Chemoselective Reduction of the P=O Bond in the Presence of P–O and P–N Bonds in Phosphonate and Phosphinate Derivatives

Article abstract of DOI:10.1002/ejoc.201801518

Chemoselective reduction of the strong P=O bond in the presence of weaker P–O (ester) and P–N (amide) bonds in phosphonic acid derivatives has constituted an unresolved problem in organophosphorus chemistry for years. This long-standing problem is now solved for biologically relevant α-hydroxy and α-amino phosphonic as well as phosphinic acids esters and amides. The reduction of the P=O bond without concomitant scission of the ester and amide bonds is affected by use of BH₃, a mild reducing agent, which affords the corresponding borane protected P^III phosphonite and phosphinite derivatives in one step. A mechanistic rationale is proposed for the role played by neighboring OH and NHR groups in facilitating the reduction, and for the observed chemo- and stereoselectivity. The reduction methodology described opens previously unavailable synthetic options in chemistry of α-functionalized phosphonic and phosphinic acids by offering a unique possibility for direct modifications of oxidation level of the P-center in these compounds.

Full text of DOI:10.1002/ejoc.201801518

A Journal of
Accepted Article
Title: Chemoselective reduction of the P=O bond in the presence of P-
O and P-N bonds in phosphonate and phosphinate derivatives
Authors: Sylwia Sowa and Kazimierz Michał Pietrusiewicz
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201801518
Link to VoR: http://dx.doi.org/10.1002/ejoc.201801518
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10.1002/ejoc.201801518
European Journal of Organic Chemistry
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Chemoselective reduction of the P=O bond in the presence of P-
O and P-N bonds in phosphonate and phosphinate derivatives
Sylwia Sowa, K. Michał Pietrusiewicz*[a]
Abstract: Chemoselective reduction of the strong P=O bond in the
presence of weaker P-O (ester) and P-N (amide) bonds in
phosphonic acid derivatives has constituted an unresolved problem
in organophosphorus chemistry for years. This long-standing
problem is now solved for biologically relevant -hydroxy and -
amino phosphonic as well as phosphinic acids esters and amides.
The reduction of the P=O bond without concomitant scission of the
ester and amide bonds is effected by use of BH3, a mild reducing
agent, which affords the corresponding borane protected P(III)
phosphonite and phosphinite derivatives in one step. A mechanistic
rationale is proposed for the role played by neighboring OH and
NHR groups in facilitating the reduction, and for the observed
chemo- and stereoselectivity. The reduction methodology described
opens up previously unavailable synthetic options in chemistry of -
functionalized phosphonic and phosphinic acids by offering a unique
possibility for direct modifications of oxidation level of the P-centre in
these compounds.
of reducing agents with two early[13] and one recent[14] reported
exceptions. A demand for methods enabling chemoselective
reduction of the P=O bond inthe presence of either ester or
amide bonds because these could open up completely new
possibilities for preparation of various P(III) ester and amide
derivatives directly from their usually much more readily
available and robust pentavalent P=O counterparts.
Phosphine borane adducts, soon after their introduction[15a] as
easily handled and storable equivalents of P(III) compounds,
and versatile synthetic reagents per se,[15b] quickly started to
become preferred targets in synthesis of P(III) compounds
replacing sensitive and difficult-to-handle non-protected
phosphines. In this context, the direct transformation of
phosphine oxides into phosphine-boranes, thus avoiding
handling and/or isolation of the free phosphines has become a
new challenge in the synthesis of trivalent phosphorus
compounds.[14,16] In much the same vein, the development of
new reducing procedures that could use BH3 as the complexing
agent and also as the reducing agent is gaining growing
attention due character of BH3.[17-19]
Recently, we[19] and Buono[20] demonstrated that the reduction of
P=O bond by BH3 complexes in functionalized tertiary phosphine
oxides bearing neighboring assisting groups, e.g., –OH, -SH,
and –NHR, is possible, and that it can be regarded as an
attractive alternative to the conventional reduction protocols.
Furthermore, earlier observations by Kiełbasiński[17e,21] and more
recent work by Buono[20,22] have shown that the phosphinate
P=O bond can be also reduced by BH3 to give the
corresponding phosphinite-borane with high chemoselectivity
when a hydroxy group is present in the proximity of the
phosphoryl group. For the first time, it therefore seems
reasonable to assume that there is a really good prospect for
successfully addressing a long-sought possibility of reduction of
P=O bond in phosphonic acid esters and amides without
affecting their P-O and P-N bonds.
Introduction
Many strategies for the preparation of phosphines are based on
the reduction of a strong P=O bond in the final synthetic step.[1-2]
The stability of P-C bond allows for the use of strong reducing
agents (metal hydrides,[3] silanes[4]) which usually leads to highly
efficient deoxygenation of phosphine oxides. However, these
typically harsh reagents are a major drawback when the
reductions of compounds possessing other reactive
functionalities[5] or chirality centres[3f,6] at the phosphorus need to
be performed, though some progress in this field has been
made.7 Nevertheless, these methods are generally useless for
the reduction of strong P=O bonds in phosphonic and
phosphinic acid derivatives that contain much weaker and more
reactive P-O or P-N bonds is to be accomplished. The reaction
of various reducing agents (metal hydrides,[8] organoboron
hydride,[9] PHMS,[10] Ph2SiH2,[10] Ph2SiH2/Lewis acid or
Herein, we present our results concerning unprecedented
chemoselective BH3 reductions of phosphonic P=O bond
assisted by neighboring –OH and –NHR groups. The reductions
lead directly to the formation of the pertinent -hydroxy and -
amino phosphonite-boranes from their easily available and
robust P=O precursors. This seems valuable, given that
functionalized -hydroxy phosphonite-boranes have currently
only been obtained through multistep protocols.[23] To the best
of our knowledge, -amino phosphonite-boranes as well as -
amino phosphinite-boranes have been neither studied nor
synthesized before, despite their direct structural analogy to
biologically highly relevant -amino phosphonic and -amino
phosphinic acid derivatives.[24]
PhSiH3/Lewis acid[11]
) with phosphinates or phosphonates
typically leads to the reduction of all phosphorus-oxygen bonds
in what constitutes a valuable preparation of secondary and
primary phosphines, respectively. Similarly, phosphinic acid
amides typically undergo P-N bond[12] cleavage in the presence
[a]
Dr. S. Sowa, Prof. K. M. Pietrusiewicz
Department of Organic Chemistry
University of Maria Curie-Sklodowska
Gliniana 33 St., 20-614 Lublin, Poland
E-mail: kazimierz.pietrusiewicz@poczta.umcs.lublin.pl
www: https://orgchem.umcs.lublin.pl
Supporting information for this article is given via a link at the end of
the document.
1
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10.1002/ejoc.201801518
European Journal of Organic Chemistry
FULL PAPER
Results and Discussion
(isolated) together with two over-reduction products 3a and 5a
(not isolated) (Table 1, entry 5). Changing the BH3 source to
BH3-SMe2 gave promising results according to 31P NMR but the
desired 2a was isolated only in very poor 7% yield (Table 1,
entry 6). Increasing the amount of BH3-SMe2 to 5 or 10
equivalents under the same conditions gave only traces of 2a
and provided primary phosphine-borane 5a as the major product
(Table 1, entries 7-8). Therefore, for further study we choose the
conditions used in entry 5, i.e., BH3-THF, 60 C, 24 h,
considered as the most appropriate.
The initial experiments were carried out with diisopropyl
hydroxymethylphosphonate (1a) as a model compound (Table
1). As shown in entries 1 and 4 of Table 1, 1a was found to be
practically unreactive or slowly reacting when exposed to 3 or 10
equiv. of BH3-THF at room temperature. Increasing the
o
temperature to 60 C with 3-fold excess of BH3-THF resulted in
the formation of primary phoshine 4a (Table 1, entry 2). When
1a was treated with 10 equiv. of BH3-THF at 60 C for 24 h, it

partially successfully underwent reduction of the P=O bond, the
desired phosphonite-borane 2a was obtained in only 20 yield
Table 1. Attempted optimizing of the reaction conditions for reduction of 1a with BH3 complexes.
BH3
P
BH3
P
O
P
X
P
BH3 complex
OH
+
OH
OH
OH
+
i-PrO
i-PrO
H
i-PrO
i-PrO
H
THF, conditions,
24 h
H
i-PrO
2a
4a X = lone pair
5a X = BH3
1a
3a
No
Conditions
Yields of Products (%)[a,b]
1
2
3
4
5
6
7
8
BH3-THF (3.0), rt
BH3-THF (3.0), 60 C
BH3-THF (5.0), 60 C
BH3-THF (10.0), rt
2a 0 (0)
2a 0 (0)
3a 0 (0)
3a 0 (0)
3a 0 (39)
3a 0 (0)
3a 0 (12)
3a 0 (0)
3a 0 (8)
3a 0 (11)
4a/5a 0 (0)
4a 0 (100)
5a 0 (40)
5a 0 (0)
2a 6 (20)
2a traces
2a 20 (28)
2a 7 (41)
2a 0 (8)
BH3-THF (10.0), 60 C
BH3-SMe2 (3.0), 60 C
BH3-SMe2 (5.0), 60 C
BH3-SMe2 (10.0), 60 C
5a 0 (60)
4a 0 (59)
5a 0 (77)
5a 0 (74)
2a 0 (17)
[a] Isolated yields of product. [b] Numbers in parentheses indicate yields according to 31P NMR.
Results of the reductions subsequently carried out with a series
of structurally diversified -hydroxy phosphonates 1b-g under
these conditions are presented in Table 2 and are compared to
the reduction of 1a. Quite unexpectedly, analogous reduction of
sterically more demanding di-t-butyl phosphonate 1b failed to
give any identifiable product. Instead, complete decomposition
of the starting material was observed even at 0 C (Table 2,
entries 2 and 3). This result is in sharp contrast to the earlier
its pure form, or after attempted boranation or oxidation, led to
its decomposition. In contrast to analogous BH3 reductions of -
hydroxy phosphinates,[17e,22b] it seems clear that increased steric
demand of the phosphonate ester groups, or their incorporation
into a ring, dramatically increases their reactivity under the
studied reaction conditions.
We next investigated the effect of -substitution pattern on the
chemoselectivity of P=O bond reduction in -hydroxy
phosphonates. For phosphonate 1d, which has a single Me
substituent at the  carbon the reduction chemoselectivity was
slightly higher than for the unsubstituted 1a and gave -hydroxy
phosphonite-borane 2d in 25 yield (isolated) with palpably
diminished contribution from over-reduction products 3d and 5d
(not isolated). (Table 2, entry 4). To our delight, use of
compounds with double substitution at the  carbon resulted in
significantly more selective reduction of the P=O bond. Both 1e
and 1g underwent reduction with an excess of BH3-THF (10
equiv.) at room temperature to afford the corresponding
phosphonite-boranes 2e and 2g as the major products isolated
observations
on
similar
BH3
reductions
of
hydroxymethylphosphinates for which chemoselectivity towards
P=O bond cleavage increased with the steric demand of the
ester group.[17e,22b]
Reduction of a cyclic phosphonate 1c went faster than for 1a
and was completed with
3 equiv. of BH3-THF at room
temperature within 4 h. Interestingly, it led to complete reduction
of not only the P=O bond but also the two P-O bonds (Table 2,
entry 3), providing the primary hydroxymethylphosphine (4a) as
essentially the only product (by 31P NMR of the crude reaction
mixture, P = -121.52 ppm). Attempted isolation of 4a, in either
2
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10.1002/ejoc.201801518
European Journal of Organic Chemistry
FULL PAPER
in 72 and 49 yield, respectively (Table 2, entries 5 and 7). In
these cases, small amounts of over-reduction products 3e and
3g, from reduction of both phosphoryl P=O and one P-O bond
were also isolated in 9 and 6 yield, respectively. Products
resulting from complete reduction of all phosphorus-oxygen
bonds were also observed in both cases in the 31P NMR spectra
The data collected in Table 2 indicate that in favourable cases
the P=O bond in -hydroxy phosphonates can be indeed
reduced by BH3 without simultaneous cleavage of the ester
bonds. However, the observed degree of chemoselectivity
depends on the substitution pattern in both the ester groups and
the chain. Bulky or cyclic ester groups, promote nonselective
of the crude reaction mixtures but their attempted isolation failed. reduction while increased substitution at the -carbon leads to
Interestingly, attempted reduction of a cyclic ,-dimethyl-
substituted -hydroxy phosphonate 1f failed completely and led
to decomposition of the substrate in spite of its apparently
promising geminal ,-disubstitution pattern (Table 2, entry 6).
This behaviour of 1f seems to resemble cyclic
hydroxymethylenephosphonate 1c although in the case of 1f the
primary phosphine product has not been even detected.
selective P=O bond cleavage with chemoselectivity of up to
75being achieved in the best case. In all cases, both BH3-THF
and BH3-SMe2 complexes were evaluated and, generally, the
former gave superior results. These results clearly show that the
developed protocol can constitute a very practical alternative to
the known protocols for the synthesis of -hydroxy phosphonite-
boranes.[23]
Table 2. Reactivity of-hydroxy phosphonates 1 towards BH3-THF.
BH3
P
BH3
P
O
X
P
BH3-THF (10 equiv.)
THF, 60 oC, 24 h
P
OH
R4
OH
R4
OH
+
+
OH
R4
R1O
R2O
R1O
H
H
4
H
R2O
R2O
R3
R3
R
R3
R3
1
2
3
4 X = lone pair
5 X = BH3
Entry
Compound
R1 = R2
R3
R4
Yields of Products (%)[a,b]
1
2
1a
1b
1b
1c
1c
1d
1d
1e
1e
1f
i-Pr
H
H
H
H
2a 20 (28)
2b 0 (0)
3a 0 (12)
3b 0 (0)
3b 0 (0)
3c 0 (0)
3c 0 (0)
3d 0 (10)
3d 0 (17)
3e 0 (9)
3e 9 (11)
3f 0 (0)
5a 0 (60)
-
t-Bu
3[c,d]
4
t-Bu
H
H
2b 0 (0)
-
-CH(CH3)CH2CH2-
H
H
2c 0 (0)
5a 0 (98)
4a 0 (90)
5d 0 (30)
5d 0 (33)
5e 0 (10)
5e 0 (5)
5e 0 (95)
5g 0 (7)
5g 0 (10)
5[e]
6
-CH(CH3)CH2CH2-
H
H
2c 0 (0)
i-Pr
i-Pr
Me
Me
Me
Me
Me
H
2d 31 (60)
2d 25 (35)
2e 71 (78)
2e 72 (75)
2f 0 (5)
7[f]
8
H
i-Pr
Me
Me
Me
9[g,h]
10
11
12[i]
i-Pr
-(CH2)3-
i-Pr
1g
1g
-(CH2)5-
-(CH2)5-
2g 67 (88)
2g 49 (60)
3g 0 (5)
3g 6 (9)
i-Pr
[a] Isolated yields of product. [b] Numbers in parentheses indicate yields according to 31P NMR. [c] BH3-THF (10.0), 0 C, 4 h. [d] Complete decomposition of
starting material was observed. [e] BH3-THF (3.0), rt, 4 h. [f] BH3-SMe2 (3.0), 60 C, 16 h (seemingly the best conditions suggested by the optimization study of
reductions of 1a; Table 1, entry 5). [g] Reaction was run at rt. [h] 3e was isolated only in a mixture together with 2e (9 yield determined by 1H NMR). [i] BH3-THF
(5.0), rt, 16 h.
To check the generality of the influence of -substitution we also
carried out experiments with structurally related -hydroxy
phosphinates 6 possessing single ester group at P and differing
in substitution at the -carbon atom (Scheme 1).
3
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10.1002/ejoc.201801518
European Journal of Organic Chemistry
FULL PAPER
BH3
P
BH3
O
BH3 complex
P
OH
R2
OH
P
OH
R2
+
EtO
Ph
H
EtO
THF, conditions
2
R1
R1
Ph
R
Ph
R1
1
2
47%[a] (61%)[b]
10%[a] (28%)[b]
8a
6a
BH3-THF (10.0), 60 oC, 24 h
BH3-SMe2 (5.0), rt, 16 h
(R = H, R = Me)
7a
6a (R1 = H, R2 = Me)
6b (R1 = R2 = Me)
7a 16%[a] (30%)[b]
8a 19%[a] (54%)[b]
8b 0%[a] (10%)[b]
BH3-THF (10.0), 60 oC, 24 h
BH3-THF (3.0), rt, 24 h
75%[a] (87%)[b]
74%[a] (91%)[b]
7b
7b
1
2
0%[a] (0%)[b]
6b
(R = R = Me)
8b
6b (R1 = R2 = Me)
BH3-SMe2 (3.0), rt, 16 h
7b 57%[a] (66%)[b]
8b 0%[a] (10%)[b]
8c 0%[a] (14%)[b]
BH3-THF (10.0), 60 oC, 24 h
BH3-SMe2, (3.0), 60 oC, 16 h
6c (R1 = R2 = -(CH2)5-
7c
7c
71%[a] (81%)[b]
62%[a] (67%)[b]
1
2
14%[a] (20%)[b]
6c
(R = R = -(CH2)5-
8c
[a] Isolated yields of product. [b] Numbers in parentheses indicate yields according to 31P NMR.
Scheme 1. Reduction of P=O bond in -substituted -hydroxy phosphinates 6.
As with the reductions of
discussed above, the best results were obtained for the
phosphinates 6b and 6c which have double substitution at

-hydroxy phosphonates
1
reductions occur with clean inversion of configuration at the P-
center as already established[21] and as implied by the proposed
mechanisms.[19,22b] Such
a
chemo- and stereoselective
the

carbon atom. The target phosphinite-boranes 7b and
and 62
transformation is thus likely to gain considerable importance in
the field of synthesis of optically active P-stereogenic P(III)
compounds since the starting P-resolved -hydroxy
phosphinates can be easily obtained from (RP)-9 and a rich
variety of carbonyl compounds based on cheap L-menthol as
the chiral auxiliary (cf. Scheme 2).
