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S. E. Gibson et al. / Tetrahedron 60 (2004) 6945–6958
from dark red to an opaque yellow-brown. Saturated
aqueous ammonium chloride (100 mL) was added with
stirring. The organic layer was decanted and the aqueous
layer was extracted with diethyl ether (3£100 mL). The
combined organic layers were washed with demineralised
water (200 mL), dried (MgSO4) and evaporated in vacuo to
afford a viscous brown oil. Upon addition of hexane,
triphenylphosphine oxide precipitated. It was removed by
vacuum filtration through Kieselguhr and the filtrate was
concentrated in vacuo. The precipitation, filtration and
evaporation steps were repeated until no further precipi-
tation of triphenylphosphine oxide occurred. Vacuum
distillation of the resultant oil gave the title compound 13
as a pale yellow oil [10.80 g, 34.18 mmol, 97%, (E):(Z)
1.5:1], bp 140–148 8C at ,1 mmHg [Found (MHþ):
317.0393. C13H19IO requires M, 317.0402]; nmax(neat)/
cm21 1650s (CvC), 1206s (C–O–C), 1108s (C–O);
dH(360 MHz) 1.31–1.39 [4H, m, (E)-ArCH2CH2CH2CH2–
CH], 1.53–1.63 [4H, m, (Z)-ArCH2CH2CH2CH2CH], 1.94
[2H, q, J¼7 Hz, (E)-CH2CvCH], 2.07 [2H, q, J¼7 Hz, (Z)-
CH2CvCH], 2.53 [4H, t, J¼7 Hz, (E)- and (Z)-ArCH2],
3.48 [3H, s, (E)-CH3], 3.56 [3H, s, (Z)-CH3], 4.30 [1H, q,
J¼8 Hz, (Z)-CHvCHOCH3], 4.69 [1H, dt, J¼8, 12 Hz,
(E)-CHvCHOCH3), 5.86 [1H, d, J¼8 Hz, (Z)-CHOCH3],
6.26 [1H, d, J¼12 Hz, (E)-CHOCH3], 6.90–6.92 [4H, m,
(E)- and (Z)-H-2 and H-6], 7.55–7.58 [4H, m, (E)- and (Z)-
H-3 and H-5); dC{1H} (90 MHz) 23.96, 29.6 [(Z)-ArCH2-
CH2CH2CH2CH], 27.9, 30.6 [(E)-ArCH2CH2CH2CH2CH],
31.0 [(E)-CH2CH], 31.2 [(Z)-CH2CH], 35.6 [(E)- and (Z)-
ArCH2], 56.3 [(E)-OCH3], 59.9 [(Z)-OCH3], 90.9, 91.0 [(E)-
and (Z)-C-4], 103.1 [(E)-CHvCHOCH3], 106.9 [(Z)-
CHvCHOCH3], 131.0 [(E)- and (Z)-C-2 and C-6], 137.6
[(E)- and (Z)-C-3 and C-5], 142.7, 142.9 [(E)- and (Z)-C-1],
146.6 [(Z)-CHOCH3], 147.5 [(E)-CHOCH3]; m/z (EI) 316
(Mþ, 100%), 284 (M2OCH3–H, 43).
used for 1a and 2a except that 1,3-di-iodobenzene and
5-hexen-1-ol (9.0 mL, 75.02 mmol, 1.5 equiv) were used.
The experiment afforded the title compounds 14c and 15c as
a pale yellow oil (7.75 g, 25.66 mmol, 51%; 78:22 linear to
branched aldehyde); spectroscopic data for 6-(3-iodo-
phenyl)hexanal 14c: nmax(neat)/cm21 1723vs (CvO);
dH(360 MHz) 1.35–1.72 (6H, m, ArCH2CH2CH2CH2CH2–
CHO), 2.46 (2H, dt, J¼7, 2 Hz, CH2CHO), 2.58 (2H, t,
J¼7 Hz, ArCH2), 7.02–7.04 (1H, m, H-5), 7.15–7.17 (1H,
m, H-6), 7.53–7.57 (2H, m, H-2 and H-4), 9.79 (1H, t,
J¼2 Hz, CHO); dC{1H} (90 MHz) 22.3, 29.1, 31.4
(ArCH2–CH2CH2CH2CH2CHO), 35.7 (ArCH2), 44.2
(CH2CHO), 95.1 (C-3), 128.1, 130.5, 135.2, 137.8 (C-2,
C-4, C-5, C-þ6), 145.3 (C-1), 203.0 (CHO); m/z (CI, NH3)
320 (MNH4 , 100), 194 (MNHþ4 –IþH, 2); discernible
spectroscopic data for 5-(3-iodophenyl)hexanal 15c:
dH(360 MHz) 1.21 [3H, d, J¼7 Hz, CH(CH3)], 1.37–1.54
(4H, m, CH2CH2CH2CHO), 2.46 (2H, dt, J¼7, 2 Hz,
CH2CHO), 2.61 [1H, q, J¼7 Hz, CH(CH3)], 7.05–7.06 (1H,
m, H-5), 7.17–7.18 (1H, m, H-6), 7.58–7.60 (2H, m, H-2
and H-4), 9.75 (1H, t, J¼2 Hz, CHO); dC{1H} (90 MHz)
20.6 (CH2CH2CH2CHO), 22.6 [CH(CH3)], 37.9 (CH2CH2-
CHO), 40.1 [CH(CH3)], 44.2 (CH2CHO), 94.9 (C-3), 126.7,
130.7, 135.6, 136.4 (C-2, C-4, C-5, C-6), 149.9 (C-1), 202.8
(CHO).
