Claisen rearrangements of equilibrating allylic azides

Article abstract of DOI:10.1039/c1ob05972f

Equilibrating mixtures of allylic azide-containing allylic alcohols or allylic 2-tolylsulfonylacetic esters undergo Johnson-Claisen or Ireland-Claisen rearrangement reactions to give unsaturated γ-azidoesters and -acids, respectively. Decarboxylation of t

Full text of DOI:10.1039/c1ob05972f

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Claisen rearrangements of equilibrating allylic azides†
Donald Craig,*a John W. Harvey,b Alexander G. O’Briena and Andrew J. P. Whitec
Received 13th April 2011, Accepted 30th June 2011
DOI: 10.1039/c1ob05972f
Equilibrating mixtures of allylic azide-containing allylic alcohols or allylic 2-tolylsulfonylacetic esters
undergo Johnson–Claisen or Ireland–Claisen rearrangement reactions to give unsaturated g-azidoesters
and -acids, respectively. Decarboxylation of the acids under basic conditions gives azidosulfones, with
moderate to high diastereoselectivity.
Introduction
Results and discussion
Allylic azides have seen limited use in synthesis,1,2 because they
exist as equilibrating mixtures of regioisomers,3 which interconvert
via [3,3]-sigmatropic rearrangement (Winstein rearrangement).4–6
It occurred to us that Claisen rearrangement of allylic azide-
containing substrates would take place regardless of the position
of equilibrium if the isomers unreactive in the sigmatropic process
were inert with respect to competing reaction pathways.7 Thus,
ketene acetals 1 and 2, generated from allylic alcohols under
Johnson–Claisen conditions, would react to give esters 3. We were
interested additionally in any 1,2-asymmetric induction associated
with C–C bond formation (Scheme 1).8
Allylic azidoalcohol substrate mixtures 5 and 6 were prepared by
reaction of vinylic oxiranes 49 with sodium azide (Scheme 2).†
That 5 and 6 were formed by initial attack on 4 by azide by an SN2
mechanism, rather than in an SN2¢ sense, followed by equilibration
was suggested by the observation that only allylic nitrile 7 (together
with hydrolysis product 810) was formed upon analogous treatment
of 4a with potassium cyanide (Scheme 2).11
Scheme 2 Preparation of allylic azidoalcohols 5/6.
Mixtures of 5 and 6 were heated in the presence of triethyl
orthoacetate (as solvent) and sub-stoichiometric propionic acid to
give unsaturated g-azidoesters 9 (Scheme 3, Table 1). Substrates
bearingstraight-chainandbranchedalkyl R groups reacted in high
yield, although longer reaction times were required for the more
sterically demanding congeners. Where R¢ = Me (Table 1, entries b–
d), moderate syn stereoselectivity was observed. This was assigned
by NOESY-NMR of the derived lactam 10 (Scheme 4), and the
Scheme 1 Proposed tandem rearrangement.
aDepartment of Chemistry, Imperial College London, South Kensing-
ton Campus, London, UK, SW7 2AZ. E-mail: d.craig@imperial.ac.uk;
Fax: +44 (0)20 7594 5804; Tel: +44 (0)20 7594 5771
bDiscovery Chemistry, Pfizer Global Research and Development, Ramsgate
Road, Sandwich, Kent, UK, CT13 9NJ
cChemical Crystallography Laboratory, Imperial College London, South
Kensington Campus, London, UK, SW7 2AZ
† Electronic supplementary information (ESI) available: Full experimental
procedures and characterisation of compounds 4–12 and 14. CCDC
reference number 813338. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c1ob05972f
Scheme 3 Johnson–Claisen rearrangement reactions of 5/6.