7c were isolated as major products in 74


isolated yield, respectively. In two cases, small amounts of
over-reduction products were observed and the
corresponding secondary phosphine-boranes 8a and 8c
were isolated in 19
 and 14 yield, respectively. The use
of BH3-THF was again found to be more appropriate than
BH3-SMe2.
Next, in order to address the stereoselectivity of the
reductions of the P=O bond in the presence of an ester P-O
bond, we turned our attention to P-resolved stereogenic (L)-
O
[a]
P
PhPCl2
MenthylO
Ph
(RP)-9 38% (1 dia)
H
menthyl
-hydroxy phosphinates (SP)-10a and (SP)-10b
whose relatively ready availability contrasts with the
potentially very inaccessible, and probably currently
[b]
[c]
unknown, resolved P-stereogenic -hydroxy phosphonates.
O
P
O
P
The P-resolved phosphinates were obtained from (RP)-9 which
had been prepared in 38 yield according to the procedure
reported by Mislow,[6c] Letsinger[6d] and Han,[25] (Scheme 2, step
a). (RP)-9 was reacted with formaldehyde and with
cyclohexanone (Scheme 2, steps b and c) to afford the requisite
-hydroxy phosphinates (SP)-10a and (SP)-10b, respectively, in
good yields and with excellent stereoselectivity (Scheme 2,
steps d).
Reduction of (SP)-10a (Scheme 2, step d) with 5 equivalents of
BH3-SMe2 at 60 C for 24 h led to the complete conversion of the
substrate. The expected formation of the desired phosphinite-
borane (RP)-11a (45 yield, isolated; 80 by 31P NMR) was
accompanied by the formation of the corresponding secondary
phosphine-borane 12 (15 yield, isolated), in good accord with
the previously reported reduction of (SP)-10a.[22b]
OH
OH
MenthylO
MenthylO
Ph
Ph
10a
(SP)-
89% (1 dia)
10b
(SP)-
40% (dr = 10:1)
[d]
[d]
BH3
OH
P
BH3
P
OH
Ph
Ph
MenthylO
MenthylO
45%(80%)[e] (1 dia)
(RP)-11b 60% (1 dia)
(100% dr = 10:1)[e,f]
11a
(RP)-
[a] According to reported procedures.6c,25
In turn, reduction of (SP)-10b (dr = 10:1) under the same
conditions (Scheme 2, step d) proceeded with complete
chemoselectivity and afforded phosphinite-borane (RP)-11b (dr =
10:1) as the sole product (100 by 31P NMR) isolated in 60
yield in the form of a pure diastereoisomer. The latter result
confirms again that geminal substitution at the  carbon
markedly enhances chemoselectivity of the reduction towards
reduction of the P=O bond. Importantly also, the studied
[b] DBU (0.01 equiv.), (CH2O)n (3 equiv.), THF, rt, 6 d.
[c] Cyclohexanone (4 equiv.), 60 oC, 48 h.
[d] BH3-SMe2 (5 equiv.), 60 oC, 24 h. [e] Numbers in
parentheses indicate yields according to 31P NMR
spectrum of crude reaction mixture. [f] Only major
diastereoisomer was isolated.
4
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10.1002/ejoc.201801518
European Journal of Organic Chemistry
FULL PAPER
Scheme 2. Synthesis of P-stereogenic (L)-menthyl -hydroxy phosphinates
10a and 10b and their reactivity towards BH3-SMe2 complexes.
It was rewarding to find that two of these three compounds
underwent completely chemoselective
-OH-assisted
reduction of P=O bonds by BH3 complexes. In case of
monoester monoamide 13 and N,N-diisopropyl bis(amide)
15 the only products observed in the crude reaction mixture
were the desired borane-protected P(III) derivatives 16 and
The next classes of hydroxymethylphosphonic acid derivatives
used for test reactions were represented by phosphonic acid
monoester monoamide 13 and bis(amides) 14 and 15 (Scheme
3).
18. Their isolated yields were moderate to good (60
 and
78 , respectively) probably because of decomposition

during purification on silica. Intriguingly, N,N-diethyl
bis(amide) 14 appeared to be less stable under the reaction
conditions and the desired product 17 was obtained in an
BH3
O
BH3-THF (10 equiv.)
P
OH
P
OH
unexpectedly low yield (22
The utility of BH3 as a mild and highly chemoselective
reducing agent for the direct reductive conversion of
hydroxy phosphinates and -hydroxy phosphonates into the
pertinent -hydroxy phosphinite-boranes and -hydroxy
phosphonite-boranes described above prompted us to
check if -amino phosphinates and -amino phosphonates
).
R2N
R1
R2N
R1
THF, rt, 24 h
-
13 R = Et, R1 = i-PrO
16-18

1
14
R = Et, R = Et2N
15 R = i-Pr, R1 = i-Pr2N


BH3
BH3
P


BH3
P
could also undergo an analogous chemoselective reduction
of their P=O bonds by BH3 complexes. These compounds
are important classes of organophosphorus compounds
which function in biology, medicine, pharmacology,
agriculture, as well as in synthetic chemistry as phosphorus
OH
P
OH
OH
i-Pr2N
i-Pr2N
20%[a] (30%)[b] 18
Et2N
i-PrO
16
Et2N
Et2N
17
60%[a] (100%)[b]
78%[a] (100%)[b,c]
[a] Isolated yields of product. [b] Numbers in parentheses
indicate yields according to 31P NMR. [c] Reaction was
run at 60 oC.
analogues of naturally occurring

-amino acids.[24] The
chemoselective reduction of their P=O bonds would enable
access to their new borane protected P(III) derivatives and,
by extension,[26] to other P(V) chalcogenide counterparts.
Scheme 3. Reduction of monoester monoamide 13 and bis(amides) 14 and
15 by BH3-THF.
First, we checked the possibility of chemoselective P=O bond
reduction assisted by NH group in -amino phosphinates 19
differing in size of the ester group (Scheme 4).
BH3
BH3
P
O
H
N
H
H
BH3-SMe2 (3 equiv.)
THF, 60 oC, 20 h
N
P
N
P
+
Ph
Ph
RO
Ph
RO
H
Ph
Ph
Ph
Br
Br
Br
20a R = i-Pr 84%[a] (100%)[b] dr = 1:0.7
19a R = i-Pr dr = 1:0.9
19b
20b
R = Et dr = 1:0.8
R = Et 60%[a] (64%)[b] dr = 1:0.8
0%[a] (36%)[b] dr = 1: 0.7
21
[a] Isolated yields of the product. [b] Numbers in parentheses indicate yields according to 31P NMR.
Scheme 4. Reaction of -amino phosphinates 19a and 19b with BH3-SMe2.
As found in a preliminary experiment, 19a remained unchanged
upon reaction with 10 equiv. of BH3-THF at 60 oC for 24 h, i.e.,
under conditions used above in reductions of -hydroxy
phosphinates (cf. Scheme 1). On the other hand, treatment of
19a and 19b with 3 equiv. of BH3-SMe2 at 60 C for 20 h led to
complete conversion of the substrates and afforded the target
markedly less selective and gave a 2:1 mixture of the desired
phosphinite-borane 20b (major) and a secondary phosphine-
borane 21 (minor) according to the 31P NMR spectrum of the
crude reaction mixture.
Encouraged by these promising results we turned to examine
the reactivity of -amino phosphonates 22a-l[27] towards BH3
phosphinite-boranes 20a and 20b in 84 and 60 isolated yield, complexes (Table 3). Given the higher stability of isopropyl
respectively. Reduction of isopropyl phosphinate 19a was
completely chemoselective and occurred with full preservation of
the ester P-O bond. Under the same conditions, reduction of
phosphinate 19b possessing the smaller ethyl ester group was
esters in the previous reactions we decided to focus only on
diisopropyl -amino phosphonates 22a-l which were all readily
prepared by Kabachnik-Fields reaction (see: Supplementary
Information).
5
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10.1002/ejoc.201801518
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Table 3. Reduction of N-aryl substituted -amino phosphonates 22 by BH3-SMe2.
BH3
P
O
H
H
H
N
R1
N
BH3-SMe2 (5 equiv.)
THF, 60 oC, 16 h
P
N
+
i-PrO
i-PrO
i-PrO
i-PrO
R1
22
R1
23
R2
R2
R2
24
Entry
Compound
R1
R2
Yields of Products (%)[a,b,c]
1
2[d]
3[e]
4[d]
5f
22a
22b
22b
22c
22d
22e
22f
Ph
Br
Br
Br
Br
Br
Br
Br
Br
23a 77 (100)
p-Br-C6H4
23b 47 [67]
23b 85 [100]
23c 38 [100]
23d 60 (96)
23e 79 (100)
23f 64 [100]
23g 50 (90)
23h 67 (90)
23i 63 (100)
23j 70 [100]
23k 24 [100]
23l 49 (77)
24b 7
24b 10
24c 45
p-Br-C6H4
o-Br-C6H4
m-NO2-C6H4
6
p-NO2-C6H4
7
p-An
H
traces
8[e,h]
9
22g
22h
22i
Ph
Ph
Ph
t-Bu
H
OH
OMe
Me
10
11
12
13[e,g]
22j
traces
traces
22k
Me
22l
Me
[a] Isolated yields. [b] Numbers in parentheses indicate yields according to 31P NMR of the crude reaction mixture. [c] Numbers in brackets indicate conversion of
the starting material. [d] Reaction run for 72 h. [e] Reaction run with 10 equiv. of BH3-SMe2. [f] Reaction run for 48 h. [g] Reaction run for 4 h; longer reaction time
led to lower yield of 23l.
Preliminary reduction attempts revealed that complete
conversion of 22 can be best achieved using 5 equiv. of
reducing agent at 60 C for 16 h, and that BH3-SMe2 performed
better than BH3-THF.The results of reductions performed on 22
are presented in Table 3.
In almost all cases the only product isolated from the
reaction mixture was the desired -amino phosphonite-borane
23. Importantly, no traces of any products resulting from ester
bond scission were detected even in cases when the reduction
was slow and required use of a larger excess of BH3-SMe2
and/or prolonged heating for 72 h.
Although, in general, the reduction of -amino
phosphonates was found to be little affected by substitution at
the N-phenyl group, the highest isolated yields of phosphonite-
boranes were achieved for -amino phosphonates possessing
the N-p-bromophenyl group, e.g., 22a,b, and e, respectively,
(Table 3, entries 1, 3 and 6). Similarly, the near quantitative 31P
NMR yields and conversions that were observed in most cases
show that, the substituents at the  carbon atom did not interfere
with the reduction process. Somewhat lower yields of isolated
products bearing either bulky aryl or bulky alkyl -substituent
(e.g., 23c,k) or of those not having -substituent, (e.g., 23g,l)
probably reflect their lower stability during workup (Table 3,
entries 4, 8, 12, 13).
The formation of small amounts of secondary amines 24
was observed in reductions of 22b,c and 22j,k (Table 3, entries
2-4,7,11,12). Of those substrates, 22c decomposed most
extensively under the reduction conditions and gave secondary
amine 24c as the main reaction product (Table 3, entry 4). The
reaction of 22c was very slow and heating for 72 h was
necessary to make conversion of this substrate complete. Under
the same conditions, 22b was even less reactive and full
conversion was not achieved under the standard reduction
conditions. However, use of 10-fold amount of reducing agent
led eventually to complete conversion and to production of the
6
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10.1002/ejoc.201801518
European Journal of Organic Chemistry
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Scheme 5. Reactivity of N-alkyl -aminophosphonates 24 and 25 towards
BH3-SMe2.
desired phosphonite-borane 23b in 85 yield together with 10
of amine byproduct 24b (Table 3, entry 2,3).
The observed formation of amine byproducts in these
reactions can be attributed to an instability of -amino
phosphinates 22b,c which underwent a retro-Kabachnik-Fields
process under the reaction conditions to give secondary
phosphite and an imine. These decomposition products reacted
further with BH3 to give the observed amine and, most probably,
(i-PrO)2P(BH3)OH ( 90.15 ppm according to 31P NMR, not
isolated).[28] It is also worth noting that 21c was checked to have
been thermally stable while heated without BH3 at 60 C for 24 h.
Apparently, the reaction conditions under study allow BH3 to act
also as a Lewis acid and facilitate the observed retro-Kabachnik-
Fields reaction in the more susceptible cases. It seems that the
substitution pattern and stability with respect to Lewis acid have
the biggest impact on the observed degradation of 22 by the
retro-Kabachnik-Fields process.
It was found that N-alkyl substituted phosphonate 25 underwent
complexation at nitrogen prior to reduction. Subsequent
reduction of P=O bond in this -amino phosphonate by 5 equiv.
of BH3-SMe2 was incomplete even after 48
h
at 60 C.
Nevertheless, we were able to isolate the expected P,N-
diborane 27 in 24 yield and, importantly, no traces of any
products with reduced ester bonds were detected. Increasing of
the amount of BH3-SMe2 to 10 equiv. did not lead to any
progress in the conversion of the substrate. Apparently, lowered
N-H acidity effectively slows down evolution of hydrogen and an
apparently prerequisite[19] formation of an N-BH2 bond. In this
context, it was not too surprising that compound 26 possessing
tertiary amine substituent failed to yield the reduction product 28
under the same reaction conditions. It should be noted however,
that a single precedent for BH3 reduction of P=O bond in a
tertiary phosphine oxide assisted by tertiary amine substituent at
the  position is on record.[20]
For comparison, we also briefly checked the reactivity of
N-alkyl substituted -amino phosphonates 25 and 26 under the
same reaction conditions (Scheme 5).
BH3
BH3
P
To check the possibility of deprotection of phosphonite-boranes
23 to their P(III) counterparts we subjected 23a to the reaction
conditions reported by Jugé and co-workers (Scheme 6).[26b] To
simplify the isolation process the deprotected phosphonite was
sulfurized in situ with S8 to give 29. It turned out that use of a
twofold excess of DABCO secures practically quantitative
conversion of 23a to 29 without detectable traces of oxidation or
decomposition.
O
P
R1
R2
R1
BH3-SMe2 (5 equiv.)
THF, 60 oC, 48 h
N
N
i-PrO
i-PrO
R2
i-PrO
i-PrO
27 24%[a](67%)[b]
28
25 R1 = CH2Ph, R2 = H
0%[a](traces)[b]
1
2
26
R = R = Et
[a] Isolated yields of product. [b] Numbers in parentheses
indicate yields according to 31P NMR
of crude reaction mixture.
DABCO (2 equiv.)
S8 (35 equiv.)
PhMe, 40 oC, 48 h
BH3
P
S
H
H
N
N
P
i-PrO
i-PrO
i-PrO
i-PrO
Ph
23a
Ph
Br
Br
29 88%[a](100%)[b]
[a] Isolated yields of product. [b] Numbers in parentheses indicate yields according
to 31P NMR of crude reaction mixture.
Scheme 6. Deprotection of -amino phosphonite 23a.
Finally, in order to compare the reactivity of different classes of
phosphonate compounds towards BH3-THF complex we have
of their substittion pattern (Table 4, entries 5-7). These results
confirm again that BH3-SMe2 complex should be considered as
collected in Table 4 the results of reductions of 1a,d,g,e and 19a, the reagent of choice for reduction of the P=O bond in -amino
22b, 25 under unified conditions. While -hydroxy phosphonates
1a,d,g,e underwent the expected reduction by BH3-THF (Table 4,
entries 1-4), the -amino phosphonates 19a, 22b, 25 were all
found to be inert to BH3-THF under these conditions, regardless
phosphonates as already demonstrated above in Table 3.
Table 4. Comparison of reductions of different classes of phosphonate compounds under unified conditions.
BH3
BH3
P
O
X
P
H
BH3-THF (10 equiv.)
THF, 60 oC, 24 h
P
XR4
R3
XR4
R3
XR4
R3
P
XR4
R3
+
+
H
i-PrO
R1
i-PrO
R1
H
R1
R2
R2
R2
R2
7
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10.1002/ejoc.201801518
European Journal of Organic Chemistry
FULL PAPER
No
Compound
Structure
Yields of Products (%)[a,b]
1
2
1a
1d
R1 = i-PrO, R2 = R3 = H, R4 = H, X = O
R1 = i-PrO, R2 = H, R3 = Me, R4 = H, X = O
R1 = i-PrO, R1 = R2 = -(CH2)5-, R4 = H, X = O
R1 = i-PrO, R1 = R2 = Me, R4 = H, X = O
2a 20 (28)
2d 31 (60)
2g 67 (88)
2e 71 (78)
20a 0 (0)
23 0 (0)
3a 0 (12)
5a 0 (60)
3a 0 (10)
4a 0 (30)
3
1g
3g 0 (5)
5d 0 (7)
4
1e
3e 0 (9)
5c 0 (10)
5[c]
6[c]
7[c]
19a
22b
25
R1 = Ph, R2 = Ph, R3 = H, R4 = p-Br-C6H4-, X = N
R1 = i-PrO, R2 = o-Br-C6H4-, R3 = H, R4 = p-Br-C6H4-, X = N
R1 = i-PrO, R2 = R3 = H, R4 = PhCH2, X = N
-
-
-
-
-
-
27 0 (0)
[a] Isolated yields of product. [b] Numbers in parentheses indicate yields according to 31P NMR. [c] Unreacted starting material present in the reaction mixture.
