A versatile route to (E)- and (Z)-2-hydroxy-3,4-unsaturated disubstituted sulfilimines and their haloamidation reaction

Article abstract of DOI:10.1021/jo900569z

(Chemical Equation Presented) α-Chloro ynones have been reduced using Noyori's Ru catalyst to furnish R-chloro propargylic alcohols with excellent enantioselectivity. These have been used as a common precursor for the preparation of (E)- and (Z)-2-hydroxy

Full text of DOI:10.1021/jo900569z

A Versatile Route to (E)- and (Z)-2-Hydroxy-3,4-unsaturated
Disubstituted Sulfilimines and Their Haloamidation Reaction
Sadagopan Raghavan,* Shaik Mustafa, and B. Sridhar†
Organic DiVision I, Indian Institute of Chemical Technology, Hyderabad 500 007, India, and Lab of X-ray
Crystallography, Indian Institute of Chemical Technology, Hyderabad 500 007, India
sraghaVan@iict.res.in
ReceiVed March 18, 2009
R-Chloro ynones have been reduced using Noyori’s Ru catalyst to furnish R-chloro propargylic alcohols
with excellent enantioselectivity. These have been used as a common precursor for the preparation of
(E)- and (Z)-2-hydroxy-3,4-unsaturated disubstituted sulfilimines. The latter serve as precursors for the
highly regio- and stereoselective preparation of bromo carbamates.
Introduction
Vicinal haloamines,1 obtained by the addition of amine and
halogen moieties across carbon-carbon double bonds, are useful
building blocks in organic synthesis2 and medicinal chemistry.3
Halo amines have been obtained by (a) aminohalogenation1a,4
via an aziridinium intermediate followed by attack of a halogen
nucleophile or (b) haloamination5 which involves a source of
halonium ion and nitrogen nucleophiles.
FIGURE 1. Preparation of bromo sulfonamide.
ides using N-sulfinylbenzylcarbamate8 (CbzNSO), Burgess
reagent,9a and their stereoselective conversion to bromo
carbamates (Figure 2).9b
We had reported a novel stereoselective method of preparation
of bromo sulfonamides by haloamidation6 of alkenes using
N-Ts-sulfilimines as intramolecular nucleophiles (Figure 1).
The drawbacks with the reported methodology were that
(i) the cis-disubstituted alkenes were accessible by a multistep
sequence of reactions,7 (ii) the N-Ts group in the product
could be removed only using harsh reaction conditions which
is not ideal for a substrate with sensitive functional groups,
and (iii) it only provided access to racemic products.
Subsequently, we reported a route to optically active 2-siloxy-
3,4-unsaturated sulfilimines from the corresponding sulfox-
This methodology also suffered from the drawback of
having to protect the ꢀ-hydroxy group of the sulfoxide and
allowed ready preparation of trans-disubstituted alkenes.10
We felt that a more direct route to both (E)- and (Z)-3,4-
(5) (a) Rawal, G. K.; Kumar, A.; Tawar, U.; Vankar, Y. D. Org. Lett. 2007,
9, 5171–5174. (b) Kirschning, A.; Hashem, M. D.; Monenschein, H.; Rose, L.;
Schonng, K. U. J. Org. Chem. 1999, 64, 6522–6526. (c) Bellucci, G.; Bianchini,
R.; Chiappe, C. J. Org. Chem. 1991, 56, 3067–3073. (d) Jung, S. H.; Kohn, H.
J. Am. Chem. Soc. 1985, 107, 2931–2943. (e) Wang, Z. G.; Warren, J. D.; Dudkin,
V. Y.; Zhang, X.; Iserloh, U.; Visser, M.; Eckhardt, M.; Seeberger, P. H.;
Danishefsky, S. J. Tetrahedron 2006, 62, 4954–4978. (f) Castro, M. D.;
Marzabadi, C. H. Tetrahedron Lett. 2004, 45, 6501–6504. (g) Boschi, A.;
Chiappe, C.; De Rubertis, A.; Russe, M. F. J. Org. Chem. 2000, 65, 8470–
8477. (h) Kumar, V.; Ramesh, N. G. Tetrahedron 2006, 62, 1877–1885. (i)
Owens, J. M.; Yung, B. K. S.; Hill, D. C.; Petillo, P. A. J. Org. Chem. 2001,
66, 1484–1486. (j) Kim, H. M.; Kim, J. J.; Danishefsky, S. J. J. Am. Chem. Soc.
2001, 123, 35–48. (k) Spassova, M. K.; Bornmann, W. G.; Ragupathi, G.;
Sukenick, G.; Livingston, P. O.; Danishefsky, S. J. J. Org. Chem. 2005, 70,
3383–3395. (l) Garcia, J. I.; Mateo, F. H.; Flores, F. G. C.; Gonzalez, F. S. J.
Org. Chem. 2004, 69, 202–205. (m) Raghavan, S.; Reddy, S. R.; Tony, K. A.;
Kumar, C. N.; Nanda, S. Synlett 2001, 851–853. (n) Griffith, D. A.; Danishefsky,
S. J. J. Am. Chem. Soc. 1996, 118, 9526–9538. (o) Yeung, Y. Y.; Gau, X.;
Corey, E. J. J. Am. Chem. Soc. 2006, 128, 9644–9645. (p) Nyffeler, P. T.; Duron,
S. G.; Burkart, M. D.; Vincet, S. P.; Wong, C. H. Angew. Chem., Int. Ed. 2005,
44, 192–212.
† Lab of X-ray Crystallography.
(1) Reviews: (a) Li, G. G.; Kotti, S. R. S. S.; Timmons, C. Eur. J. Org.
Chem. 2007, 2745–2758. (b) Cardillo, G.; Orena, M. Tetrahedron 1990, 46,
3321–3408.
(2) (a) Kemp, J. E. G. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 3, pp 471-513. (b) Griffith,
D. A.; Danishefsky, S. J. J. Am. Chem. Soc. 1991, 113, 5863–5864. (c) Orlek,
B. S.; Stemp, G. Tetrahedron Lett. 1991, 32, 4045–4048.
(3) Qiu, J.; Silverman, R. B. J. Med. Chem. 2000, 43, 706–720.
(4) (a) Li, G.; Wei, H. X.; Kim, S. H. Org. Lett. 2000, 2, 2249–2252. (b)
Karur, S.; Kott, S. R. S. S.; Xu, X.; Canno, J. F.; Headley, A. D.; Li, G. J. Am.
Chem. Soc. 2003, 125, 13340–13341. (c) Klepacz, A.; Zwierzak, A. Tetrahedron
Lett. 2001, 42, 4539–4540. (d) Han, J. L.; Zhi, S. J.; Wang, L. Y.; Pan, Y.; Li,
G. Eur. J. Org. Chem. 2007, 1332–1337.
(6) Raghavan, S.; Naveen Kumar, Ch.; Tony, K. A.; Ramakrishna Reddy,
S.; Ravikumar, K. Tetrahedron Lett. 2004, 45, 7231–7234.
10.1021/jo900569z CCC: $40.75
Published on Web 05/15/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 4499–4507 4499

Raghavan et al.
SCHEME 1. Enantioselective Preparation of Propargyl
Alcohol
propargyl alcohol 7a from phenyl acetylene 2a and p-tolythio
acetaldehyde12 1 in only moderate enantiomeric excess
Scheme 1.13
FIGURE 2. Preparation of bromo carbamate.
We therefore considered catalytic asymmetric reduction
of ynones 4.14 Commercially available Weinreb amide 3 on
reaction with lithium acetylides derived from alkynes 2a-d
afforded ynone 4 after the reaction mixture was quenched
with aq HCl.15 Chiral Rh hydrogenation catalysts have been
reported to efficiently convert R-halogenated ketones to
optically active alcohols though in moderate ee.16 Ikariya
and co-workers have reported highly efficient asymmetric
transfer hydrogenation of R-chloro acetophenones using a
well-defined chiral Rh complex.17 The catalyst, however,
when used for the reduction of R-chloro ketones possessing
conjugated double or triple bonds, gave the corresponding
products with only moderate ee ranging from 58-68%. The
ynone 4a has been reduced by Ikariya via transfer hydroge-
nation using the Rh catalyst under optimized conditions to
afford propargylic alcohol 6a in 68% ee. In this context, it
was very pleasing to note that the transfer hydrogenation of
ketones 4 using 2.5 mol % of Noyori’s catalyst,18 CpRu-
Cl[(S,S)-Tsdpen]5,inthepresenceofformicacid-triethylamine
azeotrope in dichloromethane as solvent at rt furnished
propargylic alcohols 6 in good yield (70-80%) and enanti-
oselectivity19 (er 94-97 to 6-3), Scheme 2. To the best of
our knowledge, the conditions reported herein for the
enantioselective transfer hydrogenation of R-chloro ynones
afford the corresponding propargylic alcohols with the highest
enantioselectivity reported to date. A mixture of formic acid/
triethylamine was found to be an optimal hydrogen source
as no reduction was observed using 2-propanol. The catalyst
disubstituted-2-hydroxy sulfilimines was essential for a wide
application of our methodology. Toward this goal, we dis-
close herein a versatile route to both cis- and trans-disub-
stituted ꢀ-hydroxy sulfilimines from a common intermediate
and their regio- and stereoselective conversion to bromo
carbamates.
Results and Discussion
Optically active propargylic alcohols were reasoned to be
suitable precursors to both cis- and trans-allylic alcohols.
Thus, we initially considered preparing propargyl alcohols
by introducing chirality simultaneously with carbon-carbon
bond formation. Using Pu’s protocol,11 we could prepare
(7) The cis-alkenes were obtained in nine steps from cis-2-butene-1,4-diol
as depicted below.
(11) Gao, G.; Xie, R.-G.; Pu, L. Proc. Natl. Acad. Sci. U.S.A. 2004, 101,
5417–5420.
