Organolithium-induced synthesis of acyclic unsaturated amino alcohols from epoxides of dihydropyrroles and tetrahydropyridines

Article abstract of DOI:10.1016/j.tet.2003.10.010

The alkylative double ring-opening of Bus-protected 2,5-dihydropyrrole epoxides 13 and 29 with organolithiums to give 3-substituted 1-aminobut-3-en-2-ols 13-19 and 30-32 are described. Bus-protected tetrahydropyridine epoxide 38 reacts with organolithiums to give 4-substituted 1-aminobut-4-en-3-ols 39 and tetrahydropyridinol 40.

Full text of DOI:10.1016/j.tet.2003.10.010

Tetrahedron 59 (2003) 9729–9742
Organolithium-induced synthesis of acyclic unsaturated amino
alcohols from epoxides of dihydropyrroles
and tetrahydropyridines
a
b
David M. Hodgson,a Timothy J. Miles and Jason Witherington
,
*
aThe Dyson Perrins Laboratory, Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QY, UK
bNeurology and GI Centre of Excellence for Drug Discovery, GlaxoSmithKline Research Limited, New Frontiers Science Park,
Third Avenue, Harlow, Essex, CM19 5AW, UK
Received 2 July 2003; revised 3 September 2003; accepted 1 October 2003
Abstract—The alkylative double ring-opening of Bus-protected 2,5-dihydropyrrole epoxides 13 and 29 with organolithiums to give 3-substi-
tuted 1-aminobut-3-en-2-ols 13–19 and 30–32 are described. Bus-protected tetrahydropyridine epoxide 38 reacts with organolithiums to
give 4-substituted 1-aminobut-4-en-3-ols 39 and tetrahydropyridinol 40.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
dihydropyran epoxides 1 to generate unsaturated diols 2
(Scheme 2, X¼O).4,5 This process most likely proceeds via
a-deprotonation and insertion (possibly by a 1,2-metallate
shift)6 of a second equivalent of organolithium into the
resulting lithiated epoxide, followed by elimination.
Epoxides are versatile synthetic intermediates.1 Their
reactions are dominated by cleavage of the strained three-
membered ring by nucleophilic opening and acid or base-
induced isomerization reactions. The alkylative deoxygena-
tion of epoxides using organolithiums to give substituted
alkenes (Scheme 1) was originally discovered by Crandall
and Lin,2 and a number of research groups have sub-
sequently made contributions to this area.3
In connection with the above studies, we considered
whether the chemistry outlined in Scheme 2 could be
developed to provide unsaturated amino alcohols 2
(X¼NR1).7 The 1,2-amino alcohol motif is frequently
found in bioactive natural products, many pharmaceutical
agents and in useful synthetic intermediates, auxiliaries, and
ligands in catalysis.8 As a consequence, considerable
importance is attached to new methods to access this
moiety. However, it was unclear at the outset of the current
work if the corresponding dihydropyrrole epoxide 3 would
undergo initial deprotonation with an organolithium a-to
the epoxide oxygen as desired, or a-to nitrogen to give 4
(Scheme 3),9 the latter potentially giving pyrroles 6 via the
allylic alkoxide 5.10
Scheme 1.
In one development of this methodology, we recently
reported the alkylative deoxygenation of dihydrofuran and
Scheme 2.
Keywords: epoxides; organolithiums; amino alcohols; eliminations and alkenes.
*
Corresponding author. Tel.: þ44-1865-275697; fax: þ44-1865-275674; e-mail: david.hodgson@chem.ox.ac.uk
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.10.010

9730
D. M. Hodgson et al. / Tetrahedron 59 (2003) 9729–9742
Scheme 3.
2. Results and discussion
(TMEDA, entry 5), variation of reaction temperature
(entries 6 and 7), or extended reaction time (5 h at 2788C,
entry 8) gave reduced yields of amino alcohol 10a, whereas
varying in the quantity of BunLi (entries 9 and 10) made
little difference to the yield of amino alcohol 10a.
Our initial investigations focused on the reductive alkyl-
ation of Boc-protected epoxide 9a (Scheme 2).11 Prepa-
ration of epoxide 9a was readily achieved by ring-closing
metathesis of commercially available N-Boc protected
diallylamine 712 – 14 and subsequent epoxidation
(Scheme 4).15
Variation of the organolithium under the conditions
described in Table 1, entry 2 was examined. However,
with BusLi, PriLi, ButLi and Me3SiCH2Li, yields of the
corresponding amino alcohols (16–22%) were significantly
reduced compared to that found with BunLi (46%); with
PriLi, ButLi and Me3SiCH2Li, N-Boc pyrrole 11a was also
isolated in 22, 34 and 19% yields, respectively.
Table 1. Reaction of epoxide 9a with BunLi
Entrya BunLi Solvent Temperature Yield of 10ab Yield of 11ab
(equiv)
(8C)
(%)
(%)
Scheme 4. Reagents and conditions: (i) (PCy3)2Cl2RuvCHPh
(0.02 equiv.), CH2Cl2, 258C, 14 h;12 (ii) CF3COCH3 (11 equiv.), Na2EDTA
(0.002 equiv.), NaHCO3 (8 equiv.), Oxone (5 equiv.), MeCN, 08C, 14 h.15
1
2
3
3
3
3
3
3
3
3
3
2.2
5
THF
Et2O
Toluene
Hexane
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
278
278
278
278
278
250
2100
278
278
278
9
22
–
–
–
3
–
22
–
8
15
46
22
19
9
22
8d
26
47
48
4
Under conditions that led to clean formation of alkenediols
from dihydrofuran epoxide 1 (Scheme 2, X¼O, n¼1),4,5
addition of nBuLi (2.5 equiv.) to Boc-protected 2,5-dihydro-
pyrrole epoxide 9a gave mainly N-Boc pyrrole 11a (77%),
along with a small amount of the desired amino alcohol 10a
(16%, Scheme 5). Diagnostic proton NMR spectroscopic
details for the amino alcohol 10a are two one proton singlets
(dH¼5.13 and 4.92) for the vinylic protons and well defined
signals for the protons attached to the oxygen and nitrogen
bearing carbons [dH¼4.18–4.10 (1H, m, CHO), 3.48–3.39
(1H, m, H of CH2N) and 3.15–3.08 (1H, m, H of CH2N)].
5c
6
7
8e
9
10
a
Reactions carried out by dropwise addition of a solution of the epoxide 9a
to nBuLi at 2788C (1 h, followed by warming to 258C) unless stated
otherwise.
b
c
d
e
Isolated yields.
TMEDA (3 equiv.) was also present.
45% Epoxide 9a was recovered.
After addition of BunLi, reaction was maintained at 2788C for 5 h before
warming.
We considered that an alternative protecting group might
result in better yields of the desired amino alcohols.
Organosulfonyl protection was examined with the view
that pyrrole 6 by-product formation might be reduced, since
deprotonation a-to N to give 4 (Scheme 3) could be
relatively less favourable (compared to R1¼Boc), due to a
potentially reduced sulfonamide co-ordinative effect with
the organolithium. Using the conditions of Table 1, entry 2
with tosyl protected epoxide 9b (Scheme 5) gave the
corresponding amino alcohol 10b, but in poor yield (20%,
36% based on recovered starting material). The use of
5 equiv. of BunLi gave the amino alcohol 10b in 31% yield
with no recovery of starting epoxide, and in neither of these
reactions was N-Ts pyrrole detected as a by-product.
Although not probed experimentally, one possible reason
for the recovery of starting tosyl-protected epoxide could
be competing ortho-lithiation of the protecting group.16
To avoid the latter issue we were attracted to the tert-
butylsulfonyl (Bus) group, introduced by Weinreb and
co-workers, as it is base stable and can be deprotected under
Scheme 5. Reagents and conditions: (i) nBuLi (3 equiv.), THF, 2788C, 1 h
to 258C, 1 h.
Further experimentation with Boc-protected epoxide 9a is
summarised in Table 1. Reversing the order of addition, that
is dropwise addition of a solution of the epoxide 9a to BunLi
at 2788C (THF, 1 h, followed by warming to 258C),
significantly reduced the formation of N-Boc pyrrole 11a
but the yield of amino alcohol 10a was also very low (Table
1, entry 1). No N-Boc pyrrole 11a, was isolated from similar
reactions carried out in Et2O, toluene or hexane (entries
2–4), with the best yield of amino alcohol 10a (46%) being
obtained in Et2O (entry 2). In Et2O the addition of a ligand

D. M. Hodgson et al. / Tetrahedron 59 (2003) 9729–9742
9731
Scheme 6. Reagents and conditions: (i) TFA (19 equiv.), CH2Cl2, 258C, 4 h; (ii) Et3N (10 equiv.), CH2Cl2, 258C, 1 h, then ButSOCl17 (2 equiv.), CH2Cl2, 08C,
4 h; (iii) CF3COCH3 (11 equiv.), Na2EDTA (0.002 equiv.), NaHCO3 (8 equiv.), Oxone (5 equiv.), CH3CN, 08C, 14 h;15 (iv) NaH (2.2 equiv.), DMF, 08C, 1 h,
then allyl bromide (2.2 equiv.), 08C, 14 h; (v) (PCy3)2Cl2RuvCHPh (0.02 equiv.), CH2Cl2, 258C, 14 h.12
fairly mild acidic conditions.17 The Bus-protected 2,5-di-
hydropyrrole epoxide 13 could be readily prepared in
excellent yield, either from Boc-protected pyrroline 8 by a
protecting group interchange, or from tert-butylsulfonamide
14,18 as indicated in Scheme 6.
The synthesis of diene 22 is particularly noteworthy, since
to the best of our knowledge this is the first report of reaction
via a-lithiation of an epoxide with vinyllithium3 and
provides a new entry to conjugated dienes. Allylsilanes, of
considerable utility in organic synthesis,19 are also readily
accessible, as indicated by the formation of 23 and 24.
Formation of allylsilane 23 makes use of the addition of
organolithiums to vinylsilane to give substituted a-silyl
anions20 and in the present case allows a straightforward
way to prepare more highly substituted allylsilanes.
We were pleased to observe that reaction of N-Bus epoxide
13 with BunLi under the best conditions found for N-Boc
epoxide 9a (Table 1, entry 2) gave a significant improve-
ment in yield (76%) of the corresponding Bus-protected
amino alcohol 17 (Scheme 7). The reaction of N-Bus
epoxide 13 was then examined with other organolithiums
(3 equiv.) to provide a range of 3-substituted 1-aminobut-3-
en-2-ols 18–24 in generally satisfactory yields (Scheme 7).7
In order to examine the scope of this chemistry with a
trisubstituted epoxide, we investigated the methyl-substi-
tuted epoxide 29 (Scheme 8). The latter was synthesised via
Scheme 7.

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D. M. Hodgson et al. / Tetrahedron 59 (2003) 9729–9742
Scheme 8. Reagents and conditions: (i) NaH (2.2 equiv.), DMF, 08C, 1 h, then 3-bromo-2-methylpropene (2.2 equiv.), 08C, 14 h (ii) 27 (0.02 equiv.), CH2Cl2,
258C, 14 h;21,22 (iii) TFA (19 equiv.), CH2Cl2, 258C, 4 h; (iv) Et3N (10 equiv.), CH2Cl2, 258C, 1 h, then ButSOCl (2 equiv.), CH2Cl2, 08C, 4 h; (v) CF3COCH3
(11 equiv.), Na2EDTA (0.002 equiv.), NaHCO3 (8 equiv.), Oxone (5 equiv.), CH3CN, 08C, 14 h;15 (vi) RLi (3 equiv.), Et2O, 2788C, 1 h.
methallylation of commercially available Boc-protected
allyl amine 25 and subsequent ring-closing metathesis.
Protecting group interchange, oxidation and epoxidation
gave epoxide 29 in 49% overall yield from Boc-protected
allyl amine 25 (Scheme 8). The reductive alkylation
conditions developed for the N-Boc epoxide 9 were applied
to trisubstituted epoxide 29 and, pleasingly, gave in good
yields the tertiary alcohols 30–32 with three representative
organolithiums (Scheme 8).
epoxide to the organolithium at 2788C (1 h) then warming
to room temperature over 1 h] only resulted in 5% yield of
the desired amino alcohol 34, with the cyclic allylic alcohol
35 also being isolated in 39% yield (Scheme 9). Attempted
variation of the reaction conditions [slow warm-up (16 h),
warming to room temperature immediately after the
addition of the epoxide, addition of MeOH after 1 h at
2788C, or addition of the organolithium to the epoxide at
2788C] failed to improve the yield of amino alcohol 34,
although the allylic alcohol 35 was isolated in up to 88%
yield under the slow warm-up conditions.
Extension of the reductive alkylation process to produce
1,3-amino-alcohols from tetrahydropyidine epoxides was
next examined (Scheme 2, X¼NR1, n¼2). However,
reaction of the known23 Boc-protected epoxide 33 with
nBuLi under the standard conditions [addition of the
Similarly to the earlier dihydropyrrole epoxide studies, the
Bus-protected tetrahydropyridine epoxide 38, readily pre-
pared from 1,2,3,6-tetrahydropyridine 36 (Scheme 10), gave
Scheme 9. Reagents and conditions: (i) nBuLi (3 equiv.), Et2O, 2788C, 1 h.
Scheme 10. Reagents and conditions: (i) Et3N (10 equiv.), CH2Cl2, 258C, 1 h, then ButSOCl (2 equiv.), CH2Cl2, 08C, 4 h; (ii) mCPBA (1.2 equiv.), CH2Cl2,
258C, 1 h; (iii) RLi (3 equiv.), Et2O, 2788C, 1 h.

