 6b

4c, 6c

4d, 6d

4e, 6e

4g, 6g

4h, 6h

a

The products were identiﬁed by comparison with samples prepared earlier.¹

Using 3 mol equiv of aldehyde relative to germane apart from the reactions of 4-

b

methoxybenzaldehyde and benzyloxyacetaldehyde when 1.1 equiv of aldehyde

were used. The transmetallation time was 15 min except for the reaction of the

germane (E)-9, when only 7 min was allowed.

Scheme 4. Reactions of the 4-benzyloxypent-2-enylgermane 15. Reagents and con-

ditions: i, Et₃GeH, TMEDA, THF, ^tBuLi, pentane, 30 min, 0 ^ꢁC, CuI, 10 min, 0 ^ꢁC, ꢀ23 ^ꢁC,

add (E)-14, 30 min (83%); ii, SnCl₄, DCM, ꢀ78 ^ꢁC, 15 min, then RCHO, ꢀ78 ^ꢁC, 45 min

(16a, 40%, 89:11; 16b, 34%; 16c, 11%).

c

Estimated by integration of the doublets attributed to the methyl or benzyl

substituents in ¹H NMR spectra of 4 or the corresponding 4-nitrobenzoates 10

and 11.

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E.J. Thomas, A.P. Weston / Tetrahedron 70 (2014) 7253e7267

2.2. 1,6-Stereocontrol using hex-2-enylgermanes

(Z)-28. These were desilylated to give the corresponding 5-

hydroxyhex-2-enylgermanes (E)- and (Z)-23, (E)-and (Z)-25 and

(Z)-29. The 5-hydroxyhex-2-enyl(triethyl)germanes were also

methylated to give the methyl ethers (E)- and (Z)-26, see Scheme 5.

Attempts to promote reactions between the 5-hydroxyhex-2-

enyl(triphenyl)- and -(triethyl)gemanes (E)-23, (Z)-23 and (Z)-25,

and the (Z)-5-methoxyhex-2-enyl(triethyl)germane (Z)-26, with

benzaldehyde using tin(IV) chloride, were not successful in that

mixtures of products were formed that included signiﬁcant

amounts of products 30 and 31 formed by reaction of the hex-2-

enylgermane at the 3-position.^2,8These products may have been

formed by the tin(IV) chloride promoting the reaction with the hex-

2-enylgermanes by co-ordination to the aldehyde rather than by

transmetallation, but this would require the transmetallation not to

have taken place during the 15 min prior to the addition of the

aldehyde. Alternatively perhaps the initially formed hex-1-en-3-

yltin trichlorides undergo 1,3-migration of the trichlorotin moiety

leading to the hex-3-en-1-yltin trichlorides that would be expected

to give the branched products 30 and 31 on reaction with

aldehydes.

1,6-Stereocontrol in favour of (Z)-1,6-syn-alkenols has been

observed in reactions of 5-substituted hex-2-enyl(tributyl)stan-

nanes with aldehydes but useful results required transmetallation

of the 5-hydroxy- and 5-methoxyhex-2-enylstannanes 17 and 18

using tin(IV) bromide rather than tin(IV) chloride.¹More bulky O-

substituents resulted in lower 1,6-stereocontrol. It was therefore

decided to see whether useful 1,6-stereocontrol could be achieved

using hex-2-enylgermanes.

Although slightly enhanced 1,5-anti-stereoselectivities had been

obtained using (Z)-pent-2-enylgermanes, with transmetallation

using tin(IV) bromide limited to triethylgermanes, it was decided to

check the use of both (E)- and (Z)-hex-2-enylgermanes, trans-

metallation using both tin(IV) chloride and bromide and the use of

triphenyl- and trialkyl-germanes, for 1,6-stereocontrol.

The required (E)- and (Z)-hex-2-enylgermanes were prepared

from the corresponding (E)- and (Z)-5-tert-butyldimethylsilylox-

yhex-2-en-1-yl acetates (E)-¹⁵and (Z)-21, the latter being prepared

by acetylation of the hex-2-en-1-ol (Z)-27,¹⁶see Scheme 5. Dis-

placement of the acetoxy substituents using the corresponding bis-

(triaryl- or -trialkyl-germyl)cuprate gave the 5-tert-butyldime-

thylsilyloxyhex-2-enylgermanes (E)- and (Z)-22, (E)-and (Z)-24 and

As before, transmetallation of the hex-2-enyl(triphenyl)ger-

manes using tin(IV) bromide was unsuccessful, the germanes being

recovered from the reaction mixtures. In contrast, when the re-

actions of the 5-hydroxy- and 5-methoxy-hex-2-enyl(triethyl)- and

-(tributyl)germanes with aldehydes were promoted using tin(IV)

bromide, good yields of products were obtained with useful levels

of stereocontrol, see Tables 4 and 5. Products were identiﬁed from

these reactions by comparison with samples prepared earlier,¹with

the structures of new compounds being assigned by analogy, see

Experimental section. The product ratios were estimated by ¹H

NMR using the doublets assigned to the terminal methyl groups

and/or ¹³C NMR (see Experimental section).

Table 4

Reactions of 5-hydroxyhex-2-enylgermanes with aldehydes

Aldehyde (R)

Germane

Products^a

Yield^b(%)

1,6-syn/1,6-anti^c

Ph

(CH₃)₂CH

Ph

(E)-25

(Z)-25

19a, 32a

19b, 32b

19a, 32a

19b, 32b

19c, 32c

19d, 32d

19e, 32e

19f, 32f

19g, 32g

19h, 32 h

19a, 32a

19c, 32c

19d, 32d

63

51

80

82

75

81

83

81

73

81

78

68

73

89:11

91:9

94:6

93:7

92:8

93:7

91:9

92:8

91:9

92:8

90:10

91:9

(CH₃)₂CH

CH₃(CH₂)₂

4-ClC₆H₄

3-ClC₆H₄

4-NO₂C₆H₄

(E)-CH₃CH]CH

(E)-PhCH]CH

Ph

(Z)-29

Scheme 5. Synthesis of 5-substituted hex-2-enylgermanes for studies of 1,6-

CH₃(CH₂)₂

4-ClC₆H₄

stereocontrol. Reagents and conditions: i, Ac₂O, py, rt, 16

h (97%); ii, Ph₃GeH,

TMEDA, THF, ^tBuLi, pentane, 30 min, 0 ^ꢁC, CuI, 10 min, 0 ^ꢁC, ꢀ23 ^ꢁC, add (E)- or (Z)-21,

30 min [(E)-22, 69%; (Z)-22, 44%]; iii, TBAF, THF, rt, 16 h [(E)-23, 93%; (E)-25, 97%); (Z)-

23, 48%; (Z)-25, 95%; (Z)-29, 78% from (Z)-21]; iv, Et₃GeH, TMEDA, THF, ^tBuLi, pentane,

30 min, 0 ^ꢁC, CuI, 10 min, 0 ^ꢁC, ꢀ23 ^ꢁC, add (E)- or (Z)-21, 30 min [(E)-24, 92%; (Z)-24,

93%]; v, NaH, MeI, rt [(E)-26, 84%; (Z)-26, 73%]; vi, Bu₃GeH, TMEDA, THF, ^tBuLi, pentane,

30 min, 0 ^ꢁC, CuI, 10 min, 0 ^ꢁC, ꢀ23 ^ꢁC, add (Z)-21, 30 min.

a

The products were identiﬁed by comparison with samples prepared earlier.¹

Using 3 mol equiv of aldehyde relative to germane. The transmetallation time

b

was 15 min.

c

Estimated by ¹H NMR, integration of the doublets attributed to the CHCH₃or by

¹³C NMR.

E.J. Thomas, A.P. Weston / Tetrahedron 70 (2014) 7253e7267

7257

for the formation of the tetrahydropyran from the hept-2-

enylgermane 42. This would appear to have competed with the

expected transmetallation.

Table 5

Reactions of 5-methoxyhex-2-enylgermanes with aldehydes

Aldehyde (R)

Germane

Products^a

Yield^b(%)

1,6-syn/1,6-anti^c

Ph

(E)-26

(Z)-26

20a, 33a

20b, 33b

20d, 33d

83

94

86

61

86:14

94:6

95:5

CH₃(CH₂)₂

4-ClC₆H₄

90:10

a

The products were identiﬁed by comparison with samples prepared earlier.¹

Using 3 mol equiv of aldehyde relative to germane. The transmetallation time

b

was 15 min.

c

Estimated by ¹H NMR, integration of the doublets attributed to the CHCH₃or by

¹³C NMR.

There would appear to be a slight improvement in 1,6-

stereoselectivity if (Z)- rather than (E)-hex-2-enyl(triethyl)ger-

manes were used. This was true for both the 5-methoxy- and 5-

hydroxy-hexenylgermanes. The 1,6-stereoselectivities in favour of

the (Z)-1,6-syn-products were 90:10 or better for both the (Z)-5-

methoxy- and (Z)-5-hydroxyhex-2-enylgermanes with a range of

aromatic and aliphatic aldehydes. These results, if anything, were

better than those that had been obtained with the hex-2-

enylstannanes 17 and 18. Little difference was observed between

the tin(IV) bromide promoted reactions of the triethyl- or tribu-

tylgermanes (Z)-25 and (Z)-29.

Scheme 6. Preparation and reaction with benzaldehyde of the 6-hydroxyhept-2-

enylgermane 42. Reagents and conditions: i, DMSO, DCM, (COCl)₂, ꢀ78 ^ꢁC, 5 min,

add 36, 15 min, ꢀ78 ^ꢁC, Et₃N (93%); ii, MeO₂CCH₂P(O)(OCH₂CF₃)₂, 18-c-6, THF, KHMDS,

5 min, ꢀ78 ^ꢁC, add 37, ꢀ60 to ꢀ78 ^ꢁC, 30 min [70%; (Z)/(E)¼20:1]; iii, DIBAL-H, hex-

anes, ꢀ78 ^ꢁC, 45 min, ꢀ40 ^ꢁC, 1 h (96%); iv, Ac₂O, py, rt, 16 h (89%); v, (a) Et₃GeH,

TMEDA, THF, ^tBuLi, pentane, 30 min, 0 ^ꢁC, CuI, 10 min, 0 ^ꢁC, ꢀ23 ^ꢁC, add 40, 30 min; (b)

TBAF, THF, rt, 16 h (73% from 40); vi, SnBr₄, DCM, ꢀ78 ^ꢁC, 15 min, then PhCHO, ꢀ78 ^ꢁC,

45 min (55%).

2.3. Attempted 1,7-stereocontrol using hept-2-enylgermanes

3. Summary and conclusions

Transmetallation of allylstannanes using tin(IV) bromide has

also been used to provide 1,7-stereocontrol in reactions with al-

dehydes.¹For example, the tin(IV) bromide promoted reaction of

the 6-hydroxyhept-2-enyl(tributyl)stannane 34 with benzaldehyde

proceeded with useful levels of stereoselectivity to give mainly the

(Z)-1,7-syn-oct-3-ene-1,7-diol 35. It was therefore of interest to see

whether analogous 1,7-stereocontrol could be achieved using hept-

2-enylgermanes.

This work has shown that effective 1,5- and 1,6-open-chain

stereocontrol can be achieved in reactions of allylgermanes with

aldehydes promoted by tin(IV) halides. Indeed the yields and

stereoselectivities in many cases are better than those that had

been obtained using the corresponding allylstannanes.¹

With the allylgermanes, slightly better stereoselectivities were

observed for the (Z)-alkenylgermanes than for the (E)-isomers.

This is consistent with the transmetallation processes discussed

previously.⁵Transmetallation of the allylgermanes by tin(IV) ha-

lides would appear to be a ﬁnely balanced process. It is of interest

that transmetallation using tin(IV) bromide was only successful for

the alk-2-enyl(trialkyl)germanes and was not observed for the

corresponding alk-2-enyl(triaryl)germanes. The formation of the

branched products 30 and 31 from the tin(IV) chloride promoted

reactions of the 5-hydroxy- and 5-methoxy-hex-2-enylgermanes

is consistent with either the transmetallation not having oc-

curred before the benzaldehyde was added²⁰or a competing 1,3-

isomerisation of the intermediate hex-1-en-3-yltin trichloride.

Similarly the formation of the tetrahydropyran 43 during the

tin(IV) bromide promoted reaction of the 6-hydroxyhept-2-

enylgermane 42 with benzaldehyde is consistent with no re-

action taking place until the aldehyde is added²⁰or a 1,3-

isomerisation of the intermediate hept-1-en-3-yltin tribromide.

Just why these reactions are so dependent on the structure of the

allylgermane is not clear. It may be that the rate of trans-

metallation and/or the stability of the co-ordinated intermediate

tin trihalide is affected by the separation of the co-ordination site

from the allylgermane moiety.

(S,Z)-6-Hydroxyhept-2-enyl(triethyl)germane 42 was prepared

from (S)-4-tert-butyldimethylsilyloxypentan-1-ol 36,¹⁷see Scheme

6. Aldehyde 37¹⁸was prepared by oxidation of the alcohol and was

condensed with bis(triﬂuoroethyl) (methoxycarbonylmethyl)

phosphonate giving the (Z)-unsaturated ester 38, (Z)/(E)¼20:1.

Reduction using DIBAL-H and acetylation of the resulting alcohol

39 gave the hept-2-en-1-yl acetate 40. This was taken through to

the (Z)-hept-2-enyl(triethyl)germane 41 using the bis(-

triethylgermyl)cuprate and desilylation gave the (Z)-6-

hydroxyhept-2-enyl(triethyl)germane 42. However, the reaction

of this allylic germane with benzaldehyde when promoted by

tin(IV) bromide under the standard conditions gave the tetrahy-

dropyran 43 (55%) as the major product, see Scheme 6. The

structure of this tetrahydropyran was established by spectroscopic

methods with ¹H NMR, in particular NOEs, being used to conﬁrm

the conﬁguration as shown. Tetrahydropyran 43 is a known com-

pound having been prepared from the trimethylsilyl analogue of

germane 42 via a Prins reaction.¹⁹A similar process would account

Notwithstanding this complication, the tin(IV) halide promoted

reactions of 5-substituted pent-2-enyl- and hex-2-enyl-germanes

with aldehydes were clean and reliable. They provide an organic-

tin free process for useful 1,5- and 1,6-stereocontrol.

7258

E.J. Thomas, A.P. Weston / Tetrahedron 70 (2014) 7253e7267

4. Experimental

at rt, the ﬂask was removed from the bath and heated to 45 ^ꢁC for

4 h. Saturated aqueous ammonium chloride (60 mL) was added

and the aqueous layer washed with ether (3ꢃ30 mL). The organic

extracts were washed with water (30 mL) and brine (30 mL), dried

(MgSO₄) and concentrated under reduced pressure. Chromatog-

raphy using light petroleum/ether (25:1) as eluent gave the title

compound 9 (2.76 g, 85%), a 55:45 mixture of (E)-and (Z)-isomers

as a colourless oil, R_f0.58 in 10:1 light petroleum/ether; n_max/cm^ꢀ1

3066, 2852, 2362, 1484, 1453, 1430, 1091 and 733; d_H(CDCl₃,

300 MHz) 0.82 (1.35H, d, J 6.5, 4-CH₃), 0.94 (1.65H, d, J 6.5, 4-CH₃),

2.37e2.61 (2.45H, m, 1-H₂and 4-H), 2.75 (0.55H, m, 4-H),

3.08e3.13 (0.9H, m, 5-H₂), 3.14 and 3.24 (each 0.55H, dd, J 7.0, 8.0,

5-H), 4.43 and 4.46 (each 0.55H, d, J 12.0, PhHCH), 4.48 and 4.50

(each 0.45H, d, J 12.0, PhHCH), 5.14 (0.45H, dd, J 10.5, 9.5, 3-H),

5.33 (0.55H, dd, J 15.5, 7.5, 3-H), 5.64 (1H, m, 2-H), 7.29e7.45 (15H,

m, ArH) and 7.50e7.56 (5H, m, ArH); d_C(CDCl₃, 75 MHz) 15.8, 17.6,

17.7, 19.9, 32.4, 37.3, 73.1(2), 75.3, 75.8, 125.4, 125.7, 127.7, 127.8(2),

128.4(2) 128.6, 129.2, 129.3, 131.9, 133.2, 135.3(2), 136.9, 137.0 and

139.1; m/z (ESI) 517 (M^þþ23, 100%), 515 (M^þþ23, 80), 513

(M^þþ23, 60), 338 (30) and 242 (65); HRMS: M^þþNa, found

517.1560. C₃₁H₃₂⁷⁴GeNaO requires 517.1557.

4.1. General experimental procedures

¹H and ¹³C NMR spectra were recorded on Varian Unity 500,

Varian Unity Inova 400 and Varian Unity Inova 300 spectrometers

with residual non-deuterated solvent as the internal standard.

Coupling constants are rounded to the nearest 0.5 Hz. IR spectra

were recorded on an ATI Mattson Genesis FTIR as thin ﬁlms pro-

duced by evaporation of a DCM solution on sodium chloride plates

unless otherwise stated. Mass spectra were recorded on Fison VG

Trio 2000 and Kratos Concept spectrometers. Chemical ionisation

(CI) was performed using ammonia. Characteristic clumps of peaks

were observed for the alkenylgermanes due to the germanium

isotopes, ⁷⁴Ge, ⁷²Ge and ⁷⁰Ge. Accurate mass measurements were

taken for the major peaks corresponding to ⁷⁴Ge. Chromatography

refers to ﬂash column chromatography using Merck silica gel 60H

(230e300 mesh). Tetrahydrofuran (THF) was dried and distilled

from sodium metal using benzophenone as an indicator under an

atmosphere of nitrogen. Dichloromethane (DCM) was dried and

distilled from calcium hydride under an atmosphere of nitrogen.

Ether refers to diethyl ether, which was dried and distilled from

sodium metal using benzophenone as an indicator under an at-

mosphere of nitrogen. Light petroleum refers to the fraction of

petroleum ether distilled between 40 and 60 ^ꢁC. Benzene and

hexane were dried over sodium metal. Butyllithium (1.6 M in

hexanes) was titrated against a solution of propan-2-ol in xylene

with 2,2⁰-bipyridine as an indicator. Triethylamine and diisopro-

pylamine were dried over potassium hydroxide pellets. Brine refers

to saturated aqueous sodium chloride.

