Communications
sequence that involved alkaline ester hydrolysis and coupling
rial. The stereochemistry of 23 was assigned by analogy to
similar examples[8] and confirmed by its eventual conversion
into (ꢀ)-1. Cleavage of the auxiliary group with MeLi
(91%)[8] gave the required methyl ketone 24 with greater
than 98% ee by HPLC,[11] reflecting the diastereomeric purity
of recrystallized 23. Ketone 24 was converted into its enol
triflate using Cominsꢀ reagent (85%), and the allylsilane
moiety was introduced by Kumada coupling to furnish
compound 26 in 90% yield. The phenol group was then
released in 26 through alkaline cleavage of the TBS group to
afford the phenolic allylsilane 5 (quant.) as the substrate for
the crucial dearomatization step.
The key cyclodearomatization reaction of 5 was then
investigated using iodine(III) reagents.[12] A survey of the
literature revealed fewexamples of the use of non-aromatic
carbon-centered nucleophiles in oxidative dearomatiza-
tions[13,14] and an allylsilane has only been employed in a
single system, in which allyltrimethylsilane was reacted in an
intermolecular setting with a naphthol system.[15] Despite the
lack of precedent for the involvement of allylsilane nucleo-
philes in such dearomatizing cyclizations, exposure of 5 to
either PhI(OAc)2 or PhI(O2CCF3)2 in a variety of solvents
afforded the desired spirocyclic dienone 27 in various yields.
The most efficient conditions identified to date involved the
use of PhI(OAc)2 in trifluoroethanol at ꢀ108C and gave
dienone 27 in 68% yield. The enantiomeric excess of 27 was
determined at this stage by HPLC (98% ee; Table 1)[16] to
ensure that no racemization had occurred during the preced-
ing sequence. Finally, removal of the ethylene acetal group
under acidic conditions led to the enantiomerically enriched
aldehyde 3 in 90% yield ([a]3D2 = ꢀ68.0, c = 0.60, CHCl3). This
key intermediate was then converted into (ꢀ)-1 by using the
previously described route.[2] The spectroscopic properties of
synthetic (ꢀ)-1 (1H and 13C NMR, IR, MS) were identical to
those reported previously[1b,2] and the optical rotation ([a]D32 =
with 2-mercaptopyridine N-oxide 12. Photolysis (visible light)
of a solution of 13 and nBu3SnH in benzene led to the
unexpected decarboxylation product 16 (50% overall yield
from 10), in which the olefin had migrated into the ring at the
position indicated in Scheme 2. This product presumably
arises through a 1,3 hydrogen atom shift from the initially
generated vinylic radical 14 to form the allylic radical 15.
Hydrogen atom capture from the tin hydride reagent then
occurs at the less hindered primary end of the allylic system,
giving the product 16. Removal of the acetal group (90%)
gave the aldehyde 17, which was then subjected to the same
cyclization conditions as used in our previous study,[2] leading
to the desired secondary alcohol 18 in moderate yield (39%)
as a single diastereoisomer. The excellent stereoselectivity of
this reaction contrasts with that observed from the cyclization
of the exo methylene substrate 3[2] and reflects the subtle
effects governing such processes. Gratifyingly, the endocyclic
olefin 18 was found to undergo a smooth cyclization reaction
to give the previously prepared intermediate 2,[2] in enan-
tioenriched form ([a]D = ꢀ22.3, c = 0.52, CHCl3) in 87%
yield.
Alongside the enantioselective catalysis approach, we also
investigated an auxiliary-based asymmetric synthesis of 3 by
the oxidative cyclodearomatization of a phenol bearing a
pendant allylsilane group. The required chiral substrate was
prepared in enantioenriched form by using Myersꢀ asymmet-
ric alkylation method.[8] Thus, acylation of (S,S)-pseudoephe-
drine (20) with carboxylic acid 19[9] via the corresponding
mixed anhydride (quant., Scheme 3) gave amide 21. Alkyl-
ation of the dianion formed from 21 with the known benzylic
bromide 22[10] gave product 23 in high yield (87%) and
stereoselectivity (ca. 85% de as indicated by 1H NMR
spectroscopy (500 MHz)). A single recrystallization of 23
from hexane gave essentially diastereomerically pure mate-
Table 1: Selected physical properties for compounds 5, 10, 17, and 27.
