Diastereoselective desymmetrization of diarylphosphinous acid-borane amides under Birch reduction

Article abstract of DOI:10.1039/c4ob02440k

Treatment of diarylphosphinous acid-borane amides possessing chiral amido functionality with an alkali metal solution in liquid ammonia induced a preferential dearomatization of one aryl substituent at phosphorus leading to the formation of non-equimolar amounts of diastereomers. Diastereoselectivity of dearomatization depends strongly on the structure of a chiral auxiliary.

Full text of DOI:10.1039/c4ob02440k

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Diastereoselective desymmetrization of
diarylphosphinous acid-borane amides under
Cite this: DOI: 10.1039/c4ob02440k
Birch reduction†
Marek Stankevič
Received 20th November 2014,
Accepted 15th December 2014
Treatment of diarylphosphinous acid-borane amides possessing chiral amido functionality with an alkali
metal solution in liquid ammonia induced a preferential dearomatization of one aryl substituent at phos-
phorus leading to the formation of non-equimolar amounts of diastereomers. Diastereoselectivity of
dearomatization depends strongly on the structure of a chiral auxiliary.
DOI: 10.1039/c4ob02440k
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Introduction
Desymmetrization of non-chiral symmetrical substrates is one
of the most convenient methods for the synthesis of chiral
molecules. This process is based on the stereoselective trans-
formation of a symmetrical fragment by a chiral reagent. The
prominent example of such a reagent is a combination of a
organolithium reagent and (−)-sparteine which is used for
stereoselective deprotonation of prochiral groups or hydrogen
atoms (Scheme 1).1
In organophosphorus chemistry this approach has found
some applications, especially for the synthesis of P-stereogenic
compounds in a non-racemic form. Deprotonation of one of
the methyl groups in dimethylphenyl-phosphine-borane with a
chiral base followed by the addition of an electrophile led to
the formation of 4 with good yield and enantioselectivity
(Scheme 2).2
Scheme 2 Desymmetrization of phosphine-borane 3.
The main feature of all the examples discussed above is
that desymmetrization of organophosphorus compounds is
affected through the transformation of alkyl groups. But, when
considering the applications of organophosphorus com-
pounds in the synthesis and catalysis a lot of examples of
Ph2P(X)-substituted compounds (X = lone pair, BH3, O, S)
could be found in the literature. Regarding all the above, these
compounds could serve as excellent precursors for the prepa-
ration of P-stereogenic organophosphorus compounds
through selective functionalization of one aryl moiety.
This methodology was applied for the synthesis of many
P-chiral organophosphorus compounds, including secondary
phosphine-boranes,3 MiniPHOS ligands,4 proline analogues,5
1-phenyl-phosphol-2-ene-borane6 or PHOX-type ligands.7
Desymmetrization of the Ph2P(X) fragment was a topic of
several studies. Williams and coworkers used desymmetriza-
tion of diphenylphosphinic amides through the Directed
ortho-Metallation (DoM) strategy in the synthesis of P,P-
ligands.8 A good example of the stereoselective desymmetriza-
tion of the Ph2P(O) moiety in phosphinic amides using the
same approach was presented by Lopez Ortiz and coworkers
(Scheme 3).9
Scheme 1 Desymmetrization of amide 1.
Department of Organic Chemistry, Marie Curie-Skłodowska University, 33 Gliniana
Street, 20-614 Lublin, Poland. E-mail: marek.stankevic@poczta.umcs.lublin.pl;
Fax: +48 81 524 22 51; Tel: +48 81 537 77 52
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c4ob02440k
Scheme 3 Desymmetrization of diphenylphosphinic amide
(−)-sparteine.
5 using
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The same authors attempted the desymmetrization of the
However, to achieve the transformation in a stereoselective
Ph2P(O) fragment in diphenylphosphinic amides with chiral manner an additional source of chirality is needed and the
amido functionality using the Directed ortho-Metallation easiest way to fulfill this requirement is to use chiral amido
(DoM) methodology.10 The diastereoselectivity level reached functionality. Regarding the size of the reagent (an electron)
the highest 5 : 1 ratio when triphenyltin chloride was used as the formation of an equimolar mixture of diastereomers is
an electrophile. All this lead to the conclusion that despite the expected and a careful separation of both isomers is needed to
limited number of precedences the synthesis of P-stereogenic get access to pure P-stereogenic compounds.
organophosphorus compounds through desymmetrization of
the Ar2P(X) moiety seems to have high synthetic potential.
In the course of our studies on the use of Birch reduction
in organophosphorus chemistry11 we attempted the dearomati-
Results and discussion
zation of phosphinic acid amides and phosphinous acid-borane
amides.12 Whereas diarylphosphinic amides tend to undergo
For initial screening, (S)-α-methylbenzylamine 9 was chosen as
a chiral amine (Scheme 5).
double Birch reduction of two arenes, dearomatization of diaryl-
phosphinous acid-borane amides led preferentially to the for-
Treatment of 9 with the Ph2PCl–NEt3 mixture followed by
mation of products with only one reduced aryl substituent.
the addition of either the BH3 complex or H2O2 led to the for-
Our observations lead to the conclusion that Birch
mation of 10a and 11a in good yields. These compounds were
then used as substrates for the synthesis of N-methyl and
reduction could be successfully applied for the synthesis of
P-stereogenic organophosphorus compounds as dearomatiza-
N-ethyl derivatives 10b,c and 11b,c by treatment with a strong
tion of symmetrically substituted diarylphosphinous acid-
base followed by the addition of the corresponding alkyl
borane amides should lead to the formation of a new com-
halide. N-Isopropyl substituted amides 10d and 11d were
obtained by a slightly different method. Treatment of 9 with
an excess of acetone led to the formation of the corresponding
pound with a chirality centre at the phosphorus atom
(Scheme 4).
imine which was in situ treated with NaBH4 yielding a second-
ary amine 12 in good yield. Furthermore, a treatment of 12
with the Ph2PCl–NEt3 mixture followed by the addition of
either the BH3 complex or H2O2 led to 10d and 11d,
respectively.
To get insight into the desymmetrization process Birch
reduction of the obtained compounds was performed
Scheme 4 Desymmetrization of diphenylphosphorus acid amides 7.
(Scheme 6, Table 1).
Scheme 5 The synthesis of (S)-α-phenylethylamine-derived diphenylphosphorus amides.
Scheme 6 Initial desymmetrization experiments.
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Table 1 Dearomatization of 10 and 11
Nr
Compound NR2*
Products (de)
1
10a
10b
10b
10b
10c
10d
11a
11b
11c
(S)-NHCHMePh
No reaction
2
(S)-N(Me)CHMePh 13b (71%, 52% de)
(S)-N(Me)CHMePh 13b (76%, 72% de)
(S)-N(Me)CHMePh 13b (20%, 60% de)
(S)-N(Et)CHMePh
(S)-N(iPr)CHMePh
(S)-NHCHMePh
(S)-N(Me)CHMePh 14b (20%, 0% de)/15b (50%)
(S)-N(Et)CHMePh
(S)-N(iPr)CHMePh
3a
4b
5
13c (77%, 42% de)
13d (21%, 10% de)
No reaction
6
7
8c
9c
14c (18%, 0% de)/15c (24%)
14d (14%, 9% de)/15d (24%)
10c 11d
a The reaction was performed at −97 °C. b The reaction was performed
at −115 °C. c The yields of the products were assigned based on NMR
analysis.
Scheme 7 The synthesis of L-prolinol-derived phosphorus acid amides.
nitrogen. Regarding this, we attempted to prepare a set of
diphenylphosphinous acid-borane amides possessing different
amido functions.
L-Prolinol-derived phosphinous acid-borane amides have
been prepared in a few step synthesis starting from L-proline
(Scheme 7).
A reduction of this amino acid with LiAlH4 led to a corres-
ponding aminoalcohol which upon treatment with PhP(NEt2)2
yielded a bicyclic oxazaphospholane as a single diastereomer.
Its reaction with phenyllithium followed by the addition of the
BH3 complex led to the formation of 16a in 73% yield after 4
steps. The free OH group in 16a was further protected either
with methyl (16b) or trimethylsilyl (16c) groups yielding new
C-chiral phosphinous acid-borane amides.
It was found that amides 10a and 11a remained intact
under the reaction conditions which could be attributed to the
presence of an acidic amide proton in both substrates. The use
of higher excess of an alkali metal led to the decomposition of
the starting material. On the other hand, N-alkyl-substituted
amides 10b–d smoothly underwent Birch reduction of only
one phenyl substituent yielding mixtures of two diastereomers.
Regarding the size of the reagent (an electron) we rather
expected the formation of an equimolar mixture of two
diastereomers but to our surprise the obtained products were
enriched in one diastereomer (Table 1, entries 2–6). In the
case of N-methyl substituted amide 10b Birch reduction led to
the formation of a product with the highest diastereoselectivity
(52% de) under the standard reaction conditions. The
diastereoselectivity of the reaction could be additionally
improved by lowering the temperature (Table 1, entry 3) but
further cooling led to solidification of ammonia which
impeded the reaction rate and diastereoselectivity (Table 1,
entry 4). A further increase in the steric crowd at nitrogen by
replacing the methyl group with ethyl or i-propyl groups
dropped the diastereoselectivity of dearomatization down to
10% de in the case of 10d (Table 1, entry 6).
In contrast to phosphinous acid-borane amides 10b–d,
attempted Birch reduction of phosphinic amides 11b–d led
predominantly to the formation of double Birch reduction pro-
ducts 15b–d. This observation is in accordance with previous
results obtained with racemic diarylphosphinic amides.12 The
minor single Birch reduction products obtained from 11b–d
were generally equimolar mixtures of diastereomers. Such a
striking difference in the behavior of phosphinous acid-borane
amides 10b–d and phosphinic amides 11b–d must evolve from
different organizations of two phenyl substituents in 10 and in
11. In 10, there must be an interaction between the chiral
amido group and two phenyls which lead to differentiation of
SOMO+1 orbitals of both phenyl groups. Interestingly, there is
no such differentiation in phosphinic amides 11, which
means that the presence of the PvO bond perturbs the inter-
action between the amido group and the aryl substituent.
The diastereoselectivity of this desymmetrization could be
possibly raised by the modification of a chiral auxiliary at
Other compounds have been prepared in a common syn-
thetic pathway which included the preparation of primary
C-chiral amines in the first step (Scheme 8).
An amine 22d has been prepared in a two-step synthesis
from camphor 17. First, ketone was treated with hydroxyl-
amine hydrochloride and the obtained oxime 18 was further
treated with NaBH4 in the presence of NiCl2. The product was
obtained as a mixture of two isomers in a 1 : 0.2 ratio in favor
of an exo isomer. Amines 22a–c derived from L-menthol 19a,
quinine 19b and quinidine 19c were obtained in a three-step
synthesis. First, three alcohols were transformed into the
corresponding mesylates which were further treated with
sodium azide yielding azides 21a–c. Azide–amine group trans-
formation was achieved using the Staudinger reaction. A pre-
pared set of four amines plus two commercially available
α-(1-naphthyl)ethylamine and α-(2-naphthyl)ethylamine were
further subjected to the reaction with methyl chloroformate
and the products were treated with LiAlH4 yielding the corres-
ponding secondary N-methylamines 24a–f. In the final step
amines have been reacted with the Ph2PCl–NEt3 mixture fol-
lowed by the addition of the BH3 complex leading to the for-
mation of the desired diphenylphosphinous acid-borane
amides 25a,d–f. In the case of 25b and 25c the formation of a
complex mixture of products was observed. Amide 25d was
prepared from a 1 : 0.2 mixture of exo-/endo-bornylamine as a
1 : 0.4 mixture of isomers. An attempted separation of diaster-
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Scheme 8 Preparation of phosphinous acid-borane amides.
eomers yielded only a partially enriched mixture (dr = 1 : 0.1) derivative 28. Similarly, a treatment of N-bornyl-substituted
which was used in the desymmetrization reaction. amide 25d with an excess of sodium in liquid ammonia led to
A prepared set of diphenylphosphinous acid-borane amides the formation of H-phosphinous acid-borane amide 29 as the
has been subjected to dearomatization reaction (Scheme 9, main product and the Birch reduction product 26d as the
Table 2).
minor compound (Table 2, entry 6). Both products were
First, L-prolinol-derived phosphinous acid amides 16a–c obtained with moderate diastereoselectivities but the diaster-
have been subjected to a reaction with sodium in liquid eomeric excess of 29 was slightly higher.
ammonia. Similar to the previous observations, an attempted
A much more complex reaction was Birch reduction of
Birch reduction of 16a possessing an acidic hydrogen atom amides 25e and 25f possessing naphthyl moieties in the
failed to produce the desired product. Protected amides 16b,c amide fragment (Table 2, entries 7–10). In both cases the reac-
underwent Birch reduction yielding the desired products in tion with sodium in liquid ammonia led to the formation of
both low yields and diastereoselectivities (Table 2, entries 2 complex reaction mixtures. The naphthalene unit present in
and 3). The diastereoselectivity of reduction of 16b and 16c the substrates undergoes most probably Birch reduction along
was markedly lower than that for 10b, probably due to the with dearomatization of one of the phenyl groups at phos-
small difference in both substituents at nitrogen. Additionally, phorus. This process generates two additional chirality centers
in the case of 16c the formation of secondary phosphine- (at phosphorus and at carbon atoms) leading to a complex
borane 27 was observed. Similarly, N-neomenthyl-derived mixture of compounds. The use of higher excess of sodium led
amide 25a poorly underwent Birch reduction under the stan- to decomposition of substrates and the formation of P–H-type
dard reaction conditions (Table 2, entry 4) but the use of a compounds (Ph2P(BH3)H for 25e and P–H amides (58.90 ppm
higher excess of sodium improved the conversion remarkably and 59.68 ppm) for 25f).
(Table 2, entry 5). In the latter example the formation of H-
Unfortunately, despite many attempts, α-methylbenzyl-
phosphinous acid-borane amide 28 was observed as well. This amine remained the best chiral auxiliary for desymmetrization
compound could be formed through competitive P-aryl bond of diphenylphosphinous acid-borane amides through Birch
cleavage reaction. The diastereoselectivity of desymmetrization reduction. A replacement of this functionality with those
of 25a was moderate (22–23% de) and surprisingly there was derived from prolinol, L-menthol or camphor failed to improve
no selectivity in the formation of H-phosphinous acid-borane the diastereoselectivity of the desymmetrization reaction.
In the next step, desymmetrization of other symmetrically
substituted diarylphosphinous acid-borane amides has been
attempted. Two types of symmetrical secondary phosphine
oxides were chosen. The first type (oTol2P(O)H, pTol2P(O)H,
pAn2P(O)H) constitutes the molecules possessing either
unsymmetrically substituted arene substituents or arene sub-
stituents possessing para-substituted aryls. Birch reduction of
amides derived from these substrates should lead to the for-
Scheme 9 Desymmetrization of 16a–c and 25a–f.
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Table 2 Desymmetrization of 16a–c and 25a–f
Nr
Substrate
Products
1
2
16a
16b
No reaction
3
4
16c
25a
5b
25a
25d
6b
7
8c
25e
25e
A mixture of products (69.15 ppm, 70.94 ppm, 72.66 ppm and 73.16 ppm)
9
25f
25f
A mixture of products (71.41 ppm, 72.45 ppm and 74.69 ppm)
A mixture of products (58.90 ppm, 59.68 ppm, 71.41 ppm, 72.45 ppm and 74.69 ppm)
10c
a Isolated as a mixture of products. b 4.0 equiv. of sodium was used. c 5.0 equiv. of sodium was used.
mation of up to 8 isomers. The second type (mXyl2P(O)H, (3,5- ration of chlorophosphines. Additionally, oXyl2P(O)H and (3,5-
(MeO)2-C6H3)2P(O)H, oXyl2P(O)H, (3,5-(CF3)2-C6H3)2P(O)H) (CF3)2-C6H3)2P(O)H failed to produce the corresponding
constitutes the molecules with symmetrical aryl substituents. amides 32. Instead, secondary phosphines 33 were observed
Birch reduction of amides derived from these oxides should which could arise from P–Cl bond reduction by borane. In the
yield mixtures of two diastereomers only.
case of oXyl2P(O)H lack of the reactivity might arise from the
The substrates for test reactions were prepared from sec- steric crowd around phosphorus generated by four methyl groups
ondary phosphine oxides by treatment with PCl3, followed by at the ortho position. Compound 33a appeared to be sufficiently
the addition of a chiral amine–NEt3 mixture and then the stable to resist oxidation during chromatographic purification.
BH3–THF complex (Scheme 10).
The obtained set of symmetrically substituted diarylpho-
Generally, products 32 were obtained in moderate yields sphinous acid-borane amides has been subjected to the reac-
which could be attributed to the difficulties with the prepa- tion with sodium in liquid ammonia (Scheme 11, Table 3).
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Scheme 10 Synthesis of diarylphosphinous acid-borane amides.
Scheme 11 Desymmetrization of 32.
Table 3 Desymmetrization of 32
Nr
1
Compound
Productsa
32a
2
32b
3
4
32c
32d
5
32e
a In brackets, yields based on NMR analysis are presented.
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- selectivity of reaction can be controlled by the reaction
temperature – the lower the temperature the higher the
selectivity,
- an increase in the amount of alkali metal shifts the selecti-
vity of the reaction towards P-aryl bond cleavage; diastereo-
selectivity of this process strongly depends on the structure of
the amido group,
Scheme 12 Rearomatization of 34c.
- among tested chiral auxiliaries, the one derived from com-
mercially available α-phenylethylamine appeared to give the
best selectivities,
- selectivity of Birch reduction of diarylphosphinous acid-
borane amides is partially influenced by the structure of the
aryl substituent,
- Birch reduction of 32c led to both dearomatization of the
arene group and cleavage of the C–OMe bond in the para posi-
tion of the aryl group.
Despite the fact that desymmetrization of phosphinous
acid-borane amides by the developed method is underdeve-
loped it offers an operationally simple way for the synthesis of
P-stereogenic compounds. The development of more effective
chiral auxiliaries would make this approach more reliable for
practical applications.
An attempted desymmetrization of 32a with 3 equiv. of
sodium led to the formation of the expected product 34a albeit
in low yields. The product has been obtained as a mixture of
four isomers in a 30 : 11 : 40 : 19 ratio. Under identical reaction
conditions amide 32b afforded the corresponding product
which appeared to be an almost an equimolar mixture of trans
and cis isomers. The diastereomeric excesses of both isomers
were identical and reached 44% de. In the case of 32c Birch
reduction of one aryl substituents proceeded with a cleavage of
the carbon–oxygen bond. Compound 34c was obtained as a
mixture of diastereomers with a moderate selectivity (58% de).
The structure of this compound was additionally confirmed by
rearomatization of the cyclohexadienyl substituent which
afforded 36 (Scheme 12).
Dearomatization of 32d and 32e in both cases led to Birch
reduction products 34d and 34e as well as H-phosphinous
acid-borane amides 35a and 35b. The latter compounds arose
most probably through P-aryl bond cleavage and subsequential
protonation of the formed P-anion. In each case, both Birch
reduction products and H-phosphinous acid-borane amides
were formed as mixtures of diastereomers in moderate excess.
A brief look at Table 3 led to the conclusion that para and
meta-diarylphosphinous acid-borane amides undergo Birch
desymmetrization with a diastereoselectivity comparable with
the diastereoselectivity obtained for parent amide 10b (Table 3,
entries 2–5 and Table 1, entry 2). For ortho-substituted amide
32a the diastereoselectivity of the desymmetrization is difficult
to establish due to the presence of an additional chirality centre.