4.2.3. Syntheses of pent-2-enylgermanes 9 and 13 from acetates (E)-

and (Z)-12

4.2.3.1. (2E)-5-Benzyloxy-4-methylpent-2-enyl(triphenyl)ger-

mane (E)-(9); standard procedure. To triphenylgermanium hydride

(305 mg, 1.08 mmol) and TMEDA (170

mL, 1.19 mmol) in THF

(2 mL) at 0 ^ꢁC was added ^tBuLi (1.7 M in pentane, 0.70 mL,

1.19 mmol). After 30 min, copper(I) iodide (95 mg, oven dried,

0.54 mmol) was added. After a further 10 min, the solution was

cooled to ꢀ23 ^ꢁC and the acetate (E)-12 (124 mg, 0.50 mmol)

added in THF (1 mL). After 30 min at ꢀ23 ^ꢁC, an aqueous phos-

phate buffer (pH 7, 5 mL) and aqueous ammonium chloride (4%,

10 mL) were added. The mixture was extracted with ether

(3ꢃ15 mL) and the organic extracts washed with aqueous am-

monium chloride (4%, 2 15 mL), water (15 mL) and brine (15 mL).

After drying (Na₂SO₄) and concentration under reduced pressure,

chromatography using light petroleum/ether (30:1) gave the title

compound (E)-9 (43 mg, 17%) as a colourless oil, R_f0.40 in 9:1 light

petroleum/ether; n_max/cm^ꢀ13067, 3048, 2937, 2857, 1484, 1453,

1430, 1092, 1027 and 734; d_H(CDCl₃, 300 MHz) 0.96 (3H, d, J 6.5,

4-CH₃), 2.45 (1H, m, 4-H), 2.48 (2H, d, J 8.0, 1-H₂), 3.16 (1H, dd, J

9.0, 7.0, 5-H), 3.26 (1H, dd, J 9.0, 6.5, 5-H⁰), 4.48 and 4.50 (each 1H,

d, J 12.0, PhHCH), 5.34 (1H, dd, J 15.0, 7.5, 3-H), 5.64 (1H, dt, J 15.0,

7.5, 2-H), and 7.29e7.58 (20H, m, ArH); d_C(CDCl₃, 75 MHz) 17.6,

19.9, 37.3, 73.1, 75.8, 125.7, 127.7, 127.8, 128.4, 128.6, 129.2, 133.2,

135.3, 137.0 and 139.0; m/z (CI) 512 (M^þþ18, 28%), 510 (M^þþ18,

20), 508 (M^þþ18, 18), 322 (100), 320 (75), 318 (60) and 208 (37);

HRMS: M^þþNH₄, found 512.2002. C₃₁H₃₆⁷⁴GeNaO requires

512.2003.

Many of the products were known having been prepared using

alkenylstannanes.¹The structures of new compounds were

assigned by analogy. The ratios of the products were estimated by

¹H and ¹³C NMR. For the products prepared using aromatic alde-

hydes, the methyl doublets or the benzylic hydrogen peaks were

most useful in this respect. It was more difﬁcult to estimate accu-

rately the ratios of products prepared using aliphatic aldehydes,

and so, for example, the major products 4b,c were converted into

the minor products 6b,c for direct comparison.¹

4.2. Experimental procedures

4.2.1. (2E,4RS)-5-Benzyloxy-1-chloro-4-methylpent-2-ene

(8). Triphenylphosphine (2.1 g, 8.24 mmol) was added to racemic

(E)-5-benzyloxy-4-methylpent-2-en-1-ol¹(1.0 g, 4.85 mmol) in

carbon tetrachloride (10 mL) and the mixture was stirred at rt for

42 h. Ether (150 mL) was added and the organic extracts were

washed with water (30 mL) and brine (30 mL), dried (MgSO₄) and

concentrated under reduced pressure. Chromatography using 5%

ether in light petroleum as eluent gave the title compound 8 (0.8 g,

74%) as a colourless oil, R_f0.42 in 9:1 light petroleum/ether; n_max

/

cm^ꢀ13064, 2960, 2857, 1453, 1360,1250, 1098, 969, 737 and 698; d_H

(CDCl₃, 300 MHz) 1.11 (3H, d, J 7.0, 4-CH₃), 2.59 (1H, hept, J 6.5, 4-H),

3.39 and 3.41 (each 1H, dd, J 14.0, 9.0, 1-H), 4.10 (2H, d, J 6.5, 5-H₂),

4.56 (2H, s, PhCH₂), 5.71 (1H, dt, J 15.5, 6.5, 2-H), 5.82 (1H, dd, J 15.5,

6.5, 3-H) and 7.30e7.45 (5H, m, ArH); d_C(CDCl₃, 75 MHz) 16.9, 36.8,

45.7, 73.3, 75.0, 126.0, 127.8, 127.9, 128.7, 138.5 and 138.7; m/e (CI)

244 (M^þþ18, 35%) and 242 (M^þþ18, 100); HRMS: M^þ, found

224.0966. C₁₃H₁₇³⁵ClO requires 224.0962.

4.2.3.2. (2Z)-5-Benzyloxy-4-methylpent-2-enyl(triphenyl)ger-

mane (Z)-(9). Triphenylgermanium hydride (0.87 g, 2.82 mmol)

and the acetate (Z)-12 (350 mg, 1.41 mmol) after chromatography

using light petroleum/ether (30:1) as eluent gave the title com-

pound (Z)-9 (363 mg, 52%) as a colourless oil, R_f0.41 in 9:1 light

petroleum/ether; n_max/cm^ꢀ13067, 3048, 3006, 2957, 2925, 2853,

1484, 1430, 1092 and 734; d_3H(CDCl₃, 300 MHz) 0.84 (3H, d, J 6.5,

4-CH₃), 2.40e2.65 (2H, m, 1-H₂), 2.76 (1H, m, 4-H), 3.13 (2H, d, J 7.0,

5-H₂), 4.43 and 4.50 (each 1H, d, J 12.5, PhHCH), 5.16 (1H, t, J 10.0,

3-H), 5.66 (1H, dt, J 10.0, 9.0, 2-H), 7.28e7.63 (20H, m, ArH); d_C

(CDCl₃, 75 MHz) 15.9, 17.8, 32.4, 73.1, 75.3, 125.5, 127.8, 128.5, 128.6,

129.3, 131.9, 134.7, 135.3, 135.8 and 136.9; m/z (CI) 512 (M^þþ18,

25%), 510 (M^þþ18, 15), 508 (M^þþ18, 14), 322 (100), 320 (75), 318

(50) and 208 (40); HRMS: M^þþNH₄, 512.1995. C₃₁H₃₆⁷⁴GeNaO re-

quires 512.2003.

4.2.2. (2E,Z,4RS)-5-Benzyloxy-4-methylpent-2-enyl(triphenyl)ger-

mane (E,Z)-(9). A mixture of magnesium turnings (0.38 g, oven

dried, 15.6 mmol), iodine (1 crystal) and triphenylgermanium

bromide (2.52 g, 6.57 mmol) in THF (15 mL) was placed in an

ultrasonic bath. The chloride (E)-8 (2.67 g, 11.9 mmol) in THF

(15 mL) was added dropwise. After 30 min in the ultrasonic bath

E.J. Thomas, A.P. Weston / Tetrahedron 70 (2014) 7253e7267

7259

4.2.3.3. (2E)-5-Benzyloxy-4-methylpent-2-enyl(triethyl)germane

(E)-(13). The standard procedure but with addition of the solution

of triethylgermanium hydride (0.25 mL, 1.55 mmol), TMEDA

as eluent gave the title compound (Z)-12 (0.81 g, 95%) as a colourless

oil, R_f0.28 in 4:1 light petroleum/ether; n_max/cm^ꢀ13027, 2960, 2929,

2857,1739,1454,1372,1232,1099,1027 and738; d_H(CDCl₃, 300 MHz)

1.07 (3H, d, J 6.5, 4-CH₃), 2.10 (3H, s, CH₃CO), 2.91 (1H, m, 4-H),

3.30e3.42 (2H, m, 5-H₂), 4.56 (2H, s, PhCH₂), 4.66 (1H, dd, J 12.5, 6.0,

1-H), 4.74 (1H, dd, J 12.5, 7.0,1-H⁰), 5.54 (1H, dd, J 11.0, 9.5, 3-H), 5.63

(1H, dt, J 11.0, 6.5, 2-H) and 7.29e7.43 (5H, m, ArH); d_C(CDCl₃,

75 MHz) 17.9, 21.3, 33.1, 60.9, 73.2, 75.1,124.2,127.8,128.6,138.1,138.8

and 171.2; m/z (CI) 266 (M^þþ18, 100%) and 249 (M^þþ1, 5); HRMS:

M^þþNH₄, found 266.1748. C₁₅H₂₄NO₃requires 266.1751.

t

(0.26 mL, 1.70 mmol) in THF (2 mL) and BuLi (1.7 M in pentane,

1.09 mL, 1.85 mmol) to the suspension of copper(I) iodide (147 mg,

oven dried, 0.775 mmol) in THF (3 mL), followed by addition of the

acetate (E)-12 (192 mg, 0.78 mmol) in THF (2 mL), after chroma-

tography using light petroleum/ether (60:1), gave the title com-

pound (E)-13 (151 mg, 29%) as a colourless oil, R_f0.66 in 19:1 light

petroleum/ether; n_max/cm^ꢀ13414, 2963, 2916, 1719, 1655, 1364,

1260, 1018 and 799; d_H(CDCl₃, 300 MHz) 0.76 (6H, q, J 8.0, 3ꢃ

GeCH₂), 0.98e1.15 (12H, m, 3ꢃ GeCH₂CH₃and 4-CH₃), 1.65 (2H, d, J

8.0, 1-H₂), 2.49 (1H, m, 4-H), 3.28 (1H, dd, J 9.0, 7.5, 5-H), 3.39 (1H,

dd, J 9.0, 6.5, 5-H⁰), 4.56 (2H, s, PhCH₂), 5.25 (1H, dd, J 15.0, 7.0, 3-H),

5.55 (1H, dt, J 15.0, 7.0, 2-H) and 7.29e7.43 (5H, m, ArH); d_C(CDCl₃,

75 MHz) 4.1, 9.2, 17.3, 17.9, 37.3, 73.2, 76.2, 127.7, 127.8, 128.6, 130.5

and 139.0; m/z (EI) 350 (M^þ, 10%), 348 (M^þ, 9), 346 (M^þ, 7), 321

(100), 319 (95), 317 (70) and 267 (70); HRMS: M^þ, found 350.1659.

4.2.5. Tin(IV) halide promoted reactions of pent-2-enylgermanes 9

and 13 with aldehydes

4.2.5.1. (1RS,5SR,3Z)-6-Benzyloxy-5-methyl-1-phenylhex-3-en-1-

ol (4a); standard procedure. Tin(IV) chloride (1 M in DCM, 0.22 mL,

0.22 mmol) in DCM (0.5 mL) cooled to ꢀ78 ^ꢁC, was added to the

(E,Z)-pent-2-enyl(triphenyl)germane (E,Z)-9 (100 mg, 0.20 mmol)

in DCM (0.8 mL) at ꢀ78 ^ꢁC and the solution stirred at ꢀ78 ^ꢁC for

C

₁₉H₃₂⁷⁴GeO requires 350.1659.

15 min. Benzaldehyde (70 mL, 0.69 mmol) was added and the re-

action mixture was stirred at ꢀ78 ^ꢁC for 45 min. Saturated meth-

anolic ammonium chloride (1 mL) was added followed by water

(30 mL). The mixture was extracted using ether (3ꢃ20 mL) and the

organic extracts were washed with water (20 mL) and brine

(20 mL), then dried (MgSO₄) and concentrated under reduced

pressure. Chromatography of the residue using light petroleum/

ether (4:1) as eluent gave the title compound 4a¹(46 mg, 77%) as

4.2.3.4. (Z)-5-Benzyloxy-4-methylpent-2-enyl(triethyl)germane

(Z)-(13). The standard procedure with addition of the solution of

t

triethylgermanium hydride, TMEDA and BuLi to the copper(I) io-

dide, using triethylgermanium hydride (0.21 mL, 1.26 mmol) and

the acetate (Z)-12 (156 mg, 0.63 mmol), after chromatography us-

ing 2% ether in light petroleum as eluent gave the title compound

(Z)-13 (210 mg, 96%) as a colourless oil, R_f0.74 in 9:1 light petro-

leum/ether; n_max/cm^ꢀ12951, 2928, 2905, 2870, 1643, 1454, 1113,

1096, 1019 and 735; d_H(CDCl₃, 300 MHz) 0.80 (6H, q, J 8.0, 3ꢃ

GeCH₂), 1.02e1.13 (12H, m, 3ꢃ GeCH₂CH₃and 4-CH₃), 1.67 and 1.76

(each 1H, ddd, J 14.0, 8.5, 1.5,1-H), 2.84 (1H, m, 4-H), 3.28 (1H, dd, J

9.0, 8.0, 5-H), 3.40 (1H, dd, J 9.0, 5.5, 5-H⁰), 4.55 and 4.61 (each 1H, d,

J 14.5, PhHCH), 5.06 (1H, dd, J 10.5, 9.5, 3-H), 5.51 (1H, q, J 9.5, 2-H)

and 7.30e7.42 (5H, m, ArH); d_C(CDCl₃, 75 MHz) 4.2, 9.2, 13.3, 18.2,

32.2, 73.2, 75.6, 127.5, 127.7, 127.8, 128.6, 129.4 and 139.1; m/z (CI)

368 (M^þþ18, 15%), 366 (M^þþ18, 13), 364 (M^þþ18, 10), 351 (M^þþ1,

5), 349 (M^þþ1, 4), 347 (M^þþ1, 3), 178 (100), 176 (70) and 174 (50):

HRMS: M^þþNH₄, 368.2005. C₁₉H₃₆⁷⁴GeNO requires 368.2003.

a colourless oil, 4a/6a¼96:4 (¹H NMR; 5-CH₃4a,

d 0.91, d; 6a, d 0.95,

d), R_f0.16 in 4:1 light petroleum/ether.

Tin(IV) chloride (1 M in DCM, 0.074 mL, 0.074 mmol) in DCM

(0.3 mL), the (E)-pent-2-enyl(triphenyl)germane (E)-9 (34 mg,

0.069 mmol) in DCM (0.5 mL) and benzaldehyde (27 mL, 0.26 mmol)

gave the title compound 4a (16 mg, 86%) as a colourless oil, 4a/

6a¼90:10.

Tin(IV) chloride (1 M in DCM, 0.37 mL, 0.37 mmol) in DCM

(0.5 mL), the (E)-pent-2-enyl(triethyl)germane (E)-13 (120 mg,

0.34 mmol) in DCM (1.0 mL) and benzaldehyde (118 mL, 1.02 mmol)

gave the title compound 4a (64 mg, 63%) as a colourless oil, 4a/

6a¼88:12.

Tin(IV) chloride (1 M in DCM, 0.18 mL, 0.18 mmol) inDCM (0.5mL),

the (Z)-pent-2-enyl(triphenyl)germane (Z)-9 (84 mg, 0.203 mmol) in

4.2.4. Synthesis of acetates (E)- and (Z)-12

4.2.4.1. (2E,4RS)-5-Benzyloxy-4-methylpent-2-en-1-yl

acetate

DCM (0.8 mL) and benzaldehyde (60 mL, 0.59 mmol) gave the title

(E)-(12); standard procedure. Acetic anhydride (0.57 mL, 6.0 mmol)

was added to (E)-5-benzyloxy-4-methylpent-2-en-1-ol^1,11(1.13 g,

5.5 mmol) in pyridine (1.3 mL, 16.5 mmol) and the solution stirred

at rt overnight. Ether (100 mL) was added and the organic extracts

were washed with water (40 mL), aqueous hydrogen chloride

(0.1 M, 40 mL) and saturated aqueous sodium bicarbonate (40 mL).

After drying (MgSO₄) and concentration under reduced pressure,

chromatography of the residue using light petroleum/ether (2:1)

as eluent, gave the title compound¹¹(E)-12 (1.30 g, 95%) as a col-

ourless oil, R_f0.61 in 1:1 light petroleum/ether; n_max/cm^ꢀ12961,

2858, 1739, 1453, 1364, 1235, 1097, 1027, 964 and 737; d_H(CDCl₃,

300 MHz) 1.09 (3H, d, J 7.0, 4-CH₃), 2.10 (3H, s, CH₃CO), 2.58 (1H,

m, 4-H), 3.38 (1H, dd, J 18.5 and 9.0, 5-H), 3.40 (1H, dd, J 18.5 and

9.0, 5-H⁰), 4.48e4.62 (4H, m, 1-H₂and PhCH₂), 5.66 (1H, dt, J 15.5

and 6.0, 2-H), 5.80 (1H, dd, J 14.5 and 6.5, 3-H) and 7.29e7.42 (5H,

m, ArH); d_C(CDCl₃, 75 MHz) 17.0, 21.3, 36.9, 65.5, 73.2, 75.1, 123.9,

127.8(2), 128.6, 138.8(2) and 171.1; m/z (CI) 266 (M^þþ18, 100%),

249 (M^þþ1, 10) and 189 (100); HRMS: M^þþH, 249.1489. C₁₅H₂₁O₃

requires 249.1485.

compound 4a (37 mg, 73%) as a colourless oil, 4a/6a¼98:2.

Tin(IV) chloride (1 M in DCM, 0.18 mL, 0.18 mmol) in DCM

(0.5 mL), the (Z)-pent-2-enyl(triethyl)germane (Z)-13 (84 mg,

0.203 mmol) in DCM (0.8 mL) and benzaldehyde (60 mL, 0.59 mmol)

gave the title compound 4a (58 mg, 98%) as a colourless oil, 4a/

6a¼98:2.

Tin(IV) bromide (84 mg, 0.12 mmol) in DCM (0.65 mL), the (Z)-

pent-2-enyl(triethyl)germane (Z)-13 (55 mg, 0.16 mmol) in DCM

(0.8 mL) and benzaldehyde (58

mL, 0.57 mmol) gave the title

compound 4a (32 mg, 67%) as a colourless oil, 4a/6a¼99:1.