H
H
unfavoured
B
H
R1O
R2
B
H
O
P
O
P
H
O
P
O
P
path a
BH2
X
O
B
BH3
-H2
R1O
R2
X
X
R1O
XH
P
H
H
R1O
X
R1O
when R2 = Ph
or NEt2 or Oi-Pr
R2
H
R2
III
I
II
IV
V
R2
H
H
B
H
X = NR, O
S
path b
stereomutation
-H2
R1O
R2
O
B
OR1
BH2
X
O
P
R2
H
R2
P
X
H
O
P
VI
H
BH2
OR1
1. BH3
2. hydrolysis
X
(Buono )
X = O
VIIIb
VIIIa
BH3
P
XH
R2
R1O
c
path
BH2
X
BH2
X
O
R2
H
O
P
O
P
BH2
inversion
stereomutation
H
R2
H
P
X
when R2 = OR1
H
OR1
H
X
IX
XIV
H
H
S
B
H
O
H
H
H
O
B
P
H
B
R2
X
H
P
X
H
H
XV
H
H
XI
- H2
Y
O
B
1. BH3
2. hydrolysis
H
H
BH3
P
P
P
XH
O
R2
H
X
H
XH
R2
H
H
P
B
X
H
H
XVI
Y = BH3 or lp
XVII
racemic
XIII
XII
Figure 1. Unified mechanism for reduction of -hydroxy and -aminophosphinates/phosphonates by BH3 complexes.
8
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10.1002/ejoc.201801518
European Journal of Organic Chemistry
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In light of the above data, our earlier work[19] and previous
mechanistic proposals[20-22] we would like to propose a unified
mechanistic picture which addresses all the reaction paths and
current observations (Figure 1).
and Table 1, entries 5,7). Ultimately, by combining quaternary
substitution at the -carbon with a bulky, and therefore less
apicophilic[29] menthyl ester group in (SP)-10b, it was possible to
achieve the complete suppression of path b and allow fully
chemoselective reduction of the P=O bond via path a; this whilst
leaving the ester bond intact. Similar success was achieved with
the isopropyl -amino phosphinate 19a which bears a single -
phenyl substituent and with -aryl substituted diisopropyl -
amino phosphonates 22 (Scheme 4, and Table 2, respectively).
It is clear that when the -carbon is unsubstituted or bears small
(e.g., single methyl) substituent or, equally, if the ester group is
small, path b can become either competitive or dominant. Thus,
after departure of the OR1 group from VIIIb (or VIIIa), the
protonated cyclic intermediate IX picks up a hydride from
another molecule of BH3 to form TBP X. Subsequent opening of
the five-membered ring leads to XI which is stabilized by
evolution of a hydrogen molecule yielding free secondary
In the first step, BH3 undergoes reaction with the XH group of I
affording II along with evolution of a hydrogen molecule. The
formation of intermediate II is prerequisite for the coordination of
the resulting proximal boron functionality to the phosphoryl
oxygen which leads to a cyclic zwitterionic intermediate III. Such
a facile intramolecular coordination is made possible by the
presence of an assisting group at the  position which promotes
the formation of a five-membered dioxaboraphospholane ring.
The incorporation of the phosphoryl oxygen into a boronic acid
moiety makes it now a leaving group that is good enough to
compete for departure with the alkoxy ester groups. The
subsequent reduction entails a hydride attack trans-to the ring P-
O bond and allows a five-membered ring in trigonal bipyramide
(TBP) IV to be made between the favored apical (for P-O) and
equatorial (for P-C) positions.[29] This lowers its energy and
greatly facilitates the reduction process. The apical position of
the activated P-O bond allows its prompt stereoinvertive
departure in an SN2-like process that affords protonated
phosphine V; this promptly liberates a hydrogen molecule to give
phosphine XII (or H-phosphinite, when R2
=
OR1) which
undergoes complexation with BH3 (Figure 1).
For phosphonates where two single P-O bonds are present,
stereomutation[30] of X into XIV (path c) can again occur and this
places the second OR1 group in an apical position that enables
its departure. This path concludes with the observed formation
of a primary phosphine or phosphine-borane XVII.
a
free phosphine VI. Finally, complexation and hydrolytic
deprotection of the activating group in VI yields the product
phosphine-borane VII (Figure 1, path a).
In summary, it can be assumed that substitution at the -position
of the five-membered ring of III and/or the presence of bulky
ester or amide substituents (the latter constituting less
apicophilic and very poor leaving groups) aid the reduction
pathway that passes through a by making stereomutation of IV
less favorable. This proposal is nicely aligned with our
experimental results (vide supra) except in the case of cyclic
hydroxymethylphosphonate 1c, which was found to undergo
cleavage of all phosphorus-oxygen bonds upon treatment with
BH3. This result may reflect a swift stereomutation of TBP IV
(R1,R2 = -CH(CH3)CH2CH2O-) into a TBP of type VIIIb, which
allows both the six-membered dioxaphosphorinane ring and the
five-membered dioxaboraphospholane ring to adopt their
energetically favored apical-equatorial positions. Subsequent
preferential cleavage of an apical P-O ester bond starts a
Any competing BH3 attack on III trans- to the OR1 group would
require the five-membered ring to adopt a diequatorial span and
this is energetically disfavored.[29] Thus, the cleavage of the P-
OR bond in -hydroxy phosphinates that leads to formation of
the observed secondary phosphine-boranes must require
stereomutation[30] of TBP IV to place the OR group in the apical
position suitable for its departure.
Such a sequence of events has already been proposed by
Buono and coworkers[22b] in their recent mechanistic analysis of
the BH3 reduction of -hydroxy phosphinates.[20] As these
authors argued,[22b] the stereomutation of IV to VIIIa to place
OR1 in the (leaving) apical position requires the migration of the
apicophilic O-B substituent from its leaving apical position into a
less favored and non-leaving equatorial position. Simultaneously, sequence of events according to path b and c (Figure 1) that
the CH2-X substituent is forced into adopting an unfavorable
apical position.[29b,c] This will raise energy of the resulting TBP
VIIIa (Figure 1, path b) relative to IV but maybe not to the extent
which could effectively prevent its formation.
leads to the formation of the primary phosphine XVII (X = lone
pair).
It can be also concluded that the reduction of the ester P-O
bonds, when observed, must precede reduction of the P=O bond
because such bonds, albeit less directly than the P=O, have to
benefit from the activating presence of the five-membered ring in
III and IX, as described in paths b and c.
The proposed reduction mechanism seems to be general
regardless of the type of the activating group, e.g., OH or NH
present in the starting phosphinate or phosphonates. Importantly,
it also implies that the reductive conversion of the P=O bond into
a P-BH3must operate according to path a in these compounds;
this implies an inversion of configuration at P as has already
been confirmed in the closely related reductions of
hydroxymethylphosphinates.[17e,20,21-22]
Based on our results we have become more inclined to also
consider stereomutation of IV to VIIIb where OR1 adopts the
leaving apical position and the five-membered ring retains a
favored apical-O equatorial-C configuration. If this configuration
becomes competitive, the departure of the OR1 is likely to be
preferred, in that it probably constitutes a better leaving group
than the OB¯ group whose initially vacant boron p orbital is
already filled. Thus, to make the preferential departure of the
ring oxygen possible, and to avoid ester bond cleavage, the
stereomutation of TBP IV should be impeded.
It seems reasonable to expect[29a] that as the CH2-X ligand
becomes bulkier or quaternary, its preference for the equatorial
position should increase; this can be expected to stabilize the
critical -substituted TBP IV significantly and therefore make it
less prone to stereomutation. Indeed, under these
circumstances, we were able to achieve much greater selectivity
for the direct departure of the phosphoryl oxygen (cf. Scheme 1
Conclusions
In summary, a general and efficient method has been developed
for the chemoselective reduction of P=O bond by commercially
9
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10.1002/ejoc.201801518
European Journal of Organic Chemistry
FULL PAPER
silica gel. The reaction mixtures were purified by column chromatography over
silica gel (60−240 mesh) or basic Al2O3 (70-230 mesh).
available BH3 complexes for phosphinates and phosphonates
bearing either ester or amide functionaiities that have an
activating group (OH or NH) in close proximity to the phosphorus
atom. The key role of the  functional groups in the reduction
A. General procedure for the reaction of -hydroxy phosphonates 1
and -hydroxy phosphinates 6 with BH3-THF: In the two-necked
round-bottom flask (25 mL) equipped with a magnetic stirrer and an
process is to assure the formation of
a five-membered
dioxaboraphospholane ring that converts the robust phosphoryl
oxygen into a leaving group. The method nicely complements
known synthetic protocols for the synthesis of -hydroxy
phosphonite-boranes and -hydroxy phosphinite-boranes, and
provides possibly the most straightforward procedure for their
synthesis in a one-step reaction from the requisite (and readily
available) P=O precursors. The same simple route is now also
available for the first time for the preparation of -amino
argon inlet -hydroxy phosphonate
1 (0.5 mmol) or -hydroxy
phosphinate 6 (0.5 mmol) in anhydrous THF (5 mL) was placed. Then,
BH3-THF complex (5 mL, 5 mmol, 1M solution in THF) was slowly added
via syringe to avoid uncontrolled bubbling. After addition of BH3 complex
the reaction mixture was stirred and heated at 60 C for 24 h. Then, the
reaction mixture was evaporated to dryness and the residue was purified
by column chromatography on basic Al2O3 using hexane/AcOEt (v/v =
10:1) or hexane/AcOEt (v/v = 6:1) as eluent.
phosphonite-boranes and -amino phosphinite-boranes.
detailed mechanistic proposal of the reduction process
accounting for the observed chemoselectivity and
stereoselectivity of the reduction process has also been
presented.
An important implication that arises from the stereochemical
course of the developed reduction methodology deserves
attention. Once the direct reduction of P-stereogenic -hydroxy
phosphinates and -amino phosphinates to phosphinite-boranes
with clean inversion of configuration has been achieved, a
subsequentand straightforward stereoretentive oxidation[26]
provides the prospect of a two-step sequence for configurational
inversion at P. It also provides a route to P-stereogenic P=S
analogues.
A
Hydroxymethylphosphonous acid-borane diisopropyl ester (2a). 1a
(0.098 g, 0.5 mmol) was reacted according to general procedure A to
afford 2a (0.0194 g, 0.1 mmol, 20) as an oil: Rf = 0.93 (hexane/AcOEt
2:1). IR (ATR, thin film): 3446, 2979, 2384, 1375, 972 cm-1. 1H NMR (500
MHz, CDCl3)  4.63-4.73 (m, 2H), 3.83 (s, 2H), 1.99 (bs, 1H), 1.34 (d, 3JP-
3
= 6.31 Hz, CH3), 1.31 (d, JP-C = 6.31 Hz, CH3), 0.20-0.86 (m, 3H).
C
13C NMR (125 MHz, CDCl3)  72.7 (d, 2JP-C = 4.5 Hz, CH), 61.7 (d, 1JP-C
=
3
3
68.1 Hz, CH), 24.1 (d, JP-C = 3.6 Hz, CH3), 24.0 (d, JP-C = 4.5 Hz,
CH3).31P NMR (202 MHz, CDCl3)  134.58 (bm). 11B NMR (160.5 MHz,
CDCl3)  -43.70 (bm). GC-MS m/z (rel. int. %): 180 [(M-BH3)+, 18]. HRMS
(ESI/TOF) Found m/z: 247.1062; C9H24BO3PNa ([M-BH3+O+Et+Na])+
requires m/z: 247.1070. Anal. Calcd for C7H20BO3P: C, 43.33; H, 10.39.
Found: C, 43.70; H, 10.55.
Hydroxymethylphosphine-borane (5a). 1c (0.083 g, 0.5 mmol) was
reacted according to general procedure A to afford 5a (98, according to
31P NMR spectrum of crude reaction mixture, not isolated). 31P NMR (202
MHz, CDCl3)  -46.88 (bm). {1H}31P NMR (202 MHz, CDCl3)  -46.82 (t,
JP-H = 340.83 Hz).
Experimental Section
Hydroxymethylphosphine (4a).:1c (0.083 g, 0.5 mmol) was reacted
with BH3-THF (1.5 mL, 1.5 mmol, 1M solution in THF) at rt for 4 h
according to procedure A to afford 4a (90, according to 31P NMR
spectrum of crude reaction mixture, not isolated). 31P NMR (121.5 MHz,
CDCl3)  -121.52 (s). {1H}31P NMR (121.5 MHz, CDCl3)  -125.32 (t, JP-H
= 202.71 Hz).
General information. All reactions were performed under an argon
atmosphere using Schlenk techniques. Only dry solvents were used and
glassware was heated under vacuum prior use. All chemicals were used as
received unless noted otherwise. Solvents for chromatography and
crystallization were distilled once before use and the solvents for extraction
were used as received. THF and toluene were distilled from
sodium/benzophenone ketyl under argon. Water work-up of the reductions run
in up to 300-400 mg scale was intentionally omitted to minimize the vast loss
of ester products usually observed when hydrolytic reaction work-up preceded
the column chromatography. Caution: All reactions and column
chromatography have to be carried out under efficient fume hood because of
irritating odour accompanying isolation of products.
1-Hydroxy-ethylphosphonous acid-borane diisopropyl ester (2d).1d
(0.106 g, 0.5 mmol) was reacted according to general A procedure to
afford 2d (0.032 g, 0.155 mmol, 31) as a volatile oil: Rf = 0.28
(hexane/AcOEt 10:1). IR (ATR, thin film): 3502, 2979, 2386, 1374, 1103,
970, 787 cm-1. 1H NMR (500 MHz, CDCl3)  4.62-4.72 (m, 2H), 3.89-3.91
(m, 1H), 1.90 (bs, 1H), 1.39 (dd, JH-H = 6.94 Hz, JP-H = 15.45 Hz, 3H),
1.34 (d, JH-H= 2.52 Hz, 3H), 1.33 (d, J = 2.52 Hz, 6H), 1.31 (d, JH-H= 3.78
Hz, 3H), 1.30 (d, JH-H= 4.10 Hz, 3H), 0.15-0.83 (bm, 3H); 13C NMR (125
Equipment.1H NMR, 31P NMR and 13C NMR spectra were recorded on Bruker
Advance 500 or 400 or 300 spectrometer at ambient temperature in CDCl3
unless otherwise noted. Chemical shifts () are reported chemical shift in ppm
from tetramethylsilane with the solvent as an internal indicator (CDCl3 7.27
ppm for 1H and 77 ppm for 13C, DMSO 2.50 ppm for 1H and 39.5 ppm for 13C).
Mass spectra were recorded on Shimadzu GC-MS QP2010S in electron
ionization (EI). IR spectra were recorded on Thermo Scientific Nicolet iS50 FT-
IR ATR mode with diamond prism (4000 - 400 cm-1 window) as solids or thin
films. In the IR spectra, only the strongest/structurally most important peaks
(cm–1) are listed. Melting points were determined on Büchi Melting Point M-
560 in a capillary tube and were uncorrected. HPLC-HRMS was performed on
Shimazu HRMS ESI-IT-TOF using reverse phase stationary phase with
water/MeCN 65:35 as eluent, electrospray ionization (ESI), and IT-TOF
detector. Optical rotations were measured on Perkin Elmer 341LC using a 1
mL cell with a 10 mm path length and are reported as follows: []25D (c: g/100
mL, in solvent). Elementary analyses were performed on PERKIN ELMER
CHN 2400.Thin-layer chromatography (TLC) was performed with precoated
silica gel plates and visualized by UV light or KMnO4 solution or iodide on
2
MHz, CDCl3)  72.8 (d, 2JP-C = 4.6 Hz, CH), 72.7 (d, JP-C = 6.9 Hz, CH),
67.3 (d, 1JP-C = 70.5 Hz, CH), 24.1 (d, 3JP-C = 2.3 Hz, CH3), 24.0 (d, 3JP-C
= 4.6 Hz, CH3), 16.1 (d, 3JP-C = 4.6 Hz, CH3).31P NMR (202 MHz, CDCl3)
 137.58 (bm); 11B NMR (160.5 MHz, CDCl3)  -44.94 (bm). GC-MS m/z
(rel. int. %): 194 ([M-BH]+, 13); HRMS (ESI/TOF): Found m/z: 248.1580;
C10H24O3BPN ([M-O+NAc])+ requires m/z: 248.1579.
1-Hydroxy-1-methylethylphosphonous
acid-borane
diisopropyl
ester (2e). 1e (0.112 g, 0.5 mmol) was reacted according to general
procedure A to afford 2e (0.079 g, 0.355 mmol, 71) as an oil. Rf = 0.28
(hexane/AcOEt 10:1). IR (ATR, thin film): 3502, 2978, 2385, 1374, 973,
774 cm-1. 1H NMR (500 MHz, CDCl3)  4.64-4.74 (m, 2H), 1.79 (bs, 1H),
1.38 (d, JH-P = 13.56 Hz, 6H), 1.33 (d, J = 5.99 Hz, 6H), 1.31 (d, J = 5.99
Hz, 6H), 0.18-0.84 (bm, 3H).13C NMR (125 MHz, CDCl3)  72.8 (d, 2JP-C
=
1
2
5.5 Hz, CH), 71.0 (d, JP-C = 70.8 Hz), 24.1 (d, JP-C = 1.8 Hz, CH3), 23.8
(d, 3JP-C = 4.5 Hz, CH3), 23.7 (d, 3JP-C = 9.1 Hz, CH3). 31P NMR (202 MHz,
CDCl3)  138.91 (bm). 11B NMR (160.5 MHz, CDCl3)  -45.50 (bm). GC-
MS m/z (rel. int. %): 208 ([M-BH3]+, 1), 191 ([M-BH3-OH]+, 2), 150 [(M-
10
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201801518
European Journal of Organic Chemistry
FULL PAPER
BH3-C3H6O)+] (37). HRMS (ESI/TOF) Found m/z: 262.1730;
C11H26O3BPN ([M-O+NAc])+ requires m/z: 262.1735. Anal. Calcd for
C9H24BO3P: C, 48.68; H, 10.89; Found: C, 49.01; H, 11.00.