(12) p-Tolylthio acetaldehyde was obtained by IBX oxidation of p-tolylthio
ethanol.
(13) In future, with an efficient catalyst becoming available for the preparation
of propargylic alcohols, by the direct reaction of aldehydes and alkynes, we can
prepare optically active sulfilimines with excellent enantioselectivity readily in
only three steps.
The trans alkenes were obtained in only three steps as illustrated below.
(14) For other alternative approaches to the reduction of ynones, see: (a)
Helal, C. J.; Magriotis, P. A.; Corey, E. J. J. Am. Chem. Soc. 1996, 118, 10938–
1939. (b) Schubert, T.; Hummel, W.; Mu¨ller, M. Angew. Chem., Int. Ed. 2002,
41, 634–637.
(15) Choudhary, A.; Breslav, M.; Grimm, J. S.; Xiao, T.; Xu, D.; Sorgi,
K. L. Tetrahedron Lett. 2007, 48, 3069–3072.
(16) Devocelle, M.; Mortreux, A.; Agbossou, F.; Dormoy, J.-P. Tetrahedron
Lett. 1999, 40, 4551–4554.
(17) Hamada, T.; Torii, T.; Izawa, K.; Ikariya, T. Tetrahedron 2004, 60,
7411–7417.
(8) Raghavan, S.; Mustafa, S. Tetrahedron Lett. 2008, 49, 3216–3220.
(9) (a) Raghavan, S.; Mustafa, S.; Rathore, K. Tetrahedron Lett. 2008, 49,
4256–4259. (b) Raghavan, S.; Mustafa, S. Tetrahedron Lett. 2008, 49, 5169–
5171.
(10) The ꢀ-hydroxy γ,δ-cis-alkenes cannot be derived from the reaction of
cis esters with the lithio anion of aryl methyl sulfoxide followed by reduction
of the resulting ꢀ-keto sulfoxides since the cis ester undergoes isomerization to
the trans ester. The alternative reaction of acetylenic esters with lithio anion of
aryl methyl sulfoxide followed by reduction of the resulting ynones suffers from
poor stereoselectivity; see: Sanchez-Obregon, R.; Ortiz, B.; Walls, F.; Yuste,
F.; Garcia Ruano, J. L. Tetrahedron: Asymmetry 1999, 10, 947–955.
(18) (a) Hashiguchi, S.; Fujii, A.; Takehara, J.; Ikariya, T.; Noyori, R. J. Am.
Chem. Soc. 1995, 117, 7562–7563. (b) Fujii, A.; Hashiguchi, S.; Uematsu, N.;
Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1996, 118, 2521–2522. (c) Haack,
K.-J.; Hashiguchi, S.; Fujii, A.; Ikariya, T.; Noyori, R. Angew. Chem., Int. Ed.
1997, 36, 285–288. (d) Hashiguchi, S.; Fujii, A.; Haack, K.-J.; Matsumura, K.;
Ikariya, T.; Noyori, R. Angew. Chem., Int. Ed. 1997, 36, 288–290. (e) Matsumura,
K.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1997, 119, 8738–
8739. (f) Noyori, R.; Hashiguchi, S. Acc. Chem. Res. 1997, 30, 97–102.
(19) The enantioselectivity was determined by chiral HPLC; see the
Supporting Information. The S configuration was assigned on the basis of
literature precedent.
4500 J. Org. Chem. Vol. 74, No. 12, 2009

Route to (E)- and (Z)-2-Hydroxy-3,4-unsaturated Disubstituted Sulfilimines
SCHEME 2. Enantioselective Transfer Hydrogenation of
Prochiral r-Chloro Ynones
SCHEME 3. Preparation of cis- and trans-ꢀ-Hydroxy
Sulfilimines
was prepared in situ, and dichloromethane was found to be
the solvent of choice.20
Incidentally, the chloropropargylic alcohols are useful syn-
thons and can be converted directly or via the corresponding
epoxides into chiral R-functionalized alkynes,21a,b heterocycles,21c,d
and allenes21e,f and subjected to nucleophilic displacement.21g
Proceeding further, the chlorine was displaced by treatment of
6 with p-thiocresol in the presence of DBU in toluene to furnish
sulfide 7. Reduction of the triple bond using nickel boride22
and Red-Al23 afforded cleanly cis- and trans-allylic alcohols 8
and 9, respectively. Further treatment of the sulfide with
N-chloro-N-sodiobenzylcarbamate (NaNCbzCl) in acetonitrile
as the solvent yielded an equimolar mixture of separable anti-
and syn-sulfilimines,24 Scheme 3. Diastereoselective imination
using a chiral metal complex would furnish either anti- or syn-
sulfilimines selectively if not exclusively.25 It is noteworthy that
selective oxidation of sulfides 8 and 9 using sodium metape-
riodate or m-chloroperoxybenzoic acid at low temperatures
would afford the corresponding ꢀ-hydroxy-γ,δ-disubstituted
sulfoxides.
Having prepared the unsaturated sulfilimines, their regio- and
stereoselective bromoamidation was next investigated, Table 1.
An inspection of Table 1 reveals that the intramolecular transfer
of the N-Cbz group from sulfur to carbon is highly regioselective
affording 5-exo opening products in all cases except the styrene
derivatives 10a and 11a which afford 6-endo opening products,
both modes of opening being in accordance with Markovnikov’s
rule. The anti- and syn-sulfilimines behave stereoconvergently
(compare entries 1,2, 3,4, etc.) to afford bromocarbamates with
identical configuration at carbon but differing at sulfur, which
was proven by oxidation of the sulfinyl moiety in the products
individually to an identical sulfone. This therefore avoids the
necessity of having to prepare diastereomerically pure anti- or
syn-ꢀ-hydroxy sulfilimines or, if prepared as a mixture, to
separate them. The reaction is general and proceeds under mild
reaction conditions. The reaction probably proceeds via the
reversibly formed π-complex of the bromonium ion with the
alkenes (anti,cis and syn,trans chosen for illustration) which
on intramolecular attack by the sulfilimine group via 6-endo or
5-exo pathways would furnish intermediates I and III or II and
IV, respectively, which then upon hydrolysis by attack of water
at sulfur would yield the bromo carbamate sulfoxide with an
inversion of sulfur configuration, Figure 3.
The outcome of electrophile-induced addition to allylic
π-systems is determined by a delicate balance between steric,
viz. minimization of A1,3 strain26 and the stereoelectronic
effect27 of the allylic hydroxy (siloxy) group.28 An electron-
withdrawing allylic hydroxyl (siloxy) at the equatorial position
of an intermediate (for instance I/ II) is better aligned for σ*
C-O orbital interaction with the π-system,29 which results in
a decrease in the rate through it. The rate-retarding effect30 is
avoided when the allylic hydroxyl (siloxy) is orthogonal to the
π-system (for instance, intermediates III/IV). Sulfilimine
anti11a probably reacts via twist-chair VI, favored for stereo-
electronic and steric reasons, instead of chair intermediate V,
which suffers from diaxial interactions between OH and p-Tol
substituents, to furnish product syn13. The reaction via chair
intermediate VII, favored by steric but disfavored by stereo-
electronic effects, which would have afforded product syn13X,
was not observed. Previously, it has been practically observed6
that the silyl ether protected N-Ts sulfilimine 4da related to
(20) The hydrogenation in EtOAc as the solvent afforded the alcohol in poor
yield. The substrate to catalyst ratio (25:1) was found to be optimal. With a
higher substrate to catalyst ratio (100:1) side reactions were observed.
(21) (a) Takahashi, A.; Endo, T.; Nozoe, S. Chem. Pharm. Bull. 1992, 40,
3181–3184. (b) Bohlmann, F.; Burkhardt, T.; Zdero, C. Naturally Occurring
Acetylenes; Academic Press: New York, 1973. (c) Piotti, M. E.; Alper, H. J.
Org. Chem. 1997, 62, 8484–8489. (d) Pale, P.; Chuche, J. Tetrahedron Lett.
1987, 28, 6447–6448. (e) Oehlschlager, A. C.; Czyzewska, A. Tetrahedron Lett.
1983, 24, 5587–5590. (f) Alexakis, A.; Marek, I.; Mangeney, P.; Normant, J. F.
Tetrahedron 1991, 47, 1677–1696. (g) Bernet, B.; Vassella, A. Tetrahedron Lett.
1983, 24, 5491–5494.
(26) For reviews of the effects of 1,3-allylic strain on conformation and
stereoselectivity, see: (a) Johnson, F. Chem. ReV. 1968, 68, 375–413. (b)
Hoffmann, R. W. Chem. ReV. 1989, 89, 1841–1860.
(27) Deslongchamps, P. In Stereoelctronic Effects in Organic Chemistry, 1st
ed.; Baldwin, J. E., Ed.; Pergamon Press: New York, 1983; Vol. 1.
(28) Guindon, Y.; Soucy, F.; Yaokim, C.; Ogilvie, W. W.; Plamondon, L. J.
Org. Chem. 2001, 66, 8992–8996.
(22) Richardson, T.; Rychnovsky, S. D. J. Org. Chem. 1996, 61, 4219–4231.
(23) Spino, C.; Beaulieu, C. J. Am. Chem. Soc. 1998, 120, 11832–11833.
(24) Structures were assigned to syn- and anti-sulfilimines by comparison
(29) Danishefsky, S. J.; Larson, E.; Springer, J. P. J. Am. Chem. Soc. 1985,
107, 1274–1280.
1
of their H NMR to the corresponding N-Ts-sulfilimines.
(25) Collet, F.; Dodd, R. H.; Dauban, P. Org. Lett. 2008, 10, 5473–5476,
and references cited therein.
(30) Houk, K. N.; Moses, S. R.; Wu, Y.-D.; Rondan, N. G.; Jager, V.; Schohe,
R.; Froncek, F. R. J. Am. Chem. Soc. 1987, 109, 650–663.
