Regioselective aliphatic retro-[1,4]-Brook rearrangements

Article abstract of DOI:10.1002/anie.200702539

A turn-up for the Brook: The relative ease of silyl migration in the aliphatic retro-Brook rearrangements of α,γ-disilyloxy organolithium compounds (see scheme) has been revealed for the first time to be [1,2] ? [1,4]. The increasing size of the silyloxy group at the γ position relative to that at the α position induces higher [1,4] selectivity. (Chemical Equation Presented).

Full text of DOI:10.1002/anie.200702539

Angewandte
Chemie
DOI: 10.1002/anie.200702539
Asymmetric Rearrangements
Regioselective Aliphatic Retro-[1,4]-Brook Rearrangements**
Yuji Mori,* Yutaka Futamura, and Kazumi Horisaki
The migration of silicon is a ubiquitous process in reactions,
and the Brook rearrangement is an intramolecular migration
of a silicon atom from a carbon to an oxygen atom.[1] The
reverse process—migration of a silicon atom from an oxygen
to a carbon atom—is referred to as the retro-or reverse-
Brook rearrangement and is a common occurrence.[2] Studies
on retro-[1,2]-Brook rearrangements have revealed that the
rearrangement is highly stereospecific with regard to the
configuration at the carbon atom and proceeds with retention
Scheme 1. Retro-[1,2]- and [1,4]-Brook rearrangements.
of configuration in the a-silyloxy carbanions generated from
aliphatic substrates, whereas inversion is observed for ben-
zylic and allylic carbanions.[3] As the retro-Brook rearrange-
ment requires excess base, the driving force for the reaction
may be the formation of a lithium alkoxide that is more stable
than the starting organolithium compound. Higher-order
retro-[1,3]-, -[1,4]-, -[1,5]-, and -[1,6]-Brook rearrangements
have also been the subject of numerous investigations, and
have been utilized for the preparation of functionalized
organosilane derivatives.[4–8] The general trend of the ease of
silyl migration has been reported to be [1,2] > [1,3] @ [1,4] >
[1,5] based on the logic that the shorter transfer distance is
more favored,[9] and this order of migration has long been
accepted without question.[5a,6c] It has recently been reported
that the regioselectivity of the retro-[1,2]- and [1,4]-Brook
rearrangements in an allyllithium system depends upon the
reaction conditions, and that the addition of hexamethyl-
phosphoramide (HMPA) as a cosolvent improves the [1,4]
selectivity.[5l] However, there has been no study of competitive
silyl migration occurring in aliphatic retro-Brook rearrange-
ments. We decided to investigate the relative ease of
otherwise comparable [1,2] and [1,4] migrations. We report
here the first documented example of the preference of retro-
[1,4]-migration over retro-[1,2] migration in an a,g-disilyloxy
organolithium system.
lithium[10] and an aldehyde prepared from methyl (R)-3-
hydroxybutylate (98% ee) followed by silylation and separa-
tion by flash chromatography (Scheme 2). The configurations
of 4 and 5 were determined to be syn and anti, respectively, by
formation of the acetonide[11] and by 13C NMR analysis using
the Rychnovsky method.[12]
Scheme 2. Synthesis of 1,3-disilyloxy-1-tributylstannylbutane deivatives.
DIBALH=diisobutylaluminum hydride
Initial experiments focused on the retro-Brook rearrange-
ment of the syn-1,3-disilyloxystannane derivatives 4 (Table 1).
Treatment of 4a with nBuLi (5.0 equiv) in THF at À788C for
30 minutes did indeed give C-silyl products. However, instead
of the expected C-trimethylsilylated product 6a, the C-
triethylsilylated product 7a was obtained as a major product
in a stereochemically pure form (Table 1, entry 1). This result
was particularly surprising, considering that the relative ease
of migration of silyl groups has been reported as [1,2] @
To evaluate the regioselectivity of the retro-Brook
rearrangement, we examined 1,3-disilyloxy-1-tributylstannyl-
butane derivatives 1, which can form [1,2] and [1,4] products 2
and 3, respectively, after transmetalation and rearrangement
(Scheme 1). The optically active stannanes 4 and 5 were
synthesized in a pure form by the reaction of tributylstannyl-
Table 1: Rearrangement of syn-1,3-disilyloxystannane derivatives 4a–g.
Entry
4
R13Si[a]
R23Si[a]
Yield [%][b]
6:7[c]
[*] Prof. Y. Mori, Y. Futamura, K. Horisaki
Faculty of Pharmacy
1
2
3
4
5
6
7
4a
4b
4c
4d
4e
4 f
4g
TES
TES
TBS
TBS
TBDPS
TBDPS
TBDPS
TMS
TES
TMS
TES
TMS
TES
TBS
91
90
95
98
98
98
NR
11:89
15:85
3:97
3:97
0.3:99.7
8:92
Meijo University
Tempaku-ku, Nagoya 468-8503 (Japan)
Fax: (+81)52-834-8090
E-mail: mori@ccmfs.meijo-u.ac.jp
[**] This research was supported by a Grant-in-Aid for Scientific
Research on Priority Areas 18032079 from The Ministry of
Education, Culture, Sports, Science, and Technology (MEXT).
–
[a] TMS=trimethylsilyl, TES=triethylsilyl, TBS=tert-butyldimethylsilyl,
TBDPS=tert-butyldiphenylsilyl. [b] Yield of isolated product. NR=no
reaction. [c] Determined from the yieldsof 6 and 7.
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[1,4],[5a,6c,9] and that a-silyloxyalkylstannane derivatives
exhibited high [1,4] selectivity, which is in sharp contrast to
the reaction with 4g.
undergo rapid retro-[1,2]-Brook rearrangement (< 15 min)