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Table 1 Johnson–Claisen rearrangement reactions of 5/6
Table 2 Preparation and isomer ratios of esters 11/12
Ratio syn-:
anti-9a
Entry
R
R¢
Ratio 5:6a
Yield (%)
Ratio 11:12a
Entry
R
R¢
Ratio 5:6
t (h) Yield (%)
a
b
c
d
e
f
nC5H11
nC5H11
Me
cHex
Ph
2-Pyridyl
Me
H
73 : 27
61 : 39
64 : 36
63 : 37
100 : 0
100 : 0
0 : 100
99
69
97
92
97
52
75
58 : 42
32 : 68
30 : 70
36 : 65
100 : 0
100 : 0
0 : 100
a
b
c
d
e
f
nC5H11
nC5H11
Me
cHex
Ph
2-Pyridyl Me 100 : 0
Me Ph
H
73 : 27
6
99
72
86
94
0
50 : 50
59 : 41
60 : 40
63 : 37
—
(77 : 23)
50 : 50
Me
Me
Me
H
Me
Ph
Me 61 : 39
Me 64 : 36
Me 63 : 37
24
12
26
48
48
24
H
100 : 0
<4
75
g
g
0 : 100b
a Determined by 1H NMR analysis
a Determined by 1H NMR analysis; b 6g was present as a 3 : 1 E : Z mixture
of attack on the allylic moiety.8a The recently developed18 decar-
boxylative variant (dCr) of the Ireland–Claisen rearrangement
reaction of a-tosyl esters was particularly attractive for this
study, since the decarboxylation step obviated the incorporation
of a third stereocentre. The required dCr substrates 11/12 were
prepared by treatment of azidoalcohols 5/6 with tosylacetic acid–
DCC–DMAP (Scheme 5, Table 2). Interestingly, in cases where
the allylic azide could contain a trisubstituted olefin (entries b–
d) inversion of the ratio to favour the 1,4-azidoesters 12 occurred.
This effect was attenuated in substrate 11/12a, where both isomers
possess disubstituted olefins, and substrates e and f possessing
conjugating aryl groups existed solely as isomers 11. The decrease
in the proportion of vicinal isomers may be a consequence of the
removal upon esterification of the possibility of hydrogen-bonding
between the azide and alcohol –OH groups.19,20
Scheme 4 Assignment of structures 9 and proposed origin of selectivity.
selectivities of the other rearrangements were inferred from this
result. Where R or R¢ was an aryl group (Table 1, entries e–g), the
allylic azidoalcohols 5e, 5f and 6g existed as single isomers, with
the olefin in conjugation with the aryl group.12–14 When R = Ph, the
substrate existed solely as the conjugated allylic isomer 5e, and no
reaction was observed (Table 1, entry e). In the reaction of the less
aromatic15 pyridine 5f, small amounts of impure 9f were formed
after extended reaction times (Table 1, entry f).16 In contrast, the
allylic azidoalcohol 6g reacted efficiently, reflecting the inferred
absence in the equilibrium mixture of the unreactive, less highly
conjugated ketene acetal corresponding to 5g. Selectivity for the
3,4-syn products where R¢ = Me may result from unfavourable 1,3-
diaxial interactions in the transition states leading to the 3,4-anti
isomers. In this model, in line with our previous studies,8h internal
approach of the ketene acetal takes place along a trajectory in
proximity to the s*C–N orbital (Scheme 4).
Our attention turned to the modest stereoselectivities observed
for the rearrangement reactions described above. We had shown
previously that analogous Z-allylic thioethers reacted in Johnson–
Claisen rearrangements with higher syn stereoselectivity than the
E-isomers.8h However, Z-allylic azides could isomerise to the
more reactive17 E-isomers by [3,3]-sigmatropic rearrangement,
and therefore it was considered that changing olefin geometry
would not result in an increase in stereoselectivity. However, it
was anticipated that increased steric bulk at the terminal position
of the ketene acetal would increase the diastereofacial selectivity
Scheme 5 Formation of ester substrates 11/12 from alcohols 5/6.
Attempted dCr reactions of 11/12 using the BSA–KOAc
conditions18 gave low yields of 14.21 Carrying out the rearrange-
ment and decarboxylation as two discrete steps improved the
yield. Thus, microwave irradiation of 11/12 in the presence of
BSA–TEA afforded acids 13. After removal of residual BSA
and TEA, decarboxylation with sodium hydrogencarbonate–
DMF gave 14. With the exception of 11/12f, all esters 11/12
underwent rearrangement under these conditions (Scheme 6, Table
3). More hindered substrates required increased amounts of BSA
and TEA to react. In contrast to the unreactive phenyl-bearing
azidoalcohol 5e, the single-regioisomer azidoester 11e underwent
dCr reaction to give 14e, albeit in relatively low yield. Substrate 11f
decomposed under these conditions, possibly triggered by BSA-
mediated pyridine N-silylation. X-Ray crystallographic analysis
of syn-14a confirmed its structure (Fig. 1);22 syn stereochemistry
for the other major products was inferred from this result. In each
case, the predominance of the syn product was more pronounced
than that observed for Johnson–Claisen rearrangement of the
corresponding allylic azidoalcohols.