J. Org. Chem. Vol. 74, No. 12, 2009 4501

Raghavan et al.
TABLE 1. Regio- and Stereoselective Preparation of
Bromocarbamatesa
FIGURE 3. Probable reaction pathway.
a All reactions were done using 0.5 mmol of the sulfilimine in the
presence of 1.2 equiv of NBS and 1.5 equiv of water in toluene (0.2 M)
at rt. b The structure of the sole or major product depicted. c Yield refers
to isolated yields. d Diastereoselectivity (at C3 relative to C2) is based
on 1H NMR of the crude reaction mixture. e The isomers were insepa-
rable; structures could be unambiguously assigned to the major products
only.
anti11a afforded two products in a 3:1 ratio. The major product
5ds probably is formed via intermediate VI which suffers from
a severe gauche interaction between the bulky OBPS group and
Br atom. This guache interaction is avoided in intermediate VII,
which affords 5dsX. This probably explains for the erosion of
selectivity observed in the case of 4da, Figure 4.
FIGURE 4. Probable reaction pathway.
Alkene syn10b probably reacts via intermediate VIII to
furnish anti14 as the sole product. The intermediate IX, which
is expected to furnish anti14X, is favored for stereoelectronic
reasons but disfavored by A1,3 strain. The related silyl-
protected N-Ts sulfilimine 4cs affords a 2:1 mixture of
products.6 The major product 5ca probably is formed through
intermediate VIII and the minor product via IX. The
interactions between OBPS and Br observed in intermediate
VIII are avoided in IX, Figure 5.
The structure of anti13 was unambiguously assigned by X-ray
crystallography.31 The structure of anti12 was assigned by
debromination using n-tributyltin hydride to afford an amino
alcohol derivative which was identical to the debrominated
product obtained from anti13.31 The structure of syn15 was
confirmed by debromination and relating it to a known com-
(31) See the Supporting Information.
4502 J. Org. Chem. Vol. 74, No. 12, 2009

Route to (E)- and (Z)-2-Hydroxy-3,4-unsaturated Disubstituted Sulfilimines
petroleum ether (v/v) to afford the propargyl alcohol 6b (1.5 g, 8
mmol) in 80% yield as a gummy liquid, er 94:6 (column: Chiralpack
AD-H; mobile phase: 20% EtOH in hexane; flow rate: 1 mL/min).
IR (KBr): 3376, 2928, 1697, 1385, 1035 cm-1. 1H NMR (200 MHz,
CDCl3): δ 4.6-4.5 (m, 1H), 3.7 (dd, J ) 10.6, 3.8 Hz, 1H), 3.6
(dd, J ) 10.6, 6.8 Hz, 1H), 2.2 (dt, J ) 1.5, 6.8 Hz, 2H), 1.6-1.1
(m, 8H), 0.9 (t, J ) 6.8 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ
87.6, 77.2, 62.7, 49.5, 31.2, 28.4, 28.3, 22.5, 18.6, 14.0. [R]D25
)
-5.0 (c 0.5, CHCl3). MS (FAB): 189 [M + H]+. HRMS (FAB):
m/z calcd for C10H18OCl 189.1041, found 189.1044.
Alcohol 6c. Similarly, ynone 4c (3.8 g, 10 mmol) was hydro-
genated over a period of 3.5 h to afford a crude compound which
was purified by column chromatography using 8% EtOAc/
petroleum ether (v/v) to afford the propargyl alcohol 6c (2.8 g, 7.3
mmol) in 73% yield as a gummy liquid, er 98:2 (column: OD-H;
mobile phase: 2% 2-propanol in hexane; flow rate: 1 mL/min). IR
(KBr): 3422, 2925, 2275, 1645, 1064 cm-1. H NMR (200 MHz,
1
FIGURE 5. Probable reaction pathway.
CDCl3): δ 7.7-7.6 (m, 4H), 7.5-7.3 (m, 6H), 4.6-4.4 (m, 1H),
3.8 (t, J ) 6.6 Hz, 2H), 3.6 (dd, J ) 11.1, 4.4 Hz, 1H), 3.5 (dd, J
) 11.1, 6.6 Hz, 1H), 2.5 (dt, J ) 1.5, 6.6 Hz, 2H), 2.1 (d, J ) 5.9
Hz, 1H, OH), 1.1 (s, 9H). 13C NMR (75 MHz, CDCl3): δ 135.5,
133.4, 129.7, 127.7, 84.5, 78.4, 62.6, 62.1, 49.2, 26.7, 22.8, 19.2.
[R]2D5 ) -6.0 (c 2.0, CHCl3). MS (ESI): 409 [M + Na]+. HRMS
(ESI): m/z calcd for C22H27O2NaSiCl 409.1366, found 409.1370.
Alcohol 6d. Similarly, ynone 4d (2.5 g, 10 mmol) was hydro-
genated over a period of 3 h to afford a crude compound which
was purified by column chromatography using 15% EtOAc/
petroleum ether (v/v) to afford the propargyl alcohol 6d (1.8 g, 7.0
mmol) in 70% yield as a gummy liquid, er 93:7 (column: Eurocel
01; mobile phase: 10% 2-propanol in hexane; flow rate: 1 mL/
pound.8 Bromo carbamate anti18 was debrominated and further
converted to an acetonide. The NOE studies on the acetonide
confirm the structure assigned to anti18.31 The structures were
assigned to products 14, 16, and 17 by analogy.
In conclusion, we have described a highly enantioselective
preparation of R-chloropropargylic alcohols (useful synthons)
by transfer hydrogenation using Noyori’s catalyst and the
preparation of γ,δ-cis- and trans-disubstituted ꢀ-hydroxysul-
filimines from a common precursor by a straightforward
sequence of reactions in few steps from readily available starting
materials. The sulfilimines have been shown to be excellent
intramolecular nucleophiles for the preparation of bromo
carbamates regio- and stereoselectively. The products possess
functional group handles for further manipulation and should
serve as key intermediates for natural product synthesis and other
bioactive molecules. In comparison to our earlier methodology
using N-Ts sulfilimine, the methodology described herein has
several advantages, in particular the stereoconvergent behavior
of the diastereomeric sulfilimines, better stereoselectivity of
bromo carbamate formation, and the nitrogen protecting group
that can be removed under mild conditions.
min). IR (KBr): 3416, 2926, 2360, 1650, 1560, 1394, 1067 cm-1
.
1H NMR (300 MHz, CDCl3): δ 7.2 (d, J ) 9.1 Hz, 2H), 6.8 (d, J
) 9.1 Hz, 2H), 4.6-4.5 (m, 1H), 4.5 (s, 2H), 4.1 (s, 2H), 3.8 (s,
3H), 3.7-3.6 (m, 2H). 13C NMR (75 MHz, CDCl3): δ 159.4, 129.8,
128.6, 113.8, 83.7, 82.4, 71.3, 62.5, 56.8, 55.2, 48.8. [R]2D5 ) -32.0
(c 2.0, CHCl3). MS (ESI): 277 [M + Na]+. HRMS (ESI): m/z calcd
for C13H15O3NaCl 277.0607, found 277.0614.
General Procedure for Preparation of Sulfilimines 10 and
11. To a stirred suspension of NaNCbzCl (5 equiv) in dry
acetonitrile (2 M) at rt was added a solution of the sulfide (1 equiv)
in dry acetonitrile (0.4 M) and the mixture stirred until TLC
examination revealed completion (2-3 h). The reaction mixture
was diluted with EtOAc, washed with water and brine, and dried
over Na2SO4, and the solvent was evaporated under reduced
pressure to afford the crude product, which was purified by column
chromatography to afford the sulfilimine as a 1:1 mixture of syn
and anti isomers. The anti isomer eluted first during column
chromatography.
Experimental Section
General Procedure for the Preparation of Propargyl Alcohol
6 by Transfer Hydrogenation. To a solution of the ynone 4 (1
equiv) in DCM (0.83 M) were added formic acid (8 equiv) and
triethylamine (3.2 equiv) followed by Ru catalyst 5 (2.5 mol %) at
once and the mixture stirred at rt until TLC examination revealed
completion (2-3.5 h). The reaction mixture was diluted with
EtOAc, washed successively with water and brine, and dried over
Na2SO4. The solvent was evaporated under reduced pressure to
afford the crude product, which was purified by column chroma-
tography to afford the propargyl alcohol 6.
