Deprotection of homoallyl (hAllyl) derivatives of phenols, alcohols, acids, and amines

Full text of DOI:10.1021/jo900012z

carboxylic acid following treatment with Et3N (eq 1).6 More
recently, a single example from the Cossy group described a
ruthenium-catalyzed isomerization of a homoallyl ether to an
enol ether, which was subsequently hydrolyzed under aqueous
acidic conditions to the free alcohol in modest overall yield (eq
2).7
Deprotection of Homoallyl (hAllyl) Derivatives of
Phenols, Alcohols, Acids, and Amines
Bruce H. Lipshutz,* Subir Ghorai, and
Wendy Wen Yi Leong
Department of Chemistry and Biochemistry, UniVersity of
California, Santa Barbara, California 93106
lipshutz@chem.ucsb.edu
ReceiVed January 7, 2009
In a recent report, we described the use of a one-pot tandem
metathesis/elimination sequence for preparing polyenic arrays
(eq 3).8 In this report, a related strategy has been utilized, where
the focus is on deprotection of the homoallyl moiety that can
be used for a variety of functional group maskings: phenols,
alcohols, amine derivatives, and acids (Scheme 1; EWG )
electron-withdrawing group).
h
The homoallyl moiety, Allyl, is presented as a general
protecting group for several functionalities. It can be
chemoselectively removed via a sequential, one-pot cross-
metathesis/elimination sequence.
SCHEME 1. Deprotection of Homoallyl Derivatives
Chemoselective deprotection is among the most desirable
features associated with a protecting group.1 The extent of
inertness and the conditions under which unmasking of a
protecting group take place are of prime consideration. Avail-
ability and economics can also play important, albeit oftentimes
secondary, roles. Surprisingly, the readily available hydrocarbon-
based homoallyl residue is rarely seen in synthesis. Indeed, in
the latest edition of Greene’s ProtectiVe Groups in Organic
Synthesis (2007),2 the homoallyl moiety is not even listed among
the myriad of hydroxyl protecting groups. The potential for this
relatively unreactive 4-carbon unit to serve as a protecting group
for alcohols,3 amines,4 and acids5 has been recognized for
decades, but existing conditions for removal may be responsible
for its lack of utility to date. Thus, Barrett reported on the
ozonolysis of homoallylic esters as a means of revealing a
Conditions were developed using phenols derivatized as their
homoallyl (hAllyl) ethers.9a The coupling partner, methyl vinyl
ketone (MVK), was selected given its availability, attractive
economics, and loss on workup. Moreover, γ-proton abstraction
en route to elimination was found to be far more facile from an
intermediate enone 1 than is removal in the corresponding enoate
2 (Figure 1). Commercially available Grubbs-Hoveyda-2
catalyst10 (GH-2; 2 mol %) in refluxing CH2Cl2 overnight led,
(1) Jarowicki, K.; Kocienski, P. J. Chem. Soc., Perkin Trans. 1 1999, 1589-
1615; J. Chem. Soc., Perkin Trans. 1 2000, 2495-2527.
(6) Barrett, A. G. M.; Lebold, S. A.; Zhang, X. Tetrahedron Lett. 1989, 30,
7317–7320.
(7) Cadot, C.; Dalko, P. I.; Cossy, J. Tetrahedron Lett. 2002, 43, 1839–
1841.
(2) Wuts, P. G. M.; Green, T. W. Greene’s ProtectiVe Groups in Organic
Synthesis, 4th ed.; Wiley: Hoboken, NJ, 2007.
(3) (a) Kaleta, Z.; Makowski, B. T.; Soo´s, T.; Dembinski, R. Org. Lett. 2006,
8, 1625–1628. (b) Youn, S. W.; Pastine, S. J.; Sames, D. Org. Lett. 2004, 6,
581–584. (c) Zhu, X.-Z.; Chen, C.-F. J. Am. Chem. Soc. 2005, 127, 13158–
13159. (d) Nicolaou, K. C.; Cho, S. Y.; Hughes, R.; Winssinger, N.; Smethurst,
C.; Labischinski, H.; Endermann, R. Chem.sEur. J. 2001, 7, 3798–3823.