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Scheme 6 Formation of azidosulfones 14.
Table 3 Claisen rearrangement and decarboxylation of esters 11/12
for 8 h, the reaction mixture was cooled to rt and NH4Cl (5.0 g)
was added. Water (50 mL) was added and the reaction mixture
was concentrated under reduced pressure to remove acetone. The
remaining aqueous layer was extracted with dichloromethane (3 ¥
100 mL). The combined organic extracts were dried (Na2SO4) and
concentrated under reduced pressure to afford a 73 : 27 mixture
of (E)-2-azidonon-3-en-1-ol 5a and (E)-4-azidonon-2-en-1-ol 6a
respectively (4.04 g, 70%) as a colourless oil after purification
over silica gel (30% TBME/petrol).
Data for the mixture: nmax (film) 3352, 2101, 1667, 1462,
1240, 1072 cm-1; m/z (CI) 201 [MNH4]+, 191, 158, 126 (Found:
[MNH4]+, 201.1715. C9H17N3O requires [MNH4]+, 201.1715.
NMR data for 5a: dH (500 MHz, CDCl3) 5.85 (1H, dt, J 15.5,
6.5, H-4), 5.40 (1H, ddt, J 15.5, 8.0, 1.5, H-3), 4.03 (1H, dt, J 11.5,
5.0, H-2), [3.60 (1H, dd, J 11.5, 5.0) and 3.52 (1H, dd, J 11.5, 7.5),
H-1], 2.09–2.11 (2H, m, H-5), 1.66 (2H, s (br), OH), 1.43–1.25
(12H, m, H-6,7,8), 0.89 (6H, t, J 7.0, H-9); dC (101 MHz, CDCl3)
138.2, 123.4, 66.3, 65.0, 32.3, 31.2, 28.7, 22.4, 14.0.
Ratio syn- :
Conditionsa t (min) Yield (%) anti-14b
Entry
R
R¢
a
b
c
d
e
f
nC5H11
nC5H11
Me
cHex
Ph
2-Pyridyl Me
Me Ph
H
A
B
A
B
B
A
A
15
30
30
30
90
30
40
86
68
82
44
22
0
84 : 16
68 : 32
91 : 9
82 : 18
75 : 25
—
Me
Me
Me
H
g
32
73 : 27
a Conditions A: BSA (3.0 equiv), TEA (1.2 equiv); conditions B: BSA
(5.0 equiv), TEA (2.0 equiv). b Determined by 1H NMR analysis
NMR data for 6a: dH (500 MHz, CDCl3) 5.88 (1H, dt, J 15.0,
5.5, H-2), 5.66 (1H, ddt, J 15.5, 7.5, 1.5, H-3), 4.21 (2H, dd, J 5.5,
1.5, H-1), 3.85 (1H, dt, J 14.0, 7.5, H-4), 1.66 (2H, s (br), OH),
1.56–1.49 (2H, m, H-5), 1.43–1.25 (12H, m, H-6,7,8), 0.89 (6H, t,
J 7.0, H-9); dC (101 MHz, CDCl3) 132.9, 128.9, 64.0, 62.6, 34.5,
31.4, 35.5, 22.5, 14.0.
Ethyl 4-azido-3-ethenylnonanoate (9a)
Fig. 1 The molecular structure of syn-14a.