4.2.5.2. (3RS,7SR,5Z)-8-Benzyloxy-2,7-dimethyloct-5-en-3-ol

(4b). Tin(IV) chloride (1 M in DCM, 0.22 mL, 0.22 mmol) in DCM

(0.5 mL), the (E,Z)-pent-2-enyl(triphenyl)germane (E,Z)-9 (100 mg,

0.203 mmol) in DCM (1.0 mL) and 2-methylpropanal (60

mL,

0.60 mmol), after chromatography using light petroleum/ether

(5:1) as eluent, gave the title compound 4b¹(41 mg, 78%) as a col-

ourless oil, 4b/6b¼99:1 (¹H NMR, PhCH₂), R_f0.26 in 4:1 light pe-

troleum/ether.

Tin(IV) chloride (1 M in DCM, 0.23 mL, 0.23 mmol) in DCM

(0.5 mL), (Z)-pent-2-enyl(triethyl)germane (Z)-13 (74 mg,

4.2.4.2. (2Z,4RS)-5-Benzyloxy-4-methylpent-2-en-1-yl

acetate

0.212 mmol) in DCM (1 mL) and 2-methylpropanal (58

mL,

(Z)-(12). Acetic anhydride (0.37 mL, 3.77 mmol), (Z)-5-benzyloxy-4-

methylpent-2-en-1-ol¹²(0.71 g; 3.43 mmol) and pyridine (0.84 mL,

10.2 mmol), after chromatography using light petroleum/ether (5:1)

0.60 mmol) gave the title compound 4b (32 mg, 57%) as a colourless

oil, 4b/6b¼99:1.

7260

E.J. Thomas, A.P. Weston / Tetrahedron 70 (2014) 7253e7267

4.2.5.3. (4RS,8RS,6Z)-9-Benzyloxy-8-methylnon-6-en-4-ol

(4c). Tin(IV) chloride (1 M in DCM, 0.22 mL, 0.22 mmol) in DCM

(0.5 mL), the (E,Z)-pent-2-enyl(triphenyl)germane (E,Z)-9 (100 mg,

137.5, 138.0 and 147.3; m/z (CI) 350 (M^þþ18, 10%), 348 (M^þþ18, 25),

332 (M^þ, 5), 330 (M^þ, 10), 102 (90) and 85 (100); HRMS: M^þþNH₄

found 348.1726. C₂₀H₂₇³⁵ClNO₂requires 348.1725.

0.203 mmol) in DCM (1.0 mL) and butanal (60 mL, 0.6 mmol), after

chromatography using light petroleum/ether (5:1) as eluent, gave

the title compound 4c^3c(36 mg, 67%) as a colourless oil, 4c/6c¼98:2

(¹H NMR, PhCH₂), R_f0.21 in 4:1 light petroleum/ether.

Tin(IV) chloride (1 M in DCM, 0.26 mL, 0.26 mmol) in DCM

(0.5 mL), the (Z)-pent-2-enyl(triethyl)germane (Z)-13 (75 mg,

0.215 mmol) in DCM (1.0 mL) and butanal (59 mL, 0.64 mmol) after

chromatography using light petroleum/ether (4:1) as eluent, gave

the title compound 4c (42 mg, 74%) as a colourless oil, 4c/6c¼99:1.

4.2.5.7. (1RS,5SR,3Z)-6-Benzyloxy-1-(4-methoxyphenyl)-5-

methylhex-3-en-1-ol (4g). Tin(IV) chloride (1 M in DCM, 0.44 mL,

0.44 mmol) in DCM (0.5 mL), the (E,Z)-pent-2-enyl(triphenyl)ger-

mane (E,Z)-9 (200 mg, 0.406 mmol) in DCM (2.0 mL) and 4-

methoxybenzaldehyde (54 mL, 0.45 mmol), after chromatography

using light petroleum/ether (2:1), gave the title compound 4g¹

(56 mg, 42%) as a colourless oil, 4g/6g¼93:7 (¹H NMR), R_f0.17 in

2:1 light petroleum/ether.

Tin(IV) chloride (1 M in DCM, 0.24 mL, 0.24 mmol) in DCM

(0.5 mL), the (Z)-pent-2-enyl(triethyl)germane (Z)-13 (70 mg,

0.20 mmol) in DCM (1.0 mL) and 4-methoxybenzaldehyde (27 mL,

2.2 mmol) after chromatography using light petroleum/ether (2:1)

as eluent gave the title compound 4g (53 mg, 81%) as a colourless

oil, 4g/6g¼96:4.

4.2.5.4. (2RS,6SR,4Z)-1,7-Bis(benzyloxy)-6-methylhept-4-en-2-ol

(4d). Tin(IV) chloride (1 M in DCM, 0.22 mL, 0.22 mmol) in DCM

(0.5 mL), the (E,Z)-pent-2-enyl(triphenyl)germane (E,Z)-9 (100 mg,

0.203 mmol) in DCM (1.5 mL) and 2-benzyloxyethanal (31 mL, 1.1

0.22 mmol), after chromatography using light petroleum/ether

(4:1) as eluent, gave the title compound 4d (48 mg, 69%) as a col-

ourless oil, 4d/6d¼96:4 (¹H NMR, 6-CH₃), R_f0.35 in 1:1 light pe-

troleum/ether.

4.2.5.8. (1RS,5SR,3Z)-6-Benzyloxy-5-methyl-1-(4-nitrophenyl)

hex-3-en-1-ol (4h). Tin(IV) chloride (1

M in DCM, 0.18 mL,

Tin(IV) chloride (1 M in DCM, 0.20 mL, 0.2 mmol) in DCM (0.5 mL),

the (Z)-pent-2-enyl(triethyl)germane (Z)-13 (65 mg, 0.186 mmol) in

0.18 mmol) in DCM (0.5 mL), the (E,Z)-pent-2-enyl(triphenyl)ger-

mane (E,Z)-9 (80 mg, 0.162 mmol) in DCM (1.3 mL) and 4-

nitrobenzaldehyde (74 mg, 0.49 mmol) in DCM (0.3 mL), after

chromatography using light petroleum/ether (3:1), gave the title

compound 4h (49 mg, 88%) as a colourless oil 4h/6h¼94:6, R_f0.18 in

2:1 light petroleum/ether.

DCM (1.0 mL) and 2-benzyloxyethanal (29

mL, 0.2 mmol), after

chromatography using light petroleum/ether (3:1) as eluent, gave

the title compound 4d (36 mg, 57%) as a colourless oil, 4d/6d¼97:3;

n_max/cm^ꢀ13426, 2954, 2925, 2859,1453,1094,1075,1028 and 735; d_H

(CDCl₃, 300 MHz) 0.98 (3H, d, J 6.5, 6-CH₃), 2.20e2.45 (2H, m, 3-H₂),

2.90(1H, m, 6-H), 3.18 (1H, s, OH), 3.26 (1H, t, J 8.5, 7-H), 3.36 (1H, dd, J

8.5, 6.0, 7-H⁰), 3.51 (2H, m, 1-H₂), 3.87 (1H, m, 2-H), 4.56 and 4.61

(each2H, s, PhCH₂), 5.37 (1H, t, J 11.0, 6-H), 5.53(1H, td, J 11.0, 7.0, 5-H)

and 7.30e7.50 (10H, m, ArH); d_C(CDCl₃, 75 MHz) 17.6, 32.5, 32.6, 70.3,

73.2, 73.7, 74.5, 75.0, 126.0, 127.9, 128.0, 128.6, 128.7, 128.8, 134.4,

136.3 and 138.5; m/z (CI) 358 (M^þþ18, 100%) and 341 (M^þþ1, 30);

HRMS: M^þþH, found 341.2123. C₂₂H₂₉O₃requires 341.2111.

Tin(IV) chloride (1 M in DCM, 0.22 mL, 0.22 mmol) in DCM

(0.5 mL), the (Z)-pent-2-enyl(triethyl)germane (Z)-13 (70 mg,

0.20 mmol) in DCM (1.0 mL) and 4-nitrobenzaldehyde (65 mg,

0.60 mmol) in DCM (0.3 mL), after chromatography using light

petroleum/ether (3:1), gave the title compound 4h (58 mg, 85%) as

a colourless oil, 4h/6h¼99:1 (¹H NMR); n_max/cm^ꢀ13424, 2925,

2858, 1602, 1520, 1454, 1345, 1073, 855 and 744; d_H(CDCl₃,

300 MHz) 0.93 (3H, d, J 7.0, 5-CH₃), 2.70 (1H, m, 2-H), 2.59 (1H, dt, J

14.0, 10.0, 2-H⁰), 2.92 (1H, m, 5-H), 3.20 (1H, t, J 8.5, 6-H), 3.46 (1H,

dd, J 8.5, 4.5, 6-H⁰), 4.16 (1H, br s, OH), 4.61 (2H, s, PhCH₂), 4.80 (1H,

dd, J 10.0, 3.0, 1-H), 5.46 (1H, t, J 11.0, 4-H), 5.63 (1H, dt, J 5.5, 11.0, 3-

H), 7.30e7.49 (5H, m, ArH) and 7.53 and 8.21 (each 2H, d, J 9.0, ArH);

d_C(CDCl₃, 75 MHz) 17.3, 32.6, 39.0, 72.5, 73.5, 75.0, 123.8, 125.8,

126.7, 128.2, 128.4, 128.8, 134.4, 137.9, 138.0, 147.3 and 152.9; m/z

(CI) 359 (M^þþ18, 50%), 342 (M^þþ1, 10), 294 (100) and 106 (95);

HRMS: M^þþNH₄, found 359.1962. C₂₀H₂₇N₂O₄requires 359.1965.

4.2.5.5. (1RS,5SR,3Z)-6-Benzyloxy-1-(4-chlorophenyl)-5-

methylhex-3-en-1-ol (4e). Tin(IV) chloride (1 M in DCM, 0.18 mL,

0.18 mmol) in DCM (0.5 mL), the (E,Z)-pent-2-enyl(triphenyl)ger-

mane (E,Z)-9 (80 mg, 0.162 mmol) in DCM (1.3 mL) and 4-

chlorobenzaldehyde (68 mg, 0.49 mmol) in DCM (0.3 mL), after

chromatography using light petroleum/ether (4:1) as eluent, gave

the title compound 4e¹(30 mg, 56%) as a colourless oil, 4e/6e¼99:1

(¹H NMR), R_f0.13 in 4:1 light petroleum/ether.

Tin(IV) chloride (1 M in DCM, 0.20 mL, 0.2 mmol) in DCM

(0.5 mL), the (Z)-pent-2-enyl(triethyl)germane (Z)-13 (58 mg,

0.166 mmol) in DCM (1.0 mL) and 4-chlorobenzaldehyde (70 mg,

0.5 mmol) in DCM (0.3 mL), after chromatography using light pe-

troleum/ether (4:1) as eluent, gave the title compound 4e (46 mg,

84%) as a colourless oil, 4e/6e¼99:1.

4.2.5.9. (4RS,8SR,2E,6Z)-9-Benzyloxy-8-methylnona-2,6-dien-4-

ol (4i). Tin(IV) chloride (1 M in DCM, 0.22 mL, 0.22 mmol) in DCM

(0.5 mL), the (E,Z)-pent-2-enyl(triphenyl)germane (E,Z)-9 (100 mg,

0.203 mmol) in DCM (1.0 mL) and (E)-but-2-enal (60 mL,

0.60 mmol), after chromatography using light petroleum/ether

(5:1) gave the title compound 4i (46 mg, 86%) as a colourless oil, 4i/

6i¼97:3 (¹H NMR, 8-CH₃), R_f0.19 in 4:1 light petroleum/ether; n_max

/

4.2.5.6. (1RS,5SR,3Z)-6-Benzyloxy-1-(3-chlorophenyl)-5-

methylhex-3-en-1-ol (4f). Tin(IV) chloride (1 M in DCM, 0.18 mL,

0.18 mmol) in DCM (0.5 mL), the (E,Z)-pent-2-enyl(triphenyl)ger-

mane (E,Z)-9 (80 mg, 0.162 mmol) in DCM (1.3 mL) and 3-

chlorobenzaldehyde (55 mL, 0.49 mmol), after chromatography

using light petroleum/ether (4:1) as eluent, gave the title compound

4f (18 mg, 34%) as a colourless oil, 4f/6f¼98:2 (¹H NMR, 5-CH₃), R_f

0.15 in 4:1 light petroleum/ether; n_max/cm^ꢀ13426, 2957, 2925,

2862, 1598, 1573, 1476, 1454, 1198, 1094, 1073 and 786; d_H(CDCl₃,

300 MHz) 0.93 (3H, d, J 6.5, 5-CH₃), 2.38 (1H, m, 2-H), 2.60 (1H, dt, J

13.5, 10.5, 2-H⁰), 2.91 (1H, m, 5-H), 3.22 (1H, t, J 9.5, 6-H), 3.78 (1H,

br s, OH), 3.41 (1H, dd, J 8.5, 5.0, 6-H⁰), 4.60 (2H, s, PhCH₂), 4.67 (1H,

dd, J 10.0, 3.5,1-H), 5.41 (1H, t, J 10.0, 4-H), 5.60 (1H, td, J 10.5, 6.0, 3-

H) and 7.22e7.44 (9H, m, ArH); d_C(CDCl₃, 75 MHz) 17.3, 32.6, 38.9,

72.8, 73.4, 74.9, 124.1, 126.1, 127.5, 128.0, 128.2, 128.7, 129.8, 134.4,

cm^ꢀ13426, 3004, 2959, 2927, 2855, 1453, 1434, 1094, 966 and 737;

d_H(CDCl₃, 300 MHz) 0.97 (3H, d, J 6.5, 8-CH₃), 1.75 (3H, d, J 7.0, 1-

H₃), 2.27 (2H, dt, J 14.0, 5.5, 5-H), 2.42 (1H, dt, J 14.0, 9.0, 5-H⁰),

2.87e2.98 (2H, m, OH and 8-H), 3.23 (1H, t, J 9.0, 9-H), 3.37 (1H, dd,

J 9.0, 5.5, 9-H⁰), 4.09 (1H, m, 4-H), 4.57 (2H, s, PhCH₂), 5.38 (1H, dd, J

11.0, 10.0, 7-H), 5.48e5.62 (2H, m, 3-H and 6-H), 5.74 (1H, dq, J 15.0,

6.5, 2-H) and 7.28e7.54 (5H, m, ArH); d_C(CDCl₃, 75 MHz) 17.6, 18.0,

32.6, 36.5, 72.1, 73.3, 75.0, 126.2, 126.5, 127.9, 128.1, 128.3, 134.2,

136.6 and 138.4; m/z (CI) 278 (M^þþ18, 7%), 260 (M^þ, 15), 243

(M^þꢀ17, 90), 225 (40) and 137 (100); HRMS: M^þþNH₄, 278.2116.

C₁₇H₂₈NO₂requires 278.2115.

4.2.5.10. (3RS,7SR,1E,5Z)-8-Benzyloxy-7-methyl-1-phenylocta-

1,5-dien-3-ol (4j). Tin(IV) chloride (1

M in DCM, 0.33 mL,

0.33 mmol) in DCM (0.5 mL), the (E,Z)-pent-2-enyl(triphenyl)

E.J. Thomas, A.P. Weston / Tetrahedron 70 (2014) 7253e7267

7261

germane (E,Z)-9 (150 mg, 0.304 mmol) in DCM (2 mL) and (E)-

cinnamaldehyde (120 L, 0.90 mmol), after chromatography using

triethylamine (39

m

L, 0.24 mmol), DMAP (a few crystals) in THF

m

(1 mL) and 4-nitrobenzoyl chloride (33 mg, 0.18 mmol) in THF

(0.5 mL) with stirring overnight, after chromatography using light

petroleum/ether (7:1) as eluent, gave the title compound 10d

(38 mg, 66%) as a yellow oil containing about 4% of its syn-epimer

11d, R_f0.27 in 4:1 light petroleum/ether; n_max/cm^ꢀ12860, 2361,

1724, 1527, 1349, 1269, 1103, 720 and 698; d_H(CDCl₃, 300 MHz)

major 10d 1.02 (3H, d, J 6.5, 6-CH₃), 2.62 (2H, t, J 6.5, 3-H₂), 2.89 (1H,

m, 6-H), 3.30 (2H, d, J 6.5, 7-H₂), 3.70 (2H, m, 1-H₂), 4.49 (2H, s,

PhCH₂), 4.55 and 4.63 (each 1H, d, J 12.0, PhHCH), 5.36e5.53 (3H, m,

2-H, 4-H and 5-H), 7.25e7.40 (5H, m, ArH) and 8.22 and 8.30 (each

2H, d, J 9.0, ArH); minor 11d 0.98 (3H, d, J 6.5, 6-CH₃); d_C(CDCl₃,

75 MHz) 17.9, 29.4, 32.9, 70.7, 73.2, 73.5, 74.5, 75.3, 123.7, 123.9,

127.7(2), 127.9, 128.0, 128.6, 128.7, 131.1, 136.1, 136.6, 138.2, 138.8,

150.8 and 164.5; m/z (CI) 490 (M^þþ1, 100%), 489 (M^þ, 60), 473 (40)

and 459 (40); HRMS: M^þþNH₄, found 507.2488. C₂₉H₃₅N₂O₆re-

quires 507.2490.

light petroleum/ether (3:1) as eluent gave the title compound 4j

(66 mg, 67%) as a colourless oil, 4j/6j¼95:5 (¹H NMR, 7-CH₃), R_f0.11

in 4:1 light petroleum/ether; n_max/cm^ꢀ13417, 3026, 2960, 2926,

2858, 1453, 1432, 1095, 967 and 738; d_H(CDCl₃, 300 MHz) 0.96 (3H,

d, J 6.5, 7-CH₃), 2.36 (1H, dt, J 14.0, 4.5, 4-H), 2.52 (1H, dt, J 14.0, 9.0,

4-H⁰), 2.93 (1H, m, 7-H), 3.23 (1H, t, J 9.0, 8-H), 3.38 (1H, dd, J 9.0,

5.5, 8-H⁰), 4.32 (1H, m, 3-H), 4.57 (2H, s, PhCH₂), 5.41 (1H, t, J 11.0, 6-

H), 5.57 (1H, dt, J 6.5, 10.5, 5-H), 6.28 (1H, dd, J 16.0, 6.0, 2-H), 6.65

(1H, d, J 16.0, 1-H) and 7.20e7.52 (10H, m, ArH); d_C(CDCl₃, 75 MHz)

17.5, 32.6, 36.5, 71.9, 73.3, 75.0, 125.9, 126.7, 127.9, 128.1, 128.6,

128.7, 129.8, 130.3, 132.6, 134.3, 137.0 and 138.3; m/z (CI) 340

(M^þþ18, 5%), 322 (M^þ, 20), 305 (100), 287 (30) and 199 (45).