(4) (a) Zhang, M.; Vedantham, P.; Flynn, D. L.; Hanson, P. R. J. Org. Chem.
2004, 69, 8340–8344. (b) Wipf, P.; Aslan, D. C. J. Org. Chem. 2001, 66, 337–
343. (c) Kiyooka, S.-I.; Wada, Y.; Ueno, M.; Yokoyama, T.; Yokoyama, R.
Tetrahedron 2007, 63, 12695–12701. (d) Corey, E. J.; Guzman-Perez, A.; Noe,
M. C. Tetrahedron Lett. 1995, 36, 3481–3484.
(5) (a) Grote, R. E.; Jarvo, E. R. Org. Lett. 2009, 11, 485–488. (b) Veenstra,
S. J.; Schmid, P. Tetrahedron Lett. 1997, 38, 997–1000. (c) Vallee, E.; Loemba,
F.; Etheve-Quelquejeu, M.; Vale´ry, J.-M. Tetrahedron Lett. 2006, 47, 2191–
2195. (d) Yamamoto, Y.; Asao, N. Chem. ReV. 1993, 93, 2207–2293.
(8) (a) Lipshutz, B. H.; Ghorai, S.; Bosˇkovic´, Z. V. Tetrahedron 2008, 64,
6949–6954. For related tandem reactions, see the following recent examples: (b)
Bourcet, E.; Virolleaud, M.-A.; Fache, F.; Piva, O. Tetrahedron Lett. 2008, 49,
6816–6818. (c) Niethe, A.; Fischer, D.; Blechert, S. J. Org. Chem. 2008, 73,
3088–3093. (d) Hiebel, M.-A.; Pelotier, B.; Goekjian, P.; Piva, O. Eur. J. Org.
Chem. 2008, 713–720. (e) Jin, T.; Yamamoto, Y. Org. Lett. 2008, 10, 3137–
3139. (f) Chen, J.-R.; Li, C.-F.; An, X.-L.; Zhang, J.-J.; Zhu, X.-Y.; Xiao, W.-J.
Angew. Chem., Int. Ed. 2008, 47, 2489–2492. (g) Murelli, R. P.; Catala´n, S.;
Gannon, M. P.; Snapper, M. L. Tetrahedron Lett. 2008, 49, 5714–5717.
(9) (a) Homoallylic ethers (3) and amine derivatives (5) were prepared by
O- or N-alkylation of the corresponding phenols or amines; see Experimental
Section. (b) Homoallylic alcohol esters 6 were obtained using a Mitsunobu
dehydration, as described in the Experimental Section.
2854 J. Org. Chem. 2009, 74, 2854–2857
10.1021/jo900012z CCC: $40.75 2009 American Chemical Society
Published on Web 03/11/2009

TABLE 2. Bases Screened for Elimination of Alkanols
entry
base
solvent
yield (%)a
1
2
3
4
5
6
7
8
9
DBU
CH2CI2
DMF
CH2Cl2
toluene
THF
DMF
DMF
CH2Cl2
DMF
NR
NR
57
60
82
92
90
62
94
NaOAc
KOtBu
KOtBu
KOtBu
KOtBu
NaOMe
NaOMe
NaH
FIGURE 1. Grubbs-Hoveyda-2 (GH-2) catalyst; enone versus enoate
intermediates.
