P -stereogenic phospholanes or phosphorinanes from o -biarylylphosphines: Two bridges not too far

Article abstract of DOI:10.1021/jo400565b

The discovery of a concise regiodivergent asymmetric route to nonclassical P-stereogenic 5- or 6-membered benzophosphacycles, under conditions-dependent radical (oxidative addition) versus anionic (S_NAr) benzannulation, is reported.

Full text of DOI:10.1021/jo400565b

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P‑Stereogenic Phospholanes or Phosphorinanes from
o‑Biarylylphosphines: Two Bridges Not Too Far
‡
§
,†,‡,∥
Barbara Mohar,*,†,‡ Alen Cusak, Barbara Modec, and Michel Stephan*
̌
†National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia
‡EN-FIST CO, Dunajska 156, SI-1000 Ljubljana, Slovenia
§Department of Chemistry and Chemical Technology, University of Ljubljana, Ask
erceva 5, SI-1000 Ljubljana, Slovenia
̌ ̌
S
* Supporting Information
ABSTRACT: The discovery of a concise regiodivergent
asymmetric route to nonclassical P-stereogenic 5- or 6-
membered benzophosphacycles, under conditions-dependent
radical (oxidative addition) versus anionic (SNAr) benzannu-
lation, is reported.
́
Of interest, the Juge−Stephan asymmetric route to P-
INTRODUCTION
■
stereogenic phosphines via P-borane intermediates furnishes
selectively either P-enantiomer in good overall yield. It relies
upon the regio- and stereoselective two-step sequential
displacement of the (+)- or (−)-ephedrine auxiliary from an
enantiopure 1,3,2-oxazaphospholidine-2-borane complex (ox-
azaPB).2b,e
Enantiopure P-based organic compounds have been an ever-
increasing research interest for over a century.1 In particular,
numerous phosphines were designed by an array of synthetic
strategies encompassing chiral pool skeletal modification,
resolution or desymmetrization techniques, and asymmetric
synthesis.2 Notably, backbone or P-atom stereogenic phospha-
cyclic motifs (Figure 1) have endowed excellent properties to
transition-metal catalysts in a variety of asymmetric trans-
formations.3 Stereogenic mono- or di- (bridged) carbocyclic
phosphetanes, phospholanes, and phosphepanes are predom-
inantly encountered in the literature in contrast to phosphor-
inanes.4,5
In our ongoing reasearch and development of (P-ortho-
substituted aryl)-borne ethane-bridged diphosphines following
the latter methodology,6 we explored the synthesis of P-o-
biarylyl congeners. The preparation of the basic enantiomeric
1,2-bis[(o-biphenylyl)(phenyl)phosphino]ethane diphosphine
has been accomplished from its P-oxide derivative via a Cu-
mediated dimerization.7 Curiously, no reports existed on its
preparation via the P-borane adduct variant, though P-o-
biphenylyl-containing advanced P-borane intermediates have
been earlier applied to various phosphines’ syntheses by several
research groups.8
RESULTS AND DISCUSSION
■
Our low-temperature CuCl2-catalyzed attempted homocou-
pling of (SP)-(o-biphenylyl)(methyl)(phenyl)phosphine-P-bor-
ane (3a) P-α-lithio anion gave rise, unfortunately, to a complex
mixture (Scheme 1). Nevertheless, meticulous 1H and 31P
NMR analyses identified the unexpected P-cyclic 9-phenyl-
9,10-dihydro-9-phosphaphenanthrene-P-borane. This new chi-
ral structure consists of a phosphorinane-P-borane wedged in
the bay area of the biphenylic system, further bridging the two
aryls. Unsubstituted phosphorinanes are inherently more
flexible than phospholanes but a biphenyl-fused moiety confers
a conformational restriction to the overall structure.
Following this discovery, the potential reactivity of such (P-o-
biarylyl)-substituted (methyl)phosphine-P-boranes was inves-
tigated. Thus, screening the (2R,4S,5R)-(+)-oxazaPB ring-
Figure 1. Generic representation of the most encountered cyclic
phosphines in metal-catalyzed asymmetric hydrogenation and a
selection thereof.