Experimental section
All reactions were performed under an argon atmosphere by
using Schlenk techniques. Only dry solvents were used and the
glassware was heated under vacuum prior to use. All chemicals
were used as received unless otherwise noted. Solvents for
chromatography and crystallization were distilled once before
use and the solvents for extraction were used as received. Tetra-
hydrofuran was dried over sodium/benzophenone ketyl and
dichloromethane was dried over P2O5. Secondary phosphine
oxides 31 were prepared according to the literature procedure.13
NMR spectra were recorded with Bruker Ascend (500 MHz)
and Varian Mercury (400 MHz) and Bruker Avance (300 MHz)
spectrometers in CDCl3 as a solvent at room temperature
unless otherwise noted. Chemical shifts (δ) are reported in
ppm relative to residual solvent peak. Mass spectra were
Conclusions
recorded on
a Shimadzu GC-MS QP2010S spectrometer
The main goal of this work was to develop a method for the
synthesis of P-chiral organophosphorus compounds by desym-
metrization through Birch reduction of symmetrically substi-
tuted diarylphosphorus amides possessing chiral amido
functionality.
working in electron ionization (EI) mode using a Phenomenex
Zebron ZB-35HT INFERNO column (pressure – 65 kPa, total
flow – 23.9 mL min−1, column flow – 1.2 mL min−1, linear vel-
ocity – 36.8 cm s−1, split – 20, temperature program (80 °C –
hold
3 – hold 5 min,
min, 80–250 °C/10 °C min−1
It has been found that:
250–280 °C/10 °C min−1 – hold 4.67 min, 280–340 °C/10 °C
min−1 – hold 4 min – total 35 min)). Thin-Layer Chromato-
graphy (TLC) was performed with precoated silica gel plates
and visualized by UV light or KMnO4 solution. The reaction
mixtures were purified by column chromatography over silica
gel (60–240 mesh).
- phosphinous acid-borane amides undergo preferentially
Birch reduction of only one aryl substituent whereas phosphi-
nic acid amides undergo preferential double Birch reduction,
- the substitution pattern at nitrogen influences the reaction
course; the presence of a hydrogen atom at nitrogen or the
presence of any acidic hydrogen atom in the molecule stops
the dearomatization reaction,
The synthesis of 10a and 11a
- the size of the non-chiral substituent at nitrogen influ-
ences the reaction course; an increase of steric bulk of this In a flame-dried, two-neck, round-bottom 100 mL flask
group decreases the selectivity of desymmetrization,
equipped with a magnetic stirrer and an inert gas inlet were
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placed (S)-α-methylbenzylamine
9
(1.212 g, 1.289 mL, ated. The residue was purified by flash chromatography using
0.01 mol) and triethylamine (1.012 g, 1.394 mL, 0.01 mol) in hexane–EtOAc = 6 : 1 (for 10b and 10c) or CHCl3–MeOH =
dichloromethane (20 mL). Then, diphenylchlorophosphine 15 : 1 (for 11b and 11c) as the eluent.
(2.206 g, 1.795 mL, 0.01 mol) was added slowly dropwise. The
Diphenylphosphinous acid-borane N-methyl-(S)-α-methyl-
reaction was stirred overnight and then 1 M BH3–THF (15 mL, benzylamide (10b). Prepared from 10a (0.160 g, 0.0005 mol)
0.015 mol) or 30% H2O2 (20 mL) was added to the reaction and MeI (0.062 mL, 0.142 g, 0.001 mol). Yield 0.113 g (68%).
mixture. After stirring for 1 h, the reaction mixture was White solid, mp 105.3–106.9 °C. RF 0.60 (hexane–EtOAc 6 : 1).
quenched by the addition of water (30 mL), the mixture was [α]D 35.7 (c 1.1, CHCl3). 1H NMR (CDCl3, 400 MHz,) δ 0.74–1.50
extracted with DCM (3 × 20 mL), an organic phase was dried (3 H, bm), 1.51 (3 H, d, J = 6.9 Hz), 2.24 (3 H, d, J = 7.9 Hz),
over Na2SO4 and evaporated. The residue was purified by flash 5.31–5.41 (1 H, m), 7.26–7.29 (1 H, m), 7.32–7.37 (2 H, m),
chromatography using hexane–EtOAc = 6 : 1 (for 10a) or 7.39–7.44 (4 H, m), 7.44–7.55 (6 H, m), 7.65–7.71 (2 H, m); 13C
CHCl3–MeOH = 15 : 1 (for 11a) as the eluent.
NMR (CDCl3, 75 MHz) δ 16.5 (d, J = 1.7 Hz), 28.9 (d, J = 4.0
Diphenylphosphinous acid-borane (S)-α-methylbenzylamide Hz), 55.4 (d, J = 11.2 Hz), 127.1, 127.9, 128.2, 128.4 (d, J = 10.4
(10a). Yield 2.681 g (84%). White solid, mp 76.1–77.8 °C. Hz), 128.5 (d, J = 10.4 Hz), 130.8 (d, J = 50.8 Hz), 130.9 (d, J =
RF 0.53 (hexane–EtOAc 6 : 1). [α]D −39.8 (c 1.21, CHCl3). 1H 2.6 Hz), 131.1 (d, J = 2.6 Hz), 131.6 (d, J = 42.8 Hz), 132.2 (d, J =
NMR (CDCl3, 500 MHz) δ 0.57–1.55 (3 H, bm), 1.41 (3 H, d, J = 10.4 Hz), 132.4 (d, J = 10.6 Hz); 31P NMR (CDCl3, 121.5 MHz) δ
7.0 Hz), 2.48 (1 H, bs), 4.36–4.48 (1 H, m), 7.13–7.27 (5 H, m), 54.35 (bm); GC (Phenomenex Zebron ZB-35 HT) RT 22.63 min;
7.30–7.51 (6 H, m), 7.53–7.62 (4 H, m); 13C NMR (CDCl3, GC–MS (EI, 70 eV) m/z (%) 319 (M − BH3) (8), 318 (12), 263
126 MHz) δ 25.9 (d, J = 4.9 Hz), 53.0 (d, J = 2.30 H), 125.8, (18), 262 (93), 214 (45), 185 (14), 183 (36), 152 (10), 134 (28),
126.9, 128.3 (d, J = 8.3 Hz), 128.4, 128.5 (d, J = 8.1 Hz), 131.1 122 (14), 109 (100), 108 (27), 105 (25), 104 (17), 91 (11);
(d, J = 2.6 Hz), 131.8 (d, J = 6.0 Hz), 131.9 (d, J = 6.3 Hz); 31P C21H25BNP (333.21): calcd C 75.69, H 7.56, N 4.20; found C
NMR (CDCl3, 202 MHz) δ 54.35 (bm); GC (Phenomenex Zebron 75.50, H 7.49, N 4.45.
ZB-35 HT) RT 21.85 min; GC–MS (EI, 70 eV) m/z (%) 304 (5),
Diphenylphosphinous acid-borane N-ethyl-(S)-α-methyl-
262 (16), 200 (42), 122 (33), 104 (100), 78 (57), 77 (49); benzylamide (10c). Prepared from 10a (0.160 g, 0.0005 mol)
C20H23BNP (319.19): calcd C 75.26, H 7.26, N 4.39; found C and EtBr (0.075 mL, 0.109 g, 0.001 mol). Yield 0.127 g (73%).
75.44, H 7.30, N 4.55.
Diphenylphosphinic
Colorless thick oil. RF 0.67 (hexane–EtOAc 2 : 1). [α]D 9.8
(S)-α-methylbenzylamide (c 1.055, CHCl3). H NMR (CDCl3, 500 MHz) δ 0.55–1.26 (3 H,
1
acid
(11a). Yield 3.053 g (95%). White solid, mp 179.1–180.6 °C (lit. bm), 0.45 (3 H, t, J = 7.3 Hz), 0.71–1.72 (3 H, bm), 1.64 (3 H, d,
178–179 °C).14 RF 0.85 (CHCl3–MeOH 15 : 1). [α]D −29.3 (c 1.07, J = 7.3 Hz), 2.91–3.14 (2 H, m), 5.23–5.32 (1 H, m), 7.24–7.29
CHCl3) (lit.14 −35.5 (c 0.78, methanol). 1H NMR (CDCl3, (1 H, m), 7.30–7.35 (2 H, m), 7.39–7.47 (6 H, m), 7.47–7.52 (2
500 MHz,) δ 1.58 (3 H, d, J = 6.9 Hz), 3.19–3.25 (1 H, m), H, m), 7.57–7.63 (2 H, m), 7.66–7.72 (2 H, m); 13C NMR
4.35–4.45 (1 H, m), 7.23–7.34 (5 H, m), 7.35–7.40 (2 H, m), (CDCl3, 125 MHz) δ 16.6, 19.4 (d, J = 1.8 Hz), 39.4 (d, J = 1.8
7.42–7.47 (3 H, m), 7.47–7.52 (1 H, m), 7.80–7.86 (2 H, m), Hz), 56.1 (d, J = 10.0 Hz), 127.1, 128.0, 128.1, 128.33 (d, J = 10.0
7.89–7.94 (2 H, m); 13C NMR (CDCl3, 126 MHz) δ 26.0 (d, J = Hz), 128.34 (d, J = 10.0 Hz), 130.8 (d, J = 2.7 Hz), 130.9 (d, J =
2.7 Hz), 51.0, 125.9, 127.1, 128.4 (d, J = 12.7 Hz), 128.5 (d, J = 2.7 Hz), 131.7 (d, J = 52.7 Hz), 132.2 (d, J = 52.7 Hz), 132.3 (d,
12.7 Hz), 128.5, 131.7 (d, J = 2.7 Hz), 131.8 (d, J = 2.7 Hz), 131.9 J = 6.4 Hz), 132.4 (d, J = 6.4 Hz), 142.2 (d, J = 5.5 Hz); 31P NMR
(d, J = 10.0 Hz), 132.3 (d, J = 10.0 Hz), 132.4 (d, J = 10.0 Hz), (CDCl3, 202 MHz) δ 69.22 (bm); GC (Phenomenex Zebron
132.1 (d, J = 135.3 Hz), 133.1 (d, J = 132.6 Hz), 145.0 (d, J = 6.4 ZB-35 HT) RT 15.37 min; GC–MS (EI, 70 eV) m/z (%) 333 (M −
Hz); 31P NMR (CDCl3, 202 MHz) δ 68.88 (bm); GC (Phenom- BH3) (6), 332 (8), 263 (19), 262 (100), 229 (6), 228 (37), 214 (9),
enex Zebron ZB-35 HT) RT 17.17 min; GC–MS (EI, 70 eV) m/z 185 (24), 184 (9), 183 (55), 152 (10), 148 (19), 122 (8), 118 (12),
(%) 306 (18), 202 (7), 201 (39), 121 (9), 120 (100); C20H20NOP 109 (44), 108 (24), 107 (11), 105 (25); C22H27BNP (347.24): calcd
(321.35): calcd C 74.75, H 6.47, N 4.36; found C 74.88, H 6.70, C 76.10, H 7.84, N 4.03; found C 75.99, H 7.77, N 4.05.
N 4.58. Spectral data are in accordance with those reported in
the literature.14
Diphenylphosphinic acid N-methyl-(S)-α-methylbenzylamide
(11b). Prepared from 11a (0.161 g, 0.0005 mmol) and MeI
(0.062 mL, 0.142 g, 0.001 mol). Yield 0.159 g (95%). Colorless
The synthesis of 10b, 10c, 11b and 11c
1
thick oil. RF 0.32 (CHCl3). [α]D −51.3 (c 1.0, CHCl3). H NMR
In a flame-dried Schlenk tube (50 mL) equipped with a mag- (CDCl3, 500 MHz) δ 1.57 (3 H, d, J = 6.9 Hz), 2.35 (3 H, d, J =
netic stirrer and an inert gas inlet amide 10a or 11a 10.7 Hz), 4.68–4.78 (1 H, m), 7.21–7.26 (1 H, m), 7.32–7.37 (2
(0.5 mmol) was dissolved in THF (5 mL). The solution was H, m), 7.39–7.49 (8 H, m), 7.86–7.94 (4 H, m); 13C NMR
cooled to −78 °C and nBuLi (0.46 mL, 1.6 M solution in (CDCl3, 126 MHz) δ 16.9 (d, J = 2.7 Hz), 27.7 (d, J = 3.6 Hz),
hexane, 0.75 mmol) was added dropwise via a syringe. After 53.1 (d, J = 2.7 Hz), 126.9, 127.5, 128.1, 128.4 (d, J = 11.8 Hz),
stirring for 1 h at −78 °C an electrophile (2.0 mmol) was 131.5 (d, J = 3.6 Hz), 131.5 (d, J = 2.7 Hz), 131.8 (d, J = 129.0
added and the mixture was allowed to warm to rt overnight. Hz), 132.0 (d, J = 128.1 Hz), 132.2 (d, J = 9.1 Hz), 132.2 (d, J =
The reaction was quenched by the addition of aqueous NH4Cl 10.0 Hz), 140.9 (d, J = 5.5 Hz); 31P NMR (CDCl3, 202 MHz)
(5 mL), the mixture was extracted with DCM (3 × 10 mL), the δ 30.74; GC (Phenomenex Zebron ZB-35 HT) RT 17.44 min;
combined organic phases were dried over Na2SO4 and evapor- GC–MS (EI, 70 eV) m/z (%) 320 (4), 202 (6), 201 (35), 135 (10),
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134 (100), 105 (6); C21H22NOP (335.38): calcd C 75.21, H 6.61, (CHCl3). [α]D −15.3 (c 1.025, CHCl3). 1H NMR (CDCl3,
N 4.18; found C 75.44, H 6.79, N 4.22. 500 MHz) δ 1.14 (3 H, d, J = 6.9 Hz), 1.22 (3 H, d, J = 6.9 Hz),
Diphenylphosphinic acid N-ethyl-(S)-α-methylbenzylamide 1.71 (3 H, d, J = 7.3 Hz), 3.52–3.62 (1 H, m), 4.52–4.61 (1 H, m),
(11c). Prepared from 11a (0.161 g, 0.0005 mmol) and EtBr 7.16–7.20 (1 H, m), 7.21–7.25 (2 H, m), 7.25–7.30 (2 H, m),
(0.075 mL, 0.109 g, 0.001 mol). Yield 0.126 g (72%). Colorless 7.35–7.49 (6 H, m), 7.70–7.76 (2 H, m), 7.88–7.94 (2 H, m); 13C
thick oil. RF 0.26 (CHCl3). [α]D −47.2 (c 0.835, CHCl3). 1H NMR NMR (CDCl3, 126 MHz) δ 20.6 (d, J = 3.6 Hz), 23.4 (d, J = 4.5
(CDCl3, 500 MHz) δ 0.73 (3 H, t, J = 7.3 Hz), 1.63 (3 H, d, J = 6.9 Hz), 23.7 (d, J = 1.8 Hz), 48.8 (d, J = 4.5 Hz), 53.1 (d, J = 3.6 Hz),
Hz), 2.83–3.06 (2 H, m), 4.69–4.78 (1 H, m), 7.22–7.28 (1 H, m), 126.6, 127.7, 127.9 (d, J = 12.7 Hz), 128.1 (d, J = 11.8 Hz), 131.0
7.31–7.36 (2 H, m), 7.41–7.52 (8 H, m), 7.90–7.99 (4 H, m); 13C (d, J = 2.7 Hz), 131.2 (d, J = 2.7 Hz), 132.4 (d, J = 9.1 Hz), 132.5
NMR (CDCl3, 126 MHz) δ 17.0 (d, J = 2.7 Hz), 19.3 (d, J = 2.7 (d, J = 9.1 Hz), 133.43 (d, J = 126.2 Hz), 134.13 (d, J = 127.2 Hz),
Hz), 37.9 (d, J = 3.6 Hz), 54.0 (d, J = 3.6 Hz), 127.0, 127.9, 128.3 143.26 (d, J = 1.8 Hz); 31P NMR (CDCl3 202 MHz,) δ 28.19; GC
(d, J = 12.7 Hz), 128.3 (d, J = 12.7 Hz), 131.5 (d, J = 2.7 Hz), (Phenomenex Zebron ZB-35 HT) RT 17.50 min; GC–MS (EI, 70
131.5 (d, J = 2.7 Hz), 132.4 (d, J = 10.0 Hz), 132.5 (d, J = 128.1 eV) m/z (%) 363 (M) (1), 321 (15), 320 (66), 306 (8), 258 (8), 244
Hz), 132.6 (d, J = 128.1 Hz), 141.9 (d, J = 4.5 Hz); 31P NMR (33), 202 (15), 201 (100), 162 (26), 120 (5), 105 (32), 103 (7);
(CDCl3, 202 MHz,) δ 30.05; GC (Phenomenex Zebron ZB-35 C23H26NOP (363.43): calcd C 76.01, H 7.21, N 3.85; found C
HT) RT 17.48 min; GC–MS (EI, 70 eV) m/z (%) 334 (3), 320 (8), 76.15, H 7.17, N 3.99.
230 (5), 202 (9), 201 (54), 149 (11), 148 (100), 105 (13);
C22H24NOP (349.41): calcd C 75.62, H 6.92, N 4.01; found C
75.90, H 6.88, N 4.14.
The synthesis of 16a
L-Prolinol was obtained according to the literature procedure.16
The synthesis of 10d and 11d
In a flame-dried Schlenk tube (100 mL) equipped with a
Compound 12 was prepared according to the literature magnetic stirrer and an inert gas inlet was placed. L-prolinol
procedure.15
(0.427 mL, 0.438 g, 0.004 mol) and PhP(NEt2)2 (1.093 g,
In a flame-dried, two-neck, round-bottom 100 mL flask 0.004 mol) (prepared from PhPCl2 and HNEt2)17 were dis-
equipped with a magnetic stirrer and an inert gas inlet were solved in toluene (20 mL) and refluxed for 4 h. The mixture
placed 12 (0.163 g, 0.001 mol) and triethylamine (0.101 g, was cooled to rt and evaporated to dryness. NMR analysis of
0.139 mL, 0.001 mol) in dichloromethane (5 mL). Then, diphe- the residue showed the presence of the corresponding bicyclic
nylchlorophosphine (0.221 g, 0.180 mL, 0.001 mol) was added oxazaphospholane as
a
single diastereomer (31P NMR
slowly dropwise. The reaction was stirred overnight and then 1 147.74 ppm). The intermediate was dissolved in THF (20 mL)
M BH3–THF (1.5 mL, 0.0015 mol) or 30% H2O2 (2 mL) was under an inert atmosphere and cooled to −78 °C. Then, PhLi
added to the reaction mixture. After stirring for 1 h, the reac- (2.89 mL, 1.8 M in dibutyl ether, 0.005 mol) was added via a
tion mixture was quenched by the addition of water (10 mL), syringe and the mixture was allowed to warm to rt overnight.
the mixture was extracted with DCM (3 × 10 mL), an organic BH3–THF (6.5 mL, 1 M in THF, 0.0065 mol) was added and the
phase was dried over Na2SO4 and evaporated. The residue was mixture was stirred for an additional 1 h. The reaction was
purified by flash chromatography using hexane–EtOAc = 2 : 1 quenched by the addition of aqueous NH4Cl (20 mL), the
(for 10d) or CHCl3 (for 11d) as the eluent.
mixture was extracted with DCM (3 × 20 mL), dried over
Diphenylphosphinous acid-borane N-i-propyl-(S)-α-methyl- Na2SO4 and evaporated. The residue was purified by flash
benzylamide (10d). Yield 0.195 g (54%). Colorless thick oil. RF chromatography using hexane–EtOAc = 2 : 1 as the eluent.