To a solution of a 73 : 27 mixture of allylic azides 5a and 6a re-
spectively (100 mg, 0.546 mmol, 1.0 equiv) in triethyl orthoacetate
(20.4 mmol, 13.0 equiv) was added propionic acid (0.314 mmol,
0.2 equiv) dropwise via syringe. After heating under reflux for 6 h,
the reaction mixture was cooled to rt and concentrated under
reduced pressure to afford ethyl 4-azido-3-ethenylnonanoate 9a
(137 mg, 99%, 50 : 50 syn:anti mixture of diastereomers) as a
colourless oil without further purification: nmax (film) 2102, 1736,
1641, 1465, 1257, 923 cm-1; dH (400 MHz, CDCl3) [5.74 (1H, ddd,
J 17.0, 10.0, 4.0), and 5.65 (1H, ddd, J 17.0, 10.0, 4.0), syn+anti
CHCH2), 5.19–5.13 (4H, m, syn+anti CHCH2), [4.14 (2H, q, J
7.5) and 4.15 (2H, q, J 7.5), syn+anti OCH2], [3.84–3.43 (1H, m)
and 3.26–3.06 (1H, m), syn+anti H-4], 2.77–2.69 (2H, m, syn+anti
H-3), [2.56 (2H, dd, J 15.0, 5.0) and 2.41 (2H, dd, J 15.0, 8.0),
syn+anti H-2], 1.62–1.32 (16H, m, syn+anti H-5,6,7,8), [1.27 (3H,
t, J 7.5), and 1.26 (3H, t, J 7.5), syn+anti OCH2CH3], 0.91 (6H,
t, J 6.0 syn+anti H-9); dC (101 MHz, CDCl3) 172.0 (C-1), [137.2
and 135.6, (CHCH2)], [118.3 and 117.8, (CHCH2)], [65.8 and 65.3,
(C-4)], 60.5 (OCH2), [44.9 and 44.5, (C-3)], [37.0 and 36.3, (C-2)],
32.2, 32.0, 31.5, 26.0, 25.8, 22.5, 14.2, 14.0; m/z (CI) 271 [MNH4]+,
254 [MH]+, 226 (Found: [MH]+, 254.1858. C13H23N3O2 requires
[MH]+, 254.1869).
Conclusions
In conclusion, equilibrating mixtures of allylic azides participate
effectively in Claisen rearrangements, in most cases regardless of
the position of equilibrium. Diastereoselectivity can be achieved
by selection of the appropriate olefin substitution pattern and
rearrangement type.
Experimental
Procedures for the preparation of 4a–g, 7, 8, 10,and characteri-
sation data for all compounds are detailed in the ESI.† Repre-
sentative procedures for the preparation of allylic azidoalcohols
5a/6a, ester 9, esters 11a/12a and homoallylic sulfone 14a are
given below.
(E)-2-Azidonon-3-en-1-ol (5a) and (E)-4-azidonon-2-en-1-ol (6a)
To a solution of 4a (31.5 mmol, 1.0 equiv) in acetone (45 mL) and
water (19 mL) was added sodium azide (94.5 mmol, 3.0 equiv)
in one portion. After heating the resulting solution under reflux
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(E)-2-Azidonon-3-enyl 2-tosylacetate (11a) and
(E)-4-azidonon-2-enyl 2-tosylacetate (12a)
Data for syn-14a: m.p 72–74 C; nmax (film) 2902, 2100, 1456,
1142, 880, 771, 706, 670 cm-1; dH (400 MHz, CDCl3) 7.81 (2H, d,
J 8.5, o-Ts), 7.39 (2H, d, J 8.5, m-Ts), 5.60 (1H, ddd, J 17.0,
10.0, 8.5, CHCH2), 5.17 (1H, d, J 10.0, trans-CHCH2), 5.12
(1H, d, J 17.0, cis-CHCH2), 3.70 (1H, ddd, J 8.5, 5.5, 3.0, H-
3), [3.40 (1H, dd, J 14.0, 7.0) and 3.15 (1H, dd, J 14.0, 6.0),
H-1], 2.90 (1H, dddd, J 12.5, 9.5, 6.0, 3.0, H-2), 2.48 (3H, s,
TsMe), 1.62–1.31 (8H, m, H-4,5,6,7), 0.92 (3H, t, J 6.0, H-8);
dC (101 MHz, CDCl3) 144.9 (Ts), 136.9 (Ts), 133.7 (CHCH2),
130.0 (m-Ts), 128.0 (o-Ts), 119.5 (CHCH2), 64.3 (C-3), 58.1 (C-
1), 42.5 (C-2), 32.2 (C-4), 31.5 (C-5), 25.8 (C-6), 22.5 (C-7), 21.7
(TsMe), 14.0 (C-8); m/z (CI) 353 [MNH4]+, 310, 226, 174, 152;
m/z (CI) 353 [MNH4]+, 310, 226, 152 (Found: [MNH4]+, 353.2020.
