Halogen cation induced stereoselective semipinacol-type rearrangement of allylic alcohols: A highly efficient approach to α-quaternary β-haloketo compounds

Article abstract of DOI:10.1055/s-2003-40855

Allylic alcohols were found to undergo a semipinacol-type rearrangement induced by halogen cation generated from the chloramine-T/ZnX₂ combination, which provided a highly efficient and stereoselective method for the preparation of α-quaternary β-haloketo compounds. This reaction is valuable and versatile since a quaternary carbon could be constructed effectively and three kinds of β-haloketo compounds (X = Cl, Br, I) could be achieved readily.

Full text of DOI:10.1055/s-2003-40855

LETTER
1497
Halogen Cation Induced Stereoselective Semipinacol-type Rearrangement of
Allylic Alcohols: A Highly Efficient Approach to a-Quaternary b-Haloketo
Compounds
A
H
ighly Efficien
a
t
A
pproac
o
a
-Quaternary
b
M
-Haloketo Compound
in Wang, Zhen Lei Song, Chun An Fan, Yong Qiang Tu,* Wei Ming Chen
Department of Chemistry and State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. China
Fax +86(931)8912582; E-mail: tuyq@lzu.edu.cn
Received 26 April 2003
nary carbon centers, still remaining a crucial aspect of
Abstract: Allylic alcohols were found to undergo a semipinacol-
several areas in organic synthesis, is of particular impor-
type rearrangement induced by halogen cation generated from the
tance. Quaternary carbon has long been an important class
chloramine-T/ZnX2 combination, which provided a highly efficient
and stereoselective method for the preparation of a-quaternary b-
of structure, although much progress has been achieved in
haloketo compounds. This reaction is valuable and versatile since a the area.7 Herein, we wish to present the experiment re-
quaternary carbon could be constructed effectively and three kinds
sults in detail.
of b-haloketo compounds (X = Cl, Br, I) could be achieved readily.
Key words: alcohols, halogenation, rearrangements, oxidations,
zinc
Organohalo compounds are a very important class of syn-
thetic intermediates, which can effect many transforma-
tions in synthetic organic chemistry, thus numerous
Scheme 1
halogenating methods have been developed in terms of
different substrate style and halogenating reagents. As
compared with their a-homologues, the b-haloketo com- The allylic alcohols investigated in our study were pre-
pounds, especially those with a-quaternary carbon cen- pared by the addition of the corresponding vinyl lithium
ters, are relatively much less studied, albeit this kind of or vinyl magnesium to the appropriate ketones and alde-
molecules have important synthetic utility1 and bioactivi- hydes according to our previously reported method.6 Thus
ty.2 Thirty years ago Johnson described the chlorinative a typical experimental procedure of the halogen cation in-
ring homologation of simple cyclobutanes, -pentanes, and duced rearrangement of these allylic alcohols was as the
-hexanes and isopropenyl [2.2.1]-heptanol with potential- following: To a suspension of chloramine-T (1.1 mmol) in
ly explosive t-BuOCl.3 Very recently an improved version 5 mL acetonitrile was added ZnBr2 (1.1 mmol). The reac-
of this reaction was reported by Maleczka by the use of tion mixture was stirred at room temperature for 5 minutes
bleach/acetic acid system as the chlorinating reagent.4 and a nearly clear yellow solution was formed. The allylic
Both methods could merely afford b-chloroketones with alcohol (1.0 mmol) was then added to the solution and the
ring expansion. To our knowledge, no other systematic yellow disappeared immediately. TLC check indicated
studies have been performed toward the preparation of b- that the allylic alcohol disappeared and the b-bromoketo
haloketo compounds.5 In connection with our continuous compound was formed in good to excellent yield. The re-
interest in the semipinacol rearrangement of 2,3-epoxy al- action mixture thus formed was filtered through a short
cohols and 2,3-aziridino alcohols,6 which are prepared neutral Al2O3 column. The filtrate was evaporated and the
from the corresponding allylic alcohols, we developed a residue was purified by column chromatography on silica
halogen cation induced semipinacol rearrangement of al- gel to afford the b-bromoketo compound as a single dias-
lylic alcohols, which gave rise to a-quaternary b-haloketo tereoisomer which was judged from the NMR spectra.
compounds with excellent diastereoselectivity in good to The stereochemistry of the b-bromoketo compounds was
excellent yields (Scheme 1). The halogen cation source determined by 1D NOE and 2D NOESY experiments of
we used in our study is a chloramine-T/ZnX2 combina- the product of entry 4 in Table 1, which was selected as a
tion. A significant value of this procedure features that model. It is worthy to note that the p-toluenesulfonyl
two adjacent stereocenters, with one being the quaternary, amine formed from chloramine-T could be recovered
were formed simultaneously starting from the simple al- quantitatively. In addition, several other solvents were
lylic alcohols. The stereoselective construction of quater- studied, and it was found that ether, dichloromethane and
acetone were also good reaction media.
Synlett 2003, No. 10, Print: 05 08 2003.
Art Id.1437-2096,E;2003,0,10,1497,1499,ftx,en;U07703ST.pdf.
© Georg Thieme Verlag Stuttgart · New York