128.5 (d, 1JP-C = 52.7 Hz, C, minor), 128.7 (d, 3JP-C = 10.0 Hz, CH, major),
1
128.6 (d, 3JP-C = 9.1 Hz, CH, minor), 68.4 (d, JP-C = 50.9 Hz, CH, major),
68.0 (d, 1JP-C = 50.0 Hz, CH, minor), 64.5 (d, 2JP-C = 3.6 Hz, CH2, major),
2
64.3 (d, 2JP-C = 3.6 Hz, CH2, minor), 16.8 (d, JP-C = 5.5 Hz, CH3, major),
3
3
16.74 (d, JP-C = 2.7 Hz, CH3, major), 16.69 (d, JP-C = 2.7 Hz, CH3,
major), 16.1 (d, 2JP-C = 4.5 Hz, CH3, minor). 31P NMR (202 MHz, CDCl3) 
112.97 (bm, major), 111.97 (bm, minor). 11B NMR (160.5 MHz, CDCl3)  -
43.70 (bm). GC-MS m/z (rel. int. %): 154 [(M-BH3-C2H5O)+] (45), 126 (10),
109 (22), 108 (12), 107 (17), 79 (100), 78 (25), 77 (39), 58 (23), 57 (10).
Anal. Calcd for C10H18BO2P: C, 56.65; H, 8.56. Found: C, 56.80; H, 8.65.
1-Hydroxy-1-methylethyl-H-phosphinous acid-borane isopropyl
ester(3e). 1e (0.112 g, 0.5 mmol) was reacted with BH3-THF (5 mL, 1.5
mmol, 1M solution in THF) at rt for 24 h according to procedure A to
afford 2e (0.08 g, 0.36 mmol, 72) and 3e (9, according to 1H NMR
spectrum). 3e (isolated in a mixture with 2e): Rf = 0.5 (hexane/AcOEt 4:1).
1H NMR (500 MHz, CDCl3)  6.24 (dm, JH-P= 384.62 Hz, 1H), 4.51-4.57
(m, 1H), 2.18 (bs, 1H), 1.47 (t, JH-P= 15.13 Hz, 6H), 1.32 (d, JH-P= 7.41 Hz,
6H), 0.16-0.91 (bm, 3H). 31P NMR (202 MHz, CDCl3)  111.89 (bm).
8a: (1-Hydroxy-ethyl)phenylphosphine-borane. Volatile oil with
irritating odour. Rf = 0.17 (hexane/AcOEt 4:1). IR (ATR, thin film): 3216,
2381, 1436, 1061, 772, 692, 642 cm−1 1H NMR (500 MHz, CDCl3) 
.
1-Hydroxy-1-methylethylphosphine-borane (5e). 1f (0.09 g, 0.5 mmol)
was reacted according to general procedure A to afford 5a (95,
according to 31P NMR spectrum of crude reaction mixture, not isolated).
31P NMR (202 MHz, CDCl3)  -18.28 (bm). {1H}31P NMR (202 MHz,
CDCl3) -18.05(t, JP-H = 365.71 Hz).
7.70-7.81 (m, 4H), 7.52-7.60 (m, 2H), 7.42-7.52 (m, 4H), 5.45 (dm, JP-H
=
372.81 Hz, 1H), 5.41 (dm, 372.81 Hz, 1H), 4.42-4.48 (m, 1H), 4.36-4.42
(m, 1H), 2.24 (bs, 2H), 1.46 (dd, JH-P = 16.08 Hz, JH-H = 6.94 Hz, 3H),
1.43 (dd, JH-P = 15.45 Hz, JH-H = 6.94 Hz, 3H), 0.39-1.15 (bm, 6H).
2
13C NMR (125 MHz, CDCl3)  133.9 (d, JP-C = 8.18 Hz, CH), 133.7 (d,
2JP-C = 8.17 Hz, CH), 132.2 (d, 4JP-C = 1.8 Hz, CH), 129.1 (d, 3JP-C = 10.0
1-Hydroxy-1-cyclohexylphosphonous acid-borane diisopropyl ester
(2g). 1g (0.083 g, 0.5 mmol) was reacted according to general procedure
A to afford 2g (0.0885 g, 0.335 mmol, 67) as an oil. Rf = 0.46
(hexane/AcOEt 10:1). IR (ATR, thin film): 3503, 2978, 2934, 2959, 2385,
1449, 1385, 1260, 1177, 1140, 974, 883 cm-1. 1H NMR (500 MHz, CDCl3)
3
1
Hz, CH), 129.0 (d, JP-C = 10.0 Hz, CH), 122.8 (d, JP-C = 52.7 Hz, C),
122.2 (d, 1JP-C = 53.6 Hz, C), 65.1 (d, 1JP-C = 40.0 Hz, CH), 64.8 (d, 1JP-C
=
2
2
40.0 Hz, CH), 19.02 (d, JP-C = 4.5 Hz, CH3), 18.98 (d, JP-C = 4.5 Hz,
CH3). 31P NMR (202 MHz, CDCl3)  12.65 (bm). {1H}31P NMR (202 MHz,
CDCl3)  12.81 (dm, JP-H = 355.76 Hz). 11B NMR (160.5 MHz, CDCl3)  -
43.32 (bm). GC-MS m/z (rel. int. %): 154 ([M-BH3]+, 2), 138 ([M-BH3-OH]+,
6).
 61-4.70 (m, 2H), 1.73-1.80 (m, 2H), 1.54-1.71 (m, 8H), 1.31 (d, JH-P
=
6.31 Hz, 6H), 1.28 (d, JH-P = 6.15 Hz, 6H), 0.12-0.85 (bm, 3H). 13C NMR
(125 MHz, CDCl3)  72.6 (d, 2JP-C = 5.5 Hz, CH), 72.4 (d, 1JP-C = 72.7 Hz,
3-.
C), 30.3 (d, JP-C = 6.4 Hz, CH2), 25.4 (s, CH2), 24.2 (d,
J
= 1.8 Hz,
P-C
CH3), 23.9 (d, 3JP-C = 4.5 Hz, CH3), 20.1 (d, JP-C = 9.9 Hz, CH2). 31P NMR
(202 MHz, CDCl3)  138.00 (bm). 11B NMR (160.5 MHz, CDCl3)  -45.29
(bm). HRMS (ESI/TOF) Found m/z: 23=1.1497; C12H24O2P ([M-BH3-
OH])+ requires m/z: 231.1508. Anal. Calcd for C12H28BO3P: C, 54.98; H,
10.77. Found: C, 54.59; H, 10.27.
(1-Hydroxy-1-methylethyl)phenylphosphinous acid-borane ethyl
ester (7b). 6b (0.083 g, 0.5 mmol) was reacted according to general
procedure A to afford 7b (0.0848 g, 0.375 mmol, 75) as an oil with
irritating odour. Rf = 0.60 (hexane/AcOEt 2:1). IR (ATR, thin film): 3502,
2976, 2383, 1436, 1025, 730 cm-1. 1H NMR (300 MHz, CDCl3)  7.73-
7.84 (m, 2H), 7.44-7.58 (m, 3H), 4.07-4.23 (m, 1H), 3.95-4.07 (m, 1H),
2.18 (bs, 1H), 1.39 (d, JH-P = 12.81 Hz, 3H), 1.34 (t, JH-P = 7.04 Hz, 3H),
1.30 (d, JH-P = 13.72 Hz, 3H), 0.18-1.08 (bm, 3H). 13C NMR (75 MHz,
CDCl3)  131.96 (d, 2JP-C = 10.1 Hz, CH), 131.92 (d, 4JP-C = 2.6 Hz, CH),
128.9 (d, 1JP-C = 51.2 Hz, C), 128.3 (d, 3JP-C = 10.1 Hz, CH), 71.4 (d, 1JP-C
= 50.6 Hz, C), 64.5 (d, 2JP-C = 4.0 Hz, CH2), 24.8 (d, 2JP-C = 9.5 Hz, CH3),
1-Hydroxy-1-cyclohexyl-H-phosphinous
acid-borane
isopropyl
ester(3g).1g (0.083 g, 0.5 mmol) was reacted with BH3-THF (2.5 mL, 2.5
mmol, 1M solution in THF) at rt for 16 h according to procedure A to
afford 2g (0.0642 g, 0.245 mmol, 49) and 3g (0.0061 g, 0.03 mmol,
6). 3g: an oil. Rf = 0.31 (hexane/AcOEt 10:1). IR (ATR, thin film): 3495,
2977, 2933, 2956, 2384, 1449, 1375, 1104, 936, 754 cm-1. 1H NMR (500
MHz, CDCl3)  6.19 (dq,1JP-H = 384.03 Hz, JH-H = 5.04 Hz, 1H), 4.45-4.56
(m, 1H), 1.57-1.80 (m, 11H), 1.31 (d, J = 6.15 Hz, 6H), 0.20-0.92 (bm,
3H). 13C NMR (125 MHz, CDCl3)  73.7 (d, 2JP-C = 5.5 Hz, OCH), 71.4 (d,
1JP-C = 52.7 Hz, C), 32.3 (d, JP-C = 6.4 Hz, CH2), 31.3 (d, JP-C = 7.2 Hz,
CH2), 25.6 (s, CH2), 24.0 (d, 3JP-C = 4.5 Hz, CH3), 23.3 (d, 3JP-C = 3.6 Hz,
CH3), 20.4 (d, JP-C = 7.2 Hz, CH2), 20.2 (d, JP-C = 9.1 Hz, CH2).31P NMR
(202 MHz, CDCl3) 109.97 (bm). {1H}31P NMR (202 MHz, CDCl3) 
109.86 (dq, JP-H = 395.64 Hz). 11B NMR (160.5 MHz, CDCl3)  -43.81
(bm). HRMS (ESI/TOF) Found m/z: 407.2824; C18H43O4B2P2 [2M-
H]+requires m/z: 407.2812.
23.8 (d, JP-C = 9.8 Hz, CH3), 16.7 (d, JP-C = 5.8 Hz). 31P NMR (121.5
MHz, CDCl3)  116.35 (bm); 11B NMR (160.5 MHz, CDCl3)  -43.21 (bm).
GC-MS m/z (rel. int. %): 154 [(M-BH3-C2H5O)+] (30), 125 (99). Anal.
Calcd for C11H20BO2P: C, 58.44; H, 8.92. Found: C, 58.61; H, 8.39.
2
3
(1-Hydroxy-1-cyclohexyl)phenylphosphinous
acid-borane
ethyl
ester (7c). 6c (0.134 g, 0.5 mmol) was reacted with BH3-THF complex
(1.5 mL, 1.5 mmol, 1M solution in THF) at 60 C for 24 h according to
general procedure A to afford 7c (0.0944 g, 0.355 mmol, 71).
7c: a colourless oil with an irritating odour. Rf = 0.45 (hexane/AcOEt 6:1).
IR (ATR, thin film): 3502, 2934, 2380, 1436, 1113, 1067, 1024, 1024, 967,
945, 896, 844, 728, 692, 621, 609 cm-1. 1H NMR (500 MHz, CDCl3) 
7.72-7.78 (m, 2H), 7.52-7.55 (m, 1H), 7.45-7.50 (m, 2H), 4.08-4.17 (m,
(1-Hydroxy-ethyl)phenylphosphinous acid-borane ethyl ester (7a).
6a (0.107 g, 0.5 mmol) was reacted according to general procedure A to
afford 7a as a mixture of diastereoisomers (0.05 g, 0.235 mmol, 47 dr =
59:41) and 8a as a mixture of diastereoisomers (0.084 g, 0.05 mmol,
10, dr = 50:50).
1H), 3.94-4.02 (m, 1H), 1.80 (bs, 1H), 1.49-1.75 (m, 9H), 1.34 (t, JH-P
=
6.94 Hz, 3H), 1.11-1.25 (m, 1H), 0.03-1.19 (bm, 3H). 13C NMR (125 MHz,
2
4
CDCl3)  132.2 (d, JP-C = 10.0 Hz, CH), 131.8 (d, JP-C = 2.7 Hz, CH),
128.7 (d, 1JP-C = 51.2 Hz, C), 128.2 (d, 3JP-C = 10.0 Hz, CH), 72.7 (d, 1JP-C
= 52.7 Hz, C), 64.4 (d, 2JP-C = 4.5 Hz, CH2), 31.1 (d, 2JP-C = 6.4 Hz, CH2),
7a:
(hexane/AcOEt 4:1). IR (ATR, liquid): 3502, 2978, 2379, 1437, 1025, 946,
772, 733, 693 cm−1 1H NMR (500 MHz, CDCl3)  7.75-7.85 (m, 4H),
a volatile oil with an irritating odour. Rf = 0.34 and 0.29
2
4
30.5 (d, JP-C = 8.2 Hz, CH2), 25.2 (d, JP-C = 1.1 Hz, CH2), 20.2 (d, 3JP-C
3
3
= 9.1 Hz, CH2), 20.1 (d, JP-C = 10.0 Hz), 16.7 (d, JP-C = 5.75 Hz,
CH3).31P NMR (202 MHz, CDCl3)  114.89 (bm). 11B NMR (160.5 MHz,
CDCl3)  -43.27 (bm). HRMS (ESI/TOF) Found m/z: 235.1242 C14H20OP
([M-BH3-OH]+) requires m/z: 235.1246. Anal. Calcd for C14H24BO2P: C,
63.18; H, 9.09; Found: C, 62.88; H, 9.19.
.
7.59-7.59 (m, 2H), 7.43-7.58 (m, 4H), 4.23-4.29 (m, 1H, minor), 4.15-4.20
(m, 1H, major), 4.08-4.16 (m, 2H, minor), 3.93-4.02 4.23-4.29 (m, 2H,
major), 2.00 (bs, 2H), 1.33 (t, JH-P = 6.94 Hz, 3H, major), 1.33 (t, JH-P
=
6.94 Hz, 3H, minor), 1.33 (dd, JH-P = 7.09 Hz, JH-H = 3.31 Hz, 3H, minor),
1.30 (dd, JH-P = 7.09 Hz, JH-H = 2.36 Hz, 3H, major), 0.40-1.10 (bm,
4
6H).13C NMR (125 MHz, CDCl3)  132.3 (d, JP-C = 2.7 Hz, CH, minor),
Reduction of 6a-c by BH3-SMe2 complex. In the two-necked round-
bottom flask (25 mL) equipped with a magnetic stirrer and an argon inlet
was placed-hydroxy phosphonite 6 (0.5 mmol) in anhydrous THF (5
132.2 (d, 4JP-C = 2.7 Hz, CH, major), 131.8 (d, 2JP-C = 10.9 Hz, CH, minor),
131.5 (d, 2JP-C = 10.0 Hz, CH, major), 128.1 (d, 1JP-C = 53.6 Hz, C, major),
11
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201801518
European Journal of Organic Chemistry
FULL PAPER
mL). Then, BH3-SMe2 complex (0.142 mL, 1.5 mmol) or (0.237 mL, 2.5
mmol) was slowly added via syringe to avoid uncontrolled bubbling. After
addition of BH3 complex the reaction mixture was stirred for indicated
time and temperature. Then, the reaction mixture was evaporated to
dryness and the residue was purified by column chromatography on
silica gel using hexane/AcOEt (v/v = 10:1) or hexane/AcOEt (v/v = 6:1)
as eluent.
equiv. of BH3-THF at 60 oC for 24 h according to general procedure A to
afford 18 (0.108 g, 0.39 mmol, 78) as a white solid, m.p. 77.7-78.8 C.
Rf = 0.47 (hexane/AcOEt 10:1). IR (ATR, solid): 3308, 2969, 2394, 1366,
1177, 1012, 973, 541 cm-1. 1H NMR (500 MHz, CDCl3)  3.99 (d, JH-H
=
4.41 Hz, 2H), 3.57-3.69 (m, 4H), 2.32 (bs, 1H), 1.31 (d, JH-H = 6.94 Hz,
12H), 1.27 (d, JH-H = 6.94 Hz, 12H), 0.51-1.19 (bm, 3H).13C NMR (125
MHz, CDCl3)  59.9 (d, 1JP-C = 61.8 Hz, CH2), 47.7 (d, 2JP-C = 4.5 Hz, CH),
24.5 (d, 3JP-C = 1.8 Hz, CH3), 23.5 (d, 3JP-C = 1.8 Hz, CH3). 31P NMR (202
MHz, CDCl3)  83.69 (bm). 11B NMR (160.5 MHz, CDCl3)  -35.79 (bm).
GC-MS m/z (rel. int. %): 232 [(M-BH3-CH2O)+] (2), 148 (39), 106 (100),
88 (11), 86 (68), 78 (12), 77 (11), 58 (31). Anal. Calcd for C13H34BN2OP:
C, 56.53; H, 12.41; N, 10.14. Found: C, 56.20; H, 12.11; N, 9.98.
(1-Hydroxy-ethyl)phenylphosphinous acid-borane ethyl ester (7a).
6a (0.107 g, 0.5 mmol) was reacted with BH3-SMe2 (0.237 mL, 2.5 mmol)
at rt for 16 h according to general procedure A to afford 7a as a mixture
of diastereoisomers (0.0169 g, 0.08 mmol, 16 dr = 56:45) and 8a as a
mixture of diastereoisomers (0.016 g, 0.095 mmol, 19, dr = 50:50).
B. General procedure for reduction of P-stereogenic -
hydroxyphosphinates 10 by BH3-SMe2. In the two-necked round-
bottom flask (25 mL) equipped with a magnetic stirrer and an argon inlet
was placed-hydroxyphosphinate 10 (0.3 mmol) in anhyd. THF (5 mL).
Then, BH3-SMe2 (142 L, 1.5 mmol) was slowly added via syringe to
avoid uncontrolled bubbling. After addition of BH3 complex the reaction
mixture was stirred and heated at 60 C for 16 h. Then, the reaction
mixture was evaporated to dryness and the residue was purified by
column chromatography on basic Al2O3 using hexane/AcOEt (v/v = 10:1)
and hexane/AcOEt (v/v = 6:1) as eluent.
1-Hydroxy-1-cyclohexyl)phenylphosphinous acid-borane ethyl ester
(7b). 6b (0.083 g, 0.5 mmol) was reacted with BH3-SMe2 (0.142 mL, 1.5
mmol) at rt for 16 h according to general procedure to afford 7b (0.064 g,
0.285 mmol, 57).