Received: March 21, 2013
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo400565b | J. Org. Chem. XXXX, XXX, XXX−XXX

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Spectroscopic data (1H, 13C, and 31P NMR) of the crude
indicated the formation of 1a−g as a single diastereomer,9c and
X-ray crystal-structure analysis of 1b confirmed the retention of
P-configuration.11
Scheme 1. Attempted Preparation of (SP,SP)-1,2-Bis[(o-
biphenylyl)(phenyl)phosphino-P-borane]ethane Led to a
Dibenzophosphorinane-P-borane
a
Following, H2SO4-promoted rt methanolysis of the (SP)-
aminophosphine-P-boranes 1a−f (step ii) provided after
recrystallization enantiomerically pure methyl (RP)-phosphin-
ite-P-boranes 2a−f in 40−83% yield.12,13
Low-temperature displacement of the P-OMe group of (RP)-
2a−f with MeLi (1.2 equiv) afforded (SP)-(methyl)phosphine-
P-boranes 3a−f in 43−81% (step iii).12b It was noticed with
methyl phosphinite-P-borane 2c that operating at up to rt with
>2 equiv of MeLi (step v) induced the formation of the new 4-
methoxy-9-phenyl-9,10-dihydro-9-phosphaphenanthrene-P-
borane heterocycle (4c) by annulation onto the o-biarylyl
group. An identical result was obtained with the generated P-α-
lithio carbanion from the isolated (methyl)phosphine-P-borane
3c (step iv). Clearly, a ready intramolecular nucleophilic
aromatic substitution (SNAr) of the activated Csp2-OMe group
was occurring. This displacement is accelerated by the MeO
a
Reagents and conditions: (i) s-BuLi, THF, −30 °C, 1 h, then CuCl2,
−30 °C, 1 h.
opening with various o-biarylyllithiums, a series of (o-biarylyl)-
(N-ephedrino)(phenyl)phosphine-P-boranes 1a−h was pre-
pared in 22−90% isolated yields (Scheme 2, step i).9,10
a
Scheme 2
̀
coordinative nature and suitable proximal disposition vis-a-vis
the strongly reactive P-α-lithio anion with carbocyclization as a
net result. Alternatively, in a convenient one-pot conversion via
in situ formation of the reactive species, crystalline unsym-
metrical dibenzophosphorinane-P-boranes 4b,c,e were obtained
in 73−79% yield upon treatment of 2b,c,e with excess (>2
equiv) MeLi (step v).14 Under the same conditions, compound
2d gave a mixture of 4d (10%) and 3d (78%). Compound 4b
1
was found to have H and 31P NMR spectra identical to those
of the phosphacycle of Scheme 1.
In view of the simultaneous determination of absolute P-
configuration and anticipated axial chirality of 4, α-functional-
ization using (R)-styrene oxide was performed. Its condensa-
tion with the preformed P-α-lithio carbanion of 4c,15 and
subsequent BH3 removal followed by P-oxidation,16 furnished
the P-oxide 7 which facilitated the growth of a single crystal
(Scheme 3). X-ray crystal-structure analyses of 4c and 7
confirmed the (SP)-configuration of 4c. With an identical M-
atropisomery (or Ra) in both cases, the P-phenyl group
occupies a less congested quasi-axial position. It is noteworthy
that two structurally similar conformers (having M-atropisom-
ery) were found in the 4c cell unit. The twisted axial orientation
is locked in all cases.17
a
Reagents and conditions: (i) o-Ar-PhLi, THF, −20 °C to rt (22−90%
yield); (ii) MeOH, H2SO4, rt (40−83% yield); (iii) MeLi (1.2 equiv),
THF, −20 °C (43−81% yield); (iv) s-BuLi (1.1 equiv) or MeLi (>1
equiv), THF, −30 °C to rt (81% yield for 4c from 3c); (v) MeLi (>2
equiv), THF, −20 °C to rt, o/n (73% yield for 4b; 79% for 4c; 10% for
4d with 78% of 3d; 77% for 4e); (vi) Et2NH, 55−60 °C (93−99%
yield); (vii) 50% aq H2O2, Me2CO, 0 °C (98% yield).
a
Scheme 3. ORTEP Drawings of 4c (Left) and Its Derivative 7 (Right) at the 50% Probability Level and Preparation of 7
a
Reagents and conditions: (i) s-BuLi, THF, −30 °C, then (R)-styrene oxide (70% yield); (ii) Et2NH, 55−60 °C; (iii) 50% aq H2O2, Me2CO, 0 °C
(99% yield for two steps).