Sulfilimine 10a. To a stirred suspension of NaNCbzCl (1 g, 5
mmol) in dry acetonitrile (3 mL) at rt was added a solution of sulfide
8a (270 mg, 1 mmol) in dry acetonitrile (2 mL). After 3 h, the
reaction mixture was diluted with EtOAc (25 mL), washed with
water (2 × 10 mL) and brine (10 mL), and dried over Na2SO4, and
the solvent was evaporated under reduced pressure to afford the
crude product, which was purified by column chromatography using
40% EtOAc/petroleum ether (v/v) to afford the sulfilimine 10a (352
mg, 0.84 mmol) as a 1:1 mixture of syn and anti isomers in a
combined yield of 84%. Data for anti10a. Gummy liquid. IR (KBr):
Alcohol 6a. Following the general procedure, ynone 4a (1.78 g,
10 mmol) afforded the crude product, which was purified by column
chromatography using 10% EtOAc/petroleum ether (v/v) to afford
the propargyl alcohol 6a (1.35 g, 7.5 mmol) in 75% yield as a
gummy liquid, er 94:6 (column: Eurocel 01; mobile phase: 10%
1
3351, 2927, 1719, 1611, 1334, 1051 cm-1. H NMR (300 MHz,
CDCl3): δ 7.6 (d, J ) 8.7 Hz, 2H), 7.5-7.1 (m, 12H), 6.5 (d, J )
11.7 Hz, 1H), 5.7 (dd, J ) 11.7, 8.9 Hz, 1H), 5.2-5.1 (br s, 1H-
OH), 5.1-5.0 (m, 3H), 3.2 (dd, J ) 13.0, 9.6 Hz, 1H), 3.0 (dd, J
) 13.0, 2.1 Hz, 1H), 2.4 (s, 3H). 13C NMR (75 MHz, CDCl3): δ
165.0, 143.0, 137.1, 135.6, 132.1, 130.5, 130.4, 129.9, 128.5, 128.3,
1
2-propanol in hexane; flow rate: 1 mL/min). H NMR (300 MHz,
CDCl3): δ 7.5-7.4 (m, 2H), 7.3-7.2 (m, 3H), 4.8 (q, J ) 6.0 Hz,
1H), 3.8 (dd, J ) 11.1, 4.3 Hz, 1H), 3.7 (dd, J ) 11.1, 6.2 Hz,
1H), 2.4 (d, J ) 6.0 Hz, 1H, OH). 13C NMR (75 MHz, CDCl3): δ
133.3, 131.8, 128.8, 128.3, 86.3, 85.9, 63.0, 49.0. [R]2D5 ) -7.5 (c
128.2, 127.9, 127.6, 127.4, 126.6, 67.8, 63.0, 57.0, 21.4. [R]D25
)
1.0, CHCl3). MS (FAB): 181 [M + H]+
-16.5 (c 0.75, CHCl3). MS (ESI): 420 [M + H]+. HRMS (ESI):
m/z calcd for C25H26NO3S 420.1633, found 420.1642. Data for
syn10a. Gummy liquid. IR (KBr): 3351, 2927, 1719, 1611, 1334,
.
Alcohol 6b. Similarly, ynone 4b (1.86 g, 10 mmol) was
hydrogenated over a period of 2.5 h to afford a crude product, which
was purified by column chromatography using 10% EtOAc/
1
1051 cm-1. H NMR (300 MHz, CDCl3): δ 7.6 (d, J ) 8.3 Hz,
J. Org. Chem. Vol. 74, No. 12, 2009 4503

Raghavan et al.
2H), 7.3-7.1 (m, 10H), 7.1-7.0 (m, 2H), 6.5 (d, J ) 11.5 Hz,
1H), 5.6 (dd, J ) 11.5, 8.7 Hz, 1H), 5.1 (dd, J ) 12.5 Hz, 1H), 4.9
(dd, J ) 12.5 Hz, 1H), 4.8 (dt, J ) 1.5, 8.7 Hz, 1H), 3.4 (dd, J )
CDCl3): δ 7.6 (d, J ) 8.3 Hz, 2H), 7.4-7.2 (m, 9H), 6.9 (d, J )
8.7 Hz, 2H), 5.7-5.6 (m, 2H), 5.1 (dd, J ) 12.5 Hz, 1H), 5.0 (dd,
J ) 12.5 Hz, 1H), 4.9-4.8 (m, 1H), 4.3 (ABq, J ) 11.3 Hz, 2H),
4.0-3.9 (m, 2H), 3.8 (s, 3H), 3.1 (dd, J ) 12.8, 9.8 Hz, 1H), 3.0
(dd, J ) 12.8, 2.3 Hz, 1H), 2.4 (s, 3H). 13C NMR (75 MHz, CDCl3):
δ 165.1, 159.2, 143.0, 137.1, 132.0, 130.5, 129.8, 129.4, 129.3,
128.4, 128.2, 127.9, 127.7, 126.7, 113.8, 72.2, 67.8, 65.6, 63.0,
58.3, 55.2, 21.4. [R]2D5 ) -12.0 (c 1.0, CHCl3). MS (ESI): 494 [M
+ H]+. HRMS (ESI): m/z calcd for C28H32NO5S 494.2001, found
494.1995. Data for syn10d. Gummy liquid. IR (KBr): 3446, 2928,
1636, 1258, 776 cm-1. 1H NMR (300 MHz, CDCl3): δ 7.6 (d, J )
7.6 Hz, 2H), 7.4-7.2 (m, 9H), 6.9 (d, J ) 8.3 Hz, 2H), 5.7-5.6
(m, 2H), 5.1 (dd, J ) 12.8 Hz, 1H), 5.0 (dd, J ) 12.8 Hz, 1H),
4.8-4.7 (m, 1H), 4.4 (s, 2H), 4.0 (t, J ) 4.5 Hz, 2H), 3.8 (s, 3H),
3.3 (dd, J ) 12.8, 9.1 Hz, 1H), 3.0 (dd, J ) 12.8, 2.3 Hz, 1H), 2.4
(s, 3H). 13C NMR (75 MHz, CDCl3): δ 164.5, 159.4, 143.3, 137.3,
132.8, 131.7, 130.7, 130.6, 129.5, 129.3, 128.3, 128.0, 127.7, 126.8,
113.9, 72.4, 67.7, 65.8, 64.6, 57.1, 55.3, 21.5; [R]2D5 ) +10.0 (c
1.0, CHCl3). MS (ESI): 494 [M + H]+. HRMS (ESI): m/z calcd
for C28H32NO5S 494.2001, found 494.1992.
13.0, 9.6 Hz, 1H), 3.0 (dd, J ) 13.0, 2.3 Hz, 1H), 2.4 (s, 3H). 13
C
NMR (75 MHz, CDCl3): δ 164.2, 143.6, 137.0, 135.6, 132.5, 131.0,
130.7, 130.5, 128.5, 128.2, 128.0, 127.7, 127.5, 127.0, 124.1, 67.8,
64.0, 56.9, 21.5. [R]2D5 ) +25.3 (c 0.75, CHCl3). MS (ESI): 420
[M + H]+. HRMS (ESI): m/z calcd for C25H26NO3S 420.1633,
found 420.1637.
Sulfilimine 10b. Similarly sulfide 8b (278 mg, 1 mmol) was reacted
with NaNCbzCl (1 g, 5 mmol) over 2.5 h period to afford the crude
product, which was purified by column chromatography using 35%
EtOAc/petroleum ether (v/v) to afford the sulfilimine 10b (363 mg,
0.85 mmol) as a 1:1 mixture of syn and anti isomers in a combined
yield of 85%. Data for anti10b. Gummy liquid. IR (KBr): 3424,
2924, 1638, 1520, 1335, 1060 cm-1. 1H NMR (300 MHz, CDCl3): δ
7.7 (d, J ) 7.5 Hz, 2H), 7.4-7.1 (m, 7H), 5.5-5.3 (m, 2H), 5.2 (dd,
J ) 12.1 Hz, 1H), 5.0 (dd, J ) 12.1 Hz, 1H), 4.8-4.7 (m, 1H), 4.7
(d, J ) 6.8 Hz, 1H, OH), 3.1 (dd, J ) 12.8, 10.6 Hz, 1H), 2.8 (dd, J
) 12.8, 2.3 Hz, 1H), 2.4 (s, 3H), 1.9-1.7 (m, 2H), 1.4-1.1 (m, 8H),
0.9 (t, J ) 6.8 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ 165.0, 142.0,
139.3, 133.5, 130.7, 130.1, 129.6, 128.5, 128.2, 128.1, 124.0, 66.9,
64.9, 62.9, 31.6, 29.7, 29.4, 28.9, 22.6, 21.4, 14.0. [R]2D5 ) -15.0
(c 0.5, CHCl3). MS (ESI): 428 [M + H]+. HRMS (ESI): m/z calcd
for C25H34NO3S 428.2259, found 428.2250. Data for syn10b.
Sulfilimine 11a. Similarly sulfide 9a (270 mg, 1 mmol) was
reacted with NaNCbzCl (1 g, 5 mmol) over a 2.5 h period to afford
the crude product, which was purified by column chromatography
using 40% EtOAc/petroleum ether (v/v) to furnish the sulfilimine
11a (356 mg, 0.85 mmol) as a 1:1 mixture of syn and anti isomers
in a combined yield of 85%. Data for anti11a. Gummy liquid. IR
Gummy liquid. IR (KBr): 3424, 2924, 1638, 1520, 1335, 1060 cm-1
.
1H NMR (300 MHz, CDCl3): δ 7.7 (d, J ) 8.3 Hz, 2H), 7.4-7.1 (m,
7H), 5.6-5.3 (m, 2H), 5.2 (dd, J ) 12.1 Hz, 1H), 5.0 (dd, J ) 12.1
Hz, 1H), 4.9-4.8 (m, 1H), 3.4 (dd, J ) 12.8, 9.8 Hz, 1H), 2.9 (dd, J
) 12.8, 2.3 Hz, 1H), 2.4 (s, 3H), 2.1-1.9 (m, 2H), 1.4-1.1 (m, 8H),
0.9 (t, J ) 6.8 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ 164.5, 143.3,
137.4, 134.4, 132.0, 130.6, 129.0, 128.2, 127.9, 127.6, 126.9, 67.7,
63.9, 57.7, 31.6, 29.3, 28.8, 27.8, 22.5, 21.4, 14.0. [R]2D5 ) +20.0 (c
0.5, CHCl3). MS (ESI): 428 [M + H]+. HRMS (ESI): m/z calcd for
C25H34NO3S 428.2259, found 428.2249.
