Aminosugar motifs via an allene aziridination strategy

Article abstract of DOI:10.1016/j.tet.2014.03.084

Aminosugar motifs occur in many biologically active natural products and pharmaceuticals; however, stereocontrolled access to diverse structures with minimal use of protecting groups and oxidation state changes is challenging. This paper describes a chemo-, regio-, and stereoselective approach to aminosugar motifs that utilizes an allene aziridination strategy to rapidly install three of the contiguous heteroatom-bearing carbons with stereochemical flexibility.

Full text of DOI:10.1016/j.tet.2014.03.084

Tetrahedron xxx (2014) 1e7
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Aminosugar motifs via an allene aziridination strategy
*
Christopher S. Adams, R. David Grigg, Jennifer M. Schomaker
University of Wisconsin-Madison, Madison, WI 53706, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Aminosugar motifs occur in many biologically active natural products and pharmaceuticals; however,
stereocontrolled access to diverse structures with minimal use of protecting groups and oxidation state
changes is challenging. This paper describes a chemo-, regio-, and stereoselective approach to amino-
sugar motifs that utilizes an allene aziridination strategy to rapidly install three of the contiguous
heteroatom-bearing carbons with stereochemical flexibility.
Received 25 February 2014
Received in revised form 20 March 2014
Accepted 24 March 2014
Available online xxx
Ó 2014 Published by Elsevier Ltd.
Keywords:
Allenes
Aziridination
Aminosugars
Rh catalysis
Methylene aziridines
1. Introduction
exploring important problems in the areas of chemistry, biology,
and medicine.3
Aminosugars are components of a variety of biologically active
and important compounds, including mono- and polysaccharides,
glycolipids, nucleotides, anthracycline antitumor agents, and anti-
biotics.1 Neuraminic acid, glucosamine, and galactosamine (Fig. 1)
are among the most common examples of aminosugars found in
nature, but there is also significant interest in the synthesis of un-
natural aminosugars.2 Indeed, modular approaches to construct
libraries of such compounds for incorporation into glycoconjugates
are highly desirable, as glycodiversification has been successful for
The broad interest in aminosugars has led to the development of
several approaches for the synthesis of these classes of molecules.
The most common methods employ sugars as starting materials,
particularly glucose, mannose and galactose.4 The advantages of
utilizing substrates from the chiral pool are the intrinsic chirality
and the ready availability of sugars. However, the two major chal-
lenges associated with using carbohydrate-based substrates are the
need to protect the amino and hydroxyl groups and the difficulty of
inverting stereocenters at will. While a more diverse range of
aminosugars can be obtained via the oxidation of stereodefined and
enantioenriched allylic alcohols/amines, multiple starting mate-
rials must be employed and issues with poor reactivity, regio- and
stereoselectivity often arise.5
Our group has been engaged in developing allene aziridination
as a strategy for synthesizing aminated stereotriads,7 and we felt
that aminosugars would be a challenging target on which to test
the scope of our methodology. The hope was that the allene func-
tionality could be utilized to flexibly install three contiguous
heteroatom-bearing stereocenters within the aminosugar core. In
addition, we aimed to control the relative stereochemistries of the
three adjacent stereocenters, with the added benefit of setting the
absolute stereochemistry via axial-to-central chirality transfer.6
Fig. 1. Examples of aminosugars.
2. Results and discussion
Our strategy for the synthesis of a simple aminosugar motif is
* Corresponding author. E-mail address: schomakerj@chem.wisc.edu (J.M.
Schomaker).
shown in Scheme 1. Treatment of the homoallenic sulfamate 1 with
0040-4020/$ e see front matter Ó 2014 Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tet.2014.03.084
Please cite this article in press as: Adams, C. S.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.03.084

2
C.S. Adams et al. / Tetrahedron xxx (2014) 1e7
a Rh catalyst leads to an intermediate (E)-bicyclic methylene azir-
idine 2. Ring-opening of 2 with water, followed by protection of the
resulting alcohol, would yield enesulfamate 3. We have previously
demonstrated that treatment of simple enesulfamates with dime-
thyldioxirane (DMDO) and a reductant leads to 2-amino-1,3-diol
motifs;7c the successful application of this strategy to 3 would
generate stereotetrad 4 as a direct precursor to aminosugar prod-
ucts. However, the use of homoallenic sulfamate 1 presented an
additional challenge, since the effect of the vicinal diol on the ste-
reo- and regiochemical outcome of the allene oxidation was not
clear. In particular, the stability of the sensitive methylene aziridine
motif 2 in the presence of other potentially nucleophilic hetero-
atoms was unknown.
Scheme 3. Preventing competing cyclopropane formation.
Scheme 1. Allene aziridination strategy in aminosugar synthesis.
The substrate for our initial studies was easily prepared from the
enantioenriched aldehyde 5 (Scheme 2).8 Protection of the 1,2-diol
as the diethylketal 5 was necessary for reasons that will be dis-
cussed in relation to Schemes 3 and 4 (vide infra). Addition of a Ti
acetylide to aldehyde 5 gave 6 in a dr of ca. 5:1.9 The propargyl
alcohol was converted to the tosylate 7, treated with an organo-
copper reagent and reduced to yield the allenic alcohol 8.10 Finally,
sulfamoylation of the alcohol gave the key building block 9 for our
aminosugar synthesis. This sequence of reactions could be run on
multi-gram scales with reproducible yields.
Scheme 4. Rationale for cyclopropylimine formation.
important to the successful isolation of the methylene aziridine. We
hypothesize that rearrangement occurs when the proximal oxygen
of the dimethylketal is aligned in such a fashion that it can readily
ring-open the sensitive bicyclic methylene aziridine (Scheme 4). In
11a, the oxygen attacks the methylene aziridine, leading to an in-
termediate that could be represented as either A or B. This reactive
intermediate undergoes ring closure to generate the cyclopropane
11b. In contrast, 10a cannot easily adopt a conformation that per-
mits nucleophilic attack on the methylene aziridine, due to un-
favorable steric interactions that would occur between the
dimethylketal and the six-membered ring of the bicyclic methylene
aziridine. Consequently, less rearrangement of 10a occurs, although
some of the cyclopropane 10b is still observed.
Ultimately, we found that replacing the dimethylketal with
a diethylketal, as in 9, minimized the production of the cyclopro-
pane due to the increased steric bulk of this protecting group. With
the methylene aziridine accessible in good selectivity from this
substrate, a facile ring-opening was carried out by the addition of
water under neutral conditions, followed by a TBS protection of the
alcohol (Scheme 5). Presumably, the considerable ring strain of this
intermediate permits ring-opening without the need for exogenous
Lewis acid additives.13
Scheme 2. Synthesis of homoallenic sulfamate 9.