TABLE 1. Deprotection of Homoallyl Ethers of Phenols
a Isolated yield of chromatographically pure materials.
entry
3
R
yield (%)a
SCHEME 2. Comparison with the Existing Literature
Approach
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
H
98
92
91
92
98
93
90
86
4-OMe
4-NO2
4-I
2-OMe, 4-Me
3-OMe
4-Bz
4-CHO
4-Ph
9
97
90
10
11
12
13
14
15
16
4-tBu
4-CN
4-OTBS
4-OAc
4-OBn
d
82b, 40c
92
TABLE 3. Deprotection of Activated Amines
85
94
93
88
e
a Isolated yield of chromatographically pure materials. b Based on
recovered starting materials. c Isolated. d 2-Naphthyl homoallyl ether was
used as educt. e Estrone homoallyl ether was the educt used.
entry
5
R,R′
yield (%)a
1
2
5a
5b
R ) Bn, R′ ) Ts
96
95
b
in general, to high levels of conversion to R,ꢀ-unsaturated
ketones. After cooling to room temperature, addition of DBU
quickly led to the free phenol upon acidic work up (Table 1).
High levels of efficiency and functional group tolerance were
observed. Thus, substituted aromatics, including nitro (entry 3),
ester (entry 13), aldehyde (entry 8), and ketone (entries 7 and
16), all afforded high isolated yields of the desired phenols.
Only the benzonitrile derivative 3k was sluggish (entry 11), as
expected from metathesis reactions involving this functionality.11
Other common phenolic protecting groups such as methyl
(entries 2, 5, and 6), TBS (entry 12), acetate (entry 13), and
benzyl (entry 14) were found to be orthogonal to the relatively
inert homoallylic residue and characteristically withstood these
mild metathesis/elimination conditions.
a Isolated yield of chromatographically pure materials. b The hAllyl
derivative of phthalimide is the substrate.
TABLE 4. Deprotection of Homoallyl Esters
entry
6
R
yield (%)a
1
2
3
4
5
6
6a
6b
6c
6d
6e
6f
Ph
95
94
91
92
90
90
4-MeC6H4
PhCH2CH2
n-C11H23
1-naphthyl
(Z-NH)CH(Bn)
h
Nonphenolic Allyl-protected alcohols required a stronger
base than DBU to effect elimination. Several bases were
screened, as shown in Table 2. Of those identified as successful
(KOtBu, NaOMe, or NaH in DMF), the final set of conditions
was selected for enone 4. Use of this procedure for deprotection
of hAllyl benzyl alcohol compares very favorably with this single
known literature example (Scheme 2).7
a Isolated yield of chromatographically pure materials.
This combination of NaH in DMF was also found to be the
most effective for the two cases of protected amines 5,9a which
were smoothly deprotected following metathesis with MVK
(Table 3). Neither DBU nor NaH in CH2Cl2 afforded any
elimination at room temperature.
(10) Garber, S. B.; Kingsbury, J. S.; Grey, B. L.; Hoveyda, A. H. J. Am.
Chem. Soc. 2000, 122, 8168–8179.
(11) (a) Lipshutz, B. H.; Aguinaldo, G. T.; Ghorai, S.; Voigtritter, K. Org.