1
0.69 (hexane–EtOAc 2 : 1). [α]D −23.3 (c 0.98, CHCl3). H NMR
Diphenylphosphinous acid-borane (2S)-2-(hydroxymethyl)-
(CDCl3, 500 MHz,) δ 0.32–1.20 (3 H, bm), 0.74 (3 H, d, J = 6.9 pyrolidinamide (16a). Yield 0.944 g (73%, after 4 steps). Color-
Hz), 1.06 (3 H, d, J = 6.6 Hz), 1.73 (3 H, d, J = 7.3 Hz), 3.61–3.71 less thick oil. RF 0.33 (hexane–EtOAc 2 : 1). [α]D −24.5 (c 0.935,
(1 H, m), 5.08–5.18 (1 H, m), 7.21–7.26 (1 H, m), 7.27–7.31 (2 CHCl3). 1H NMR (CDCl3, 500 MHz) δ 0.71–1.41 (3 H, bm),
H, m), 7.40–7.53 (8 H, m), 7.70–7.76 (2 H, m), 7.76–7.81 (2 H, 1.63–1.76 (2 H, m), 1.84–2.00 (3 H, m), 2.86–2.96 (1 H, m),
m); 13C NMR (CDCl3, 126 MHz,) δ 20.8 (d, J = 1.8 Hz), 23.4 (d, 3.05–3.14 (1 H, m), 3.51 (1 H, dd, J = 6.3 Hz, 11.0 Hz), 3.60
J = 1.8 Hz), 23.6 (d, J = 1.8 Hz), 55.3 (d, J = 10.0 Hz), 126.9, (1 H, dd, J = 4.7 Hz, 11.0 Hz), 4.05–4.11 (1 H, m), 7.42–7.54
127.9, 128.2, 128.3 (d, J = 10.0 Hz), 128.3 (d, J = 10.0 Hz), 130.8 (6 H, m), 7.56–7.61 (2 H, m), 7.64–7.70 (2 H, m); 13C NMR
(d, J = 1.8 Hz), 130.8 (d, J = 1.8 Hz), 132.4 (d, J = 63.6 Hz), 132.6 (CDCl3, 126 MHz) δ 25.3 (d, J = 4.5 Hz), 28.9 (d, J = 4.5 Hz),
(d, J = 10.9 Hz), 143.3 (d, J = 4.5 Hz); 31P NMR (CDCl3, 48.5 (d, J = 2.7 Hz), 61.4 (d, J = 7.3 Hz), 65.78, 128.5 (d, J = 10.0
202 MHz) δ 67.93 (bm); GC (Phenomenex Zebron ZB-35 HT) RT Hz), 128.5 (d, J = 10.0 Hz), 130.7 (d, J = 69.0 Hz), 131.1 (d, J =
15.05 min; GC–MS (EI, 70 eV) m/z (%) 347 (M − BH3) (3), 346 1.8 Hz), 131.2 (d, J = 1.8 Hz), 131.2 (d, J = 76.3 Hz), 131.9 (d, J =
(4), 304 (7), 263 (20), 262 (100), 242 (22), 228 (6), 185 (34), 184 10.0 Hz), 132.3 (d, J = 10.0 Hz); 31P NMR (CDCl3, 202 MHz,)
(9), 183 (50), 162 (8), 152 (9), 122 (18), 109 (17), 108 (21), 107
(10), 105 (25); C23H29BNP (361.27): calcd C 76.47, H 8.09, RT 13.43 min; GC–MS (EI, 70 eV) m/z (%) 299 (M) (3), 255 (13),
N 3.88; found C 76.50, H 7.99, N 3.81. 254 (69), 186 (14), 185 (100), 184 (10), 183 (70), 178 (9),
δ
60.18 (bm); GC (Phenomenex Zebron ZB-35 HT)
Diphenylphosphinic acid N-i-propyl-(S)-α-methylbenzyla- 152 (13), 109 (11), 108 (11), 107 (13); C17H23BNOP (299.16):
mide (11d). Yield 0.218 g (60%). Colorless thick oil. RF 0.25 calcd C 68.24, H 7.75, N 4.68; found C 68.50, H 7.82, N 4.50.
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The synthesis of 16b
5.5 Hz), 28.6 (d, J = 5.5 Hz), 28.4 (d, J = 2.7 Hz), 61.0 (d, J = 7.3
Hz), 65.1, 128.4 (d, J = 10.0 Hz), 130.8 (d, J = 1.8 Hz), 131.0 (d,
J = 2.7 Hz), 131.03 (d, J = 70.8 Hz), 131.5 (d, J = 72.7 Hz), 131.9
(d, J = 10.0 Hz), 132.3 (d, J = 10.0 Hz); (minor rotamer) δ 1.3,
25.3 (J = 4.5 Hz), 28.9 (d, J = 5.5 Hz), 28.5 (d, J = 2.7 Hz), 61.4
(d, J = 7.3 Hz), 65.7, 128.5 (d, J = 10.9 Hz), 128.5 (d, J = 10.0
Hz), 130.7 (d, J = 76.3 Hz), 131.0 (d, J = 1.8 Hz), 131.2 (d, J = 1.8
Hz), 131.2 (d, J = 76.3 Hz), 131.9 (d, J = 10.0 Hz), 132.2 (d, J =
10.9 Hz); 31P NMR (CDCl3, 202 MHz) (major rotamer) δ 59.01
(bm); (minor rotamer) δ 60.17 (bm); GC (Phenomenex Zebron
ZB-35 HT) RT 13.73 min; GC–MS (EI, 70 eV) m/z (%) 203 (16),
201 (11), 183 (9), 125 (7), 108 (7), 84 (68), 83 (100), 82 (15);
C20H31BNOPSi (371.34): calcd C 64.69, H 8.41, N 3.77; found C
64.85, H 8.13, N 3.52.
In a flame-dried Schlenk tube (50 mL) equipped with a mag-
netic stirrer and an inert gas inlet amide 16a (0.150 g,
0.5 mmol) was dissolved in THF (5 mL). The solution was
cooled to −78 °C and NaH (0.020 g, 60% in mineral oil,
0.55 mmol) was added. After stirring for 30 min at −78 °C MeI
(0.047 mL, 0.106 g, 0.75 mmol) was added and the mixture
was allowed to warm to rt overnight. The reaction was
quenched by the addition of aqueous NH4Cl (5 mL), the
mixture was extracted with DCM (3 × 10 mL), the combined
organic phases were dried over Na2SO4 and evaporated. The
residue was purified by flash chromatography using hexane–
EtOAc = 2 : 1 as the eluent.
Diphenylphosphinous acid-borane (2S)-2-(methoxymethyl)-
pyrolidinamide (16b). Yield 0.047 g (30%). White thick oil. RF
0.65 (hexane–EtOAc 2 : 1). [α]D −37.3 (c 1.0, CHCl3). 1H NMR
(CDCl3, 500 MHz,) δ 0.69–1.42 (3 H, bm), 1.67–1.74 (1 H, m),
1.87–2.00 (3 H, m), 2.81–2.89 (1 H, m), 3.06–3.13 (1 H, m), 3.28
(3 H, s), 3.29–3.33 (1 H, m), 3.36–3.41 (1 H, m), 4.06–4.14 (1 H,
m), 7.39–7.54 (6 H, m), 7.55–7.62 (2 H, m), 7.63–7.70 (2 H, m);
13C NMR (CDCl3, 126 MHz) δ 25.3 (d, J = 4.5 Hz), 29.1 (d, J =
6.4 Hz), 48.4 (d, J = 1.8 Hz), 58.7, 58.9 (d, J = 7.3 Hz), 75.6, 128.4
(d, J = 10.0 Hz), 128.4 (d, J = 10.9 Hz), 130.8 (d, J = 2.7 Hz), 130.9
(d, J = 62.7 Hz), 131.0 (d, J = 2.7 Hz), 131.7 (d, J = 65.4 Hz), 131.8
(d, J = 10.9 Hz), 132.3 (d, J = 10.0 Hz); 31P NMR (202 MHz,
CDCl3) δ 58.99 (bm); GC (Phenomenex Zebron ZB-35 HT) RT
13.43 min; GC–MS (EI, 70 eV) m/z (%) 299 (M − BH3) (3), 255
(13), 254 (68), 186 (13), 185 (100), 184 (10), 183 (71), 178 (8), 152
(13), 109 (10), 108 (11), 107 (13); C18H25BNOP (313.18): calcd C
69.03, H 8.05, N 4.47; found C 69.27, H 7.98, N 4.40.
D-Camphor oxime (18). This compound was prepared
according to the literature procedure.17 Data are in accordance
with those reported in the literature.17
exo-Bornylamine (22d). This compound was prepared
according to the literature procedure.17 Data are in accordance
with those reported in the literature.17
L-Menthyl methanesulfonate (20a). This compound was pre-
pared according to the literature procedure.18 Data are in
accordance with those reported in the literature.
9-Mesyl-quinine (20b). This compound was prepared
according to the literature procedure.19 Data are in accordance
with those reported in the literature.19
9-Mesyl-quinidine (20c). This compound was prepared
according to the literature procedure.19 Data are in accordance
with those reported in the literature.19
Neomenthyl azide (21a). This compound was prepared
according to the literature procedure.20 Data are in accordance
with those reported in the literature.20
The synthesis of 16c
9-epi-9-Azidoquinine (21b). This compound was prepared
In a flame-dried Schlenk tube (50 mL) equipped with a mag- according to the literature procedure.21 Data are in accordance
netic stirrer and an inert gas inlet amide 16a (0.150 g, with those reported in the literature.21
0.5 mmol) was dissolved in DCM (5 mL). Then, NEt3
9-epi-9-Azidoquinidine (21c). This compound was prepared
(0.209 mL, 0.125 g, 1.5 mmol) was added followed by TMSCl according to the literature procedure.21 Data are in accordance
(0.095 mL, 0.081 g, 0.75 mmol). The mixture was allowed to with those reported in the literature.21
stir overnight at rt and then quenched by the addition of
Neomenthylamine (22a). This compound was prepared
aqueous NH4Cl (10 mL). The mixture was extracted with DCM according to the literature procedure.22 Data are in accordance
(3 × 10 mL), the organic phase was dried over Na2SO4 and with those reported in the literature.17
evaporated. The residue was purified by flash chromatography
9-epi-9-Aminoquinine (22b). This compound was prepared
using hexane–EtOAc = 2 : 1 as the eluent.
according to the literature procedure.23 Data are in accordance
Diphenylphosphinous acid-borane (2S)-2-(trimethylsililoxy- with those reported in the literature.23
methyl)-pyrolidinamide (16c). Yield 0.087 g (47%) (isolated as
9-epi-9-Aminoquinidine (22c). This compound was prepared
a mixture of rotamers). Colorless oil. RF 0.73 (hexane–EtOAc according to the literature procedure.24 Data are in accordance
1
2 : 1). H NMR (CDCl3, 500 MHz) (major rotamer) δ 0.08 (9 H, with those reported in the literature.24
s), 0.65–1.45 (3 H, bm), 1.67–1.75 (1 H, m), 1.83–1.98 (2 H, m),
1.98–2.05 (1 H, m), 2.81–2.89 (1 H, m), 3.06–3.13 (1 H, m),
The synthesis of 23a–f
3.37–3.44 (1 H, m), 3.57–3.63 (1 H, m), 3.96–4.04 (1 H, m), In a flame-dried Schlenk tube (25 mL) equipped with a mag-
7.40–7.53 (6 H, m), 7.56–7.62 (2 H, m), 7.63–7.71 (1 H, m); netic stirrer and an inert gas inlet was placed amine (1 equiv.)
(minor rotamer) δ 0.17 (9 H, s), 0.65–1.45 (3 H, bm), 1.67–1.75 in DCM (10 mL). Then, NEt3 (1 equiv.) was added followed by
(1 H, m), 1.83–1.98 (3 H, m), 2.89–2.96 (1 H, m), 3.06–3.13 (1 ClCOOMe (1 equiv.). The mixture was allowed to stir at rt for
H, m), 3.49–3.54 (1 H, m), 3.57–3.63 (1 H, m), 4.05–4.13 (1 H, 16 h, then water (10 mL) was added. The mixture was extracted
m), 7.40–7.53 (6 H, m), 7.56–7.62 (2 H, m), 7.63–7.71 (2 H, m); with DCM (3 × 20 mL), combined organic phases were dried
13C NMR (CDCl3, 126 MHz) (major rotamer) δ −0.5, 25.0 (J = over Na2SO4 and evaporated. The residue was purified by flash
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chromatography using hexane–EtOAc = 6 : 1 or CHCl3–MeOH = 1.52–1.60 (2 H, m), 1.66–1.74 (2 H, m), 1.82–1.89 (1 H, m),
15 : 1 as the eluent. 3.60–3.68 (1 H, m), 3.64 (3 H, s), 4.59–4.66 (1 H, m); (minor
N-Neomenthyl methyl carbamate (23a). Prepared from neo- diastereomer) δ 0.82 (3 H, s), 0.87 (3 H, s), 0.93 (3 H, s),
menthylamine (22a) (0.276 g, 0.0018 mol), ClCOOMe 1.26–1.32 (1 H, m), 1.32–1.40 (1 H, m), 1.43–1.50 (1 H, m),
(0.137 mL, 0.168 g, 0.0018 mol) and NEt3 (0.248 mL, 0.180 g, 1.52–1.61 (1 H, m), 1.63–1.72 (2 H, m), 2.31–2.39 (1 H, m), 3.66
0.0018 mol). Yield 0.302
g
(79%). White solid, mp (3 H, s), 3.92–3.98 (1 H, m), 4.69–4.76 (1 H, m); 13C NMR
92.6–93.4 °C. RF 0.50 (hexane–EtOAc 6 : 1). [α]D 50.0 (c 0.87, (CDCl3, 126 MHz) (major diastereomer) δ 11.6, 13.5, 20.2, 26.9,
1
CHCl3). H NMR (CDCl3, 500 MHz) δ 0.87 (3 H, d, J = 6.6 Hz), 35.9, 39.3, 44.7, 46.9, 48.4, 51.9, 58.6, 156.7; (minor diastereo-
0.89 (3 H, d, J = 6.9 Hz), 0.91 (3 H, d, J = 6.6 Hz), 0.86–0.95 (2 mer) δ 14.1, 19.8, 18.6, 22.7, 27.7, 28.3, 31.9, 37.8, 47.9, 49.2,
H, m), 0.98–1.08 (2 H, m), 1.33–1.451 (1 H, m), 1.41–1.51 (1 H, 55.7, 157.1; GC (Phenomenex Zebron ZB-35 HT) RT 8.45 min;
m), 1.69–1.74 (1 H, m), 1.78–1.84 (1 H, m), 1.84–1.90 (1 H, m), (major diastereomer); RT 8.51 min (minor diastereomer);
3.66 (3 H, s), 4.05–4.10 (1 H, m), 4.72–4.78 (1 H, m); 13C NMR GC–MS (EI, 70 eV) m/z (%) (major diastereomer) 211 (M) (4),
(CDCl3, 126 MHz,) δ 20.8, 20.9, 22.2, 25.2, 26.6, 29.4, 34.7, 196 (4), 136 (14), 121 (37), 110 (10), 109 (12), 102 (23), 101 (10),
40.4, 46.4, 47.8, 51.9, 156.4; C12H23NO2 (213.32): calcd C 67.57, 96 (11), 95 (100), 93 (14); (minor diastereomer) 211 (M) (4), 196
H 10.87, N 6.57; found C 67.44, H 10.99, N 6.59.
(4), 136 (14), 121 (37), 110 (10), 109 (12), 102 (23), 101 (10), 96
9-epi-9-((Methoxycarbonyl)amino)quinine (23b). Prepared (11), 95 (100), 93 (14); C12H21NO2 (211.30): calcd C 68.21, H
from 9-epi-9-aminoquinine (22b) (0.504 g, 0.0016 mol), 10.02, N 6.63; found C 68.00, H 10.16, N 6.70.
ClCOOMe (0.120 mL, 0.147 g, 0.0016 mol) and NEt3 (0.217 mL,
N-(R)-1-(1-Naphthyl)ethyl methyl carbamate (23e). Prepared
0.158 g, 0.0016 mol). Yield 0.444 g (75%). Pale yellow foam. RF from (R)-1-(1-naphthyl)ethylamine (0.937 mL, 1.000 g,
1
0.39 (CHCl3–MeOH 15 : 1). [α]D −3.4 (c 1.03, CHCl3). H NMR 0.0058 mol), ClCOOMe (0.451 mL, 0.552 g, 0.0058 mol) and
(CDCl3, 500 MHz) δ 0.89–0.96 (1 H, m), 1.34–1.44 (1 H, m), NEt3 (0.814 mL, 0.591 g, 0.0058 mol). Yield 1.194 g (89%).
1.58–1.64 (2 H, m), 1.64–1.69 (1 H, m), 2.26–2.33 (1 H, m), White solid, mp 87.8–88.5 °C. RF 0.45 (hexane–EtOAc 6 : 1).
2.67–2.81 (2 H, m), 3.01–3.22 (2 H, m), 3.23–3.30 (1 H, m), 3.56 [α]D 92.4 (c 0.99, CHCl3). 1H NMR (CDCl3, 500 MHz) δ 1.66
(3 H, bs), 3.97 (3 H, s), 4.92–5.01 (2 H, m), 5.04–5.19 (1 H, bm), (3 H, d, J = 6.6 Hz), 3.69 (3 H, s), 5.03–5.12 (1 H, m), 5.64–5.71
5.67–5.76 (1 H, m), 6.19 (1 H, bs), 7.36–7.42 (2 H, m), 7.63 (1 H, m), 7.44–7.48 (1 H, m), 7.49–7.53 (2 H, m), 7.55–7.59 (2
(1 H, bs), 8.03 (1 H, d, J = 9.1 Hz), 8.74 (1 H, d, J = 4.4 Hz); 13C H, m), 7.78–7.82 (1 H, m), 7.87–7.90 (1 H, m), 8.13–8.17 (1 H,
NMR (CDCl3, 126 MHz) δ 26.0, 27.3, 27.9, 39.5, 40.8, 52.1, 55.6, m); 13C NMR (CDCl3, 126 MHz) δ 21.6, 46.6, 52.1, 122.2, 123.2,
55.9, 60.0 (bs), 101.7, 114.6, 119.4 (bs), 121.5, 128.2, 131.8, 125.2, 125.7, 126.4, 128.2, 128.8, 130.8, 133.9, 138.7, 156.1; GC
141.2, 144.8, 147.6, 156.8, 157.7; GC (Phenomenex Zebron (Phenomenex Zebron ZB-35 HT) RT 12.10 min; GC–MS (EI,
ZB-35 HT) RT 18.40 min; GC–MS (EI, 70 eV) m/z (%) 137 (11), 70 eV) m/z (%) 229 (M) (30), 215 (15), 214 (100), 182 (16), 171
136 (100), 95 (5), 82 (5), 81 (11); C22H27N3O3 (381.47): calcd C (30), 170 (13), 155 (35), 154 (40), 153 (35), 152 (19), 143 (17),
69.27, H 7.13, N 11.02; found C 69.44, H 7.01, N 11.00.
129 (28), 128 (45), 127 (42), 126 (11), 115 (12); C14H15NO2
9-epi-9-((Methoxycarbonyl)amino)quinidine (23c). Prepared (229.27): calcd C 73.34, H 6.59, N 6.11; found C 73.55, H 6.71,
from 9-epi-9-aminoquinidine (22c) (0.387 g, 0.0012 mol), N 6.12. Data are in accordance with those reported in the
ClCOOMe (0.092 mL, 0.113 g, 0.0012 mol) and NEt3 (0.167 mL, literature.25
0.121 g, 0.0012 mol). Yield 0.241 g (53%). Pale yellow foam. RF
N-(S)-1-(2-Naphthyl)ethyl methyl carbamate (23f). Prepared
1
0.29 (CHCl3–MeOH 15 : 1). [α]D 160.2 (c 0.84, CHCl3). H NMR from (S)-1-(2-naphthyl)ethylammonium sulfonate (1.034 g,
(CDCl3, 500 MHz) δ 0.90–1.02 (1 H, m), 1.24–1.34 (1 H, m), 0.0038 mol), ClCOOMe (0.297 mL, 0.363 g, 0.0038 mol) and
1.44–1.62 (2 H, m), 1.62–1.70 (1 H, m), 2.26–2.36 (1 H, m), NEt3 (0.535 mL, 0.388 g, 0.0038 mol). Yield 0.215 g (25%).