To generate the core of the aminosugar backbone, the DMDO
oxidation/imine reduction sequence was carried out on enesulfa-
mate 14. The use of DMDO in CH2Cl2 gave the sensitive a-hydrox-
Our initial attempts to carry out allene aziridination on the
dimethylketal-substituted allene 10 (generated in a manner anal-
ogous to that shown in Scheme 2) were fraught with unexpected
difficulties. Treatment of 10 with Rh2(OAc)4 and PhIO gave some of
the desired (E)-methylene aziridine 10a, along with an undesired
side-product identified as the cyclopropane 10b.11
Interestingly, the diastereomeric allene 11 (Scheme 3), prepared
by an alternative protocol,12 gave only the cyclopropane 11b
upon treatment with Rh2(OAc)4, suggesting that the relative ste-
reochemistry between the allenic hydroxyl group and the allene is
yimine intermediate 15 in greater than 10:1 dr, followed
immediately by reduction with Zn(BH4)2 to yield the stereotetrad
16 as a 4:1 mixture of easily separable diastereomers (Scheme 6).
The stereochemical outcome of the DMDO oxidation was inferred
from our previous work,7c while the relationship between the C1-
OTBS and C2-amine groups was inferred by analysis of 1H NMR
coupling constants between the C1 and C2 protons.14 The anti re-
lationship between the C2-amine and C3-hydroxyl agrees with
Please cite this article in press as: Adams, C. S.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.03.084

C.S. Adams et al. / Tetrahedron xxx (2014) 1e7
3
the
a-hydroxy imine 15 to an
a
-aminoketone of the form 20 was
employed (Scheme 8). Such isomerizations of a-hydroxy ketones
and imines are known to be catalyzed by a variety of Lewis and
Brønsted acids,17 and we found that Al(OtBu)3 catalyzed this
transformation with good transfer of the imine stereochemistry.
The stereochemical configuration of 20 was inferred from 1H NMR
coupling between the C1 and C2 hydrogens, analogous to 16a and
16b. Reduction of 20 with LiBEt3H resulted in a second O/N/O di-
astereomer 16c with the stereochemical configuration of 3-amino-
3-deoxy-D-gulose. Reduction with DIBAL-H provided the already
accessible diastereomer 16a.
Scheme 5. Synthesis of enesulfamate 14.
Scheme 8. Synthesis of an alternative stereoisomer 16c.
Scheme 6. Synthesis of aminosugar precursors 16a and 16b.
3. Conclusions
related findings in the Zn(BH4)2-mediated reduction of a-hydroxy
ketones.15
In conclusion, we have demonstrated that allene aziridination is
a viable approach toward the synthesis of aminosugar motifs.
Aziridination of a stereodefined allene derived from D-mannitol
delivered a strained, bicyclic methylene aziridine that could be
rapidly elaborated in a regio-, chemo-, and stereoselective manner
to two different stereoisomeric 2-amino-1,3-diol aminosugar cores.
Current efforts are focused on exploring ways to obtain all four
possible diastereomeric aminosugar motifs from the same allene
precursor and introducing other heteroatoms to gain access to
novel aminosugars for biological testing.
Compound 16a could be easily converted in two steps to an
aminosugar motif (Scheme 7). A one-pot removal of the sulfamoyl
group was achieved through N-Boc protection and subsequent
nucleophilic displacement using an aryl selenide to give 17.16 Ad-
dition of peroxide to 17 promoted a facile, in situ selenoxide
elimination and the resulting olefin was cleaved via ozonolysis to
give a protected derivative of 3-deoxy-3-amino- -allose 19.
D
4. Experimental section
4.1. General
All glassware was either oven-dried overnight at 130 ꢀC or
flame-dried under a stream of dry nitrogen prior to use. Unless
otherwise specified, reagents were used as obtained from the
vendor without further purification. Tetrahydrofuran and diethyl
ether were freshly distilled from purple Na/benzophenone ketyl.
Dichloromethane, acetonitrile, and toluene were dried over CaH2
and freshly distilled prior to use. All other solvents were purified in
accordance with ‘Purification of Laboratory Chemicals’.18 Air- and
moisture-sensitive reactions were performed using standard
Schlenk techniques under an atmosphere of nitrogen. Analytical
thin layer chromatography (TLC) was performed utilizing pre-
coated silica gel 60 F254 plates containing a fluorescent indicator,
while preparative chromatography was performed using SilicaFlash
P60 silica gel (230e400 mesh) via Still’s method.19 Unless other-
wise stated, the mobile phases for column chromatography were
Scheme 7. Transformation of 16 to protected aminosugar 19.
The possibility for accessing multiple aminosugar stereoisomers
using allene aziridination as a key step was investigated. Both the
enesulfamate oxidation and imine reduction steps proved to be
highly substrate controlled in their stereochemical preference;
therefore, an alternative approach involving the isomerization of
Please cite this article in press as: Adams, C. S.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.03.084

4
C.S. Adams et al. / Tetrahedron xxx (2014) 1e7
mixtures of hexanes/ethyl acetate. Columns were typically run
using a gradient method, beginning with 100% hexanes and grad-
ually increasing the polarity using ethyl acetate. Various stains
were used to visualize reaction products, including p-anisaldehyde,
KMnO4, ceric ammonium molybdate (CAM stain), and iodine
powder. 1H NMR and 13C NMR spectra were obtained using Bruker-
300, Varian-300, Varian Inova-500, or Varian Unity-500 spec-
trometers. For 1H NMR, chemical shifts are reported relative to
2.42 (d, J¼2.2 Hz, 1H), 1.55e1.72 (m, 4H), 0.88 (t, J¼7.5 Hz, 3H), 0.87
(t, J¼7.5 Hz, 3H). 13C NMR (125.7 MHz, CDCl3)
d 145.1, 133.5, 129.7,
128.2, 114.8, 77.3, 76.5, 76.4, 69.8, 65.9, 29.3, 28.7, 21.7, 8.0, 8.0.
HRMS m/z [MþH]þ predicted, 339.1261; observed, 339.1263.