D. M. Hodgson et al. / Tetrahedron 59 (2003) 9729–9742
9733
a much improved yield (51%) of the desired amino alcohol
39 (R¼Bun), although the corresponding cyclic allylic
alcohol 40 was still observed (17%).
transformations4,5 and manipulations of these adducts
towards targets of biological interest are currently under
investigation.
Interestingly, under otherwise identical conditions but using
THF as the solvent, led to the cyclic alcohol 40
preferentially (65%, 3% of 39 R¼Bun); use of toluene
compared with Et2O gave a higher isolated yield of the
sought after amino alcohol 39 (65%, R¼Bun), but a higher
proportion of cyclic allylic alcohol 40 (25%). Use of LiCl as
an additive in a reaction under otherwise standard
conditions (BunLi (3 equiv.), LiCl (3 equiv.), Et2O at
2788C) gave only the desired amino alcohol 39 (R¼Bun),
with no cyclic allylic alcohol 40 observed; however, the
yield of 39 (R¼Bun) was reduced compared to the LiCl-free
reaction (40% vs 51%).
4. Experimental
4.1. General
All reactions requiring anhydrous conditions were con-
ducted in flame- or oven- dried apparatus under an
atmosphere of argon. Syringes and needles for the transfer
of reagents were dried at 1408C and allowed to cool in a
desiccator over P2O5 before use. Ethers were distilled from
sodium benzophenone ketyl under argon; CH2Cl2, pentane,
hexane and toluene from CaH2 under argon. External
reaction temperatures are reported unless stated otherwise.
Reactions were monitored by TLC using commercially
available aluminium-backed plates, pre-coated with a
0.25 mm layer of silica containing fluorescent indicator
(Merck). Column chromatography was carried out on
Kieselgel 60 (40–63 mm). Petrol refers to the fraction
with bp 40–608C. Melting points were determined using a
Gallenkamp hot stage apparatus and are uncorrected.
Elemental analyses were performed by Elemental Micro-
A range of organolithiums were reacted with epoxide 38 in
Et2O (Table 2), and in most cases mixtures of amino alcohol
39 and cyclic allylic alcohol 40 were isolated, with the
desired amino alcohol 39 usually being marginally pre-
ferred. Two notable exceptions were the use of MeLi
(Table 2, entry 2) and PhLi (entry 6), where cyclic allylic
alcohol 40 was exclusively or highly preferred, respectively.
Table 2. Reaction of epoxide 38 with a range of organolithiums
analysis Limited, Okehampton, Devon, UK. H and 13C
1
RLia
Yield of 39b (%)
Yield of 40b (%)
NMR spectra were recorded in CDCl3 using Bruker JEOL
EX400 or Bruker AM500 spectrometers. Chemical shifts
are reported relative to CDCl3 [dH 7.26, dC (central line of
triplet) 77.0]. Coupling constants (J) are given in Hz, to the
nearest 0.5 Hz. Mass spectra were obtained by the EPSRC
National Mass Spectrometry Service Centre at the Uni-
versity of Swansea, using a Micromass Quattro II low
resolution triple quadrupole mass spectrometer or, for
accurate masses, using a Finnigan MAT 900 XLT high
resolution double focusing mass spectrometer with tandem
Ion Trap.
1
2
3
4
5
6
7
BunLi
MeLi
51
–
23
41
45
5
17
100
–
34
41
60
31
PriLi
BusLi
ButLi
PhLi
TMSCH2Li
43
a
Reactions carried out by dropwise addition of a solution of the epoxide 38
to RLi (3 equiv.) in Et2O at 2788C (1 h, followed by warming to 258C).
Isolated yields.
b
The desired 1,3-amino alcohols, 34 and 39 respectively,
arise from a-deprotonation of epoxide where the N-Boc and
N-Bus groups direct the epoxide lithiation vicinal to
themselves. A similar observation has been reported with
the corresponding dihydropyran epoxides.4 Competitive
formation of the cyclic alcohols 35 and 40 possibly arises
from deprotonation a-to the N-Boc and N-Bus groups,
although an intermediate similar to 4 (Scheme 3) may be
by-passed and the transformation may resemble more a
(syn)24 E2 elimination.10b The increased proportion of
cyclic alcohols 35 and 40 in the reductive alkylation
of tetrahydropyridine epoxides 33 and 38, compared
with pyrrole by-product formation from dihydropyrrole
epoxides, may reflect the reduced acidity of the a-hydro-
gens of an epoxide fused to a six-membered rather than a
five-membered ring.10b
4.1.1. tert-Butyl 6-oxa-3-aza-bicyclo[3.1.0]hexane-3-
carboxylate 9a.11,14 1,1,1-Trifluoroacetone (5.93 mL,
65.0 mmol) was added dropwise to a stirred solution of
alkene
8
(1.00 g, 5.91 mmol) and aq. Na2EDTA
(4.00£1024 mol dm23, 29.5 mL, 0.0118 mmol) in MeCN
(50 mL) at 08C. A mixture of NaHCO3 (3.85 g, 47.3 mmol)
and Oxonew (18.2 g, 29.5 mmol) was then added portion-
wise over a period of 1 h. After 1.5 h, the reaction mixture
was diluted with water (50 mL), filtered and extracted with
CH2Cl2 (3£50 mL). The combined organic extracts were
dried (Na2SO4) and concentrated under reduced pressure to
give a yellow oil. Purification of the residue by column
chromatography [elution gradient 30–60% Et2O in petrol]
gave epoxide 9a (1:1 mixture of rotamers) as a clear
colourless oil (0.97 g, 89%); Rf 0.20 (50% Et2O in petrol);
n
max (film)/cm21 3051, 2976, 2876, 1698, 1423, 1389, 1338,
1174, 1116, 1027 and 964; dH (500 MHz) 3.78 (1H, d,
J¼13.0 Hz, H of CH2N), 3.66 (1H, d, J¼13.0 Hz, H of
CH2N), 3.63 (2H, d, J¼3.5 Hz, CHO), 3.27 (2H, dd, J¼
13.0, 3.5 Hz, H of CH2N) and 1.40 (9H, s, C(CH3)3); dC
(125 MHz) 154.6 (CvO), 79.6 (C(CH3)3), 55.4 (CHO),
54.9 (CHO), 47.1 (CH2N), 46.7 (CH2N) and 28.3
(C(CH3)3); m/z [EI þ] 185 (100%, MHþ) and 170 (50)
(Found: MHþ, 185.1055. C9H16NO3 requires 185.1052).
3. Conclusion
In conclusion, we have demonstrated that treatment of
dihydropyrrole and tetrahydropyridine epoxides with a
diverse array of organolithiums provides a new route to
substituted unsaturated amino alcohols. Extension of this
process to other epoxides and organolithiums, asymmetric