B
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Scheme 4. Transformation Pathways of the P-α-Radical of (SP)-3
Closing the synthetic sequence of Scheme 2, (SP)-4b,c,e
decomplexation under mild conditions in Et2NH (55−60 °C)
(step vi) furnished the corresponding homochiral dibenzo-
phosphorinanes 5b,c,e in 93−99% yield (31P NMR δ ∼−40
ppm), and oxidation of 5c gave 6c (step vii).14,16 The simplest
free monophosphine 5b was dubbed “6TwistP” alluding to its
6-membered twisted structure and reminiscent of the
unexpected outcome of this chemistry.
In a second surprising turn of events, treatment of (SP)-3c
with s-BuLi and CuCl2 did not lead to the expected
dimerization product but instead gave the new unusual
spiro[(2,6-dimethoxy-2,5-cyclohexadiene)-1,1′-(3-phenyl-3-
phosphindane-P-borane)] chiral structure 8c (dubbed
“5TwistP·BH3”) (Scheme 4).18
This spiro benzophospholane-P-borane arose from favored
P-α-radical trapping by the neighboring 2,6-dimethoxyphenyl
ring and leading to its dearomatization. Analysis of this case
coupled with Scheme 1 result with 3a (Scheme 3, R = R′ = R′′
= H) points out that, under the same reaction conditions, a
switch in regioselectivity occurs depending on o′-MeO-
substituents’ availability on the top aryl. Investigating this
Figure 2. ORTEP drawing of (SP)-8d at the 50% probability level.
phosphinite-P-boranes 2 providing the biphenyl-fused phos-
phorinane-P-boranes 4 and the radical-initiated dearomatizing
spirocyclization toward benzophospholane-P-boranes 8 repre-
sent a new twist in P-stereogenic cyclic phosphines’ synthesis.
Such “chiral or achiral” frameworks constitute interesting
precursors for the elaboration of new diversified families of
P-heterocycles. The progress of this ongoing research will be
communicated in due course.
1
reaction with 3b led to a complex mixture. Nevertheless, H
and 31P NMRs revealed the formation of a benzophospholane-
P-borane 8b (31P NMR δ ∼+32 ppm; not isolated, with an
unconfirmed geometry of the non-meso-cycle) and 4c but not
4b. Also, the spiro-dienonic structure (SP)-8d was obtained
from (SP)-3d by loss of a CH3 radical (Figure 2).
The polar cases experiments show that the P-α-radical
preferentially adds intramolecularly onto the ipso-position of
the top aryl furnishing a 5-membered ring (formal 5-exo-trig
carbocyclization) if at least a substituent occupies an o′-position
(R″ ≠ H), and in its absence (R″ = H) addition on the
neighboring o′-position prevails leading to a 6-membered ring
(6-endo-trig). The formation of compounds 4b,c was
accompanied by the partial recovery of starting 3. This could
have arguably formed in part via intermolecular quench of the
P-CH2 radical by H-abstraction from the transient cyclic radical
evolving toward 4. Such a pathway is excluded with 3c.19
EXPERIMENTAL SECTION
■
General Methods. All reactions were conducted under an inert
atmosphere using anhydrous solvents. 1H (300 MHz, internal Me4Si),
13C (75 MHz, internal CDCl3; JC−P is indicated), and 31P NMR (120
MHz, external 85% H3PO4) were recorded for solutions in CDCl3.