(1-Hydroxy-1-cyclohexyl)phenylphosphinous
acid-borane
ethyl
ester (7c). 6c (0.134 g, 0.5 mmol) was reacted with BH3-SMe2 (0.142 mL,
1.5 mmol) at 60 C for 24 h according to general procedure A to afford 7c
(0.082 g, 0.31 mmol, 62) and 8c (0.0155 g, 0.07 mmol, 14).
(RP)-Hydroxymethyl(phenyl)phosphinous acid-borane (L)-menthyl
ester (RP)-(11a).[22b] (SP)-10a (0.093 g, 0.3 mmol) was reacted according
to general procedure B to afford (RP)-(11a) as a single diastereoisomer
(0.0416 g, 0.135 mmol, 45) and 12 (0.007 g, 0.045 mmol, 15).
8c: (1-Hydroxy-1-cyclohexyl)phenylphosphine-borane. A colourless
oil. Rf = 0.34 (hexane/AcOEt 6:1). 1H NMR (500 MHz, CDCl3)  7.68-7.72
(m, 2H), 7.54-7.59 (m, 1H), 7.45-7.51 (m, 2H), 5.29 (dq, JP-H = 371.38 Hz,
1H), 1.50-1.89 (m, 11H), 0.42-1.10 (bm, 3H). 13C NMR (125 MHz, CDCl3)
2
4
 134.3 (d, JP-C = 7.3 Hz, CH), 132.0 (d, JP-C = 2.7 Hz, CH), 128.9 (d,
3JP-C = 9.1 Hz, CH),123.0 (d, 1JP-C = 51.8 Hz, C), 71.4 (d,1JP-C = 40.0 Hz,
C), 33.63 (d, 2JP-C = 7.3 Hz, CH2), 30.56 (d, 2JP-C = 6.4 Hz, CH2), 25.0 (d,
4JP-C = 1.0 Hz, CH2), 20.7 (d, 3JP-C = 8.2 Hz, CH2), 20.6 (d, 3JP-C = 7.3 Hz,
CH2). 31P NMR (202 MHz, CDCl3)  24.05 (bm). {1H}31P NMR (202 MHz,
CDCl3)  23.86 (dm, JP-H = 355.37 Hz). HRMS (ESI/TOF) Found m/z:
225.1046; C12H17O2P ([M-BH3+O+H]+) requires m/z: 225.1039.
(RP)-(11a): a colourless oil. Rf = 0.78 (hexane/AcOEt 2:1). []D= -69.52 (c
1.25, CHCl3). IR (ATR, thin film): 3482, 2954, 2379, 1437, 980, 844,
692 cm−1 1H NMR (500 MHz, CDCl3)  7.84-7.89 (m, 2H), 7.54-7.58 (m,
.
1H), 7.47-7.51 (m, 2H), 4.05-4.12 (m, 2H), 2.23-2.29 (m, 1H), 1.72-1.78
(m, 2H), 1.61-1.70 (m, 2H), 1.42-1.53 (m, 1H), 1.30-1.40 (m, 1H), 1.11-
1.14 (m, 1H), 0.95 (d, JH-H = 6.62 Hz, 3H), 0.83-1.00 (m, 2H), 0.80 (d, JH-
= 6.94 Hz, 3H), 0.50-0.89 (m, 3H), 0.50 (d, JH-H = 6.94 Hz, 3H).
H
13C NMR (125 MHz, CDCl3)  132.2 (d, 4JP-C = 1.8 Hz, CH), 131.3 (d, 2JP-
Hydroxymethylphosphonous acid-borane isopropyl ester N,N-
diethylamide (16). 13 (0.105 g, 0.5 mmol) was reacted with 10 equiv. of
BH3-THF at rt for 24 h according to general procedure A to afford 16
(0.062 g, 0.3 mmol, 60) as an oil. Rf = 0.6 (hexane/AcOEt 2:1). IR (ATR,
thin film): 3502, 2974, 2380, 1381, 969, 791 cm-1. 1H NMR (500 MHz,
CDCl3)  4.41-4.50 (m, 1H), 3.82 (bs, 1H), 3.14-3.25 (m, 2H), 3.05-3.25
(m, 2H), 1.85 (bs, 1H), 1.25 (d, JH-H= 5.99 Hz, 3H), 1.23 (d, JH-H= 6.15 Hz,
3H), 1.12 (t, JH-P = 7.09 Hz, 6H), 0.12-0.86 (bm, 3H). 13C NMR (125 MHz,
CDCl3)  70.4 (d, 2JP-C = 3.6 Hz, CH), 59.7 (d, 1JP-C = 73.6 Hz, CH2), 39.5
C = 10.0 Hz, CH), 129.5 (d, 1JP-C = 61.7 Hz, C), 128.6 (d, 3JP-C = 10.0 Hz,
2
1
CH), 80.4 (d, JP-C = 4.5 Hz), 63.5 (d, JP-C = 49.1 Hz, CH2), 48.8, 43.5,
34.0, 31.5, 25.5, 22.7, 22.1, 20.9, 15.3. 31P NMR (202 MHz, CDCl3) 
105.87 (bm). Anal. Calcd for C17H30BO2P: C, 66.25; H, 9.81. Found: C,
66.20; H, 9.80.
12: (Hydroxymethyl)phenylphosphine-borane.[22b] A colourless oil. Rf =
0.49 (hexane/AcOEt 2:1). 1H NMR (500 MHz, CDCl3)  7.74-7.78 (m, 2H),
7.48-7.60 (m, 3H), 5.59 (dm, JH-P = 375.40 Hz, 1H), 4.23-4.31 (m, 2H),
1.93 (bs, 1H), 0.37-1.11 (bm, 3H).13C NMR (125 MHz, CDCl3)  133.5 (d,
2JP-C = 8.17 Hz, CH), 132.3 (d, 4JP-C = 2.7 Hz, CH), 129.2 (d, 2JP-C = 10.0
2
(d, JP-C = 3.6 Hz, CH2), 24.0 (d, 3JP-C = 4.5 Hz, CH), 23.9 (d, 3JP-C = 3.6
Hz, CH), 23,94; 14.4 (d, 3JP-C = 1.8 Hz, CH3). 31P NMR (202 MHz, CDCl3)
 111.56 (bm). 11B NMR (160.5 MHz, CDCl3)  -42.57 (bm). HRMS
(ESI/TOF) Found m/z: 194.1307; C8H21O3P ([(M-BH3)+H]+) requires m/z:
194.1304. Anal. Calcd for C8H23BNO2P: C, 46.41; H, 11.20; N, 6.76;
Found: C, 46.11; H, 11.00; N, 6.50.
1
1
Hz, CH), 122.6 (d, JP-C = 55.4 Hz, C), 58.5 (d, JP-C = 55.4 Hz, CH2).
31P NMR (202 MHz, CDCl3)  -0.24 (bm). HRMS (ESI/TOF) Found m/z:
313.0755; C14H19O4P2 [2(M-BH3+O)+H]+requires m/z: 313.0753.
(RP)-1-Hydroxy-1-cyclohexyl(phenyl)phosphinous acid-borane (L)-
menthyl ester (RP)-(11b). (SP)-10b (0.114 g, 0.3 mmol) was reacted
according to general procedure B (0.0677 g, 60) as an oil. Rf= 0.83
(hexane/AcOEt 2:1). []D= -114 (c 0.505, CHCl3). IR (ATR, thin film):
2930, 2862, 2392, 1448, 978, 751, 693 cm−1. 1H NMR (500 MHz, CDCl3)
 7.84-7.89 (m, 2H), 7.49-7.54 (m, 1H), 7.40-7.46 (m, 2H), 4.06-4.14 (m,
1H), 2.31-2.38 (m, 1H), 1.92 (bs, 1H), 1.78-1.80 (m, 1H), 1.76-1.80 (m,
1H), 1.40-1.79 (m, 10H), 1.08-1.15 (m, 2H), 0.93 (d, JH-H = 6.62 Hz, 3H),
Hydroxymethylphosphonous
acid-borane
N,N,N',N'-
tetraethyldiamide (17). 14 (0.111 g, 0.5 mmol) was reacted with 10
equiv. of BH3-THF at rt for 24 h according to general procedure A to
afford 17 (0.0242 g, 0.11 mmol, 22) as an oil. Rf = 0.77 (hexane/AcOEt
2:1); IR (ATR, thin film): 2972, 2345, 1377, 1015 cm−1 1H NMR (500
.
MHz, CDCl3)  3.95 (s, 2H), 2.97-3.15 (m, 8H), 1.97 (s, 1H), 1.08 (t, JP-H
= 7.09 Hz, 12H), 0.19-0.88 (bm, 3H); 13C NMR (125 MHz, CDCl3)  58.2
(d, 1JP-C = 65.4 Hz, CH2), 40.0 (d, 2JP-C = 2.7 Hz, CH2), 14.3 (d, 3JP-C = 1.8
Hz, CH2); 31P NMR (202 MHz, CDCl3)  86.70 (bm); 11B NMR (160.5
MHz, CDCl3)  -40.76 (bm); HRMS (ESI/TOF) Found m/z: 207.1615;
C9H24OPN2 [(M-BH3)+H]+requires m/z: 207.1621. Anal. Calcd for
C9H26OPBN2: C, 49.11; H, 11.91; N, 12.73. Found: C, 48.80; H, 11.55; N,
12.88.
0.82-0.91 (m, 2H), 0.75 (d, JH-H = 7.09 Hz, 3H), 0.44-0.80 (bm, 3H), 0.34
2
(d, JH-H = 6.94 Hz, 3H). 13C NMR (125 MHz, CDCl3)  132.6 (d, JP-C
=
10.0 Hz, CH), 131.7 (d, 4JP-C = 1.8 Hz, CH), 129.5 (d, 1JP-C = 54.5 Hz, C),
3
1
127.9 (d, JP-C = 10.0 Hz, CH), 80.6 (d, JP-C = 5.5 Hz, CH), 73.3 (d, JP-C
= 51.8 Hz, C), 48.9 (d, JP-C = 4.3 Hz, CH), 43.6 (s, CH2), 34.1 (s, CH2),
31.9 (d, JP-C = 7.3 Hz, CH2), 31.6 (s, CH), 30.3 (d, JP-C = 6.4 Hz, CH2),
25.4 (s, CH), 25.2 (d, JP-C = 1.2 Hz, CH2), 22.6 (s, CH2), 22.2 (s, CH3),
21.0 (s, CH3), 20.3 (d, JP-C = 1.8 Hz, CH2), 20.1 (d, JP-C = 2.7 Hz, CH2),
Hydroxymethylphosphonous
tetraisopropyldiamide (18). 15 (0.184 g, 0.5 mmol) was reacted with 10
acid-borane
N,N,N',N'-
12
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201801518
European Journal of Organic Chemistry
FULL PAPER
2
15.0 (s, CH3). 31P NMR (202 MHz, CDCl3)  112.93 (bm). GC-MS m/z (rel.
int. %): 127 [(PhPH(OH))+] (100), 126 (55), 109 (22), 95 (25), 83 (24).
Anal. Calcd for C22H38BO2P: C, 70.22; H, 10.18. Found: C, 69.95; H,
10.00.
132.0, 138.1 (s, CH, minor), 138.8 (s, CH, major), 131.2 (d, JP-C = 10.9
2
1
Hz, CH, minor), 131.0 (d, JP-C = 10.9 Hz, CH, major), 130.2 (d, JP-C
59.0 Hz, C, major), 130.2 (d, JP-C = 59.0 Hz, C, major), 128.9 (d, JP-C
=
=
1
1
57.2 Hz, C, major), 128.7, 128.5 (d, 3JP-C = 10.9 Hz, CH, major), 128.3 (d,
3JP-C = 10.0 Hz, CH, minor), 128.2 (d, JP-C = 1.8 Hz, CH), 128.18 (d, JP-C
= 3.6 Hz, CH), 128.17 (d, JP-C = 1.8 Hz, CH), 128.1 (d, JP-C = 2.7 Hz, CH),
127.95 (d, JP-C = 3.6 Hz, CH), 127.88 (d, JP-C = 2.7 Hz, CH), 127.7 (d, JP-
C. General procedurefor reduction of -amino phosphinates 19 and
-amino phosphonates 22 by BH3-SMe2. In the two-necked round-
bottom flask (25 mL) equipped with a magnetic stirrer and an argon inlet
was placed-amino phosphonate 22 (0.25 mmol) or -amino
phosphinate 19 in anhydrous THF (5 mL). Then, BH3-SMe2 (71.2 L,
0.75 mmol for 19a-b) or BH3-SMe2 (118.6 L, 1.25 mmol for 22a,c-f,
22h-k, 25) or BH3-SMe2 (0.237 mL, 2.5 mmol for 22b, 22g, 22l) was
slowly added via syringe to avoid uncontrolled bubbling. After addition of
BH3 complex the reaction mixture was stirred and heated at 60 C for
indicated time (4-24 h). Then, the reaction mixture was evaporated to
dryness and the residue was purified by column chromatography on
silica gel using hexane/AcOEt (v/v = 6:1) or hexane/AcOEt (v/v = 4:1) as
eluent.
= 2.7 Hz, CH), 115.62 (s, CH, major), 115.58 (s, CH, minor), 110.3 (s,
C, major), 110.2 (s, C, minor), 65.11 (d, JP-C = 2.7 Hz, CH2, minor),
C
2
2
1
65.01 (d, JP-C = 3.6 Hz, CH2, major), 60.7 (d, JP-C = 44.5 Hz, minor),
59.4 (d, 1JP-C = 46.3 Hz, major), 16.7 (d, 3JP-C = 6.4 Hz, CH3, minor), 16.4
(d, 3JP-C = 5.5 Hz, CH3, major). 31P NMR (202 MHz, CDCl3)  109.74 (bm,
major), 114.53 (bm, minor). HRMS (ESI/TOF) Found m/z: 428.0952;
C21H25BBrNOP ([M+H]+) requires m/z: 428.0942. Anal. Calcd for
C21H24BBrNOP: C, 58.92; H, 5.65; N, 3.27. Found: C, 58.79; H, 5.85; N,
3.10.
[1-(N-p-Bromophenylamino)]-1-phenylmethylphosphonous
acid-
borane diisopropyl ester (23a). 22a (0.107 g, 0.25 mmol) was reacted
with BH3-SMe2 (118.6 L, 1.25 mmol) for 16 h according to general
procedure C to afford 23a (0.0816 g, 0.193 mmol, 77) as an oil. Rf =
0.64 (hexane/AcOEt 10:1). IR (ATR, thin film): 3404, 2978, 2386, 1593,
[(4-Bromophenylamino)(phenyl)methyl]phenylphosphinous
acid-
borane isopropyl ester (20a). 19a (0.111 g, 0.25 mmol) was reacted
with BH3-SMe2 (71.2 L, 0.75 mmol) for 20 h according to general
procedure C to afford 20a as a mixture of diastereoisomers isolated as a
mixture (0.093 g, 0.21 mmol, 84, dr = 59:41) as an oil. Rf = 0.7
(hexane/AcOEt 6:1). IR (ATR, thin film): 3395, 2978, 2383, 1590, 1493,
1493, 1101, 973, 808, 696 cm−1 1H NMR (500 MHz, CDCl3)  7.25-7.41
.
(m, 5H), 7.16-7.22 (m, 2H), 6.44-6.52 (m, 2H), 4.60-4.69 (m, 1H), 4.59 (d,
JP-H = 17.02 Hz, 1H), 4.46-4.54 (m, 1H), 1.30 (d, JH-H = 6.15 Hz, 3H),
982, 807, 691 cm−1 1H NMR (500 MHz, CDCl3)  7.70-7.74 (m, 2H),
.
1.28 (d, JH-H = 6.31 Hz, 3H), 1.20 (d, JH-H = 5.99 Hz, 3H), 0.91 (d, JH-H
=
6.15 Hz, 3H), 0.15-0.85 (bm, 3H). 13C NMR (125 MHz, CDCl3)  145.6 (d,
3JP-C = 10.9 Hz, NC), 135.0 (d,2JP-C = 3.6 Hz, C), 131.9 (s, CH), 128.3 (d,
3JP-C = 4.5 Hz, CH), 128.2 (d, 4JP-C = 1.8 Hz, CH), 128.0 (d, 5JP-C = 2.7 Hz,
7.43-7.53 (m, 6H), 7.33-7.36 (m, 2H), 7.27-7.52 (m, 6H), 7.10-7.18 (m,
2H), 7.15-7.20 (m, 2H, minor), 7.10-7.13 (m, 2H, major), 7.01-7.03 (m,
1H, major), 6.99-7.03 (m, 1H, minor), 6.45-6.49 (m, 2H, minor), 6.39-6.40
(m, 2H, major), 4.76 (d, JP-H = 14.19 Hz, 1H, major), 4.73 (d, JP-H = 14.82
Hz, 1H, minor), 4.61-4.68 (m, 1H, minor), 4.39-4.41 (m, 1H, major), 4.02
(bs, 1H), 1.32 (d, JP-H = 6.22 Hz, 3H, minor), 1.23 (d, JH-H = 6.22 Hz, 3H,
minor), 1.16 (d, JH-H = 6.31 Hz, 3H, major), 0.92 (d, JP-H = 6.31 Hz, 3H,
2
CH), 115.4 (s, CH), 110.0 (s, C), 73.8 (d, JP-C = 3.6 Hz, CH), 73,20 (d,
2JP-C = 5.5 Hz, CH), 59.8 (d, 1JP-C = 63.6 Hz, CH), 24.13 (d, 3JP-C = 2.7 Hz,
CH3), 24.10 (d,3JP-C = 2.7 Hz, CH3), 23.7 (d, 3JP-C = 4.5 Hz, CH3), 23.8 (d,
3JP-C = 4.5 Hz, CH3). 31P NMR (202 MHz, CDCl3)  135.95 (bm). HRMS
(ESI/TOF) Found m/z: 410.0887: C19H26BrNO2P ([M-BH3+H]+) requires
m/z: 410.0879. Anal. Calcd for C19H28BrNO2PB: C, 53.81; H, 6.65; N,
3.30. Found: C, 53.90; H, 6.78; N, 3.50.
major), 0.45-0.99 (bm, 6H). 13C NMR (125 MHz, CDCl3)  145.6 (d, JP-C
3
= 10.0 Hz, NC, minor), 145.3 (d, 3JP-C = 11.8 Hz, NC, major), 134.9 (s, C,
major), 134.5 (d, 2JP-C = 3.6 Hz, C, minor), 132.10 (d, 4JP-C = 2.7 Hz, CH,
4
major), 132.06 (d, JP-C = 1.8 Hz, CH, minor), 131.83 (s, CH, minor),
131.76 (s, CH, major), 131.6 (s, C, minor) 131.5 (s, C, major), 131.2 (d,
2JP-C = 10.0 Hz, CH), 131.0 (d, 2JP-C = 10.9 Hz, CH), 130.0 (d, 1JP-C = 59.0
Hz, C), 128.8 (d, JP-C = 3.6 Hz, CH), 128.5 (d, JP-C = 10.5 Hz, CH),
[1-(N-p-Bromophenylamino)]-[1-(p-bromophenyl)methyl]phosphor-
nous acid-borane diisopropyl ester (23b). 22b (0.126 g, 0.25 mmol)
was reacted with BH3-SMe2 (0.237 mL, 2.5 mmol) for 28 h according to
general procedure C to afford 23b (0.107 g, 0.213 mmol, 85) and 24b
(0.0083 g, 0.025 mmol, 10).