(KBr): 3351, 2927, 1719, 1611, 1334, 1051 cm-1. H NMR (200
1
MHz, CDCl3): δ 7.7 (d, J ) 8.3 Hz, 2H), 7.4-7.2 (m, 12H), 6.7
(d, J ) 15.9 Hz, 1H), 6.1 (dd, J ) 15.9, 6.0 Hz, 1H), 5.1 (s, 2H),
4.8 (q, J ) 6.0 Hz), 3.2-3.1 (m, 2H), 2.4 (s, 3H). 13C NMR (75
MHz, CDCl3): δ 165.4, 143.3, 137.2, 136.1, 131.8, 131.4, 130.7,
128.6, 128.3, 128.1, 128.0, 127.7, 126.8, 126.6, 124.0, 68.0, 66.9,
58.9, 21.5. [R]2D5 ) -19.5 (c 1.0, CHCl3). MS (ESI): 420 [M +
H]+. HRMS (ESI): m/z calcd for C25H26NO3S 420.1633, found
420.1645; Data for syn11a. Gummy liquid. IR (KBr): 3351, 2927,
1719, 1611, 1334, 1051 cm-1. 1H NMR (300 MHz, CDCl3): δ 7.7
(d, J ) 7.6 Hz, 2H), 7.4-7.2 (m, 12H), 6.7 (d, J ) 15.9 Hz, 1H),
6.1 (dd, J ) 15.9, 6.0 Hz, 1H), 5.1 (s, 2H), 4.7-4.6 (m, 1H), 3.4
(dd, J ) 12.8, 9.0 Hz, 1H), 3.1 (dd, J ) 12.8, 3.0 Hz, 1H), 2.4 (s,
3H). 13C NMR (75 MHz, CDCl3): δ 164.5, 143.4, 137.1, 135.9,
131.9, 131.5, 130.6, 128.5, 128.3, 128.2, 128.0, 127.9, 127.6, 126.8,
126.6, 68.2, 67.7, 57.3, 21.4. [R]2D5 ) +64.0 (c 1.0, CHCl3). MS
(ESI): 420 [M + H]+. HRMS (ESI): m/z calcd for C25H26NO3S
420.1633, found 420.1643.
Sulfilimine 10c. Similarly sulfide 8c (476 mg, 1 mmol) was
reacted with NaNCbzCl (1 g, 5 mmol) over a 3 h period to afford
the crude product, which was purified by column chromatography
using 30% EtOAc/petroleum ether (v/v) to furnish the sulfilimine
10c (531 mg, 0.85 mmol) as a 1:1 mixture of syn and anti isomers
in a combined yield of 85%. Data for anti10c. Gummy liquid. IR
1
(KBr): 3276, 2924, 1566, 1504, 1346, 1113, 849 cm-1. H NMR
(300 MHz, CDCl3): δ 7.7-7.6 (m, 6H), 7.4-7.2 (m, 13H), 5.6-5.4
(m, 2H), 5.1 (s, 2H), 4.8-4.7 (m, 1H), 4.7 (d, J ) 7.0 Hz, 1H-
OH), 3.7-3.5 (m, 2H), 3.0 (dd, J ) 12.8, 9.8 Hz, 1H), 2.9 (dd, J
Sulfilimine 11b. Similarly, sulfide 9b (278 mg, 1 mmol) was
reacted with NaNCbzCl (1 g, 5 mmol) over a 2 h period to afford
the crude product, which was purified by column chromatography
using 35% EtOAc/petroleum ether (v/v) to furnish the sulfilimine
11b (350 mg, 0.82 mmol) as a 1:1 mixture of syn and anti isomers
in a combined yield of 82%; Data for anti11b. IR (KBr): 3424,
2924, 1638, 1520, 1335, 1060 cm-1. 1H NMR (300 MHz, CDCl3):
δ 7.7 (d, J ) 8.1 Hz, 2H), 7.5-7.1 (m, 7H), 5.8-5.6 (m, 1H), 5.4
(dd, J ) 15.4, 5.9 Hz,. 1H), 5.1 (s, 2H), 4.7 (d, J ) 5.9 Hz, 1H-
OH), 4.5-4.4 (q, J ) 6.6 Hz, 1H), 3.1-2.9 (m, 2H), 2.4 (s, 3H),
2.0 (q, J ) 6.6 Hz, 2H), 1.4-1.1 (m, 8H), 0.9 (t, J ) 6.6 Hz, 3H).
13C NMR (75 MHz, CDCl3): δ 164.6, 143.2, 134.2, 130.6, 128.7,
128.5, 128.4, 128.3, 128.0, 127.7, 126.8, 68.0, 66.8, 59.1, 32.1,
31.6, 28.8, 28.7, 22.5, 21.4, 14.0. [R]2D5 ) -35.0 (c 0.6, CHCl3).
MS (ESI): 428 [M + H]+. HRMS (ESI): m/z calcd for C25H34NO3S
428.2259, found 428.2252. Data for syn11b. Gummy liquid. IR
) 12.8, 2.5 Hz, 1H), 2.4 (s, 3H), 2.3-2.1 (m, 2H), 1.0 (s, 9H). 13
C
NMR (75 MHz, CDCl3): δ 165.4, 143.1, 137.4, 135.7, 133.7, 130.7,
130.4, 130.2, 129.8, 128.7, 128.4, 128.2, 127.8, 126.8, 124.2, 68.0,
67.1, 63.1, 58.4, 31.2, 27.0, 21.5, 19.3. [R]2D5 ) -8.0 (c 1.0, CHCl3).
MS (ESI): 626 [M + H]+. HRMS (ESI): m/z calcd for
C37H44NO4SiS 626.2760, found 626.2750. Data for syn10c. Gummy
liquid. IR (KBr): 3276, 2924, 1566, 1504, 1346, 1113, 849 cm-1
.
1H NMR (300 MHz, CDCl3): δ 7.7-7.6 (m, 6H), 7.5-7.2 (m, 13H),
5.7-5.4 (m, 2H), 5.1 (dd, J ) 12.5 Hz, 1H), 5.0 (dd, J ) 12.5 Hz,
1H), 4.7-4.6 (m, 1H), 3.6 (t, J ) 6.6 Hz, 2H), 3.4 (dd, J ) 12.5,
9.6 Hz, 1H), 2.9 (dd, J ) 12.5, 2.9 Hz, 1H), 2.4 (s, 3H), 2.3 (q, J
) 5.1 Hz, 2H), 1.0 (s, 9H). 13C NMR (75 MHz, CDCl3): δ 164.4,
143.3, 137.2, 135.5, 133.3, 131.7, 131.0, 130.5, 130.0, 129.7, 128.2,
127.9, 127.7, 127.6, 126.9, 67.6, 63.8, 62.9, 57.0, 31.0, 27.1, 21.4,
19.1. [R]2D5 ) +44.5 (c 1.0, CHCl3). MS (ESI): 626 [M + H]+.
HRMS (ESI): m/z calcd for C37H44NO4SiS 626.2760, found
626.2748.
1
(KBr): 3424, 2924, 1638, 1520, 1335, 1060 cm-1. H NMR (300
MHz, CDCl3): δ 7.6 (d, J ) 8.3 Hz, 2H), 7.3-7.1 (m, 7H), 5.7-5.6
(m, 1H), 5.3 (dd, J ) 15.1, 6.0 Hz, 1H), 5.1 (dd, J ) 12.1 Hz,
1H), 5.0 (dd, J ) 12.1 Hz, 1H), 4.4-4.3 (m, 1H), 3.3 (dd, J )
12.8, 9.1 Hz, 1H), 2.9 (dd, J ) 12.8, 3.0 Hz, 1H), 2.4 (s, 3H), 1.9
Sulfilimine 10d. Similarly sulfide 8d (344 mg, 1 mmol) was
reacted with NaNCbzCl (1 g, 5 mmol) over a 3 h period to afford
the crude product, which was purified by column chromatography
using 40% EtOAc/petroleum ether (v/v) to furnish the sulfilimine
10d (404 mg, 0.82 mmol) as a 1:1 mixture of syn and anti isomers
in a combined yield of 82%. Data for anti10d. Gummy liquid. IR
(q, J ) 6.8 Hz, 2H), 1.4-1.1 (m, 8H), 0.9 (t, J ) 6.8 Hz, 3H). 13
C
NMR (75 MHz, CDCl3): δ 164.1, 143.4, 134.5, 130.7, 129.0, 128.6,
128.5, 128.3, 128.0, 127.7, 127.0, 68.5, 67.8, 57.3, 32.1, 31.6, 29.7,
28.8, 22.6, 21.5, 14.1. [R]2D5 ) +85.0 (c 1.2, CHCl3). MS (ESI):
1
(KBr): 3446, 2928, 1636, 1258, 776 cm-1. H NMR (300 MHz,
4504 J. Org. Chem. Vol. 74, No. 12, 2009

Route to (E)- and (Z)-2-Hydroxy-3,4-unsaturated Disubstituted Sulfilimines
428 [M + H]+. HRMS (ESI): m/z calcd for C25H34NO3S 428.2259,
found 428.2255.
(KBr): 3453, 2925, 1742, 1539, 1239, 950 cm-1. H NMR (300
MHz, CDCl3): δ 7.5 (d, J ) 8.1 Hz, 2H), 7.4-7.2 (m, 12H), 5.8
(s, 1H), 5.4 (d, J ) 10.0 Hz, 1H), 5.1 (dd, J ) 12.1 Hz, 1H), 5.0
(dd, J ) 12.1 Hz, 1H), 4.7-4.6 (br s, 1H-OH), 4.4 (m, 1H), 3.8
(dt, J ) 10.2, 2.1 Hz, 1H), 3.0-2.9 (m, 2H), 2.4 (s, 3H). 13C NMR
(75 MHz, CDCl3): δ 156.1, 142.3, 138.6, 136.0, 130.2, 128.9, 128.8,
128.5, 128.3, 128.1, 127.9, 124.0, 70.7, 67.1, 60.1, 58.8, 55.3, 21.5.
[R]2D5 ) +50.0 (c 0.8, CHCl3). MS (ESI): 538 [M + Na]+. HRMS
(ESI): m/z calcd for C25H26NO4NaSBr 538.0663, found 538.0651.