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D. M. Hodgson et al. / Tetrahedron 59 (2003) 9729–9742
4.1.2. Typical experimental procedure for reductive
alkylations: tert-butyl (2-hydroxy-3-methyleneheptyl)
carbamate 10a. A solution of N-Boc epoxide 9a (0.20 g,
1.09 mmol) in Et2O (8 mL) was added dropwise to a stirred
solution of BunLi (2.30 mol dm23 in petrol, 1.42 mL,
3.26 mmol) in Et2O (1 mL) at 2788C. After 1 h at 2788C
the reaction was warmed to 258C over 1 h and then sat. aq.
NH4Cl (5 mL) was added. The reaction mixture was
extracted with Et2O (3£10 mL) and the combined organic
extracts were washed with sat. aq. NaHCO3 (15 mL), brine
(15 mL), dried (MgSO4) and evaporated under reduced
pressure. Purification of the residue by column chromato-
graphy [elution gradient 30–60% Et2O in petrol] gave
amino alcohol 10a as a white solid (0.122 g, 46%); Rf 0.20
(40% Et2O in petrol); mp 78.0–80.08C; nmax (film)/cm21
3408, 3085, 2960, 2931, 2873, 1694, 1055, 1514, 1468,
1436, 1392, 1367, 1340, 1273, 1252, 1172, 1110, 1073 and
980; dH (500 MHz) 5.13 (1H, s, H of CH2v), 4.94–4.86
(1H, br s, NH), 4.92 (1H, s, H of CH2v), 4.18–4.10 (1H, m,
CHO), 3.48–3.39 (1H, m H of CH2N), 3.15–3.08 (1H, m, H
of CH2N), 2.45 (1H, br, s, OH), 2.18 (1H, dt, J¼15.5,
7.5 Hz, H of CH2Cv), 1.98 (1H, dt, J¼15.5, 7.5 Hz, H of
CH2Cv), 1.46–1.42 (11H, m, C(CH3)3, CH2CH2CH3),
1.39–1.33 (2H, m, CH2CH3) and 0.92 (3H, t, J¼7.5 Hz,
(CH2)2CH3); dC (125 MHz) 162.1 (CvO), 150.0 (Cv),
110.0 (CH2v), 79.5 (C(CH3)3), 74.2 (CHO), 45.3 (CH2N),
31.9 (CH2Cv), 30.0 (CH2CH2CH3), 28.2 (C(CH3)3), 22.4
(CH2CH3) and 13.8 ((CH2)2CH3); m/z [EI þ] 244 (30%,
MHþ) and 188 (15); m/z [EI 2] 318 (60%), 242 (98, M2H)
and 89 (100) (Found: MHþ, 244.1915. C13H26NO3 requires
244.1912).
general procedure for (2-hydroxy-3-methylene-heptyl)-car-
bamic acid tert-butyl ester 10a, N-Boc epoxide 9a (0.20 g,
1.09 mmol) in Et2O (8 mL) was reacted with iPrLi
(1.50 mol dm23 in hexane, 2.17 mL, 3.26 mmol). Column
chromatography [elution gradient 30–60% Et2O in petrol]
gave amino alcohol 2 (X¼NBoc, n¼1, R¼iPr) as a white
solid (0.055 g, 22%); Rf 0.23 (40% Et2O in petrol); mp
76.0–76.58C; nmax (KBr)/cm21 3407, 3092, 2966, 2874,
1694, 1515, 1456, 1393, 1367, 1252, 1172, 1098, and 1075;
dH (400 MHz) 5.12 (1H, s, H of CH2v), 5.03 (1H, br s,
NH), 4.97 (1H, s, H of CH2v), 4.17 (1H, br, d, J¼19.0 Hz,
CHO), 3.44–3.38 (1H, m, CH2N), 3.07–3.01 (1H, m,
CH2N), 2.66 (1H, br s, OH), 2.24 (1H, septet, J¼7.0 Hz,
CHCv), 1.43 (9H, s, C(CH3)3), 1.51 (3H, d, J¼7.0 Hz,
CHCH3) and 1.32 (3H, d, J¼7.0 Hz, CHCH3); dC
(100 MHz) 156.6 (CvO), 156.3 (Cv), 107.9 (CH2v),
79.5 (C(CH3)3), 73.3 (CHO), 45.9 (CH2N), 30.7 (CHCv),
28.3 (C(CH3)3), 23.0 (CH3CH) and 22.0 (CH3CH); m/z
[CIþ(NH3)] 230 (10%, MHþ), 191 (17), 175 (22), 131 (17),
166 (38), 114 (100), 112 (36) and 52 (74) (Found: MHþ,
230.1758. C12H24NO3 requires 230.1756).
4.1.5. tert-Butyl (2-hydroxy-4-methyl-3-methylene-pen-
tyl)carbamate 2 (X5NBoc, n51, R5tBu). Following the
general procedure for (2-hydroxy-3-methylene-heptyl)-car-
bamic acid tert-butyl ester 10a, N-Boc epoxide 9a (0.05 g,
0.27 mmol) in Et2O (3 mL) was reacted with tBuLi
(1.70 mol dm23in hexane, 0.477 mL, 0.82 mmol). Column
chromatography [elution gradient 30–60% Et2O in petrol]
gave amino alcohol 2 (X¼NBoc, n¼1, R¼tBu) as a white
solid (0.013 g, 19%); Rf 0.22 (40% Et2O in petrol); mp
86.0–87.08C; nmax (KBr)/cm21 3405, 3096, 2969, 2873,
1695, 1639, 1510, 1457, 1392, 1366, 1251, 1173, 1071 and
955; dH (400 MHz) 5.18 (1H, s, H of CH2v), 5.12 (1H, s, H
of CH2v), 5.00 (1H, br, s, NH), 4.38–4.32 (1H, m, CHO),
3.39–3.34 (1H, m, H of CH2N), 3.07–3.03 (1H, m, H of
CH2N), 2.09 (1H, br, s, OH), 1.46 (9H, s, OC(CH3)3) and
1.12 (9H, s, C(CH3)3); dC (100 MHz) 160.0 (CvO), 153.3
(Cv), 108.8 (CH2v), 79.8 (OC(CH3)3), 69.6 (CHO),
47.73 (CH2N), 35.4 (C(CH3)3), 28.9 (C(CH3)3) and 28.3
(OC(CH3)3); m/z [EI þ] 244 (50%, MHþ) 228 (17), 205
(82), 189 (71), 172 (22), 149 (18) and 128 (100) (m/z
[CIþ(NH3)] Found: MHþ, 244.1913. C13H26NO3 requires
244.1912).
4.1.3. tert-Butyl (2-hydroxy-4-methyl-3-methylene-
hexyl)carbamate 2 (X5NBoc, n51, R5sBu). Following
the general procedure for (2-hydroxy-3-methylene-heptyl)-
carbamic acid tert-butyl ester 10a, N-Boc epoxide 9a
(0.05 g, 0.27 mmol) in Et2O (3 mL) was treated with sBuLi
(1.40 mol dm23 in light petroleum, 0.58 mL, 0.82 mmol).
Column chromatography [elution gradient 30–60% Et2O in
light petroleum] gave amino alcohol 2 (X¼NBoc, n¼1,
R¼sBu) (1:1 mixture of diastereomers A:B) as a white solid
(0.01 g, 16%); Rf 0.21 (40% Et2O in petrol); mp 83.0–
85.08C; nmax (KBr)/cm21 3413, 2966, 2931, 2876, 2361,
1694, 1512, 1456, 1392, 1367, 1251, 1172, 1081 and 903;
dH (400 MHz) 5.18 (1H, s, H of CH2v), 4.97–4.93 (2H, m,
H of CH2v, NH), 4.21–4.10 (1H, m, CHO), 3.52–3.37
(1H, m, CH2N of A), 3.12–2.92 (1H, m, CH2N of B), 2.40
(1H, br, s, OH), 2.04–1.95 (1H, m, CHCv), 1.47–1.42
(11H, m, C(CH3)3, CH2CH3), 1.07 (1.5H, d, J¼7.0 Hz,
CHCH3 of A), 1.02 (1.5H, d, J¼7.0 Hz, CHCH3 of B), 0.90
(1.5H, t, J¼6.0 Hz, CH2CH3 of A) and 0.85 (1.5H, t, J¼
6.0 Hz, CH2CH3 of B); dC (100 MHz) 161.2 (CvO), 155.1
(Cv), 108.1 (CH2v), 79.5 (C(CH3)3), 73.8 (CHO of A),
73.4 (CHO of B), 45.9 (CH2N of A), 45.7 (CH2N of B), 38.0
(CHCv of A), 37.5 (CHCv of B), 29.7 (CH2CH3 of A),
28.5 (CH2CH3 of B), 28.3 (C(CH3)3), 21.0 (CHCH3 of A),
19.6 (CHCH3 of B), 12.0 (CH2CH3 of A) and 11.6 (CH2CH3
of B); m/z [CIþ(NH3)] 244.2 (48%, MHþ) 205 (80), 189
(68), 172 (21), 144 (20), and 128 (100) (Found: MHþ,
244.1910. C13H25NO3 requires 244.1912).
4.1.6. tert-Butyl (2-hydroxy-4-methyl-3-methylene-pen-
tyl)carbamate
2
(X5NBoc, n51, R5CH2TMS).
Following the general procedure for (2-hydroxy-3-methyl-
ene-heptyl)-carbamic acid tert-butyl ester 10a, N-Boc
epoxide 9a (0.10 g, 0.54 mmol) in Et2O (8 mL) was reacted
with TMSCH2Li (1.0 mol dm23 in pentane, 1.63 mL,
1.63 mmol). Column chromatography [elution gradient
30–60% Et2O in petrol] gave amino alcohol 2 (X¼NBoc,
n¼1, R¼CH2TMS) as a white solid (0.025 g, 17%); Rf 0.22
(40% Et2O in petrol); mp 73.5–74.58C; (Found: C, 57.1; H,
9.9; N, 5.1. C8H13NO2Si requires C, 57.1; H, 10.0; N,
5.1%); nmax (KBr)/cm21 3385, 2978, 2933, 1695, 1514,
1455, 1393, 1367, 1251, 1171 and 1010; dH (400 MHz) 5.00
(1H, s, H of CH2v), 4.99 (1H, br s, NH), 4.75 (1H, s, H of
CH2v), 4.03–4.01 (1H, m, CHO), 3.48–3.43 (1H, m, H of
CH2N), 3.12–3.02 (1H, m, H of CH2N), 2.58 (1H, br, s,
OH), 1.74 (1H, d, J¼14.0 Hz, H of CH2TMS), 1.44 (9H, s,
C(CH3)3), 1.38 (1H, d, J¼14.0 Hz, H of CH2TMS) and 0.04
4.1.4. tert-Butyl (2-hydroxy-4-methyl-3-methylene-pen-
tyl)carbamate 2 (X5NBoc, n51, R5iPr). Following the

D. M. Hodgson et al. / Tetrahedron 59 (2003) 9729–9742
9735
(9H, s, TMS); dC (100 MHz) 156.7 (CvO), 147.1 (Cv),
108.0 (CH2v), 79.6 (C(CH3)3), 74.9 (CHO), 45.3 (CH2N),
28.3 (C(CH3)3), 23.0 (CH2TMS) and 21.4 (TMS); m/z
[EI 2] 272 (100%, M2H) and 126 (12) (m/z [CIþ(NH3)]
Found: MHþ, 274.1836. C13H28NO3Si requires 274.1838).
4.1.9. 1-(2-Methyl-propane-2-sulfinyl)-2,5-dihydro-1H-
pyrrole 12. Alkene 811,14 (1.00 g, 5.91 mmol) in CH2Cl2
(100 mL) was stirred with TFA (8.65 mL, 112 mmol) at
room temperature for 4 h. The solvent was removed under
reduced pressure. The residue was then co-evaporated with
toluene (15 mL) to give the desired amine as a black oil
(0.40 g, quant.). No other purification was required; nmax
(film)/cm21 3422, 1678, 1435, 1205 and 1144; dH
(500 MHz) 8.73 (2H, br s, NH2), 5.92 (2H, s, 2£ CHv)
and 4.16 (4H, s, 2£CH2N); dC (125 MHz) 124.7 (CHv) and
52.6 (CH2N); m/z [EI þ] 68 (100%, MHþ), 51 (48), 45 (76)
and 41 (72) (Found: MHþ, 68.0501. C4H8N requires
68.0500).
4.1.7. 3-(Toluene-4-sulfonyl)-6-oxa-3-azabicyclo[3.1.0]-
hexane 9b. A solution of 1-[(4-methylphenyl)sulfonyl]-2,
5-dihydro-1H-pyrrole25 (0.92 g, 4.13 mmol) and aq.
Na2EDTA (4£1024 mol dm23, 20.6 mL, 0.008 mmol) in
acetonitrile (70 mL) was cooled to 08C. 1,1,1-Trifluoro-
acetone (4.06 mL, 45.4 mmol) was added dropwise to this
homogeneous solution. A mixture of NaHCO3 (2.77 g,
33.0 mmol) and Oxonew (12.7 g, 20.6 mmol) was then
added portionwise over a period of 1 h. After 4 h, a mixture
of NaHCO3 (2.77 g, 33.0 mmol) and Oxonew (12.7 g,
20.6 mmol) was added and the reaction was then stirred
overnight. The reaction mixture was then diluted with water
(50 mL), filtered and extracted with CH2Cl2 (3£50 mL).
The combined organic extracts were dried (Na2SO4) and
concentrated under reduced pressure to give the title
epoxide as a white crystalline solid (0.97 g, 98%), which
did not require further purification; Rf 0.18 (50% Et2O in
petrol); mp 124.0–124.58C; (Found: C, 55.4; H, 5.4; N, 5.7.
C11H13NO3S requires C, 55.2; H, 5.5; N, 5.9%); nmax
(KBr)/cm21 3063, 2932, 2876, 1747, 1597, 1495, 1457,
1406, 1332, 1257, 1228, 1159, 1101, 1010 and 892; dH
(400 MHz) 7.24 (2H, d, J¼8.0 Hz, 2£H of Ar), 7.44 (2H, d,
J¼8.0 Hz, 2£H of Ar), 3.70 (2H, d, J¼12.0 Hz, 2£H of
CH2N), 3.67 (2H, s, 2£CHO), 3.35 (2H, d, J¼12.0 Hz, 2£H
of CH2N) and 2.41 (3H, s, CH3); dC (100 MHz) 143.6
(SO2C), 134.5 (CH3C), 129.6 (CH of Ar), 127.2 (CH of Ar),
55.1 (CHO), 48.7 (CH2N) and 21.5 (CH3); m/z [CIþ(NH3)]
257 (100%, MNHþ4 ), 240 (14, MHþ) and 86 (10) (Found:
MHþ, 240.0692. C11H14NO3S requires 240.0694).
To a solution of the above amine (0.40 g, 5.91 mmol) in
CH2Cl2 (45 mL) at 258C was added dropwise Et3N
(8.24 mL, 59.1 mmol). After 1 h the reaction was cooled
to 08C and ice-cold tert-butylsulfinyl chloride17 (1.66 g,
11.8 mmol) in CH2Cl2 (5 mL) was added. After 1 h (TLC
monitoring, 30% Et2O in petrol), the mixture was diluted
with sat. aq. NaHCO3 (30 mL). The aqueous layer was then
extracted with CH2Cl2 (3£10 mL). The organic extracts
were combined, dried (MgSO4) and concentrated under
reduced pressure to give a brown oil. Purification of the
residue by column chromatography [SiO2, elution gradient
0–30% Et2O in petrol] gave the sulfinamide 12 as a clear
colourless oil (0.99 g, 97%); Rf 0.30 (30% Et2O in petrol);
nmax (CHCl3)/cm21 3460, 2959, 2915, 2857, 1716, 1644,
1474, 1390, 1363, 1345, 1301, 1175, 1107, 1070 and 1028;
dH (400 MHz) 5.71 (2H, s, 2£CHv), 4.26–4.23 (2H, s,
2£H of CH2N), 3.87–3.83 (2H, s, 2£H of CH2N) and
1.14 (9H, s, C(CH3)3); dC (100 MHz) 126.5 (CHv) 57.4
(C(CH3)3), 54.7 (CH2N) and 23.1 (C(CH3)3); m/z
[CIþ(NH3)] 191 (28%, MHþ4 ), 174 (89, MHþ), 158 (13),
72 (25), 70 (100), 68 (94) and 52 (26) (Found: MHþ,
174.0959. C8H16NOS requires 174.0953).
4.1.8. N-(2-Hydroxy-3-methylene-heptyl)-4-methylben-
zenesulfonamide 10b. Following the general procedure
for (2-hydroxy-3-methylene-heptyl)-carbamic acid tert-
butyl ester 10a, N-tosyl epoxide 9b (0.10 g, 0.42 mmol) in
4.1.10. 2-Methyl-propane-2-sulfonic acid diallylamide
t
15. BuSO2NH2 1418 (0.695 g, 5.07 mmol) was added
dropwise to a solution of NaH (0.45 g, 60% dispersion in
mineral oil, 11.2 mmol) in DMF (70 mL) at 258C. After 1 h
the reaction was cooled to 08C and allyl bromide (0.97 mL,
11.2 mmol) was added. After 1 h the reaction was quenched
with MeOH (10 mL) and the residue was diluted with H2O
(70 mL) and washed with Et2O (4£50 mL). The organic
phases were combined, dried (Na2SO4) and evaporated
under reduced pressure to give a yellow oil. Purification of
the residue by column chromatography [elution gradient
0–40% Et2O in petroleum] gave the diene 15 as a clear
colourless oil (1.10 g, quant.); Rf 0.8 (40% Et2O in petrol);
n
Et2O (8 mL) was reacted with BuLi (2.46 mol dm23 in
hexane, 0.510 mL, 1.26 mmol). Column chromatography
[elution gradient 30–70% Et2O in petrol] gave amino
alcohol 10b as a white solid (0.039 g, 31%); Rf 0.18 (50%
Et2O in petrol); mp 92.5–93.08C; nmax (KBr)/cm21 3488,
3293, 2957, 2927, 2872, 2858, 1663, 1636, 1498, 1458,
1396, 1366, 1309, 1548, 1127, 1090, 1042 and 891; dH
(400 MHz) 7.85 (2H, d, J¼8.0 Hz, 2£H of Ar), 7.33 (2H, d,
J¼8.0 Hz, 2£H of Ar), 5.05 (1H, s, H of CH2v), 5.03–4.98
(1H, m, NH), 4.93 (1H, s, H of CH2v), 4.26–4.10 (1H, m,
CHO), 3.21–3.13 (1H, m, H of CH2N), 2.90–2.82 (1H, m,
H of CH2N), 2.41 (3H, s, CH3 of Ar), 2.22 (1H, br, s, OH),
1.97 (1H, dt, J¼15.5, 7.5 Hz, H of CH2Cv), 1.84 (1H,
dt, J¼15.5, 7.5 Hz, H of CH2Cv), 1.41–1.34 (4H, m,
CH2CH2CH3, CH2CH3) and 0.89 (3H, t, J¼7.0 Hz,
CH3(CH2)3); dC (100 MHz) 148.7 (SO2C), 143.5 (Cv),
136.7 (CH3C), 129.7 (CH of Ar), 127.1 (CH of Ar), 110.8
(CH2v), 72.9 (CHO), 47.5 (CH2N), 31.8 (CH2Cv), 30.9
(CH2CH2CH3), 22.4 (CH2CH3), 21.5 (CH3 of Ar) and 13.9
(CH3(CH2)3); m/z [CIþ(NH3)] 315 (80%, MNHþ4 ), 300 (23),
298 (41, MHþ), 280 (21), 190 (30), 189 (100), 146 (16), 144
(70), 142 (22), 128 (60), 126 (23) and 111 (36) (Found:
MNHþ4 , 315.1738. C15H27N2O3S requires 315.1742).
n
max (film)/cm21 3082, 2984, 2927, 2872, 1642, 1482, 1453,
1438, 1420, 1395, 1364, 1335, 1317, 1217, 1204, 1162,
1125, 1045 and 995; dH (400 MHz) 5.93–5.69 (2H, m,
CHv), 5.24–5.12 (4H, m, CH2v), 3.82 (4H, d, J¼6.0 Hz,
CH2) and 1.38 (9H, s, C(CH3)3); dC (100 MHz) 133.4
(CH2v), 119.1 (CHv), 61.1 (C(CH3)3), 49.8 (CH2) and
24.5 (C(CH3)3); m/z [CIþ(NH3)] 235 (63%, MNHþ4 ), 218
(47, MHþ), 98 (98.2), 82 (11), 58 (22) and 52 (12) (Found:
MHþ, 218.1214. C10H20NO3S requires 218.1215).
4.1.11. 1-(2-Methyl-propane-2-sulfonyl)-2,5-dihydro-
1H-pyrrole 16. Diene 15 (0.16 g, 0.74 mmol) was
added to
a homogeneous purple-black solution of