High-resolution mass spectra were obtained with a Q-TOF instrument
equipped with orthogonal Z-spray ESI interface. 2-Bromobiphenyl, 2′-
bromo-2,6-dimethoxybiphenyl, 2′-bromo-2,6-diisopropoxybiphenyl, 2-
methoxy-1-naphthaleneboronic acid, and (R)-styrene oxide (ee
≥98.0% (GC)) are commercially available. (2R,4S,5R)-(+)-3,4-
Dimethyl-2,5-diphenyl-1,3,2-oxazaphospholidine-2-borane ((+)-oxa-
zaPB derived from (1R,2S)-(−)-ephedrine),2b 2′-bromo-2-methox-
ybiphenyl,20 and 2′-bromo-2,4,6-trimethoxybiphenyl21 were prepared
according to the literature.
CONCLUSIONS
■
2′-Bromo-2,6-dimethoxy-4-methylbiphenyl. To a solution of
1,3-dimethoxy-5-methylbenzene (11.00 g, 72.3 mmol) in THF (100
mL) was added under stirring n-BuLi (1.3 M in hexane, 56 mL) at rt.
After 1 h, it was cooled to 0 °C, 1,2-dibromobenzene (17.05 g, 72.3
We have presented a controlled serendipitous divergent
asymmetric synthesis of either 5- or 6-membered cyclic
phosphine-P-boranes. The cascade reactions from methyl
C
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mmol) was slowly added, and the mixture was allowed to stir
overnight at rt. After H2O quenching and extraction with CH2Cl2, the
crude was purified by recrystallization (i-Pr2O/CH2Cl2) affording off-
white crystals (11.50 g, 52%): mp 143−145 °C; Rf 0.49 (toluene/
(ESI) m/z 470.2 (56) [M+ + H]; HRMS (ESI) calcd for
C29H34BNO2P [M+ + H] 470.2420, found 470.2419.
(SP)-(2′,6′-Dimethoxybiphenyl-2-yl)[(1R,2S)-N-ephedrino]-
(phenyl)phosphine P-Borane ((SP)-1c). From 2′-bromo-2,6-
dimethoxybiphenyl (7.62 g, 26.0 mmol) following the procedure as
for 1a. Purification on silica gel eluting with toluene then toluene/
EtOAc 9:1 (Rf 0.48) and recrystallization (toluene/MeOH) afforded
white crystals (9.00 g, 90%). (SP)-1c: mp 122−124 °C; [α]30D +14.7 (c
1
hexane 7:3); H NMR δ 2.42 (s, 3H), 3.72 (s, 6H), 6.47 (s, 2H),
7.14−7.24 (m, 2H), 7.30−7.36 (m, 1H), 7.64 (dd, J = 8, 1 Hz, 1H);
13C NMR δ 22.2, 55.8, 104.9, 116.0, 125.4, 126.8, 128.3, 132.2, 132.5,
136.1, 139.6, 157.3; MS (ESI) m/z 307.0 (100) [M+ + H]; HRMS
(ESI) calcd for C15H1679BrO2 [M+ + H] 307.0334, found 307.0345.
2′-Bromo-2,6-dimethylbiphenyl. To a solution of 1-bromo-2-
iodobenzene (8.49 g, 30.0 mmol) and Pd(PPh3)4 (1.04 g, 0.9 mmol)
in toluene (80 mL) was added 2,6-dimethylbenzeneboronic acid (5.85
g, 39.0 mmol) in EtOH (40 mL) then aq Na2CO3 (19.08 g in 80 mL
H2O). The resulting mixture was stirred at 85 °C for 6 days. After
toluene/H2O extraction, the product was purified on silica gel eluting
with hexane (Rf 0.40) and recrystallized (hexane/MeOH) at 0 °C to
afford white crystals (4.93 g, 63%): mp 47−50 °C; 1H NMR δ 1.98 (s,
6H), 7.09−7.22 (m, 5H), 7.32−7.37 (m, 1H), 7.66 (dd, J = 8, 1 Hz,
1H); 13C NMR δ 20.3, 123.9, 127.1, 127.6, 128.6, 130.5, 132.7, 135.8,
140.7, 141.7.