Bromo Carbamate anti12. Similarly, sulfilimine syn10a (257
mg, 0.5 mmol) was reacted with NBS (106 mg, 0.6 mmol) to afford
the crude product, which was purified by column chromatography
using 40% EtOAc/petroleum ether (v/v) to furnish bromo carbamate
anti12 (200 mg, 0.39 mmol) in 78% yield as a white solid. Mp:
1
Sulfilimine 11c. Similarly, sulfide 9c (476 mg, 1 mmol) was
reacted with NaNCbzCl (1 g, 5 mmol) over a 3 h period to afford
the crude product, which was purified by column chromatography
using 30% EtOAc/petroleum ether (v/v) to furnish the sulfilimine
11c (512 mg, 0.82 mmol) as a 1:1 mixture of syn and anti isomers
in a combined yield of 82%. Data for anti11c. Gummy liquid. IR
1
(KBr): 3276, 2924, 1566, 1504, 1346, 1113, 849 cm-1. H NMR
(300 MHz, CDCl3): δ 7.7-7.6 (m, 6H), 7.5-7.2 (m, 13H), 5.8-5.6
(m, 1H), 5.4 (dd, J ) 15.6, 6.3 Hz, 1H), 5.1 (s, 2H), 4.7 (d, J )
7.0 Hz, 1H-OH), 4.5 (q, J ) 6.3 Hz, 1H), 3.7 (t, J ) 6.3 Hz, 2H),
3.0 (d, J ) 6.3 Hz, 2H), 2.4 (s, 3H), 2.3 (q, J ) 7.0 Hz, 2H). 1.0
(s, 9H). 13C NMR (75 MHz, CDCl3): δ 164.9, 142.9, 137.0, 135.3,
133.6, 130.7, 130.4, 129.9, 129.4, 128.5, 128.3, 128.1, 127.8, 127.5,
126.6, 67.7, 66.4, 63.0, 58.8, 35.3, 26.7, 21.2, 19.0. [R]2D5 ) -9.5
(c 1.0, CHCl3). MS (ESI): 626 [M + H]+. HRMS (ESI): m/z calcd
for C37H44NO4SiS 626.2760, found 626.2755. Data for syn11c.
Gummy liquid. IR (KBr): 3276, 2924, 1566, 1504, 1346, 1113,
174-176 °C. IR (KBr): 3453, 2925, 1742, 1539, 1239, 950 cm-1
.
1H NMR (300 MHz, CDCl3): δ 7.5-7.2 (m, 14H), 5.7 (s, 1H), 5.1
(d, J ) 10.4 Hz, 1H), 5.1 (dd, J ) 12.1 Hz, 1H), 5.0 (dd, J ) 12.1
Hz, 1H), 4.8 (d, J ) 3.2 Hz, OH), 4.2 (t, J ) 9.6 Hz, 1H), 3.9 (dt,
J ) 2.5, 10.2 Hz, 1H), 3.2 (dd, J ) 14.0, 9.4 Hz, 1H), 2.7 (dd, J
) 14.0, 1.1 Hz, 1H), 2.4 (s, 3H). 13C NMR (75 MHz, DMSO-d6):
δ 156.1, 141.9, 140.5, 139.4, 137.1, 129.8, 128.3, 128.2, 127.9,
127.5, 127.1, 123.6, 65.5, 65.1, 61.9, 60.8, 56.4, 20.8. [R]2D5 ) -10.0
(c 0.4, CHCl3). MS (ESI): 538 [M + Na]+. HRMS (ESI): m/z calcd
for C25H26NO4NaSBr 538.0663, found 538.0655.
849 cm-1 1H NMR (300 MHz, CDCl3): δ 7.8-7.6 (m, 6H),
.
7.5-7.2 (m, 13H), 5.8-5.7 (m, 1H), 5.5 (dd, J ) 15.1, 6.0 Hz,
1H), 5.1 (dd, J ) 12.8, 1H), 5.0 (dd, J ) 12.8, 1H), 4.5-4.4 (m,
1H), 3.7 (t, J ) 6.0 Hz, 2H), 3.3 (dd, J ) 12.8, 9.8 Hz, 1H), 3.0
(dd, J ) 12.8, 1.5 Hz, 1H), 2.4 (s, 3H), 2.3 (q, J ) 6.0 Hz, 2H),
1.0 (s, 9H). 13C NMR (75 MHz, CDCl3): δ 164.4, 143.5, 137.2,
135.5, 133.8, 131.6, 131.1, 130.6, 129.6, 128.5, 128.3, 128.0, 127.6,
126.9, 68.4, 67.8, 63.1, 57.2, 35.5, 26.8, 21.5, 19.2. [R]2D5 ) +38.0
(c 1.5, CHCl3). MS (ESI): 626 [M + H]+. HRMS (ESI): m/z calcd
for C37H44NO4SiS 626.2760, found 626.2753.
Bromo Carbamate syn13. Similarly sulfilimine anti11a (210
mg, 0.5 mmol) was reacted with NBS (106 mg, 0.6 mmol) to afford
the crude product, which was purified by column chromatography
using 40% EtOAc/petroleum ether (v/v) to furnish to afford bromo
carbamate syn13 (200 mg, 0.39 mmol) in 78% yield as a white
solid. Mp: 80-82 °C. IR (KBr): 3453, 2925, 1742, 1539, 1239,
Sulfilimine 11d. Silmilarly, sulfide 9d (344 mg, 1 mmol) was
reacted with NaNCbzCl (1 g, 5 mmol) over a 2.5 h period to afford
the crude product, which was purified by column chromatography
using 40% EtOAc/petroleum ether (v/v) to furnish the sulfilimine
11d (394 mg, 0.8 mmol) as a 1:1 mixture of syn and anti isomers
in a combined yield of 80%. Data for anti11d. Gummy liquid. IR
950 cm-1. H NMR (300 MHz, CDCl3): δ 7.5-7.2 (m, 14H), 6.3
1
(d, J ) 8.9 Hz, 1H), 5.2 (m, 3H), 4.5 (d, J ) 3.4 Hz, OH), 4.4-4.2
(m, 2H), 3.1 (dd, J ) 13.2, 3.0 Hz, 1H), 2.8 (dd, J ) 13.2, 4.9 Hz,
1H), 2.4 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 156.4, 142.2, 139.3,
135.5, 130.2, 129.0, 128.5, 128.3, 128.1, 127.0, 124.0, 67.3, 65.8,
61.4, 60.3, 59.5, 21.6. [R]2D5 ) +25.0 (c 0.4, CHCl3). MS (ESI):
538 [M + Na]+. HRMS (ESI): m/z calcd for C25H26NO4NaSBr
538.0663, found 538.0652.
1
(KBr): 3446, 2928, 1636, 1258, 776 cm-1. H NMR (300 MHz,
CDCl3): δ 7.7 (d, J ) 8.3 Hz, 2H), 7.5-7.2 (m, 9H), 6.8 (d, J )
9.1 Hz, 2H), 5.9 (td, J ) 5.3, 15.1 Hz, 1H), 5.7 (dd, J ) 15.1, 5.3
Hz, 1H), 5.1 (s, 2H), 4.6 (q, J ) 6.0 Hz, 1H), 4.4 (s, 2H), 3.9 (d,
J ) 5.3 Hz, 2H), 3.8 (s, 3H), 3.1-3.0 (m, 2H), 2.4 (s, 3H). 13C
NMR (75 MHz, CDCl3): δ 161.8, 160.2, 137.1, 136.0, 132.2, 130.8,
130.7, 129.3, 128.6, 128.3, 128.1, 127.7, 126.7, 113.8, 72.1, 69.3,
68.0, 66.3, 58.6, 55.3, 21.5. [R]2D5 ) -10.0 (c 0.5, CHCl3). MS
(ESI): 494 [M + H]+. HRMS (ESI): m/z calcd for C28H32NO5S
494.2001, found 494.1987. Data for syn11d. Gummy liquid. IR
Bromo Carbamate anti13. Similarly, sulfilimine syn11a (210
mg, 0.5 mmol) was reacted with NBS (106 mg, 0.6 mmol) to afford
the crude product, which was purified by column chromatography
using 40% EtOAc/petroleum ether (v/v) to furnish bromo carbamate
anti13 (206 mg, 0.4 mmol) in 80% yield as a white solid. Mp:
74-76 °C. IR (KBr): 3453, 2925, 1742, 1539, 1239, 950 cm-1. 1H
NMR (300 MHz, CDCl3): δ 7.5-7.2 (m, 14H), 5.9 (d, J ) 8.8 Hz,
1H), 5.4 (t, J ) 9.1 Hz, 1H), 5.1 (dd, J ) 12.1 Hz, 1H), 5.0 (dd,
J ) 12.1 Hz, 1H), 4.6 (t, J ) 7.2 Hz, 1H), 4.1 (dd, J ) 9.1, 7.2
Hz, 1H), 3.2-3.0 (m, 2H), 2.4 (s, 3H). 13C NMR (75 MHz, CDCl3):
δ 155.3, 142.0, 138.4, 137.2, 136.1, 130.1, 128.5, 128.2, 128.1,
127.9, 124.1, 68.1, 67.1, 61.3, 58.8, 55.3, 21.4. [R]2D5 ) -6.0 (c
0.5, CHCl3). MS (ESI): 538 [M + Na]+. HRMS (ESI): m/z calcd
for C25H26NO4NaSBr 538.0663, found 538.0658.
1
(KBr): 3446, 2928, 1636, 1258, 776 cm-1. H NMR (300 MHz,
CDCl3): δ 7.7 (d, J ) 8.3 Hz, 2H), 7.4-7.1 (m, 9H), 6.8 (d, J )
8.3 Hz, 2H), 5.9 (td, J ) 5.3, 15.1 Hz, 1H), 5.7 (dd, J ) 15.1, 5.3
Hz, 1H), 5.1 (dd, J ) 12.8 Hz, 1H), 5.0 (dd, J ) 12.8 Hz, 1H),
4.5-4.4 (m, 1H), 4.4 (s, 2H), 3.9 (d, J ) 4.5 Hz, 2H), 3.8 (s, 3H),
3.3 (dd, J ) 12.8, 9.1 Hz, 1H), 3.0 (dd, J ) 12.8, 3.0 Hz, 1H), 2.4
(s, 3H). 13C NMR (75 MHz, CDCl3): δ 164.5, 160.3, 143.5, 139.8,
137.2, 131.3, 130.7, 130.1, 129.6, 129.4, 128.3, 128.0, 127.7, 126.8,
113.8, 72.2, 69.3, 67.9, 67.8, 60.0, 55.3, 21.5; [R]2D5 ) +13.0 (c
0.5, CHCl3). MS (ESI): 494 [M + H]+. HRMS (ESI): m/z calcd
for C28H32NO5S 494.2001, found 494.1990.