Lett. 2008, 10, 1325–1328. (b) Ettari, R.; Micale, N. J. Organomet. Chem. 2007,
692, 3574–3576. (c) Rivard, M.; Blechert, S. Eur. J. Org. Chem. 2003, 2225–
2228. (d) Michrowska, A.; Bujok, R.; Harutyunyan, S.; Sashuk, V.; Dolgonos,
G.; Grela, K. J. Am. Chem. Soc. 2004, 126, 9318–9325. (e) Love, J. A.; Morgan,
J. P.; Trnka, T. M.; Grubbs, R. H. Angew. Chem., Int. Ed. 2002, 41, 4035–4037.
Several homoallyl alcohol-derived esters 69b were deprotected
in a one-pot fashion using the standard conditions of MVK, cat
GH-2/DBU (Table 4). In the case of Z-protected (S)-phenyla-
lanine derivative 6f, epimerization during the elimination step
J. Org. Chem. Vol. 74, No. 7, 2009 2855

SCHEME 3. Selective Unmasking of Homoallylic Ethers
dried over anhydrous Na2SO4, and then concentrated in vacuo. The
resulting residue was purified by flash column chromatography on
silica gel (eluting with 6% EtOAc/hexane) to provide the 1-bromo-
4-((but-3-enyloxy)methyl)benzene (precursor to compound 4; 0.35 g,
87%) as a colorless liquid: IR (neat) 3078, 2979, 2858, 1641, 1594,
1488, 1431, 1393, 1358, 1096, 1070, 1011, 996, 914, 803, 734
1
cm-1; H NMR (400 MHz, CDCl3) δ 7.48 (d, J ) 8.4 Hz, 2H),
7.22 (d, J ) 8.4 Hz, 2H), 5.85 (ddt, J ) 17.2, 10.4, 6.8 Hz, 1H),
5.12 (dq, J ) 17.2, 1.2 Hz, 1H), 5.07 (dq, J ) 10.2, 1.2 Hz, 1H),
4.48 (s, 2H), 3.53 (t, J ) 6.8 Hz, 2H), 2.39 (qt, J ) 6.8, 1.2 Hz,
2H); 13C NMR (100 MHz, CDCl3) δ 137.7, 135.3, 131.6, 129.4,
121.6, 116.7, 72.3, 69.9, 34.4; MS (EI) m/z (%) 242 (M + 2, 2),
240 (M, 2), 171 (97), 169 (100), 161 (29), 90 (25), 89 (16);
HREIMS calcd for C11H12BrO [M - H]+ ) 239.0072, found
h
SCHEME 4. Deprotection of Compound 10
239.0066. To a solution of this Allyl ether (0.22 g, 0.91 mmol)
and methyl vinyl ketone (0.22 mL, 2.74 mmol) in CH2Cl2 (4.5 mL)
was added GH-2 catalyst (11.5 mg, 0.018 mmol, 2.0 mol %), and
the mixture was refluxed for 15 h. It was then reduced in volume
under vacuum to 0.5 mL and purified directly on a silica gel flash
column chromatography (eluting with 11% EtOAc/hexane) to
provide the title compound 4 (0.25 g, 98%) as a colorless oil: IR
(neat) 3032, 2862, 1697, 1673, 1628, 1592, 1488, 1424, 1395, 1360,
1254, 1202, 1176, 1096, 1070, 1011, 978, 804 cm-1; 1H NMR (400
MHz, CDCl3) δ 7.46 (d, J ) 8.4 Hz, 2H), 7.19 (d, J ) 8.4 Hz,
2H), 6.80 (dt, J ) 16.0, 6.8 Hz, 1H), 6.13 (dt, J ) 16.0, 1.2 Hz,
1H), 4.46 (s, 2H), 3.58 (t, J ) 6.8 Hz, 2H), 2.52 (qd, J ) 6.8, 1.2
Hz, 2H), 2.24 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 198.3, 144.5,
137.3, 132.9, 131.7, 129.4, 121.7, 72.4, 68.6, 32.9, 27.0; MS (ESI)
m/z 305 (M + Na); HRESIMS calcd for C13H15BrO2Na [M + Na]+
) 305.0153, found 305.0158.
General Procedure for Homoallylation of Carboxylic
Acids. A solution of DCAD12 (2.75 mmol) in CH2Cl2 (10 mL)
was slowly added at 22 °C via cannula to a solution of PPh3 (2.75
mmol), but-3-ene-1-ol (2.75 mmol), and carboxylic acid (2.50
mmol) in CH2Cl2 (10 mL). The resulting cloudy mixture was stirred
at this temperature for 12 h. Filtration gave reduced DCAD as a
white powder. The filtrate was removed in vacuo to afford the crude
product, which was subsequently purified by silica gel flash
chromatography to provide the title compounds. See the Supporting
Information for spectral details on compounds 6a-f.