4.2.3. (P)-5-((S)-2,2-Diethyl-1,3-dioxolan-4-yl)penta-3,4-dien-1-ol
(8). Diisopropylamine (20.6 mL, 147 mmol, 1.0 equiv) was placed
in a 2 L round-bottomed flask and 600 mL of dry THF was added
under a stream of nitrogen. The flask was cooled to ꢁ78 ꢀC and
58.9 mL nBuLi (2.5 M in hexanes, 147 mmol, 1.0 equiv) was added
dropwise. The solution was stirred for 15 min at ꢁ78 ꢀC and 20 min
at 0 ꢀC before the reaction mixture was recooled to ꢁ78 ꢀC. EtOAc
(14.4 mL, 147 mmol, 1.0 equiv) in 90 mL THF was added dropwise
and the solution stirred for 30 min. CuI (28.0 g, 147.3 mmol,
1.0 equiv) was added under nitrogen and the resulting tan slurry
was stirred for 75 min. The tosylate 7 (49.8 g, 147.3 mmol,
1.0 equiv) dissolved in 60 mL of dry THF was added and the slurry
stirred for 15 min. The cold bath was removed and the green so-
lution stirred until it turned yellow (about 7 min). The reaction was
quenched with 1 L of saturated aqueous NH4Cl and the mixture
extracted with EtOAc (4ꢂ250 mL). The combined organic fractions
were dried with Na2SO4 and the volatiles removed under reduced
pressure to yield a crude brown oil (Note: The product ester can be
purified at this point, however it is usually more convenient to
immediately reduce the compound to avoid undesired isomeri-
zation of the homoallenic ester.). The brown oil was dissolved in
50 mL dry THF and slowly added to a stirring suspension of LiAlH4
(10.4 g, 274.0 mmol, 1.9 equiv) in 550 mL dry THF at 0 ꢀC. After
stirring for 20 min, the hydride was carefully quenched using
a typical Fieser workup. The reaction mixture was filtered, the
volatiles removed and the crude residue purified by column
chromatography (8e40% EtOAc in hexanes) to yield 16.6 g of 8 as
a pale brown oil (78.06 mmol, 53%). 1H NMR (500.0 MHz, CDCl3)
residual protiated solvent peaks (d 7.26, 2.49, 7.15, and 7.09 ppm for
CDCl3, (CD3)2SO, C6D6, and CD3C6D5, respectively). 13C NMR spectra
were measured at either 125 MHz or 75 MHz on the same in-
struments noted above for recording 1H NMR spectra. Chemical
shifts were again reported in accordance to residual protiated sol-
vent peaks (d 77.0, 39.5, 128.0, and 137.9 ppm for CDCl3, (CD3)2SO,
C6D6, and CD3C6D5, respectively). Accurate mass measurements
were acquired at the University of Wisconsin-Madison using
a Micromass LCT (electrospray ionization, time-of flight analyzer or
electron impact methods). The NMR and mass spectrometry facil-
ities are funded by the NSF (CHE-9974839, CHE-9304546, CHE-
9208463, CHE-9629688) and the University of Wisconsin, as well as
the NIH (RR08389-01).
4.2. Preparation of homoallenic alcohol 8 from 5
4.2.1. (S)-1-((R)-2,2-Diethyl-1,3-dioxolan-4-yl)prop-2-yn-1-ol (6). A
2 L round-bottomed flask was charged with 450 mL dry ether. A
portion of 25.7 mL ethynyl trimethylsilane (180 mmol, 1.1 equiv)
was added and the flask was cooled to 0 ꢀC. A solution of 72.1 mL
nBuLi (2.5 M in hexanes, 180 mmol, 1.1 equiv) was added dropwise,
the mixture stirred for 10 min and then cooled to ꢁ78 ꢀC. After
stirring for 30 min, 43.1 mL (iPrO)3TiCl (180 mmol, 1.1 equiv) in
180 mL dry ether was added to the reaction vessel. The solution was
stirred for 30 min and 25.9 g aldehyde 5 (164 mmol, 1.0 equiv) in
180 mL ether was added over a period of 10 min. The reaction
mixture was stirred at ꢁ78 ꢀC for 1 h, and then warmed to 0 ꢀC for
2 h. A solution of 650 mL of saturated Rochelle’s salt was added and
the phases separated. The aqueous phase was extracted with EtOAc
(3ꢂ400 mL) and the combined organic fractions were washed with
brine. After drying with Na2SO4 and removing the volatiles under
reduced pressure, the crude oil was treated with 500 mL of MeOH
saturated with K2CO3 for 20 min. The mixture was concentrated to
200 mL, diluted with 400 mL H2O, and extracted with EtOAc
(4ꢂ200 mL). The volatiles were removed under reduced pressure to
provide a yellow oil of sufficient purity for the subsequent step
(28.95 g, 157 mmol, 96%, dr¼5.25:1). 1H NMR (500 MHz, CDCl3)
d
5.30 (qd, J¼6.5, 1.6 Hz, 1H), 5.23 (tt, J¼7.0, 2.9 Hz, 1H), 4.57 (dddd,
J¼8.0, 7.0, 6.2, 1.6 Hz, 1H), 4.13 (dd, J¼8.0, 6.2 Hz, 1H), 3.71e3.76 (m,
2H), 3.64 (app t, J¼8.0 Hz, 1H), 2.31 (m, 2H), 1.79 (br s, 1H), 1.67 (q,
J¼7.5 Hz, 2H), 1.64 (q, J¼7.5 Hz, 2H), 0.92 (t, J¼7.5 Hz, 3H), 0.91 (t,
J¼7.5 Hz, 3H). 13C NMR (125.7 MHz, CDCl3)
d 205.4, 113.5, 91.0, 89.8,
74.8, 70.0, 61.6, 31.7, 29.9, 29.6, 8.1, 8.1. HRMS m/z [MþNH4]þ
predicted, 230.1751; observed, 230.1744.
4.3. General preparation of homoallenic sulfamates
Chlorosulfonyl isocyanate (1.5 equiv) was placed in a round-
bottomed flask equipped with a drying tube and cooled to 0 ꢀC.
Formic acid (1.5 equiv) was added dropwise (caution: vigorous gas
evolution), resulting in solidification of the mixture after 5 min.
CH2Cl2 (1.9 M in formic acid) was added and the mixture allowed to
stir at rt overnight. The solution was cooled to 0 ꢀC and a mixture of
the alcohol (1.0 equiv), pyridine (1.5 equiv), and CH2Cl2 (1.4 M in
alcohol) was added dropwise. The reaction mixture was stirred at rt
for 50 min before it was quenched with EtOAc and H2O. Additional
EtOAc and H2O were added and the phases separated. The aqueous
phase was extracted once with EtOAc, the combined organic frac-
tions washed twice with brine, dried with MgSO4, and concen-
trated under reduced pressure. The crude residue was purified by
column chromatography (40e50% EtOAc in hexanes).
d
4.51 (td, J¼4.5, 2.3 Hz, 1H), 4.24 (td, J¼6.7, 4.5 Hz, 1H), 4.11 (dd,
J¼8.4, 6.7 Hz, 1H), 4.01 (dd, J¼8.4, 6.8 Hz, 1H), 2.48 (d, J¼2.3 Hz, 1H),
2.31 (d, J¼4.5 Hz, 1H), 1.68e1.76 (m, 2H), 1.65 (q, J¼7.5 Hz, 2H), 0.94
(t, J¼7.5 Hz, 3H), 0.90 (t, J¼7.5 Hz, 3H). 13C NMR (125.7 MHz, CDCl3)
d
114.0, 81.0, 77.8, 74.5, 65.5, 62.3, 29.3, 28.8, 8.2, 8.0. HRMS m/z
[MþH]þ predicted, 185.1173; observed, 185.1166.