1
1.0, CHCl3); H NMR δ 0.57−1.56 (br m, 3H), 0.97 (d, J = 7 Hz,
3H), 1.80 (br d, J = 4 Hz, 1H), 2.65 (d, J = 8 Hz, 3H), 3.50 (s, 3H),
3.63 (s, 3H), 3.95 (m, 1H), 4.83 (m, 1H), 6.33 (d, J = 8 Hz, 1H), 6.42
(d, J = 8 Hz, 1H), 7.11−7.36 (m, 11H), 7.41−7.56 (m, 4H). NMR
data were consistent with those reported in the literature.10b 2-Butyl-
1
2′,6′-dimethoxybiphenyl was also isolated: H NMR δ 0.75 (t, J = 7
Hz, 3H), 1.17 (m, 2H), 1.40 (m, 2H), 2.35 (m, 2H), 3.69 (s, 6H), 6.63
(d, J = 8 Hz, 2H), 7.09 (m, 1H), 7.19−7.43 (m, 4H).
(SP)-[(1R,2S)-N-Ephedrino](phenyl)(2′,4′,6′-trimethoxybi-
phenyl-2-yl)phosphine P-Borane ((SP)-1d). From 2′-bromo-2,4,6-
trimethoxybiphenyl (4.43 g, 13.7 mmol) following the procedure as for
1a. Purification on silica gel eluting with toluene and then toluene/
EtOAc 9:1 (Rf 0.38) and recrystallization (hexane/MeOH) afforded
1-(2-Bromophenyl)-2-methoxynaphthalene. To a hot (85 °C)
solution of 1-bromo-2-iodobenzene (4.24 g, 15.0 mmol), K2CO3 (4.15
g, 30.0 mmol), and Pd(PPh3)4 (0.35 g, 0.3 mmol) in EtOH (1 mL)/
H2O (4 mL)/dioxane (10 mL) was added a solution of 2-methoxy-1-
naphthaleneboronic acid (2.02 g, 10.0 mmol) in dioxane (10 mL) over
4 h. The resulting mixture was stirred at 85 °C for 2 days. The reaction
was allowed to cool to rt, quenched with 3 M HCl and extracted with
EtOAc. Purification of the residue on silica gel eluting with hexane/
EtOAc 19:1 and recrystallization (CH2Cl2/hexane) afforded white
crystals (1.65 g, 50%): mp 119−121 °C; Rf 0.36 (hexane/EtOAc
white crystals (4.79 g, 86%): mp 129−131 °C; [α]25 +11.9 (c 1.1,
D
1
CHCl3); H NMR δ 0.45−1.50 (br m, 3H), 1.01 (d, J = 7 Hz, 3H),
1.72 (br d, J = 4 Hz, 1H), 2.66 (d, J = 8 Hz, 3H), 3.48 (s, 3H), 3.62 (s,
3H), 3.77 (s, 3H), 4.00 (m, 1H), 4.83 (m, 1H), 5.86 (d, J = 2 Hz, 1H),
5.96 (d, J = 2 Hz, 1H), 7.09−7.36 (m, 10H), 7.43−7.56 (m, 4H); 13C
NMR δ 10.7 (d, J = 4 Hz), 31.7 (d, J = 2 Hz), 54.8, 55.1, 55.2, 57.7 (d,
J = 9 Hz), 78.7 (d, J = 2 Hz), 89.8, 89.9, 110.8 (d, J = 3 Hz), 125.8−
133.9 (m), 139.8 (d, J = 11 Hz), 142.7, 158.2, 158.3, 161.0; 31P NMR
δ +71.7 (br m); MS (ESI) m/z 528.2 (38) [M+ − H]; HRMS (ESI)
calcd for C31H36BNO4P 528.2475 [M+ − H], found 528.2496.
(SP)-(2′,6′-Dimethoxy-4′-methylbiphenyl-2-yl)[(1R,2S)-N-
ephedrino](phenyl)phosphine P-Borane ((SP)-1e). From 2′-
bromo-2,6-dimethoxy-4-methylbiphenyl (6.36 g, 20.7 mmol) following
procedure as for 1a. Purification on silica gel eluting with toluene then
toluene/EtOAc 9:1 (Rf 0.52) and recrystallization (toluene/MeOH)
1
19:1); H NMR δ 3.84 (s, 3H), 7.19−7.43 (m, 7H), 7.72−7.76 (m,
1H), 7.79−7.85 (m, 1H), 7.90 (d, J = 9 Hz, 1H); 13C NMR δ 56.6,
113.6, 123.6, 124.1, 124.6, 125.3, 126.6, 127.2, 127.9, 128.8, 128.9,
129.7, 132.4, 132.6, 132.9, 137.7, 153.8; MS (ESI) m/z 312.0 (93)
[M+]; HRMS (ESI) calcd for C17H1379BrO [M+] 312.0150, found
312.0157.