General Procedure for Deprotection of Homoallyl
Derivatives. To a solution of a homoallyl derivative (0.50 mmol)
and methyl vinyl ketone (122 µL, 1.50 mmol) in CH2Cl2 (2.5 mL)
was added GH-2 catalyst (6.3 mg, 0.01 mmol, 2.0 mol %), and the
mixture refluxed for 15 h. It was then cooled to 22 °C and DBU
(149 µL, 1.00 mmol) was added dropwise and the mixture stirred
for another 1 h at the same temperature. Then, 1.0 M HCl (3 mL)
was added, and the mixture was extracted with CH2Cl2 (2 × 10
mL). The combined extracts were washed with water (2 × 10 mL),
dried over anhydrous Na2SO4, and concentrated in vacuo. The
resulting residue was purified by silica gel flash chromatography
to provide the deprotected compounds.
1-(But-3-enyloxy)-4-((but-3-enyloxy)methyl)benzene (7). But-
3-ene-1-ol (0.05 mL, 0.58 mmol) was added dropwise to a stirred
suspension of NaH (0.018 g, 0.76 mmol) in THF (1.0 mL) at 0 °C.
After the addition, the mixture was stirred at 22 °C for 15 min. A
solution of 1-(bromomethyl)-4-(but-3-enyloxy)benzene (see Sup-
porting Information for procedure) (0.17 g, 0.69 mmol) in THF
(1.0 mL) was added dropwise to the mixture at 0 °C, and stirring
continued for 30 min. The mixture was then heated under reflux
for 6 h after which it was cooled to 0 °C and a few drops of water
were added to quench excess NaH. After concentration of the
mixture under vacuum, the residue was extracted with CH2Cl2 (2
× 10 mL). The combined organic extracts were washed with water
(2 × 10 mL), dried over anhydrous Na2SO4, and concentrated in
vacuo. The resulting residue was purified by flash chromatography
is not an issue, as DBU is known to have no effect on such
educts.6 High overall yields were obtained in all cases.
Selective unmasking of a phenolic homoallyl ether over a
protected aliphatic derivative is readily accomplished. Thus, in
the case of diether 7 (Scheme 3), metathesis at each olefinic
site leads to an initial bisenone, which in the presence of DBU
affords exclusively phenol 8. Subsequent treatment with excess
NaH in DMF ultimately affords diol 9. The prognosis for use
in more complex educts is apparent based on the case of
homoallylic ether 10 (Scheme 4).
In summary, a simple, single vessel protocol has been
developed for unmasking several functional groups protected
as homoallylic derivatives. An initial olefin metathesis using
methyl vinyl ketone is performed, after which the addition of
base effects elimination to return the desired functionality in
high overall yields.
Experimental Section
General Procedure for Homoallylation of Phenols and
Amines. To a solution of aromatic alcohol or amine (2.00 mmol)
and K2CO3 (5.00 mmol) in CH3CN (8 mL) was added 4-bromobut-
1-ene (0.40 mL, 4.00 mmol), and the mixture was refluxed for 12 h.
The reaction mixture was then cooled to 22 °C, and the solvent
was removed in vacuo. The residue was partitioned between CH2Cl2
and water, and the aqueous layer was extracted with CH2Cl2 (2 ×
10 mL). The combined organic extracts were washed with water
(2 × 10 mL), dried over anhydrous Na2SO4, and removed in vacuo.
The resulting residue was purified by silica gel flash chromatog-
raphy to provide the title compounds. See Supporting Information
for details on compounds 3a-p and 5a,b.