General Procedure for the Preparation of Bromo Carbam-
ates. To a solution of sulfilimine (1 equiv) in toluene (0.25 M) was
added water (1.5 equiv) followed by freshly recrystallized NBS (1.2
equiv) and the mixture stirred at rt for 30 min. The reaction mixture
was then diluted with EtOAc, washed with saturated aq NaHCO3,
water, and brine, and dried over Na2SO4. The solvent was evaporated
under reduced pressure to afford the crude product, which was purified
by column chromatography to afford bromo carbamate.
Bromo Carbamate syn14. Similarly sulfilimine anti10b (214
mg, 0.5 mmol) was reacted with NBS (106 mg, 0.6 mmol) to afford
the crude product, which was purified by column chromatography
using 35% EtOAc/petroleum ether (v/v) to furnish bromo carbamate
syn14 (199 mg, 0.38 mmol) in 76% yield as a white solid. Mp:
122-124 °C. IR (KBr): 3383, 2960, 1678, 1518, 1284 cm-1. H
1
NMR (300 MHz, CDCl3): δ 7.4 (d, J ) 7.6 Hz, 2H), 7.4-7.2 (m,
7H), 5.2-5.0 (m, 3H), 4.7 (t, J ) 7.6 Hz, 1H), 4.5-4.4 (br s, OH),
4.4-4.3 (m, 1H), 3.6 (t, J ) 9.8 Hz, 1H), 3.0-2.8 (m, 2H), 2.4 (s,
3H), 1.9-1.6 (m, 3H), 1.6-1.1 (m, 7H), 0.9 (t, J ) 6.8 Hz, 3H).
13C NMR (75 MHz, CDCl3): δ 156.4, 142.1, 140.4, 136.1, 130.2,
128.5, 128.3, 128.0, 124.0, 70.6, 67.2, 58.9, 58.2, 57.7, 36.3, 31.5,
29.6, 28.5, 22.4, 21.4, 13.9. [R]2D5 ) +35 (c 0.6, CHCl3). MS (ESI):
546 [M + Na]+. HRMS (ESI): m/z calcd for C25H34NO4NaSBr
546.1289, found 546.1281.
Bromo Carbamate syn12. Following the general procedure,
sulfilimine anti10a (257 mg, 0.5 mmol) afforded the crude product,
which was purified by column chromatography using 40% EtOAc/
petroleum ether (v/v) to afford bromo carbamate syn12 (195 mg,
0.38 mmol) in 76% yield as a white solid. Mp:130-132 °C. IR
Bromo Carbamate anti14. Similarly, sulfilimine syn10b (214
mg, 0.5 mmol) was reacted with NBS (106 mg, 0.6 mmol) to afford
J. Org. Chem. Vol. 74, No. 12, 2009 4505

Raghavan et al.
the crude product, which was purified by column chromatography
using 35% EtOAc/petroleum ether (v/v) to furnish bromo carbamate
anti14 (209 mg, 0.4 mmol) in 80% yield as a white solid. Mp:
3H), 3.2 (dd, J ) 14.0, 9.6 Hz, 1H), 2.6 (d, J ) 14.0 Hz, 1H), 2.5 (s,
3H), 2.1-1.9 (m, 2H), 1.0 (s, 9H). 13C NMR (75 MHz, CDCl3): δ
156.4, 141.8, 139.0, 136.1, 135.7, 133.5, 130.3, 129.8, 128.7, 128.5,
128.2, 127.8, 124.1, 68.4, 67.3, 61.1, 58.9, 58.3, 54.7, 39.1, 26.9, 21.6,
19.3. [R]2D5 ) -11.0 (c 0.5, CHCl3). MS (ESI): 722 [M + H]+. HRMS
(ESI): m/z calcd for C37H44NO5NaSiSBr 744.1790, found 744.1787.
Bromo Carbamate syn17. Similarly, sulfilimine anti11c (313
mg, 0.5 mmol) was reacted with NBS (106 mg, 0.6 mmol) to afford
the crude product, which was purified by column chromatography
using 30% EtOAc/petroleum ether (v/v) to furnish bromo carbamate
syn17 (306 mg, 0.43 mmol) in 85% yield as a gummy liquid. IR
1
158-160 °C. IR (KBr) 3383, 2960, 1678, 1518, 1284 cm-1. H
NMR (300 MHz, CDCl3): δ 7.4 (d, J ) 8.3 Hz, 2H), 7.4-7.2 (m,
7H), 5.1 (dd, J ) 12.1 Hz, 1H), 5.0 (dd, J ) 12.1 Hz, 1H), 4.8 (d,
J ) 9.8 Hz, 1H), 4.7-4.6 (m, 2H, H + OH), 4.0 (t, J ) 9.8 Hz,
1H), 3.7 (t, J ) 9.8 Hz, 1H), 3.1 (dd, J ) 13.6, 9.1 Hz, 1H), 2.7
(d, J ) 13.6 Hz, 1H), 2.4 (s, 3H), 1.9-1.7 (m, 2H), 1.6-1.1 (m,
8H), 0.9 (t, J ) 6.8 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ 156.4,
141.7, 138.8, 136.1, 130.1, 128.5, 128.3, 128.0, 124.0, 68.7, 67.2,
58.0, 57.97, 57.7, 36.3, 31.5, 29.6, 28.5, 27.5, 22.5, 21.4, 13.9. [R]2D5
) -12.0 (c 0.3, CHCl3). MS (ESI): 546 [M + Na]+. HRMS (ESI):
m/z calcd for C25H34NO4NaSBr 546.1289, found 546.1282.
Bromo Carbamate syn15. Similarly, sulfilimine anti11b (214
mg, 0.5 mmol) was reacted with NBS (106 mg, 0.6 mmol) to afford
the crude product, which was purified by column chromatography
using 35% EtOAc/petroleum ether (v/v) to furnish bromo carbamate
syn15 (214 mg, 0.41 mmol) in 82% yield as a white solid. Mp:
1
(KBr): 3429, 2925, 2859, 1741, 1606, 1108 cm-1. H NMR (300
MHz, CDCl3): δ 7.7-7.6 (m, 6H), 7.5-7.2 (m, 13H), 5.3 (d, J )
10.1 Hz, 1H), 5.0 (m, 3H), 4.5-4.3 (m, H + OH), 3.9-3.7 (m,
3H), 2.9 (dd, J ) 13.2, 9.8 Hz, 1H), 2.7 (dd, J ) 13.2, 2.4 Hz,
1H), 2.4 (s, 3H), 1.9-1.7 (m, 2H), 1.0 (s, 9H). 13C NMR (75 MHz,
CDCl3): δ 156.4, 142.7, 142.2, 140.4, 135.7, 135.6, 133.6, 130.4,
129.8, 128.7, 128.3, 127.8, 124.0, 68.4, 67.3, 67.1, 61.5, 60.2, 51.7,
37.4, 27.0, 21.6, 19.3. [R]2D5 ) +45 (c 1.0, CHCl3). MS (ESI): 722
[M + H]+. HRMS (ESI): m/z calcd for C37H44NO5NaSiSBr
744.1790, found 744.1785.
Bromo Carbamate anti17. Similarly, sulfilimine syn11c (313 mg,
0.5 mmol) was reacted with NBS (106 mg, 0.6 mmol) to afford the
crude product, which was purified by column chromatography using
30% EtOAc/petroleum ether (v/v) to furnish bromo carbamate anti17
(296 mg, 0.41 mmol) as a 6:1 mixture of inseparable isomers in a
combined yield of 82% yield as a gummy liquid. 1H NMR of major
isomer (300 MHz, CDCl3): δ 7.6-7.5 (m, 6H), 7.5-7.2 (m, 13H),
5.4 (d, J ) 9.8 Hz, 1H), 5.2-5.0 (m, 2H), 5.0-4.9 (br s, OH), 4.7 (d,
J ) 9.1 Hz, 1H), 4.3 (t, J ) 9.1 Hz, 1H), 3.9-3.7 (m, 2H), 3.6 (t, J
) 9.1 Hz, 1H), 3.2-3.0 (m, 1H), 2.5 (d, J ) 12.8 Hz, 1H), 2.4 (s,
3H), 2.3-2.1 (m, 1H), 1.9-1.7 (m, 1H), 1.0 (s, 9H).
13C NMR (75 MHz, CDCl3): δ 156.3, 141.9, 138.4, 135.6, 135.5,
133.4, 130.2, 129.6, 128.5, 128.2, 127.9, 127.6, 124.1, 67.2, 65.9, 61.4,
59.7, 58.3, 52.0, 37.4, 26.8, 21.4, 19.2. 1H NMR of minor isomer (300
MHz, CDCl3): δ 7.6-7.5 (m, 6H), 7.5-7.2 (m, 13H), 5.5 (d, J )
11.3 Hz, 1H), 5.2-5.0 (m, 2H), 4.6 (d, J ) 9.1 Hz, 1H), 4.5-4.4 (m,
1H), 4.2-4.0 (m, 1H), 3.9-3.7 (m, 2H), 3.2-3.0 (m, 2H), 2.7 (dd, J
) 13.6, 2.3 Hz, 1H), 2.4 (s, 6H), 2.3-2.1 (m, 1H), 1.9-1.7 (m, 1H),
1.0 (s, 9H). MS (ESI): 722 [M + H]+.