afforded white crystals (7.35 g, 90%): mp 140−143 °C; [α]25 +16.4
D
1
(SP)-(Biphenyl-2-yl)[(1R,2S)-N-ephedrino](phenyl)phosphine
P-Borane ((SP)-1a). To a cold solution (−78 °C) of 2-bromobiphenyl
(2.50 g, 10.7 mmol) in Et2O (35 mL) was added n-BuLi (1.5 M in
hexane, 7.2 mL). After being stirred at −78 °C for 2 h, the reaction
mixture was warmed to −20 °C for 15 min. To this suspension at −78
°C was added a solution of (+)-oxazaPB (2.37 g, 8.3 mmol) in THF
(20 mL) then the suspension allowed to warm to rt with overnight
stirring. CH2Cl2/H2O extraction followed by purification on silica gel
eluting with toluene then toluene/EtOAc 19:1 (Rf 0.51) afforded white
(c 1.0, CHCl3); H NMR δ 0.45−1.50 (br m, 3H), 0.98 (d, J = 7 Hz,
3H), 1.74 (br d, J = 4 Hz, 1H), 2.27 (s, 3H), 2.65 (d, J = 8 Hz, 3H),
3.48 (s, 3H), 3.61 (s, 3H), 3.99 (m, 1H), 4.81 (m, 1H), 6.09 (s, 1H),
6.19 (s, 1H), 7.09−7.34 (m, 10H), 7.43−7.53 (m, 4H); 13C NMR δ
10.5 (d, J = 4 Hz), 22.0, 31.7 (d, J = 2 Hz), 54.7, 55.1, 57.6 (d, J = 9
Hz), 78.6 (d, J = 2 Hz), 103.9, 115.1 (d, J = 3 Hz), 125.7−139.5 (m),
142.6, 157.3; 31P NMR δ +72.0 (br m); MS (ESI) m/z 514.3 (42) [M+
+ H]; HRMS (ESI) calcd for C31H38BNO3P [M+ + H] 514.2682,
found 514.2689.
crystals (2.70 g, 74%): mp 104−106 °C; [α]25 +52.7 (c 1.2, CHCl3)
D
(SP)-(2′,6′-Diisopropoxybiphenyl-2-yl)[(1R,2S)-N-ephedrino]-
(phenyl)phosphine P-Borane ((SP)-1f). From 2′-bromo-2,6-diiso-
propoxybiphenyl (8.00 g, 22.9 mmol) following procedure as for 1a.