2.85–3.05 (5 H, m), 3.56 (3 H, bs), 3.97 (3 H, s), 5.07–5.19 (3 H, White solid mp 70.1–71.7 °C. RF 0.46 (hexane–EtOAc 6 : 1). [α]D
1
m), 5.87–5.97 (1 H, m), 6.21–6.34 (1 H, m), 7.34–7.44 (2 H, m), −93.2 (c 1.02, CHCl3). H NMR (CDCl3, 500 MHz,) δ 1.56 (3 H,
7.50–7.61 (1 H, m), 7.98–8.05 (1 H, m), 8.71–8.76 (1 H, m); 13C d, J = 6.6 Hz), 3.69 (3 H, s), 5.00–5.11 (1 H, m), 5.42–5.52 (1 H,
NMR (CDCl3, 126 MHz) δ 25.2, 26.5, 27.2, 39.0, 46.9, 49.2, 52.1, m), 7.42–7.53 (3 H, m), 7.75–7.80 (1 H, m), 7.80–7.86 (3 H, m);
55.4, 60.3 (bs), 101.1, 114.7, 119.1 (bs), 121.9, 128.2 (bs), 131.8, 13C NMR (CDCl3, 126 MHz) δ 22.1, 50.5, 51.9, 124.2, 124.3,
140.4, 144.7, 147.6, 156.9, 157.7; GC (Phenomenex Zebron 125.6, 126.0, 127.4, 127.7, 128.2, 132.5, 133.2, 140.9, 156.2; GC
ZB-35 HT) RT 18.44 min; GC–MS (EI, 70 eV) m/z (%) 349 (5), (Phenomenex Zebron ZB-35 HT) RT 12.31 min; GC–MS (EI,
308 (6), 294 (5), 214 (3), 159 (6), 137 (19), 136 (100), 108 (5), 95 70 eV) m/z (%) 229 (M) (39), 215 (15), 214 (100), 182 (17), 171
(12), 94 (8), 82 (11), 81 (26); C22H27N3O3 (381.47): calcd C (42), 170 (19), 155 (41), 154 (38), 153 (24), 152 (15), 143 (13),
69.27, H 7.13, N 11.02; found C 69.11, H 6.92, N 11.15.
129 (32), 128 (52), 127 (45), 126 (12), 115 (13), 102 (8);
N-Bornyl methyl carbamate (23d). Prepared from bornyl- C14H15NO2 (229.27): calcd C 73.34, H 6.59, N 6.11; found C
amine (22d) (3.400 g, 0.022 mol), ClCOOMe (1.714 mL, 73.17, H 6.41, N 6.09.
2.096 g, 0.022 mol) and NEt3 (3.092 mL, 2.245 g, 0.022 mol).
The synthesis of 24a–f
Yield 1.128 g (24%). Isolated as a mixture of two diastereomers
1
in a 1 : 0.3 ratio. White solid. RF 0.44 (hexane–EtOAc 6 : 1). H In a flame-dried, two-neck, round-bottom 100 mL flask
NMR (CDCl3, 500 MHz,) (major isomer) δ 0.82 (3 H, s), 0.85 equipped with a magnetic stirrer and an inert gas inlet sub-
(3 H, s), 0.87 (3 H, s), 1.10–1.17 (1 H, m), 1.20–1.28 (1 H, m), strate (1 equiv.) was mixed with THF (20 mL). The mixture was
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cooled to 0 °C and LiAlH4 (1.5 equiv.) was slowly added by por- 0.0080 mol). Yield 0.782 g (88%). Isolated as a mixture of two
tions (CAUTION: a violent gas evolution was observed). After diastereomers in a 1 : 0.3 ratio.
all of the LiAlH4 was added, the mixture was refluxed for 1 h
N-Methyl-(R)-1-(1-naphthyl)ethylamine (24e). Prepared from
and then cooled again to 0 °C. Aqueous KOH (20% m/m) was N-(R)-1-(1-naphthyl)ethyl methyl carbamate (23e) (1.194 g,
added dropwise until the slurry changed colour from grey to 0.0028 mol) and LiAlH4 (0.297 g, 0.0078 mol). Yield 0.911 g
1
white. The obtained mixture was filtered through silica gel, the (94%). Colorless oil. [α]D 63.4 (c 1.14, CHCl3). H NMR (CDCl3,
solid was washed with Et2O (3 × 30 mL), the filtrate was dried 500 MHz,) δ 1.52 (3 H, d, J = 6.6 Hz), 1.71 (1 H, bs), 2.43 (3 H,
over Na2SO4 and evaporated yielding a crude product. NMR s), 4.54 (1 H, q, J = 6.6 Hz), 7.47–7.55 (3 H, m), 7.63–7.66 (1 H,
analysis of the sample showed essentially no impurities so it m), 7.75–7.78 (1 H, m), 7.87–7.91 (1 H, m), 8.18–8.22 (1 H, m);
was decided to use the amine without further purification.
13C NMR (CDCl3, 126 MHz) δ 23.1, 34.7, 55.4, 122.5, 122.9,
N-Methylneomenthylamine (24a). Prepared from N-neo- 125.3, 125. 7, 125.8, 127.2, 128.9, 131.3, 133.9, 140.8; GC (Phe-
menthyl methyl carbamate (23a) (0.302 g, 0.0014 mol) and nomenex Zebron ZB-35 HT) RT 9.40 min; GC–MS (EI, 70 eV)
LiAlH4 (0.081 g, 0.0021 mol). Yield 0.216 g (90%). Colorless m/z (%) 185 (M) (5), 171 (14), 170 (100), 155 (13), 154 (11), 153
1
liquid. H NMR (CDCl3, 500 MHz,) δ 0.85 (3 H, d, J = 6.6 Hz), (17), 152 (12), 129 (10), 128 (15), 127 (17). Data are in accord-
0.90 (3 H, d, J = 6.6 Hz), 0.91 (3 H, d, J = 6.3 Hz), 0.82–0.96 ance with those reported in the literature.25
(2 H, m), 1.15–1.27 (1 H, m), 1.43–1.52 (1 H, m), 1.56–1.77
N-Methyl-(S)-1-(2-naphthyl)ethylamine (24f). Prepared from
(4 H, m), 1.93–1.99 (1 H, m), 2.39 (3 H, s), 2.76–2.79 (1 H, m); N-(S)-1-(2-naphthyl)ethyl methyl carbamate (23f) (0.215 g,
13C NMR (CDCl3, 126 MHz) δ 20.6, 21.6, 22.5, 25.0, 25.5, 28.9, 0.0009 mol) and LiAlH4 (0.053 g, 0.0014 mol). Yield 0.138 g
1
34.4, 35.4, 37.3, 48.4, 55.9; GC (Phenomenex Zebron ZB-35 HT) (79%). Colorless oil. [α]D 63.7 (c 1.04, CHCl3). H NMR (CDCl3,
RT 4.66 min; GC–MS (EI, 70 eV) m/z (%) 169 (M) (5), 154 (4), 500 MHz) δ 1.46 (3 H, d, J = 6.6 Hz), 1.81 (1 H, bs), 2.36 (3 H,
112 (6), 85 (6), 84 (100).
s), 3.84 (1 H, q, J = 6.6 Hz), 7.44–7.51 (3 H, m), 7.74–7.77 (1 H,
9-epi-9-(Methylamino)quinine (24b). Prepared from 9-epi-9- m), 7.82–7.86 (3 H, m); 13C NMR (CDCl3, 126 MHz) δ 23.9,
((methoxycarbonyl)amino)quinine (23b) (0.444 g, 0.0012 mol) 34.5, 60.3, 124.8, 125.3, 125.4, 125.9, 127.6, 127.7, 128.2, 132.8,
and LiAlH4 (0.066 g, 0.0017 mol). Yield 0.333 g (85%) (con- 133.4, 142.6; GC (Phenomenex Zebron ZB-35 HT) RT 9.44 min;
tained some impurities). Pale yellow waxy solid. 1H NMR GC–MS (EI, 70 eV) m/z (%) 185 (M) (3), 171 (14), 170 (100), 155
(CDCl3, 500 MHz) (some peaks are very broad, probably due to (13), 154 (10), 153 (12), 152 (8), 129 (9), 128 (15), 127 (15), 115
the restricted rotation) δ 0.76–0.88 (1 H, m), 1.46–1.71 (4 H, (7), 85 (11).
m), 2.13–2.41 (4 H, m), 2.61–2.85 (2 H, m), 2.89–3.10 (1 H, m),
3.13–3.30 (2 H, m), 3.67–3.81 (1 H, m), 3.97 (3 H, bs), 4.85–5.04
The synthesis of 25a,d–f
(2 H, m), 5.64–5.83 (2 H, m), 7.33–7.43 (1 H, m), 7.48–7.74 (1 In a flame-dried Schlenk tube (25 mL) equipped with a mag-
H, m), 7.99–8.11 (1 H, m), 8.52–8.87 (2 H, m); GC (Phenom- netic stirrer and an inert gas inlet was placed amine (1 equiv.)
enex Zebron ZB-35 HT) RT 16.62 min; GC–MS (EI, 70 eV) m/z in DCM (10 mL). Then, NEt3 (1 equiv.) was added followed by
(%) 337 (M) (2), 308 (19), 202 (16), 201 (100), 199 (8), 186 (7), Ph2PCl (1 equiv.). The mixture was allowed to stir at rt for 16 h,
173 (11), 160 (15), 157 (7), 137 (28), 136 (50), 122 (11), 117 (5), then BH3–THF (1.5 equiv., 1 M in THF) was added and the
108 (38), 95 (10), 94 (10), 82 (45), 81 (22), 80 (24).
9-epi-9-(Methylamino)quinidine (24c). Prepared from 9-epi- (10 mL) was added to the reaction mixture. The mixture was
9-((methoxycarbonyl)amino)quinidine (23c) (0.241 g, extracted with DCM (3 × 20 mL), combined organic phases
mixture was allowed to stir for an additional hour. Then, water
0.006 mol) and LiAlH4 (0.036 g, 0.009 mol). Yield 0.166 g were dried over Na2SO4 and evaporated. The residue was puri-
1
(78%) (contained some impurities). Pale yellow waxy solid. H fied by flash chromatography using hexane–EtOAc = 6 : 1 or
NMR (CDCl3, 500 MHz) (some peaks are very broad, probably CHCl3–MeOH = 15 : 1 as the eluent.
due to the restricted rotation) δ 0.67–0.88 (1 H, m), 1.10–1.24
Diphenylphosphinous acid-borane N-methylneomenthyl-
(1 H, m), 1.37–1.60 (3 H, m), 2.16 (3 H, s), 2.13–2.31 (1 H, m), amide (25a). Prepared from N-methylneomenthylamine (24a)
2.70–3.06 (6 H, m), 3.93 (3 H, s), 4.23–4.41 (1 H, m), 4.97–5.13 (0.211 g, 0.0012 mol), Ph2PCl (0.224 mL, 0.275 g, 0.0012 mol),
(2 H, m), 5.82–5.94 (1 H, m), 7.30–7.40 (1 H, m), 7.39–7.54 (1 NEt3 (0.174 mL, 0.126 g, 0.0012 mol) and BH3–THF (1.87 mL,
H, m), 7.58–7.72 (1 H, m), 7.95–8.05 (1 H, m), 8.62–8.81 (1 H, 0.0019 mol). Yield 0.163 g (36%). Colorless oil. RF 0.56
m); 13C NMR (CDCl3, 126 MHz,) (some peaks are very broad, (hexane–EtOAc 6 : 1). [α]D −15.7 (c 0.825, CHCl3). 1H NMR
probably due to the restricted rotation) δ 24.5, 26.5, 27.4, 34.2, (500 MHz, CDCl3): δ = 0.66–1.37 (bm, 3 H), 0.80 (d, JH–H
=
39.4, 47.5, 49.3, 55.3, 59.1, 62.3, 100.5, 114.3, 119.6, 121.3, 6.3 Hz, 3 H), 0.86–0.98 (m, 1 H), 0.95 (d, JH–H = 6.6 Hz, 3 H),
129.9, 131.6, 140.6, 144.3, 146.8, 147.9, 157.5; GC (Phenom- 1.09 (d, JH–H = 6.3 Hz, 3 H), 1.19–1.29 (m, 1 H), 1.27–1.36 (m,
enex Zebron ZB-35 HT) RT 16.62 min; GC–MS (EI, 70 eV) m/z 1 H), 1.42–1.53 (m, 1 H), 1.62–1.78 (m, 2 H), 1.79–1.86 (m,
(%) 337 (M) (2), 308 (17), 202 (15), 201 (100), 199 (8), 186 (6), 2 H), 1.98–2.04 (m, 1 H), 2.76 (d, JP–H = 7.9 Hz, 3 H), 4.18–4.25
173 (10), 160 (14), 157 (6), 137 (29), 136 (15), 122 (10), 108 (37), (m, 1 H), 7.41–7.53 (m, 6 H), 7.58–7.63 (m, 2 H), 7.65–7.71 (m,
95 (9), 94 (9), 82 (45), 81 (19), 80 (23). Data are in accordance 2 H) ppm. 13C NMR (126 MHz, CDCl3): δ = 21.2 22.82, 23.1,
with those reported in the literature.26
26.6, 28.7, 29.0, 34.8, 36.6 (d, JP–C = 4.5 Hz), 43.4, 47.5 (d, JP–C =
N-Methylbornylamine (24d). Prepared from N-bornyl methyl 8.2 Hz), 53.5 (d, JP–C = 10.9 Hz), 128.2 (d, JP–C = 10.0 Hz), 128.3
carbamate (23d) (1.128 g, 0.0053 mol) and LiAlH4 (0.304 g, (d, JP–C = 10.0 Hz), 130.7 (d, JP–C = 2.7 Hz), 130.8 (d, JP–C = 1.8
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Hz), 131.4 (d, JP–C = 69.0 Hz), 131.7 (d, JP–C = 57.2 Hz), 132.1 (d, MS (EI, 70 eV) m/z (%) 369 (M − BH3) (12), 368 (10), 313 (12),
JP–C = 10.9 Hz), 132.5 (d, JP–C = 10.0 Hz) ppm. 31P NMR 312 (52), 311 (30), 215 (9), 214 (52), 185 (7), 184 (7), 183 (25),
(202 MHz, CDCl3): δ = 72.33 ppm (bm). GC (Phenomenex 155 (15), 153 (15), 152 (10), 128 (9), 127 (8), 122 (13), 115 (9),
Zebron ZB-35 HT): RT = 14.65 min. GC–MS (EI, 70 eV): m/z (%) 109 (100), 108 (10), 107 (8), 104 (12); C25H27BNP (383.27): calcd
= 353 (M − BH3) (6), 268 (13), 215 (24), 214 (23), 186 (24), 185 C 78.34, H 7.10, N 3.65; found C 78.55, H 7.00, N 3.49.
(27), 183 (37), 169 (13), 168 (100), 109 (20), 108 (37), 107 (9), 84
(7). C23H35BNP (367.32): calcd C 75.21, H 9.60, N 3.81; found C naphthyl)ethylamide (25f). Prepared from N-methyl-(S)-1-(2-
75.02, H 9.59, N 4.03. naphthyl)ethylamine (24f) (0.138 g, 0.0007 mol), Ph2PCl
Diphenylphosphinous
acid-borane
N-methyl-(S)-1-(2-
Diphenylphosphinous acid-borane N-methyl-bornylamide (0.133 mL, 0.164 g, 0.0007 mol), NEt3 (0.104 mL, 0.075 g,
(25d). Prepared from N-methylbornylamine (24d) (0.782 g, 0.0007 mol) and BH3–THF (1.12 mL, 0.0011 mol). Yield
0.0047 mol), Ph2PCl (0.840 mL, 1.032 g, 0.0047 mol), NEt3 0.185 g (65%). White solid, mp 145.0 °C (dec.). RF 0.63
(0.652 mL, 0.473 g, 0.0047 mol) and BH3–THF (7.01 mL, (hexane–EtOAc 6 : 1). [α]D −15.0 (c 1.045, CHCl3). 1H NMR
0.0070 mol). Isolated as a mixture of exo–endo isomers in a (CDCl3, 500 MHz) δ 0.82–1.72 (3 H, bm), 1.64 (3 H, d, J = 6.6
1 : 0.4 ratio. Crystallization of this mixture afforded a product Hz), 2.26 (3 H, d, J = 7.3 Hz), 5.50–5.58 (1 H, m), 7.40–7.45 (2
in a 1 : 0.1 ratio. Yield 1.205 g (71%). White sticky oil. RF 0.77 H, m), 7.47–7.52 (5 H, m), 7.53–7.60 (3 H, m), 7.61–7.64 (1 H,
1
(hexane–EtOAc 6 : 1). H NMR (CDCl3, 500 MHz) (exo isomer) m), 7.70–7.75 (2 H, m), 7.77 (1 H, bs), 7.81–7.88 (3 H, m); 13C
δ 0.41–1.29 (3 H, bm), 0.85 (3 H, s), 0.94 (3 H, s), 0.95 (3 H, s), NMR (CDCl3, 126 MHz) δ 16.5, 28.9 (d, J = 4.5 Hz), 55.6 (d, J =
1.19–1.29 (2 H, m), 1.37–1.45 (1 H, m), 1.47–1.56 (1 H, m), 11.8 Hz), 125.8, 125.9, 126.0, 127.0, 127.5, 127.9, 127.9, 128.4
1.63–1.72 (4 H, m), 1.93–2.02 (1 H, m), 2.70 (3 H, d, J = 10.1 (d, J = 10.9 Hz), 128.5 (d, J = 10.0 Hz), 130.8 (d, J = 68.1 Hz),
Hz), 2.73–2.83 (1 H, m), 3.78–3.86 (1 H, m), 5.64–5.71 (1 H, m), 130.9 (d, J = 1.8 Hz), 131.1 (d, J = 2.7 Hz), 131.4 (d, J = 60.0 Hz),
5.79–5.94 (3 H, m), 7.42–7.52 (3 H, m), 7.61–7.66 (2 H, m); 132.2 (d, J = 10.9 Hz), 132.4 (d, J = 10.0 Hz), 132.6, 133.0, 139.1
(endo isomer) δ 0.41–1.29 (3 H, bm), 0.76 (3 H, s), 0.83 (3 H, s), (d, J = 5.5 Hz); 31P NMR (CDCl3, 202 MHz) δ 69.59 (bm); GC
0.90 (3 H, s), 1.19–1.29 (2 H, m), 1.37–1.45 (1 H, m), 1.47–1.56 (Phenomenex Zebron ZB-35 HT) RT 19.77 min; GC–MS (EI,
(1 H, m), 1.63–1.72 (4 H, m), 1.93–2.02 (1 H, m), 2.72 (3 H, d, 70 eV) m/z (%) 369 (M − BH3) (11), 368 (9), 313 (16), 312 (65),
J = 10.7 Hz), 2.73–2.83 (1 H, m), 3.42–3.49 (1 H, m), 3.92–4.01 215 (11), 214 (58), 184 (11), 183 (25), 155 (19), 154 (9), 153 (15),
(1 H, m), 5.74–5.79 (1 H, m), 5.79–5.94 (3 H, m), 7.42–7.52 (3 152 (10), 128 (10), 127 (10), 122 (13), 115 (10), 110 (7),
H, m), 7.71–7.76 (2 H, m); 13C NMR (CDCl3, 126 MHz,) (only 109 (100), 108 (16), 107 (9), 104 (12); C25H27BNP (383.27): calcd
some peaks are described due to overlapping of signals) (exo C 78.34, H 7.10, N 3.65; found C 78.33, H 7.12, N 3.88.
isomer) δ 50.6 (d, J = 3.6 Hz), 67.4 (d, J = 5.5 Hz), 121.6 (d, J =
N-Methyl-(S)-1-phenylethylamine (31). This compound was
2.7 Hz), 121.8 (d, J = 5.5 Hz), 127.6 (d, J = 10.0 Hz), 127.7 (d, J = prepared according to the literature procedure.27 Data are in
8.2 Hz), 128.8 (d, J = 10.0 Hz), 130.8 (d, J = 10.0 Hz), 131.2 (d, accordance with those reported in the literature.28
J = 1.8 Hz), 132.1 (d, J = 74.5 Hz); (endo isomer) δ 50.4 (d, J =
The synthesis of 32a–e and 33a,b
3.6 Hz), 68.5 (d, J = 5.5 Hz), 121.6 (d, J = 2.7 Hz), 122.0 (d, J =
6.4 Hz), 127.3 (d, J = 7.3 Hz), 127.5 (d, J = 10.0 Hz), 128.8 (d, J = In a flame-dried Schlenk tube (25 mL), equipped with a mag-
10.0 Hz), 131.2 (d, J = 9.1 Hz), 131.3 (d, J = 1.8 Hz); 31P NMR netic stirrer and inert gas inlet was placed secondary phos-
(CDCl3, 202 MHz) (exo isomer) δ 79.95 (bm); (endo isomer) phine oxide (1 equiv.) in DCM (10 mL). Then, PCl3 (1.5 equiv.)
