Radical phosphinylation of α,α-diaryl allylic alcohols with concomitant 1,2-aryl migration

Article abstract of DOI:10.1039/c4cc02114b

A novel radical phosphinylation of α,α-diaryl allylic alcohols with arylphosphine oxides was described for the direct preparation of α-aryl-β-phosphinylated carbonyl ketones in medium to good yields via 1,2-aryl migration. In this reaction, formation of new C(Ar)-C(sp³) and C(sp³)-P bonds was observed.

Full text of DOI:10.1039/c4cc02114b

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Radical phosphinylation of a,a-diaryl allylic
alcohols with concomitant 1,2-aryl migration†
Cite this: Chem. Commun., 2014,
50, 7642
Xue-Qiang Chu, You Zi, Hua Meng, Xiao-Ping Xu* and Shun-Jun Ji*
Received 21st March 2014,
Accepted 20th May 2014
DOI: 10.1039/c4cc02114b
www.rsc.org/chemcomm
A novel radical phosphinylation of a,a-diaryl allylic alcohols with
arylphosphine oxides was described for the direct preparation of
a-aryl-b-phosphinylated carbonyl ketones in medium to good
yields via 1,2-aryl migration. In this reaction, formation of new
C(Ar)–C(sp3) and C(sp3)–P bonds was observed.
Organophosphorus compounds are privileged and important,
which have attracted considerable attention because of their wide
applications in pharmaceuticals1 and agrochemicals,2 organic
synthesis,3 as well as materials science.4 They have also been
utilized as excellent ligands for transition-metal catalysis and
organocatalysts.5 As such, intense research interests have been
paid to explore practical synthesis via C–P bond construction.
The addition of P(O)–H bonds to alkenes (hydrophosphina-
tion) represents one of the most important processes (Scheme 1a),
which is often promoted by radical initiators,6 strong bases,7
acids,8 UV- or microwave-irradiation.9,10 Although diverse
C(sp3)–P,11 C(sp2)–P12 bond forming reactions via transition
metal-catalyzed phosphination have proven to be efficient in the
Scheme 1 Phosphinylation of alkenes.
past few decades, new types of C–P formation are still highly P-centered radical18 addition to allylic alcohols 1, leading to a
desirable and present a considerable challenge. In 2011, Ji and variety of a-aryl-b-phosphinylated carbonyl compounds has never
coworkers established a copper/iron cocatalyzed oxidative synth- been previously reported (Scheme 1e). As a continuation of our
esis of b-ketophosphonates (Scheme 1b).13 Recently, Li’s group interest in the radical pathway transformations,19 herein, we
described a silver-mediated C–P and C–F bond formation reaction describe a novel reaction of radical phosphinylation of a,a-diaryl
of unactivated alkenes via condensation with diethyl phosphite allylic alcohols, which is emerging as a versatile and powerful tool
and selectfluor (Scheme 1c).14 Very recently, Yang et al. found for C(sp3)–C and C(sp3)–P bond formation.
that the active [Ph2P(O)Ag] complexes can be employed to the
Previous studies14–16 revealed that phosphonyl radicals can be
phosphorylation-initiated cascade annulation of functionalized generated from Ph2P(O)H with silver salts. Based on this assump-
alkenes (Scheme 1d).15 In addition, there are a series of studies tion, we initiated our work by using allylic alcohol 1a and
devoted to incorporate the phosphonic functionality.16 To the diphenyl phosphine oxide 2a as a model reaction in the presence
best of our knowledge, a neophyl-type rearrangement17 driven by of AgOAc as an oxidant in toluene at 120 1C under air (Table 1,
for more details, see ESI†). Gratifyingly, phosphinylation with
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry,
Chemical Engineering and Materials Science & Collaborative Innovation Center of
Suzhou Nano Science and Technology, Soochow University, Suzhou, 215123,
People’s Republic of China. E-mail: xuxp@suda.edu.cn, shunjun@suda.edu.cn;
Fax: +86-512-65880307; Tel: +86-512-65880307
concomitant 1,2-migration of a phenyl group was achieved, and
the targeted a-aryl-b-phosphinylated carbonyl compound 3aa was
obtained in 35% LC-yield after 2 h (Table 1, entry 1). Note that a
silver mirror was formed during the reaction. Encouraged by the
results, we further optimized the reaction conditions. Solvent
screening showed that 1,4-dioxane was optimal, providing 3aa in
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c4cc02114b
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Table 1 Optimization of the reaction conditionsa
Table 3 Phosphinylation of asymmetrical a,a-diaryl allylic alcoholsa
Entry
Oxidant (equiv.)