Purification on silica gel eluting with toluene then toluene/EtOAc 9:1
(Rf 0.62) afforded a colorless syrup (7.93 g, 81%): [α]25D −40.4 (c 1.3,
(SP-enantiomer: [α]20D +64.9 (c 0.297, CH2Cl2)8a); 1H NMR δ 0.55−
1.65 (br m, 3H), 0.68 (d, J = 7 Hz, 3H), 1.50 (br d, J = 4 Hz, 1H), 2.55
(d, J = 7 Hz, 3H), 3.94 (m, 1H), 4.84 (m, 1H), 7.13−7.49 (m, 17H),
7.64−7.72 (m, 2H). NMR data were consistent with those reported in
the literature.8a,b
1
CHCl3); H NMR δ 0.45−1.55 (br m, 3H), 1.00 (d, J = 6 Hz, 3H),
(SP)-[(1R,2S)-N-Ephedrino](2′-methoxybiphenyl-2-yl)-
(phenyl)phosphine P-Borane ((SP)-1b). To a cold solution (−78
°C) of 2′-bromo-2-methoxybiphenyl (5.00 g, 19.0 mmol) in THF
(200 mL) was added n-BuLi (1.5 M in hexane, 12.7 mL). After being
stirred at −78 °C for 1 h, a solution of (+)-oxazaPB (4.16 g, 14.6
mmol) in THF (20 mL) was slowly added. Treatment as for 1a and
purification on silica gel eluting with toluene then toluene/EtOAc 9:1
(Rf 0.53) followed by recrystallization (toluene/MeOH) afforded
1.03 (d, J = 7 Hz, 3H), 1.05 (d, J = 6 Hz, 3H), 1.14 (d, J = 6 Hz, 3H),
1.17 (d, J = 6 Hz, 3H), 1.86 (br s, 1H), 2.68 (d, J = 8 Hz, 3H), 4.06
(m, 1H), 4.32 (m, 2H), 4.84 (d, J = 3 Hz, 1H), 6.31 (d, J = 8 Hz, 1H),
6.33 (d, J = 8 Hz, 1H), 6.99−7.04 (m, 2H), 7.11−7.31 (m, 9H), 7.39
(m, 1H), 7.45−7.57 (m, 3H); 13C NMR δ 10.5 (d, J = 4 Hz), 21.9,
22.4, 22.5, 32.2 (d, J = 3 Hz), 57.6 (d, J = 10 Hz), 69.8, 70.9, 79.0 (d, J
= 2 Hz), 105.4, 106.3, 121.0 (d, J = 3 Hz), 125.8−134.5 (m), 140.9 (d,
J = 11 Hz), 142.7, 156.7, 156.8; 31P NMR δ +71.8 (br m); MS (ESI)
m/z 556.3 (18) [M+ + H]; HRMS (ESI) calcd for C34H44BNO3P [M+
+ H] 556.3152, found 556.3142.
(SP)-(2′,6′-Dimethylbiphenyl-2-yl)[(1R,2S)-N-ephedrino]-
(phenyl)phosphine P-Borane ((SP)-1g). From 2′-bromo-2,6-
dimethylbiphenyl following procedure as for 1a. The organolithium
was prepared as follows: to a cold solution (−78 °C) of 2′-bromo-2,6-
dimethylbiphenyl (0.23 g, 0.88 mmol) in THF (10 mL) was added t-
BuLi (1.5 M in pentane, 1.17 mL). After the solution was stirred at
−78 °C for 30 min, the temperature was gradually raised to −50 °C to
ensure complete lithiation. Purification on silica gel eluting with
white crystals (7.13 g, 80%): mp 132−134 °C; [α]30 +80.9 (c 1.2,
D
CHCl3); 1H NMR δ 0.40−1.55 (br m, 3H), 0.47 (d, J = 7 Hz, 1.2H),
1.13 (d, J = 7 Hz, 1.8H), 1.43 (br d, J = 4 Hz, 0.4H) 1.65 (br d, J = 4
Hz, 0.6H), 2.50 (d, J = 7 Hz, 1.2H), 2.70 (d, J = 7 Hz, 1.8H), 3.63 (s,
1.8H), 3.71 (s, 1.2H), 3.80 (m, 0.4H), 4.10 (m, 0.6H), 4.81 (m, 1H),
6.58 (d, J = 8 Hz, 0.6H), 6.72−6.84 (m, 1.4H), 7.08−7.55 (m, 15H),
7.74 (m, 1H); 13C NMR δ 9.5 (d, J = 6 Hz), 10.8 (d, J = 5 Hz), 31.3
(d, J = 4 Hz), 31.6 (d, J = 4 Hz), 54.7, 54.9, 57.7 (d, J = 10 Hz), 58.0
(d, J = 10 Hz), 78.3, 78.8, 109.9, 110.2, 119.0, 119.4, 125.5−133.9 (m),
142.4−143.7 (m), 156.0 (d, J = 2 Hz); 31P NMR δ +70.7 (br m); MS
D
dx.doi.org/10.1021/jo400565b | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
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toluene/hexane 4:1 and then toluene afforded (RP)-trans-(N-
methylamino)(phenyl)(1-phenyl-1-propenyloxy)phosphine P-borane
as white crystals (0.12 g, 73%). Further elution with toluene/EtOAc
(19:1) then toluene/EtOAc 9:1 (Rf 0.56) afforded 1g as a white foam
(61 mg, 22%): [α]30D −7.6 (c 1.0, CHCl3); 1H NMR δ 0.35−1.50 (br
m, 3H), 1.04 (d, J = 7 Hz, 3H), 1.87 (s, 3H), 1.96 (s, 3H), 2.75 (d, J =
7 Hz, 3H), 3.96 (m, 1H), 4.99 (d, J = 3 Hz, 1H), 6.87 (d, J = 7 Hz,
1H), 6.95 (d, J = 7 Hz, 1H), 7.14−7.29 (m, 2H), 7.31−7.65 (m, 13H);
13C NMR δ 10.3 (d, J = 5 Hz), 21.3, 21.4, 31.9 (d, J = 3 Hz), 57.8 (d, J
= 10 Hz), 79.2, 125.8−136.6 (m), 140.0 (d, J = 3 Hz), 142.6, 146.2 (d,
J = 14 Hz); 31P NMR δ +72.2 (br m); MS (ESI) m/z 468.3 (100) [M+
+ H]; HRMS (ESI) calcd for C30H36BNOP [M+ + H] 468.2628, found
468.2638.