δ 81.78 (bm); C23H33BNP (365.30): calcd C 75.62, H 9.11, was added and the mixture was allowed to stir at rt for 2 h.
N 3.83; found C 75.70, H 9.30, N 3.88.
Diphenylphosphinous acid-borane
Then, the solution was transferred to a flame-dried, round-
N-methyl-(R)-1-(1- bottom, inert gas-flushed flask (25 mL) and evaporated under
naphthyl)ethylamide (25e). Prepared from N-methyl-(R)-1-(1- reduced pressure. The residue was dissolved in DCM (5 mL).
naphthyl)ethylamine (24e) (0.910 g, 0.0049 mol), Ph2PCl In a separate flame-dried Schlenk tube (25 mL), equipped with
(0.881 mL, 1.083 g, 0.0049 mol), NEt3 (0.684 mL, 0.497 g, a magnetic stirrer and an inert gas inlet were placed N-methyl-
0.0049 mol) and BH3–THF (7.37 mL, 0.0074 mol). Yield (S)-1-phenylethylamine (31) (1 equiv.) and NEt3 (1 equiv.) in
1.357 g (72%). White solid, mp 144.2–145.8 °C. RF 0.63 DCM (5 mL). A solution of chlorophosphine in DCM, prepared
(hexane–EtOAc 6 : 1). [α]D −172.7 (c 1.24, CHCl3). 1H NMR in a separate flask, was transferred to the amine solution using
(CDCl3, 500 MHz) δ 1.05–1.88 (3 H, bm), 1.67 (3 H, d, J = 6.9 a syringe. After complete addition of chlorophosphine, the
Hz), 2.11 (3 H, d, J = 7.3 Hz), 5.99–6.06 (3 H, m), 7.28–7.34 mixture was allowed to stir at rt for 23 h. Then, BH3–THF (1.5
(2 H, m), 7.40–7.57 (10 H, m), 7.74–7.80 (2 H, m), 7.82–7.86 equiv.) was added and the mixture was stirred for an
(1 H, m), 7.88–7.91 (1 H, m), 8.66–8.69 (1 H, m); 13C NMR additional hour. Then, water (10 mL) was added to the reac-
(CDCl3, 126 MHz,) δ 17.2, 29.6 (d, J = 4.5 Hz), 53.0 (d, J = 10.9 tion mixture. The mixture was extracted with DCM (3 × 20 mL),
Hz), 124.6, 125.3 (d, J = 1.8 Hz), 125.4, 125.8, 126.1, 128.2 (d, combined organic phases were dried over Na2SO4 and evapor-
J = 10.9 Hz), 128.3, 128.4 (d, J = 10.0 Hz), 128.5, 130.5 (d, J = ated. The residue was purified by flash chromatography using
64.5 Hz), 130.7 (d, J = 2.7 Hz), 131.2 (d, J = 1.8 Hz), 131.4 (d, J = hexane–EtOAc = 6 : 1 as the eluent.
53.6 Hz), 131.9, 132.0 (d, J = 10.9 Hz), 132.8 (d, J = 10.0 Hz),
Di(o-tolyl)phosphinous acid-borane N-methyl-(S)-α-methyl-
134.0, 136.6 (d, J = 9.1 Hz); 31P NMR (CDCl3, 202 MHz) δ 68.05 benzylamide (32a). Prepared from di(o-tolyl)phosphine oxide
(bm); GC (Phenomenex Zebron ZB-35 HT) RT 19.37 min; GC– (0.401 g, 0.0017 mol), PCl3 (0.228 mL, 0.359 g, 0.0026 mol), 31
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(0.236 g, 0.0017 mol), NEt3 (0.243 mL, 0.176 g, 0.0017 mol) J = 3.6 Hz), 55.2, 55.2, 113.95 (d, J = 10.9 Hz), 113.98 (d, J =
and BH3–THF (2.61 mL, 0.0026 mol). Yield 0.261 g (41%). Col- 11.8 Hz), 122.0 (d, J = 73.6 Hz), 122.7 (d, J = 64.5 Hz), 126.9,
orless thick oil. RF 0.69 (hexane–EtOAc 6 : 1). [α]D −71.0 (c 127.8, 128.1, 133.8 (d, J = 10.9 Hz), 134.0 (d, J = 11.8 Hz), 141.7
1.135, CHCl3). 1H NMR (CDCl3, 500 MHz) δ 1.04–1.77 (3 H, (d, J = 6.4 Hz), 161.6 (d, J = 2.7 Hz), 161.7 (d, J = 2.7 Hz);
bm), 1.64 (3 H, d, J = 6.9 Hz), 2.34 (3 H, s), 2.35 (3 H, s), 31P NMR (CDCl3, 202 MHz) δ 67.07 (bm); GC (Phenomenex
5.46–5.56 (1 H, m), 7.01–7.12 (2 H, m), 7.17–7.23 (1 H, m), Zebron ZB-35 HT) RT 19.14 min; GC–MS (EI, 70 eV) m/z (%)
7.23–7.27 (1 H, m), 7.28–7.45 (9 H, m); 13C NMR (CDCl3, 379 (M − BH3) (9), 378 (13), 323 (18), 322 (83), 274 (43), 245
126 MHz) δ 17.1 (d, J = 1.8 Hz), 22.2 (d, J = 3.6 Hz), 22.5 (d, J = (19), 214 (9), 152 (9), 139 (100), 138 (54), 134 (24), 113 (10), 105
2.7 Hz), 29.0 (d, J = 2.7 Hz), 55.6 (d, J = 10.0 Hz), 125.4 (d, (20), 95 (10); C23H29BNO2P (393.27): calcd C 70.24, H 7.43, N
J = 9.1 Hz), 125.6 (d, J = 9.1 Hz), 127.3, 128.0, 128.4, 129.8 (d, 3.56; found C 70.38, H 7.33, N 3.70.
J = 61.8 Hz), 130.7 (d, J = 1.8 Hz), 130.7 (d, J = 60.4 Hz), 131.0
(d, J = 1.8 Hz), 131.8 (d, J = 9.1 Hz), 132.0 (d, J = 9.1 Hz), 132.3 (S)-α-methylbenzylamide
Di(3,5-dimethylphenyl)phosphinous acid-borane N-methyl-
(32d). Prepared from di(3,5-
(d, J = 7.3 Hz), 132.8 (d, J = 8.2 Hz), 141.2 (d, J = 3.6 Hz), 141.5 dimethylphenyl)phosphine oxide (0.384 g, 0.0015 mol), PCl3
(d, J = 12.7 Hz), 142.3 (d, J = 12.7 Hz); 31P NMR (CDCl3, (0.195 mL, 0.306 g, 0.0022 mol), 31 (0.201 g, 0.0015 mol), NEt3
202 MHz,) δ 70.92 (bm); GC (Phenomenex Zebron ZB-35 HT) (0.207 mL, 0.150 g, 0.0015 mol) and BH3–THF (2.23 mL,
RT 15.29 min; GC–MS (EI, 70 eV) m/z (%) 347 (M − BH3) (26), 0.0023 mol). Yield 0.136 g (24%). Colorless thick oil. RF 0.67
346 (4), 290 (13), 275 (11), 243 (17), 242 (100), 214 (8), 213 (24), (hexane–EtOAc 6 : 1). [α]D 32.3 (c 0.95, CHCl3). 1H NMR (CDCl3,
212 (12), 211 (29), 197 (10), 196 (22), 179 (12), 165 (18), 152 500 MHz,) δ 0.75–1.60 (3 H, bm), 1.53 (3 H, d, J = 6.9 Hz), 2.27
(11), 150 (52), 136 (16), 135 (43), 134 (76), 133 (10), 123 (19), (3 H, d, J = 7.3 Hz), 2.31 (6 H, s), 2.38 (6 H, s), 7.11 (2 H, bs),
122 (23), 121 (32), 105 (40), 103 (9), 91 (25); C23H29BNP 7.14 (1 H, bs), 7.16 (1 H, bs), 7.28–7.33 (3 H, m), 7.34–7.39
(361.27): calcd C 76.47, H 8.09, N 3.88; found C 76.43, H 8.30, (2 H, m), 7.43–7.47 (2 H, m); 13C NMR (CDCl3, 126 MHz) δ 16.5
N 4.00.
(d, J = 1.8 Hz), 21.3, 21.4, 28.9 (d, J = 3.6 Hz), 55.3 (d, J = 10.9
Di(p-tolyl)phosphinous acid-borane N-methyl-(S)-α-methyl- Hz), 127.0, 127.97, 127.99, 129.7 (d, J = 10.0 Hz), 129.9 (d, J =
benzylamide (32b). Prepared from di(p-tolyl)phosphine oxide 10.0 Hz), 130.7 (d, J = 67.2 Hz), 131.2 (d, J = 60.9 Hz), 132.5 (d,
(0.419 g, 0.0018 mol), PCl3 (0.238 mL, 0.375 g, 0.0027 mol), 31 J = 1.8 Hz), 132.8 (d, J = 2.7 Hz), 137.9 (d, J = 10.9 Hz), 137.9 (d,
(0.246 g, 0.0018 mol), NEt3 (0.254 mL, 0.184 g, 0.0018 mol) J = 10.9 Hz), 141.7 (d, J = 5.5 Hz); 31P NMR (CDCl3, 202 MHz,) δ
and BH3–THF (2.73 mL, 0.0027 mol). Yield 0.154 g (23%). Col- 69.57 (bm); GC (Phenomenex Zebron ZB-35 HT) RT 15.60 min;
orless thick oil. RF 0.58 (hexane–EtOAc 6 : 1). [α]D −31.4 (c 0.81, GC–MS (EI, 70 eV) m/z (%) 375 (M − BH3) (8), 374 (12),
CHCl3). 1H NMR (CDCl3, 500 MHz) δ 0.74–1.63 (3 H, bm), 1.49 319 (22), 318 (100), 271 (8), 270 (44), 241 (15), 211 (9), 193 (8),
(3 H, d, J = 6.9 Hz), 2.22 (3 H, d, J = 7.3 Hz), 2.39 (3 H, s), 2.42 149 (15), 137 (58), 136 (32), 135 (15), 134 (40), 133 (16),
(3 H, s), 7.20–7.24 (2 H, m), 7.25–7.30 (3 H, m), 7.32–7.37 (2 H, 119 (16), 109 (12), 105 (40), 103 (10), 92 (18), 91 (41);
m), 7.38–7.44 (4 H, m), 7.54–7.60 (2 H, m); 13C NMR (CDCl3, C25H33BNP (389.32): calcd C 77.13, H 8.54, N 3.60; found
126 MHz,) δ 16.4, 21.4, 21.4, 28.7 (d, J = 3.6 Hz), 55.2 (d, J = C 77.30, H 8.55, N 3.55.
11.8 Hz), 127.0, 127.6 (d, J = 71.8 Hz), 127.9, 128.0, 128.2 (d, J =
61.8 Hz), 129.1 (d, J = 10.9 Hz), 129.1 (d, J = 10.9 Hz), 132.1 (d, (S)-α-methylbenzylamide
Di(3,5-dimethoxyphenyl)phosphinous acid-borane N-methyl-
(32e). Prepared from di(3,5-
J = 10.0 Hz), 132.3 (d, J = 10.9 Hz), 141.0 (d, J = 1.8 Hz), 141.3 dimethoxyphenyl)phosphine oxide (0.458 g, 0.0014 mol), PCl3
(d, J = 1.8 Hz), 141.7 (d, J = 5.5 Hz); 31P NMR (CDCl3, 202 MHz) (0.186 mL, 0.293 g, 0.0021 mol), 31 (0.192 g, 0.0014 mol), NEt3
δ
68.45 (bm); GC (Phenomenex Zebron ZB-35 HT) (0.198 mL, 0.144 g, 0.0014 mol) and BH3–THF (2.13 mL,
RT 15.92 min; GC–MS (EI, 70 eV) m/z (%) 347 (M − BH3) (9), 0.0021 mol). Yield 0.191 g (30%). Colorless thick oil. RF 0.42
346 (16), 291 (22), 290 (100), 243 (9), 242 (52), 213 (14), 211 (hexane–EtOAc 6 : 1). [α]D 45.2 (c 0.75, CHCl3). 1H NMR (CDCl3,
(14), 197 (6), 183 (10), 165 (11), 136 (20), 135 (9), 134 (30), 123 500 MHz) δ 0.91–1.74 (3 H, bm), 1.55 (3 H, d, J = 7.3 Hz), 2.28
(90), 122 (37), 121 (29), 118 (15), 105 (27), 91 (20); C23H29BNP (3 H, d, J = 7.3 Hz), 3.71 (6 H, s), 3.80 (6 H, s), 5.28–5.39 (1 H,
(361.27): calcd C 76.47, H 8.09, N 3.88; found C 76.70, H 8.19, m), 6.54 (1 H, t, J = 2.2 Hz), 6.59 (1 H, t, J = 2.2 Hz), 6.66 (2 H,
N 3.77.
Di(p-anisyl)phosphinous
dd, J = 2.5 Hz, 12.0 Hz), 6.84 (2 H, dd, J = 2.2 Hz, 11.7 Hz),
N-methyl-(S)- 7.25–7.29 (1 H, m), 7.33–7.37 (2 H, m), 7.44–7.47 (2 H, m);
acid-borane
α-methylbenzylamide (32c). Prepared from di(p-anisyl)phos- 13C NMR (CDCl3, 126 MHz) δ 16.5, 29.0 (d, J = 3.6 Hz), 55.30,
phine oxide (0.461 g, 0.0018 mol), PCl3 (0.230 mL, 0.362 g, 55.38, 55.37 (d, J = 11.8 Hz), 102.8, 103.2, 109.6 (d, J = 11.8 Hz),
0.0026 mol), 31 (0.238 g, 0.0017 mol), NEt3 (0.245 mL, 0.178 g, 110.1 (d, J = 11.8 Hz), 127.1, 127.9, 128.1, 132.7 (d, J = 67.2 Hz),
0.0017 mol) and BH3–THF (2.64 mL, 0.0026 mol). Yield 133.3 (d, J = 60.9 Hz), 141.4 (d, J = 6.4 Hz), 160.5 (d, J = 5.5 Hz),
0.380 g (55%). Colorless thick oil. RF 0.44 (hexane–EtOAc 6 : 1). 160.7 (d, J = 4.5 Hz); 31P NMR (CDCl3, 202 MHz) δ 72.17 (bm);
[α]D 27.6 (c 0.87, CHCl3). 1H NMR (CDCl3, 500 MHz) GC (Phenomenex Zebron ZB-35 HT) RT 20.81 min; GC–MS (EI,
δ 0.83–1.54 (3 H, bm), 1.50 (3 H, d, J = 6.9 Hz), 2.24 (3 H, d, J = 70 eV) m/z (%) 439 (9), 438 (M − BH3) (14), 383 (24), 382 (100),
7.6 Hz), 3.84 (3 H, s), 3.86 (3 H, s), 5.29–5.39 (1 H, m), 334 (31), 305 (8), 196 (11), 182 (17), 181 (10), 169 (16), 168 (14),
6.92–6.96 (2 H, m), 6.98–7.02 (2 H, m), 7.25–7.29 (1 H, m), 167 (18), 151 (12), 139 (9), 137 (9), 134 (40), 121 (9), 105 (36),
7.32–7.37 (2 H, m), 7.40–7.44 (2 H, m), 7.45–7.50 (2 H, m), 95 (11); C25H33BNO4P (453.22): calcd C 66.24, H 7.34, N 3.09;
7.61–7.67 (2 H, m); 13C NMR (CDCl3, 126 MHz,) δ 16.3, 28.5 (d, found C 66.50, H 7.45, N 3.00.
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Di(2,6-dimethylphenyl)phosphine (33a). Prepared from (d, J = 2.7 Hz), 122.2 (d, J = 7.3 Hz), 127.1, 127.7, 128.0, 128.1
di(2,6-dimethylphenyl)phosphine oxide (0.517 g, 0.002 mol), (d, J = 10.0 Hz), 128.4 (d, J = 6.4 Hz), 128.5 (d, J = 5.5 Hz), 130.5
PCl3 (0.262 mL, 0.412 g, 0.003 mol), 31 (0.271 g, 0.002 mol), (d, J = 2.7 Hz), 131.1 (d, J = 9.1 Hz), 131.4 (d, J = 51.1 Hz); 31P
NEt3 (0.279 mL, 0.202 g, 0.002 mol) and BH3–THF (3.00 mL, NMR (CDCl3, 202 MHz) (major diastereomer) δ 72.85 (bm);
0.003 mol). Yield 0.140 g (29%) (the product partially oxidized (minor diastereomer) δ 75.09 (bm).
to the corresponding phosphine oxide during analysis).
(1,4-Cyclohexadien-3-yl)phenylphosphinous
acid-borane
1
RF 0.95 (hexane–EtOAc 6 : 1). H NMR (CDCl3, 500 MHz) δ 2.34 N-ethyl-(S)-α-methylbenzylamide (13c). Prepared from 10c
(12 H, s), 5.35 (1 H, d, J = 232.7 Hz), 7.01–7.06 (4 H, m), (0.093 g, 0.0003 mol) and sodium (0.015 g, 0.0007 mol). Iso-
7.12–7.17 (2 H, m); 31P NMR (CDCl3, 202 MHz) δ −91.57. Data lated as a mixture with a substrate. Yield 77% (a mixture of
are in accordance with those reported in the literature.29
two diastereomers in 42% de) (based on NMR analysis). RF
1
Di(3,5-bis(trifluoromethyl)phenyl)phosphine
(33b). 0.67 (hexane–EtOAc 2 : 1). H NMR (CDCl3, 500 MHz,) (major
Obtained from di(2,6-dimethylphenyl)phosphine oxide diastereomer) δ 0.55–1.35 (3 H, bm), 0.64 (3 H, t, J = 7.3 Hz),
(0.474 g, 0.001 mol), PCl3 (0.131 mL, 0.206 g, 0.0015 mol), 31 1.57 (3 H, d, J = 6.9 Hz), 2.77–2.85 (2 H, m), 2.89–2.97 (1 H, m),
(0.135 g, 0.001 mol), NEt3 (0.139 mL, 0.101 g, 0.001 mol) and 3.05–3.13 (1 H, m), 4.00–4.10 (1 H, m), 5.06–5.17 (1 H, m),
BH3–THF (1.50 mL, 0.0015 mol) as a mixture with other com- 5.67–5.73 (1 H, m), 5.77–5.82 (1 H, m), 5.87–5.93 (1 H, m),
pounds. 31P NMR (202 MHz, CDCl3) δ −40.59. Data are in 5.96–6.02 (1 H, m), 7.30–7.35 (2 H, m), 7.45–7.54 (6 H, m),
accordance with those reported in the literature.13a
7.83–7.89 (2 H, m); (minor diastereomer) δ 0.55–1.35 (3 H,
bm), 0.78 (3 H, t, J = 7.3 Hz), 1.56 (3 H, d, J = 6.9 Hz), 2.83–2.88
(2 H, m), 2.95–3.03 (1 H, m), 3.05–3.13 (1 H, m), 3.97–4.07
(1 H, m), 5.24–5.33 (1 H, m), 5.72–5.77 (1 H, m), 5.84–5.89 (1
H, m), 5.91–5.99 (2 H, m), 7.30–7.35 (2 H, m), 7.45–7.54 (6 H,
A general procedure of Birch reduction of arylphosphorus acid
amides
A
flame-dried, two-neck, round-bottom flask (100 mL), m), 7.73–7.77 (2 H, m); 13C NMR (CDCl3, 126 MHz,) (major dia-
equipped with a dry-ice condenser, a magnetic stirring bar and stereomer) δ 17.2, 18.8, 26.6 (d, J = 5.5 Hz), 36.1 (d, J = 40.9
an inert gas inlet was cooled to −78 °C. Gaseous ammonia was Hz), 38.8, 56.0 (d, J = 7.3 Hz), 121.4 (d, J = 4.5 Hz), 121.4 (d, J =
passed through the system until 10 mL was collected. Then, 1.8 Hz), 127.1, 128.0, 127.98, 128.00 (d, J = 4.5 Hz), 128.1 (d, J =
sodium (2.5–5 equiv.) was added and the mixture was allowed 3.6 Hz), 128.6 (d, J = 9.1 Hz), 130.9 (d, J = 1.8 Hz), 131.4 (d, J =
to stir at −78 °C for 5 min. Then, amide (1 equiv.) in 52.7 Hz), 131.7 (d, J = 9.1 Hz); (minor diastereomer) δ 17.6,
THF (5 mL) was added and the mixture was stirred for 5 min. 19.4, 26.6 (d, J = 5.5 Hz), 37.2 (d, J = 38.2 Hz), 39.6, 56.4 (d, J =
Solid NH4Cl (0.5 g) was added to quench the reaction, 8.2 Hz), 121.5 (d, J = 5.5 Hz), 121.7 (d, J = 1.8 Hz), 127.1,
ammonia was evaporated under reduced pressure, the in- 127.96, 127.98, 128.3 (d, J = 4.5 Hz), 128.4 (d, J = 3.6 Hz), 128.6
organic solid was filtered off and the filtrate was evaporated. (d, J = 9.1 Hz), 130.7 (d, J = 1.8 Hz), 131.5 (d, J = 9.1 Hz), 131.7
The residue was purified by flash chromatography using (d, J = 51.8 Hz); 31P NMR (CDCl3, 202 MHz,) (major diastereo-
hexane–EtOAc = 6 : 1, hexane–EtOAc = 2 : 1 or CHCl3–MeOH = mer) δ 72.54 (bm); (minor diastereomer) δ 74.49 (bm).