1
145-147 °C. IR (KBr): 3383, 2960, 1678, 1518, 1284 cm-1. H
NMR (300 MHz, CDCl3): δ 7.5 (d, J ) 8.1 Hz, 2H), 7.4-7.2 (m,
7H), 5.4 (d, J ) 10.0 Hz, 1H), 5.1 (m, 3H), 4.4-4.3 (br s, OH),
4.1 (dt, J ) 2.3, 9.4 Hz, 1H), 3.9 (t, J ) 10.0 Hz, 1H), 2.9 (dd, J
) 13.2, 9.8 Hz, 1H), 2.8 (dd, J ) 13.2, 1.5 Hz, 1H), 2.4 (s, 3H),
2.0-1.5 (m, 3H), 1.5-1.1 (m, 7H), 0.9 (t, J ) 6.8 Hz, 3H). 13C
NMR (75 MHz, CDCl3): δ 156.2, 142.2, 139.9, 130.2, 128.5, 128.1,
127.8, 124.0, 123.8, 68.2, 67.0, 60.1, 59.7, 55.5, 34.4, 31.6, 28.6,
27.3, 22.5, 21.4, 14.0. [R]2D5 ) +40 (c 0.75, CHCl3). MS (ESI):
546 [M + Na]+. HRMS (ESI): m/z calcd for C25H34NO4NaSBr
546.1289, found 546.1277.
Bromo Carbamate anti15. Similarly, sulfilimine syn11b (214
mg, 0.5 mmol) was reacted with NBS (106 mg, 0.6 mmol) to afford
the crude product, which was purified by column chromatography
using 35% EtOAc/petroleum ether (v/v) to furnish bromo carbamate
anti15 (209 mg, 0.4 mmol) as a 3:1 mixture of inseparable isomers
in a combined yield of 80% yield. White solid. 1H NMR of major
isomer (300 MHz, CDCl3): δ 7.5 (d, J ) 8.1 Hz, 2H), 7.4-7.2 (m,
7H), 5.4 (d, J ) 10.2 Hz, 1H), 5.2-4.8 (m, 4H), 4.0 (dt, J ) 3.0,
9.4 Hz, 1H), 3.6 (t, J ) 9.6 Hz, 1H), 3.2-3.1 (m, 1H), 2.6 (dd, J
) 13.6, 1.5 Hz, 1H), 2.4 (s, 3H), 1.9-1.5 (m, 3H), 1.5-1.1 (m,
7H), 0.9 (t, J ) 7.0 Hz, 3H). 1H NMR of minor isomer (300 MHz,
CDCl3): δ 7.4 (d, J ) 8.1 Hz, 2H), 7.4-7.2 (m, 7H), 5.2-4.8 (m,
4H), 4.4-4.1 (m, 3H), 3.2-3.1 (m, 1H), 2.8 (dd, J ) 0.9, 13.2 Hz,
1H) 2.4 (s, 3H), 1.9-1.5 (m, 3H), 1.5-1.1 (m, 7H), 0.9 (t, J ) 7.0
Hz, 3H). MS (ESI): 546 [M + Na]+.
Bromo Carbamate syn18. Similarly, sulfilimine anti10d (247
mg, 0.5 mmol) was reacted with NBS (106 mg, 0.6 mmol) to afford
the crude product, which was purified by column chromatography
using 40% EtOAc/petroleum ether (v/v) to furnish bromo carbamate
syn18 (218 mg, 0.37 mmol) in 74% yield as a white solid. Mp:
1
Bromo Carbamate syn16. Similarly, sulfilimine anti10c (313
mg, 0.5 mmol) was reacted with NBS (106 mg, 0.6 mmol) to afford
the crude product, which was purified by column chromatography
using 30% EtOAc/petroleum ether (v/v) to furnish bromo carbamate
syn16 (274 mg, 0.38 mmol) in 76% yield as a gummy liquid. IR
142-144 °C. IR (neat): 3416, 2924, 2854, 1705, 1404 cm-1. H
NMR (300 MHz, CDCl3): δ 7.5 (d, J ) 8.1 Hz, 2H), 7.4-7.1 (m,
9H), 6.9 (d, J ) 8.5 Hz, 2H), 5.2-5.0 (m, 3H), 4.8 (t, J ) 6.4 Hz,
1H), 4.5 (br s, 1H), 4.4-4.3 (m, 3H), 4.0 (t, J ) 9.6 Hz, 1H), 3.8
(s, 3H), 3.7-3.5 (m, 2H), 3.0-2.9 (m, 2H), 2.4 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ 159.1, 156.0, 142.2, 133.1, 132.3, 130.1,
129.5, 129.3, 128.5, 128.2, 128.0, 123.9, 113.7, 72.8, 70.6, 70.2,
67.3, 58.8, 55.2, 54.8, 52.3, 21.5. [R]2D5 ) +22.0 (c 0.4, CHCl3).
MS (ESI): 612 [M + Na]+. HRMS (ESI): m/z calcd for
C28H32NO6NaSBr 612.1031, found 612.1032.
1
(KBr): 3429, 2925, 2859, 1741, 1606, 1108 cm-1. H NMR (300
MHz, CDCl3): δ 7.7-7.6 (m, 6H), 7.5-7.2 (m, 13H), 5.1-5.0 (m,
3H), 4.5 (t, J ) 6.8 Hz, 1H), 4.4-4.3 (m, 1H), 3.8 (t, J ) 5.3 Hz,
2H), 3.6 (t, J ) 9.8 Hz, 1H), 2.9 (d, J ) 5.3 Hz, 2H), 2.4 (s, 3H),
2.1-1.9 (m, 2H), 1.0 (s, 9H). 13C NMR (75 MHz, CDCl3): δ 156.2,
142.4, 140.4, 135.73, 135.66, 133.8, 130.4, 129.8, 128.7, 128.5,
128.2, 127.8, 124.1, 70.7, 67.4, 67.1, 61.1, 58.9, 54.2, 39.1, 26.9,
21.6, 19.3. [R]2D5 ) +24.0 (c 0.5, CHCl3). MS (ESI): 722 [M +
H]+. HRMS (ESI): m/z calcd for C37H44NO5NaSiSBr 744.1790,
found 744.1781.
Bromo Carbamate anti18. Similarly, sulfilimine syn10d (247
mg, 0.5 mmol) was reacted with NBS (106 mg, 0.6 mmol) to afford
the crude product, which was purified by column chromatography
using 40% EtOAc/petroleum ether (v/v) to furnish bromo carbamate
anti18 (236 mg, 0.4 mmol) in 80% yield as a white solid. Mp:
1
Bromo Carbamate anti16. Similarly sulfilimine syn10c (313 mg,
0.5 mmol) was reacted with NBS (106 mg, 0.6 mmol) to afford the
crude product, which was purified by column chromatography using
30% EtOAc/petroleum ether (v/v) to furnish bromo carbamate anti16
(270 mg, 0.38 mmol) in 75% yield as a white solid. Mp: 108-110
181-183 °C. IR (neat): 3416, 2924, 2854, 1705, 1404 cm-1. H
NMR (300 MHz, CDCl3): δ 7.4 (d, J ) 8.1 Hz, 2H), 7.4-7.2 (m,
9H), 6.9 (d, J ) 8.7 Hz, 2H), 5.1 (dd, J ) 12.1 Hz, 1H), 5.0 (dd,
J ) 12.1 Hz, 1H), 4.9 (d, J ) 8.9 Hz, 1H), 4.8 (t, J ) 7.0 Hz, 1H),
4.4 (s, 2H), 4.2-4.0 (m, 2H), 3.8 (s, 3H), 3.7-3.5 (m, 2H), 3.1
(dd, J ) 13.8, 8.7 Hz, 1H), 2.7 (dd, J ) 13.8, 1.5 Hz, 1H), 2.4 (s,
3H). 13C NMR (75 MHz, CDCl3): δ 159.1, 156.0, 141.6, 138.8,
136.1, 130.1, 129.6, 129.4, 128.0, 128.4, 127.9, 124.0, 113.7, 72.8,
70.8, 67.0, 60.5, 60.4, 55.2, 54.6, 53.3, 21.4. [R]2D5 ) -8.0 (c 0.4,
1
°C. IR (KBr): 3429, 2925, 2859, 1741, 1606, 1108 cm-1. H NMR
(200 MHz, CDCl3): δ 7.7-7.6 (m, 6H), 7.5-7.2 (m, 13H), 5.1 (dd, J
) 12.1 Hz, 1H), 5.0 (dd, J ) 12.1 Hz, 1H), 4.7 (d, J ) 10.3 Hz, 1H),
4.4-4.3 (m, 2H, 1H + OH), 4.0 (t, J ) 9.6 Hz, 1H), 3.9-3.6 (m,
4506 J. Org. Chem. Vol. 74, No. 12, 2009

Route to (E)- and (Z)-2-Hydroxy-3,4-unsaturated Disubstituted Sulfilimines
CHCl3). MS (ESI): 612 [M + Na]+. HRMS (ESI): m/z calcd for
Supporting Information Available: Experimental details for
the preparation of ynones 4, sulfide 7, cis-alkenes 8, trans-
alkenes 9, debromination products from anti13, syn15, and
sulfones from bromo carbamates including data and X-ray
structure of anti13. This material is available free of charge
via the Internet at http://pubs.acs.org.
C28H32NO6NaSBr 612.1031, found 612.1035.
Acknowledgment. S.R. is thankful to Dr. J. M. Rao, Head,
Org. Div. I, and Dr. J. S. Yadav, Director, IICT, for constant
support and encouragement. S.M. is thankful to CSIR, New
Delhi, for a fellowship. Financial assistance from DST (New
Delhi) is gratefully acknowledged.
JO900569Z
J. Org. Chem. Vol. 74, No. 12, 2009 4507