Zinc-catalyzed transformation of diarylphosphoryl azides to diarylphosphate esters and amides

Article abstract of DOI:10.1002/asia.202000154

We have developed a facile and efficient procedure for the synthesis of diarylphosphate esters and amides. Using Zn(acac)₂ as the catalyst, the reaction of diarylphosphoryl azides with aliphatic alcohols and phenols through an unusual P?N bond cleavage provided a number of diarylphosphate esters in good yields (22 examples, up to 94%). Additionally, various diarylphosphate amides were obtained from the corresponding amines in excellent yields as well (8 examples, up to 96%).

Full text of DOI:10.1002/asia.202000154

CHEMISTRY
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Accepted Article
Title: Zinc-catalyzed transformation of diarylphosphoryl azides to
diarylphosphate esters and amides
Authors: Jun Ying, Qian Gao, and Xiao-Feng Wu
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To be cited as: Chem. Asian J. 10.1002/asia.202000154
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10.1002/asia.202000154
Chemistry - An Asian Journal
COMMUNICATION
Zinc-catalyzed transformation of diarylphosphoryl azides to
diarylphosphate esters and amides
Jun Ying,a Qian Gao,a and Xiao-Feng Wu*[a,b]
[a]
Dr. J. Ying, Q. Gao, Prof. Dr. X.-F. Wu, Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou 310018, People’s Republic of China
E-mail: xiao-feng.wu@catalysis.de
[b]
Leibniz-Institut für Katalyse e. V. an der Universität Rostock, Albert-Einstein-Straβe 29a, 18059 Rostock, Germany
Supporting information for this article is given via a link at the end of the document.
Abstract: In this communication, we have developed a facile and efficient
procedure for the synthesis of diarylphosphate esters and amides. Using
Zn(acac)2 as the catalyst, the reaction of diarylphosphoryl azides with
aliphatic alcohols and phe-nols through an unusual P-N bond cleavage
provided a number of diarylphosphate esters in good yields (22 examples,
up to 94%). Additionally, various diarylphosphate amides were achieved
from the corresponding amines in excellent yields as well (8 examples, up
to 96%).
Phosphate esters and amide s have been considere d as ke y
structural moieties in organophosphorous che mistry, which
are fre quently found in natural products, mate rials,
pharmaceutical pre cursors, and bioactive compounds.1-4 For
example, DHPP -OH-BAC, be aring a couple of phosphate unit s,
can be employe d as an excellent flame retardant for epoxy
resin.5 PB-1 is an ichthyotoxin re sulting in the de ath of
numerous se a cre atures and was isolate d from Ptychodiscus
brevis.6 Compound A can be use d as an e ffective nucleotide
prodrug for the treatment of HIV disease.7
Scheme 1. Selected examples of phosphate esters and amides.
In order to establish the se intriguing motifs in a wide
range of applications, treme ndous synthetic methods have
been reporte d.8-10 Over the past decade s, phosphoryl azide s
have bee n widely utilized as a powerful phosphorus re age nts
in various transition-metal-catalyze d transformations to
construct organophosphorous compounds.11 Among the m,
phosphate amide s can be synthe size d via direct C-H
amidation of phosphoryl azide s using transition metal
catalysts such as Co, Rh, and Ir.10 In this procedure, with the
cleavage of N-N bond followed by the formation of a M-N
bond, a nitrogen atom can be introduced into phosphate
amides from phosphoryl azides. Very recently, Jiao and Ma
At the outset, when the diphenylphosphoryl azide 1a was
treate d with 2 equiv of Me OH in the abse nce of a metal
catalyst, the e xpecte d product 2aa was not observed (Table 1,
entry 1). Then, a couple of zinc catalysts were inve stigate d,
and the re sults were summarize d (Table 1, entries 2 -8). It was
found that the re action employing Zn(acac)2 as the catalyst
gave the highe st yield (51%; Table 1, entry 6). Gratifyingly,
with the addition of 0.5 equiv of Na2CO3, the re action yield
was re markably improve d to 74% (Table 1, entry 9).
Moreover, extending the reaction time to 3.5 h can furthe r
increase the yield of 2aa (82%), while the yield was re duce d
to 68% as it furthe r prolonge d (Table 1, entries 10 and 11).
Subse quently, a se ries of solvents were te ste d, and it was
shown that the re action using dioxane as the solve nt can
enhance the yield to 90 % (Table 1, e ntries 12 -15). Finally,
either lowe ring or raising the te mpe rature hampered the
reaction (Table 1, entries 16 and 17). Additionally, when CuCl
was used as the catalyst, only 31% of 2aa was obtained.
disclosed
transformation
the
first
of
example
diphenylphosphoryl
on
coppe r-catalyze d
azide s to
diphenylphosphate e sters.12 Notably, this method fe ature s
an unusual cle avage of P -N bond of diphe nylphosphoryl
azide s in comparisons with the pre vious re ports. Howeve r,
the reaction requires a large exce ss of aliphatic alcohols as