3.1.18. N-[6-(3-Iodophenyl)hexyl]serine methyl ester
16c. (^)-Serine methyl ester hydrochloride (2.32 g,
14.90 mmol, 1.5 equiv), 6-(3-iodophenyl)hexanal 14c and
5-(3-iodophenyl)hexanal 15c (3.0 g, 9.93 mmol, 1.0 equiv)
were introduced into a reaction vessel which contained
anhydrous magnesium sulfate (1.1 g) suspended in dry
DCM (19.9 mL, 0.5 M) under nitrogen. Triethylamine
(2.77 mL, 19.86 mmol, 2.0 equiv) was added and the
reaction was stirred at room temperature for 24 h. The
contents of the flask were transferred to another reaction
vessel via filter cannula under nitrogen and the filtrate was
evaporated in vacuo to give a yellow oil. The oil was
dissolved in dry methanol (19.9 mL, 0.5 M) and cooled to
0 8C under nitrogen. Sodium borohydride (0.75 g,
19.86 mmol, 2.0 equiv) was added portionwise and the
reaction was allowed to warm to room temperature and
stirred for 48 h. Work-up and purification as for 3a afforded
the title compound 16c as a white solid (1.80 g, 4.48 mmol,
45%), mp 34–35 8C (Found: C, 47.5; H, 6.1; N, 3.4.
C16H24INO3 requires C, 47.40; H, 5.97; N, 3.46%);
3.1.16. 6-(4-Iodophenyl)hexanal 1c. Formic acid (52 mL)
was added to a pale yellow solution of (E)- and (Z)-6-(4-
iodophenyl)-1-methoxyhex-1-ene 13 (8.6 g, 27.21 mmol) in
DCM (40 mL). Upon addition, the solution immediately
deepened to a bright yellow colour. The reaction was stirred
at room temperature in a foil covered vessel for 64 h.
Demineralised water (50 mL) was then added to the reaction
and the two layers were partitioned. The organic layer was
removed and the aqueous layer extracted with DCM
(2£100 mL). The combined organic layers were washed
with saturated aqueous sodium hydrogencarbonate
(2£50 mL) and sodium chloride (50 mL), dried (MgSO4)
and evaporated in vacuo to give the title compound 1c as a
pale yellow oil (7.0 g, 23.18 mmol, 85%) (Found: C, 47.4;
H, 4.8. C10H11IO requires C, 47.70; H, 5.00%); nmax(neat)/
cm21 1721vs (CvO); dH(360 MHz) 1.31–1.39 (2H, m,
ArCH2CH2CH2), 1.42–1.78 (4H, m, ArCH2CH2 and CH2–
CH2CHO), 2.43 (2H, dt, J¼8, 2 Hz, CH2CHO), 2.55 (2H, t,
J¼8 Hz, ArCH2), 6.91–6.94 (2H, m, H-2 and H-6), 7.58–
7.60 (2H, m, H-3 and H-5), 9.71 (1H, t, J¼2 Hz, CHO);
dC{1H} (90 MHz) 22.0, 28.8, 31.2 (ArCH2CH2CH2CH2–
CH2CHO), 35.3 (ArCH2), 43.0 (CH2CHO), 91.5 (C-4),
130.9 (C-2 and C-6), 137.8 (C-3 and C-5), 142.4 (C-1),
202.8 (CHO); m/z (CI, NH3) 320 (MNHþ4 , 100%).
n
max(CHCl3)/cm21 3600–3200br s (NH and OH), 1736vs
(CvO); dH(400 MHz) 1.25–1.55 (8H, m, ArCH2CH2CH2–
CH2CH2CH2N), 2.39–2.63 (4H, m, ArCH2 and CH2N),
3.29 (1H, dd, J¼7, 5 Hz, CHCO2CH3), 3.49 (1H, dd, J¼11,
7 Hz, CHHOH), 3.68 (3H, s, CO2CH3), 3.70 (1H, dd, J¼11,
5 Hz, CHHOH), 6.91–6.95 (1H, m, H-5), 7.04–7.06 (1H,
m, H-6), 7.42–7.46 (2H, m, H-2 and H-4); dC{1H}
(100 MHz) 26.4, 28.4, 29.5, 31.8 (ArCH2CH2CH2CH2CH2–
CH2N), 34.8 (ArCH2), 47.6 (CH2N), 51.6 (CO2CH3), 61.7
(CH2OH), 62.1 (CHCO2CH3), 93.9 (C-3), 127.1, 129.4,
134.1, 136.8 (C-2, C-4, C-5, C-6), 144.6 (C-1), 173.0
(CO2CH3); m/z (EI) 405 (Mþ, 11%), 374 (M2CH2OH, 50),
346 (M2CO2CH3, 84).
3.1.19. Methyl 2-{N-[(6-(3-iodophenyl)hexyl]-N-(tert-
butyloxycarbonyl)-amino}prop-2-enoate 17c. Di-tert-
butyl dicarbonate (3.17 g, 14.53 mmol, 1.1 equiv) was
3.1.17. 6-(3-Iodophenyl)hexanal 14c and 5-(3-iodo-
phenyl)hexanal 15c. The procedure was identical to that