9736
D. M. Hodgson et al. / Tetrahedron 59 (2003) 9729–9742
(PCy3)2Cl2RuvCHPh12 (0.01 g, 0.01 mmol) in anhydrous
CH2Cl2 (20 mL) under argon. The resulting mixture was
stirred at 258C for 14 h, after which time TLC showed
complete consumption of starting material (eluent 50%
Et2O in petrol). The reaction was quenched by exposure to
air for ,2 h and then evaporated under reduced pressure.
Purification of the residue by column chromatography
[elution gradient 0–30% Et2O in petrol] gave alkene 16 as a
clear colourless oil (0.14 g, 100%); Rf 0.54 (40% Et2O in
petrol); dH (400 MHz) 5.77 (2H, s, CHv), 4.30 (4H, s,
CH2N) and 1.42 (9H, s, C(CH3)3); dC (100 MHz) 125.5
(CHv), 60.6 (C(CH3)3), 56.6 (CH2N) and 24.3 (C(CH3)3);
m/z [CIþ(NH3)] 207 (26%, MNHþ4 ), 190 (26, MHþ), 70
(63) and 68 (38) (Found: MHþ, 190.0899. C8H16NO2S
requires 190.0902).
cedure for (2-hydroxy-3-methylene-heptyl)-carbamic acid
tert-butyl ester 10a, N-Bus epoxide 13 (0.10 g, 0.49 mmol)
in Et2O (8 mL) was reacted with BunLi (2.50 mol dm23 in
pentane, 0.585 mL, 1.46 mmol). Column chromatography
[elution gradient 30–60% Et2O in petrol] gave amino
alcohol 17 as a white solid (0.098 g, 76%); Rf 0.13 (40%
Et2O in petrol); mp 87.0–87.58C; (Found: C, 54.3; H, 9.5;
N, 5.2. C12H25NO3S requires C, 54.7; H, 9.6; N, 5.3%); nmax
(KBr)/cm21 3488, 3297, 2958, 2932, 2873, 1480, 1458,
1405, 1366, 1307, 1209, 1126 and 1029; dH (400 MHz) 5.15
(1H, s, H of CH2v), 4.98 (1H, s, H of CH2v), 4.53–4.51
(1H, m, NH), 4.25–4.22 (1H, m, CHO), 3.43–3.36 (1H, m,
H of CH2N), 3.14–3.08 (1H, m, H of CH2N), 2.31 (1H, br, s,
OH), 2.09 (1H, dt, J¼16.0, 8.0 Hz, H of CH2Cv), 2.00
(1H, dt, J¼16.0, 8.0 Hz, H of CH2Cv), 1.48–1.31 (13H,
m, C(CH3)3, CH2CH2CH3, CH2CH3) and 0.94 (3H, t, J¼
7.5 Hz, CH3(CH2)2); dC (100 MHz) 150.0 (Cv), 110.0
(CH2v), 79.5 (C(CH3)3), 74.2 (CHO), 45.3 (CH2N), 31.9
(CH2Cv), 30.0 (CH2CH2CH3), 28.2 (C(CH3)3), 22.4
(CH2CH3), and 13.8 ((CH2)2CH3); m/z [CIþ(NH3)] 281
(53%, MNHþ4 ), 264 (20, MHþ), 246 (13), 169 (100), 155
(33), 146 (40), 128 (94), 114 (29), 100 (25), 86 (19) and 72
(40) (Found: MNHþ4 , 281.1892. C12H29N2O3S requires
281.1899).
4.1.12. 3-(2-Methyl-propane-2-sulfonyl)-6-oxa-3-aza-
bicyclo[3.1.0]hexane 13. Method 1. 1,1,1-Trifluoroacetone
(10.8 mL, 121 mmol) was added dropwise to a stirred
solution of sulfinamide 12 (1.90 g, 11.0 mmol) and aq.
Na2EDTA (4£1024 mol dm23, 54.9 mL, 0.02 mmol) in
MeCN (150 mL) at 08C. A mixture of NaHCO3 (6.54 g,
87.9 mmol) and Oxonew (33.8 g, 54.9 mmol) was then
added portionwise over a period of 1 h. After 4 h, a mixture
of NaHCO3 (6.54 g, 87.9 mmol) and Oxonew (33.8 g,
54.9 mmol) was added and the reaction was stirred over-
night. The reaction mixture was diluted with water (50 mL),
filtered and extracted with CH2Cl2 (3£50 mL). The
combined organic layers were dried (Na2SO4) and concen-
trated under reduced pressure to give a yellow solid.
Purification of the residue by column chromatography
[elution gradient 0–60% Et2O in petrol] gave epoxide 13 as
a white solid (2.16 g, 96%); Rf 0.11 (50% Et2O in petrol);
mp 106.0–106.58C; (Found: C, 46.5; H, 7.6; N, 6.8.
C8H15NO3S requires C, 46.8; H, 7.4; N, 6.8%); nmax
(film)/cm21 3063, 2984, 2939, 2878.5, 1910, 1731, 1642,
1482, 1464, 1407, 1366, 1309, 1254, 1228, 1195, 1135,
1090, 1011 and 962; dH (500 MHz) 3.92 (2H, br, d,
J¼12.0 Hz, 2£H of CH2N), 3.70 (2H, s, 2£CHO), 3.44 (2H,
d, J¼12.0 Hz, 2£H of CH2N) and 1.39 (9H, s, C(CH3)3); dC
(100 MHz) 79.0 (C(CH3)3), 55.5 (CHO), 49.9 (CH2N) and
24.4 (C(CH3)3); m/z [CIþ(NH3)] 223 (100%, MNHþ4 ), 170
(30), 86 (37), 70 (23), 68 (28) and 52 (32) (Found: MNHþ4 ,
223.1111. C8H19N2O3S requires 223.1116).
4.1.14. 2-Methyl-propane-2-sulfonic acid (2-hydroxy-4-
methyl-3-methylenehexyl)amide 18. Following the
general procedure for (2-hydroxy-3-methylene-heptyl)-
carbamic acid tert-butyl ester 10a, N-Bus epoxide 13
(0.10 g, 0.49 mmol) in Et2O (8 mL) was reacted with BusLi
(1.40 mol dm23 in light petroleum, 1.05 mL, 1.46 mmol).
Column chromatography [elution gradient 30–60% Et2O in
petrol] gave amino alcohol 18 (1:1 mixture of diastereomers
A/B) as a white solid (0.069 g, 54%); Rf 0.21 (50% Et2O in
petrol); mp 87.5–89.08C; nmax (KBr)/cm21 3433, 3248,
2974, 2935, 2877, 1648, 1480, 1431, 1396, 1366, 1301,
1233, 1119, 1074 and 1035; dH (400 MHz) 5.18 (1H, d, J¼
8.5 Hz, H of CH2v), 4.96–4.93 (2H, m, H of CH2v, NH),
4.21–4.16 (1H, m, CHO), 3.38–2.64 (1H, m, CH2N of A),
3.05–3.00 (1H, m, CH2N of B), 2.87 (1H, br s, OH), 1.99
(0.5H, sextet, J¼7.0 Hz, CHCH3 of A), 1.97 (0.5H, sextet,
J¼7.0 Hz, CHCH3 of B), 1.57–1.29 (11H, m, CH2CH3,
C(CH3)3), 1.05 (3H, d, J¼7.0 Hz, CHCH3 of A), 1.01 (3H,
d, J¼7.0 Hz, CHCH3 of B), 0.87 (1.5H, t, J¼4.0 Hz,
CH2CH3 of A) and 0.82 (1.5H, t, J¼4.0 Hz, CH2CH3 of B);
dC (100 MHz) 154.6 (Cv of A), 154.5 (Cv of B), 109.4
(CH2v of A), 109.3 (CH2v of B), 74.0 (CHO of A), 73.5
(CHO of B), 59.9 (C(CH3)3), 49.9 (CH2N of A), 49.7 (CH2N
of B), 38.3 (CHCH3 of A), 37.7 (CHCH3 of B), 29.5
(CH2CH3 of A), 28.5 (CH2CH3 of B), 24.2 (C(CH3)3), 20.9
(CHCH3 of A), 19.6 (CHCH3 of B), 12.0 (CH2CH3 of A)
and 11.6 (CH2CH3 of B); m/z [CIþ(NH3)] 281 (26%,
MNHþ4 ), 264 (42, MHþ), 169 (15), 155 (49), 144 (19),
128 (68) and 111 (100) (Found: MNHþ4 , 281.1900.
C12H29N2O3S requires 281.1899).
Method 2. 1,1,1-Trifluoroacetone (0.521 mL, 5.82 mmol)
was added dropwise to a stirred solution of alkene 16
(0.10 g, 0.53 mmol) and aq. Na2EDTA (4£1024 mol dm23
,
2.65 mL, 0.001 mmol) in MeCN (8 mL) at 08C. A mixture
of NaHCO3 (0.356 g, 4.23 mmol) and Oxonew (1.63 g,
2.65 mmol) was then added portionwise over a period of
1 h. After 4 h, a mixture of NaHCO3 (0.356 g, 4.23 mmol)
and Oxonew (1.63 g, 2.65 mmol) was added and the
reaction was stirred overnight. The reaction mixture was
diluted with water (5 mL), filtered and extracted with
CH2Cl2 (3£5 mL). The combined organic layers were dried
(Na2SO4) and concentrated under reduced pressure to give a
yellow solid. Purification of the residue by column chroma-
tography [elution gradient 0–60% Et2O in petrol] gave
epoxide 13 as a white solid (0.11 g, 98%); data as above.
4.1.15. 2-Methyl-propane-2-sulfonic acid (2-hydroxy-4-
methyl-3-methylenepentyl)amide 19. Following the
general procedure for (2-hydroxy-3-methylene-heptyl)-
carbamic acid tert-butyl ester 10a, N-Bus epoxide 13
(0.10 g, 0.49 mmol) in Et2O (8 mL) was reacted with PriLi
(1.70 mol dm23in light petroleum, 0.861 mL, 1.46 mmol).
Column chromatography [elution gradient 30–60% Et2O in
4.1.13. 2-Methyl-propane-2-sulfonic acid (2-hydroxy-3-
methyleneheptyl)amide 17. Following the general pro-