1498
B. M. Wang et al.
LETTER
Table 1 Semipinacol-type Rearrangement of the Allylic Alcohols
Table 1 Semipinacol-type Rearrangement of the Allylic Alcohols
Induced by Halogen Cationa
Induced by Halogen Cationa (continued)
En- Substrate
try
Product
Yield (%)b
94
En- Substrate
try
Product
Yield (%)b
94
1
2
3
4
12
13
92
88
90
90
65
87
14
15
16
75
5
6
7
85
85
87
a All reactions were complete in 1 min.
b Isolated yields.
All the results were tabulated in Table 1, from which it
can be seen that all reactions were complete in 1 minute at
room temperature with the formation of the b-haloketo
compounds in good to excellent yields. The reaction time
is much shorter than that of literature reported.3,4 The ste-
reocontrolling of the rearrangement reaction is excellent
as only one single form of the diastereoisomeric b-haloke-
to compound in each example was obtained. In entries 1–
3, tertiary allylic alcohols were investigated, and the re-
sults indicated that the phenyl group easily migrated to
give b-bromo ketones in excellent yields while the migra-
tion of methyl group appeared a little unfavorable and af-
forded lower yield. The secondary allylic alcohols (entries
4–7) could also undergo the rearrangement smoothly to
furnish b-bromo aldehydes in excellent yields. It was ob-
served in our investigation that it seems essential to effect
the rearrangement that the secondary allylic alcohols
should bear an electron-rich aryl group. When a bulky
t-butyldimethylsilyloxy group is installed in the cyclohex-
ene ring of the substrate (entry 7), the reaction could also
proceed smoothly. In addition, when the substrates bear-
ing a five-membered ring (entries 8–10) instead of a six-
membered one were subjected to the reaction, the corre-
sponding b-bromoketo compounds could also be obtained
with almost the same efficiency.
8
9
92
88
10
11
87
75
Synlett 2003, No. 10, 1497–1499 © Thieme Stuttgart · New York

LETTER
A Highly Efficient Approach to a-Quaternary b-Haloketo Compounds
1499
To investigate the substrate scope of this rearrangement In summary, we discovered that chloramine-T/ZnX2 com-
reaction, we examined the bicyclic allylic alcohols (en- bination is a very effective promoter for the semipinacol-
tries 11 and 12) and the acyclic systems (entries 13 and type rearrangement of allylic alcohols to form b-haloketo
14). To our delight, both kinds of starting materials could compounds with excellent diastereoselectivity in good to
rearrange to the expected products, indicating that this re- excellent yields. The reaction is very mild and highly ef-
action is applicable to a broad scope of allylic alcohols. It ficient as compared with literature methods. We anticipate
is of particular interest that the spiro b-bromo ketones that the procedure would find use in synthetic organic
could be achieved readily (entries 11 and 12), since spiro chemistry.
compounds have been currently used as excellent chiral
ligands for catalytic asymmetric reactions.8
Acknowledgment
In order to prepare other b-haloketo compounds, investi-
gation was expanded to the employment of ZnCl2 and
ZnI2. Therefore, to our delight, when ZnCl2 (entry 15) or
ZnI2 (entry 16) was used as the halogen source instead of
This work was supported by NSFC (29972019, 29925205 and QT
program), FUKTME of China, the Young Teachers’ Fund of Mini-
stry of Education and the Fund of Ministry of Education (99209).
ZnBr2, the corresponding b-chloro or b-iodo aldehyde
References
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Scheme 2
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Synlett 2003, No. 10, 1497–1499 © Thieme Stuttgart · New York