under the same conditions.[3e] Silyl groups of various size
migrate in high yields and the predominance of [1,4] migra-
tion over [1,2] migration is general (Table 1). Notably, a larger
silyl group at the g position enhances the preferential
[1,4] selectivity for the rearrangement (Table 1, entries 3–6).
Under the standard transmetalation/rearrangement con-
ditions, the retro-Brook rearrangement of stannane 4g
containing bulky TBDPS and TBS groups did not occur
because of the steric bulk around the Sn atom. This limitation
of the transmetalation was addressed by increasing the
reaction temperatures from À78 to À 358C, which yielded
three products, 8, 9, and 10 (Scheme 3). Compound 10 was
Characterization of the C-and O-silyl groups of the
rearranged products is a critical point for the discussion of the
regioselectivity of the retro-Brook rearrangement and has
been carried out in the following manner. The migrated C-
silyl group was unambiguously determined by removing the
O-silyl group of the rearranged products under acidic
conditions to give the corresponding 1-trialkylsilyl-1,3-buta-
nediols. The position of the O-silyl group was then established
1
by H NMR analysis of the acetylated compounds derived
from the rearranged products (Scheme 4). The proton on the
Scheme 4. Diagnostic 1H NMR data of the acetatesof the [1,2]- and
[1,4]-rearranged products 6a and 7a.
acetoxylated carbon atom of the [1,2]-rearranged products
appeared at about d = 4.9 ppm as a double doublet, whereas
that of the [1,4]-rearranged products was observed as a
multiplet. These coupling patterns allowed us to definitively
assign the position of the acetoxy group, and in turn, that of
O-silyl group.
The stereochemistry of the rearranged products was
determined by NMR analysis of the corresponding aceto-
nides.[12] The acetonides prepared from the [1,4]-migration
products 7a and 12a were assigned to be syn and anti,[14]
respectively, thereby indicating that the retro-Brook rear-
rangements proceeded stereospecifically with retention of
configuration at the carbanion center, as previously report-
ed.[5c]
The competitive experiments summarized in Table 1 and
Table 2 clearly demonstrated that the retro-[1,4] rearrange-
ment occurs more easily than the retro-[1,2] rearrangement.
This selectivity could plausibly be explained by the relative
stability of intermediates: the five-membered pentacoordi-
nated silicate 13[5f] would be more favored than the three-
membered silicate 14,[3b,h] which has higher ring strain energy
(Figure 1). In general, five-membered rings are formed faster
than three-membered rings, although entropic factors might
favor the formation of three-over fivem- embered rings in
some situations. Thus, we could expect the [1,4] migration to
be faster than the [1,2] migration according to the ease of ring
formation. The fact that the rearranged products obtained in
these experiments comprised only two products, the retro-
[1,2] and -[1,4] products, and no [1,5] oxygen to oxygen
migration product was detected except in the case of 4g
indicates that the rearrangement proceeded under kinetically
Scheme 3. Retro-Brook rearrangement of 4g.
evidently the result of the retro-[1,2]-Brook rearrangement of
the TBS group, followed by the [1,5] oxygen to oxygen
migration of the TBDPS group.[13] The net ratio of the retro-
[1,2] versus the -[1,4] rearrangement was 76:24, thus showing
opposite selectivity to the reactions of 4a–f.
We next explored the generality of the trend of the retro-
Brook rearrangement using the anti-1,3-disilyloxystannane
derivatives 5. In all of the cases examined, transmetalation
and rearrangement proceeded in good to excellent yields
(Table 2). The product ratios revealed again the relative ease
of migration to be [1,2] ! [1,4]. As in the case of a syn series,
increasing the size of the silyl group at the g position relative
to that at the a position caused complete [1,4] rearrangement
(Table 2, entries 5 and 6). Considering that the rate of retro-
[1,4]-Brook rearrangements decreases with increasing bulki-
ness of the silyl group,[5b,d] it is noteworthy that the reaction of
stannane 5g with bulky TBDPS and TBS groups also
Table 2: Rearrangement of anti-1,3-disilyloxystannane derivatives 5a–g.
Entry
5
R13Si
R23Si
Yield [%][a]
11:12[b]
1
2
3
4
5
6
7
5a
5b
5c
5d
5e
5 f
5g
TES
TES
TBS
TBS
TBDPS
TBDPS
TBDPS
TMS
TES
TMS
TES
TMS
TES
TBS
85
96
84
97
98
99
94
32:68
17:83
8:92
3:97
0.4:99.6
0.4:99.6
10:90
[a] Yield of isolated product. [b] Determined based on the yields of 11
and 12.
Figure 1. Intermediatesof retro-Brook rearrangements.
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tert-butyldimethylsilyloxy group has to adopt an unstable
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In summary, we have demonstrated unprecedented exam-
ples of competitive aliphatic retro-[1,2]- and -[1,4]-Brook
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Received: June 12, 2007
Revised: October 6, 2007
Published online: January 4, 2008
Keywords: asymmetric synthesis · diols · rearrangement ·
.
regioselectivity · silanes
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