4.2.2. (S)-1-((R)-2,2-Diethyl-1,3-dioxolan-4-yl)prop-2-ynyl 4-
methylbenzenesulfonate (7). The propargyl alcohol
6 (28.9 g,
157.1 mmol, 1.0 equiv) was dissolved in 320 mL CH2Cl2. DMAP
(0.96 g, 7.86 mmol, 0.05 equiv) and 24.1 mL triethylamine
(173 mmol, 1.10 equiv) were added, followed by TsCl (30.0 g,
157.1 mmol, 1.0 equiv). The solution was stirred at rt for 2 h, then
diluted with water (300 mL) and extracted with CH2Cl2
(3ꢂ150 mL). The combined organic fractions were washed with
brine, dried with Na2SO4, and concentrated by rotary evaporation.
The crude residue was purified by column chromatography (%e40%
EtOAc in hexanes) to give 7 as a pale yellow oil (49.8 g, 147.3 mmol,
4.3.1. (P)-5-((S)-2,2-Diethyl-1,3-dioxolan-4-yl)penta-3,4-dienyl sul-
famate (9). The alcohol (13.0 g, 61.4 mmol) 8 yielded 9 as a pale
amber oil using the general procedure described above (16.7 g,
57.5 mmol, 93%). 1H NMR (500 MHz, CDCl3)
d 5.40 (br s, 2H), 5.32
(app q, J¼5.4 Hz, 1H), 5.21 (ddt, J¼7.5, 5.4, 3.5 Hz, 1H), 4.61 (ddd,
J¼8.0, 7.5, 6.3 Hz), 4.31 (m, 2H), 4.17 (dd, J¼8.4, 6.3 Hz, 1H), 3.65 (dd,
J¼8.4, 8.0 Hz, 1H), 2.40e2.55 (m, 2H), 1.66 (2 q, J¼7.5 Hz, 4H), 0.91
(t, J¼7.5 Hz, 3H), 0.90 (t, J¼7.5 Hz, 3H). 13C NMR (125.7 MHz, CDCl3)
94%). 1H NMR (500 MHz, CDCl3)
d
7.83 (d, J¼8.5 Hz, 2H), 7.34 (d,
J¼8.5 Hz, 2H), 5.07 (dd, J¼5.6, 2.2 Hz,1H), 4.26 (app q, J¼6.1 Hz, 1H),
4.09 (dd, J¼8.8, 6.4 Hz, 1H), 3.92 (dd, J¼8.8, 5.9 Hz, 1H), 2.45 (s, 3H),
Please cite this article in press as: Adams, C. S.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.03.084

C.S. Adams et al. / Tetrahedron xxx (2014) 1e7
5
d
206.0, 113.8, 92.1, 88.7, 75.6, 69.8, 68.4, 29.8, 29.5, 26.6, 8.0, 8.0.
2 mol %) was added and the solution stirred for 5 min prior to the
addition of 0.453 g PhIO (2.06 mmol, 1.2 equiv). The reaction
mixture was stirred for 2 h, filtered through Celite, and concen-
trated by rotary evaporation. The crude methylene aziridine was
treated with 0.150 mL H2O (8.58 mmol, 5.00 equiv) in 4.3 mL
CH3CN, stirred for 2 h, and diluted with 30 mL CH2Cl2. The mixture
was dried with MgSO4, filtered, and concentrated under reduced
pressure. The crude enesulfamate 13 was dissolved in 6 mL dry
CH2Cl2 and cooled to 0 ꢀC. A portion of 2,6-lutidine (0.200 mL,
1.72 mmol, 1.0 equiv) and 0.395 mL TBSOTf (1.72 mmol, 1.0 equiv)
were added successively, the mixture stirred for 30 min, quenched
with water, and extracted with CH2Cl2. Final purification was ac-
complished by column chromatography (2e10% EtOAc in hexanes)
to give 0.235 g 14 (0.557 mmol, 32%) as a pale yellow oil that so-
HRMS m/z [MþH]þ predicted, 292.1214; observed, 292.1210.
4.3.2. (P)-5-((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)penta-3,4-dienyl
sulfamate (10). The alcohol (1.34 g, 7.28 mmol, 1.0 equiv) yielded 10
as a pale yellow oil (1.12 g, 4.25 mmol, 59%). 1H NMR (500 MHz,
CDCl3)
d
5.41 (br s, 2H), 5.32 (app q, J¼5.9 Hz, 1H), 5.23 (ddt, J¼8.5,
5.9, 3.5 Hz, 1H), 4.61 (ddd, J¼8.5, 7.2, 6.2 Hz, 1H), 4.30 (m, 2H), 4.15
(dd, J¼8.5, 6.2 Hz, 1H), 3.69 (dd, J¼8.5, 7.2 Hz, 1H), 2.45e2.52 (m,
2H), 1.43 (s, 3H), 1.40 (s, 3H). 13C NMR (125.7 MHz, CDCl3)
d 205.9,
109.6, 92.1, 88.7, 75.2, 69.3, 68.5, 26.7, 26.7, 25.7. HRMS m/z [MþH]þ
predicted, 264.0901; observed, 264.0896.
4.3.3. (M)-5-((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)penta-3,4-dienyl
sulfamate (11). The alcohol (0.63 g, 3.44 mmol) yielded 11 as a pale
yellow oil (0.60 g, 2.29 mmol, 66%). 1H NMR (500 MHz, CDCl3)
lidified upon standing. 1H NMR (500 MHz, CDCl3)
d 6.52 (br s, 1H),
5.77 (d, J¼8.8 Hz, 1H), 4.96 (t, J¼3.0 Hz, 1H), 4.70 (t, J¼13.0 Hz, 1H),
4.68 (dd, J¼14.6, 8.3 Hz, 1H), 4.18 (dt, J¼13.0, 3.0 Hz, 1H), 4.08 (dd,
J¼8.3, 6.1 Hz, 1H), 3.62(t, J¼8.3 Hz, 1H), 2.05 (ddt, J¼15.0, 12.2,
3.0 Hz, 1H), 1.89 (dt, J¼15.0, 3.2 Hz, 1H), 1.66 (qd, J¼7.5, 1.3 Hz, 2H),
1.65 (q, J¼7.5 Hz, 2H), 0.92e0.89 (m, 15H), 0.13 (s, 3H), 0.11 (s, 3H).
d
5.30e5.38 (m, 2H), 5.09 (br s, 2H), 4.61 (qd, J¼6.0, 2.3 Hz, 1H),
4.23e4.33 (m, 2H), 4.11 (dd, J¼8.3, 6.0 Hz, 1H), 3.82 (dd, J¼8.3,
6.3 Hz, 1H), 2.41e2.54 (m, 2H), 1.45 (s, 3H), 1.38 (s, 3H). 13C NMR
(125.7 MHz, CDCl3)
d 204.6, 109.7, 92.6, 89.0, 73.7, 69.3, 68.9, 27.8,
26.7, 25.7. HRMS m/z [MþNH4]þ predicted, 281.1166; observed,
13C NMR (125.7 MHz, CDCl3)
d 135.7, 126.2, 113.9, 71.1, 69.5, 64.9,
281.1169.