D. M. Hodgson et al. / Tetrahedron 59 (2003) 9729–9742
9737
petrol] gave amino alcohol 19 as a white solid (0.066 g,
54%); Rf 0.21 (50% Et2O in petrol); mp 88.5–90.08C;
(Found: C, 52.6; H, 9.2; N, 5.7. C11H23NO3S requires C,
53.0; H, 9.3; N, 5.6%); nmax (KBr)/cm21 3494, 3295, 3093,
2963, 2934, 2875, 1717, 1646, 1480, 1463, 1434, 1397,
1366, 1307, 1210, 1126, 1095, 1072, 1023 and 964; dH
(400 MHz) 5.15 (1H, s, H of CH2v), 5.01 (1H, s, H of
CH2v), 4.91–4.84 (1H, m, NH), 4.27–4.25 (1H, m, CHO),
3.45–3.33 (1H, m, H of CH2N), 3.09–3.01 (1H, m, H of
CH2N), 2.23 (1H, septet, J¼7.0 Hz, CH(CH3)2), 1.39 (9H, s,
C(CH3)3), 1.19 (3H, d, J¼7.0 Hz, CHCH3) and 1.17 (3H, d,
J¼7.0 Hz, CHCH3); dC (100 MHz) 156.1 (Cv), 109.1
(CH2v), 73.9 (CHO), 60.4 (C(CH3)3), 50.3 (CH2N), 31.4
(CH(CH3)2), 24.6 (C(CH3)3), 23.3 (CHCH3) and 22.4
(CHCH3); m/z [CIþ(NH3)] 267 (36%, MNHþ4 ), 250 (51,
MHþ), 223 (21), 169 (22), 155 (61), 130 (33), 114 (98), 97
(100), 86 (18) and 70 (13) (Found: MNHþ4 , 267.1734.
C11H27N2O3S requires 267.1742).
(39), 119 (35) and 72 (20) (Found: MNHþ4 , 301.1578.
C14H25N2O3S requires 301.1586).
4.1.18. 2-Methyl-propane-2-sulfonic acid (2-hydroxy-3-
methylene-pent-4-enyl)-amide 22. Following the general
procedure for (2-hydroxy-3-methylene-heptyl)-carbamic
acid tert-butyl ester 10a, N-Bus epoxide 13 (0.10 g,
0.49 mmol) in Et2O (8 mL) was reacted with vinyllithium26
(1.46 mol dm23 in Et2O, 1.0 mL, 1.46 mmol). Column
chromatography [elution gradient 30–60% Et2O in petrol]
gave amino alcohol 22 as a white solid (0.060 g, 53%); Rf
0.21 (50% Et2O in petrol); mp 87.5–88.58C; nmax (KBr)/
cm21 3496, 3309, 2982, 2936, 2877, 1719, 1638, 1481,
1460, 1397, 1366, 1309, 1204, 1130, 1092, 1021 and 917;
dH (400 MHz) 6.33 (1H, dd, J¼18.0 Hz, 11.5, CHv), 5.40–
5.38 (2H, m, H of CH2v, H of CH2vCH), 5.22 (1H, s, H of
CH2v), 5.13 (1H, d, J¼11.5 Hz, H of CH2vCH), 4.84–
4.81 (1H, m, NH), 4.65–4.62 (1H, m, CHO), 3.52–3.47
(1H, m, H of CH2N), 3.07–3.00 (1H, m, H of CH2N), 1.38
(9H, s, C(CH3)3); dC (100 MHz) 145.8 (Cv), 135.8 (CHv),
116.0 (CH2vCH), 114.6 (CH2v), 70.9 (CHO), 60.0
(C(CH3)3), 50.0 (CH2N) and 24.2 (C(CH3)3); m/z
[CIþ(NH3)] 251 (26%, MNHþ4 ), 223 (100), 207 (14), 169
(12), 155 (37), 114 (10), 98 (12), 86 (16) and 52 (23)
(Found: MNHþ4 , 251.1433. C10H23N2O3S requires
251.1429).
4.1.16. 2-Methyl-propane-2-sulfonic acid (2-hydroxy-
4,4-dimethyl-3-methylene-pentyl)-amide 20. Following
the general procedure for (2-hydroxy-3-methylene-heptyl)-
carbamic acid tert-butyl ester 10a, N-Bus epoxide 13
(0.10 g, 0.49 mmol) in Et2O (8 mL) was reacted with ButLi
(2.5 mol dm23 in light petroleum, 0.585 mL, 1.46 mmol).
Column chromatography [elution gradient 30–60% Et2O in
petrol] gave amino alcohol 20 as a white solid (0.083 g,
65%); Rf 0.15 (40% Et2O in petrol); mp 92.5–93.08C; nmax
(KBr)/cm21 3498, 3301, 3092, 2954, 2932, 2881, 1720,
1642, 1483, 1461, 1440, 1395, 1367, 1301, 1207, 1129,
1096, 1072, 1024 and 967; dH (400 MHz) 5.19–5.11 (2H,
m, H of CH2v, NH), 5.09 (1H, s, H of CH2v), 4.41–4.33
(1H, m, CHO), 3.34–3.25 (1H, m, H of CH2N), 3.11–3.03
(1H, m, H of CH2N), 2.90–2.75 (1H, m, OH), 1.36 (9H, s,
SO2C(CH3)3) and 1.09 (9H, s, C(CH3)3); dC (100 MHz)
158.9 (Cv), 109.2 (CH2v), 70.4 (CHO), 59.9 (SO2C
(CH3)3), 51.8 (CH2N), 35.4 (C(CH3)3), 28.8 (SO2C(CH3)3)
and 24.2 (C(CH3)3); m/z [CIþ(NH3)] 281 (18%, MNHþ4 ),
264 (15, MHþ), 246 (10), 206 (11), 169 (80), 155 (100), 144
(32), 126 (97), 112 (46), 100 (44), 94 (26), 86 (43) and 72
(67) (Found: MNHþ4 , 281.1898. C12H29N2O3S requires
281.1899).
4.1.19. 2-Methyl-propane-2-sulfonic acid (2-hydroxy-3-
trimethylsilylmethyl-but-3-enyl)amide 24. Following the
general procedure for (2-hydroxy-3-methylene-heptyl)-car-
bamic acid tert-butyl ester 10a, N-Bus epoxide 13 (0.10 g,
0.49 mmol) in Et2O (8 mL) was reacted with TMSCH2Li
(1.00 mol dm23 in pentane, 1.46 mL, 1.46 mmol). Column
chromatography [elution gradient 30–60% Et2O in petrol]
gave amino alcohol 24 as a white solid (0.099 g, 69%); Rf
0.16 (40% Et2O in petrol); mp 83.5–84.08C; (Found: C,
48.8; H, 9.6; N, 4.8. C12H27NO3 SSi requires C, 49.1; H,
9.3; N, 4.8%); nmax (KBr)/cm21 3436, 2955, 1480, 1420,
1366, 1306, 1249, 1159, 1126, 1094 and 1010; dH
(400 MHz) 5.04 (1H, s, H of CH2v), 4.80 (1H, s, H of
CH2v), 4.47–4.42 (1H, m, NH), 4.12–4.05 (1H, m, CHO),
3.46–3.40 (1H, m, H of CH2N), 3.11–3.05 (1H, m, H of
CH2N), 1.66 (1H, d, J¼ 14.0 Hz, H of CH2TMS), 1.42–1.35
(10H, m, C(CH3)3, H of CH2TMS) and 0.05 (9H, s, TMS);
dC (100 MHz) 146.6 (CvCH2), 108.6 (CH2v), 74.8
(CHOH), 60.0 (C(CH3)3), 48.9 (CH2N), 24.3 (C(CH3)3),
23.0 (CH2TMS) and 21.4 (TMS); m/z [CIþ(NH3)] 311
(100%, MNHþ4 ), 294 (28, MHþ), 278 (16), 240 (22), 223
(60) and 210 (22) (Found: MNHþ4 , 311.1818. C12H31N2O3-
SSi requires 311.1825).
4.1.17. 2-Methyl-propane-2-sulfonic acid (2-hydroxy-3-
phenyl-but-3-enyl)-amide 21. Following the general pro-
cedure for (2-hydroxy-3-methylene-heptyl)-carbamic acid
tert-butyl ester 10a, N-Bus epoxide 13 (0.10 g, 0.49 mmol)
in Et2O (8 mL) was reacted with PhLi (1.50 mol dm23 in
light petroleum, 0.98 mL, 0.146 mmol). Column chroma-
tography [elution gradient 30–60% Et2O in petrol] gave
amino alcohol 21 as a white solid (0.061 g, 44%); Rf 0.15
(40% Et2O in petrol); mp 90.0–90.58C; nmax (KBr)/cm21
3479, 3305, 2983, 2936, 1691, 1632, 1600, 1479, 1450,
1398, 1367, 1306, 1229, 1208, 1126 and 1025; dH
(400 MHz) 7.42–7.31 (5H, m, 5£H of Ar), 5.51 (1H, s, H
of CH2v), 5.47 (1H, s, H of CH2v), 4.89 (1H, d, J¼5.5 Hz,
NH), 4.71–4.69 (1H, m, CHO), 3.44–3.38 (1H, m, H of
CH2N), 3.09–3.03 (1H, m, H of CH2N), 2.95 (1H, br, s, OH)
and 1.36 (9H, s, C(CH3)3); dC (100 MHz) 148.2 (CCv),
138.7 (Cv), 128.6 (2£CH of Ar), 128.1 (CH of Ar), 126.5
(2£CH of Ar), 114.1 (CH2v), 72.9 (CHO), 60.0 (C(CH3)3),
49.5 (CH2N) and 24.2 (C(CH3)3); m/z [CIþ(NH3)] 301
(36%, MNHþ4 ), 284 (24, MHþ), 169 (100), 152 (67), 131
4.1.20. 2-Methyl-propane-2-sulfonic acid (2-hydroxy-3-
methylene-4-trimethylsilyl-nonyl)amide
23.
BunLi
(2.30 mol dm23 in hexane, 0.636 mL, 1.46 mmol) was
added dropwise to a solution of trimethylvinylsilane
(0.236 mL, 1.61 mmol) in THF (1 mL) at 08C. After 1 h at
08C the reaction was cooled to 2788C where upon a solution
of N-Bus epoxide 13 (0.10 g, 0.49 mmol) in THF (8 mL)
was added dropwise. After another 1 h at 2788C the
reaction was warmed to 258C for 1 h and then sat. aq. NH4Cl
(5 mL) was added. The reaction mixture was extracted with
Et2O (3£10 mL) and the combined organic extracts were
washed with sat. aq. NaHCO3 (15 mL), brine (15 mL), dried