C17H25N3O2S requires [MNH4]+, 353.2011) (Found: C, 60.95; H,
7.47; N, 12.48. C17H25N3O2S requires C, 60.87; H, 7.51; N, 12.53).
NMR data for anti-14a: dH (400 MHz, CDCl3) 7.79 (2H, d, J
8.0, o-Ts), 7.38 (2H, d, J 8.0, m-Ts), 5.68 (1H, ddd, J 17.5, 10.0,
8.5, CHCH2), 5.17 (1H, d, J 10.0, trans-CHCH2), 5.16 (1H, d, J
17.5, cis-CHCH2), 3.41–3.36 (1H, m, H-3), [3.31 (1H, dd, J 14.5,
3.5) and 3.20 (1H, dd, J 14.5, 9.0), H-1], 2.80–2.74 (1H, m, H-
2), 2.48 (3H, s, TsMe), 1.63–1.28 (8H, m, H-4,5,6,7), 0.91 (3H, t,
J 7.0, H-8); dC (101 MHz, CDCl3) 144.4 (Ts), 135.9 (Ts), 135.5
(CHCH2), 129.9 (m-Ts), 128.1 (o-Ts), 118.9 (CHCH2), 65.8 (C-3),
56.9 (C-1), 43.0 (C-2), 31.6 (C-4), 31.4 (C-5), 25.3 (C-6), 22.4 (C-7),
21.7 (TsMe), 13.6 (C-8).
To a solution of a 73 : 27 mixture of allylic azides 5a and 6a
respectively (1.00 g, 5.46 mmol, 1.0 equiv) in dichloromethane
(10 mL) was added DMAP (0.546 mmol, 0.1 equiv), followed by
a solution of DCC (6.01 mmol, 1.1 equiv) in dichloromethane
(10 mL) at rt. The mixture was stirred for 5 min before addition of
2-p-toluenesulfonylacetic acid (1.29 g, 6.01 mmol, 1.1 equiv). After
stirring the colourless suspension for 16 h, the reaction mixture
was filtered through Celite and the filtrate was concentrated under
reduced pressure to afford a 58 : 42 mixture of the esters (E)-2-
azidonon-3-enyl 2-tosylacetate 11a and (E)-4-azidonon-2-enyl 2-
tosylacetate 12a (2.05 g, 99%) respectively as a colourless oil after
purification over silica gel (25% ether/petrol).
Data for the mixture: nmax (film) 2932, 2099, 1747, 1598, 1455,
1330, 1152, 1085, 975, 814, 728, 646, cm-1; dC (126 MHz, CDCl3)
162.2, 162.1, 138.7, 133.2, 129.9, 128.5, 125.9, 128.5, 125.9, 122.3,
67.1, 65.5, 63.5, 62.0, 60.8, 34.2, 32.2, 31.4, 31.2, 28.5, 25.4,
22.5, 22.4, 21.7, 14.0; m/z (CI) 397 [MNH4]+, 352, 243 (Found:
[MNH4]+, 397.1926. C18H25N3O4S requires [MNH4]+, 397.1910).
1H-NMR data for 11a: dH (500 MHz, CDCl3) 7.85–7.81 (2H,
m, o-Ts), 7.39–7.37 (2H, m, m-Ts), 5.82 (1H, dt, J 15.0, 7.0, H-4),
5.31 (1H, ddt, J 15.0, 7.0, 1.5, H-3), 4.62 (2H, d, J 5.0, H-1), 4.13
(2H, d, J 5.0, CH2Ts), 4.10–3.90 (1H, m, H-2), 2.47 (3H, s, TsMe),
2.10–2.15 (2H, m, H-5), 1.57–1.28 (6H, m, H-6,7,8), 0.89 (3H, t, J
7.5, H-9).