Solvent
LC-yield (%)b
1
2
3
4
5
6
7
8
AgOAc (2)
AgOAc (2)
AgOAc (2)
AgNO3 (2)
AgCO3 (2)
AgOAc (1)
AgOAc (3)
AgOAc (0.2) + Cu(OAc)2 (0.5)
AgOAc (0.2) + K2S2O8 (2)
AgOAc (0.2) + DTBPd (3)
AgOAc (0.2) + PhI(OAc)2(2)
AgOAc (0.2) + TBHPe (3)
AgOAc (0.2) + TBPBg (3)
—
Toluene
35
Trace
79
ClCH2CH2Cl
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
36
Trace
21
88 (86)c
16
9
Messy
47
Messy
24 (29) f
37 (39) f
0
10
11
12
13
14
a
All reactions are carried out under the optimal conditions; yields of
b
c
isolated products. Yields only of major products. The ratio of 3 to its
a
All reactions were carried with 1a (0.3 mmol), 2a (0.45 mmol), and
isomer was determined by 1H NMR of the crude product. Yields of 3
d
b
oxidant in solvent (2 mL) at 120 1C under air for 2 h. Yields were
e
and its isomer, only major products are shown. The ratio of 3 to its
determined by LC-MS with an internal standard (biphenyl) as the ratio
between the formed products and the initial amount of limiting
isomer was determined by 1H NMR analysis of the isolated product.
c
d
e
reactant. Isolated yields. DTBP = di-tert-butyl peroxide. TBHP =
f
tert-butyl hydroperoxide (70% in aqueous solution). The reaction
was carried out under Ar. TBPB = tert-butylperoxybenzoate.
g
The current method was applied for symmetrical compounds 1
bearing methyl (1b) and methoxyl (1c) groups on the aromatic
ring, affording the desired a-aryl-b-phosphinyl ketones 3ba and
3ca in 88% and 90% yields, respectively. Although the electronic
effect on the aryl ring reduced the yields to some extent, still
good yields of 3da, 3ea and 3fa were obtained. Meanwhile, the
meta-substituted aryl group also worked as a migrating group
and product 3ga was isolated in 76% yield.
To gain further insight into the selectivity of the aryl migration
in this silver-promoted rearrangement reaction, allylic alcohols
containing two different aryl groups were used, and the results
are listed in Table 3. To our delight, ketone 3ha was detected as a
major product in 34% yield, and the ratio of 3ha and its isomer was
1.8 : 1. For substrates 1j–l and heterocyclic 1m, it was also found
that electron-poor aryl groups migrate preferentially. Importantly,
this chemoselective manner suggested that the reaction might be a
radical (‘‘neophyl’’) rearrangement route17 to the observed pro-
ducts. On the other hand, ortho-substituted aryl rings (1i) migrated
less effectively, indicating that steric hindrance had a detrimental
effect on the migration. Notably, the mono-aryl-type allylic alcohol
1n was almost inert under our conditions.
79% LC-yield (Table 1, entries 1–3). Next, changing AgOAc to other
silver salts such as AgNO3 or Ag2CO3 just led to lower yields (Table 1,
entries 4–5). Additionally, higher oxidant loading (3 equiv.)
improved the LC-yield of the model reaction to 88%, along with
an isolated yield of 86% (Table 1, entry 7), while an attempt to
decrease the oxidant loading was unsuccessful (Table 1, entry 6).