4.2.6. Synthesis of 4-nitrobenzoates by esteriﬁcation using 4-

nitrobenzoyl chloride

4.2.6.1. (3RS,7SR,5Z)-8-Benzyloxy-2,7-dimethyloct-5-en-3-yl 4-

nitrobenzoate (10b); standard procedure. A solution of alcohol 4b

4.2.6.4. (1RS,5SR,3Z)-6-Benzyloxy-1-(4-chlorophenyl)-5-

(16 mg, 0.061 mmol), triethylamine (20

m

L, 0.12 mmol) and DMAP

methylhex-3-enyl 4-nitrobenzoate (10e). The alcohol 4e (36 mg,

(2/3 crystals) in THF (0.6 mL) was cooled to 0 ^ꢁC. After 10 min, 4-

nitrobenzoyl chloride (17 mg, 0.91 mmol) in THF (0.4 mL) was

added and the solution stirred at rt for 4.5 h. More DMAP (2/3

crystals) was added and the reaction mixture stirred at rt overnight.

Saturated aqueous sodium hydrogen carbonate (1 mL) and water

(10 mL) were added and the mixture extracted with ether

(3ꢃ15 mL). The organic extracts were washed with water (15 mL)

and brine (15 mL) before drying (Na₂SO₄) and concentration under

reduced pressure. Chromatography of the residue using light pe-

troleum/ether (10:1) as eluent gave the title compound 10b (15 mg,

59%) as a yellow oil containing ca. 1% of its syn-epimer 11b, R_f0.28

in 9:1 light petroleum/ether; n_max/cm^ꢀ12963, 2930, 2874, 1723,

1529, 1348, 1274, 1115, 1102 and 720; d_H(CDCl₃, 300 MHz) major

10b 1.03 (6H, d, J 6.5, 1-H₃and 2-CH₃), 1.06 (3H, d, J 7.0, 7-CH₃), 2.07

(1H, m, 2-H), 2.45e2.65 (2H, m, 4-H₂), 2.85 (1H, m, 7-H), 3.36 (2H,

dd, J 6.5, 2.0, 8-H₂), 4.46 (2H, s, PhCH₂), 5.10 (1H, dt, J 7.5, 5.5, 3-H),

5.34 (1H, dd, J 11.0, 9.5, 6-H), 5.46 (1H, dt, J 11.0, 7.5, 5-H), 7.25e7.40

(5H, m, ArH) and 8.24 and 8.32 (each 2H, d, J 9.0, ArH); minor 11b

4.52 and 4.53 (each 1H, d, J 12.0, PhHCH); d_C(CDCl₃, 75 MHz) 17.8,

18.0, 19.0, 29.8, 31.4, 32.9, 73.1, 75.3, 80.2, 123.7, 124.8, 127.6, 127.7,

128.2, 128.5, 130.9, 134.6, 135.6, 138.7 and 164.6; m/z (ESI) 434

(M^þþ23, 12%), 412 (M^þþ1, 5), 337 (30) and 305 (100); HRMS:

M^þþNa, found 434.1937. C₂₄H₂₉NNaO₅requires 434.1938.

0.11 mmol), triethylamine (36 mL, 0.22 mmol), DMAP (a few crys-

tals) in THF (1 mL) and 4-nitrobenzoyl chloride (30 mg, 0.16 mmol)

in THF (0.5 mL), after chromatography using light petroleum/ether

(8:1) as eluent, gave the title compound 10e (35 mg, 67%) as a yellow

oil containing about 1% of its syn-epimer 11e, R_f0.16 in 9:1 light

petroleum/ether; n_max/cm^ꢀ12958, 2923, 2852, 1726, 1528, 1345,

1271, 1101, 1014 and 720; d_H(CDCl₃, 300 MHz) major 10e 0.91 (3H,

d, J 6.5, 5-CH₃), 2.68e2.86 (2H, m, 2-H₂), 2.92 (1H, m, 5-H),

3.20e3.35 (2H, m, 6-H₂), 4.52 (2H, s, PhCH₂), 5.35e5.42 (2H, m, 3-H

and 4-H), 6.02 (1H, t, J 7.0,1-H), 7.28e7.41 (9H, m, ArH) and 8.24 and

8.30 (each 2H, d, J 9.0, ArH); minor 11e 0.97 (3H, d, J 6.5, 5-CH₃); d_C

(CDCl₃, 75 MHz) 17.9, 33.0, 34.8, 73.3, 75.2, 76.9, 123.8, 123.9,

127.8(2), 128.5, 128.6, 129.1, 131.0, 134.4, 135.8, 136.7, 138.3, 138.8,

150.9 and 164.1; m/z (CI) 497 (M^þþ18, 50%), 467 (25), 330 (40) and

106 (100); HRMS: M^þþNH₄, found 497.1848. C₂₇H₃₀³⁵ClN₂O₅re-

quires 497.1838.

4.2.6.5. (1RS,5SR,3Z)-6-Benzyloxy-5-methyl-1-(4-nitrophenyl)

hex-3-enyl 4-nitrobenzoate (10h). The alcohol 4h (31 mg,

0.09 mmol), triethylamine (30 mL, 0.18 mmol), DMAP (a few crys-

tals) in THF (1 mL) and 4-nitrobenzoyl chloride (25 mg, 0.14 mmol)

in THF (0.5 mL), after chromatography using light petroleum/ether

(3:1) as eluent, gave the title compound 10h (38 mg, 85%) as a yellow

oil containing ca. 10% of its syn-epimer 11h, R_f0.41 in 4:1 light

petroleum/ether; n_max/cm^ꢀ12958, 2927, 2855, 1727, 1606, 1525,

1347, 1270, 1101 and 720; d_H(CDCl₃, 300 MHz) major 10h 0.92 (3H,

d, J 7.0, 5-CH₃), 2.80 (2H, m, 2-H and 5-H), 2.97 (1H, dt, J 14.5, 6.5, 2-

H⁰), 3.20e3.40 (2H, m, 6-H₂), 4.54 (2H, s, PhCH₂), 5.32e5.49 (2H, m,

3-H and 4-H), 6.13 (1H, t, J 7.0, 1-H), 7.28e7.42 (5H, m, ArH), 7.60

(2H, d, J 9.0, ArH) and 8.23e8.36 (6H, m, ArH); minor 11h 0.98 (3H,

d, J 6.5, 5-CH₃) and 4.50 and 4.51 (each 1H, d J 12.0, PhHCH); d_C

(CDCl₃, 75 MHz) 17.7, 33.1, 34.6, 73.4, 75.3, 76.5, 122.8, 123.9, 124.1,

127.7, 127.8, 127.9, 128.7, 131.1, 135.3, 137.7, 138.7, 146.9, 148.0, 151.0

and 164.0; m/z (CI) 508 (M^þþ18, 30%), 294 (100) and 155 (40);

HRMS: M^þþNH₄, found 508.2094. C₂₇H₃₀N₃O₇requires 508.2078.

4.2.6.2. (4SR,8SR,6Z)-9-Benzyloxy-8-methylnon-6-en-4-yl 4-

nitrobenzoate (10c). The alcohol 4c (25 mg, 0.095 mmol), triethyl-

amine (31 mL, 0.19 mmol), DMAP (a few crystals) in THF (1 mL) and

4-nitrobenzoyl chloride (27 mg, 0.13 mmol) in THF (0.5 mL) with

stirring overnight, after chromatography using light petroleum/

ether (10:1) as eluent, gave the title compound 10c (17 mg, 44%) as

a yellow oil containing ca. 2% of its syn-epimer 11c, R_f0.22 in 9:1

light petroleum/ether; n_max/cm^ꢀ12960, 2931, 2872, 1723, 1529,

1349, 1274, 1116, 1102 and 720; d_H(CDCl₃, 300 MHz) major 10c 0.97

(3H, t, J 7.5, 1-H₃), 1.02 (3H, d, J 6.5, 8-CH₃), 1.30e1.55 and 1.60e1.87

(each 2H, m, 2-H₂or 3-H₂), 2.53 (2H, m, 5-H₂), 2.86 (1H, m, 8-H),

3.29 (2H, m, 9-H₂), 4.49 (2H, s, PhCH₂), 5.25 (1H, quin, J 6.5, 4-H),

5.37 (1H, dd, J 11.0, 9.5, 7-H), 5.48 (1H, dt, J 11.0, 7.0, 6-H), 7.27e7.40

(5H, m, ArH) and 8.26 and 8.32 (each 2H, d, J 9.0, ArH); minor 11c

4.52 (2H, s, PhCH₂); d_C(CDCl₃, 75 MHz) 14.2, 18.0, 19.0, 32.5, 32.9,

36.1, 73.2, 75.3, 75.9, 123.7, 124.5, 127.7(2), 128.6, 130.9, 135.9, 136.3,

138.8, 150.7 and 164.6; m/z (CI) 429 (M^þþ18, 100%), 412 (M^þþ1, 10)

and 245 (40); HRMS: M^þþH, found 412.2114. C₂₄H₃₀NO₅requires

412.2118.

4.2.7. Synthesis of 4-nitrobenzoates via a Mitsunobu reaction

4.2.7.1. (3RS,7RS,5Z)-8-Benzyloxy-2,7-dimethyloct-5-en-3-yl 4-

nitrobenzoate (11b); standard procedure. Di-isopropyl azodi-

carboxylate (216 mL, 1.09 mmol) was added dropwise to the alcohol

4b (225 mg, 0.456 mmol), 4-nitrobenzoic acid (92 mg, 0.50 mmol)

and triphenylphosphine (288 mg, 1.09 mmol) in THF (4 mL) at 0 ^ꢁC

and the solution stirred at rt for 7 h. After concentration under

reduced pressure, chromatography of the residue using light pe-

troleum/ether (15:1) as eluent gave the title compound 11b (101 mg,

54%) as a yellow oil containing ca. 3% of its anti-epimer 10b, R_f0.26

4.2.6.3. (2RS,6SR,4Z)-1,7-Bis(benzyloxy)-6-methylhept-4-en-2-yl

4-nitrobenzoate (10d). The alcohol 4d (40 mg, 0.12 mmol),

7262

E.J. Thomas, A.P. Weston / Tetrahedron 70 (2014) 7253e7267

in 9:1 light petroleum/ether; n_max/cm^ꢀ12964, 2930, 2874, 1723,

1608, 1529, 1348, 1274, 1116, 1102 and 720; d_H(CDCl₃, 300 MHz)

major 11b 0.93 (3H, d, J 7.0, 7-CH₃), 1.02 and 1.04 (each 3H, d, J 5.0,

1-H₃or 2-CH₃), 2.10 (1H, m, 2-H), 2.46 (1H, dt, J 15.0, 5.0, 4-H), 2.60

(1H, dt, J 8.0, 7.0, 4-H⁰), 2.84 (1H, m, 7-H), 3.26e3.35 (2H, m, 8-H₂),

4.52 and 4.53 (each 1H, d, J 12.0, PhHCH), 5.10 (1H, dt, J 8.0, 5.0, 3-

H), 5.32 (1H, dd, J 11.0, 9.5, 6-H), 5.49 (1H, dt, J 11.0, 7.5, 5-H),

7.27e7.42 (5H, m, ArH) and 8.24 and 8.32 (each 2H, d, J 9.0, ArH);

minor 10b 4.46 (2H, s, PhCH₂); d_C(CDCl₃, 75 MHz) 17.9, 18.0, 19.1,

30.0, 31.6, 32.9, 73.3, 75.4, 80.3, 123.8, 125.1, 127.7, 128.6, 130.9,

134.7, 135.7, 136.3, 138.8, 150.7 and 164.6; m/z (ESI) 434 (M^þþ23,

100%), 393 (40) and 288 (80); HRMS: M^þþNa, found 434.1941.

and 263 (M^þþ1, 25); HRMS: M^þþH, found 263.2006. C₁₇H₂₇O₂

requires 263.2006.

4.2.7.3. (2SR,6SR,4Z)-1,7-Bis(benzyloxy)-6-methylhept-4-en-2-yl

4-nitrobenzoate (11d). Di-isopropyl azodicarboxylate (23

mL,

0.14 mmol), the alcohol 4d (31 mg, 0.091 mmol), 4-nitrobenzoic

acid (20 mg, 0.11 mmol) and triphenylphosphine (31 mg,

0.11 mmol) in THF (2.5 mL), after stirring at rt for 4 h and chro-

matography using light petroleum/ether (8:1), gave the title com-

pound 11d (33 mg, 68%) as a yellow oil containing about 4% of its

anti-epimer 10d, R_f0.35 in 4:1 light petroleum/ether; n_max/cm^ꢀ1

2959, 2924, 2857, 1724, 1528, 1454, 1349, 1275, 1103 and 720; d_H

(CDCl₃, 300 MHz) major 11d 0.98 (3H, d, J 6.5, 6-CH₃), 2.50e2.75

(2H, m, 3-H₂), 2.87 (1H, m, 6-H), 3.32 (2H, d, J 6.5, 7-H₂), 3.71 (2H, d,

J 5.0, 1-H₂), 4.52, 4.53, 4.56 and 4.59 (each 1H, d, J 12.0, PhHCH),

5.35e5.43 (3H, m, 2-H, 4-H and 5-H), 5.48 (1H, dt, J 11.0, 7.0, 4-H),

7.30e7.39 (10H, m, ArH) and 8.24 and 8.32 (each 2H, d, J 9.0, ArH);

minor 10d 1.02 (3H, d, J 6.5, 6-CH₃); d_C(CDCl₃, 75 MHz) 18.0, 29.5,

32.8, 70.8, 73.2, 73.4, 74.5, 75.3, 123.7, 124.1, 127.7, 127.8, 128.0,

128.6,128.7,131.1,136.1,136.6,138.2,138.8,150.8 and 164.5; m/z (CI)

507 (M^þþ18, 13%) and 108 (100); HRMS: M^þþNH₄, found 507.2510.

C

₂₄H₂₉NNaO₅requires 434.1938.

Sodium hydroxide (69 mg, 3.8 mmol) was added to a suspen-

sion of the ester 11b (90 mg, 0.218 mmol) in methanol (1 mL) and

the mixture stirred at rt for 2 h. After concentration under re-

duced pressure, ether (15 mL) and saturated aqueous ammonium

hydroxide (7 mL) were added. The aqueous layer was washed

with ether (2ꢃ15 mL) and the ether extracts dried (Na₂SO₄)

and concentrated under reduced pressure. Chromatography of

the residue using light petroleum/ether (4:1) as eluent gave the

alcohol 6b (35 mg, 60%) as a colourless oil containing ca. 1% of its

anti-epimer 4b, R_f0.15 in 4:1 light petroleum/ether; n_max/cm^ꢀ1

3427, 3004, 2957, 2928, 2871, 1453, 1366, 1096 and 736; d_H(CDCl₃,

300 MHz) 0.94 and 0.98 (each 3H, d, J 4.5, 1-H₃or 2-CH₃), 1.01

(3H, d, J 6.5, 7-CH₃), 1.70 (1H, m, 2-H), 2.12 (1H, s, OH), 2.27 (1H,

dt, J 14.0, 7.0, 4-H), 2.34 (1H, m, 4-H⁰), 2.91 (1H, m, 7-H),

3.27e3.42 (3H, m, 3-H and 8-H₂), 4.56 (2H, s, PhCH₂), 5.44 (1H,

dd, J 11.0, 9.5, 6-H), 5.53 (1H, dt, J 11.0, 7.5, 5-H), and 7.30e7.42

(5H, m, ArH); d_C(CDCl₃, 75 MHz) 17.9, 18.4, 19.2, 32.6, 32.7, 33.3

73.3, 75.3, 76.5, 126.1, 127.8, 127.9, 128.6, 136.6 and 138.6; m/z (CI)

280 (M^þþ18, 100%) and 263 (30); HRMS: M^þþNH₄, found

280.2272. C₁₇H₃₀NO₂requires 280.2271.

C₂₉H₃₅N₂O₆requires 507.2490.