1H-NMR data for 12b: dH (500 MHz, CDCl3) 7.85–7.81 (2H,
m, o-Ts), 7.39–7.37 (2H, m, m-Ts), 5.74–5.65 (2H, m, H-2,3), 4.62
(2H, d, J 5.0, H-1), 4.13 (2H, d, J 5.0, CH2Ts), 3.82 (1H, dt, J
14.0, 7.0, H-4), 2.47 (3H, s, TsMe), 1.57–1.28 (8H, m, H-5,6,7,8),
0.89 (3H, t, J 7.5, H-9).
Acknowledgements
We thank EPSRC and Pfizer for support (supported DTA
studentship to A.G.O.).
Notes and references
1-[(3-Azido-2-ethenyloctane)sulfonyl]-4-methylbenzene (14a)
1 D. Askin, C. Angst and S. Danishefsky, J. Org. Chem., 1985, 50, 5005.
2 A. K. Feldman, B. Colasson, K. B. Sharpless and V. V. Fokin, J. Am.
Chem. Soc., 2005, 127, 13444.
3 (a) A. Gagneux, S. Winstein and W. G. Young, J. Am. Chem. Soc., 1960,
82, 5956; (b) C. A. VanderWerf and V. L. Heasley, J. Org. Chem., 1966,
31, 3534.
To a solution of a 58 : 42 mixture of allylic azides 11a and
12a respectively (50 mg, 0.132 mmol, 1.0 equiv) in acetonitrile
(1.0 M) was added N,O-bistrimethylsilylacetamide (0.396 mmol,
3.0 equiv) and TEA (0.158 mmol, 1.2 equiv) in a capped microwave
vial. The mixture was heated by microwave at 160 ◦C until
TLC showed consumption of the starting material. The reaction
mixture was cooled to rt, quenched with aqueous HCl (2 M,
10 mL) and extracted with dichloromethane (3 ¥ 10 mL). The com-
bined organic extracts were passed though an SCX ion-exchange
column (conditioned with 10% MeOH/dichloromethane) and
concentrated under reduced pressure to afford the acid inter-
mediate 13a without further purification. To solution of the
crude acid (1.0 equiv) in DMF (1.0 M) was added sodium
hydrogencarbonate (1.2 equiv) in a microwave vial. The mixture
4 A. Padwa and M. M. Sa´, Tetrahedron Lett., 1997, 38, 5087.
5 For an example of rearrangement via an ionic transition state see: G.
L. Closs and A. M. Harrison, J. Org. Chem., 1972, 37, 1051.
6 (a) B. M. Trost and S. R. Pulley, Tetrahedron Lett., 1995, 36, 8737;
(b) F. Klepper, E.-M. Jahn, V. Hickmann and T. Carell, Angew. Chem.,
Int. Ed., 2007, 46, 2325; (c) H. Guo and G. A. O’Doherty, Org. Lett.,
2006, 8, 1609; (d) S. Lauzon, F. Tremblay, D. Gagnon, C. Godbout, C.
Chabot, C. Mercier-Shanks, S. Perreault, H. DeSe`ve and C. Spino, J.
Org. Chem., 2008, 73, 6239.
7 In conceptually related processes the vinylic, rather than allylic portion
of the ketene acetal is established by isomerisation: (a) K. Wang, C. J.
Bungard and S. G. Nelson, Org. Lett., 2007, 9, 2325; (b) B. D. Stevens
and S. G. Nelson, J. Org. Chem., 2005, 70, 4375; (c) B. D. Stevens, C. J.
Bungard and S. G. Nelson, J. Org. Chem., 2006, 71, 6397; (d) K. Wang
and S. G. Nelson, J. Am. Chem. Soc., 2006, 128, 4232; (e) H. B. Ammar,
J. Le Noˆtre, M. Salem, M. T. Kaddachi, L. Toupet, J.-L. Renaud, C.
Bruneau and P. H. Dixneuf, Eur. J. Inorg. Chem., 2003, 4055; (f) C.
C. Bausch and J. S. Johnson, J. Org. Chem., 2008, 73, 1575; (g) U.
Kazmaier, Tetrahedron Lett., 1996, 37, 5351; (h) B. Schmidt, Synlett,
2004, 1541.