64.6, 38.3, 29.9, 29.5, 25.7, 18.1, 8.11, 8.08, ꢁ5.0, ꢁ5.1. HRMS m/z
[MþNH4]þ predicted, 439.2293; observed, 439.2297.
4.4. Aziridination of 10
4.5.2. (4S,5S)-4-[(S)-[(4R)-2,2-Diethyl-1,3-dioxolan-4-yl]-(hydroxyl)
methyl]-5-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-1,2,3-
oxathiazepane 2,2-dioxide (16a). The enesulfamate 14 (52.1 mg,
0.123 mmol, 1 equiv) was added to a 2 mL screw-cap flask, along
The sulfamate 10 (0.0850 g, 0.323 mmol, 1.0 equiv) was dis-
solved in 3 mL dry CH2Cl2. Rh2(OAc)4 (0.0029 g, 0.0065 mmol,
ꢀ
2 mol %) was added with 0.0850 g powdered 4 A molecular sieves
ꢀ
and the solution stirred for 5 min prior to the addition of 0.0850 g
PhIO (0.387 mmol, 1.2 equiv). The reaction mixture was stirred for
2 h, filtered through Celite, and concentrated by rotary evaporation.
1H NMR analysis of the crude mixture showed 10a and 10b. A
mesitylene standard could be used to quantify the amounts of the
materials. Compound 10a gives a distinct doublet at 5.88 ppm in
the 1H NMR spectrum, but was too sensitive to isolate and char-
acterize. However, silica gel chromatography yielded a water-
opened enesulfamate of 10a. The cyclopropane 10b was also sen-
sitive, but small amounts could be isolated by chromatography
(15e75% EtOAc/hexane) for characterization.
with 50 mg 4 A powdered molecular sieves. The flask was cooled to
0
ꢀC in an ice bath, and DMDO (1.35 mL of a 0.22 M solution in
CH2Cl2, 0.297 mmol, 2.4 equiv) was added. The solution was stirred
for 2 h at 0 ꢀC, at which point TLC (30% EtOAc/hexanes, CAM stain)
indicated completion. The solution was concentrated under re-
duced pressure, and fresh CH2Cl2 (1.2 mL) was added. The solution
was cooled to ꢁ78 ꢀC and Zn(BH4)2 (0.240 mL of a 0.5 M solution in
THF, 0.120 mmol, 1 equiv) was added in one portion. The reaction
mixture was stirred for 2 h, and then quenched by the addition of
saturated NH4Cl solution. The mixture was extracted twice with
CH2Cl2, and the combined organic layers were washed with brine
and dried over Na2SO4. The resulting crude oil was purified by
column chromatography (10e25% EtOAc/hexane) to give 32.0 mg of
16a in addition to 10.5 mg of two minor diastereomers in a 3:1 ratio
(favoring 16b). Combined, this equates to a 78% yield and 4.1:1:0.33
dr. The third diastereomer is not mentioned in this report due to its
very low yield of formation. Major diastereomer (16a): 1H NMR
4.4.1. (4E,5S)-4-{[(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl]methyl-
idene}-1,2,3-oxathiazepan-5-ol 2,2-dioxide (water-opened 10a). 1H
NMR (500 MHz, CDCl3)
d
6.72 (br s, 1H), 5.77 (d, J¼8.6 Hz, 1H), 5.03
(t, J¼3.5 Hz, 1H), 4.65e4.80 (m, 2H), 4.21 (dt, J¼12.8, 3.6 Hz, 1H),
4.12 (dd, J¼8.7, 6.7 Hz, 1H), 3.69 (dd, J¼8.3, 7.5 Hz, 1H), 2.60 (br s,
1H), 2.08e2.12 (m, 2H), 1.43 (s, 3H), 1.40 (s, 3H). 13C NMR
(500 MHz, CDCl3)
d
5.44 (d, J¼4.7 Hz, 1H), 4.51 (ddd, J¼12.5, 9.1,
(125.7 MHz, CDCl3)
d
136.0, 127.1, 110.1, 70.8, 69.2, 64.9, 64.1, 36.8,
1.4 Hz, 1H), 4.37 (q, J¼6.6 Hz, 1H), 4.26 (dds, J¼12.6, 6.6, 2.2 Hz, 1H),
4.23 (td, J¼6.0, 3.0 Hz, 1H), 3.87 (t, J¼7.5 Hz, 1H), 3.19 (dt, J¼7.5,
5.2 Hz, 1H), 2.90 (d, J¼2.3 Hz, 1H), 2.34 (ddt, J¼15.6, 9.3, 2.6 Hz, 1H),
1.95 (dtd, J¼15.6, 6.6, 1.2 Hz, 1H), 1.66 (m, 4H), 0.91 (m, 15H), 0.12 (s,
26.6, 25.8. HRMS m/z [MꢁH]ꢁ predicted, 278.0703; observed,
278.0696.
4.4.2. 8-[(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl]-4-oxa-3-thia-2-
3H), 0.12 (s, 3H). 13C NMR (125.7 MHz, CDCl3)
d 113.6, 75.9, 70.7,
azabicyclo[5.1.0]oct-1-ene 3,3-dioxide (10b). 1H NMR (500.0 MHz,
70.7, 66.2, 65.5, 61.1, 35.4, 29.4, 28.8, 25.7, 17.9, 8.2, 8.0, ꢁ4.5, ꢁ4.9.
CDCl3)
d
5.10 (dd, J¼6.3, 3.6 Hz, 1H), 4.97 (dd, J¼12.0, 3.7 Hz, 1H),
HRMS m/z [MþNH4]þ predicted, 457.2399; observed, 457.2404.