3
128.47 (d, JP-C = 3.6 Hz, CH), 128.63 (d, 3JP-C = 10.9 Hz, CH), 128.11 (d,
JP-C = 1.8 Hz, CH), 128.08 (d, JP-C = 2.7 Hz, CH), 128.01 (d, JP-C = 1.8 Hz,
CH), 127.98 (d, JP-C = 1.52 Hz, CH), 127.8 (d, JP-C = 2.7 Hz, CH), 115.6
(s, CH, major), 115.5 (s, CH, minor), 110.3 (s, C, major), 110.1 (s, C,
23b: Colourless oil. Rf = 0.62 (hexane/AcOEt 10:1). IR (ATR, thin film):
.
3403, 2978, 2386, 1487, 972, 810 cm−1 1H NMR (500 MHz, CDCl3) 
2
2
minor), 74.3 (d, JP-C = 3.6 Hz, CH, major), 74.2 (d, JP-C = 3.6 Hz, CH,
1
1
minor), 61.1 (d, JP-C = 46.3 Hz, minor), 59.9 (d, JP-C = 49.1 Hz, major),
24.2 (d, 3JP-C = 2.7 Hz, CH3), 24.17 (d, 3JP-C = 4.5 Hz, CH3), 23.6 (d, 3JP-C
= 4.5 Hz, CH3). 31P NMR (202 MHz, CDCl3)  107.53 (bm, major), 111.70
(bm, minor). HRMS (ESI/TOF) Found m/z: 442.1099; C22H27BBrNOP
([M+H]+) requires m/z: 442.1098. Anal. Calcd for C22H26BBrNOP: C,
59.76; H, 5.93; N, 3.17; Found: C, 59.79; H, 5.85; N, 3.10.
7.43-7.47 (m, 2H), 7.25-7.29 (m, 2H), 7.18-7.21 (m, 2H), 6.43-6.46 (m,
2H), 4.72 (bs, 1H), 4.60-4.68 (m, 2H), 4.54 (d, JP-H = 16.55 Hz, 1H), 4.49-
4.58 (m, 1H), 1.30 (d, JH-H = 6.31 Hz, 3H), 1.29 (d, JH-H = 6.15 Hz, 3H),
1.21 (d, JH-H = 6.15 Hz, 3H), 0.99 (d, JH-H = 6.15 Hz, 3H),0.10-0.87 (bm,
3
3H). 13C NMR (125 MHz, CDCl3)  145.2 (d, JP-C = 11.8 Hz, NC), 134.3
2
4
(d, JP-C = 2.7 Hz, C), 131.9 (s, CH), 128.5 (d, JP-C = 1.8 Hz, CH),130.0
3
(d, JP-C = 4.5 Hz, CH), 121.8 (d, 5JP-C = 3.6 Hz, C), 115.4 (s, CH), 110.4
2
2
[(N-4-Bromophenyl)amino](phenyl)methyl]phenylphosphinous acid-
borane ethyl ester (20b). 19b (0.107 g, 0.25 mmol) was reacted with
BH3-SMe2 (71.2 L, 0.75 mmol) for 20 h according to general procedure
C to afford 20b as a mixture of diastereoisomers isolated as a mixture
(0.064 g, 0.15 mmol, 60, dr = 51:49, 31P NMR). An oil. IR (ATR, thin
(s, C), 74.0 (d, JP-C = 3.7 Hz, CH), 73.5 (d, JP-C = 4.9 Hz, CH), 59.4 (d,
1JP-C = 62.7 Hz, CH), 24.12 (d, 3JP-C = 2.7 Hz, CH3), 24.09 (d, 3JP-C = 3.6
3
3
Hz, CH3), 23.8 (d, JP-C = 4.5 Hz, CH3), 23.3 (d, JP-C = 5.4 Hz, CH3).
31P NMR (202 MHz, CDCl3)  134.81 (bm). HRMS (ESI/TOF) Found m/z:
487.9997;C19H25Br2NO2P ([M-BH3]+H+) requires m/z: 487.9984. Anal.
Calcd for C19H27Br2NO2PB: C, 45.37; H, 5.41; N, 2.78; Found: C, 45.50;
H, 5.79; N, 3.00.
film): 3395, 3059, 2384, 1591, 1488, 1042, 810, 692 cm−1 1H NMR (500
.
MHz, CDCl3)  7.69-7.73 (m, 2H); 7.50-7.56 (m, 1H), 7.43-7.50 (m, 4H),
7.28-7.38 (m, 9H), 7.11-7.20 (m, 2H), 7.15-7.19 (m, 2H, minor), 7.11-7.14
(m, 2H, major), 7.01-7.04 (m, 1H, major), 6.90-7.01 (m, 1H, minor), 6.45-
6.49 (m, 2H, minor), 6.38-6.41 (m, 2H, major), 4.94 (bs, 1H), 4.77-4.80
(m, 2H), 4.09-4.18 (m, 1H, minor), 4.00-4.08 (m, 1H, minor), 3.80-3.90 (m,
1H, major), 3.64-3.71 (m, 1H, major), 1.31 (t, JP-H = 7.04 Hz, 3H, minor),
1.14 (t, JP-H = 6.94 Hz, 3H, major), 0.05-1.10 (bm, 6H). 13C NMR (125
24b: 4-bromo-N-(-4-bromobenzyl)aniline.[31] Waxy white solid. Rf
0.45 (hexane/AcOEt 10:1). IR (ATR, solid): 3397, 2390, 1589, 1487,
1010, 810 cm−1 1H NMR (500 MHz, CDCl3)  7.44-7.48 (m, 2H), 7.25-
=
.
7.30 (m, 2H), 7.21-7.25 (m, 2H), 6.51-6.61 (m, 2H), 4.28 (bs, 2H).
13C NMR (125 MHz, CDCl3)  155.1, 138.1, 132.1, 131.8, 129.4, 121.6,
116.0, 48.7. HRMS (ESI/TOF) Found: m/z: 339.9323 C13H12Br2N
([M+H]+) requires m/z: 339.9331.
3
3
MHz, CDCl3)  145.6 (d, JP-C = 10.0 Hz, NC, minor), 145.3 (d, JP-C
=
2
11.8 Hz, NC, major), 134.8 (s, C, major), 134.3 (d, JP-C = 3.6 Hz, C,
minor), 132.3 (d, JP-C = 2.7 Hz, major), 132.2 (d, JP-C = 2.7 Hz, minor),
4
4
13
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201801518
European Journal of Organic Chemistry
FULL PAPER
[1-(N-p-Bromophenylamino)]-[1-(o-bromophenyl)methyl]phospho-
nous acid-borane diisopropyl ester (23c). 22c (0.126 g, 0.25 mmol)
was reacted with BH3-SMe2 (118.6 L, 1.25 mmol) for 72 h according to
general procedure C to afford 23c (0.0567 g, 0.113 mmol, 45) and 24c
(0.0322 g, 0.095 mmol, 38).
2.30 Hz, C), 132.1 (s, CH), 129.1 (d, JP-C = 3.6 Hz, CH), 123.3 (d, JP-C =
2.7 Hz, CH), 115.3 (s, CH), 110.8 (s, C), 74.2 (d,2JP-C = 3.6 Hz, CH), 73.9
2
3
(d, JP-C = 4.5 Hz, CH), 59.7 (d,1JP-C = 60.9 Hz, CH), 24.1 (d, JP-C = 2.7
3
Hz, CH3), 23.8 (d, JP-C = 3.60 Hz, CH3), 23.4 (d, JP-C = 4.5 Hz, CH3).
31P NMR (202 MHz, CDCl3)  134.81 (bm). HRMS (ESI/TOF) Found:
m/z: 455.0722; C19H25BrN2O4P ([M-BH3+H]+) requires m/z: 455.0730.
Anal. Calcd for C19H27BrN2O4PB: C, 48.65; H, 5.80; N, 5.97. Found: C,
48.82; H, 6.20; N, 5.58.
23c: Colourless oil. Rf = 0.57 (hexane/AcOEt 10:1). IR (ATR, thin film):
3405, 2978, 2408, 1497, 987, 741 cm−1 1H NMR (500 MHz, CDCl3) 
.
7.55-7.57 (m, 1H), 7.44-7.47 (m, 1H), 7.26-7.28 (m, 1H), 7.20-7.22 (m,
2H), 7.12-7.14 (m, 1H), 6.47-6.50 (m 2H), 5.31 (d, JH-H = 18.34 Hz, 1H),
4.89 (bs, 1H), 4.70-4.77 (m, 1H), 4.45-4.50 (m, 1H), 1.30 (d, JH-H = 6.05
Hz, 3H), 1.29 (d, JH-H = 6.05 Hz, 3H), 1.27 (d, JH-H = 6.24 Hz, 3H), 0.80 (d,
JH-H = 6.05 Hz, 3H), 0.23-0.74 (bm, 3H). 13C NMR (125 MHz, CDCl3) 
145.0 (d,3JP-C = 12.6 Hz, NC), 135.1 (d, JP-C = 4.4 Hz, C), 132.6 (s, CH),
132.0 (s, CH), 129.4 (d, JP-C = 2.2 Hz, CH), 127.6 (d, 4JP-C = 3.2 Hz, CH),
[1-(N-p-Bromophenylamino)]-[1-(p-anisyl)methyl]phosphonous acid-
borane diisopropyl ester (23f). 22f (0.114 g, 0.25 mmol) was reacted
with BH3-SMe2 (118.6 L, 1.25 mmol) for 16 h according to general
procedure C to afford 23f (0.0727 g, 0.16 mmol, 64) as an oil. Rf = 0.89
(hexane/AcOEt 2:1). IR (ATR, thin film): 3402, 2978, 2386, 1594, 1494,
1247, 1102, 972, 811 cm−1 1H NMR (500 MHz, CDCl3)  7.28-7.31 (m,
.
3
2
125.5 (d, JP-C = 5.5 Hz, C), 115.2 (s, CH), 110.2 (s, C), 74.2 (d, JP-C
=
2H); 7.17-7.20 (m, 2H), 6.84-6.87 (m, 2H), 6.45-6.50 (m, 2H), 4.60-4.67
(m, 1H), 4.54 (d, JP-H = 17.02 Hz, 1H), 4.47-4.52 (m, 1H), 3.79 (s, 3H),
2
1
4.2 Hz, CH), 73.0 (d, JP-C = 5.5 Hz, CH), 59.1 (d, JP-C = 65.2 Hz, CH),
24.10 (d, 3JP-C = 2.2 Hz, CH3), 24.08 (d, 3JP-C = 2.2 Hz, CH3), 24.0 (d, 3JP-
1.29 (d, JH-H = 6.15 Hz, 3H), 1.28 (d, JH-H = 6.47 Hz, 3H), 1.20 (d, JH-H
=
3
= 4.2 Hz, CH3), 22.8 (d, JP-C = 4.2 Hz, CH3). 31P NMR (202 MHz,
6.15 Hz, 3H), 0.96 (d, JH-H = 6.15 Hz, 3H), 0.12-0.83 (bm, 3H). 13C NMR
C
5
3
CDCl3)

136.64 (bm). HRMS (ESI/TOF) Found m/z: 487.9983;
(125 MHz, CDCl3)  159.4 (d, JP-C = 2.7 Hz, OC), 145.7 (d, JP-C = 11.8
3 2
C19H25Br2NO2P ([M-BH3+H]+) requires m/z: 487.9984. Anal. Calcd for
C19H27Br2NO2PB: C, 45.37; H, 5.41; N, 2.78. Found: C, 45.50; H, 5.79; N,
3.00.
Hz, NC), 131.9 (s, CH), 129.5 (d, JP-C = 4.5 Hz, CH), 126.8 (d, JP-C =
4
2.7 Hz, C), 115.5 (s, CH), 113.6 (d, JP-C = 2.7 Hz, CH), 110.0 (s, BrC),
73.8 (d, 2JP-C = 3.6 Hz, CH), 73.2 (d, 2JP-C = 5.5 Hz, CH), 59.1 (d, 1JP-C
=
64.5 Hz, CH), 55.2 (s, CH3), 24.18 (d, 3JP-C = 2.7 Hz, CH3), 24.12 (d, 3JP-C
= 2.7 Hz, CH3), 23.9 (d, JP-C = 4.5 Hz, CH3), 23.3 (d, JP-C = 5.5 Hz, CH3).
31P NMR (202 MHz, CDCl3)  135.27 (bm). 11B NMR (160.5 MHz, CDCl3)
 -44.76 (bm). GC-MS m/z (rel. int. %): 292 [(p-AnCH2NHC6H4-Br+] (15),
291 (99), 290 (98), 289 (100), 288 (83), 167 [(i-PrO)2POH+] (26), 166 (16),
156 (25), 155 (26). Anal. Calcd for C20H30BBrNO3P: C, 52.89; H, 6.66; N,
3.08. Found: C, 52.70; H, 6.16; N, 2.88.
24c: N-(2-Bromobenzyl)-4-bromoaniline). A colourless oil. Rf = 0.46
(hexane/AcOEt 10:1). IR (ATR, solid): 3426, 2921, 1593, 1495, 1023,
809, 745 cm−1. 1H NMR (500 MHz, CDCl3)  7.58-7.59 (m, 1H), 7.35-7.38
(m, 1H), 7.29-7.30 (m, 1H), 7.23-7.27 (m, 2H), 7.14-7.17 (m, 1H), 6.48-
6.51(m, 2H), 4.39 (bs, 2H), 4.25 (bs, 1H); 13C NMR (125 MHz, CDCl3) 
146.6 (s, C), 137.6 (s, C), 132.9 (s, CH), 132.0 (s, CH), 129.1 (s, CH),
128.9 (s, CH), 127.6 (s, CH), 123.3 (s, C), 114.6 (s, CH), 109.4 (s, C),
48.4 (s, CH2). GC-MS m/z (rel. int. %): 343 ([M]+, 17), 342 (8), 341 (37),
340 (8), 339 (19). HRMS (ESI/TOF) Found m/z: 339.9327;
C13H12NBr2([M+H]+) requires m/z: 339.9934.
N-p-Bromophenylaminomethylphosphonous
acid-borane
diisopropyl ester (23g). 22g (0.0875 g, 0.25 mmol) was reacted with
BH3-SMe2 (0.237 mL, 2.5 mmol) for 4 h according to general procedure
C to afford 23g (0.0435 g, 0.125 mmol, 50) as an oil. Rf = 0.51
(hexane/AcOEt 6:1). IR (ATR, thin film): 3403, 2978, 2384, 1497, 971,
[1-(N-p-Bromophenylamino)]-1-(m-nitrophenyl)methylphosphonous
acid-borane diisopropyl ester (23d).22d (0.118 g, 0.25 mmol) was
reacted with BH3-SMe2 (118.6 L, 1.25 mmol) for 48 h according to
general procedure C to afford 23d (0.0704 g, 0.15 mmol, 60) as a
yellow oil. Rf = 0.40 (hexane/AcOEt 10:1). IR (ATR, thin film): 3400, 2979,
2390, 1527, 1360, 975, 810 cm−1.1H NMR (500 MHz, CDCl3): 8.28-8.29
(m, 1H), 8.15-8.18 (m, 1H), 7.43-7.73 (m, 1H), 7.50-7.53 (m, 1H), 7.20-
7.23 (m, 2H), 6.44-6.48 (m, 2H), 4.78 (bs, 1H), 4.69 (d, JP-H = 15.92 Hz,
1H), 4.69-4.63 (m, 1H), 4.59-4.63 (m, 1H), 1.31 (d, JH-H = 6.15 Hz, 3H),
809 cm−1 1H NMR (500 MHz, CDCl3)  7.25-7.28 (m, 2H), 6.54-6.55 (m,
.
2H), 4.60-4.71 (m, 2H), 3.91 (bs, 1H), 3.42 (d, JP-H = 4.41 Hz, 2H), 1.32
(d, JH-H = 6.15 Hz, 6H), 1.25 (d, JH-H = 6.15 Hz, 6H), 0.20-0.91 (bm, 3H).