9738
D. M. Hodgson et al. / Tetrahedron 59 (2003) 9729–9742
(MgSO4) and evaporated under reduced pressure. Purifi-
cation of the residue by column chromatography [elution
gradient 30–60% Et2O in petrol] gave amino alcohol 23
(2:1 mixture of diastereomers A:B) as a white solid
(0.127 g, 72%); Rf 0.23 (50% Et2O in petrol); mp 81.0–
82.58C; nmax (KBr)/cm21 3562, 3353, 3000, 2995, 1501,
1466, 1403, 1398, 1352, 1256, 1163, 1102, 1001 and 964;
dH (400 MHz) 5.18 (0.66H, s, H of CH2v of B), 5.03
(0.33H, s, H of CH2v of A), 4.99–4.92 (1H, m, NH), 4.75
(0.33H, s, H of CH2v of A), 4.72 (0.66H, s, H of CH2v of
B), 4.06–4.04 (0.33H, m, CHO of A), 3.93 (0.66H, m, CHO
of B), 4.50–4.42 (0.66H, m, H of CH2N of B), 4.34–4.26
(0.33H, m, H of CH2N of A), 3.13–3.04 (0.33H, m, H of
CH2N of A), 2.92–2.83 (0.66H, m, H of CH2N of B), 2.80
(0.66H, br s, CHCv of B), 2.65 (0.33H, br s, CHCv of A),
1.65–1.42 (2H, m, CH2CH2CH), 1.37 (9H, s, (CH3)3C),
1.30–1.00 (6H, m, CH2CH3, CH2CH, CH2CH2CH3),
0.89–0.81 (3H, m, CH3(CH2)4) and 20.03 (9H, s, TMS);
dC (100 MHz) 151.3 (Cv), 108.6 (CH2v of A), 105.9
(CH2v of B), 75.8 (CHO of A), 75.4 (CHO of B), 59.9
(C(CH3)3), 49.6 (CH2N), 33.4 (CHCv), 31.1 (CH2CH),
29.3 (CH2CH2CH), 28.7 (CH2CH2CH3), 24.3 ((CH3)3C),
22.6 (CH2CH3), 14.1 (CH3CH2), 22.1 (TMS of A) and –2.8
(TMS of B); m/z [CIþ(NH3)] 381 (63%, MNHþ4 ), 348 (23),
309 (19), 293 (17), 274 (20), 218 (24), 154 (100) and 90
(33) (Found: MNH4þ, 381.2609. C17H41N2O3SSi requires
381.2607).
the residue by column chromatography [elution gradient
0–30% Et2O in petrol] gave alkene 28 (1:1 mixture of
rotamers A and B) as a clear colourless oil (2.08 g, 94%); Rf
0.62 (50% Et2O in petrol); nmax (film)/cm21 3067, 2975,
2930, 2856, 2360, 2341, 1704, 1666, 1479, 1449, 1404,
1366, 1337, 1256, 1183, 1114 and 1019; dH (400 MHz)
5.47 (1H, br, d, J¼19.0 Hz, CHv), 4.12–3.93 (4H, br, m,
2£CH2N), 1.77 (1.5H, s, CH3 of A), 1.74 (1.5H, s, CH3 of
B) and 1.51 (9H, s, (CH3)3C); dC (100 MHz) 154.2 (CvO),
135.3 (Cv), 135.2 (Cv), 119.4 (CHv), 119.3 (CHv),
79.1 (C(CH3)3), 79.0 (C(CH3)3), 56.3 (CH2N), 55.9
(CH2N), 53.4 (CH2N), 53.1 (CH2N), 28.5 ((CH3)3C), and
19.9 (CH3).
4.1.23. 1-Methyl-3-(2-methyl-propane-2-sulfonyl)-6-oxa-
3-azabicyclo[3.1.0]hexane 29. Alkene 28 (0.50 g,
2.73 mmol) in CH2Cl2 (20 mL) was stirred with TFA
(4.00 mL, 51.9 mmol) at room temperature for 4 h. The
solvent was removed under reduced pressure and the residue
co-evaporated with toluene (15 mL) to give the amine as a
black oil (0.22 g, quant.); no other purification was required;
n
max (film)/cm21 3420, 2987, 2786, 2361, 2342, 1780, 1682,
1456, 1436, 1204, 1142, 1029 and 840; dH (400 MHz) 9.38
(2H, br s, NH2), 5.47 (1H, s, CHv), 4.11 (2H, br, s, CH2N),
3.98 (2H, br, s, CH2N) and 1.84 (3H, s, CH3); dC (100 MHz)
134.9 (vC), 118.1 (CHv), 54.5 (CH2N), 52.4 (CH2N), and
13.3 (CH3); m/z [CIþNH3] 82 (70%, MHþ), 80 (18), 69
(29), 68 (100), 67 (30), 55 (15), 45 (30) and 41 (31) (Found:
MHþ, 82.0656. C5H10N requires 82.0657).
4.1.21. tert-Butyl allyl(2-methylallyl)carbamate 26. Boc-
protected allylamine 25 (2.00 g, 12.7 mmol) was added to a
solution of NaH (0.42 g, 60% dispersion in mineral oil,
14 mmol) in DMF (100 mL) at ambient temperature. After
1 h the reaction was cooled to 08C and methallyl bromide
(1.41 mL, 14.0 mmol) was added. After 1 h the reaction was
quenched with MeOH (10 mL) and then diluted with H2O
(70 mL) and washed with Et2O (4£50 mL). The organic
phases were combined, dried and the solvent removed to
give a yellow oil. Purification of the residue by column
chromatography (elution gradient 0–40% Et2O in petrol)
gave diene 26 (1:1 mixture of rotamers) as a clear colourless
oil (2.55 g, 95%); Rf 0.71 (50% Et2O in petrol); nmax (film)/
cm21 3080, 2976, 2927, 1699, 1657, 1478, 1456, 1406,
1366, 1244, 1173, 1144, 1098 and 1024; dH (400 MHz)
5.82–5.70 (1H, m, CHv), 5.17–5.06 (2H, m, CH2v), 4.86
(1H, s, H of CH2v), 4.74 (1H, s, H of CH2v), 3.89–3.70
(4H, m, 2£NCH2), 1.69 (3H, s, CH3), and 1.48 (9H, s,
(CH3)3C); dC (100 MHz) 155.6 (CvO), 142.4 (Cv), 141.4
(Cv), 133.8 (CHv), 116.6 (CH2v), 116.1 (CH2v), 111.5
(CH2v), 79.5 (C(CH3)3), 51.5 (CH2N), 48.6 (CH2N), 48.2
(CH2N), 28.3 ((CH3)3C) and 19.9 (CH3); m/z [CIþ(NH3)]
212 (42%, MHþ), 173 (100), 156 (39), 152 (62), 112 (47),
98 (29), 95 (49), 81 (35) and 72 (24) (Found: MHþ,
212.1651. C12H22NO2 requires 212.1650).
To a solution of the above amine (0.22 g, 2.73 mmol) in
CH2Cl2 (20 mL) at 258C was added Et3N (3.81 mL,
27.3 mmol) dropwise. After 1 h the reaction was cooled to
08C and ice-cold tert-butylsulfinyl chloride17 (0.767 g,
5.46 mmol) in CH2Cl2 (0.5 mL) was added. After 1 h
(TLC monitoring, 30% Et2O in petrol), the mixture was
diluted with sat. aq. NaHCO3 (30 mL). The aqueous layer
was then extracted with CH2Cl2 (3£10 mL). The organic
extracts were combined, dried (MgSO4) and concentrated
under reduced pressure to reveal a brown oil. Purification of
the residue by column chromatography [elution gradient
0–40% Et2O in petrol] gave the desired alkene as a clear
colourless oil (0.501 g, 98%); Rf 0.56 (50% Et2O in petrol);
n
max (film)/cm21 3424, 2985, 2714, 2509, 1680, 1476, 1394,
1300, 1203, 1180, 1135, 1030, and 801; dH (400 MHz)
5.38–5.32 (1H, m, CHv), 4.29–4.14 (2H, m, CH2N),
3.97–3.87 (1H, m, H of CH2N), 3.77–3.71 (1H, m, H
of CH2N), 1.74 (3H, br, s, CH3Cv) and 1.22 (9H, s,
(CH3)3C); dC (100 MHz) 136.1 (vC), 120.2 (CHv), 68.1
(C(CH3)3), 57.4 (CH2N), 55.8 (CH2N), 23.0 (C(CH3)3) and
13.9 (CH3).
1,1,1-Trifluoroacetone (3.56 mL, 39.8 mmol) was added
dropwise to a stirred solution of the above alkene (0.501 g,
4.1.22. tert-Butyl 3-methyl-2,5-dihydropyrrole-1-car-
boxylic acid 28. Grubbs’ 2nd generation catalyst22 27
(0.45 mg, 0.61 mmol) was added to a solution of diene 26
(2.55 g, 12.1 mmol) in anhydrous CH2Cl2 (750 mL) at
reflux. The resulting mixture was stirred at reflux overnight,
after which time TLC showed complete consumption of
starting material (eluent 50% Et2O in petrol). The reaction
was quenched by exposure to air for ,2 h and the solvent
was then removed under reduced pressure. Purification of
2.68 mmol) and aq. Na2EDTA (4£1024 mol dm23
,
13.4 mL, 0.005 mmol) in MeCN (70 mL) at 08C. A mixture
of NaHCO3 (1.80 g, 21.4 mmol) and Oxonew (8.24 g,
13.4 mmol) was then added portionwise over a period of
1 h. After 4 h, a mixture of NaHCO3 (1.80 g, 21.4 mmol)
and Oxonew (8.24 g, 13.4 mmol) was added and the
reaction was stirred overnight. The reaction mixture was
then diluted with water (50 mL), filtered and extracted with
CH2Cl2 (3£50 mL). The combined organic extracts were

