PCC-mediated novel oxidation reactions of homobenzylic and homoallylic alcohols

Article abstract of DOI:10.1016/S0040-4039(02)02784-3

A new PCC-mediated carbon-carbon bond cleavage reaction during oxidation of homobenzylic alcohols leading to the formation of benzylic carbonyl compounds has been observed. Homobenzylic alcohols with no benzylic substitution (R¹=H) gave benzylic aldehydes without further oxidation, while those with benzylic substitution (R¹=Me, Et, Ar) gave benzylic ketones. In contrast, homoallylic alcohols gave products arising from double bond migration, cis- to trans-olefin isomerization and/or allylic oxidation.

Full text of DOI:10.1016/S0040-4039(02)02784-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 1275–1278
PCC-mediated novel oxidation reactions of homobenzylic and
homoallylic alcohols
Rodney A. Fernandes and Pradeep Kumar*
Division of Organic Chemistry: Technology, National Chemical Laboratory, Pune-411008, India
Received 27 November 2002; accepted 6 December 2002
Abstract—A new PCC-mediated carbonꢀcarbon bond cleavage reaction during oxidation of homobenzylic alcohols leading to the
1
formation of benzylic carbonyl compounds has been observed. Homobenzylic alcohols with no benzylic substitution (R =H) gave
1
benzylic aldehydes without further oxidation, while those with benzylic substitution (R =Me, Et, Ar) gave benzylic ketones. In
contrast, homoallylic alcohols gave products arising from double bond migration, cis- to trans-olefin isomerization and/or allylic
oxidation. © 2003 Elsevier Science Ltd. All rights reserved.
1
Before the studies of Corey and co-workers, the reac-
tivity of PCC had been little investigated. PCC is well
known to convert alcohols into aldehydes or ketones
Swern oxidation of 2-(4-benzyloxyphenyl)ethanol 1
proceeded smoothly to give 2-(4-benzyloxyphenyl)-
acetaldehyde 2 in good yield.
2
a
with high efficiency. This reagent also converts ter-
tiary cyclopropyl carbinols into the corresponding b,g-
To avoid the work-up procedure involving malodorous
dimethylsulfide, we carried out a PCC oxidation. Sur-
prisingly the oxidation of 1 with 1.5 equiv. of PCC
afforded a mixture of expected 2-(4-benzyloxyphenyl)-
acetaldehyde 2 and 4-benzyloxybenzaldehyde 3 in a 1:3
ratio (Scheme 1).
2b
2c,d
unsaturated ketones,
1,4-dienes into dienones,
2e
hydroquinone silyl ethers into quinones, enol ethers to
2
f
2g
esters and lactones and oximes to ketones. Other
known important conversions using this reagent are: (i)
3a
furan rings undergo oxidative ring expansion, (ii)
5
D -3b-tetrahydropyranyl ethers are oxidized to the cor-
4
3b
responding carbonyl D -3,6-diones, (iii) olefins are
Thus, the scission of a CꢀC bond leading to loss of one
carbon atom was observed in the PCC oxidation and
yet to add to our enthusiasm the end product was still
an aldehyde without any further oxidation to the corre-
sponding acid. The product mixture was confirmed by
oxidized to carbonyl compounds via the oxidation of
3
c–g
organoboranes.
Furthermore, PCC is well known
for selective oxidation of steroidal allylic alcohols,
oxidative cleavage of aryl substituted olefins, specific
4a
4
b
4c
1
oxidative cleavage of allylic and benzylic ethers, oxi-
4e
H NMR analysis where the benzylic methylene of 2
4
d
dation of benzylic and active methylene compounds,
oxidative cleavage of 1,4-dioxenyl carbinols to a-
was characteristic. The aldehyde proton of 3 appeared
as a sharp singlet at l 10.1 indicating a benzylic alde-
hyde, while a triplet was seen at l 9.8 indicating a small
amount of homobenzylic aldehyde 2. Thus, this degra-
dative oxidation involving CꢀC bond cleavage adds a
novel and new oxidation reaction of PCC.
4f
hydroxy acids and a-ketoacids, one-pot oxidation of
4g
4h
glycals to lactams, cleavage of vicinal diols and
modified oxidation of aldehydes to carbamoyl azides/
4i
acyl azides or carboxylic acids. Thus, the varied and
numerous oxidative reactions of PCC makes it a ver-
5
satile oxidant in organic synthesis.
In our recent synthetic endeavor on the total synthesis
6
of the anticoccidial antibiotic (+)-diolmycin A2, we
were in need of 2-(4-benzyloxyphenyl)acetaldehyde 2.
*
0
Corresponding author. Tel.: +91-020-5893300, ext. 2050; fax: +91-
20-5893614; e-mail: tripathi@dalton.ncl.res.in
0
Scheme 1. Swern and PCC oxidations.
040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02784-3