13C NMR (125 MHz, CDCl3)  146.5 (d, JP-C = 7.3 Hz, NC), 131.8 (s, CH),
2
1
114.9 (s, CH), 109.9 (s, C), 72.9 (d, JP-C = 4.5 Hz, CH), 44.8 (d, JP-C
=
3
3
67.2 Hz, CH2), 24.12 (d, JP-C = 2.7 Hz, CH3), 23.97 (d, JP-C = 4.5 Hz,
CH3). 31P NMR (202 MHz, CDCl3)  136.33 (bm). GC-MS m/z (rel.
int. %): 335 ([M-BH3]+, 6), 333 (6). HRMS (ESI/TOF) Found m/z:
334.0573; C13H22BrNO2P ([M-BH3+H]+) requires m/z: 334.0566. Anal.
Calcd for C13H24BBrNO2P: C, 44.86; H, 6.95; N, 4.02. Found: C, 44.90; H,
6.80; N, 3.99.
1.30 (d, JH-H = 6.15 Hz, 3H), 1.23 (d, JH-H = 6.15 Hz, 3H), 1.01 (d, JH-H
=
6.15 Hz, 3H), 0.10-0.87 (bm, 3H). 13C NMR (125 MHz, CDCl3)  148.1
(d,4JP-C = 2.7 Hz, NC), 144.9 (d, 3JP-C = 11.8 Hz, NC), 137.9 (d, JP-C = 2.7
Hz, C), 134.1 (d, JP-C = 3.6 Hz, CH), 132.1 (s, CH), 129.2 (d, JP-C = 1.8
Hz, CH), 123.3 (d, JP-C = 3.6 Hz, CH), 123.1 (d, JP-C = 2.7 Hz, CH), 115.4
(s, CH), 110.8 (s, C), 72.4 (d, 2JP-C = 3.6 Hz, CH), 73.9 (d, 2JP-C = 5.5 Hz,
CH), 59.4 (d, 1JP-C = 61.8 Hz, CH), 24.0 (s, CH3), 23.8 (d, 3JP-C = 4.5 Hz,
CH3), 23.4 (d, 3JP-C = 4.5 Hz, CH3). 31P NMR (202 MHz, CDCl3)  134.81
(bm). HRMS (ESI/TOF) Found m/z: 503.9927; C19H28BrN2O4PB ([M+H]+)
requires m/z: 503.9933. Anal. Calcd for C19H27BrN2O4PB: C, 48.65 H,
5.80 N, 5.97. Found: C, 48.90, H, 5.75, N, 5.90.
1-[N-p-Hydroxyphenylamino]-(1-phenyl)methylphosphonous acid-
borane diisopropyl ester (23h). 22h (0.0908 g, 0.25 mmol) was reacted
with BH3-SMe2 (118.6 L, 1.25 mmol) for 16 h according to general
procedure C to afford 23h (0.0605 g, 0.168 mmol, 67) as a solid, m.p.
78.5-79.0 C. Rf = 0.27 (hexane/AcOEt 6:1). IR (ATR, solid): 3247, 2980,
2394, 1511, 1103, 975, 696 cm−1. 1H NMR (500 MHz, CDCl3)  7.39-7.40
(m, 2H), 7.24-7.31 (m, 3H), 6.60-6.64 (m, 2H), 6.48-6.51 (m, 2H), 4.61-
4.64 (m, 1H), 4.58 (d, JP-H = 16.71 Hz, 1H), 4.47-4.51 (m, 1H), 4.33 (bs,
1H), 1.29 (d, JH-H = 6.31 Hz, 3H), 1.28 (d, JH-H = 6.15 Hz, 3H), 1.21 (d, JH-
[1-(N-p-Bromophenylamino)]-1-(p-nitrophenyl)methylphosphonous
acid-borane diisopropyl ester (23e). 22e (0.118 g, 0.25 mmol) was
reacted with BH3-SMe2 (118.6 L, 1.25 mmol) for 16 h according to
general procedure C to afford 23e (0.093 g, 0.198 mmol, 79) as a
yellow solid, m.p. 85.9-86.9 C. Rf = 0.40 (hexane/AcOEt 10:1). IR (ATR,
= 6.15 Hz, 3H), 0.93 (d, JH-H = 6.15 Hz, 3H). 13C NMR (125 MHz,
H
CDCl3)  148.2 (s, OC), 140.6 (d, 3JP-C = 11.8 Hz, NC), 145.6 (d, 2JP-C
=
4
3
3.6 Hz, C), 128.5 (d, JP-C = 4.5 Hz, CH), 128.1 (d, JP-C = 1.8 Hz, CH),
127.8 (d, 5JP-C = 1.8 Hz, CH), 116.0 (s CH), 115.3 (s CH), 73.6 (d, 2JP-C
=
2
1
solid): 3401, 2976, 2401, 1592, 1499, 1348, 1105, 733, 499 cm−1
.
4.5 Hz, CH), 73.1 (d, JP-C = 5.5 Hz, CH), 60.8 (d, JP-C = 63.6 Hz, CH),
24.1 (d, 3JP-C = 1.8 Hz,CH3), 23.8 (d, 3JP-C = 4.5 Hz,CH3), 23.8 (d, 3JP-C
1H NMR (500 MHz, CDCl3)  8.18-8.21 (m, 2H), 7.55-7.60 (m, 2H), 7.18-
7.21 (m, 2H), 6.41-6.43 (m, 2H), 4.79 (bs, 1H), 4.68 (d, JP-H = 15.76 Hz,
1H), 4.63-4.70 (m, 1H), 4.53-4.60 (m, 1H), 1.31 (d, JH-H = 6.18 Hz, 3H),
=
5.5 Hz,CH3). 31P NMR (202 MHz, CDCl3)  136.02 (bm). 11B NMR (160.5
MHz, CDCl3)  -44.58 (bm). HRMS (ESI/TOF) Found m/z: 362.2050;
C19H30BNO3P ([M+H]+) requires m/z: 362.2048. Anal. Calcd for
C19H29BNO3P: C, 63.18; H, 8.09; N, 3.88; Found: C, 63.45; H, 8.20; N,
4.00.
1.30 (d, JH-H = 6.31 Hz, 3H), 1.23 (d, JH-H = 5.99 Hz, 3H), 1.02 (d, JH-H
=
6.31 Hz, 3H), 0.10-0.90 (bm, 3H). 13C NMR (125 MHz, CDCl3)  147.6 (d,
3
2
5JP-C = 2.7 Hz, NC), 144.91 (d, JP-C = 10.9 Hz, NC), 143.2 (d, JP-C
=
14
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201801518
European Journal of Organic Chemistry
FULL PAPER
[1-(N-p-Anisylamino)-(1-phenyl)methyl]phosphonous
acid-borane
2H), 3.75 (bs, 1H), 3.44 (d, JP-H = 4.57 Hz, 2H), 2.26 (s, 3H), 1.33 (d, JH-H
= 6.15 Hz, 6H), 1.27 (d, JH-H = 6.15 Hz, 6H), 0.22-0.94 (bm, 3H).
diisopropyl ester (23i). 22i (0.0944 g, 0.25 mmol) was reacted with BH3-
SMe2 (118.6 L, 1.25 mmol) for 16 h according to general procedure C to
afford 23i (0.059 g, 0.158 mmol, 63) as an oil. Rf = 0.51 (hexane/AcOEt
10:1). IR (ATR, thin film): 3399, 2978, 2386, 1509, 1236, 1102, 977,
.
815 cm−1 1H NMR (400 MHz, CDCl3)  7.39-7.40 (m, 2H), 7.30-7.33 (m,
2H), 7.24-7.27 (m, 1H), 6.69-6.72 (m, 2H), 6.54-6.58 (m, 2H), 4.62-4.69
13C NMR (125 MHz, CDCl3)  145.2 (d, 3JP-C = 8.2 Hz, C), 129.6 (s, CH),
2
127.6 (s, C), 113.5 (s, CH), 72.7 (d, JP-C = 4.5 Hz, CH), 45.1 (d,1JP-C
=
66.3 Hz, CH2), 24.1 (d, 3JP-C = 2.7 Hz, CH3), 24.0 (d, 3JP-C = 4.5 Hz, CH3),
20.4 (s, CH3). 31P NMR (202 MHz, CDCl3)  136.86 (bm).GC-MS m/z (rel.
int. %): 269 ([M-BH3+], 3), 150 (5), 121 (10), 120 (100). HRMS (ESI/TOF)
Found m/z: 270.1616; C14H25NO2P ([M-BH3+H]+) requires m/z: 270.1617.
Anal. Calcd for C14H27BNO2P: C, 59.38; H, 9.61; N, 4.95. Found: C,
59.45; H, 9.80; N, 4.90.
(m, 1H), 4.59 (d, JH-H = 6.31 Hz, 1H), 4.47-4.55 (m, 1H), 3.70 (s, 3H),
1.30 (d, JH-H = 6.15 Hz, 3H), 1.28 (d, JH-H = 6.15 Hz, 3H), 1.22 (d, JH-H
=
6.15 Hz, 3H), 0.93 (d, JH-H = 6.15 Hz, 3H), 0.17-0.81 (bm, 3H). 13C NMR
(125 MHz, CDCl3)  152.5 (s, OC), 140.7 (d, 3JP-C = 11.8 Hz, NC), 139.7
2
4
(d, JP-C = 2.7 Hz, C), 128.5 (d, 3JP-C = 4.5 Hz, CH), 128.1 (d, JP-C = 1.8
N-Phenylmethylaminomethylphosphonous
acid-P,N-bisborane
Hz, CH), 127.4 (d, 5JP-C = 2.7 Hz, CH), 115.2 (s, CH), 114.7 (s, CH), 73.6
diisopropyl ester (27). 25 (0.0713 g, 0.25 mmol) was reacted with BH3-
SMe2 (118.6 L, 1.25 mmol) for 48 h according to general procedure C to
afford 27 (0.178 g, 0.06 mmol, 24) as an oil. Rf = 0.58 (hexane/AcOEt
2
1
(d,2JP-C = 4.5 Hz, CH), 73.1 (d, JP-C = 5.5 Hz, CH), 60.7 (d, JP-C = 63.6
3
3
Hz, CH), 55.8 (s, CH3), 24.1 (d, JP-C = 1.8 Hz, CH3), 23.8 (d, JP-C = 4.5
3
Hz, CH3), 23.2 (d, JP-C = 4.5 Hz, CH3).31P NMR (202 MHz, CDCl3) 
4:1). IR (ATR, thin film): 2930, 2383, 1374, 969, 784, 697 cm−1 1H NMR
.
136.02 (bm). 11B NMR (160.5 MHz, CDCl3)  -44.62 (bm). HRMS
(ESI/TOF) Found m/z: 362.1895; C20H29NO3P ([M-BH3+H]+)requires m/z:
362.1880. Anal. Calcd for C20H31BNO2P: C, 64.01; H, 8.33; N, 3.73.
Found: C, 64.30; H, 8.50; N, 3.68.
(500 MHz, CDCl3) 7.34-7.51 (m, 5H), 4.63-4.71 (m, 2H), 4.18 (bs, 1H),
3.95-4.15 (m, 2H), 3.03-3.26 (m, 2H), 1.42-2.07 (bm, 3H), 1.35 (d, JH-H
=
6.31 Hz, 3H), 1.34 (d, JH-H= 6.15 Hz, 3H), 1.31 (d, JH-H= 6.15 Hz, 3H),
1.27 (d, JH-H= 5.99 Hz, 3H), 0.22-0.95 (bm, 3H).13C NMR (125 MHz,
CDCl3)  133.4 (s, C), 130.0 (s, CH), 129.9 (s, CH), 128.8 (s, CH), 74.0
(d, 2JP-C = 2.7 Hz, CH), 73.7 (d, 2JP-C = 2.7 Hz, CH), 60.8 (d, 3JP-C = 2.7 Hz,
[1-(N-p-Tolylamino)-1-phenylmethyl]phosphonous
diisopropyl ester (23j). 22j (0.0903 g, 0.25 mmol) was reacted with BH3-
SMe2 (118.6 L, 1.25 mmol) for 16 h according to general procedure C to
acid-borane
1
CH2), 54.9 (d, JP-C = 55.4 Hz, CH2), 24.1 (d, 3JP-C = 2.7 Hz, CH3), 24.05
3
3
3
(d, JP-C = 3.6 Hz, CH3), 23.91 (d, JP-C = 1.8 Hz, CH3), 23.88 (d, JP-C
=
afford 23j (0.0629 g, 0.175 mmol, 70) as an oil. Rf
(hexane/AcOEt 10:1). IR (ATR, thin film): 3404, 2978, 2386, 1517, 1236,
1102, 976, 803 cm−1 1H NMR (500 MHz, CDCl3)  7.40-7.47 (m, 2H),
=
0.56
1.8 Hz, CH3). 31P NMR (202 MHz, CDCl3)  134.86 (bm). 11B NMR (160.5
MHz, CDCl3)  -42.76 (bm), -12.94 (bm). HRMS (ESI/TOF) Found m/z:
270.1610; C14H25NO2P ([M-2BH3+H]+) requires m/z: 270.1617. Anal.
Calcd for C14H30B2NO2P: C, 56.62, H, 10.18; N, 4.72. Found: C, 56.40, H,
10.30; N, 4.50.
.
7.30-7.37 (m, 2H), 7.24-7.26 (m, 1H), 6.92-6.95 (m, 2H), 6.50-6.54 (m,
2H), 4.62-4.69 (m, 1H), 4.65 (d, JP-H = 16.55 Hz, 1H), 4.49-4.57 (m, 1H),
2.20 (s, 3H), 1.31 (d, JH-H = 6.78 Hz, 3H), 1.29 (d, JH-H = 6.78 Hz, 3H),
1.22 (d, JH-H = 6.15 Hz, 3H), 0.94 (d, JH-H = 6.15 Hz, 3H),0.12-0.84 (bm,
Diisopropyl
[1-(N-p-Bromophenylamino)]-1-phenylmethylthio-
3
3H). 13C NMR (125 MHz, CDCl3)  144.3 (d, JP-C = 11.8 Hz, NC), 135.6
phosphonate (29). In a Schlenk tube (25 mL) equipped with a magnetic
stirrer and an argon inlet was placed-aminophosphonite-borane 23a
(0.0323 g, 0.076 mmol) in anhydrous toluene (2 mL). Then, was added
DABCO (0.0172 mg, 0.152 mmol) and sulfur (0.068 g, 0.266 mmol). The
resulting mixture was heated at 40 C for 48 h. Then, the reaction mixture
was evaporated to dryness and the residue was purified by column
chromatography on silica gel using hexane/AcOEt (v/v = 10:1) as eluent
to afford 29 (0.03 g, 0.068 mmol, 88%). A colourless oil. Rf = 0.61
(hexane/AcOEt 6:1). 1H NMR (500 MHz, CDCl3)  7.41-7.44 (m, 2H);
7.28-7.31 (m, 3H), 7.15-7.19 (m, 2H), 6.48-6.52 (m, 2H), 4.80-4.89 (m,
1H), 4.70 (d, JP-H = 23.96 Hz, 1H), 4.45-4.52 (m, 1H), 1.31 (d, JH-H = 6.31
Hz, 3H), 1.25(d, JH-H = 6.31 Hz, 3H), 1.23(d, JH-H = 5.99 Hz, 3H), 0.77(d,
(d, 2JP-C = 3.6 Hz, C), 129.6 (s, CH), 128.4 (d, 3JP-C = 4.5 Hz, CH), 128.1
(d, 4JP-C = 2.7 Hz, CH), 127.7 (d, 5JP-C = 2.7 Hz, CH), 127.4 (s, C), 113.9
(s, CH), 73.6 (d,2JP-C = 3.6 Hz, CH), 73.0 (d, 2JP-C = 5.5 Hz, CH), 60.0 (d,
1JP-C = 63.6 Hz, CH), 24.1 (d, 3JP-C = 1.8 Hz, CH3), 23.8 (d, 3JP-C = 4.5 Hz,
3
CH3), 23.2 (d, JP-C = 4.5 Hz, CH3), 20.3. 31P NMR (202 MHz, CDCl3) 
136.02 (bm). 11B NMR (160.5 MHz, CDCl3)  -44.66 (bm). HRMS
(ESI/TOF) Found m/z: 360.2245; C20H32BNO2P([M+H]+) requires m/z:
360.2255. Anal. Calcd for C20H31BNO2P: C, 66.87; H, 8.70; N, 3.90.
Found: C, 66.99; H, 8.85; N, 4.00.
[1-(N-p-Tolylamino)-(1-t-butyl)-methyl]phosphonous
acid-borane
3
diisopropyl ester (23k). 22k (0.0853 g, 0.25 mmol) was reacted with
BH3-SMe2 (118.6 L, 1.25 mmol) for 72 h according to general procedure
C to afford 23k (0.0203 g, 0.06 mmol, 24) as an oil. Rf = 0.72
(hexane/AcOEt 10:1). IR (ATR, thin film): 2976, 2384, 1518, 970,
JH-H = 6.31 Hz, 3H). 13C NMR (125 MHz, CDCl3)  145.3 (d, JP-C = 15.4
Hz, NC), 131.5 (s, C), 131.9 (s, CH), 128.4 (d, 4JP-C = 5.5 Hz, CH), 128.1
3
5
(d, JP-C = 2.7 Hz, CH), 128.0 (d, JP-C = 3.6 Hz, CH), 115.5 (s, CH),
109.9 (s, BrC), 73.3 (d, 2JP-C = 8.2 Hz, CH), 73.2 (d, JP-C = 7.3 Hz, CH),
2
753 cm−1
.
1H NMR (500 MHz, CDCl3)  6.95-6.99 (m, 2H), 6.56-6.59 (m,
60.4 (d, 1JP-C = 123.5 Hz, CH), 24.0 (d, 3JP-C = 2.7 Hz, CH3), 23.97 (d, 3JP-
C = 2.7 Hz, CH3), 23.5 (d, JP-C = 6.4 Hz, CH3), 22.6 (d, JP-C = 7.3 Hz, CH3).
31P NMR (202 MHz, CDCl3)  89.59 (bm). GC-MS m/z (rel. int. %): 262
[(C6H4-CH2NH-C6H4-Br)+] (13), 261 (92, 259 (91), 258 (100), 257 (79),
228 (63), 226 (25), 183 [(i-PrO)2P+] (10) 182 (10). Anal. Calcd for
C19H25BrNO2PS: C, 51.59; H, 5.70; N, 3.17. Found: C, 51.99; H, 5.88; N,
3.05.