4.64 (td, J¼12.2, 3.6 Hz, 1H), 4.51 (ddd, J¼12.2, 5.5, 1.9 Hz, 1H), 4.12
(d, J¼11.0 Hz,1H), 3.99 (dd, J¼11.0, 3.6 Hz,1H), 3.16 (d, J¼6.3 Hz,1H),
2.34 (dtd, J¼14.5, 12.2, 5.5 Hz, 1H), 2.17 (dtd, J¼14.5, 3.6, 1.9 Hz, 1H),
Minor diastereomer (16b): 1H NMR (500 MHz, CDCl3)
d 5.45 (d,
J¼10.5 Hz,1H), 4.61 (t, J¼12.4 Hz,1H), 4.39 (t, J¼2.9 Hz,1H), 4.19 (dt,
J¼13.0, 3.2 Hz,1H), 4.17 (dd, J¼8.4, 6.1 Hz,1H), 4.03 (app q, J¼6.9 Hz,
1H), 3.87 (app t, J¼7.9 Hz, 1H), 3.61 (m, 2H), 2.43 (d, J¼2.3 Hz, 1H),
2.21 (ddt, J¼15.6, 12.0, 2.7 Hz, 1H), 1.91 (dt, J¼15.6, 3.7 Hz, 1H), 1.63
(m, 4H), 0.93 (s, 9H), 0.90 (t, J¼7.5 Hz, 3H), 0.89 (t, J¼7.5 Hz, 3H),
1.36 (s, 3H), 1.33 (s, 3H). 13C NMR: (125.7 MHz, CDCl3)
d 194.1, 85.7,
84.6, 80.3, 72.1, 68.9, 60.5, 30.4, 27.8, 24.6. HRMS m/z
[MþNH4þH2O]þ predicted, 297.1115; observed, 297.1112.
0.15 (s, 3H), 0.13 (s, 3H). 13C NMR (125.7 MHz, CDCl3)
d 113.3, 76.2,
4.5. Preparation of 19 from 9
73.9, 70.6, 67.5, 64.3, 57.7, 36.9, 29.6, 29.1, 25.8, 17.9, 8.2, 8.1, ꢁ4.1,
ꢁ4.8. HRMS m/z [MþH]þ predicted, 440.2133; observed, 440.2137.
4.5.1. (4E,5S)-4-{[(4S)-2,2-Diethyl-1,3-dioxolan-4-yl]methyl-idene}-
5-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-1,2,3-oxathiazepane 2,2-
dioxide (14). The sulfamate 9 (0.50 g, 1.72 mmol, 1.0 equiv) was
dissolved in 12 mL dry CH2Cl2. Rh2(OAc)4 (0.0150 g, 0.034 mmol,
4.5.3. tert-Butyl{(1S,2S,3S)-1-[(4R)-2,2-diethyl-1,3-dioxolan-4-yl]-1-
hydroxy-3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]pent-4-en-2-yl}car-
bamate (18). The triad 16a (0.0650 g, 0.148 mmol, 1.0 equiv) was
Please cite this article in press as: Adams, C. S.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.03.084

6
C.S. Adams et al. / Tetrahedron xxx (2014) 1e7
dissolved in 1.5 mL CH2Cl2. The solution was cooled to 0 ꢀC and
2.0 mg DMAP (0.0148 mmol, 0.1 equiv), 0.0230 mL triethylamine
yield a crude oil. The residue was purified by column chromatog-
raphy (5e25% EtOAc/hexane) to give 28.4 mg (0.0648 mmol, 27%)
of the aminoketone 20 in a 17:1 dr and was used without further
(0.163 mmol, 1.1 equiv), and 0.0356
g Boc2O (0.163 mmol,
1.10 equiv) were added successively. After stirring for 40 min, the
solution was diluted with 5 mL ether and passed through a short
plug of silica. The solids were rinsed with ether (2ꢂ3 mL) and the
filtrate concentrated. The residue was dissolved in 3 mL of 1:1
EtOH/CH2Cl2. Meanwhile, 0.0370 g o-nitrophenyl selenocyanate
(0.163 mmol, 1.10 equiv) in 1 mL EtOH was cautiously treated with
6.70 mg NaBH4 (0.177 mmol, 1.2 equiv), and stirred for 20 min. The
solution containing the Boc-protected triad was added to the sel-
enide, and the reaction mixture stirred at rt for 4 h. The reaction
mixture was diluted with 10 mL CH2Cl2 and quenched with 10 mL
0.1 M HCl. The product was extracted into CH2Cl2, the combined
organics were washed with aqueous NaHCO3 and the volatiles re-
moved under reduced pressure. The crude residue was dissolved in
1.5 mL THF and 0.152 mL 30% by weight H2O2 (1.48 mmol,
10.0 equiv) and stirred at rt overnight. The solution was diluted
with CH2Cl2, washed with aqueous Na2S2O8, and concentrated.
Chromatography (6e30% EtOAc in hexanes) gave 18 as a colorless
purification. Major diastereomer: 1H NMR (500 MHz, CDCl3)
d 5.06
(d, J¼10.5 Hz, 1H), 4.71 (dd, J¼10.5, 9.2 Hz, 1H), 4.55 (dd, J¼6.7,
6.2 Hz, 1H), 4.33 (dd, J¼6.7, 3.4 Hz, 2H), 4.16 (d, J¼3.4 Hz, 1H), 4.15
(d, J¼2.4 Hz, 1H), 3.94 (td, J¼9.1, 5.3 Hz, 1H), 2.17 (m, 2H), 1.68 (m,
4H), 0.94 (t, J¼7.5 Hz, 3H), 0.91 (t, J¼7.5 Hz, 3H), 0.86 (s, 9H), 0.07 (s,
3H), ꢁ0.04 (s, 3H). 13C NMR (125.7 MHz, CDCl3)
d 206.8, 115.6, 80.5,
73.8, 66.6, 65.5, 57.9, 37.5, 29.2, 28.5, 25.5, 17.8, 8.2, 7.9, ꢁ4.5, ꢁ5.1.
HRMS m/z [MþNH4]þ predicted, 455.2242; observed, 455.2243.