5: Rf =0.40 (silica gel, EtOAc/hexane 30:70); [a]3D2 =ꢀ11.3 (c=0.63,
17: Rf =0.42 (silica gel, EtOAc/hexane 60:40); [a]3D5 =+57.9 (c=1.26,
CHCl3); IR (film): n˜max =3385br w, 2952w, 2886w, 1630w, 1614w, 1514s, CHCl3); IR (film): n˜max =2920w, 1721m, 1661s, 1618w, 1403w, 1033w,
1443w, 1359w, 1247s, 1137 m, 1025w, 851s cmꢀ1; 1H NMR (500 MHz,
860m; 1H NMR (500 MHz, CHCl3): d=9.85 (t, J=1.4 Hz, 1H), 6.78 (dd,
CHCl3): d=7.03–7.00 (m, 2H), 6.72–6.69 (m, 2H), 5.11 (s, 1H), 4.86 (dd, J=9.9, 2.9 Hz, 1H), 6.72 (dd, J=9.8, 2.9 Hz, 1H), 6.21 (dd, J=9.9,
J=6.6, 3.8 Hz, 1H), 4.67 (s, 2H), 3.96–3.88 (m, 2H), 3.85–3.76 (m, 2H), 1.9 Hz, 1H), 6.18 (dd, J=9.8, 1.9 Hz, 1H), 4.93 (s, 1H), 3.36–3.30 (m,
2.74 (dd, J=13.7, 6.0 Hz, 1H), 2.56 (dd, J=13.7, 8.1 Hz, 1H), 2.42–2.36 1H), 2.86 (ddd, J=17.4, 4.6, 1.2 Hz, 1H), 2.47 (ddd, J=17.4, 9.1, 1.6 Hz,
(m, 1H), 1.78 (ddd, J=14.0, 8.8, 3.8 Hz, 1H), 1.67 (ddd, J=13.9, 6.5,
5.5 Hz, 1H), 1.55 (d, J=13.7 Hz, 1H), 1.48 (d, J=13.7 Hz, 1H),
1H), 2.42 (dd, J=13.6, 7.9 Hz, 1H), 1.77 (a, 3H), 1.76 ppm (dd, J=13.4,
7.7 Hz, 1H); 13C NMR (125 MHz, CDCl3): d=200.7, 185.6, 154.2, 152.8,
0.37 ppm (s, 3H); 13C NMR (125 MHz, CDCl3): d=153.8, 149.3, 132.4, 146.5, 128.0, 127.2, 126.6, 53.2, 48.2, 42.2, 41.9, 15.0; HRMS (ESI TOF):
130.4, 114.9, 108.1. 103.4, 64.6, 44.5, 40.1, 36.9, 25.8, ꢀ1.1 ppm; HRMS m/z calcd for C13H15O2 [M+H]+: 203.1067; found 203.1060
(ESI TOF): m/z calcd for C18H29O3Si [M+H]+: 321.1880; found 321.1885
10: Rf =0.23 (silica gel, EtOAc/hexane 60:40); [a]2D0 =ꢀ51.6 (c=0.45,
CHCl3); IR (film): n˜max =2951w, 1713s, 1661s, 1623m, 1435w, 1408w,
1348w, 1259w 1210m, 1158w, 1131w, 1029w, 860m cmꢀ1; 1H NMR
27: Rf =0.42 (silica gel, EtOAc/hexane 60:40); [a]3D3 =ꢀ57.9 (c=0.44,
CHCl3); IR (film): n˜max =2950w, 2883w, 1659s, 1623m, 1430w, 1407m,
1259m, 1135m, 1091m, 1021m, 916m, 858s, 730m, 705m; 1H NMR
(500 MHz, CHCl3): d=9.82 (s, 1H), 6.91 (dd, J=10.2, 3.0 Hz, 1H), 6.79 (500 MHz, CHCl3): d=6.97 (dd, J=10.1, 3.0 Hz, 1H), 6.80 (dd, J=9.9,
(dd, J=10.0, 3.0 Hz, 1H), 6.30 (dd, J=10.0, 1.9 Hz, 1H), 6.24 (dd, 3.0 Hz, 1H), 6.25 (dd, J=9.9, 1.9 Hz, 1H), 6.22 (dd, J=10.1, 1.9 Hz, 1H),
J=10.1, 1.9 Hz, 1H), 5.81 (q, J=2.5 Hz, 1H), 3.71 (s, 3H), 3.49–3.42 (m, 5.08–5.07 (m, 1H), 5.03–5.01 (m, 1H), 4.91 (dd, J=5.1, 4.4 Hz, 1H),
1H), 3.23 (dt, J=19.1, 2.1 Hz, 1H), 3.02 (dt, J=19.1, 2.8 Hz, 1H), 2.95 4.00–3.95 (m, 2H), 3.88–3.83 (m, 2H), 2.99–2.91 (m, 1H), 2. 64 (dq,
(dd, J=18.4, 4.6 Hz, 1H), 2.81 (ddd, J=19.1, 7.8, 0.9 Hz, 1H), 2.14 (ddd, J=15.9, 2.4 Hz, 1H), 2.44 (dd, J=15.9, 1.6 Hz, 1H), 2.14 (ddd, J=14.0,
J=12.7, 7.7, 2.1 Hz, 1H), 1.74 ppm (dd, J=12.7, 11.6 Hz, 1H); 13C NMR 5.2, 4.2 Hz, 1H), 2.08 (ddd, J=13.0, 7.9, 1.7 Hz, 1H), 1.80 (dd, J=13.0,
(125 MHz, CDCl3): d=199.2, 185.6, 166.4, 153.8, 151.0, 129.2, 127.8,
114.2, 51.3, 48.2, 47.0, 43.4, 42.6, 38.3 ppm; HRMS (ESI TOF): m/z calcd (125 MHz, CDCl3): d=186.1, 155.0, 152.7, 152.2, 128.5, 127.4, 108.1,
10.4 Hz, 1H), 1.76 ppm (ddd, J=14.0, 10.1, 4.3 Hz, 1H); 13C NMR
for C15H17O4 [M+H]+: 261.1121; found 261.1119
103.3, 64.9, 64.7, 47.0, 44.3, 44.3, 39.2, 38.0 ppm; HRMS (ESI TOF): m/z
calcd for C15H19O3 [M+H]+: 247.1329; found 247.1321
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2007, 46, 3942 –3945