(E)-6-(4-Bromobenzyloxy)hex-3-en-2-one (4). But-3-ene-1-ol
(0.15 mL, 1.67 mmol) was added dropwise to a stirred suspension
of NaH (0.06 g, 2.50 mmol) in THF (7 mL) at 0 °C. After the
addition, the mixture was stirred at 22 °C for 15 min. A solution
of 4-bromobenzylbromide (0.62 g, 2.50 mmol) in THF (3 mL) was
added dropwise to the mixture at 0 °C, and stirring continued for
30 min. The mixture was then heated under reflux for 6 h after
which it was cooled to 0 °C and a few drops of water were added
to quench excess NaH. After concentration of the mixture under
vacuum, the residue was extracted with CH2Cl2 (2 × 20 mL). The
combined organic extracts were washed with water (2 × 20 mL),
(12) Lipshutz, B. H.; Chung, D. W.; Rich, B.; Corral, R. Org. Lett. 2006, 8,
5069–5072.
2856 J. Org. Chem. Vol. 74, No. 7, 2009

on silica gel (eluting with 2% EtOAc/hexane) to provide the title
compound 7 (0.13 g, 96%) as a colorless oil: IR (neat) 3077, 3002,
2979, 2928, 2858, 1642, 1613, 1585, 1512, 1472, 1431, 1387, 1361,
1301, 1245, 1173, 1097, 1038, 994, 916, 823 cm-1; 1H NMR (400
MHz, CDCl3) δ 7.27 (d, J ) 8.4 Hz, 2H), 6.90 (d, J ) 8.4 Hz,
2H), 5.98-5.80 (m, 2H), 5.21-5.05 (m, 4H), 4.47 (s, 2H), 4.03 (t,
J ) 6.8 Hz, 2H), 3.51 (t, J ) 6.8 Hz, 2H), 2.56 (q, J ) 6.8 Hz,
2H), 2.38 (q, J ) 6.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
158.6, 135.5, 134.6, 130.7, 129.4, 117.2, 116.5, 114.6, 72.7, 69.4,
67.4, 34.4, 33.8; MS (EI) m/z (%) 232 (M, 18), 161 (65), 107 (100),
55 (89); HREIMS calcd for C15H20O2 [M]+ ) 232.1463, found
232.1472.
(E)-6-(4-Hydroxybenzyloxy)-hex-3-en-2-one (8). To a solution
of 7 (0.10 g, 0.43 mmol) and methyl vinyl ketone (0.21 mL, 2.59
mmol) in CH2Cl2 (2.2 mL) was added GH-2 catalyst (0.011 g, 0.017
mmol, 4.0 mol %), and the mixture was refluxed for 15 h. It was
then cooled to 22 °C, and DBU (128 µL, 0.86 mmol) was added
dropwise and stirring continued for another 1 h at the same
temperature. Then, 1.0 M HCl (2 mL) was added, and the mixture
was extracted with CH2Cl2 (2 × 10 mL). The combined organic
extracts were washed with water (2 × 10 mL), dried over anhydrous
Na2SO4, and concentrated in vacuo. The resulting residue was
purified by flash chromatography on silica gel (eluting with 40%
EtOAc/hexane) to provide the title compound 8 (0.086 g, 91%) as
a colorless oil: IR (neat) 3374, 3024, 2862, 1668, 1614, 1597, 1517,
1445, 1361, 1266, 1170, 1092, 978, 912, 851, 830, 731 cm -1; 1H
NMR (400 MHz, CDCl3) δ 7.17 (d, J ) 8.4 Hz, 2H), 6.84 (dt, J
) 16.0, 6.8 Hz, 1H), 6.83 (s, 1H), 6.79 (d, J ) 8.4 Hz, 2H), 6.14
(dt, J ) 8.0, 1.6 Hz, 1H), 4.44 (s, 2H), 3.58 (t, J ) 6.4 Hz, 2H),
2.52 (qd, J ) 6.4, 1.6 Hz, 2H), 2.25 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 199.9, 156.1, 146.0, 132.7, 129.8, 129.5, 115.5, 73.0,
67.9, 33.0, 26.9; MS (ESI) m/z 243 (M + Na); HRESIMS calcd
for C13H16O3Na [M + Na]+ ) 243.0997, found 243.0987.