15 : 1 as eluents.
(1,4-Cyclohexadien-3-yl)phenylphosphinous
acid-borane
(1,4-Cyclohexadien-3-yl)phenylphosphinous
acid-borane N-isopropyl-(S)-α-methylbenzylamide (13d). Prepared from
N-methyl-(S)-α-methylbenzylamide (13b). Prepared from 10b 10d (0.129 g, 0.0004 mol) and sodium (0.021 g, 0.0009 mol).
(0.094 g, 0.0003 mol) and sodium (0.016 g, 0.0007 mol). Iso- Isolated as a mixture with a substrate. Yield 21% (a mixture of
lated as a mixture with unreacted starting material. Yield 71% (a two diastereomers in 10% de) (based on NMR analysis). RF
mixture of two diastereomers in 52% de) (based on NMR analysis). 0.69 (hexane–EtOAc 2 : 1). 1H NMR (CDCl3, 500 MHz) (major
1
RF 0.69 (hexane–EtOAc 2 : 1). H NMR (CDCl3, 500 MHz,) (major diastereomer) δ 0.56–1.48 (3 H, bm), 1.01 (3 H, d, J = 6.9 Hz),
diastereomer) δ 0.55–1.28 (3 H, bm), 1.48 (3 H, d, J = 6.9 Hz), 1.05 (3 H, d, J = 6.9 Hz), 1.59 (3 H, d, J = 6.9 Hz), 2.69–2.86 (2
2.37 (3 H, dd, J = 1.0 Hz, 6.9 Hz), 2.60–2.74 (2 H, m), 3.87–3.97 H, m), 3.50–3.60 (1 H, m), 3.95–4.06 (1 H, m), 4.85–4.97 (1 H,
(1 H, m), 5.09–5.19 (1 H, m), 5.59–5.65 (1 H, m), 5.73–5.85 (3 m), 5.63–5.72 (2 H, m), 5.83–5.90 (2 H, m), 7.20–7.26 (2 H, m),
H, m), 7.24–7.30 (2 H, m), 7.39–7.45 (3 H, m), 7.46–7.56 (3 H, 7.41–7.53 (6 H, m), 7.83–7.88 (2 H, m); (minor diastereomer) δ
m), 7.72–7.79 (2 H, m); (minor diastereomer) δ 0.55–1.28 (3 H, 0.56–1.48 (3 H, bm), 0.85 (3 H, d, J = 6.9 Hz), 1.02 (3 H, d, J =
bm), 1.56 (3 H, d, J = 6.9 Hz), 2.39 (3 H, dd, J = 0.6 Hz, 6.3 Hz), 6.9 Hz), 1.46 (3 H, d, J = 6.9 Hz), 2.80–2.94 (2 H, m), 3.61–3.70
2.70–2.85 (2 H, m), 3.82–3.91 (1 H, m), 5.32–5.41 (1 H, m), (1 H, m), 4.12–4.22 (1 H, m), 4.98–5.06 (1 H, m), 5.88–5.95 (2
5.63–5.68 (1 H, m), 5.78–5.88 (3 H, m), 7.31–7.38 (2 H, m), H, m), 5.96–6.06 (2 H, m), 7.20–7.26 (2 H, m), 7.41–7.53 (6 H,
7.39–7.45 (3 H, m), 7.46–7.56 (3 H, m), 7.66–7.72 (2 H, m); 13C m), 7.91–7.96 (2 H, m); 13C NMR (CDCl3, 126 MHz) (some
NMR (CDCl3, 126 MHz,) (major diastereomer) δ = 16.4, 26.4 (d, peaks were overlapped) (major diastereomer) δ 20.4, 23.5 (d,
J = 5.5 Hz), 29.0 (d, J = 4.5 Hz), 36.7 (d, J = 40.9 Hz), 55.9 (d, J = J = 1.8 Hz), 24.5, 26.7 (d, J = 5.5 Hz), 35.5 (d, J = 40.0 Hz), 50.0,
9.1 Hz), 121.2 (d, J = 2.7 Hz), 121.6 (d, J = 6.4 Hz), 127.1, 127.9, 55.2 (d, J = 5.5 Hz), 121.4 (d, J = 3.6 Hz), 121.8, 127.1, 127.8,
128.1 (d, J = 6.4 Hz), 128.1 (d, J = 5.5 Hz), 128.1, 128.7 (d, J = 128.1, 128.6 (d, J = 9.1 Hz), 130.8, 132.0 (d, J = 9.1 Hz); (minor
10.0 Hz), 130.7 (d, J = 2.7 Hz), 131.2 (d, J = 9.1 Hz), 131.7 (d, J = diastereomer) δ 19.6, 23.6 (d, J = 1.8 Hz), 24.3, 26.6 (d, J = 5.5
51.8 Hz); (minor diastereomer) δ 16.5, 26.5 (d, J = 5.5 Hz), 28.8 Hz), 35.7 (d, J = 40.9 Hz), 50.2, 55.9 (d, J = 5.5 Hz), 121.4 (d, J =
(d, J = 4.5 Hz), 38.1 (d, J = 36.3 Hz), 55.9 (d, J = 10.0 Hz), 121.8 3.6 Hz), 121.7, 127.0, 128.0, 128.1, 128.6 (d, J = 9.1 Hz), 130.8,
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131.8 (d, J = 9.1 Hz); 31P NMR (CDCl3, 202 MHz) (major 3.76–3.89 (1 H, m), 4.84–4.95 (1 H, m), 5.72–5.78 (1 H, m),
diastereomer) δ 69.12 (bm); (minor diastereomer) δ 69.36 (bm). 5.80–5.96 (3 H, m), 7.30–7.38 (3 H, m), 7.43–7.53 (5 H, m),
(1,4-Cyclohexadien-3-yl)phenylphosphinic acid N-methyl-(S)- 7.87–7.95 (2 H, m); (second diastereomer) δ 0.87 (3 H, t, J =
α-methylbenzylamide (14b). Prepared from 11b (0.095 g, 7.3 Hz), 1.66 (3 H, d, J = 6.9 Hz), 2.21–2.39 (1 H, m), 2.54–2.68
0.0003 mol) and sodium (0.016 g, 0.0007 mol). Isolated as a (1 H, m), 2.85–3.15 (2 H, m), 3.76–3.89 (1 H, m), 4.84–4.95 (1
mixture with a substrate and 15b. Yield 20% (a mixture of two H, m), 5.72–5.78 (1 H, m), 5.80–5.96 (3 H, m), 7.30–7.38 (3 H,
diastereomers in 0% de) (based on NMR analysis). RF 0.77 m), 7.43–7.53 (5 H, m), 7.87–7.95 (2 H, m); 13C NMR (CDCl3,
(CHCl3–MeOH 15 : 1). 1H NMR (CDCl3, 500 MHz) (first diaster- 126 MHz) (first diastereomer) δ 17.3 (d, J = 2.7 Hz), 19.3 (d, J =
eomer) δ 1.57 (3 H, d, J = 6.3 Hz), 2.41 (3 H, d, J = 9.2 Hz), 2.7 Hz), 26.0 (d, J = 5.5 Hz), 37.6 (d, J = 1.8 Hz), 39.7 (d, J = 89.0
2.67–2.84 (2 H, m), 3.76–3.86 (1 H, m), 4.81–4.87 (1 H, m), Hz), 40.0 (d, J = 88.1 Hz), 53.7 (d, J = 1.8 Hz), 121.2 (d, J = 6.4
5.61–5.67 (2 H, m), 5.69–5.75 (1 H, m), 5.76–5.85 (1 H, m), Hz), 121.5 (d, J = 7.3 Hz), 127.0, 127.8, 130.6 (d, J = 118.1 Hz),
7.21–7.27 (3 H, m), 7.39–7.54 (5 H, m), 7.78–7.83 (2 H, m); 132.7 (d, J = 11.8 Hz), 141.8 (d, J = 5.5 Hz); (second diastereo-
(second diastereomer) δ 1.61 (3 H, d, J = 6.9 Hz), 2.47 (3 H, d, mer) δ 17.3 (d, J = 2.7 Hz), 19.5 (d, J = 2.7 Hz), 26.1 (d, J = 6.4
J = 10.4 Hz), 2.67–2.84 (2 H, m), 3.82–3.92 (1 H, m), 4.87–4.93 Hz), 37.7 (d, J = 2.7 Hz), 53.9 (d, J = 1.8 Hz), 121.3 (d, J = 6.4
(1 H, m), 5.61–5.67 (2 H, m), 5.69–5.75 (1 H, m), 5.76–5.85 Hz), 121.6 (d, J = 7.3 Hz), 127.0, 127.9, 130.7 (d, J = 119.0 Hz),
(1 H, m), 7.21–7.27 (3 H, m), 7.39–7.54 (5 H, m), 7.83–7.89 (2 132.7 (d, J = 11.8 Hz), 142.0 (d, J = 3.6 Hz); 31P NMR (CDCl3,
H, m); 13C NMR (CDCl3, 126 MHz) (first diastereomer) δ 17.0 202 MHz) (first diastereomer) δ 35.56; (second diastereomer)
(d, J = 1.8 Hz), 26.0 (d, J = 5.5 Hz), 27.6 (d, J = 1.8 Hz), 39.2 (d, δ 35.65; GC (Phenomenex Zebron ZB-35 HT) RT 17.60 min;
J = 89.0 Hz), 53.1 (d, J = 1.8 Hz), 120.9 (d, J = 7.3 Hz), 121.1 (d, GC–MS (EI, 70 eV) m/z (%) 351 (1), 327 (1), 273 (7), 272 (30),
J = 6.4 Hz), 126.9, 127.3, 127.5, 128.0 (d, J = 11.8 Hz), 129.9 (d, 203 (5), 201 (5), 168 (42), 148 (19), 140 (6), 106 (9), 105 (100),
J = 120.8 Hz), 131.6 (d, J = 2.7 Hz), 132.7 (d, J = 9.1 Hz), 141.0 104 (6), 103 (8).
(d, J = 5.5 Hz); (second diastereomer) δ 17.3 (d, J = 1.8 Hz), 26.0
Bis(1,4-cyclohexadien-3-yl)phosphinic
acid
N-ethyl-(S)-
(d, J = 5.5 Hz), 27.7 (d, J = 1.8 Hz), 39.4 (d, J = 88.1 Hz), 53.1 (d, α-methylbenzylamide (15c). Prepared from 11c (0.094 g,
J = 1.8 Hz), 121.0 (d, J = 5.5 Hz), 121.1 (d, J = 7.3 Hz), 127.39, 0.0003 mol) and sodium (0.015 g, 0.0007 mol). Isolated as a
127.44, 127.7, 128.0 (d, J = 11.8 Hz), 130.3 (d, J = 120.8 Hz), mixture with a substrate and 14c. Yield 24% (based on NMR
131.6 (d, J = 2,7 Hz), 132.7 (d, J = 8.2 Hz), 141.2 (d, J = 5.5 Hz); analysis). RF 0.77 (CHCl3–MeOH 15 : 1). 1H NMR (CDCl3,
31P NMR (CDCl3, 202 MHz) (first diastereomer) δ 36.07; 500 MHz) δ 0.87 (3 H, t, J = 6.9 Hz), 1.61 (3 H, d, J = 6.9 Hz),
(second diastereomer) δ 36.83; GC (Phenomenex Zebron ZB-35 2.74–2.83 (4 H, m), 2.87–3.14 (2 H, m), 3.57–3.72 (2 H, m),
HT) (first diastereomer) RT 17.54 min; (second diastereomer) 5.01–5.07 (1 H, m), 5.80–5.96 (8 H, m), 7.30–7.38 (3 H, m),
RT 17.60 min; GC–MS (EI, 70 eV) (first diastereomer) m/z (%) 7.43–7.53 (2 H, m); 13C NMR (CDCl3, 126 MHz) δ 17.3 (d, J =
337 (M) (2), 259 (7), 258 (32), 203 (3), 201 (5), 154 (47), 134 (28), 1.8 Hz), 19.3 (d, J = 3.6 Hz), 26.3 (d, J = 5.5 Hz), 26.3 (d, J = 5.5
118 (6), 106 (13), 105 (100); (second diastereomer) m/z (%) 337 Hz), 37.1 (d, J = 2.7 Hz), 39.4 (d, J = 77.2 Hz), 40.0 (d, J = 76.3
(M) (2), 259 (7), 258 (32), 203 (3), 201 (5), 154 (47), 134 (28), 118 Hz), 52.2 (d, J = 1.8 Hz), 121.0 (d, J = 7.3 Hz), 121.1 (d, J =
(6), 106 (13), 105 (100).
8.2 Hz), 121.3 (d, J = 7.3 Hz), 121.5 (d, J = 7.3 Hz), 126.8,
Bis(1,4-cyclohexadien-3-yl)phosphinic acid N-methyl-(S)- 127.2 (d, J = 7.3 Hz), 127.2 (d, J = 7.3 Hz), 127.3 (d, J = 6.4 Hz),
α-methylbenzylamide (15b). Prepared from 11b (0.095 g, 127.9, 128.0, 142.5 (d, J = 3.6 Hz); 31P NMR (CDCl3, 202 MHz)
0.0003 mol) and sodium (0.016 g, 0.0007 mol). Isolated as a δ 42.27.
mixture with a substrate and 14b. Yield 50% (based on NMR
(1,4-Cyclohexadien-3-yl)phenylphosphinic acid N-isopropyl-
analysis). RF 0.77 (CHCl3–MeOH 15 : 1). 1H NMR (CDCl3, (S)-α-methylbenzylamide (14d). Prepared from 11d (0.100 g,
500 MHz) δ 1.51 (3 H, d, J = 6.9 Hz), 2.41 (3 H, d, J = 9.1 Hz), 0.0003 mol) and sodium (0.016 g, 0.0007 mol). Isolated as a
2.67–2.84 (4 H, m), 3.58–3.70 (2 H, m), 5.05–5.13 (1 H, m), mixture with a substrate and 15c. Yield 14% (a mixture of two
5.77–5.97 (8 H, m), 7.33–7.38 (3 H, m), 7.45–7.53 (2 H, m); 13C diastereomers in 9% de) (based on NMR analysis). RF 0.67
NMR (CDCl3, 126 MHz) δ 17.0 (d, J = 1.8 Hz), 26.3 (d, J = 5.5 (CHCl3–MeOH 15 : 1). 1H NMR (CDCl3, 500 MHz) (major dia-
Hz), 26.4 (d, J = 5.5 Hz), 27.4 (d, J = 2.7 Hz), 38.8 (d, J = 77.2 stereomer) δ 1.16 (3 H, d, J = 6.6 Hz), 1.18 (3 H, d, J = 6.6 Hz),
Hz), 39.7 (d, J = 76.3 Hz), 51.2 (d, J = 1.8 Hz), 120.5 (d, J = 1.61 (3 H, d, J = 6.9 Hz), 2.52–2.67 (2 H, m), 3.51–3.63 (1 H, m),
7.3 Hz), 120.9 (d, J = 7.3 Hz), 120.9 (d, J = 8.2 Hz), 121.1 (d, J = 3.67–3.78 (1 H, m), 4.47–4.68 (1 H, m), 5.60–5.66 (3 H, m),
7.3 Hz), 126.8, 127.8, 128.1, 141.3 (d, J = 3.6 Hz); 31P NMR 5.68–5.73 (1 H, m), 7.15–7.31 (3 H, m), 7.34–7.48 (5 H, m),
(CDCl3, 202 MHz) δ 41.71.
7.84–7.91 (2 H, m); (minor diastereomer) δ 1.07 (3 H, d, J = 6.9
(1,4-Cyclohexadien-3-yl)phenylphosphinic acid N-ethyl-(S)- Hz), 1.34 (3 H, d, J = 6.9 Hz), 1.71 (3 H, d, J = 6.9 Hz), 2.27–2.41
α-methylbenzylamide (14c). Prepared from 11c (0.094 g, (2 H, m), 3.51–3.63 (1 H, m), 3.78–3.89 (1 H, m), 4.47–4.68 (1
0.0003 mol) and sodium (0.015 g, 0.0007 mol). Isolated as a H, m), 5.43–5.50 (1 H, m), 5.54–5.60 (3 H, m), 7.15–7.31 (3 H,
mixture with a substrate and 15c. Yield 20% (a mixture of two m), 7.34–7.48 (5 H, m), 7.84–7.91 (2 H, m); 13C NMR (CDCl3,
diastereomers in 0% de) (based on NMR analysis). RF 0.67 126 MHz) (major diastereomer) δ 20.2 (d, J = 2.7 Hz), 23.8 (d,
(CHCl3–MeOH 15 : 1). 1H NMR (CDCl3, 500 MHz) (first diaster- J = 3.6 Hz), 23.5, 26.1 (d, J = 5.5 Hz), 40.0 (d, J = 87.2 Hz), 48.6
eomer) δ 0.83 (3 H, t, J = 6.9 Hz), 1.65 (3 H, d, J = 6.9 Hz), (d, J = 2.7 Hz), 53.2 (d, J = 3.6 Hz), 121.2 (d, J = 8.2 Hz), 121.3
2.21–2.39 (1 H, m), 2.54–2.68 (1 H, m), 2.85–3.15 (2 H, m), (d, J = 6.4 Hz), 126.8, 131.0 (d, J = 2.7 Hz), 132.0 (d, J = 8.2 Hz),
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143.0 (d, J = 2.7 Hz); (minor diastereomer) δ 20.3 (d, J = 1.8
(1,4-Cyclohexadien-3-yl)phenylphosphinous
acid-borane
Hz), 23.5 (d, J = 1.8 Hz), 24.5, 26.2 (d, J = 6.4 Hz), 39.9 (d, J = (2S)-2-(trimethylsilyloxymethyl)pyrolidinamide
(26b). Pre-
87.2 Hz), 48.2 (d, J = 2.7 Hz), 53.1 (d, J = 2.7 Hz), 121.3 (d, J = pared from 16c (0.110 g, 0.0003 mol) and sodium (0.017 g,
7.3 Hz), 121.5 (d, J = 6.4 Hz), 126.8, 131.0 (d, J = 2.7 Hz), 132.0 0.0007 mol). Isolated as a mixture with a substrate and 27.