4.2.7.4. (1SR,5SR,3Z)-6-Benzyloxy-1-(4-chlorophenyl)-5-

methylhex-3-enyl 4-nitrobenzoate (11e). Di-isopropyl azodicarbox-

ylate (32 L, 0.16 mmol), the alcohol 4e (45 mg, 0.136 mmol), 4-

m

nitrobenzoic acid (27 mg, 0.16 mmol) and triphenylphosphine

(42 mg, 0.16 mmol) in THF (2 mL) after stirring at rt for 4 h and

chromatography using light petroleum/ether (8:1) gave the title

compound 11e (41 mg, 62%) as a yellow oil containing ca. 1% of its

anti-epimer 10e, R_f0.34 in 4:1 light petroleum/ether; n_max/cm^ꢀ1

2959, 2927, 2856, 1727, 1529, 1346, 1271, 1102, 1014 and 720; d_H

(CDCl₃, 300 MHz) major 11e 0.97 (3H, d, J 6.5, 5-CH₃), 2.68e2.85

(2H, m, 2-H and 5-H), 2.92 (1H, m, 2-H⁰), 3.18 (1H, dd, J 10.0, 6.5, 6-

H), 3.25 (1H, dd, J 9.0, 7.0, 6-H⁰), 4.49 and 4.51 (each H, d, J 12.0,

PhHCH), 5.33e5.47 (2H, m, 3-H and 4-H), 6.02 (1H, dd, J 7.5, 6.5, 1-

H), 7.28e7.40 (9H, m, ArH) and 8.26 and 8.33 (each 2H, d, J 9.0,

ArH); minor 10e 0.91 (3H, d, J 6.5, 5-CH₃) d_C(CDCl₃, 75 MHz) 17.8,

33.1, 34.6, 73.3, 75.3, 76.9, 123.5, 123.8, 127.7, 127.8, 128.3, 128.6,

129.1, 131.0, 134.4, 135.8, 136.9, 138.3, 138.8, 150.8 and 164.1; m/z

(CI) 497 (M^þþ18, 6%) and 330 (100); HRMS: M^þþNH₄, found

497.1848. C₂₇H₃₀³⁵ClN₂O₅requires 497.1838.

4.2.7.2. (4RS,8SR,6Z)-9-Benzyloxy-8-methylnon-6-en-4-yl 4-

nitrobenzoate (11c). Di-isopropyl azodicarboxylate (54

mL,

0.27 mmol), the alcohol 4c (60 mg, 0.23 mmol), 4-nitrobenzoic acid

(46 mg, 0.27 mmol) and triphenylphosphine (72 mg, 0.27) in THF

(4 mL), after stirring for 4 h and chromatography using light pe-

troleum/ether (15:1) gave the title compound 11c (54 mg, 57%) as

a yellow oil containing ca. 2% of its anti-epimer 10c, R_f0.27 in 9:1

light petroleum/ether; n_max/cm^ꢀ12960, 2928, 2871, 1722, 1529,

1349, 1274, 1115, 1102 and 720; d_H(CDCl₃, 300 MHz) major 11c

0.94e1.02 (6H, m, 1-H₃, and 8-CH₃), 1.35e1.55 and 1.65e1.85 (each

2H, m, 2-H₂or 3-H₂), 2.49 (1H, dt, J 15.0, 6.0, 5-H), 2.60 (1H, dt, J

14.5, 7.5, 5-H⁰), 2.85 (1H, m, 8-H), 3.32 (2H, d, J7.5, 9-H₂), 4.52 (2H, s,

PhCH₂), 5.24 (1H, pent, J 6.0, 4-H), 5.37 (1H, dd, J 11.0, 9.5, 6-H), 5.48

(1H, dt, J 11.0, 7.0, 5-H), 7.28e7.40 (5H, m, ArH) and 8.23 and 8.31

(each 2H, d, J 9.0, ArH); minor 10c 4.49 (2H, s, PhCH₂); d_C(CDCl₃,

75 MHz) 14.2,18.0,19.0, 32.7, 32.9, 36.1, 73.2, 75.4, 76.0, 123.8, 124.7,

127.7, 127.8, 128.6, 130.9, 136.0, 136.3, 138.8, 150.7 and 164.6; m/z

(CI) 429 (M^þþ18, 15%) and 106 (100); HRMS: M^þþNH₄, found

429.2376. C₂₄H₃₃N₂O₅requires 429.2384.

Sodium hydroxide (33 mg, 1.74 mmol) and the ester 11c

(43 mg, 0.218 mmol) in methanol (1 mL), after chromatography

using light petroleum/ether (4:1) gave the alcohol 6c (25 mg, 92%)

as a colourless oil containing ca. 2% of its anti-epimer 4c, R_f0.09 in

4:1 light petroleum/ether; n_max/cm^ꢀ13414, 2957, 2928, 2871,

1454, 1096, 1075 and 737; d_H(CDCl₃, 300 MHz) 0.98 (3H, t, J 6.5, 1-

H₃), 1.03 (3H, d, J 6.5, 8-CH₃), 1.35e1.54 (4H, m, 2-H₂and 3-H₂),

2.18e2.31 (2H, m, 5-H and OH), 2.40 (1H, m, 5-H⁰), 2.92 (1H, m, 8-

H), 3.31 (1H, dd, J 9.0, 6.0, 9-H), 3.39 (1H, dd, J 9.0, 7.5, 9-H⁰), 3.70

(1H, m, 4-H), 4.56 (2H, s, PhCH₂), 5.43 (1H, dd, J 11.0, 9.5, 7-H), 5.53

(1H, dt, J 11.0, 7.5, 6-H) and 7.30e7.43 (5H, m, ArH); d_C(CDCl₃,

75 MHz) 14.4, 17.9, 19.4, 32.7, 35.4, 39.1, 71.2, 73.3, 75.3, 125.6,

127.8, 127.9, 128.6, 136.7 and 138.6; m/z (CI) 280 (M^þþ18, 100%)

4.2.7.5. (1SR,5SR,3Z)-6-Benzyloxy-5-methyl-1-(4-nitrophenyl)

hex-3-enyl 4-nitrobenzoate (11h). Di-isopropyl azodicarboxylate

(23 mL, 0.14 mmol), the alcohol 4h (40 mg, 0.117 mmol), 4-

nitrobenzoic acid (23 mg, 0.14 mmol) and triphenylphosphine

(37 mg, 0.14 mmol) in THF (2 mL), after stirring at rt for 4 h and

chromatography using light petroleum/ether (4:1) as eluent, gave

the title compound 11h (46 mg, 79%) as a yellowoil containing ca.10%

of its anti-epimer 10h, R_f0.28 in 2:1 light petroleum/ether; n_max

/

cm^ꢀ12957, 2924, 2853,1728,1606,1525,1348,1271,1102 and 720; d_H

(CDCl₃, 300 MHz) major 11h 0.98 (3H, d, J 6.5, 5-CH₃), 2.71e2.87 (2H,

m, 2-H and 5-H), 2.94 (1H, m, 2-H⁰), 3.22 (1H, dd, J 9.0, 7.0, 6-H), 3.31

(1H, dd, J 9.0, 6.5, 6-H⁰), 4.50 and 4.51 (each 1H, d, J 12.0, PhHCH),

5.35e5.52 (2H, m, 3-H and 4-H), 6.14 (1H, dd, J 7.5, 6.0, 1-H),

7.28e7.45 (5H, m, ArH), 7.58 (2H, d, J 8.5, ArH) and 8.22e8.40 (6H, m,

ArH); minor 10h 0.92 (3H, d, J 7.0, 5-CH₃) and 4.54 (2H, s, PhCH₂); d_C

(CDCl₃, 75 MHz) 17.9, 33.1, 34.8, 73.4, 75.3, 76.7, 123.2, 124.0, 124.2,

127.5, 127.7, 127.8, 128.7, 131.1, 135.4, 137.4, 138.7, 147.1, 148.0, 151.0

and 164.0; m/z (CI) 508 (M^þþ18, 6%) and 294 (100); HRMS:

M^þþNH₄, found 508.2085. C₂₇H₃₀N₃O₇requires 508.2078.

4.2.8. (4S,2E)-4-Benzyloxypent-2-enyl(triethyl)germane (15) and its

reactions with aldehydes. The standard procedure using trie-

thylgermanium hydride (0.16 mL, 1.0 mmol) and TMEDA (0.17 mL,

E.J. Thomas, A.P. Weston / Tetrahedron 70 (2014) 7253e7267

7263

1.1 mmol) in THF (1 mL), ^tBuLi (1.7 M in pentane, 0.70 mL,

1.2 mmol), and copper(I) iodide (95 mg, 0.50 mmol) in THF (2 mL)

and acetate 14 (117 mg, 0.50 mmol) in THF (1 mL), after chroma-

tography using light petroleum/ether (60:1) as eluent, gave the title

compound 15 (139 mg, 83%) as a colourless oil, R_f0.63 in 9:1 light

chromatography using 2% ether in light petroleum as eluent, gave

the title compound (E)-22 (309 mg, 69%) as a colourless oil, R_f0.20 in

1% ether in light petroleum, [

a

]

D

²³þ0.33 (c 0.59 in CHCl₃); n_max/cm^ꢀ1

3068, 2955, 2928, 2892, 2856, 1430, 1253, 1092, 834, 744 and 733;

d_H(CDCl₃, 300 MHz) 0.04 and 0.05 (each 3H, s, SiCH₃), 0.90 [9H, s,

SiC(CH₃)₃], 1.00 (3H, d, J 6.0, 6-H₃), 2.03 (1H, dt, J 13.5, 7.0, 4-H), 2.14

(1H, dt, J 13.5, 6.5, 4-H⁰), 2.46 (2H, d, J 8.0, 1-H₂), 3.67 (1H, sext, J 6.0,

5-H), 5.38 (1H, dt, J 15.0, 6.5, 2-H), 5.59 (1H, dt, J 15.0, 8.0, 3-H),

7.39e7.44 (9H, m, ArH) and 7.49e7.54 (6H, m, ArH); d_C(CDCl₃,

75 MHz) ꢀ4.5, ꢀ4.3, 18.5, 19.9, 23.3, 26.2, 43.4, 69.2, 127.3, 128.0,

128.4, 129.2, 135.3 and 137.0; m/z (CI) 536 (M^þþ18, 2%), 322 (100),

320 (80) and 318 (60); HRMS: M^þþNH₄, found 536.2396.

petroleum/ether, [

a

]

²⁴ꢀ59 (c 1.16 in CHCl₃); n_max/cm^ꢀ12951, 2905,

D

2870, 2267, 1655, 1366, 1096, 1069, 1025 and 734; d_H(CDCl₃,

300 MHz) 0.81 (6H, q, J 8.0, 3ꢃ GeCH₂), 1.08 (9H, t, J 8.0, 3ꢃ

GeCH₂CH₃), 1.31 (3H, d, J 6.5, 5-H₃), 1.72 (2H, d, J 8.5, 1-H₂), 3.90 (1H,

dq, J 8.0, 6.5, 4-H), 4.38 and 4.61 (each 1H, d, J 12.0, PhHCH), 5.30

(1H, dd, J 15.0, 8.0, 3-H), 5.55 (1H, dt, J 15.0, 8.5, 2-H) and 7.27e7.42

(5H, m, ArH); d_C(CDCl₃, 75 MHz) 4.2, 9.2, 17.2, 22.4, 69.7, 76.5, 127.5,

127.9, 128.6, 129.9, 131.4 and 139.4; m/z (ESI) 359 (M^þþ23, 50%),

357 (M^þþ23, 35) and 355 (M^þþ23, 30); HRMS: M^þþNa, found

359.1406. C₁₅H₃₀⁷⁴GeNaO requires 359.1401.

C

₃₀H₄₄⁷⁴GeNOSi requires 536.2398.

4.2.10.2. (5R,2E)-5-Hydroxyhex-2-enyl(triphenyl)germane [(E)-

Following the standard procedure, tin(IV) chloride (1 M in DCM,

0.42 mL, 0.42 mmol) in DCM (0.5 mL), the pent-2-enylgermane 15

(116 mg, 0.35 mmol) in DCM (1.0 mL) and benzaldehyde (106 mL,

1.0 mmol), after chromatography using light petroleum/ether (3:1)

as eluent, gave the syn-5-benzyloxy-1-phenylhex-3-en-1-ol 16a¹³

(39 mg, 40%) as a colourless oil containing ca. 11% of its 1,5-anti-

epimer, R_f0.15 in 4:1 light petroleum/ether.

23]; standard procedure. Tetra-n-butylammonium ﬂuoride (1 M in

THF, 0.9 mL, 0.9 mmol) was added to the (E)-5-tert-butyldime-

thylsilyloxyhex-2-enylgermane (E)-22 (309 mg, 1.6 mmol) in THF

(5 mL) and the reaction mixture stirred at rt overnight. Water was

added (15 mL) and the mixture extracted with ether (3ꢃ20 mL).

The organic extracts were washed with water (20 mL) and brine

(20 mL), dried (Na₂SO₄) and concentrated under reduced pressure.

Chromatography of the residue using light petroleum/ether (3:1)

Tin(IV) bromide (64 mg, 1.4 mmol) in DCM (0.47 mL), the pent-

2-enylgermane 15 (40 mg, 0.12 mmol) in DCM (0.53 mL) and

gave the title compound (E)-23 (223 mg, 93%) as a white crystalline

23

benzaldehyde (43

as a colourless oil containing ca. 10% of its 1,5-anti-epimer, [

m

L, 0.36 mmol) gave the alcohol 16a (9 mg, 26%)

solid, mp 86.4e87.2 ^ꢁC, R_f0.20 in 2:1 light petroleum/ether, [

a]

D

23

a

]

ꢀ7.6 (c 1.62 in CHCl₃); n_max/cm^ꢀ13384, 3067, 3048, 2967, 2902,

1484, 1430, 1091, 965 and 734; d_H(CDCl₃, 300 MHz) 1.08 (3H, d, J

6.0, 6-H₃), 1.26 (1H, m, OH), 2.02 (1H, dt, J 14.0, 7.5, 4-H), 2.16 (1H,

dt, J 14.0, 4.5, 4-H⁰), 2.50 (2H, d, J 8.0, 1-H₂), 3.61 (1H, m, 5-H), 5.34

(1H, dt, J 15.0, 6.5, 2-H), 5.71 (1H, dt, J 15.0, 8.0, 3-H), 7.40e7.46 (9H,

m, ArH) and 7.50e7.55 (6H, m, ArH); d_C(CDCl₃, 75 MHz) 20.1, 22.7,

42.9, 67.4, 126.4, 128.5, 129.4, 130.1, 135.2 and 136.7; m/z (CI) 422

(M^þþ18, 70%), 420 (M^þþ18, 60), 418 (M^þþ18, 50), 322 (100), 320

(80) and 318 (50) HRMS: M^þþNH₄, found 422.1534. C₂₄H₃₀⁷⁴GeNO

requires 422.1534.

D

þ52 (c 0.77 in CHCl₃).

Tin(IV) chloride (1 M in DCM, 0.27 mL, 0.27 mmol) in DCM

(0.5 mL), the pent-2-enylgermane 15 (75 mg, 0.22 mmol) in DCM

(1.0 mL) and 4-nitrobenzaldehyde (41 mg, 0.24 mmol) in DCM

(0.5 mL), after chromatography using light petroleum/ether (2:1) as

eluent, gave the syn-5-benzyloxy-1-(4-nitrophenyl)hex-3-en-1-ol

16b¹³(25 mg, 34%) as a yellow oil, R_f0.07 in 4:1 light petroleum/

ether, [

a

]

²³þ65 (c 0.97 in CHCl₃); HRMS: M^þþNH₄, found 345.1815.

D

C

₁₉H₂₅N₂O₄requires 345.1809.

Tin(IV) chloride (1 M in DCM, 0.69 mL, 0.69 mmol) in DCM

(1.0 mL), the pent-2-enylgermane 15 (192 mg, 0.57 mmol) in DCM

(2.0 mL) and butanal (110 L, 0.63 mmol) after chromatography

4.2.10.3. (5R,2Z)-5-Hydroxyhex-2-enyl(triphenyl)germane [(Z)-

23]. Triphenylgermanium hydride (1.02 g, 3.3 mmol) and TMEDA

(0.56 mL, 3.63 mmol) in THF (5 mL), ^tBuLi (1.7 M in pentane,

2.31 mL, 3.63 mmol), copper iodide (313 mg, 1.65 mmol) and the

(Z)-acetate (Z)-21 (450 mg,1.65 mmol), after chromatography using

1% ether in light petroleum as eluent, gave the hex-2-enylgermane

(Z)-22 (379 mg, 44%) as a colourless oil, R_f0.13 in 1% ether in petrol,

m

using light petroleum/ether (4:1) as eluent gave the syn-8-

benzyloxy-4-hydroxynon-6-en-4-ol 16c¹³(15 mg, 11%) as a yel-

23

low oil, R_f0.10 in 4:1 light petroleum/ether, [

CHCl₃).

a

]

þ23 (c 1.03 in

D

[a

]

²³þ2.4 (c 1.22 in CHCl₃); n_max/cm^ꢀ13069, 2957, 2929, 2856,1431,

4.2.9. (5R,2Z)-5-tert-Butyldimethylsilyloxyhex-2-enyl acetate [(Z)-

21]. The standard procedure using acetic anhydride (1.2 mL,

12.3 mmol), the (Z)-5-tert-butyldimethylsilyloxyhex-2-enol (Z)-27

(2.58 g, 11.2 mmol) and pyridine (2.8 mL, 33.6 mmol), after chro-

matography using light petroleum/ether (20:1), gave the title

compound (Z)-21 (2.96 mg, 97%) as a colourless oil, R_f0.28 in 9:1

D

1256, 1091, 1027, 734 and 698; d_H(CDCl₃, 300 MHz) 0.04 (6H, s, 2ꢃ

SiCH₃), 0.91 [9H, s, SiC(CH₃)₃], 1.05 (3H, d, J 6.0, 6-H₃), 2.00e2.08

(2H, m, 4-H₂), 2.50 (2H, d, J 8.5, 1-H₂), 3.63 (1H, sext, J 5.5, 5-H), 4.95

(1H, m, 2-H), 5.37 (1H, m, 3-H), 7.35e7.48 (9H, m, ArH) and

7.50e7.62 (6H, m, ArH); m/z (CI) 536 (M^þþ18, 3%), 534 (M^þþ18, 2),

532 (M^þþ18, 1.5), 519 (M^þþ1, 3) and 322 (100); HRMS: M^þꢀC₆H₅,

found 441.1663. C₂₄H₃₅⁷⁴GeOSi requires 441.1663.

The standard procedure using tetra-n-butylammonium ﬂuoride

(1 M in THF, 1.26 mL, 1.26 mmol) and the (Z)-5-tert-butyldime-

thylsilyloxyhex-2-enylgermane (Z)-22 (331 mg, 0.640 mmol) in

THF (5 mL), after chromatography using light petroleum/ether (3:1)

as eluent, gave the title compound (Z)-23 (124 mg, 48%) as a col-

light petroleum/ether, [

a]

²³ꢀ11.5 (c 1.34 in CHCl₃); n_max/cm^ꢀ12957,

D

2930, 2894, 2858, 1743, 1374, 1250, 1231, 1007, 836 and 775; d_H

(CDCl₃, 300 MHz) 0.06 and 0.07 (each 3H, s, SiCH₃), 0.89 [9H, s,

SiC(CH₃)₃], 1.14 (3H, d, J 6.0, 6-H₃), 2.07 (3H, s, CH₃CO), 2.25 (2H, m,

4-H₂), 3.92 (1H, hex, J 6.0, 5-H), 4.63 (2H, m, 1-H₂) and 5.58e5.76

(2H, m, 2-H and 3-H); d_C(CDCl₃, 75 MHz) ꢀ4.5, ꢀ4.3,18.3, 21.2, 23.8,

26.1, 37.8, 60.7, 68.4, 125.1, 131.9 and 171.2; m/z (CI) 290 (M^þþ18,

25%) and 273 (M^þþ1, 100); HRMS: M^þþNH₄, found 290.2147.

ourless oil containing about 10% of its (E)-isomer (E)-23, R_f0.25 in

21

1:1 light petroleum/ether, [

a

]

þ10.8 (c 0.74 in CHCl₃); n_max/cm^ꢀ1

C

₁₄H₃₂NO₃Si requires 290.2146.