4-(Hydroxymethyl)phenol (9). A solution of 8 (0.05 g, 0.227
mmol) in DMF (0.6 mL) was added dropwise to a stirred suspension
of NaH (0.017 g, 0.68 mmol) in DMF (0.6 mL) at 0 °C. After the
addition, the mixture was stirred at 22 °C for 1 h. Then, 1.0 M
HCl (1 mL) was added, and the mixture was extracted with EtOAc
(3 × 10 mL). The combined organic extracts were washed with
brine (2 × 10 mL), dried over anhydrous Na2SO4, and concentrated
in vacuo. The resulting residue was purified by flash chromatog-
raphy on silica gel (eluting with EtOAc) to provide the title
compound 9 (0.024 g, 87%) as a white solid. The 1H NMR obtained
was in accord to the data previously reported for this compound.13
3-(4-(But-3-enyloxy)-2-methoxyphenyl)-N-methoxy-N-methyl-
2-(2-(trimethylsilyl)ethylsulfonamido)propanamide (10). To a
solution of 11 (0.05 g, 0.12 mmol) and K2CO3 (0.04 g, 0.30 mmol)
in CH3CN (0.8 mL) was added 4-bromobut-1-ene (0.024 mL, 0.24
mmol), and the mixture was refluxed for 12 h. The reaction mixture
was then cooled to 22 °C, and the solvent was removed in vacuo.
The residue was partitioned between EtOAc and water, and the
aqueous layer was extracted with EtOAc (2 × 5 mL). The combined
organic extracts were washed with water (2 × 5 mL), dried over
anhydrous Na2SO4, and removed in vacuo. The resulting residue
was purified by flash chromatography on silica gel (eluting with
25% EtOAc/hexane) to provide the title compound 10 (0.055 g,
93%) as a colorless liquid: IR (neat) 3256, 3078, 2951, 1659, 1614,
1587, 1508, 1466, 1417, 1386, 1323, 1288, 1263, 1251, 1200, 1165,
1
1142, 1082, 1038, 990, 860, 839, 736, 699 cm-1; H NMR (400
MHz, CDCl3) δ 7.02 (d, J ) 8.4 Hz, 1H), 6.44 (d, J ) 2.4 Hz,
1H), 6.41 (dd, J ) 8.4, 2.4 Hz, 1H), 5.90 (ddt, J ) 17.2, 10.4, 6.8
Hz, 1H), 5.20-5.10 (m, 3H), 4.70 (td, J ) 9.6, 4.4 Hz, 1H), 3.97
(t, J ) 6.8 Hz, 2H), 3.81 (s, 3H), 3.76 (s, 3H), 3.21 (s, 3H), 2.97
(dd, J ) 13.2, 4.4 Hz, 1H), 2.75 (dd, J ) 13.2, 9.6 Hz, 1H),
2.58-2.40 (m, 4H), 0.82-0.73 (m, 2H), -0.06 (s, 9H); 13C NMR
(100 MHz, CDCl3) δ 172.8, 159.7, 158.8, 134.6, 132.2, 117.3,
104.7, 99.2, 67.3, 61.8, 55.6, 53.7, 49.9, 33.8, 32.4, 10.1, -2.0;
MS (ESI) m/z 495 (M
+ Na); HRESIMS calcd for
C21H36N2O6SSiNa [M + Na]+ ) 495.1961, found 495.1955.
Acknowledgment. Financial support provided by Zymes,
LLC is warmly acknowledged with thanks, as is the generous
supply of phenol 11 by the Pettus group.
Supporting Information Available: Experimental proce-
dures and spectral data for 3a-p, 5a,b, and 6a-f, including
copies of 1H and 13C NMR spectra of all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
JO900012Z
(13) Zhou, Y.; Gao, G.; Li, H.; Qu, J. Tetrahedron Lett. 2008, 49, 3260–
3263.
J. Org. Chem. Vol. 74, No. 7, 2009 2857