4.6.2. (4S,5S)-4-[(R)-[(4R)-2,2-Diethyl-1,3-dioxolan-4-yl]-(hydroxy)
methyl]-5-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-1,2,3-
oxathiazepane 2,2-dioxide (16c). The aminoketone 20 (10.0 mg,
0.0229 mmol, 1 equiv) was added to a 10 mL round-bottomed flask
and 3 mL of Et2O was added. The flask was cooled to ꢁ78 ꢀC in a dry
ice/acetone bath, and LiBEt3H (0.115 mL of a 1.0 M solution in THF,
0.115 mmol, 5 equiv) was added via syringe. The solution was
stirred for 2 h, at which point the temperature of the bath had
reached 0 ꢀC. The solution was diluted with 20 mL Et2O and washed
twice with saturated NH4Cl and once with brine. The organic layer
was dried over MgSO4 and concentrated under reduced pressure to
yield a crude oil that was purified by column chromatography
(0e30% EtOAc/hexane) to give 5.8 mg of the stereotetrad 16c and
1.1 mg of 16a as a separable minor diastereomer. Combined, this
equates to 6.9 mg (0.0158 mmol, 69%) in a 5.3:1 dr. 1H NMR
oil (0.0392 g, 0.0853 mmol, 58%). 1H NMR (500 MHz, CDCl3)
d 5.99
(ddd, J¼16.2, 10.6, 4.6 Hz, 1H), 5.38 (d, J¼16.2 Hz, 1H), 5.23 (d,
J¼10.6 Hz, 1H), 4.85 (d, J¼7.6 Hz, 1H), 4.61 (s, 1H), 4.19 (app q,
J¼6.4 Hz, 1H), 4.12 (app t, J¼6.4 Hz, 1H), 3.87 (t, J¼7.7 Hz, 1H), 3.72
(m, 2H), 3.03 (d, J¼3.2 Hz, 1H), 1.55e1.73 (m, 4H), 1.43 (s, 9H), 0.91
(m, 12H), 0.88 (t, J¼7.2 Hz, 3H), 0.09 (s, 3H), 0.05 (s, 3H). 13C NMR
(125.7 MHz, CDCl3) d 155.9, 137.2, 116.3, 112.9, 79.5, 76.4, 73.8, 73.3,
66.6, 56.1, 29.4, 28.8, 28.3, 25.8, 18.1, 8.3, 8.0, ꢁ4.7, ꢁ5.1. HRMS m/z
(500 MHz, CDCl3)
d
5.06 (d, J¼10.1 Hz, 1H), 4.28 (m, 3H), 4.16 (dd,
[MþH]þ predicted, 460.3089; observed, 460.3098.
J¼8.4, 6.5 Hz, 1H), 3.92 (m, 2H), 3.62 (dd, J¼8.4, 5.6 Hz, 1H), 2.99 (td,
J¼9.7, 0.8 Hz, 1H), 2.62 (br s, 1H), 2.17 (m, 1H), 2.04 (m, 1H), 1.66 (q,
J¼7.4 Hz, 2H), 1.63 (q, J¼7.5 Hz, 2H), 0.90 (t, J¼7.5 Hz, 3H), 0.89 (t,
J¼7.4 Hz, 3H), 0.88 (s, 9H), 0.10 (s, 3H), 0.09 (s, 3H). 13C NMR
4.5.4. tert-Butyl {(2S,3R,4R)-2-[(4R)-2,2-diethyl-1,3-dioxolan-4-yl]-
5-hydroxy-4-[[(1,1-dimethylethyl)dimethylsilyl]oxy]tetrahydrofuran-
3-yl}carbamate (19). The alkene 18 (0.0350 g, 0.0761 mmol,
1.0 equiv) was dissolved in 1.0 mL of 3:1 CH2Cl2/MeOH. The mixture
was cooled to ꢁ78 ꢀC and a stream of ozone was bubbled through
the solution until a pale blue color persisted. Oxygen was then
bubbled through the solution for 5 min prior to the addition of
0.056 mL Me2S (0.761 mmol, 10.0 equiv). The solution was gradu-
ally warmed to rt over 1 h and then concentrated to afford a crude
oil that was purified by column chromatography (5e25% EtOAc in
hexanes) to give lactol 17 as a 1:1 mixture of anomers. 1H NMR
(125.7 MHz, CDCl3)
d 113.9, 76.2, 70.0, 69.4, 67.0, 66.4, 57.9, 37.6,
29.4, 25.6, 17.8, 8.2, 7.7, ꢁ4.4, ꢁ5.2. HRMS m/z [MþNH4]þ predicted,
457.2399; observed, 457.2419.
Acknowledgements
The authors thank the NSF (_100000001) (CHE-1254397 to J.M.
S.), the University of Wisconsin and the Wisconsin Alumni Research
Foundation (_100001395) for financial support. Dr. Charles Fry and
Dr. Martha Vestling are thanked for assistance in the acquisition of
NMR and MS data, respectively.
(500 MHz, CDCl3)
d
5.30 (t, J¼4.0 Hz, 0.5H), 5.12 (s, 0.5H), 4.91 (d,
J¼7.0 Hz, 1H), 4.31 (m, 1H), 4.17 (m, 1H), 3.85e4.10 (m, 4H), 3.75 (br
s, 0.5H), 3.46 (br s, 0.5H), 1.58e1.80 (m, 4H), 1.44 (s, 9H), 0.85e0.98
(m, 15H), 0.14 (s, 1.5H), 0.13 (s, 1.5H), 0.11 (s, 3H). 13C NMR
References and notes
(125.7 MHz, CDCl3)
d 155.0 (2), 113.7, 113.5, 103.0, 96.9, 82.4, 80.9,
1. (a) Johnson, D. A.; Liu, H.-W. Curr. Opin. Chem. Biol. 1998, 2, 642e649; (b)
Weymouth-Wilson, A. C. Nat. Prod. Rep. 1997, 14, 99e110; (c) Hooper, I. R.
Aminoglycoside Antibiotics; Springer: New York, NY, 1982.
2. (a) Ogura, H. Proc. Jpn. Acad., Ser. B 2011, 87, 328e361; (b) Shikhman, A. R. Fut.
Rheumatol. 2006, 1, 67e78.
79.7, 76.6, 71.9 (2), 66.4 (2), 65.3 (2), 53.3, 52.2, 29.5, 29.4, 28.6, 28.4,
28.3 (2), 25.7 (2), 18.2, 18.2, 8.3, 8.2 (3), ꢁ4.8, ꢁ5.0, ꢁ5.2 (2).
4.6. Synthesis of alternate stereoisomer 16c from 14
3. Carbohydrate-based Drug Discovery; Wong, C.-H., Ed.; Wiley-VCH: Weinheim,
Germany, 2003.
4.6.1. (4R)-2,2-Diethyl-1,3-dioxolan-4-yl][(4S,5S)-5-[(1,1-
dimethylethyl)dimethylsilyl]oxy-2,2-dioxido-1,2,3-oxathiazepan-4-yl]
methanone (20). The enesulfamate 14 (101.1 mg, 0.240 mmol,
1 equiv) was added to a 10 mL round-bottomed flask, followed by
4. (a) Wang, J.; Chang, C.-W. T. Systematic Synthesis of Aminosugars and their
Stereoselective Glycosylation In Glycobiology and Drug Design; Klyosov, A. A.,
Ed.; ACS: Washington, DC, 2012; pp 265e286; (b) Rai, R.; McAlexander, I.;
Chang, C.-W. T. Org. Prep. Proced. Int. 2005, 37, 337e375; (c) Preparative Car-
bohydrate Chemistry; Hanessian, S., Ed.; Marcel Dekker: New York, NY, 1997; (d)
Boons, G.-J.; Hale, K. J. Organic Synthesis with Carbohydrates; Sheffield Aca-
demic: Sheffield, UK, 2000.