the nucleophile and as solvent as well. Inspire d by their
remarkable advance, we now report
a novel and facile
method to acce ss diphenylphosph ate e sters and amide s from
diphenylphosphoryl azides under zinc catalysis.
1
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Table 1. Screening of the Reaction Conditions with 1a.a
Entry
1
[Zn]
—
Additive
—
Solvent
Yield (%)
0
cyclohexane
cyclohexane
cyclohexane
cyclohexane
cyclohexane
cyclohexane
cyclohexane
cyclohexane
2
Zn(OAc)2
ZnCl2
—
17
3
—
5
4
ZnBr2
—
trace
5
5
ZnI2
—
6
Zn(acac)2
ZnSO4·7H2O
Zn(OTf)2
—
51
7
—
trace
trace
74
8
—
9
Zn(acac)2 Na2CO3 cyclohexane
Zn(acac)2 Na2CO3 cyclohexane
Zn(acac)2 Na2CO3 cyclohexane
10b
11c
12b
13b
14b
15b
16b,d
17b,e
82
68
Zn(acac)2 Na2CO3
Zn(acac)2 Na2CO3
Zn(acac)2 Na2CO3
Zn(acac)2 Na2CO3
Zn(acac)2 Na2CO3
Zn(acac)2 Na2CO3
DCM
40
MeCN
82
dioxane
DMSO
dioxane
dioxane
90
13
76
84
aReaction condition: 1a (0.5 mmol), Zn catalyst (10 mol %), CH3OH (2.0 equiv),
additive (0.5 equiv), solvent (2.0 mL), 60 ℃, 3 h, isolated yield. b3.5 h . c4 h. d40
℃. e80 ℃.
Next, the optimal re action conditions were applied to
various aliphatic alcohols and phenols (Sche me 2). The
reaction of simple linear alcohols gave the corre sponding
products 2aa-af in good yields. It was noted that substrate s
bearing functional groups such as double bond, triple bond,
trifluromethyl, and chlorine could be converted to products
2ag-aj smoothly in high yields. Furthermore, when secondary
alcohols were treate d, much lower yields of products 2ak-al
were achieve d. Unfortunately, the re action with tert -butyl
alcohol gave only trace amount of product 2am. To our
delight, a serie s of phenols with either electron -donating or
electron-withdrawing substituents afforde d the e xpecte d
products 2an-ar in excellent yields as well.
Scheme 2. Scope of Aliphatic Alcohols and Phenols.a aReaction condition: 1a (0.5
mmol), Zn( acac)2 (10 mol %), ROH (2.0 equiv), Na2CO3 (0.5 equiv), dioxane (2.0
mL), 60 ℃, 3.5 h, isolated yield. b6 h. c4.5 h. d24 h.
The n, we turn to inve stigate the re action of other
phosphoryl azides with Me OH and the results were shown in
Sche me 3. The Me-substituted phosphoryl azide could
undergo the reaction e fficiently to afford product 2ba in 89%
yield. Neve rthele ss, only 51% yield of product 2ca was
obtained for the substrate with a tBu group. For compounds
with electron-withdrawing substitue nts such as bromine and
chlorine, the reaction gave products 2da and 2ea in 57% and
60% yields, respectively.
2
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10.1002/asia.202000154
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with Me OH, affording the desired product 2aa in 88% yield
(0.69g; Sche me 5, eq 1). Moreover, when 1a was treate d
with
2 e quiv n-propanol and 2 e quiv n-propylamine
simultaneously, 41% of 2ac and 45% 3aa were obtaine d,
suggesting that they exhibite d similar reactivity in this
reaction (Sche me 5, eq 2). Finally, when 2,2,6,6-tetramethyl -
1-pipe ridinyloxy (TEMPO) was adde d as the radical scave nge r,
90% of product 2aa was achieve d (Sche me 5, eq 3). This
result indicated that the radical process was ruled out.
Scheme 3. Scope of Phosphoryl Azides.a aReaction condition : 1 (0.5 mmol) ,
Zn(acac)2 (10 mol %) , MeOH (2.0 equiv), Na2CO3 (0.5 equiv), dioxane (2.0 mL),
60 ℃, 3.5 h, isolated yield. b12 h. c20 h. d1 (0.25 mmol).
Subse quently, a variety of aliphatic primary amine s were
subjected to the modified re action conditions as well
(Sche me 4). It was shown that the line ar amines we re
succe ssfully transforme d to the desire d products 3aa-ad in
85-96% yields. Compounds be aring a branched alkyl group or
a carbocycle unit were also compatible, furnishing products
3ae-ag in good yields. In addition, the re action with 2 -
propynylamine afforded the targe t product 3ah in 44% yield.
It is also important to mention that pipe ridine and aniline
were te sted as well, low re action e fficiency was obtaine d in
these two cases.
Scheme 5 Further Investigation on the Reaction of 1a.
In conclusion, we have developed
a zinc-catalyzed
synthe sis of diphenylphosphate e sters and amide s from
diphenylphosphoryl azide s. The transformations with
alcohols and amine s procee d well under mild conditions,
affording the corresponding products in good yields.
Keywords: Zinccatalyst • diphenylphosphate esters•
diphenylphosphate amides• diphenylphosphoryl azides• Lewis
acid
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4
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Entry for the Table of Contents
A zinc-catalyzed synthesis of diphenylphosphate estersand amidesfrom diphenylphosphorylazides has been developed. The
transformationswith alcoholsand aminesproceed wellunder mild conditions, affording the corresponding products in good yields.
5
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