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R. A. Fernandes, P. Kumar / Tetrahedron Letters 44 (2003) 1275–1278
Aimed at achieving a better understanding of this new
oxidation reaction, we subjected various homobenzylic
alcohols with no benzylic substitution to PCC oxida-
tion. While the initial experiment with 1.5 equiv. of
PCC gave a small amount of homobenzylic aldehyde,
the major product obtained was benzylic aldehyde
strated with a variety of aryl substituted homobenzylic
alcohols having no benzylic substitution (Table 1).
The product was isolated virtually in pure form without
the need for further purification beyond mere filtration
and concentration.
(
entries 1 and 3, Table 1). Interestingly, when the
In order to study the scope of this oxidation, we further
extended the reaction to homobenzylic alcohols with
benzylic substitution (alkyl/aryl) such that the end
product would be an aryl ketone. The simplest sub-
strate available was 2-phenyl-1-propanol (obtained via
hydroboration of a-methylstyrene) which on oxidative
degradation should yield acetophenone as the end
product. Thus, the PCC oxidation of 2-phenyl-1-
propanol initially with 1.5 equiv. of PCC gave a mix-
ture of acetophenone and 2-phenylpropanal (9:1)
respectively (entry 1, Table 2). However, the use of 3
equiv. of PCC, furnished acetophenone as the only
product (entry 2, Table 2).
oxidation was carried out with 3 equiv. of PCC, the
benzylic aldehyde was obtained as the sole product.
The generality of this reaction was further demon-
Table 1. PCC oxidation of homobenzylic alcohols with no
benzylic substitution
7
Thus, various homobenzylic alcohols with benzylic sub-
stitution (alkyl/aryl) on oxidation with 3–4 equiv. of
PCC produced only the aryl ketones in good yields
Table 2. PCC oxidation of homobenzylic alcohols with
7
benzylic alkyl/aryl substitution

R. A. Fernandes, P. Kumar / Tetrahedron Letters 44 (2003) 1275–1278
1277
(
Table 2). It should be noted that although PCC is
to a mixture of compounds 10 and 11 in a 1:1 ratio.
The oxidation of long chain aliphatic cis-homoallylic
alcohols gave the products arising from alcohol oxida-
tion, double bond migration with concomitant isomer-
ization of the cis- to the trans-olefin and allylic
oxidation (entries 4–7). When the concentration of PCC
was lowered from 3 to 1.5 equiv. (entry 7) a mixture of
15 and 18 was obtained. Thus, a useful one-pot con-
version of homoallylic alcohols to 1,4-dicarbonyl-2E-
ene compounds was achieved with PCC.
commonly employed for the oxidation of benzylic and
active methylene compounds, no oxidation of benzylic
methylene was observed for the entries 8 and 9 (Table
2
), indicating the need for reflux conditions as reported
4d
in the literature.
8
Encouraged by the finding of CꢀC bond cleavage dur-
ing the oxidation reaction mediated by PCC on homo-
benzylic alcohols, we further proceeded to study the
same reaction on homoallylic alcohols. While the PCC-
mediated allylic oxidation to a,b-unsaturated carbonyl
compounds has been thoroughly investigated, the oxi-
dation of homoallylic alcohols, where there is ample
opportunity for double bond migration and/or allylic
oxidation, remains unexplored. In order to investigate
the course of reaction we carried out a detailed study of
PCC oxidation on homoallylic alcohols.
To summarize, we have explored a new and novel
oxidation reaction by PCC involving CꢀC bond cleav-
age during oxidation of homobenzylic alcohol to ben-
zylic aldehyde or ketone. This is one of the rare
reactions of PCC where a degradation of one carbon
occurs and yet the end product remains an aldehyde or
ketone without further oxidation. Such a reaction will
be very useful in analyzing functional group compati-
bilities in designing oxidation reactions involving PCC.
On the other hand, homoallylic alcohols produced quite
interesting results due to double bond migration, con-
comitant cis- to trans-isomerization and/or allylic oxi-
dation. Thus, this investigation led to the useful
one-pot conversion of homoallylic alcohols to 1,4-dicar-
bonyl-2E-ene compounds that may have potential as
intermediates in organic synthesis. Therefore, the
results described above may have a major impact on
the application of PCC oxidation in synthetic organic
chemistry.
As shown in Table 3, oxidation of 3-methyl-3-buten-1-
ol 4 with PCC (3 equiv.) gave 3-methyl-2-butenal 5 in
6
8% yield arising from alcohol oxidation and subse-
quent double bond migration. However oxidation of
homoallylic alcohol 6 with PCC (3 equiv.) afforded a
mixture of 7 and 8 (1:1) in 60% yield. Presumably, the
reaction proceeded initially by the oxidation of alcohol
followed by double bond migration to give 7 and
subsequent allylic/benzylic oxidation furnished com-
pound 8. Similarly, the oxidation of 9 resulted in iso-
merization of cis- to the trans-olefin eventually leading
7
Table 3. PCC oxidation of homoallylic alcohols
Acknowledgements
R.A.F. thanks CSIR, New Delhi, for financial assis-
tance. We are grateful to Dr. M. K. Gurjar for his
support and encouragement. This is NCL Communica-
tion No. 6635.
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2
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8
. 4-oxo-Pentadec-2E-enal (15): White solid; yield: 59%; mp
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3
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6
1
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1
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3
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13
CDCl ): l 14.03, 22.64, 23.66, 29.07, 29.29, 29.55, 31.86,
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4
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6
7
. Piancatelli, G.; Scettri, A.; D’ Auria, M. Synthesis 1982,
+
+
intensity,%): 238 [M ] (9.1), 209 [M −CHO] (68.2), 195
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8 (56.5), 83 (76.6), 70 (40.2), 55 (100). Anal. calcd for
2
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. General procedure: To a mixture of PCC (1.5 or 3–4
equiv.) and powdered molecular sieves (3 A, one-half the
(
9
2
C H O (238.37): C, 75.58; H, 10.99. Found: C, 75.39; H,
15 26
2
,
10.76%.