5. For selected references, see: (a) Bodkin, J. A.; Bacskay, G. B.; McLeod, M. D. Org.
Biomol. Chem. 2008, 6, 2544e2553; (b) Donohoe, T. J.; Blades, K.; Helliwell, M.
Chem. Commun. 1999, 1733e1734; (c) Csatayova, K.; Davies, S. G.; Lee, J. A.;
Roberts, P. M.; Russell, A. J.; Thomson, J. E.; Wilson, D. L. Org. Lett. 2011, 13,
2606e2609; (d) Marshall, J. A.; Beaudoin, S. J. Org. Chem. 1996, 61, 581e586; (e)
Ermolenko, L.; Sasaki, N. A.; Potier, P. Tetrahedron Lett. 1999, 40, 5187e5190; (f)
Ermolenko, L.; Sasaki, N. A.; Potier, P. J. Chem. Soc., Perkin Trans. 1 2000,
2465e2473.
ꢀ
ꢀ
100 mg 4 A powdered molecular sieves. The flask was cooled to 0 C
in an ice bath, and DMDO (2.70 mL of a 0.22 M solution in CH2Cl2,
0.594 mmol, 2.5 equiv) was added. The solution was stirred for 2 h
at 0 ꢀC, at which point TLC (30% EtOAc/hexanes, CAM stain) in-
dicated completion. The solution was concentrated under reduced
pressure and 1,2-dichloroethane (4.5 mL) was added to the residue,
followed by Al(OtBu)3 (58.3 mg, 0.237 mmol, 1 equiv). The flask was
fitted with an air condenser and heated to 50 ꢀC for 4 h. The re-
action was quenched by the addition of a saturated solution of
Rochelle’s salt and stirred for 30 min. The mixture was extracted
twice with CH2Cl2, washed with brine, and dried over Na2SO4 to
ꢁ
6. For recent reviews demonstrating the generation and transfer of allene axial
chirality, see: (a) Hoffman-Roder, A.; Krause, N. Angew. Chem., Int. Ed. 2004, 43,
1196e1216; (b) Yu, S.; Ma, S. Angew. Chem., Int. Ed. 2012, 51, 3074e3112; (c)
Allen, A. D.; Tidwell, T. T. Chem. Rev. 2013, 113, 7287e7342; (d) Campolo, D.;
€
Please cite this article in press as: Adams, C. S.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.03.084

C.S. Adams et al. / Tetrahedron xxx (2014) 1e7
7
Gastaldi, S.; Roussel, C.; Bertrand, M. P.; Nacheb, M. Chem. Soc. Rev. 2013, 42,
8434e8466.
12. The allene epimer 11 can be prepared from the aldehyde derived from
D
-man-
nitol by conducting an analogous Ti-acetylide reduction with 4-(tert-butyldi-
methylsilyloxy)-1-butyne. The propargyl alcohol can be converted directly to the
allene by following the protocol outlined in: Myers, A. G.; Zheng, B. J. Am. Chem.
Soc. 1996, 116, 4492e4493 Silyl deprotection and sulfamoylation afforded 11.
13. Hu, X. E. Tetrahedron 2004, 60, 2701e2743.
7. (a) Boralsky, L. A.; Marston, D.; Grigg, R. D.; Hershberger, J. C.; Schomaker, J. M.
Org. Lett. 2011, 13, 1924e1927; (b) Grigg, R. D.; Schomaker, J. M.; Timokhin, V.
Tetrahedron 2011, 67, 4318e4326; (c) Adams, C. S.; Boralsky, L. A.; Guzei, I. A.;
Schomaker, J. M. J. Am. Chem. Soc. 2012, 134, 10807e10810; (d) Grigg, R. D.;
Rigoli, J. W.; Pearce, S. D.; Schomaker, J. M. Org. Lett. 2012, 14, 280e283; (e)
Rigoli, J. W.; Boralsky, L. A.; Hershberger, J. C.; Marston, D.; Meis, A. R.; Guzei, I.
A.; Schomaker, J. M. J. Org. Chem. 2012, 77, 2446e2455; (f) Weatherly, C. D.;
Rigoli, J. W.; Schomaker, J. M. Org. Lett. 2012, 14, 1704e1707; (g) Weatherly, C.
D.; Guzei, I. A.; Schomaker, J. M. Eur. J. Org. Chem. 2013, 3667e3670; (h) Rigoli, J.
W.; Weatherly, C. W.; Vo, B. T.; Neale, S.; Meis, A. R.; Schomaker, J. M. Org. Lett.
2013, 15, 290e293; (i) Rigoli, J. W.; Weatherly, C. W.; Alderson, J. M.; Vo, B. T.;
Schomaker, J. M. J. Am. Chem. Soc. 2013, 135, 17238e17241.
8. (a) Ko, J. S.; Keum, J. E.; Ko, S. Y. J. Org. Chem. 2010, 75, 7006e7009; (b) Organic
Syntheses; Wiley & Sons: New York, NY, 1998, Collect. Vol. No. 9, pp 450e453.
9. Shimizu, M.; Kawamoto, M.; Niwa, Y. Chem. Commun. 1999, 1151e1152.
10. Amos, R. A.; Katzenellenbogen, J. A. J. Org. Chem. 1978, 43, 555e560.
11. (a) Stoll, A. H.; Blakey, S. B. J. Am. Chem. Soc. 2010, 132, 2108e2109; (b) Stoll, A.
H.; Blakey, S. B. Chem. Sci. 2011, 2, 112e116.
14. For an example of the 1H NMR coupling analysis that was used to determine
the relative configurations of compounds 16a, 16b, 16c, and 20, see the Sup-
plementary data in Ref. 7c.
15. (a) Nakata, T.; Tanaka, T.; Oishi, T. Tetrahedron Lett. 1983, 24, 2653e2656; (b)
Takahashi, T.; Miyazawa, M.; Tsuji, J. Tetrahedron Lett. 1985, 26, 5139e5142; (c)
Fujisawa, T.; Kohama, H.; Tajima, K.; Sato, T. Tetrahedron Lett. 1984, 25,
5155e5156.
16. For an example of nucleophilic displacement of a sulfamate, see: Espino, C. G.;
Wehn, P. M.; Chow, J.; Du Bois, J. J. Am. Chem. Soc. 2001, 123, 6935e6936.
17. (a) Paquette, L. A.; Hofferberth, J. E. Org. React. 2004, 62, 447e567; (b) Wrod-
nigg, T. M.; Eder, B. Top. Curr. Chem. 2001, 215, 115e152.
18. Armarego, W. L. F.; Chai, C. L. L. Purification of Laboratory Chemicals, 6th ed.;
Elsevier: Burlington, MA, 2009.
19. Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923e2925.
Please cite this article in press as: Adams, C. S.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.03.084