(d, J = 9.1 Hz), 142.5 (d, J = 2.7 Hz); 31P NMR (CDCl3, 202 MHz) Yield 31% (a mixture of two diastereomers in 22% de) (based
(major diastereomer) δ 34.75; (minor diastereomer) δ 34.16; on NMR analysis). RF 0.69 (hexane–EtOAc 6 : 1). 1H NMR
GC (Phenomenex Zebron ZB-35 HT) RT 17.56 min; GC–MS (CDCl3, 500 MHz) (major diastereomer) δ 0.12 (9 H, s),
(EI, 70 eV) m/z (%) 322 (M − iPr) (3), 320 (2), 286 (24), 244 (7), 0.38–1.40 (3 H, bm), 1.67–2.05 (4 H, m), 2.68–2.79 (2 H, m),
201 (8), 182 (35), 140 (17), 125 (6), 106 (10), 105 (100), 103 (7), 2.92–2.99 (1 H, m), 3.12–3.19 (1 H, m), 3.27 (1 H, dd, J = 8.8
86 (13).
Hz, 10.1 Hz), 3.63 (1 H, dd, J = 4.1 Hz, 9.8 Hz), 3.81–3.93 (2 H,
Bis(1,4-cyclohexadien-3-yl)phosphinic acid N-isopropyl-(S)- m), 5.73–5.81 (2 H, m), 5.82–5.87 (1 H, m), 5.87–5.94 (1 H, m),
α-methylbenzylamide (15d). Prepared from 11d (0.100 g, 7.40–7.52 (3 H, m), 7.67–7.74 (2 H, m); (minor diastereomer) δ
0.0003 mol) and sodium (0.016 g, 0.0007 mol). Isolated as a 0.07 (9 H, s), 0.38–1.40 (3 H, b), 1.67–2.05 (4 H, m), 2.68–2.79
mixture with a substrate and 14d. Yield 24% (based on NMR (2 H, m), 3.12–3.19 (1 H, m), 3.33 (1 H, dd, J = 7.9 Hz, 10.1 Hz),
analysis). RF 0.67 (CHCl3–MeOH 15 : 1). 1H NMR (CDCl3, 3.33–3.39 (1 H, m), 3.59 (1 H, dd, J = 3.8 Hz, 9.8 Hz), 3.81–3.93
500 MHz) δ 1.22 (3 H, d, J = 6.6 Hz), 1.27 (3 H, d, J = 6.9 Hz), (2 H, m), 5.61–5.67 (1 H, m), 5.73–5.81 (3 H, m), 7.40–7.52 (3
1.67 (3 H, d, J = 6.9 Hz), 2.64–2.75 (2 H, m), 2.77–2.87 (2 H, m), H, m), 7.67–7.74 (2 H, m); 13C NMR (CDCl3, 126 MHz) (major
3.42–3.62 (2 H, m), 4.47–4.68 (1 H, m), 5.67–5.82 (4 H, m), diastereomer) δ −0.4, 25.0 (d, J = 4.5 Hz), 26.5 (d, J = 5.5 Hz),
5.87–6.02 (4 H, m), 7.21–7.30 (3 H, m), 7.35–7.48 (2 H, m); 13C 28.1 (d, J = 5.5 Hz), 36.6 (d, J = 41.8 Hz), 47.9 (d, J = 3.6 Hz),
NMR (CDCl3, 126 MHz) δ 21.9 (d, J = 1.8 Hz), 23.82 (d, J = 61.0 (d, J = 5.5 Hz), 65.1, 121.2 (d, J = 2.7 Hz), 121.6 (d, J = 5.5
1.8 Hz), 23.84 (d, J = 2.7 Hz), 26.4 (d, J = 5.5 Hz), 26.5 (d, J = 5.5 Hz), 127.7 (d, J = 8.2 Hz), 127.8 (d, J = 9.1 Hz), 128.4 (d, J = 10.9
Hz), 40.1 (d, J = 76.3 Hz), 40.2 (d, J = 73.6 Hz), 47.9 (d, J = Hz), 130.8 (d, J = 2.7 Hz), 131.4 (d, J = 8.2 Hz); (minor diaster-
2.7 Hz), 53.6 (d, J = 2.7 Hz), 120.9 (d, J = 7.3 Hz), 121.1 (d, J = eomer) δ = −0.5, 24.9 (d, J = 3.6 Hz), 26.5 (d, J = 5.5 Hz), 28.3
7.3 Hz), 121.6 (d, J = 9.1 Hz), 121.7 (d, J = 6.4 Hz), 126.7, 127.1 (d, J = 5.5 Hz), 37.1 (d, J = 37.2 Hz), 47.9 (d, J = 3.6 Hz), 61.7 (d,
(d, J = 10.0 Hz), 127.4 (d, J = 10.0 Hz), 127.8, 128.1, 143.6 (d, J = J = 5.5 Hz), 64.9, 121.2 (d, J = 2.7 Hz), 121.7 (d, J = 6.4 Hz),
1.8 Hz); 31P NMR (CDCl3, 202 MHz) δ 43.15.
(1,4-Cyclohexadien-3-yl)phenylphosphinous
127.3 (d, J = 8.2 Hz), 127.7 (d, J = 10.0 Hz), 128.5 (d, J = 10.0
acid-borane Hz), 130.7 (d, J = 2.7 Hz), 131.3 (d, J = 9.1 Hz); 31P NMR
(2S)-2-(methoxymethyl)pyrolidinamide (26a). Prepared from (CDCl3, 202 MHz) (major diastereomer) δ 64.50 (bm); (minor
16b (0.070 g, 0.0002 mol) and sodium (0.013 g, 0.0006 mol). diastereomer) δ 63.10 (bm); GC (Phenomenex Zebron ZB-35
Isolated as a mixture with a substrate. Yield 35% (a mixture of HT) RT 13.45 min; GC–MS (EI, 70 eV) m/z (%) 357 (2), 342 (2),
two diastereomers in 54% de) (based on NMR analysis). RF 255 (16), 254 (88), 186 (14), 185 (100), 184 (8), 183 (57), 178
0.59 (hexane–EtOAc 6 : 1). 1H NMR (CDCl3, 500 MHz) (major (10), 152 (9), 108 (9), 107 (7).
diastereomer) δ 0.39–1.40 (3 H, bm), 1.68–1.78 (1 H, m),
Diphenylphosphine-borane
(27). Prepared
from
16c
1.79–2.00 (3 H, m), 2.70–2.79 (2 H, m), 2.92–2.99 (1 H, m), (0.110 g, 0.0003 mol) and sodium (0.017 g, 0.0007 mol). Iso-
3.12–3.19 (1 H, m), 3.20–3.25 (1 H, m), 3.34 (3 H, s), 3.39–3.43 lated as a mixture with a substrate and 26b. Yield 13% (based
(1 H, m), 3.82–3.92 (1 H, m), 3.99–4.06 (1 H, m), 5.72–5.81 (2 on NMR analysis). Analytical data are identical with those
H, m), 5.82–5.88 (1 H, m), 5.88–5.94 (1 H, m), 7.41–7.53 (3 H, reported in the literature.30
m), 7.65–7.73 (2 H, m); (minor diastereomer) δ 0.39–1.40 (3 H,
(1,4-Cyclohexadien-3-yl)phenylphosphinous
acid-borane
bm), 1.68–1.78 (1 H, m), 1.79–2.00 (3 H, m), 2.70–2.79 (2 H, N-methylneomenthylamide (26c). Prepared from 25a (0.084 g,
m), 3.02–3.08 (1 H, m), 3.12–3.19 (1 H, m), 3.20–3.25 (1 H, m), 0.0002 mol) and sodium (0.021 g, 0.0009 mol). Isolated as a
3.27 (3 H, s), 3.39–3.43 (1 H, m), 3.82–3.92 (1 H, m), 3.92–3.97 mixture with a substrate and 28. Yield 77% (a mixture of two
(1 H, m), 5.60–5.66 (1 H, m), 5.72–5.81 (1 H, m), 5.82–5.88 (1 diastereomers in 23% de) (based on NMR analysis). RF 0.77
H, m), 5.88–5.94 (1 H, m), 7.41–7.53 (3 H, m), 7.65–7.73 (2 H, (hexane–EtOAc 6 : 1). 1H NMR (CDCl3, 500 MHz) (major dia-
m); 13C NMR (CDCl3, 126 MHz) (major diastereomer) δ 25.2 (d, stereomer) δ 0.41–1.35 (3 H, bm), 0.77 (3 H, d, J = 6.6 Hz), 0.94
J = 4.5 Hz), 26.5 (d, J = 5.5 Hz), 28.6 (d, J = 5.5 Hz), 36.7 (d, J = (3 H, d, J = 6.9 Hz), 1.06 (3 H, d, J = 6.3 Hz), 1.13–1.25 (1 H, m),
42.7 Hz), 47.9 (d, J = 3.6 Hz), 58.8, 58.9 (d, J = 6.4 Hz), 75.6, 1.44–1.56 (1 H, m), 1.61–1.92 (9 H, m), 2.73–2.84 (1 H, m), 2.90
121.2 (d, J = 2.7 Hz), 121.5 (d, J = 6.4 Hz), 127.8 (d, J = 9.1 Hz), (3 H, d, J = 7.6 Hz), 3.88–4.02 (1 H, m), 5.59–5.68 (2 H, m),
127.9 (d, J = 10.0 Hz), 128.6 (d, J = 9.1 Hz), 130.3 (d, J = 52.7 5.79–5.89 (2 H, m), 7.43–7.52 (3 H, m), 7.71–7.77 (2 H, m);
Hz), 130.8 (d, J = 1.8 Hz), 131.4 (d, J = 9.1 Hz); (minor diaster- (minor diastereomer) δ 0.41–1.35 (3 H, bm), 0.89 (3 H, d, J =
eomer) δ 25.5 (d, J = 4.5 Hz), 26.5 (d, J = 5.5 Hz), 28.7 (d, J = 5.5 6.3 Hz), 0.92 (3 H, d, J = 6.6 Hz), 0.97 (3 H, d, J = 6.6 Hz),
Hz), 37.2 (d, J = 38.2 Hz), 47.9 (d, J = 3.6 Hz), 58.8, 59.6 (d, J = 1.13–1.25 (1 H, m), 1.44–1.56 (1 H, m), 1.61–1.92 (9 H, m),
5.5 Hz), 75.5, 121.2 (d, J = 3.6 Hz), 121.7 (d, J = 6.4 Hz), 127.4 2.73–2.84 (1 H, m), 2.94 (3 H, d, J = 6.6 Hz), 3.88–4.02 (1 H, m),
(d, J = 8.2 Hz), 127.7 (d, J = 10.9 Hz), 128.5 (d, J = 10.0 Hz), 5.70–5.77 (2 H, m), 5.92–6.02 (2 H, m), 7.43–7.52 (3 H, m),
130.7 (d, J = 1.8 Hz), 131.2 (d, J = 9.1 Hz); 31P NMR (CDCl3, 7.64–7.69 (2 H, m); 13C NMR (CDCl3, 126 MHz) (major diaster-
202 MHz) (major diastereomer) δ 64.68 (bm); (minor diastereo- eomer) δ 21.0, 23.0, 23.3, 26.3, 26.5 (d, J = 5.5 Hz), 28.5, 28.8,
mer) δ 62.95 (bm).
34.9, 36.4 (d, J = 4.5 Hz), 37.0 (d, J = 43.6 Hz), 43.4, 47.6 (d, J =
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8.2 Hz), 54.0 (d, J = 7.3 Hz), 121.5 (d, J = 2.7 Hz), 122.1 (d, J = Hz), 130.8 (d, J = 10.0 Hz), 131.2 (d, J = 1.8 Hz), 132.1 (d, J =
6.4 Hz), 127.3 (d, J = 8.2 Hz), 127.6 (d, J = 9.1 Hz), 128.5 (d, J = 74.5 Hz); (minor diastereomer) δ = 50.4 (d, J = 3.6 Hz), 68.5 (d,
9.1 Hz), 130.6 (d, J = 1.8 Hz), 131.4 (d, J = 8.2 Hz); (minor dia- J = 5.5 Hz), 121.60 (d, J = 2.7 Hz), 122.0 (d, J = 6.4 Hz), 127.3 (d,
stereomer) δ 21.2, 22.9, 23.2, 26.5 (d, J = 5.5 Hz), 26.6, 28.4, J = 7.3 Hz), 127.5 (d, J = 10.0 Hz), 128.8 (d, J = 10.0 Hz), 131.2
29.1, 34.9, 36.8 (d, J = 4.5 Hz), 38.6 (d, J = 35.4 Hz), 44.2, 47.6 (d, J = 9.1 Hz), 131.3 (d, J = 1.8 Hz); 31P NMR (CDCl3, 202 MHz)
(d, J = 8.2 Hz), 53.8 (d, J = 9.1 Hz), 122.5 (d, J = 2.7 Hz), 122.8 (major diastereomer) δ 79.95 (bm); (minor diastereomer)
(d, J = 7.3 Hz), 126.9 (d, J = 6.4 Hz), 127.2 (d, J = 10.0 Hz), 128.6 δ 81.78 (bm).
(d, J = 10.0 Hz), 130.3 (d, J = 2.7 Hz), 131.0 (d, J = 8.2 Hz); 31P
Phenylphosphinous
acid-borane
N-methylbornylamide
NMR (CDCl3, 202 MHz) (major diastereomer) δ 74.31 (bm); (29). Prepared from 25d (0.094 g, 0.0003 mol) (1 : 0.1 mixture
(minor diastereomer) δ 76.35 (bm); GC (Phenomenex Zebron of diastereomers) and sodium (0.024 g, 0.0010 mol). Isolated
ZB-35 HT) RT 14.55 min; GC–MS (EI, 70 eV) m/z (%) 355 (M − as a mixture with 26d. Yield 42% (a mixture of two diastereo-
BH3) (8), 283 (16), 282 (67), 268 (10), 267 (36), 266 (13), 265 mers in 42% de) (based on NMR analysis). RF 0.77 (hexane–
(26), 263 (10), 252 (23), 217 (11), 187 (15), 169 (12), 168 (100), EtOAc 6 : 1). 1H NMR (CDCl3, 500 MHz) (major diastereomer) δ
141 (12), 138 (16), 133 (31), 131 (20), 126 (36), 124 (13), 115 0.41–1.29 (3 H, bm), 0.85 (3 H, s), 0.94 (3 H, s), 0.95 (3 H, s),
(12), 110 (26), 109 (55), 108 (62), 107 (14), 91 (15), 84 (22), 83 1.19–1.29 (2 H, m), 1.37–1.45 (1 H, m), 1.47–1.56 (1 H, m),
(16), 82 (13), 81 (11).
1.63–1.72 (2 H, m), 1.93–2.02 (1 H, m), 2.69 (3 H, d, J = 8.2 Hz),
Phenylphosphinous acid-borane N-methylneomenthylamide 3.58–3.65 (1 H, m), 6.72 (1 H, dm, J = 396.3 Hz), 7.42–7.52 (3
(28). Prepared from 25a (0.084 g, 0.0002 mol) and sodium H, m), 7.53–7.59 (2 H, m); (minor diastereomer) δ 0.41–1.29 (3
(0.021 g, 0.0009 mol). Isolated as a mixture with a substrate H, bm), 0.83 (3 H, s), 0.87 (3 H, s), 0.93 (3 H, s), 1.19–1.29 (2 H,
and 26c. Yield 16% (a mixture of two diastereomers in 0% de) m), 1.37–1.45 (1 H, m), 1.47–1.56 (1 H, m), 1.63–1.72 (2 H, m),
(based on NMR analysis). RF 0.77 (hexane–EtOAc 6 : 1). 1H 1.93–2.02 (1 H, m), 2.61 (3 H, d, J = 7.3 Hz), 3.42–3.49 (1 H, m),
NMR (CDCl3, 500 MHz) (only few peaks could be ascribed due 6.68 (1 H, dm, J = 394.1 Hz), 7.42–7.52 (3 H, m), 7.60–7.67
to overlapping) (major diastereomer) δ 1.10 (3 H, d, J = 6.6 Hz), (2 H, m); 13C NMR (126 MHz, CDCl3) (only a few peaks could
6.55 (1 H, dm, J = 380.8 Hz); (minor diastereomer) δ 1.11 (3 H, be ascribed due to overlapping) (major diastereomer) δ 50.0 (d,
d, J = 6.6 Hz), 6.69 (1 H, dm, J = 392.5 Hz); 13C NMR (CDCl3, J = 4.5 Hz), 67.8 (d, J = 6.4 Hz), 128.6 (d, J = 9.1 Hz), 130.6 (d,
126 MHz) (only few peaks could be ascribed due to overlap- J = 1.8 Hz), 131.3 (d, J = 8.2 Hz), 131.7 (d, J = 75.4 Hz); (minor
ping) (major diastereomer) δ 20.53, 22.49, 23.07, 28.33, 28.95; diastereomer) δ 50.3 (d, J = 4.5 Hz), 66.0 (d, J = 10.9 Hz), 128.6
(minor diastereomer) δ 20.69, 22.65, 23.11, 28.73, 29.02; 31P (d, J = 9.1 Hz), 130.5 (d, J = 1.8 Hz), 131.3 (d, J = 8.2 Hz);
NMR (CDCl3, 202 MHz) (major diastereomer) δ 64.48 (bm); 31P NMR (CDCl3, 202 MHz) (major diastereomer) δ 61.13 (bm);
(minor diastereomer) δ 66.34(bm); GC (Phenomenex Zebron (minor diastereomer) δ 67.72 (bm).
ZB-35 HT) RT 11.37 min; GC–MS (EI, 70 eV) m/z (%) 277 (M −
(4-Methyl-1,4-cyclohexadien-3-yl)(o-tolyl)phosphinous acid-
BH3) (12), 262 (6), 234 (4), 193 (16), 192 (87), 168 (22), 165 (15), borane N-methyl-(S)-α-methylbenzylamide (34a). Prepared
164 (28), 152 (31), 151 (21), 140 (13), 139 (41), 138 (37), 125 from 32a (0.097 g, 0.0003 mol) and sodium (0.019 g,
(19), 124 (17), 114 (30), 110 (48), 109 (84), 108 (15), 107 (12), 97 0.0008 mol). Isolated as a mixture with a substrate. Yield 21%
(16), 96 (12), 95 (13), 91 (11), 84 (100), 83 (35), 82 (40), 81 (19).