◦
was heated by microwave at 160 C for 35 min and cooled to rt.
Water (10 mL) was added and the mixture was extracted with
dichloromethane (3 ¥ 10 mL). The combined organic extracts
were dried (MgSO4) and concentrated under reduced pressure to
afford 1-[(3-azido-2-ethenyloctane)sulfonyl]-4-methylbenzene 14a
(38 mg, 86%, 84 : 16 syn:anti mixture of diastereomers) as a
white solid after purification over silica gel (2–10% ether/petrol).
Repeated purification over silica gel (2–10% ether/petrol) followed
by recrystallisation (EtOAc/petrol) afforded an analytical sample
of syn-14a for crystallography studies and an analytical sample
enriched in anti-14a.
8 The syn product is typically formed when the ketene acetal bears a
heteroatom-containing stereocentre at the 6¢ position: (a) J. K. Cha
and S. C. Lewis, Tetrahedron Lett., 1984, 25, 5263; (b) T. Suzuki, E.
Sato, S. Kamada, H. Tada, K. Unno and T. Kametani, J. Chem. Soc.,
Perkin Trans. 1, 1986, 387; (c) S. Takano, K. Seijo and S. Hatakeyama,
Tetrahedron Lett., 1985, 26, 865; (d) J. Mulzer and M. Shanyoor,
Tetrahedron Lett., 1993, 34, 6545; (e) J. R. Hauske and S. M. Julin,
7060 | Org. Biomol. Chem., 2011, 9, 7057–7061
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16 To exclude the effects of neutralisation of the propionic acid catalyst
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19 For equilibrating mixtures of a secondary and tertiary allylic azide the
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Chem., Int. Ed., 2009, 48, 5724.
20 The Cambridge X-ray structure database contains examples of azide
˚
internal nitrogen ◊ ◊ ◊ H–O (alcohol) distances of less than 2.50 A; see:
D. Crich and H. Xu, J. Org. Chem., 2007, 72, 5183; S.-C. Hung,
S. R. Thopate and C.-C. Wang, Carbohydr. Res., 2001, 330, 177; S.
Ahmad, S. H. Spergel, J. C. Barrish, J. DiMarco and J. Gougoutas,
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13 K. Banert, M. Hagedorn, C. Liedtke, A. Melzer and C. Scho¨ffler, Eur.
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groups.2,6a
.
14 (a) D. R. Deardorff, C. M. Taniguchi, A. C. Nelson, A. P. Pace, A. J.
Kim, A. K. Pace, R. A. Jones, S. A. Tafti, C. Nguyen, C. O’Connor, J.
Tang and J. Chen, Tetrahedron: Asymmetry, 2005, 16, 1655; (b) Y. N.
Belokon, W. Clegg, R. W. Harrington, E. Ishibashi, H. Nomura and
M. North, Tetrahedron, 2007, 63, 9724.
15 By comparison of bond orders: (a) C. W. Bird, Tetrahedron, 1985,
41, 1409; (b) C. W. Bird, Tetrahedron, 1986, 42, 89. By comparison of
magnetic anisotropies: (c) K. E. Calderbank, R. L. Calvert, P. B. Lukins
and G. L. D. Ritchie, Aust. J. Chem., 1981, 34, 1835. For a general
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21 Azide thermolysis could be a significant competing pathway: (a) G.
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22 Crystal data for syn-14a: C17H25N3O2S, M = 335.46, monoclinic, P21/n
˚
(no. 14), ◦a = 5.48411(17), b = 8.0007(2), c = 41.2338(12) A, b =
3
-3
˚
90.353(3) , V = 1809.17(9) A , Z = 4, rc = 1.232 g cm , m(Mo-Ka) =
0.192 mm-1, T = 173 K, colourless platy needles, Oxford Diffraction
Xcalibur 3 diffractometer; 5800 independent measured reflections
(Rint = 0.0666), F2 refinement, R1(obs) = 0.1083, wR2(all) = 0.2018,
4035 independent observed absorption-corrected reflections [|Fo| >
4s(|Fo|), 2qmax = 63◦], 209 parameters. CCDC 813338.
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 7057–7061 | 7061
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