D

3352, 3068, 3048, 2966, 1485, 1431, 1092, 734 and 699; d_H(CDCl₃,

300 MHz) 1.12 (3H, d, J 6.0, 6-H₃), 1.32 (1H, br s, OH), 1.96e2.16 (2H,

m, 4-H₂), 2.45e2.60 (2H, m, 1-H₂), 3.61 (1H, m, 5-H), 5.34 and 5.82

(each 1H, m, 2-H or 3-H), 7.38e7.46 (9H, m, ArH) and 7.52e7.58 (6H,

m, ArH); d_C(CDCl₃, 75 MHz) 15.8, 23.0, 37.1, 67.9, 124.8, 128.2, 128.5,

129.3, 135.2 and 136.7; m/z (CI) 422 (M^þþ18, 100%), 420 (M^þþ18,

75), 418 (M^þþ18, 60), 404 (M^þþ1, 4), 322 (96), 320 (80) and 318

(50); HRMS: M^þ, found 404.1197. C₂₄H₂₆⁷⁴GeO requires 404.1190.

4.2.10. Syntheses of hex-2-enylgermanes 22e26, 28 and 29

4.2.10.1. (5R,2E)-5-tert-Butyldimethylsilyloxyhex-2-

enyl(triphenyl)germane [(E)-22]. The standard procedure using

triphenylgermanium hydride (530 mg, 1.74 mmol) and TMEDA

(0.29 mL, 1.9 mmol) in THF (2.5 mL), ^tBuLi (1.7 M in pentane,

1.20 mL, 2.04 mmol), copper iodide (164 mg, 0.87 mmol) and the

(E)-acetate (E)-21 (237 mg, 0.87 mmol) in THF (2 mL), after

7264

E.J. Thomas, A.P. Weston / Tetrahedron 70 (2014) 7253e7267

4.2.10.4. (5R,2E)-5-tert-Butyldimethylsilyloxyhex-2-enyl(triethyl)

176 (80); HRMS: M^þþH, found 261.1271. C₁₂H₂₇⁷⁴GeO requires

germane [(E)-24]. Triethylgermanium hydride (0.16 mL, 1.0 mmol)

261.1268.

t

and TMEDA (0.17 mL, 1.1 mmol) in THF (1 mL), BuLi (1.7 M in

pentane, 0.70 mL, 1.2 mol), copper iodide (95 mg, 0.50 mmol) in

THF (2 mL) and the (E)-acetate (E)-21 (137 mg, 0.50 mmol), after

chromatography using 1% ether in light petroleum as eluent, gave

4.2.10.8. (5R,2E)-5-Methoxyhex-2-enyl(triethyl)germane

[(E)-

26]; standard procedure. The (E)-5-hydroxyhex-2-enylgermane

(E)-25 (233 mg, 0.90 mmol) in THF (3.5 mL) was added to a sus-

pension of sodium hydride (60% dispersion in mineral oil, 78 mg,

1.1 mmol) in THF (2 mL) and the reaction mixture stirred at 35 ^ꢁC

for 2 h. Methyl iodide (0.3 mL, 4.5 mmol) was added. After stirring

at rt overnight, water was added (4 mL) and the mixture extracted

with ether (3ꢃ25 mL). The organic extracts were washed with

water (25 mL) and brine (25 mL), then dried (MgSO₄) and con-

centrated under reduced pressure. Chromatography of the residue

using light petroleum/ether (30:1) gave the title compound (E)-26

the title compound (E)-24 (172 mg, 92%) as a colourless oil, R_f0.63 in

21

9:1 light petroleum/ether, [

a

]

ꢀ2.6 (c 1.65 in CHCl₃); n_max/cm^ꢀ1

D

2952, 2929, 2905, 2857, 1462, 1256, 1095, 1017, 834 and 774; d_H

(CDCl₃, 300 MHz) 0.09 (6H, s, 2ꢃ SiCH₃), 0.77 (6H, q, J 7.5, 3ꢃ

GeCH₂), 0.93 [9H, s, SiC(CH₃)₃], 1.05 (9H, t, J 7.5, 3ꢃ GeCH₂CH₃), 1.14

(3H, d, J 6.0, 6-H₃), 1.64 (2H, d, J 8.0, 2-H₂), 2.09 (1H, dt, J 13.5, 7.0, 4-

H), 2.20 (1H, dt, J 13.5, 6.0, 4-H⁰), 3.80 (1H, sext, J 6.0, 5-H), 5.28 (1H,

dt, J 15.0, 7.0, 2-H) and 5.55 (1H, dt, J 15.0, 8.0, 3-H); d_C(CDCl₃,

75 MHz) ꢀ4.4, ꢀ4.3, 4.1, 9.1, 17.3, 18.5, 23.4, 26.2, 43.5, 69.5, 124.5

and 130.0; m/z (ESI) 317 (M^þꢀ57, 7%) and 159 (60); HRMS:

M^þꢀC₄H₉, found 317.1356. C₁₄H₃₁⁷⁴GeOSi requires 317.1350.

(206 mg, 84%) as a colourless oil, R_f0.46 in 9:1 light petroleum/

23

ether, [

a]

þ8.8 (c 0.77 in CHCl₃); n_max/cm^ꢀ12951, 2930, 2907,

D

2872, 1459, 1374, 1260, 1099, 1017, 963 and 805; d_H(CDCl₃,

300 MHz) 0.76 (6H, q, J 8.0, 3ꢃ GeCH₂), 1.05 (9H, t, J 8.0, 3ꢃ

GeCH₂CH₃), 1.15 (3H, d, J 6.0, 6-H₃), 1.64 (2H, d, J 8.0, 1-H₂), 2.10 (1H,

dt, J 14.0, 6.5, 4-H), 2.29 (1H, dt, J 14.0, 7.0, 4-H⁰), 3.30 (1H, m, 5-H),

3.36 (3H, s, OCH₃) and 5.28 and 5.53 (each 1H, dt, J 15.0, 7.0, 2-H or

3-H); d_C(CDCl₃, 75 MHz) 4.1, 9.2,17.3, 19.1, 39.7, 56.2, 76.9,123.8 and

130.3; m/z (CI) 275 (M^þþ1, 1.5%), 273 (M^þþ1, 1.5), 271 (M^þþ1, 1),

178 (100), 176 (75) and 174 (50); HRMS: M^þ, found 274.1344.

4.2.10.5. (5R,2Z)-5-tert-Butyldimethylsilyloxyhex-2-enyl(triethyl)

germane [(Z)-24]. Triethylgermanium hydride (0.53 mL, 3.3 mmol)

t

and TMEDA (0.56 mL, 3.63 mmol) in THF (5 mL), BuLi (1.7 M in

pentane, 2.31 mL, 3.93 mmol), copper iodide (313 mg, 1.65 mmol)

and the (Z)-acetate (Z)-21 (450 mg, 1.65 mmol), after chromatog-

raphy using 2% ether in petrol as eluent, gave the title compound (Z)-

23

24 (575 mg, 93%) as a colourless oil, R_f0.69 in light petroleum, [

a

]

C

₁₃H₂₈⁷⁴GeO requires 274.1346.

D

þ2.89 (c 1.06 in CHCl₃); n_max/cm^ꢀ12960, 2931, 2905, 2872, 1644,

1462, 1256, 1129, 1089, 834 and 774; d_H(CDCl₃, 300 MHz) 0.10 (6H,

s, 2ꢃ SiCH₃), 0.78 (6H, q, J 8.0, 3ꢃ GeCH₂), 0.93 [9H, s, SiC(CH₃)₃],

1.06 (9H, t, J 8.0, 3ꢃ GeCH₂CH₃), 1.17 (3H, d, J 6.0, 6-H₃), 1.67 (2H, d, J

8.0, 1-H₂), 2.10e2.29 (2H, m, 4-H₂), 3.84 (1H, sext, J 6.0, 5-H), 5.25

(1H, dt, J 10.5, 7.0, 2-H), 5.55 (1H, dt, J 11.0, 10.5, 3-H); d_C(CDCl₃,

75 MHz) ꢀ4.4, ꢀ4.3, 4.3, 9.2, 13.3, 18.5, 23.8, 26.2, 37.5, 69.2, 123.1

and 128.4; m/z (CI) 375 (M^þþ1, 5%), 373 (M^þþ1, 3), 371 (M^þþ1, 2),

178 (90), 176 (100) and 174 (60); HRMS: M^þꢀC₂H₅, 345.1668.

4.2.10.9. (5R,2Z)-5-Methoxyhex-2-enyl(triethyl)germane

[(Z)-

26]. The (Z)-5-hydroxyhex-2-enylgermane (Z)-25 (147 mg,

0.57 mmol) in THF (2 mL) and sodium hydride (60% dispersion in

mineral oil, 45 mg, 0.68 mmol) in THF (1 mL), and methyl iodide

(177 mL, 2.85 mmol), after chromatography using light petroleum/

ether (60:1) as eluent, gave the title compound (Z)-26 (133 mg, 73%)

as a colourless oil, R_f0.52 in 9:1 light petroleum/ether, [

a

]

²³þ15.9 (c

D

0.96 in CHCl₃); n_max/cm^ꢀ12949, 2925, 2909, 2865, 1460, 1378, 1259,

1098, 1016 and 799; d_H(CDCl₃, 300 MHz) 0.74 (6H, q, J 8.0, 3ꢃ

GeCH₂), 1.03 (9H, t, J 8.0, 3ꢃ GeCH₂CH₃), 1.15 (3H, d, J 6.0, 6-H₃), 1.60

(2H, m, 1-H₂), 2.13 (1H, dt, J 10.0, 6.5, 4-H), 2.31 (1H, dt, J 10.0, 7.0, 4-

H⁰), 3.22 (1H, m, 5-H), 3.36 (3H, s, OCH₃) and 5.29 and 5.55 (each

1H, dt, J 10.0, 7.0, 2-H or 3-H); d_C(CDCl₃, 75 MHz) 4.3, 9.2, 17.4, 19.2,

39.7, 56.3, 77.0, 123.7 and 130.2; m/z (CI) 275 (M^þþ1, 40%), 273

(M^þþ1, 30), 271 (M^þþ1, 20), 178 (100), 176 (75) and 174 (50);

HRMS: M^þ, found 274.1347. C₁₃H₂₈⁷⁴GeO requires 274.1346.

C

₁₆H₃₅⁷⁴GeOSi requires 345.1663.

4.2.10.6. (5R,2E)-5-Hydroxyhex-2-enyl(triethyl)germane

[(E)-

25]. The standard procedure using tetra-n-butylammonium

ﬂuoride (1 M in THF, 3.9 mL, 3.9 mmol) and the silyl ether (E)-24

(0.94 g, 2.52 mmol) in THF (15 mL), after chromatography using

light petroleum/ether (4:1) as eluent, gave the title compound (E)-

25 (630 mg, 97%) as a colourless oil, R_f0.25 in 4:1 light petro-

23

leum/ether, [

a

]

ꢀ8.0 (c 0.35 in CHCl₃); n_max/cm^ꢀ13404, 2950,

D

2905, 2872, 1655, 1460, 1374, 1326, 1017 and 964; d_H(CDCl₃,

300 MHz) 0.78 (6H, q, J 7.5, 3ꢃ GeCH₂), 1.06 (9H, t, J 7.5, 3ꢃ

GeCH₂CH₃), 1.21 (3H, d, J 6.0, 6-H₃), 1.64 (2H, d, J 8.0, 1-H₂), 2.05

(1H, dt, J 14.0, 7.5, 4-H), 2.23 (1H, dt, J 14.0, 6.5, 4-H⁰), 3.78 (1H, m,

5-H), 5.29 (1H, dt, J 15.0, 7.0, 2-H) and 5.57 (1H, dt, J 15.0, 8.0, 3-

H); d_C(CDCl₃, 75 MHz) 4.1, 9.1, 17.5, 22.8, 43.0, 67.6, 123.4 and

132.4; m/z (APCI) 260 (M^þ, 10%), 258 (M^þ, 8), 256 (M^þ, 5), 239

(40), 100 (50) and 79 (100); HRMS: M^þþH, found 261.1286.

4.2.10.10. (5R,2Z)-5-Hydroxyhex-2-enyl(tributyl)germane

[(Z)-

29]. The standard procedure using tributylgermanium hydride

(0.53 mL, 1.98 mmol) and TMEDA (0.34 mL, 2.2 mmol) in THF

(3 mL), ^tBuLi (1.7 M in pentane, 1.39 mL, 2.4 mmol), copper(I) iodide

(188 mg, 0.99 mmol) and the acetate (Z)-21 (270 mg, 0.99 mmol)

THF (2.5 mL) gave the 5-tert-butyldimethylsilyloxyhex-2-

enyl(tributyl)germane (Z)-28 as an oil used immediately without

chromatography, R_f0.69 in 2% ether in light petroleum, [

a

]

²¹þ8.0 (c

D

C

₁₂H₂₇⁷⁴GeO requires 261.1268.

1.10 in CHCl₃); n_max/cm^ꢀ12958, 2926, 2857, 2007, 1462, 1376, 1254,

1129, 1084, 1002, 835 and 775; d_H(CDCl₃, 500 MHz) 0.01 (6H, s, 2ꢃ

SiCH₃), 0.84 (9H, t, J 8.0, 3ꢃ CH₂CH₃), 0.93 [9H, s, SiC(CH₃)₃], 1.07

(3H, d, J 6.5, 6-H₃), 1.20-1.36 (18H, m, 9ꢃ CH₂), 1.56 (2H, d, J 9.0, 1-

H₂), 2.02e2.16 (2H, m, 4-H₂), 3.76 (1H, sext, J 6.0, 5-H) and 5.15 and

5.44 (each 1H, m, 2-H or 3-H); d_C(CDCl₃, 125 MHz) ꢀ4.7, ꢀ4.5, 12.1,

12.6, 13.8, 25.9, 26.1, 26.7, 27.6, 28.6, 37.3, 69.0, 122.8 and 128.3; m/z

(EI) 401 (M^þꢀ57, 20%) and 262 (100); HRMS: M^þꢀC₄H₉, found

401.2287. C₂₀H₄₃⁷⁴GeOSi requires 401.2289.

4.2.10.7. (5R,2Z)-5-Hydroxyhex-2-enyl(triethyl)germane

[(Z)-

25]. Tetra-n-butylammonium ﬂuoride (1

M

in THF, 2.2 mL,

2.2 mmol) and the silyl ether (Z)-24 (533 mg, 1.428 mmol) in THF

(9 mL), after chromatography using light petroleum/ether (3:1) as

eluent, gave the title compound (Z)-25 (350 mg, 95%) as a colourless

oil, R_f0.46 in 1:1 light petroleum/ether, [

a

]

²³þ21.1 (c 1.18 in CHCl₃);

D

n_max/cm^ꢀ13350, 2949, 2906, 2872, 1641, 1460, 1260, 1116, 1078,

1020 and 773; d_H(CDCl₃, 300 MHz) 0.79 (6H, q, J 8.5, 3ꢃ GeCH₂),

1.07 (9H, t, J 7.5, 3ꢃ GeCH₂CH₃), 1.26 (3H, d, J 6.5, 6-H₃), 1.63e1.80

(3H, m, 1-H₂and OH), 2.14e2.34 (2H, m, 4-H₂), 3.87 (1H, sext, J 6.5,

5-H), 5.28 (1H, dt, J 10.0, 7.5, 2-H) and 5.70 (1H, q, J 9.0, 3-H); d_C

(CDCl₃, 75 MHz) 4.3, 9.2, 13.4, 23.1, 37.1, 68.2, 122.0 and 130.7; m/z

(CI) 261 (M^þþ1, 6%), 259 (M^þþ1, 5), 257 (M^þþ1, 4), 178 (100) and

The standard procedure using tetra-n-butylammonium ﬂuoride

(1 M in THF, 1.95 mL, 1.95 mmol) and the crude silyl ether (Z)-28 in

THF (8 mL), after chromatography using light petroleum/ether (9:1),

gave the title compound (Z)-29 (235 mg, 78% over the two steps) as

23

a colourless oil, R_f0.17 in 9:1 light petroleum/ether, [

a

]

þ17.5 (c

D

1.14 in CHCl₃); n_max/cm^ꢀ13340, 2958, 2938, 2872, 2856, 1643, 1461,

E.J. Thomas, A.P. Weston / Tetrahedron 70 (2014) 7253e7267

7265

1376, 1260, 1118, 1081, 1027 and 881; d_H(CDCl₃, 400 MHz) 0.73 (6H,

m, 3ꢃ CH₂), 0.89 (9H, t, J 7.0, 3ꢃ CH₃), 1.19 (3H, d, J 7.0, 6-H₃),

1.25e1.49 (12H, m, 6ꢃ CH₂), 1.57 (1H, br s, OH), 1.62 (1H, dd, J 12.0,

8.0, 1-H), 1.70 (1H, dd, J 12.0, 9.0, 1-H⁰), 2.10e2.28 (2H, m, 4-H₂), 3.80

(1H, m, 5-H), 5.23 (1H, dt, J 9.5, 8.0, 2-H) and 5.64 (1H, dt, J 10.0, 9.0,

3-H); d_C(CDCl₃, 100 MHz) 12.5, 13.7, 14.2, 22.8, 26.5, 27.4, 36.8, 67.8,

121.6 and 130.5; m/z (CI) 345 (M^þþ1, 5%) and 260 (100): HRMS: M^þ,

found 344.2125. C₁₈H₃₈⁷⁴GeO requires 344.2129.