(1,4-Cyclohexadien-3-yl)phenylphosphinous
(a mixture of isomers in a 30 : 11 : 40 : 19 ratio) (based on NMR
acid-borane analysis). RF 0.67 (hexane–EtOAc 6 : 1). 1H NMR (CDCl3,
N-methylbornylamide (26d). Prepared from 25d (0.094 g, 500 MHz) (only selected peaks were ascribed due to signal
0.0003 mol) (1 : 0.1 mixture of diastereomers) and sodium overlapping) (first isomer) δ 1.51 (3 H, d, J = 6.9 Hz), 1.98 (3 H,
(0.024 g, 0.0010 mol). Isolated as a mixture with 29. Yield 33% bs), 2.45 (3 H, d, J = 6.3 Hz), 2.76 (3 H, s), 3.89–4.02 (1 H, m),
(a mixture of two diastereomers in 38% de) (based on NMR 5.30–5.42 (2 H, m), 5.61–5.70 (1 H, m), 5.85–5.92 (1 H, m);
analysis). RF 0.77 (hexane–EtOAc 6 : 1). 1H NMR (CDCl3, (second isomer) δ 1.57 (3 H, d, J = 6.9 Hz), 2.14 (3 H, bs), 2.46
500 MHz) (major diastereomer) δ 0.41–1.29 (3 H, bm), 0.85 (3 (3 H, d, J = 6.3 Hz), 2.71 (3 H, s), 3.89–4.02 (1 H, m), 5.30–5.42
H, s), 0.94 (3 H, s), 0.95 (3 H, s), 1.19–1.29 (2 H, m), 1.37–1.45 (2 H, m), 5.61–5.70 (1 H, m), 5.85–5.92 (1 H, m); (third isomer)
(1 H, m), 1.47–1.56 (1 H, m), 1.63–1.72 (4 H, m), 1.93–2.02 (1 δ 1.55 (3 H, d, J = 6.9 Hz), 1.95 (3 H, bs), 2.47 (3 H, d, J = 6.3
H, m), 2.70 (3 H, d, J = 10.1 Hz), 2.73–2.83 (1 H, m), 3.78–3.86 Hz), 2.66 (3 H, s), 3.89–4.02 (1 H, m), 5.30–5.42 (2 H, m),
(1 H, m), 5.64–5.71 (1 H, m), 5.79–5.94 (3 H, m), 7.42–7.52 (3 5.61–5.70 (1 H, m), 5.85–5.92 (1 H, m); (fourth isomer) δ 1.57
H, m), 7.61–7.66 (2 H, m); (minor diastereomer) δ 0.41–1.29 (3 (3 H, d, J = 6.9 Hz), 2.27 (3 H, bs), 2.49 (3 H, d, J = 6.3 Hz), 2.73
H, bm), 0.76 (3 H, s), 0.83 (3 H, s), 0.90 (3 H, s), 1.19–1.29 (2 H, (3 H, s), 3.89–4.02 (1 H, m), 5.30–5.42 (2 H, m), 5.61–5.70 (1 H,
m), 1.37–1.45 (1 H, m), 1.47–1.56 (1 H, m), 1.63–1.72 (4 H, m), m), 5.85–5.92 (1 H, m); 31P NMR (CDCl3, 202 MHz) (first
1.93–2.02 (1 H, m), 2.72 (3 H, d, J = 10.7 Hz), 2.73–2.83 (1 H, isomer) δ 73.67 (bm); (second isomer) δ 75.38 (bm); (third
m), 3.42–3.49 (1 H, m), 3.92–4.01 (1 H, m), 5.74–5.79 (1 H, m), isomer) δ 77.77 (bm); (fourth isomer) δ 75.05; GC (Phenom-
5.79–5.94 (3 H, m), 7.42–7.52 (3 H, m), 7.71–7.76 (2 H, m); 13C enex Zebron ZB-35 HT) RT 15.44 min; GC–MS (EI, 70 eV)
NMR (CDCl3, 126 MHz) (only a few peaks could be ascribed m/z (%) 364 (29), 363 (M) (48), 307 (12), 306 (22), 278 (8),
due to overlapping) (major diastereomer) δ 50.6 (d, J = 3.6 Hz), 259 (57), 258 (100), 256 (12), 231 (14), 230 (34), 229 (16), 216
67.4 (d, J = 5.5 Hz), 121.6 (d, J = 2.7 Hz), 121.8 (d, J = 5.5 Hz), (12), 215 (16), 203 (11), 202 (21), 201 (27), 200 (12), 187 (14),
127.6 (d, J = 10.0 Hz), 127.7 (d, J = 8.2 Hz), 128.8 (d, J = 10.0 169 (24), 155 (12), 154 (16), 152 (21), 147 (18), 142 (13), 141
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(11), 138 (12), 137 (11), 129 (10), 125 (11), 124 (10), 108 (16), 31P NMR (CDCl3, 202 MHz) (major diastereomer) δ 71.31 (bm);
107 (26), 92 (20), 81 (11), 80 (28).
(minor diastereomer) δ 74.11 (bm).
(6-Methyl-1,4-cyclohexadien-3-yl)(p-tolyl)phosphinous acid-
(1,5-Dimethyl-1,4-cyclohexadien-3-yl)(m-xylyl)phosphinous
borane N-methyl-(S)-α-methylbenzylamide (34b). Prepared acid-borane N-methyl-(S)-α-methylbenzylamide (34d). Pre-
from 32b (0.085 g, 0.0002 mol) and sodium (0.016 g, pared from 32d (0.071 g, 0.0002 mol) and sodium (0.013 g,
0.0007 mol). Isolated as a mixture of cis/trans isomers. Yield 0.0005 mol). Isolated as a mixture with a substrate and 35a.
76% (cis/trans 47 : 53, decis 44%, detrans 44% de) (based on Yield 43% (a mixture of two diastereomers in 37% de) (based
1
NMR analysis). RF 0.73 (hexane–EtOAc 6 : 1). H NMR (CDCl3, on NMR analysis). RF 0.67 (hexane–EtOAc 6 : 1). 1H NMR
500 MHz) (trans isomer, major diastereomer) δ 0.57–1.37 (3 H, (CDCl3, 500 MHz) (major diastereomer) δ 0.49–1.21 (3 H, bm),
bm), 1.01 (3 H, d, J = 7.3 Hz), 1.48 (3 H, d, J = 6.9 Hz), 2.35 (3 1.49 (3 H, d, J = 6.9 Hz), 1.64–1.67 (3 H, m), 1.71–1.74 (3 H, m),
H, d, J = 6.9 Hz), 2.42 (3 H, s), 2.66–2.95 (1 H, m), 3.76–3.92 (1 2.28 (3 H, d, J = 6.6 Hz), 2.39 (6 H, s), 2.41–2.48 (2 H, m),
H, m), 5.09–5.18 (1 H, m), 5.57–5.79 (4 H, m), 7.21–7.44 (7 H, 3.80–3.93 (1 H, m), 5.07–5.16 (1 H, m), 5.26–5.30 (1 H, m),
m), 7.61–7.66 (2 H, m); (trans isomer, minor diastereomer) δ 5.52–5.57 (1 H, m), 7.03–7.17 (2 H, m), 7.24–7.31 (2 H, m),
0.57–1.37 (3 H, bm), 1.17 (3 H, d, J = 7.3 Hz), 1.58 (3 H, d, J = 7.32–7.36 (2 H, m), 7.39–7.45 (2 H, m); (minor diastereomer)
6.9 Hz), 2.37 (3 H, d, J = 6.3 Hz), 2.38 (3 H, s), 2.66–2.95 (1 H, δ 0.49–1.21 (3 H, bm), 1.49 (3 H, d, J = 6.9 Hz), 1.62–1.64 (3 H,
m), 3.76–3.92 (1 H, m), 5.09–5.18 (1 H, m), 5.57–5.79 (3 H, m), m), 1.81–1.84 (3 H, m), 2.25 (3 H, d, J = 6.3 Hz), 2.30 (6 H, s),
5.86–5.92 (1 H, m), 7.21–7.44 (7 H, m), 7.56–7.60 (2 H, m); (cis 2.52–2.59 (2 H, m), 3.80–3.93 (1 H, m), 5.07–5.16 (1 H, m),
isomer, major diastereomer) δ 0.57–1.37 (3 H, bm), 1.09 (3 H, 5.35–5.39 (1 H, m), 5.74–5.78 (1 H, m), 7.03–7.17 (2 H, m),
d, J = 7.6 Hz), 1.48 (3 H, d, J = 6.9 Hz), 2.34 (3 H, d, J = 6.6 Hz), 7.24–7.31 (2 H, m), 7.32–7.36 (2 H, m), 7.39–7.45 (2 H, m); 13C
2.42 (3 H, s), 2.66–2.95 (1 H, m), 3.76–3.92 (1 H, m), 5.09–5.18 NMR (CDCl3, 126 MHz) (major diastereomer) δ 16.5, 21.5, 23.1
(1 H, m), 5.57–5.79 (4 H, m), 7.21–7.44 (7 H, m), 7.61–7.66 (2 (d, J = 2.7 Hz), 23.3 (d, J = 2.7 Hz), 28.9 (d, J = 4.5 Hz), 36.2 (d,
H, m); (cis isomer, minor diastereomer) δ 0.57–1.37 (3 H, bm), J = 5.5 Hz), 38.5 (d, J = 40.9 Hz), 55.9 (d, J = 9.1 Hz), 115.2 (d,
1.15 (3 H, d, J = 7.6 Hz), 1.57 (3 H, d, J = 7.3 Hz), 2.36 (3 H, d, J = 2.7 Hz), 115.7 (d, J = 7.3 Hz), 126.9, 127.9, 128.1, 128.7 (d,
J = 6.3 Hz), 2.38 (3 H, s), 2.66–2.95 (1 H, m), 3.76–3.92 (1 H, J = 8.2 Hz), 131.9 (d, J = 51.8 Hz), 132.3 (d, J = 1.8 Hz), 134.9 (d,
m), 5.09–5.18 (1 H, m), 5.57–5.79 (3 H, m), 5.94–5.99 (1 H, m), J = 8.2 Hz), 135.3 (d, J = 10.0 Hz), 138.1 (d, J = 10.0 Hz), 141.7
7.21–7.44 (7 H, m), 7.56–7.60 (2 H, m); 31P NMR (CDCl3, (d, J = 5.5 Hz); (minor diastereomer) δ 16.0, 21.4, 23.1 (d, J =
202 MHz) (trans isomer, major diastereomer) δ 71.59 (bm); 2.7 Hz), 23.3 (d, J = 2.7 Hz), 28.8 (d, J = 4.5 Hz), 36.3 (d, J = 5.5
(trans isomer, minor diastereomer) δ 75.20 (bm); (cis isomer, Hz), 39.8 (d, J = 36.3 Hz), 55.9 (d, J = 10.0 Hz), 115.9 (d, J = 2.7
major diastereomer) δ 72.37 (bm); (cis isomer, minor diastereo- Hz), 116.2 (d, J = 8.2 Hz), 127.1, 127.9, 128.2, 128.7 (d, J = 8.2
mer) δ 74.84.
Hz), 129.8 (d, J = 10.0 Hz), 130.0 (d, J = 10.9 Hz), 131.5 (d, J =
(1,4-Cyclohexadien-3-yl)(p-anisyl)phosphinous acid-borane 57.2 Hz), 132.1 (d, J = 1.8 Hz), 138.2 (d, J = 10.0 Hz), 141.5 (d,
N-methyl-(S)-α-methylbenzylamide (34c). Prepared from 32c J = 4.5 Hz); 31P NMR (CDCl3, 202 MHz) (major diastereomer)
(0.087 g, 0.0002 mol) and sodium (0.015 g, 0.0007 mol). Iso- δ 73.21 (bm); (minor diastereomer) δ 75.23 (bm); GC (Phenom-
lated as a mixture with a substrate. Yield 38% (a mixture of enex Zebron ZB-35 HT) RT 15.01 min; GC–MS (EI, 70 eV) m/z
two diastereomers in 58% de) (based on NMR analysis). RF (%) 377 (M − BH3) (16), 376 (7), 321 (9), 320 (46), 318 (7), 272
0.58 (hexane–EtOAc 6 : 1). 1H NMR (CDCl3, 500 MHz) (major (17), 270 (70), 246 (23), 214 (9), 213 (22), 211 (14), 166 (48), 138
diastereomer) δ 0.49–1.36 (3 H, bm), 1.44 (3 H, d, J = 6.9 Hz), (11), 137 (48), 136 (19), 135 (17), 134 (41), 133 (16), 120 (20),
2.34 (3 H, d, J = 6.9 Hz), 2.64–2.74 (1 H, m), 3.81–3.95 (1 H, m), 119 (29), 118 (14), 109 (14), 107 (37), 106 (15), 105 (100), 104
3.87 (3 H, s), 5.07–5.17 (1 H, m), 5.61–5.72 (2 H, m), 5.81–5.87 (7), 103 (13), 93 (9), 92 (16), 91 (64), 79 (34), 78 (11), 77 (34), 60
(2 H, m), 6.99–7.03 (2 H, m), 7.31–7.36 (2 H, m), 7.39–7.44 (30), 56 (10), 51 (10).
(3 H, m), 7.67–7.72 (2 H, m); (minor diastereomer) δ 0.49–1.36
m-Xylylphosphinous acid-borane N-methyl-(S)-α-methyl-
(3 H, bm), 1.55 (3 H, d, J = 6.9 Hz), 2.37 (3 H, d, J = 6.6 Hz), benzylamide (35a). Prepared from 32d (0.071 g, 0.0002 mol)
2.74–2.84 (1 H, m), 3.81–3.95 (1 H, m), 3.87 (3 H, s), 5.07–5.17 and sodium (0.013 g, 0.0005 mol). Isolated as a mixture with a
(1 H, m), 5.61–5.72 (1 H, m), 5.75–5.81 (1 H, m), 5.94–5.98 substrate and 34d. Yield 15% (a mixture of two diastereomers
(2 H, m), 6.92–6.96 (2 H, m), 7.31–7.36 (2 H, m), 7.39–7.44 (3 in 30% de) (based on NMR analysis). RF 0.67 (hexane–EtOAc
H, m), 7.61–7.66 (2 H, m); 13C NMR (CDCl3, 126 MHz) (major 6 : 1). 1H NMR (CDCl3, 500 MHz) (major diastereomer) δ
diastereomer) δ 16.4, 26.4 (d, J = 5.5 Hz), 28.7 (d, J = 3.6 Hz), 0.47–1.20 (3 H, bm), 1.51 (3 H, d, J = 6.9 Hz), 2.35 (3 H, d, J =
36.4 (d, J = 41.8 Hz), 55.3, 55.8 (d, J = 9.1 Hz), 114.3 (d, J = 10.0 9.1 Hz), 2.38 (6 H, s), 4.87–4.95 (1 H, m), 6.58 (1 H, dm, J =
Hz), 121.3 (d, J = 1.8 Hz), 121.6 (d, J = 5.5 Hz), 122.3 (d, J = 55.4 388.4 Hz), 7.07–7.17 (2 H, m), 7.24–7.44 (6 H, m); (minor dia-
Hz), 127.0, 127.7 (d, J = 8.2 Hz), 127.9, 128.0 (d, J = 7.3 Hz), stereomer) δ 0.47–1.20 (3 H, bm), 1.48 (3 H, d, J = 6.9 Hz), 2.34
128.0, 133.1 (d, J = 10.0 Hz), 141.4 (d, J = 6.4 Hz), 161.6 (d, J = (6 H, s), 2.35 (3 H, d, J = 7.3 Hz), 4.80–4.87 (1 H, m), 6.58 (1 H,
2.7 Hz); (minor diastereomer) δ 16.5, 26.5 (d, J = 5.5 Hz), 28.7 dm, J = 388.7 Hz), 7.07–7.17 (2 H, m), 7.24–7.44 (6 H, m); 31P
(d, J = 3.6 Hz), 38.0 (d, J = 37.2 Hz), 55.3, 55.3 (d, J = 8.2 Hz), NMR (CDCl3, 202 MHz) (major diastereomer) δ 59.33 (bm);
114.3 (d, J = 9.1 Hz), 121.9 (d, J = 2.7 Hz), 122.2 (d, J = 7.3 Hz), (minor diastereomer) δ 59.90 (bm).
127.0, 127.2 (d, J = 7.3 Hz), 127.9 (d, J = 6.4 Hz), 128.96, 127.98,
(1,5-Dimethoxy-1,4-cyclohexadien-3-yl)(3,5-dimethoxyphenyl)-
132.9 (d, J = 10.0 Hz), 141.5 (d, J = 6.4 Hz), 161.4 (d, J = 2.7 Hz); phosphinous acid-borane N-methyl-(S)-α-methylbenzylamide
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(34e). Prepared from 32e (0.080 g, 0.0002 mol) and sodium Hz), 132.1 (d, J = 10.0 Hz), 134.3 (d, J = 11.8 Hz), 141.7 (d, J =
(0.012 g, 0.0005 mol). Isolated as a mixture with a substrate 6.4 Hz), 161.8 (d, J = 2.7 Hz); (minor diastereomer) δ 16.5, 28.8
and 35b. Yield 11% (a mixture of two diastereomers in 50% (d, J = 3.6 Hz), 114.1 (d, J = 11.8 Hz), 127.0, 127.9, 128.1, 128.4
1
de) (based on NMR analysis). RF 0.35 (hexane–EtOAc 6 : 1). H (d, J = 10.9 Hz), 130.9 (d, J = 1.8 Hz), 132.2 (d, J = 10.9 Hz),
NMR (CDCl3, 500 MHz) (major diastereomer) δ 0.45–1.33 (3 H, 134.0 (d, J = 11.8 Hz), 141.7 (d, J = 6.4 Hz), 161.7 (d, J = 2.7 Hz);
bm), 1.69 (3 H, d, J = 6.6 Hz), 2.35 (3 H, d, J = 6.3 Hz), 31P NMR (CDCl3, 202 MHz) (major diastereomer) δ 67.94 (bm);
2.66–2.73 (2 H, m), 3.46 (3 H, s), 3.59 (3 H, s), 3.66–3.75 (1 H, (minor diastereomer) δ 71.30 (bm); GC (Phenomenex Zebron
m), 3.84 (6 H, s), 4.55–4.59 (1 H, m), 4.76–4.80 (1 H, m), ZB-35 HT) RT 16.60 min; GC–MS (EI, 70 eV) m/z (%) 349 (M −
5.08–5.18 (1 H, m), 6.57 (1 H, t, J = 2.2 Hz), 6.85 (2 H, dd, J = BH3) (9), 248 (15), 293 (21), 292 (100), 245 (9), 244 (52), 215
2.2 Hz, 10.1 Hz), 7.23–7.47 (5 H, m); (minor diastereomer) (19), 213 (12), 184 (8), 183 (14), 170 (8), 152 (18), 139 (42), 138
δ 0.45–1.33 (3 H, bm), 1.50 (3 H, d, J = 6.9 Hz), 2.33 (3 H, d, J = (16), 135 (24), 134 (43), 120 (9), 109 (40), 108 (17), 107 (11), 105
6.0 Hz), 2.81–2.87 (2 H, m), 3.43 (3 H, s), 3.66–3.75 (1 H, m), (22), 91 (11).
3.68 (6 H, s), 3.69 (3 H, s), 4.60–4.64 (1 H, m), 5.01–5.05 (1 H,
m), 5.08–5.18 (1 H, m), 6.50 (1 H, t, J = 2.2 Hz), 6.64 (2 H, dd,
J = 2.2 Hz, 10.4 Hz), 7.23–7.47 (5 H, m); 31P NMR (CDCl3,
202 MHz) (major diastereomer) δ 75.01 (bm); (minor diastereo-
Acknowledgements
mer) δ 77.42 (bm).
Financial support from the Polish Ministry of Sciences/
3,5-Dimethoxyphenylphosphinous acid-borane N-methyl-(S)- National Science Centre (research grant N N204 3539 40) is
α-methylbenzylamide (35b). Prepared from 32e (0.080 g, kindly acknowledged.
0.0002 mol) and sodium (0.012 g, 0.0005 mol). Isolated as a
mixture with a substrate and 34e. Yield 17% (a mixture of two
diastereomers in 30% de) (based on NMR analysis). RF 0.44
Notes and references
(hexane–EtOAc 6 : 1). 1H NMR (CDCl3, 500 MHz) (major dia-
stereomer) δ 0.54–1.51 (3 H, bm), 1.52 (3 H, d, J = 6.9 Hz), 2.38
(3 H, d, J = 8.8 Hz), 3.84 (6 H, s), 4.89–4.96 (1 H, m), 6.58 (1 H,
t, J = 2.2 Hz), 6.60 (1 H, dm, J = 392.2 Hz), 6.77 (2 H, dd, J = 2.2
Hz, 12.6 Hz), 7.29–7.38 (5 H, m); (minor diastereomer)
δ 0.54–1.51 (3 H, bm), 1.50 (3 H, d, J = 7.3 Hz), 2.46 (3 H, d, J =
9.1 Hz), 3.77 (6 H, s), 4.82–4.89 (1 H, m), 6.54 (1 H, t, J = 1.9
Hz), 6.60 (1 H, dm, J = 392.2 Hz), 6.66 (2 H, dd, J = 2.2 Hz, J =
12.9 Hz), 7.29–7.38 (5 H, m); 13C NMR (126 MHz, CDCl3)
(major diastereomer) δ 16.8 (d, J = 1.8 Hz), 31.3, 55.5, 103.6,
108.8 (d, J = 11.8 Hz), 127.3, 127.4, 128.3, 132.6 (d, J = 62.7 Hz),
140.9 (d, J = 4.5 Hz), 161.1 (d, J = 14.5 Hz); (minor diastereo-
mer) δ 17.0 (d, J = 1.8 Hz), 30.8, 55.5, 103.7, 108.5 (d, J =
11.8 Hz), 127.4, 127.5, 128.4, 132.4 (d, J = 64.5 Hz), 141.2 (d, J =
4.5 Hz), 161.1 (d, J = 15.4 Hz); 31P NMR (CDCl3, 202 MHz)
(major diastereomer) δ 60.72 (bm); (minor diastereomer) δ
61.38 (bm).
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5.29–5.38 (1 H, m), 6.96–7.01 (2 H, m), 7.24–7.31 (2 H, m),
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