D. Martinez-Solorio, M. P. Jennings / Tetrahedron Letters 49 (2008) 5175–5178
5177
Table 3
of a terminal alkene proceeded with PyÁBr3 in MeOH to provide the
corresponding homoallylic alcohol 9b in nearly identical yields of
78% and 76%. However, the catalyst loading was increased from 5
to 10 mol % and the reaction temperature was warmed from À20
to 0 °C to help facilitate the protecting group removal within a
few hours. It should be noted that one could utilize the standard-
ized conditions from Table 1 for silyl ethers 9a and 10a, although
the reactions times were much longer (>24 h) for appreciable con-
version to 9b. Based on this observation, we envisioned that lower
catalyst loading might allow for a chemoselective removal of a pri-
mary TBS (or TES) ether in the presence of a secondary one. Much
to our delight, treatment of the bis-TBS ether compound 11a with
5 mol % of PyÁBr3 in MeOH at 0 °C did indeed undergo chemoselec-
tive cleavage of the primary TBS ether in the presence of the sec-
ondary one and afforded the mono-protected alcohol 11b in 74%
yield. Likewise, chemoselective removal of the primary TBS moiety
resident in 12a in the presence of a secondary TES ether was also
accomplished under the exact reaction conditions for that of 11a
to provide alcohol 12b in a virtually identical yield of 72% with
respect to 11b.
PyÁBr3 catalyzed deprotection of the TBS group resident in complex organic synthonsa
Silyl ether
Product, Yield
O
O
O
O
TBSO
HO
OMe
OMe
OMe
OMe
16a
16b: 70%
O
O
HO
TBSO
TBSO
17a
17b: 65%
HO
We also examined the chemoselectivity of the TBS ether cleav-
age in the presence of other typical functional moieties. Thus, the
OH
OH
O
O
O
TBS- protected
a-hydroxy ketone 13a did undergo silyl cleavage
18a
18b: 77%
without affecting the carbonyl group to furnish the keto-alcohol
13b in a modest yield of 55%. However, the reaction was quite slug-
gish at 0 °C and required warming to rt to drive the reaction to sig-
nificant conversion with 10 mol % of PyÁBr3. Likewise, selective
deprotection of the TBS group resident in 14a at 0 °C readily affor-
ded 3-butyn-1-ol (14b) in an 81% yield. Similar to that of 10a,
chemoselective removal of the primary TBS ether of 15a in
the presence of a phenolic TBS protecting group furnished the free
benzylic alcohol 15b in an exceptional 93% yield under the
standard reaction conditions as described in Table 2.
O
O
O
HO
H
TBSO
19a
19b: 41%
O
O
As the final component of our investigation, we chose to exam-
ine the efficiency of PyÁBr3 in MeOH for the chemoselective
removal of TBS ethers in the presence of other function groups
resident in fairly complex organic synthons and/or natural product
intermediates as delineated Table 3.
Thus, treatment of the primary TBS ether b-hydroxy lactone 16a
with 5 mol % of PyÁBr3 in MeOH at 0 °C swiftly removed the TBS
protecting group, while not disturbing either the lactone or the
b-methoxy moiety and provided the desired free primary alcohol
16b in 70% yield. We were initally concerned that the reaction con-
ditions might promote b-elimination of the methoxide anion to
O
H
19c: 49%
O
O
O
O
TBSO
O
TBSO
O
TBSO
HO
N
N
Bn
Bn
20b: 89%
20a
a
Reactions were run with 5 mol % of PyÁBr3 and 0.15 mmol of substrate in 2 mL of
MeOH at 0 °C until complete by TLC analysis.
provide the corresponding
a,b-unsaturated lactenone. However,
we were quite pleased that only TBS ether cleavage was observed.
Similar to 16a, PyÁBr3-mediated chemoselective TBS cleavage of
the protected b-C-glycoside compound 17a readily proceeded to
afford the free hydroxyl group of 17b with a modest yield of 65%.
We also examined the selective removal of a secondary TBS ether
in the presence of an acetonide protecting. Unfortunately, treat-
ment of 18a9 with PyÁBr3 in MeOH at 0 °C led to concomitant
removal of both the acetonide and silyl ether after 24 h to provide
the triol 18b with a 77% yield. Similar to lactone 16a, the TBS- pro-
to afford the free hydroxy compound 20b in an 89% yield without
forming any appreciable amount of the cyclized lactone
product. Interestingly, the reaction of 20a with TBATB not only
chemoselectively removed the TBS moiety, but also promoted
cyclization to afford the corresponding lactone in approximately
50% yield.
In conclusion, we have shown that PyÁBr3 in MeOH chemoselec-
tively deprotects primary TBS (and TES) ethers in the presence of a
variety of other protecting and common functional groups in mod-
est to excellent yields when performed at 0 °C and 5 mol % catalyst
loading. Based on the various substrates investigated, the
described mild and straightforward protocol should be quite useful
in the stereoselective synthesis of natural product subunits and/or
the production of valuable organic synthons.13
tected
a,b-unsaturated lactenone 17a was subjected to standard
reaction conditions and furnished two products 17b and 17c in a
combined yield of 90%. The predicted desilylated lactenone 17b
was produced in 41% yield, whereas the bicyclic pyran-lactone
19c was formed in 49% yield via an intramolecular cyclization of
the free hydroxyl moiety onto the Michael acceptor.10,11 Not sur-
prisingly, longer reaction times led selectively to the bicyclic lac-
tone 19c (via 19 b) in nearly quantitative yields. Thus, PyÁBr3 in
MeOH can catalyze TBS group removal and also facilitate intramo-
lecular Michael additions as well. Lastly, the bis-TBS-protected
b-hydroxy carbonyl 20a, derived from an Evans’ oxazolidinone
aldol reaction,12 readily underwent primary silyl group cleavage
Acknowledgement
Support was provided by the University of Alabama and the NSF
(CHE-0115760) for the departmental NMR facility.