D. M. Hodgson et al. / Tetrahedron 59 (2003) 9729–9742
9739
dried (Na2SO4) and concentrated under reduced pressure to
give a yellow solid. Purification of the residue by column
chromatography [elution gradient 0–60% Et2O in petrol]
gave epoxide 29 as a white solid (0.340 g, 58%); Rf 0.23
(50% Et2O in petrol); mp 80.5–81.58C; (Found: C, 48.9; H,
7.9; N, 6.4. C9H17NO3S requires C, 49.2; H, 7.8; N, 6.4%);
nmax (KBr)/cm21 2984, 1481, 1468, 1452, 1312, 1138,
1108, 1050 and 961; dH (400 MHz) 3.82 (1H, d, J¼12.0 Hz,
H of CH2N), 3.73 (1H, d, J¼11.5 Hz, H of CH2N),
3.46–3.41 (2H, m, H of CH2N, CHO), 3.34 (1H, d, J¼
11.5 Hz, H of CH2N), 1.59 (3H, br, s, CH3Cv) and 1.39
(9H, s, (CH3)3C); dC (100 MHz) 77.2 (OCCH3), 76.8
(C(CH3)3), 60.4 (CHO), 53.1 (CH2N), 50.6 (CH2N), 24.5
(C(CH3)3) and 15.1 (CH3); m/z [CIþ(NH3)] 237 (100,
MNHþ4 ), 220 (12, MHþ), 124 (13), 110 (19), 100 (35), 84
(15), 69 (12), 58 (43), 52 (69) and 44 (94) (Found: MNHþ4 ,
237.1269. C9H21N2O3S requires 237.1273).
131 (12) (Found: MNHþ4 , 315.1740. C15H27N2O3S requires
315.1742).
4.1.26. 2-Methyl-propane-2-sulfonic acid (2-hydroxy-2-
methyl-3-(trimethylsilylmethyl)-but-3-enyl)amide
32.
Following the general procedure for (2-hydroxy-3-methyl-
ene-heptyl)-carbamic acid tert-butyl ester 10a, N-Bus
epoxide 29 (0.10 g, 0.46 mmol) in Et2O (8 mL) was reacted
with TMSCH2Li (1.0 mol dm23 in light petroleum,
1.37 mL, 1.37 mmol). Column chromatography [elution
gradient 30–100% Et2O in petrol] gave amino alcohol 32 as
a white solid (0.084 g, 60%); Rf 0.38 (50% Et2O in petrol);
mp 69.5–70.08C; nmax (KBr)/cm21 3497, 3306, 2987, 2955,
2898, 1629, 1480, 1458, 1420, 1396, 1366, 1309, 1248,
1168, 1127, 1082, 1022 and 941; dH (400 MHz) 5.01 (1H,
s, H of CH2v), 4.78 (1H, s, H of CH2v), 4.43 (1H, t,
J¼6.0 Hz, NH), 3.21 (2H, d, J¼6.0 Hz, CH2N), 2.28 (1H,
br, s, OH), 1.60 (1H, d, J¼14.5 Hz, H of CH2Cv), 1.47
(1H, d, J¼14.5 Hz, H of CH2Cv), 1.39 (9H, s, C(CH3)3),
1.32 (3H, s, CH3) and 0.04 (9H, s, TMS); dC (100 MHz)
150.1 (Cv), 108.9 (CH2v), 75.2 (C(CH3)3), 59.9 (COH),
52.9 (CH2N), 25.0 (CH3), 24.3 (C(CH3)3), 21.1 (CH2Cv),
and 20.79 (TMS); m/z [CIþ(NH3)] 325 (66%, MNHþ4 ), 290
(29), 218 (75), 141 (22), 98 (100), 90 (49) and 52 (12)
(Found: MNHþ4 , 325.1975. C13H33N2O3SSi requires
325.1976).
4.1.24. 2-Methyl-propane-2-sulfonic acid (2-hydroxy-2-
methyl-3-methyleneheptyl)amide 30. Following the
general procedure for (2-hydroxy-3-methylene-heptyl)-
carbamic acid tert-butyl ester 10a, N-Bus epoxide 29
(0.10 g, 0.46 mmol) in Et2O (8 mL) was reacted with BunLi
(1.60 mol dm23 in pentane, 0.856 mL, 1.37 mmol). Column
chromatography [elution gradient 30–100% Et2O in petrol]
gave amino alcohol 30 as a white solid (0.078 g, 62%);
Rf 0.35 (50% Et2O in petrol); mp 73.0–73.58C; nmax (KBr)/
cm21 3492, 3302, 2958, 2932, 2873, 1722, 1640, 1480,
1459, 1397, 1366, 1308, 1208, 1126, 1086, 1022 and 953;
dH (400 MHz) 5.19 (1H, s, H of CH2v), 4.98 (1H, s, H of
CH2v), 4.44 (1H, t, J¼5.5 Hz, NH), 3.20 (2H, d, J¼5.5 Hz,
CH2N), 2.49 (1H, br, s, OH), 2.00 (2H, t, J¼7.5 Hz,
CH2Cv), 1.52–1.31 (16H, m, CH2CH2CH3, CH2CH3,
C(CH3)3, CH3) and 1.93 (3H, t, J¼7.0 Hz, CH3(CH2)3); dC
(100 MHz) 152.3 (Cv), 109.7 (CH2v), 75.1 (C(CH3)3),
60.0 (COH), 52.8 (CH2N), 30.9 (CH2Cv), 30.6 (CH2CH2
CH3), 25.3 (CH2CH3), 24.3 (C(CH3)3), 22.6 (CH3) and 14.0
(CH3(CH2)3); m/z [CIþ(NH3)] 295 (98%, MNHþ4 ), 262
(13), 261 (19), 260 (100), 204 (12), 158 (23), 140 (89) and
125 (20) (Found: MNHþ4 , 295.2056. C13H31N2O3S requires
295.2055).
4.1.27. tert-Butyl (3-hydroxy-4-methyleneoctyl)carba-
mate 34 and tert-butyl 4-hydroxy-3,4-dihydro-2H-pyri-
dine-1-carboxylate 35. Following the general procedure for
(2-Hydroxy-3-methylene-heptyl)-carbamic acid tert-butyl
ester 10a, N-Boc epoxide 3323 (0.10 g, 0.50 mmol) in Et2O
(8 mL) was reacted with BunLi (2.50 mol dm23 in hexane,
0.603 mL, 1.51 mmol). Column chromatography [elution
gradient 30–60% Et2O in petrol] gave amino alcohol 34 as a
clear colourless oil (0.009 g, 7%); Rf 0.33 (50% Et2O in
petrol); nmax (film)/cm21 3375, 3083, 2959, 2952, 2873,
1693, 1601, 1516, 1456, 1427, 1392, 1367, 1304, 1278,
1251, 1224, 1171, 1110, 1066 and 1005; dH (400 MHz) 5.06
(1H, s, H of CH2v), 4.92–4.79 (2H, m, H of CH2v, NH),
4.16–4.08 (1H, m, CHO), 3.49–3.37 (1H, m, H of CH2N),
3.18–3.13 (1H, m, H of CH2N), 1.81–1.71 (1H, m, H of
CH2CHO), 2.15–1.93 (2H, m, CH2Cv), 1.66–1.17 (14H,
m, H of CH2CHO, CH2CH2 CH3, (CH3)3C, CH2CH3) and
0.91 (3H, t, CH3CH2); dC (100 MHz) 156.0 (CvO), 151.8
(Cv), 108.2 (CH2v), 78.7 (C(CH3)3), 72.3 (CHO), 37.0
(CH2N), 35.3 (CH2CHO), 31.0 (CH2Cv), 29.7 (CH2CH2-
CH3), 27.7 ((CH3)3C), 21.9 (CH2CH3) and 13.0 (CH3CH2);
m/z [CIþ(NH3)] 258 (23%, MHþ), 219 (20), 198 (32), 184
(23), 160 (19), 152 (29), 142 (56), 126 (32), 112 (53), 98
(100), 84 (65) and 72 (53) (Found: MHþ, 258.2069.
C14H28NO3 requires 258.2069). Also isolated was cyclic
alcohol 35 as a clear colourless oil (0.080 g, 80%); Rf 0.11
(50% Et2O in petrol); nmax (film)/cm21 3466, 3055, 2978,
2993, 2878, 1694, 1644, 1477, 1456, 1414, 1367, 1306,
1267, 1242, 1168, 1122 and 1058; dH (400 MHz) 7.07–6.79
(1H, m, NCHv), 5.11–4.91 (1H, m, vCHCHO), 4.22–
4.15 (1H, m, CHO), 3.95–3.75 (1H, m, H of CH2N), 3.38–
3.26 (1H, m, H of CH2N), 1.99–1.73 (2H, m, CH2CHO) and
1.65–1.14 (9H, m, (CH3)3C); dC (100 MHz) 158.2 (CvO),
127.6 (vCHN), 106.1 (vCHCHO), 79.9 (C(CH3)3), 60.5
(CHO), 37.2 (CH2N), 30.2 (CH2CHO) and 27.8 ((CH3)3C);
m/z [CIþ(NH3)] 200 (27%, MHþ), 182 (69), 135 (25), 98
4.1.25. 2-Methyl-propane-2-sulfonic acid (2-hydroxy-2-
methyl-3-phenylbut-3-enyl)amide 31. Following the
general procedure for (2-hydroxy-3-methylene-heptyl)-
carbamic acid tert-butyl ester 10a, N-Bus epoxide 29
(0.10 g, 0.46 mmol) in Et2O (8 mL) was reacted with PhLi
(1.80 mol dm23 in hexane, 0.761 mL, 1.37 mmol). Column
chromatography [elution gradient 30–100% Et2O in petrol]
gave amino alcohol 31 as a white solid (0.069 g, 51%); Rf
0.33 (50% Et2O in petrol); mp 75.5–76.08C; nmax (KBr)/
cm21 3451, 3295, 2986, 2937, 2875, 1480, 1454, 1442,
1425, 1396, 1376, 1307, 1207, 1162, 1120, 1094, 1077,
1026 and 960; dH (400 MHz) 7.38–7.30 (3H, m, H of Ar),
7.27–7.24 (2H, m, H of Ar), 5.59 (1H, s, H of CH2v),
5.18 (1H, s, H of CH2v), 4.51 (1H, br, t, J¼6.0 Hz, NH),
3.37–3.26 (2H, m, CH2N), 2.47 (1H, br, s, OH), 1.44 (3H, s,
CH3) and 1.35 (9H, s, C(CH3)3); dC (100 MHz) 153.4 (Cv),
140.3 (C of Ar), 128.5 (CH of Ar), 128.2 (CH of Ar),
127.4 (CH of Ar), 115.8 (CH2v), 74.6 (C(CH3)3),
60.0 (COH), 52.9 (CH2N), 25.9 (CH3), and 24.4
(C(CH3)3); m/z [CIþ(NH3)] 315 (100%, MNHþ4 ), 280
(72), 178 (18), 166 (20), 164 (41), 160 (27), 145 (22) and

9740
D. M. Hodgson et al. / Tetrahedron 59 (2003) 9729–9742
(22) and 82 (100) (Found: MHþ, 200.1286. C10H18NO3
requires 200.1286).
epoxide 38 (0.10 g, 0.46 mmol) in Et2O (8 mL) was reacted
with BunLi (2.50 mol dm23 in light petroleum, 0.548 mL,
1.37 mmol). Column chromatography [elution gradient
30–60% Et2O in petrol] gave amino alcohol 39 (R¼Bun)
as a white solid (0.065 g, 51%); Rf 0.31 (50% Et2O in
petrol); mp 76.0–76.58C; nmax (film)/cm21 3480, 3295,
2932, 2873, 1705, 1647, 1480, 1456, 1366, 1303, 1207,
1126, 1088 and 1021; dH (400 MHz) 5.09 (1H, s, H of
CH2v), 4.89 (1H, s, H of CH2v), 4.84–4.75 (1H, m, NH),
4.29–4.22 (1H, m, CHO), 2.64–2.59 (2H, m, CH2N),
2.32–2.22 (1H, m, OH), 2.08 (1H, dt, J¼16.0, 8.0 Hz, H of
CH2Cv), 1.99 (1H, dt, J¼16.0, 8.0 Hz, H of CH2Cv),
1.90–1.80 (1H, m, H of CH2CHO), 1.78–1.67 (1H, m, H of
CH2CHO), 1.49–1.26 (13H, m, (CH3)3C, CH2CH2CH3,
CH2CH3) and 0.90 (3H, t, J¼7.5 Hz, CH2CH3); dC
(100 MHz) 151.5 (Cv), 109.2 (CH2v), 73.5 (CHO),
59.8 (C(CH3)3), 42.3 (CH2N), 35.9 (CH2CHO), 31.5
(CH2CHv), 30.1 (CH2CH2CH3), 24.3 ((CH3)3C), 22.7
(CH2CH3), and 14.0 (CH3); m/z [CIþ(NH3)] 295 (100%,
MNHþ4 ), 278 (40, MHþ), 260 (18), 204 (12), 186 (10), 158
(23), and 140 (94) (Found: MNHþ4 , 295.2057. C13H31N2O3S
requires 295.2055). Also isolated was cyclic alcohol 40
as a clear colourless oil (0.017 g, 17%); Rf 0.13 (50%
Et2O in petrol); nmax (film)/cm21 3506, 2976, 2935,
2884, 2257, 1641, 1481, 1463, 1397, 1366, 1324, 1272,
1205, 1138, 1079, 1050, 1020 and 996; dH (400 MHz)
6.61 (1H, d, J¼ 8.0 Hz, NCHv), 5.07–4.97 (1H, m,
CHv), 4.22–4.13 (1H, m, CHOH), 3.88–3.77 (1H, m, H
of NCH2), 3.45 (1H, dt, J¼12.0, 3.0 Hz, H of NCH2),
2.30–2.18 (1H, m, OH), 2.00–1.75 (2H, br, m, CH2CHOH)
and 1.39 (9H, s, (CH3)3C); dC (100 MHz) 129.3 (NCHv),
105.9 (CHv), 62.1 (CHOH), 59.7 (C(CH3)3), 41.6
(NCH2), 30.9 (CH2CHOH), and 24.5 ((CH3)3C); m/z
[CIþ(NH3)] 237 (70%, MNHþ4 ), 220 (10, MHþ), 140
(12), 99 (27), 98 (32), 82 (55), 80 (47), 70 (14) and 57 (100)
(Found: MNHþ4 , 237.1272. C9H21N2O3S requires
237.1273).
4.1.28. 1-(2-Methyl-propane-2-sulfinyl)-1,2,3,6-tetra-
hydropyridine 37. Et3N (16.8 mL, 120 mmol) was added
to a solution of 1,2,3,6-tetrahydropyridine 36 (1.00 g,
12 mmol) in CH2Cl2 (100 mL) at 258C. The reaction was
allowed to stir for 1 h before tert-butylsulfinyl chloride17
(3.39 g, 24 mmol) in CH2Cl2 (5 mL) was added to the
mixture at 08C. After 4 h (TLC monitoring, 30% Et2O in
petrol), the mixture was diluted with sat. aq. NaHCO3. The
aqueous layer was extracted with CH2Cl2 (3£30 mL). The
organic extracts were combined, dried (MgSO4) and
concentrated under reduced pressure. Purification of the
residue by column chromatography [elution gradient
0–30% Et2O in petrol] gave alkene 37 as a clear colourless
oil (2.16 g, 96%); Rf 0.61 (50% Et2O in petrol); nmax (film)/
cm21 3034, 2955, 2921, 2865, 2836, 1657, 1590, 1476,
1458, 1432, 1388, 1362, 1300, 1231, 1205, 1108, 1079,
1040 and 1005; dH (400 MHz) 5.81–5.74 (1H, m, NCH2
CHv), 5.69–5.61 (1H, m, CHv), 3.72–3.61 (1H, m, H
of NCH2CH), 3.59–3.50 (1H, m, H of NCH2CHv),
3.43–3.34 (1H, m, H of CH2CH2CHv), 3.27–3.17 (1H,
m, H of CH2CH2CHv), 2.19–2.17 (2H, br, m, NCH2CH2)
and1.16(9H,s,(CH3)3C);dC(100 MHz)125.7(NCH2CHv),
124.8 (CHv), 58.2 (C(CH3)3), 44.6 (NCH2CHv), 44.1
(CH2CH2CHv), 25.5 (NCH2CH2) and 23.2 ((CH3)3C); m/z
[CIþ(NH3)] 205 (20%, MNHþ4 ), 188 (100, MHþ), 172 (18),
114 (10), 98 (19), 84 (52) and 82 (65) (Found: MHþ,
188.1111. C9H18NOS requires 188.1109).
4.1.29. 3-(2-Methyl-propane-2-sulfonyl)-7-oxa-3-aza-
bicyclo[4.1.0]heptane 38. mCPBA (9.91 g, 28.7 mmol,
50% w/w in H2O) was added to a solution of alkene 37
(1.92 g, 10.3 mmol) in CH2Cl2 (200 mL) at 258C. After 1 h
the reaction was complete (TLC) and was quenched by
addition of 10% aq. sodium bisulfite solution until all the
oxidant had been consumed (starch iodide paper). The
organic layer was separated and washed with sat. aq.
NaHCO3 and brine, the extract was dried (MgSO4) and
solvent removed to give a yellow oil. Purification of the
residue by column chromatography [elution 40%–100%
Et2O in petrol] gave epoxide 38 as a white crystalline
solid (1.62 g, 72%); Rf 0.21 (60% Et2O in petrol); mp
88.0–88.58C; (Found: C, 49.3; H, 7.8; N, 6.3. C9H17NO3S
requires C, 49.3; H, 7.8; N, 6.4%); nmax (KBr)/cm21 3000,
2983, 2940, 2920, 2876, 1480, 1453, 1426, 1397, 1366,
1308, 1257, 1181, 1158, 1121, 1093, 1070, 1047 and 1020;
dH (400 MHz) 3.93 (1H, d, J¼14.0 Hz, H of CHCH2N),
3.63 (1H, d, J¼14.0 Hz, H of CHCH2N), 3.31–3.15 (4H, m,
NCH2CHO, N(CH2)2CHO, CH2CH2N), 2.23–2.01 (2H, m,
CH2CH2N) and 1.34 (9H, s, (CH3)3C); dC (100 MHz) 60.8
(C(CH3)3), 50.0 (CHO), 49.7 (CHO), 45.0 (CHCH2N), 40.6
(CH2CH2N), 24.9 (CH2CH2N) and 23.8 ((CH3)3C); m/z
[CIþ(NH3)] 237 (100%, MNHþ4 ), 220 (26, MHþ) and 100
(27) (Found: MNHþ4 , 237.1271. C9H21N2O3S requires
237.1273).
4.1.31. 2-Methyl-propane-2-sulfonic acid (3-hydroxy-5-
methyl-4-methylenehexyl)amide 39 (R5Pri). Following
the general procedure for (2-hydroxy-3-methylene-heptyl)-
carbamic acid tert-butyl ester 10a, N-Bus epoxide 38
(0.10 g, 0.46 mmol) in Et2O (8 mL) was reacted with PriLi
(2.00 mol dm23in light petroleum, 0.685 mL, 1.37 mmol).
Column chromatography [elution gradient 30–100% Et2O
in petrol] gave amino alcohol 39 (R¼Pri) as a white solid
(0.028 g, 23%); Rf 0.34 (50% Et2O in light Petroleum); mp
96.0–96.58C; nmax (KBr)/cm21 3498, 3295, 2962, 2934,
2874, 1647, 1480, 1459, 1396, 1366, 1304, 1206, 1127,
1096 and 902; dH (400 MHz) 5.09 (1H, s, H of CH2v), 4.98
(1H, s, H of CH2v), 4.77 (1H, t, J¼5.0 Hz, NH), 4.30–4.28
(1H, m, CHO), 3.46–3.24 (2H, m, CH2N), 2.23 (1H, septet,
J¼7.0 Hz, CHCv), 1.91–1.83 (1H, m, H of CH2CHO),
1.79–1.68 (1H, m, H of CH2CHO), 1.42 (9H, s, (CH3)3C)),
1.09 (3H, d, J¼7.0 Hz, CH3CH) and 1.05 (3H, d, J¼7.0 Hz,
CH3CH); dC (100 MHz) 158.5 (Cv), 107.2 (CH2v), 72.7
(C(CH3)3), 59.7 (CHO), 42.5 (CH2N), 36.4 (CH2CHOH),
30.4 (CHCv), 24.3 ((CH3)3C), 23.2 (CH3CH) and 22.4
(CH3CH); m/z [CIþ(NH3)] 281 (23%, MNHþ4 ), 264 (27,
MHþ), 246 (13), 183 (15), 155 (44), 144 (33), 128 (100),
126 (22), 110 (10), 98 (13), 90 (10), 82 (15), 72 (10), 58 (69)
and 44 (69) (Found: MNHþ4 , 281.1898. C12H29N2O3S
requires 281.1899).
4.1.30. 2-Methyl-propane-2-sulfonic acid (3-hydroxy-4-
methyleneoctyl)amide 39 (R5Bun) and 1-(2-methyl-
propane-2-sulfonyl)-1,2,3,4-tetrahydropyridin-4-ol 40.
Following the general procedure for (2-hydroxy-3-methyl-
ene-heptyl)-carbamic acid tert-butyl ester 10a, N-Bus