73%) as a colourless oil, 19d/32d¼91:9, [

a

]

²¹þ91.7 (c 1.44 in CHCl₃);

D

n_max/cm^ꢀ13350, 3015, 2968, 2926, 1491, 1406, 1090, 1067, 1013 and

830; d_H(CDCl₃, 300 MHz) major 19d 1.23 (3H, d, J 6.0, 7-H₃), 1.23

(1H, dt, J 13.5, 3.5, 2-H or 5-H), 2.26e2.40 (2H, m, 2ꢃ 2-H or 5-H),

2.60 (1H, dt, J 14.0, 8.5, 2-H or 5-H), 3.85 (1H, m, 6-H), 4.68 (1H, dd, J

9.0, 4.0, 1-H), 5.56e5.72 (2H, m, 3-H and 4-H) and 7.33 (4H, m ArH);

minor 32d 4.79 (1H, dd, J 6.5, 4.5, 1-H); d_C(CDCl₃, 75 MHz) 23.5,

36.8, 37.5, 67.4, 72.8, 127.2, 128.1, 128.4, 129.6, 133.0 and 143.0; m/z

(CI) 260 (M^þþ18, 33%) and 258 (M^þþ18, 100); HRMS: M^þþNH₄,

found 258.1263. C₁₃H₂₁³⁵ClNO₂requires 258.1255.

4.2.11. Tin(IV) halide promoted reactions of hex-2-enylgermanes with

aldehydes

4.2.11.5. (1R,6R,3Z)-1-(3-Chlorophenyl)hept-3-ene-1,6-diol

(19e). Tin(IV) bromide (89 mg, 0.2 mmol) in DCM (0.65 mL), (Z)-

hex-2-enyl(triethyl)germane (Z)-25 (44 mg, 0.17 mmol) in DCM

4.2.11.1. (1R,6R,3Z)-1-Phenylhept-3-ene-1,6-diol

standard procedure using tin(IV) bromide (89 mg, 0.2 mmol) in

DCM (0.65 mL), the (Z)-hex-2-enyl(triethyl)germane (Z)-25 (44 mg,

0.17 mmol) in DCM (0.8 mL) and benzaldehyde (58 mL, 0.5 mmol),

(19a). The

(0.8 mL) and 3-chlorobenzaldehyde (58

mL, 0.35 mmol), after

chromatography using ether/light petroleum (3:1) as eluent gave

the title compound 19e (34 mg, 83%) as a pale yellow oil, 19e/

after chromatography using ether/light petroleum (3:1) as eluent,

gave the title compound 19a¹(28 mg, 80%) as a colourless oil, 19a/

32a¼94:6 (¹H NMR; 19a, 1-H, 4.68; 32a, 1-H, 4.77¹), R_f0.46 in ether.

Similarly the (Z)-hex-2-enyl(tributyl)germane (Z)-29 (52 mg,

0.17 mmol) in DCM (0.8 cm) gave the title compound 19a (27 mg,

78%) as a colourless oil, 19a/32a¼92:8.

21

32e¼93:7 (¹H and ¹³C NMR), R_f0.55 in ether, [

a

]

D

þ68 (c 1.33 in

CHCl₃); n_max/cm^ꢀ13351, 3015, 2968, 2925, 1598, 1574, 1432, 1063,

885, 844, 787 and 697; d_H(CDCl₃, 300 MHz) major 19e 1.23 (3H, d, J

6.0, 7-H₃), 2.13 (1H, dt, J 13.0, 3.5, 2-H or 5-H), 2.25e2.42 (2H, m, 2ꢃ

2-H or 5-H), 2.60 (1H, dt, J 14.5, 8.5, 2-H or 5-H), 3.00e3.27 (2H, br s,

2ꢃ OH), 3.85 (1H, m, 6-H), 4.67 (1H, m, 1-H), 5.59e5.71 (2H, m, 3-H

and 4-H), 7.21e7.36 (3H, m, ArH) and 7.40 (1H, s, ArH); minor 32e

4.79 (1H, m, 1-H); d_C(CDCl₃, 75 MHz) major 19e 23.7, 37.0, 37.8,

67.6, 73.0, 124.2, 126.2, 127.7, 128.3, 129.9, 134.5 and 147.0; minor

32e 23.2, 36.6 and 72.7; m/z (CI) 260 (M^þþ18, 30%), 258 (M^þþ18,

100), 242 (M^þ, 40), 240 (M^þ, 76) and 223 (70); HRMS: M^þ, found

240.0908. C₁₃H₁₇³⁵ClO₂requires 240.0912.

Similarly the (E)-hex-2-enyl(triethyl)germane (E)-25 (44 mg,

0.17 mmol) in DCM (0.8 mL) gave the title compound 19a (22 mg,

63%) as a colourless oil, 19a/32a¼89:11, R_f0.46 in ether, [

a

]

²²þ65 (c

D

1.15 in CHCl₃), lit.¹[

a]

²⁰þ75 (c 1.26 in CHCl₃).

D

4.2.11.2. (2R,7R,4Z)-8-Methylnon-4-ene-2,7ediol (19b). Tin(IV)

bromide (89 mg, 0.2 mmol) in DCM (0.65 mL), (Z)-hex-2-

enyl(triethyl)germane (Z)-25 (44 mg, 0.17 mmol) in DCM (0.8 mL)

and 2-methylpropanal (50 mL, distilled, 0.5 mmol), after chroma-

4.2.11.6. (1R,6R,3Z)-1-(4-Nitrophenyl)hept-3-ene-1,6-diol

(19f). Tin(IV) bromide (89 mg, 0.2 mmol) in DCM (0.6 mL), (Z)-hex-

2-enyl(triethyl)germane (Z)-25 (44 mg, 0.17 mmol) and 4-

nitrobenzaldehyde (77 mg, 0.5 mmol) in DCM (0.3 mL), after

chromatography using ether/light petroleum (3:1) as eluent gave

title compound 19f¹(35 mg, 81%) as a yellow oil, 19f/32f¼91:9 (¹H

tography using ether/light petroleum (3:1) as eluent, gave the title

compound 19b¹(24 mg, 82%) as a colourless oil, 19b/32b¼93:7 (¹³

C

NMR), R_f0.41 in ether.

Similarly the (E)-hex-2-enyl(triethyl)germane (E)-25 (44 mg,

0.17 mmol) in DCM (0.8 mL) gave the title compound 19b (15 mg,

51%) as a colourless oil, 19b/32b¼91:9, [

a

]

D

²³þ10.2 (c 0.90 in CHCl₃).

NMR), R_f0.32 in ether, [

a

]

²³þ84 (c 1.57 in CHCl₃), lit.¹[

a

]

²⁰þ94 (c

D

0.8 in CHCl₃); HRMS: M^þ, found 251.1152. C₁₃H₁₇NO₄requires

251.1152.

4.2.11.3. (2R,7S,4Z)-Dec-4-ene-2,7-diol (19c). Tin(IV) bromide

(89 mg, 0.2 mmol) in DCM (0.65 mL), the (Z)-hex-2-enyl(triethyl)

germane (Z)-25 (44 mg, 0.17 mmol) in DCM (0.8 mL) and butanal

4.2.11.7. (2R,7R,4Z,8E)-Deca-4,8-diene-2,7-diol

(19g). Tin(IV)

(45 mL, 0.45 mol), after chromatography using ether/light petro-

bromide (89 mg, 0.2 mmol) in DCM (0.65 mL), (Z)-hex-2-

enyl(triethyl)germane (Z)-25 (44 mg, 0.17 mmol) in DCM (0.8 mL)

and (E)-but-2-enal (42 mL, 0.5 mmol), after chromatography using

leum (3:1) as eluent, gave the title compound 19c (22 mg, 75%) as

a colourless oil, 19c/32c¼93:7 (¹³C NMR), R_f0.45 in ether.

Similarly the (Z)-hex-2-enyl(tributyl)germane (Z)-29 (52 mg,

0.17 mmol) in DCM (0.8 mL) gave the title compound 19c (20 mg,

ether/light petroleum (3:1) as eluent, gave the title compound 19g

(21 mg, 73%) as a colourless oil, 19g/32g¼92:8 (¹³C NMR), R_f0.47 in

68%) as a colourless oil, 19c/32c¼90:10, [

a

]

²³þ7.2 (c 1.34 in CHCl₃);

D

22

n_max/cm^ꢀ13349, 2961, 2931, 2873, 1459, 1374, 1122, 1075, 1023, 943,

846 and 714; d_H(CDCl₃, 500 MHz) 0.96 (3H, t, J 7.0, 10-H₃), 1.25 (3H,

d, J 6.0, 1-H₃), 1.36e1.56 (4H, m, 2ꢃ CH₂), 2.18 and 2.30 (each 2H, m,

3-H₂or 6-H₂), 2.50 (2H, br s, 2ꢃ OH), 3.67 (1H, m, 7-H), 3.87 (1H, m,

2-H) and 5.61e5.66 (2H, m, 4-H and 5-H); d_C(CDCl₃, 75 MHz) major

19c 14.3, 19.2, 23.6, 35.5, 37.2, 39.8, 67.8, 71.2, 129.1 and 129.3;

minor 32c 23.2, 35.2, 36.9, 39.3, 125.8 and 128.8; m/z (CI) 190

(M^þþ18, 100%); HRMS: M^þþNH₄, found 190.1800. C₁₀H₂₄NO₂re-

quires 190.1802.

ether, [

a]

þ12.8 (c 1.54 in CHCl₃); n_max/cm^ꢀ13350, 3015, 2967,

D

2919, 1673, 1451, 1316, 1077, 1120, 1045, 966 and 722; d_H(CDCl₃,

300 MHz) 1.22 (3H, d, J 6.5,1-H₃),1.73 (3H, d, J 6.0,10-H₃), 2.10e2.49

(6H, m, 3-H₂, 6-H₂and 2ꢃ OH), 3.83 (1H, m, 2-H), 4.12 (1H, m, 7-H)

and 5.45e5.77 (4H, m, 4-H, 5-H, 8-H and 9-H); d_C(CDCl₃, 75 MHz)

major 19g 17.9, 23.5, 35.6, 37.3, 67.7, 72.4, 127.0, 128.8, 129.0 and

134.0; minor 32g 37.0; m/z (CI) 188 (M^þþ18, 20%), 170 (M^þ, 38) and

153 (100): HRMS: M^þ, found 170.1298. C₁₀H₁₈O₂requires 170.1301.

4.2.11.8. (2R,7R,4Z,8E)-9-Phenylnona-4,8-diene-2,7-diol

(19h). Tin(IV) bromide (89 mg, 0.2 mmol) in DCM (0.65 mL), (Z)-

hex-2-enyl(triethyl)germane (Z)-25 (44 mg, 0.17 mmol) in DCM

(0.8 mL) and trans-cinnamaldehyde (64 mL, 0.5 mmol), after

chromatography using ether/light petroleum (3:1) gave the title

4.2.11.4. (1R,6R,3Z)-1-(4-Chlorophenyl)hept-3-ene-1,6-diol

(19d). Tin(IV) bromide (89 mg, 0.2 mmol) in DCM (0.6 mL), (Z)-hex-

2-enyl(triethyl)germane (Z)-25 (44 mg, 0.17 mmol) in DCM (0.7 mL)

and 4-chlorobenzaldehyde (72 mg, 0.5 mmol) in DCM (0.3 mL),

after chromatography using ether/light petroleum (3:1) as eluent,

gave the title compound 19d (33 mg, 81%) as a colourless oil, 19d/

32d¼92:8 (¹H NMR), R_f0.34 in ether.

compound 19h (32 mg, 81%) as a colourless oil, 19h/32h¼91:9 (¹H

and ¹³C NMR), R_f0.42 in ether, [

a

]

þ41.5 (c 1.36 in CHCl₃); n_max

/

21

D

cm^ꢀ13351, 3024, 2967, 2927,1657,1450,1071,1046, 967 and 750; d_H

(CDCl₃, 300 MHz) major 19h 1.27 (3H, d, J 6.5, 1-H₃), 2.10 (1H, m, 3-

H or 6-H), 2.25e2.42 (2H, m, 2ꢃ 3-H or 6-H), 2.52 (1H, dt, J 14.0, 8.5,

Similarly the (Z)-hex-2-enyl(tributyl)germane (Z)-29 (52 mg,

0.17 mmol) in DCM (0.7 mL) gave the title compound 19d (30 mg,

7266

E.J. Thomas, A.P. Weston / Tetrahedron 70 (2014) 7253e7267

3-H⁰or 6-H⁰), 2.85 (2H, br s, 2ꢃ OH), 3.90 (1H, m, 2-H), 4.38 (1H, m,

7-H), 5.63 (2H, m, 4-H and 5-H), 6.29 (1H, dd, J 16.0, 6.0, 8-H), 6.29

(1H, d, J 16.0, 9-H) and 7.23e7.44 (5H, m, ArH); minor 32h 4.43 (1H,

m, 7-H); d_C(CDCl₃, 75 MHz) major 19h 23.6, 35.7, 37.2, 67.7, 72.3,

126.7, 127.9, 128.5, 128.8, 129.5, 130.3, 132.3 and 137.0; minor 32h

23.2, 35.4, 36.9 and 72.1; m/z (CI) 250 (M^þþ18, 25%), 232 (M^þ, 24%)

and 215 (100); HRMS: M^þ, 232.1454. C₁₅H₂₀O₂requires 232.1458.

(40 mL) were added and the mixture extracted using ether

(3ꢃ30 mL). The organic extracts were washed with water (30 mL)

and brine (30 mL), then dried (MgSO₄) before concentration under

reduced pressure. Chromatography of the residue using light pe-

troleum/ether (9:1) yielded 4-tert-butyldimethylsilyloxypentanal

37 (1.24 g, 93%) as a colourless oil, R_f0.41 in 9:1 light petroleum/

23

ether, [

a]

þ13.5 (c 1.42 in CHCl₃); n_max/cm^ꢀ12957, 2937, 2858,

D

2361, 1728, 1257, 1097, 1045, 835 and 774; d_H(CDCl₃, 300 MHz) 0.06

and 0.08 (each 3H, s, SiCH₃), 0.92 [9H, s, SiC(CH₃)₃], 1.18 (3H, d, J 6.0,

5-H₃), 1.66e1.89 (2H, m, 3-H₂), 2.48e2.56 (2H, m, 2-H₂), 3.90 (1H,

m, 4-H) and 9.81 (1H, t, J 2.0, CHO); d_C(CDCl₃, 75 MHz) ꢀ4.6, ꢀ4.1,

18.3, 23.9, 26.1, 31.9, 40.4, 67.7 and 203.1; m/z (CI) 233 (42%) and 217

(M^þþ1, 100).

4.2.11.9. (1R,6R,3Z)-6-Methoxy-1-phenylhept-3-en-1-ol

(20a). Tin(IV) bromide (89 mg, 0.2 mmol) in DCM (0.65 mL), (Z)-

hex-2-enyl(triethyl)germane (Z)-26 (46 mg, 0.17 mmol) in DCM

(0.8 mL) and benzaldehyde (60 mL, 0.5 mmol), after chromatogra-

phy using light petroleum/ether (2:1), gave the title compound

20a¹(35 mg, 94%) as a pale yellow oil, 20a/33a¼94:6 (¹H NMR; 20a,

1-H, 4.76, dd; 33a, 1-H, 4.82, t¹), R_f0.33 in 1:1 ether/light

petroleum.

A solution of bis(2,2,2-triﬂuoroethyl) (methoxycarbonylmethyl)

phosphonate (95%, 1.25 mL, 11.1 mmol) and 18-crown-6 (7.23 g,

22.2 mmol) in THF (100 mL) was cooled to ꢀ78 ^ꢁC. Potassium

hexamethyldisilazide (0.5 M in toluene, 10.9 mL, 5.5 mmol) was

added. After 5 min, the aldehyde 37 (1.2 g, 5.55 mmol) in THF

(19 mL) was added dropwise so that the temperature remained

below ꢀ60 ^ꢁC. The reaction mixture was stirred for 30 min at

ꢀ78 ^ꢁC before saturated aqueous ammonium chloride (18 mL) and

water (50 cm) were added. The mixture was extracted using ether

(3ꢃ50 mL) and the organic extracts were washed with water

(50 mL) and brine (50 mL) then dried (MgSO₄). After concentration

under reduced pressure, chromatography of the residue using 2%

Similarly, the (E)-hex-2-enyl(triethyl)germane (E)-26 (46 mg,

0.17 mmol) in DCM (0.8 mL) gave the title compound 20a (31 mg,

21

83%) as a pale yellow oil, 20a/33a¼86:14, [

a

]

þ88 (c 0.96 in

D

CHCl₃), lit.¹[

a

]

²⁰þ95 (c 0.9 in CHCl₃).

D

4.2.11.10. (4S,9R,6Z)-9-Methoxydec-6-en-4-ol

(20b). Tin(IV)

bromide (107 mg, 0.24 mmol) in DCM (0.8 mL), (Z)-hex-2-

enyl(triethyl)germane (Z)-26 (56 mg, 0.205 mmol) in DCM

(0.9 mL) and butanal (55 mL, 0.6 mmol), after chromatography using

light petroleum/ether (2:1) as eluent, gave the title compound 20b

ether in light petroleum gave the title compound 38 (1.06 g, 70%), R_f

(23 mg, 61%) as a pale yellow oil, 20b/33b¼90:10 (¹³C NMR), R_f0.33

0.16 in 2% ether in light petroleum, [

a

]

þ14.9 (c 1.37 in CHCl₃);

23

D

21

in 1:1 ether/light petroleum, [

a]

þ12.9 (c 1.55 in CHCl₃); n_max

/

n_max/cm^ꢀ12956, 2931, 2858, 1730, 1647, 1439, 1257, 1174, 1092, 1041,

1007, 835 and 775; d_H(CDCl₃, 300 MHz) 0.08 (6H, s, 2ꢃ SiCH₃), 0.91

[9H, s, SiC(CH₃)₃], 1.18 (3H, d, J 6.0, 7-H₃), 1.51e1.66 (2H, m, 5-H₂),

2.68e2.78 (2H, m, 4-H₂), 3.74 (3H, s, OCH₃), 3.87 (1H, sext, J 6.0, 6-

H), 5.80 (1H, dt, J 11.5, 2.0, 2-H) and 6.28 (1H, dt, J 11.5, 7.5, 3-H); d_C

(CDCl₃, 75 MHz) ꢀ4.5, ꢀ4.1, 18.4, 24.0, 26.0, 26.1, 39.1, 51.3, 68.5,

119.4, 151.0 and 167.1; m/z (CI) 290 (M^þþ18, 10%) and 273 (M^þþ1,

100); HRMS: M^þþNH₄, found 290.2149. C₁₄H₃₂NO₃Si requires

290.2146. The second fraction was the (E)-isomer of the title

compound (52 mg, 3%), R_f0.10 in 2% ether in light petroleum.