Furthermore, a variety of oxidants in the presence of 20 mol%
AgOAc were evaluated over whether they have potential for genera-
tion of P-radicals,14–16 but the reactions did not give better results
even under an argon atmosphere (Table 1, entries 8–13). Besides, no
product was formed without AgOAc (Table 1, entry 14).
Having established the optimal conditions, we next examined
other symmetrical and asymmetrical substrates of a,a-diaryl
allylic alcohols, and the results were shown in Tables 2 and 3.
Table 2 Phosphinylation of symmetrical a,a-diaryl allylic alcoholsa
During the course of our studies, cyclic allylic alcohols were
chosen as the substrates as well (Scheme 2). It was demonstrated
that 1o also worked under the standard conditions, the desired
migrated product 3oa was obtained in 38% yield. However, when 1p,
a
All reactions are carried out under the optimal conditions; yields of
Scheme 2 Reaction of cyclic a,a-diaryl allylic alcohols with 2a.
Chem. Commun., 2014, 50, 7642--7645 | 7643
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is generated from diphenylphosphine oxide 2a with Ag(I) salt,14–16
and reacts with allylic alcohol 1 affording an alkyl radical A.
Subsequently, an intramolecular addition of the radical to the
aromatic ring to generate the spiro[2,5]octadienyl radical B,
followed by migration of the electron-deficient aryl group prefer-
entially, releases radical C. Note that ortho-substituted groups are
reluctant to migrate owing to a sterically congested radical B was
not favorable to the energy.17d Finally, single-electron transfer
(SET) from C to silver(I) produces the desired product 3 along
with loss of a proton.
Scheme 3 Phosphinylation of a,a-diaryl allylic alcohols.
In summary, we have developed a novel phosphinylation of
a,a-diaryl allylic alcohols via 1,2-aryl migration of an aryl group
involving new C(Ar)–C(sp3) and C(sp3)–P bond formation in one
step. A variety of a-aryl-b-phosphinylated carbonyl ketones were
obtained in moderate to excellent yields. In addition, chemo-
selective migration of the two different aryl groups was observed
in the reaction. Currently, experiments toward enlarging the
scope of the system to the synthesis of other phosphinylated
compounds and further mechanistic studies are underway in
our laboratory.
We gratefully acknowledge the Natural Science Foundation of
China (no. 21172162, 21372174), the Young National Natural
Science Foundation of China (no. 21202113), the Ph.D. Programs
Foundation of Ministry of Education of China (2013201130004),
Key Laboratory of Organic Synthesis of Jiangsu Province
(KJS1211), PAPD, and Soochow University for financial support.
a structurally similar heterocyclic allylic alcohol to 1o was introduced
into the reaction with 2a, no migrated product was observed, a
g-C–H bond phosphinylated product 3pa was isolated in 36% yield.
We supposed that the reaction, after diarylphosphonyl radical attack
to the g-position of 1p, was more prone to direct oxidation/deproto-
nation11d,12g than aryl rearrangement due to the presence of an
oxygen atom.
With respect to the diphenyl phosphine oxides, in addition
to dialkyl phosphonates 2c and 2d, ethyl phenylphosphinate 2b
was a suitable candidate for this transformation, also under-
went smoothly addition/rearrangement to afford the corres-
ponding products 3ab, 3cb and 3db in medium to good yields,
respectively (Scheme 3).
Further synthetic transformations of the a-aryl-b-phosphinyl
ketone products were investigated (Scheme 4). With the
reduction of lithium aluminium hydride, 3aa can be converted
into the corresponding g-benzoyl phosphine oxide 4a, which
was an important class of intermediates in the synthesis of the
cyclopropane ring20 and P-ligands.21 Moreover, the tertiary
alcohol 4b was obtained in 79% yield by the reaction of the
ketone with an aryl Grignard reagent.
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Scheme 4 Further transformations of the a-aryl-b-phosphinyl ketones.
Scheme 5 Proposed reaction mechanism.
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