2H), 4.48-4.71 (m, 2H), 3.93 (bs, 1H), 3.46 (dd, JH-H = 10.40 Hz, JP-H
15.29 Hz, 1H), 2.24 (s, 3H), 1.29 (d, JH-H = 6.15 Hz, 3H), 1.28 (d, JH-H
6.15 Hz, 3H), 1.27 (d, JH-H = 6.15 Hz, 3H), 1.12 (s, 9H), 1.00 (d, JH-H
=
=
=
6.15 Hz, 3H), 0.29-0.85 (bm, 3H). 13C NMR (125 MHz, CDCl3)  146.1 (d,
3JP-C = 3.6 Hz, NC), 129.5 (s, CH), 126.5 (s, C), 113.2 (s, CH), 72.8 (d,
2JP-C = 5.5 Hz, CH), 72.3 (d, 2JP-C = 6.4 Hz, CH), 64.1 (d, 1JP-C = 59.9 Hz,
2
3
CH), 36.5 (d, JP-C = 11.8 Hz, C), 28.1 (d, JP-C = 4.5 Hz, CH3), 24.4 (d,
3JP-C = 2.7 Hz, CH3), 24.2 (d, 3JP-C = 2.7 Hz, CH3), 23.9 (d, 3JP-C = 4.5 Hz,
3
CH3), 23.6 (d, JP-C = 4.5 Hz, CH3), 20.3 (s, CH3). 31P NMR (202 MHz,
Acknowledgments
CDCl3)
 139.14 (bm). HRMS (ESI/TOF) Found m/z: 340.2565;
C18H36BNO2P [M+H]+requires m/z: 340.2568. Anal. Calcd for
C18H35BNO2P: C, 63.72; H, 10.40; N, 4.13. Found: C, 63.45; H, 10.68; N,
4.38.
This work was financially supported by the Polish Ministry of
Science and Higher Education through the grant (N N204 111
035). The authors wish to thank Dr. Duncan Carmichael for
kindly reading the manuscript. Sylwia Sowa thanks Prof. Marek
Stankevič for his support during preparation of the manuscript.
N-p-Tolylaminomethylphosphonous acid-borane diisopropyl ester
(23l). 22l (0.111 g, 0.25 mmol) was reacted with BH3-SMe2 (0.237 mL,
2.5 mmol) for 4 h according to general procedure C to afford 23l (0.0311
g, 0.11 mmol, 44) as an oil. Rf = 0.59 (hexane/AcOEt 10:1). IR (ATR,
thin film): 3404, 2978, 2381, 1519, 1236, 1104, 971, 805 cm−1 1H NMR
.
Keywords: reduction • synthetic methods • chemoselectivity•
(500 MHz, CDCl3)  6.99-7.03 (m, 2H), 6.59-6.64 (m, 2H), 4.63-4.72 (m,
chirality• boranes•
15
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10.1002/ejoc.201801518
European Journal of Organic Chemistry
FULL PAPER
[1]
[2]
[3]
L. D. Quin,
A
Guide to Organophosphorus Chemistry, Wiley-
[14] N. P. Kenny, K. V. Rajendran, J. E. Jennings, D. G. Gilheany, Chem.
Eur. J. 2013, 19, 14210-14214.
Interscience, New York, 2000, p.74.
D. Herault, D. H. Nguyen, D. Nuel, G. Buono, Chem. Soc. Rev. 2015,
44, 2508-2528.
[15] (a) T. Imamoto, T. Kusumoto, N. Suzuki, K. Sato, J. Am. Chem. Soc.
1985, 107, 5301-5303; (b) M. Ohff, J. Holz, M. Quirmbach, A. Börner,
Synthesis 1998, 1391-1415.
For some recent examples, see: (a) G. Markl, J. Reisinger, P.
Kreitmeier, J. Langer, H. Nöth, Helv. Chim. Acta 2002, 85, 1714-1741;
(b) M. Toffano, C. Dobrota, J.-C. Fiaud, Eur. J. Org. Chem. 2006, 650-
656; (c) P. A. Byrne, K. V. Rajendran, J. Muldoon, D. G. Gilheany, Org.
Biomol. Chem. 2012, 10, 3531-3537; (d) C. A. Busacca, J. C. Lorenz, N.
Grinberg, N. Haddad, M. Hrapchak, B. Latli, H. Lee, P. Sabila, A. Saha,
M. Sarvestani, Sh. Shen, R. Varsolona, X. Wei, C. H. Senanayake, Org.
Lett. 2005, 7, 4277-4280; (e) C. A. Busacca, R. Raju, N. Grinberg, N.
Haddad, P. James-Jones, H. Lee, J. C. Lorenz, A. Saha, C. H.
Senanayake, J. Org. Chem. 2008, 73, 1524-1531; (f) A. K. Ghosh, D. R.
Nicponski, J. Kass, Tetrahedron Lett. 2012, 53, 3699-3702. (g) K.
Issleib, G. Grams, Z. Anorg. Allg. Chem. 1959, 299, 58-68.
[16] (a) K. V. Rajendran, D. G. Gilheany, Chem. Commun. 2012, 48, 817-
819; (b) S. S. Al Sulaimi, K. V. Rajendran, D. G. Gilheany, Eur. J. Org.
Chem. 2015, 5959-5965; (c) N. P. Kenny, K. V. Rajendran, D. G.
Gilheany, Chem. Comm. 2015, 51, 16561-16564.
[17] (a) R. Köster, Y. Morita, Angew. Chem. Int. Ed. 1965, 4, 593-594;
Angew. Chem. 1965, 77, 589-590; (b) R. Köster, W. Schüβler, L.
Synoradzki, Chem. Ber. 1987, 120, 1105-1115; (c) G. Keglevich, M.
Fekete, T. Chuluunbaatar, A. Dobó, V. Harmat, L. Tőke, J. Chem. Soc.,
Perkin Trans. I 2000, 4451-4455; (d) G. Keglevich, T. Chuluunbaatar, K.
Ludányi, L. Tőke, Tetrahedron 2000, 56, 1-6; (e) P. Kiełbasiński, M.
Albrycht, R. Żurawinski, M. Mikołajczyk, J. Mol. Catal. B: Enzym. 2006,
39, 45-49.
[4]
(a) Z. Huang, L. H. Lim, Z. Chen, Y. Li, F. Zhou, H. Su, J. Zhou, Angew.
Chem. Int. Ed. 2013, 52, 4906-4911; Angew. Chem. 2013, 125, 5006-
5011; (b) C. Ebner, C. A. Müller, C. Markert, A. Pfaltz, J. Am. Chem.
Soc. 2011, 133, 4710-4713; (c) N. Vinokurov, K. M. Pietrusiewicz, S.
Frynas, M. Wiebcke, H. Butenschön, Chem. Commun. 2008, 5408-
5410; (d) A. Ros, B. Estepa, A. Bermejo, E. Álvarez, R. Fernández, J.
M. Lassaletta, J. Org. Chem. 2012, 77, 4740-4750; (e) M. M. Nigra, A. J.
Yeh, A. Okrut, A. G. DiPasquale, S. W. Yeh, A. Solovyov, A.Katz,
Dalton Trans. 2013, 42, 12762-12771; (f) K. Naumann, G. Zon, K.
Mislow, J. Am. Chem. Soc. 1969, 91, 7012-7023; (g) D. Jr. Valentine, J.
F. Blount, K. Toth, J. Org. Chem. 1980, 45, 3691-3698.
[18] (a) M. Stankevič, K. M. Pietrusiewicz, Synlett 2003, 1012-1016; (b) M.
Stankevič, G. Andrijewski, K. M. Pietrusiewicz, Synlett 2004, 311-315;
(c) S. Lemouzy, M. Jean, L. Giordano, D. Hérault, G. Buono, Org. Lett.
2016, 18, 140-143.
[19] (a) S. Sowa, PhD Thesis, Maria Curie-Skłodowska University (Poland),
2015; (b) S. Sowa, M. Stankevič, A. Szmigielska, H. Małuszyńska, A. E.
Kozioł, K. M. Pietrusiewicz, J. Org. Chem. 2015, 80, 1672-1688; (b) S.
Sowa, M. Stankevič, A. Flis, K. M. Pietrusiewicz, Synthesis 2018, 50,
2106-2118.
[20] S. Lemouzy, D. H. Nguyen, V. Camy, M. Jean, D. Gatineau, L.
Giordano, J.-V. Naubron, N. Vanthuyne, D. Hérault, G. Buono, Chem.
Eur. J. 2015, 21, 15607-15621.
[5]
(a) E. Gorobets, G.-R. Sun, B. M. M. Wheatley, M. Parvez, B. A. Keay,
Tetrahedron Lett. 2004, 45, 3597-3601; (b) N. J. Lawrence, M. D. Drew,
S. M. Bushell, J. Chem. Soc., Perkin Trans. I 1999, 3381-3391; (c) B. O.
Ashburn, R. G. Carter, L. N. Zakharov, J. Am. Chem. Soc. 2007, 129,
9109-9116; (d) M. Zabłocka, B. Delest, A. Igau, A. Skowrońska, J.-P.
Majoral, Tetrahedron Lett. 1997, 38, 5997-6000.
[21] M. Kwiatkowska, G. Krasiński, M. Cypryk, T. Cierpiał, P. Kiełbasiński,
Tetrahedron: Asymmetry 2011, 22, 1581-1590.
[22] (a) D. Gatineau, D. H. Nguyen, D. Hérault, N. Vanthuyne, J. Leclaire, L.
Giordano, G. Buono, J. Org. Chem. 2015, 80, 4132-4141; (b) S.
Lemouzy, D. N. Nguyen, D. Gatineau, L. Giordano, D. Herault, G.
Buono, Pure Appl. Chem. 2016, 4, 88, 333-339.
[6]
[7]
(a) I. G. M. Campbell, J. K. Way, J. Chem. Soc. 1961, 83, 2133-2141;
(b) P. D. Henson, K. Naumann, K. Mislow, J. Am. Chem. Soc. 1969, 91,
5645-5646; (c) W. B. Farnham, R. A. Lewis, R. K. Murray, Jr., K.
Mislow, J. Am. Chem. Soc. 1970, 92, 5808-5809; (d) T. L. Emmick, R. L.
Letsinger, J. Am. Chem. Soc. 1968, 90, 3459-3465.
[23] (a) Y. Belabassi, M. I. Antczak, J. Tellez, J.-L. Montchamp, Tetrahedron,
2008, 64, 9181-9190; (b) O. Berger, J.-L. Montchamp, Angew. Chem.
Int. Ed. 2013, 52, 11377-11380; Angew. Chem. 2013, 125, 11587-
11590.
(a) M. Dutartre, J. Bayardon, S. Jugé, Chem. Soc. Rev. 2016, 45, 5771-
5794; (b) T. Coumbe, N. J. Lawrence, F. Muhammad, Tetrahedron Lett.
1994, 35, 625-628; (c) H.-C. Wu, J.-Q. Yu, J. B. Spencer, Org. Lett.
2004, 6, 4675-4678; (d) M. Berthod, A. Favre-Réguillon, J. Mohamad,
G. Mignani, G. Docherty, M. Lemaire, Synlett 2007, 10, 1545-1548; (e)
Y. Li, S. Das, S. Zhou, K. Junge, M. Beller, J. Am. Chem. Soc. 2012,
134, 9727-9732; (f) Y. Li, L.-Q. Lu, S. Das, S. Pisiewicz, K. Junge, M.
Beller, J. Am. Chem. Soc. 2012, 134, 18325-18329; (g) J. A. Buonomo,
C. G. Eiden, C. C. Aldrich, Chem. Eur. J. 2017, 23, 14434-14438; (h) T.
Imamoto, S.-I. Kikuchi, T. Miura, Y. Wada, Org. Lett. 2001, 3, 87-90.
(a) L. Horner, H. Hoffman, P. Beck, Chem. Ber.1958, 91, 1583-1588;
(c) T. Imamoto, T. Oshiki, T. Onozawa, T. Kusumoto, K. Sato, J. Am.
Chem. Soc.1990, 112, 5244-5252; (b) J.-L. Cabioch, B. Pellerin, J.-M.
Denis, Phosphorus Sulfur Silicon 1989, 44, 27-32; (c) J.-L. Cabioch, J.-
M. Denis, J. Organomet. Chem. 1989, 377, 227-233; (d) J.-C. Guillemin,
P. Savignac, J.-M. Denis, Inorg. Chem. 1991, 30, 2170-2173; (e) T.
Hanaya, H. Yamamoto, Bull. Chem. Soc. Jpn. 1989, 62, 2320-2327; (f)
C. A. Busacca, T. Bartholomeyzik, S. Cheekoori, R. Raju, M. Eriksson,
S. Kapadia, A. Saha, X. Zeng, C. H. Senanayake, Synlett 2009, 2, 287-
291; (g) R. M. Hiney, L. J. Higham, H. Müller-Bunz, D. G. Gilheany,
Angew. Chem. Int. Ed. 2006, 45, 7248-7251; Angew. Chem. 2006, 118,
7406-7409.
[24] (a) P. Kafarski, B. Lejczak Phosphorus, Sulfur and Silicon and the Relat.
Elem. 1991, 63, 193-215; (b) Aminophosphonic and Aminophosphinic
Acids.Chemistry and Biological Activity (Eds,; V. P. Kukhar, H. R.
Hudson), John Wiley & Sons, Chichester, U.K., 2000; (c) B. Lejczak, P.
Kafarski, Top. Heterocycl. Chem. 2009, 20,31-63; (d) F. Orsini, G. Sello,
M. Sisti, Curr. Med. Chem. 2010, 17, 264-289; (e) A. Mucha, P.
Kafarski, Ł. Berlicki, J. Med. Chem. 2011, 54, 5955-5980; (f) H. Studnik,
S. Liebsch, G. Forlani, D. Wieczorek, P. Kafarski, J. Lipok, New
Biotechnology 2015, 32, 1-6.
[8]
[25] Q. Xu, C.-Q. Zhao, L.-B. Han, J. Am. Chem. Soc. 2008, 130, 12648-
12655.
[26] For the direct conversions of P-BH3 bonds to P=O and P=S bonds with
retention of configuration at P, see: (a) T. Imamoto, K. Hirose, H.
Amano, H. Seki, Main Group Elements 1996, 1, 331-338; (b) J. Uziel, C.
Darcel, D. Moulin, C. Bauduin, S. Jugé, Tetrahedron: Asymmetry 2001,
12, 1441-1449.
[27] For recent use of N-aryl -amino phosphonates, see: (a) J. Lewkowski,
M. Morawska, A. Kaczmarek, D. Rogacz, P. Rychter, Molecules 2017,
22, 1132; (b) Y. Xu, K. Yan, B. Song, G. Xu, S. Yang, W. Xue, D. Hu, P.
Lu, G. Ouyang, L. Jin, Z. Chen, Molecules 2006, 11, 9, 666-676; (c) S.
Giberti, M. Bertazzini, M. Liboni, Ł. Berlicki, P. Kafarski, G. Forlani, Pest
Manag. Sci. 2017, 72, 435-443; (d) A. Rydzewska, A. Olender, A.
Mucha, P. Kafarski, ARKIVOC 2017, 2017, 107-117.
[9]
R. Köster, Y.-H. Tsay, L. Synoradzki, Chem. Ber. 1987, 120, 1117-1123.
[10] H. Fritzsche, U. Hasserodt, F. Korte, Chem. Ber. 1965, 98, 1681-1687.
[11] J.-M. Denis, H. Forintos, H. Szelke, G. Keglevich, Tetrahedron Lett.
2002, 43, 5569-5571.
[28] Similar retro Kabachnik-Fields process was also observed in BH3
reductions of -aminophosphine oxides; see ref. 18b.
[12] P. D. Henson, S. B. Ockrymiek, Jr. R. E. Markham, J. Org. Chem. 1974,
39, 15, 2296-2298.
[29] (a) D. Gorenstein, J. Am. Chem. Soc. 1970, 92, 644-650; (b) S. Trippett,
Phosphorus Sulfur Silicon Relat. Elem. 1976, 1, 89-98; (c) S.
Matsukawa, K. Kajiyama, S. Kojima, S.-Y. Furuta, Y. Yamamoto, K.-Y.
Akiba, Angew. Chem. Int. Ed. 2002, 41, 4718-4722; Angew. Chem.
2002, 114, 4912-4916.
[13] (a) I. G. M. Campbell, J. K. Way, J. Am. Chem. Soc. 1960, 82, 5034-
5041; (b) L. D. Quin, J. Szewczyk, Phosphorus Sulfur and Silicon 1984,
21, 161-170.
16
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[30] (a) R. S. Berry, J. Chem. Phys. 1960, 32, 933-938; (b) C. Moberg,
Angew. Chem. Int. Ed. 2011, 50, 10290-10292; Angew. Chem. 2011,
123, 10473-10475.
[31] J. Pan, X. Han, N. Sun, H. Wu, D. Lin, P. Tien, H.-B. Zhou, S. Wu, RSC
Advances 2015, 5, 68, 55100-55108.
17
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Entry for the Table of Contents (Please choose one layout)
Layout 1:
FULL PAPER
The chemoselective reduction of
Chemoselective reduction
P=O bond in -hydroxy and -amino
Sylwia Sowa and K. Michał
Pietrusiewicz*
phosphonic/phosphinic
acid
derivatives can be achieved without
concomitant scission of their ester
and amide bonds by the use of
1 – 16
Chemoselective reduction of the
P=O bond in the presence of P-O
and P-N bonds in phosphonate and
phosphinate derivatives
commercially
available
BH3
complexes. The reduction involves
an intramolecular assistance by the
proximal OH or NH groups enabling
preferential
removal
of
the
phosphoryl oxygen.
18
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