D

cm^ꢀ13417, 2960, 2928, 2872, 1463, 1376, 1262, 1094, 1024 and 807;

d_H(CDCl₃, 500 MHz) 0.87 (3H, t, J 7.0, 1-H₃), 1.09 (3H, d, J 6.0, 10-H₃),

1.27e1.50 (4H, m, 2-H₂and 3-H₂), 2.03e2.13 (2H, m, 2ꢃ 5-H or 8-

H), 2.15e2.23 (2H, m, 5-H or 8-H and OH), 2.31 (1H, dt, J 14.0, 7.5,

5-H or 8-H), 3.25 (3H, s, OCH₃), 3.29 (1H, m, 4-H), 3.53 (1H, m, 9-H)

and 5.45e5.55 (2H, m, 6-H and 7-H); d_C(CDCl₃, 125 MHz) major

20b 13.1, 17.9, 18.0, 33.6, 34.4, 38.4, 55.1, 69.8, 75.4, 126.9 and

128.08; minor 33b 32.9, 34.2, 38.1, 126.6 and 127.5; m/z (CI) 206

(M^þþ18, 6%) and 187 (M^þþ1, 100); HRMS: M^þþH, found 187.1695.

C

₁₁H₂₃O₂requires 187.1698.

4.2.13. (6S,2Z)-6-tert-Butyldimethylsilyloxyhept-2-en-1-ol (39). Di-

isobutylaluminium hydride (1 M in hexanes, 9 mL, 9.0 mmol) was

added to the ester 38 (1.01 g, 3.71 mmol) in DCM (11 mL) at ꢀ78 ^ꢁC

and the solution stirred at ꢀ78 ^ꢁC for 45 min then at ꢀ40 ^ꢁC for 1 h.

Saturated aqueous potassium/sodium tartrate (8 mL) and ether

(25 mL) were added and the solution stirred at rt overnight. The

organic extracts were washed with water (20 mL) and brine

(20 mL), dried (MgSO₄) and concentrated under reduced pressure.

Chromatography of the residue using light petroleum/ether (4:1) as

eluent gave the title compound 39 (0.87 g, 96%) as a colourless oil, R_f

4.2.11.11. (1R,6R,3Z)-1-(4-Chlorophenyl)-6-methoxyhept-3-en-1-

ol (20d). Tin(IV) bromide (67 mg, 0.14 mmol) in DCM (0.5 mL), (Z)-

hex-2-enyl(triethyl)germane (Z)-26 (31 mg, 0.11 mmol) in DCM

(0.6 mL) and 4-chlorobenzaldehyde (54 mg, 0.33 mmol) in DCM

(0.3 mL), after chromatography using ether/light petroleum (3:10)

as eluent, gave the title compound 20d (25 mg, 86%) as a yellow oil,

20d/33d¼95:5 (¹³C NMR), R_f0.32 in ether, [

a

]

²¹þ91 (c 1.38, CHCl₃);

D

n_max/cm^ꢀ13410, 2972, 2930, 2825, 1491, 1377, 1135, 1089, 1014, 877,

830 and 724; d_H(CDCl₃, 500 MHz) 1.09 (3H, d, J 6.5, 7-H₃), 2.03 (1H,

dt, J 14.0, 6.0, 2-H or 5-H), 2.25e2.33 (2H, m, 2ꢃ 2-H or 5-H), 2.45

(1H, dt, J 14.0, 9.0, 2-H or 5-H), 3.25 (3H, OCH₃), 3.29 (1H, m, 6-H),

4.60 (1H, dd, J 9.5, 4.0, 1-H), 5.45e5.59 (2H, m, 3-H and 4-H) and

7.21e7.27 (4H, m, ArH); d_C(CDCl₃, 125 MHz) major 20d 18.8, 34.6,

37.9, 56.1, 72.6, 76.4, 127.2, 128.4, 129.8, 132.7 and 143.1; minor 33d

128.1; m/z (CI) 274 (M^þþ18, 4%), 272 (M^þþ18, 13), 256 (M^þ, 6), 254

(M^þ, 18), 239 (35) and 237 (100); HRMS: M^þ, found 254.1065.

0.46 in 2:1 light petroleum/ether, [

a]

²¹þ13.3 (c 1.41 in CHCl₃); n_max

/

D

cm^ꢀ13340, 3016, 2957, 2938, 2858, 1657, 1462, 1375, 1255, 1137,

1093, 1053, 1004, 835 and 775; d_H(CDCl₃, 300 MHz) 0.08 (6H, s, 2ꢃ

SiCH₃), 0.92 [9H, s, SiC(CH₃)₃],1.18 (3H, d, J 6.0, 7-H₃),1.44e1.56 (2H,

m, 4-H₂) 1.63 (1H, br s, OH), 2.02e2.26 (2H, m, 5-H₂), 3.85 (1H, sext,

J 6.0, 6-H), 4.22 (2H, d, J 6.0, 1-H₂) and 5.54e5.68 (2H, m, 2-H and 3-

H); d_C(CDCl₃, 75 MHz) ꢀ4.5, ꢀ4.1,18.4, 24.0(2), 26.1, 39.8, 58.8, 68.4,

128.7 and 133.1; m/z (CI) 245 (M^þþ1, 100%) and 227 (M^þꢀ17, 43);

HRMS: M^þꢀOH, found 227.1826. C₁₃H₂₇OSi requires 227.1826.

C

₁₄H₁₉³⁵ClO₂requires 254.1068.

4.2.12. Methyl (6S,2Z)-6-tert-butyldimethylsilyloxyhept-2-enoate

(38). Dimethyl sulfoxide (0.89 mL, 12.3 mmol) in DCM (3 mL)

was added to oxalyl chloride (0.84 mL, 9.3 mmol) in DCM (3 mL) at

ꢀ78 ^ꢁC and the solution was stirred for 3 min at ꢀ78 ^ꢁC before the

addition of the 4-tert-butyldimethylsilyloxypentanol 36 (1.35 g,

6.19 mmol) in DCM (6 mL). The solution was stirred for 15 min at

ꢀ78 ^ꢁC before the addition of triethylamine (4.4 mL, 16.0 mmol).

The reaction mixture was allowed to warm to rt and stirred for

30 min. Saturated aqueous ammonium chloride (5 mL) and water

4.2.14. (6S,2Z)-6-tert-Butyldimethylsilyloxyhept-2-en-1-yl

acetate

(40). Acetic anhydride (0.38 mL, 3.9 mmol) was added to the al-

cohol 39 (0.87 g, 3.57 mmol) in pyridine (0.9 mL, 10.7 mmol) and

the solution stirred at rt overnight. Ether (30 mL) was added and

the organic extract washed with water (20 mL), aqueous hydrogen

chloride (0.1 M, 20 mL) and saturated aqueous sodium bicarbonate

(20 mL), then dried (MgSO₄) and concentrated under reduced

pressure. Chromatography of the residue using light petroleum/

E.J. Thomas, A.P. Weston / Tetrahedron 70 (2014) 7253e7267

7267

ether (9:1) as eluent gave the title compound 40 (0.91 mg, 89%) as

under reduced pressure. Chromatography of the residue using light

23

a colourless oil, R_f0.35 in 9:1 light petroleum/ether, [

a

]

þ17.5 (c

petroleum/ether (12:1) as eluent gave the title compound 43¹⁹

D

1.20 in CHCl₃); n_max/cm^ꢀ12955, 2932, 2889, 2858, 1731, 1664, 1257,

1162, 1093, 836 and 777; d_H(CDCl₃, 300 MHz) 0.06 and 0.07 (each

3H, s, SiCH₃), 0.92 [9H, s, SiC(CH₃)₃], 1.17 (3H, d, J 6.0, 7-H₃),

1.45e1.57 (2H, m, 4-H₂), 2.10 (1H, s, CH₃CO) 2.10e2.30 (2H, m, 5-

H₂), 3.84 (1H, sext, J 6.0, 6-H), 4.65 (2H, d, J 6.5, 1-H₂), 5.56 (1H,

dt, J 11.0, 7.0, 3-H) and 5.68 (1H, dt, J 11.0, 7.5, 2-H); d_C(CDCl₃,

75 MHz) ꢀ4.5, ꢀ4.1,18.4, 21.3, 24.0, 24.2, 26.1, 39.6, 60.6, 68.3,123.6,

135.5 and 171.3; m/z (CI) 287 (M^þþ1, 100%); HRMS: M^þ, found

286.1963. C₁₅H₃₀O₃Si requires 286.1959.

(19 mg, 55%) as a pale yellow oil, R_f0.47 in 9:1 light petroleum/

23

ether, [

a]

þ20.3 (c 1.54 in CHCl₃); n_max/cm^ꢀ12970, 2930, 2851,

D

1640, 1452, 1117, 1069, 912, 756 and 698; d_H(CDCl₃, 500 MHz) 1.75

(3H, d, J 6.0, 6-CH₃), 1.39 and 1.52 (each 1H, m, 4-H), 1.67 (1H, ddt, J

13.5, 3.5, 2.5, 5-H),1.88 (1H, dtd, J 13.5, 3.5, 3.0, 5-H⁰), 2.25 (1H, m, 3-

H), 3.59 (1H, dqd, J 11.0, 6.0, 2.0, 6-H), 4.02 (1H, d, J 10.0, 2-H),

4.73e4.78 (2H, m, 2⁰-H₂), 5.38 (1H, ddd, J 17.0, 11.0, 7.5, 1⁰-H) and

7.15e7.24 (5H, m, ArH); d_C(CDCl₃, 125 MHz) 22.2, 30.0, 33.1, 46.3,

74.2, 84.9, 115.3, 127.6(2), 128.1, 139.0 and 141.3; m/z (CI) 220

(M^þþ18, 100%) and 203 (M^þþ1, 15); HRMS: M^þþNH₄, found

220.1701. C₁₄H₂₂NO requires 220.1696.

4.2.15. (6S,2Z)-6-Hydroxyhept-2-en-1-yl(triethyl)germane (42). The

standard procedure using triethylgermanium hydride (0.53 mL,

3.3 mmol), TMEDA (0.56 mL, 3.63 mmol) in THF (5 mL), ^tBuLi (1.7 M

in pentane, 2.31 mL, 3.93 mmol), copper(I) iodide (313 mg,

1.65 mmol) and the acetate 40 (473 mg 1.65 mmol) in THF (4 mL),

after concentration under reduced pressure, gave the 6-tert-

Acknowledgements

We thank the Engineering and Physical Sciences Research

Council for a studentship (to A.W.) and P. Casteno for preliminary

studies.

butyldimethylsilyloxyhept-2-en-1-yl(triethyl)germane

41

(754 mg) as an oil, used without further puriﬁcation, R_f0.5 in light

23

petroleum, [

a

]

þ13.2 (c 1.16 in CHCl₃); d_H(CDCl₃, 300 MHz) 0.09

D

(6H, s, 2ꢃ SiCH₃), 0.77 (6H, q, J 8.0, 3ꢃ GeCH₂), 0.93 [9H, s,

SiC(CH₃)₃], 1.06 (9H, t, J 8.0, 3ꢃ GeCH₂CH₃), 1.17 (3H, d, J 6.0, 7-H₃),

1.38e1.57 (2H, m, 4-H₂), 1.67 (2H, d, J 8.0, 1-H₂), 2.00 and 2.15 (each

1H, m, 5-H), 3.83 (1H, sext, J 6.0, 6-H), 5.22 (1H, dt, J 10.5, 7.0, 2-H or

3-H) and 5.47 (1H, dt, J 10.5, 9.0, 3-H or 2-H); m/z (CI) 389 (M^þþ1,

40%), 387 (M^þþ1, 30), 385 (M^þþ1, 25), 178 (100), 176 (60) and 174

(40); HRMS: M^þ, found 388.2222. C₁₉H₄₂⁷⁴GeOSi requires

388.2211.

Following the standard procedure, tetra-n-butylammonium

ﬂuoride (1 M in THF, 4.0 mL, 4.0 mmol) and the silyl ether 41

(754 mg, 1.95 mmol) in THF (9 mL), after chromatography using

light petroleum/ether (4:1) as eluent, gave the title compound 42

References and notes

1. Carey, J. S.; MacCormick, S.; Stanway, S. J.; Teerawutgulrag, A.; Thomas, E. J. Org.

Biomol. Chem. 20 1 1 , 9 , 3896.

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8476.

3. (a) Dorling, K.; Thomas, E. J. Org. Biomol. Chem. 2012 , 10 , 6995; (b) Martin, N.;

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Moore, C. J.; Thomas, E. J. Org. Biomol. Chem. 2012 , 10 , 9709.

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5. Hobson, L. A.; Thomas, E. J. Org. Biomol. Chem. 2012 , 10 , 7510.

6. For preliminary communications on this work see: (a) Casteno, P.; Thomas, E. J.;

Weston, A. Tetrahedron Lett. 200 7 , 48 , 337; (b) Thomas, E. J.; Weston, A. Tetra-

hedron Lett. 200 7 , 48 , 341.

^

7. (a) David-Quillot, F.; Lunot, S.; Marsacq, D.; Duchene, A. Tetrahedron Lett. 2000 ,

(331 mg, 73% over the two steps) as a colourless oil, R_f0.22 in 4:1

41 , 4905; (b) Mauze, B.; Ongoka, P.; Miginiac, L. J. Organomet. Chem. 1984 , 264 , 1.

8. For the formation of branched products from the stannane 1 using BF₃$Et₂O,

see Ref. 2 cf. 9.

9. Yamamoto, Y.; Yatagai, H.; Ishihara, Y.; Maeda, N.; Maruyama, K. Tetrahedron

1984 , 40 , 2239.

10. Yamaguchi, J.-i.; Tamada, Y.; Takeda, T. Bull. Chem. Soc. Jpn. 1993 , 66 , 607.

11. Yadav, J. S.; Sathaiah, K.; Srinivas, R. Tetrahedron 2009 , 65 , 3545.

12. Sun, C. Q.; Guillaume, D.; Dunlap, B.; Rich, D. H. J. Med. Chem. 1990 , 33 , 1443.

13. MacNeill, A. H.; Thomas, E. J. Synthesis 1994 , 322.

23

light petroleum/ether, [

a

]

þ3.06 (c 1.08 in CHCl₃); n_max/cm^ꢀ1

D

3340, 2960, 2871, 1642, 1460, 1424, 1129, 1078, 1019, 962 and 703;

d_H(CDCl₃, 500 MHz) 0.67 (6H, q, J 8.5, 3ꢃ GeCH₂), 0.95 (9H, t, J 7.5,

3ꢃ GeCH₂CH₃), 1.13 (3H, d, J 6.5, 7-H₃), 1.40e1.48 (2H, m, 5-H₂),

1.48e1.56 (1H, br s, OH), 1.58 (2H, d, J 8.0, 1-H₂), 1.97e2.12 (2H, m,

4-H₂), 3.77 (1H, sext, J 6.5, 6-H), 5.13 (1H, dt, J 10.5, 7.0, 2-H or 3-H)

and 5.41 (1H, q, J 9.0, 3-H or 2-H); d_C(CDCl₃, 75 MHz) 4.3, 9.2, 13.1,

23.7(2), 39.4, 68.3,126.1 and 127.7; m/z (CI) 178 (100%),176 (75) and

174 (60); HRMS: M^þ, 274.1351. C₁₃H₂₅⁷⁴GeO requires 274.1346.

14. Belelie, J. L.; Chong, M. J. J. Org. Chem. 2002 , 67 , 3000.

15. Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Soc. 1980 , 102 , 4743.

16. Simpson, T. J.; Soulas, F.; Willis, C. L. Synlett 2008 , 2196.

17. (a) Suh, Y.-G.; Jung, J.-K.; Seo, S.-Y.; Min, K.-H.; Shin, D.-Y.; Lee, Y.-S.; Kim, S.-H.;

Park, H.-J. J. Org. Chem. 2002 , 67 , 4127; (b) Kitahara, T.; Mori, K. Tetrahedron

1984 , 40 , 2935; (c) Kalivretenos, A.; Stille, J. K.; Hegedus, L. S. J. Org. Chem. 1991 ,

56 , 2883.

18. (a) Mulzer, J.; Berger, M. J. Org. Chem. 2004 , 69 , 891; (b) Sugai, T.; Katoh, O.;

Ohta, H. Tetrahedron 1995 , 54 , 1 1987.

19. Mohr, P. Tetrahedron Lett. 1995 , 36 , 2453.

20. 1,3-Isomerisations of alk-3-en-1-yltin trihalides to alk-1-en-3-yltin trihalides at

ꢀ78 ^ꢁC have been postulated to account for the chemistry of 5-alkoxypent-1-

en-3-ylstannanes on transmetallation using tin(IV) chloride; see Ref. 5. In the

present work, the increased time allowed for the transmetallation may allow

the reverse 1,3-isomerisation to take place under conditions for the more re-

mote 1,6- and 1,7-stereocontrol. The positions of equilibrium of these iso-

merisations may depend on the relative positions of the tin trihalide and co-

ordinating moieties

4.2.16. (2S,3R,6S)-3-Ethenyl-6-methyl-2-phenyltetrahydro-2H-pyran

(43). A cooled solution of tin(IV) bromide (89 mg, 0.2 mmol) in

DCM (0.65 mL) was added to the 6-hydroxyhept-2-enylgermane 42

(46 mg, 0.169 mmol) in DCM (0.80 mL) at ꢀ78 ^ꢁC and the solution

stirred at ꢀ78 ^ꢁC for 15 min before the addition of benzaldehyde

(60

m

L, 0.5 mmol). The reaction mixture was stirred at ꢀ78 ^ꢁC for

45 min before the addition of saturated methanolic ammonium

chloride (1 mL) and water (30 mL). The mixture was extracted using

ether (3ꢃ20 mL) and the organic extracts were washed with water

(20 mL) and brine (20 mL), then dried (MgSO₄) and concentrated

Article Doi

Open-chain remote stereocontrol using allylgermanes

DOI: 10.1016/j.tet.2014.06.053

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