D. M. Hodgson et al. / Tetrahedron 59 (2003) 9729–9742
9741
4.1.32. 2-Methyl-propane-2-sulfonic acid (3-hydroxy-5-
methyl-4-methyleneheptyl)amide 39 (R5Bus). Following
the general procedure for (2-hydroxy-3-methylene-heptyl)-
carbamic acid tert-butyl ester 10a, N-Bus epoxide 38
(0.10 g, 0.46 mmol) in Et2O (8 mL) was reacted with BusLi
(1.20 mol dm23 in light petroleum, 1.14 mL, 1.37 mmol).
Column chromatography [elution gradient 30–60% Et2O in
petrol] gave amino alcohol 39 (R¼Bus, 1:1 mixture of
diastereomers A:B) as a white solid (0.052 g, 41%); Rf 0.33
(50% Et2O in petrol); mp 78.5–79.08C; nmax (KBr)/cm21
3489, 3295, 3088, 2963, 2633, 2875, 1646, 1480, 1456,
1422, 1396, 1366, 1304, 1207, 1127, 1090, 1022 and 955;
dH (400 MHz) 5.11 (1H, d, J¼6.5 Hz, H of CH2v), 4.89
(1H, d, J¼6.5 Hz, H of CH2v), 4.85–4.79 (1H, m, NH),
4.27–4.20 (1H, m, CHO), 3.41–3.25 (2H, m, CH2N), 2.30–
2.15 (1H, m, OH), 2.04–1.94 (1H, m, CHCv), 1.93–1.82
(1H, m, CH2CHO of A), 1.78–1.65 (1H, m, CH2CHO of B),
1.56–1.30 (11H, m, (CH3)3C, CH2CH3), 1.07 (1.5H, d,
J¼7.0 Hz, CHCH3 of A), 1.03 (1.5H, d, J¼7.0 Hz, CHCH3
of B), 0.87 (1.5H, t, J¼6.5 Hz, CH2CH3 of A) and 0.84
(1.5H, t, J¼6.5 Hz, CH2CH3 of B); dC (100 MHz) 157.3
(Cv of A), 157.2 (Cv of B), 107.9 (CH2v of A), 107.8
(CH2v of B), 73.2 (CHO of A), 72.9 (CHO of B), 59.7
(C(CH3)3), 42.5 (CH2N of A), 42.4 (CH2N of B), 37.6
(CHCv of A), 37.3 (CHCv of B), 36.4 (CH2CHO of A),
36.3 (CH2CHO of B), 29.8 (CH2CH3 of A), 28.9 (CH2CH3
of B), 24.3 ((CH3)3C of A), 24.1 ((CH3)3C of B), 21.3
(CHCH3 of A), 20.2 (CHCH3 of B), 12.0 (CH2CH3 of A)
and 11.8 (CH2CH3 of B); m/z [CIþ(NH3)] 295 (100%,
MNHþ4 ), 278 (24, MHþ), 260 (14), 158 (12), 142 (19) and
140 (100) (Found: MNHþ4 , 295.2057. C13H31N2O3S
requires 295.2055).
Column chromatography [elution gradient 30–60% Et2O in
petrol] gave amino alcohol 39 (R¼Ph) as a white solid
(0.007 g, 5%); Rf 0.31 (50% Et2O in petrol); mp 78.5–
79.08C; nmax (KBr)/cm21 3302, 2926, 1641, 1452, 1366,
1305, 1126, 1082, 1020 and 952; dH (400 MHz) 7.40–7.28
(5H, m, Ar), 5.43 (1H, s, H of CH2v), 5.37 (1H, s, H of
CH2v), 4.91–4.86 (1H, br, m, NH), 4.53–4.49 (1H, m,
CHO), 3.46–3.38 (1H, m, H of CH2N), 3.34–3.25 (1H, m,
H of CH2N), 2.30 (1H, br, s, OH), 1.93–1.82 (1H, m, H of
CH2CHO), 1.74–1.66 (1H, m, H of CH2CHO), and 1.41
(9H, s, (CH3)C); dC (100 MHz) 151.1 (CCv), 139.3 (Cv),
128.4 (2£CH of Ar), 127.8 (CH of Ar), 126.7 (2£CH of
Ar), 112.7 (CH2v), 65.7 (CHOH), 59.7 (C(CH3)3), 42.1
(CH2N), 36.0 (CH2CHOH), and 24.3 ((CH3)3C); m/z
[CIþ(NH3)] 315 (86%, MNHþ4 ), 298 (43, MHþ), 202
(25), 180 (52), 178 (84), 176 (37), 162 (70), 160 (100), 152
(51), 146 (24), 145 (22), 120 (20), 100 (21), 98 (32), 86 (25),
84 (42), 72 (27) and 61 (28) (Found: MNHþ4 , 315.1746.
C15H27N2O3S requires 315.1742).
4.1.35. 2-Methyl-propane-2-sulfonic acid (3-hydroxy-4-
trimethylsilanylmethyl-pent-4-enyl)amide 39 (R5
CH2TMS). Following the general procedure for
(2-hydroxy-3-methylene-heptyl)-carbamic acid tert-butyl
ester 10a, N-Bus epoxide 38 (0.10 g, 0.46 mmol) in Et2O
(8 mL) was reacted with TMSCH2Li (1.00 mol dm23 in
pentane, 1.37 mL, 1.37 mmol). Column chromatography
[elution gradient 30–60% Et2O in petrol] gave amino
alcohol 39 (R¼CH2TMS) as a white solid (0.060 g, 43%);
Rf 0.32 (50% Et2O in petrol); mp 72.5–73.08C; nmax (KBr)/
cm21 3492, 3295, 2954, 1638, 1480, 1454, 1421, 1366,
1303, 1249, 1205, 1127, 1087 and 853; dH (400 MHz) 4.97
(1H, s, H of CH2v), 4.79 (1H, br, t, J¼6.0 Hz, NH), 4.70
(1H, s, H of CH2v), 4.11–4.07 (1H, m, CHO), 2.67–2.63
(2H, m, CH2N), 2.26–2.21 (1H, br, m, OH), 1.96–1.82
(1H, m, H of CH2CHO), 1.76–1.66 (1H, m, H of CH2CHO),
1.62 (1H, d, J¼14.0 Hz, H of CH2TMS), 1.41–1.32 (11H,
m, (CH3)C, H of CH2TMS), and 0.03 (3H, s, TMS); dC
(100 MHz) 149.3 (Cv), 107.2 (CH2v), 74.0 (CHO), 59.7
(C(CH3)3), 42.2 (CH2N), 35.8 (CH2CHO), 24.3 ((CH3)3C),
22.6 (CH2TMS) and 21.3 (TMS); m/z [CIþ(NH3)] 325.2
(35%, MNHþ4 ), 170.1 (22) and 98.1 (100) (Found: MNHþ4 ,
325.1983. C13H33N2O3SiS requires 325.1981).
4.1.33. 2-Methyl-propane-2-sulfonic acid (3-hydroxy-
5,5-dimethyl-4-methylenehexyl)amide 39 (R5But).
Following the general procedure for (2-hydroxy-3-methyl-
ene-heptyl)-carbamic acid tert-butyl ester 10a, N-Bus
epoxide 38 (0.10 g, 0.46 mmol) in Et2O (8 mL) was
t
reacted with BuLi (1.70 mol dm23 in hexane, 0.806 mL,
1.37 mmol). Column chromatography [elution gradient
30–60% Et2O in petrol] gave amino alcohol 39 (R¼tBu)
as a white solid (0.057 g, 45%); Rf 0.31 (50% Et2O in
petrol); mp 80.0–80.58C; nmax (KBr)/cm21 3488, 3295,
2967, 2875, 1638, 1481, 1465, 1421, 1397, 1364, 1303,
1202, 1127, 1089, 1022 and 961; dH (400 MHz) 5.18 (1H, s,
H of CH2v), 5.05 (1H, s, H of CH2v), 4.84–4.77 (1H, m,
NH), 4.42–4.37 (1H, m, CHO), 3.45 (1H, dt, J¼11.0,
7.0 Hz, H of CH2N), 3.33 (1H, d, J¼11.0, 7.0 Hz, H of
CH2N), 1.99–1.91 (1H, br, m, OH), 1.87–1.78 (2H, m,
CH2CHO), 1.40 (9H, s, (CH3)3CS), and 1.10 (9H, s,
(CH3)3C); dC (100 MHz) 161.8 (Cv), 108.2 (CH2v),
69.0 (CHO), 65.8 (C(CH3)3), 59.7 (SC(CH3)3), 43.0
(CH2N), 39.1 (CH2CHO), 29.2 ((CH3)3C), and 24.3
((CH3)3CS); m/z [CIþ(NH3)] 295 (95%, MNHþ4 ), 278 (39,
MHþ), 277 (21), 260 (14), 142 (40) and 140 (100) (Found:
MNHþ4 , 295.2054. C13H31N2O3S requires 295.2054).
Acknowledgements
We thank the EPSRC for a research grant (GR/M72340) and
GlaxoSmithKline for a CASE award (to T. J. M.). We also
thank the EPSRC National Mass Spectrometry Service
Centre for mass spectra.
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9742
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