(CH2Cl2/hexane) afforded (−)-(2′,6′-dimethoxybiphenyl-2-yl)-
(hydroxy)(phenyl)phosphine P-borane as white crystals (0.34 g,
6%). Further elution with EtOAc/MeOH and recrystallization (i-
Pr2O/CH2Cl2) afforded (−)-(2′,6′-dimethoxybiphenyl-2-yl)(phenyl)-
phosphine P-oxide as white crystals (0.54 g, 10%).
(RP)-2c: mp 108−110 °C; Rf 0.35 (toluene); [α]30 +38.6 (c 1.1,
D
CHCl3) (RP-enantiomer,10b [α]D +28.4 (c 0.9, CH2Cl2)); H NMR δ
1
0.30−1.45 (br m, 3H), 3.32 (s, 3H), 3.40 (s, 3H), 3.57 (d, J = 12 Hz,
3H), 6.26 (d, J = 8 Hz, 1H), 6.38 (d, J = 8 Hz, 1H) 7.10−7.37 (m,
7H), 7.48 (tt, J = 8, 2 Hz, 1H), 7.56 (tt, J = 7, 1 Hz, 1H), 8.16 (ddd, J
= 12, 8, 1 Hz, 1H); 31P NMR δ +107.8 (br m). NMR data were
consistent with those reported in the literature.10b
(−)-(2′,6′-Dimethoxybiphenyl-2-yl)(hydroxy)(phenyl)-
phosphine P-Borane: mp 129−132 °C; Rf 0.52 (toluene/EtOAc
4:1); [α]25D −11.3 (c 1.0, CHCl3); 1H NMR δ 0.40−1.60 (br m, 3H),
3.20 (s, 3H), 3.74 (s, 3H), 6.10 (d, J = 8 Hz, 1H), 6.63 (d, J = 8 Hz,
1H), 6.71 (br s, 1H), 7.05−7.24 (m, 7H), 7.57 (m, 2H), 8.50 (m, 1H);
13C NMR δ 54.8, 57.2, 105.0, 105.2, 119.0 (d, J = 3 Hz), 127.3−137.2
(RP)-trans-(N-Methylamino)(phenyl)(1-phenyl-1-propenyl-
oxy)phosphine P-Borane: mp 65−68 °C; Rf 0.52 (toluene); [α]25
D
+63.6 (c 1.2, CHCl3) ((SP)-enantiomer,9b [α]25 −69.6 (c 1.0,
D
1
CHCl3)); H NMR δ 0.23−1.30 (br m, 3H), 1.78 (dd, J = 7, 3 Hz,
3H), 2.30 (dd, J = 11, 6 Hz, 3H), 2.89 (m, 1H), 5.67 (dq, J = 7, 3 Hz,
1H), 7.29−7.41 (m, 3H), 7.43−7.54 (m, 5H), 7.76−7.83 (m, 2H); 31P
NMR δ +105.3 (br m). NMR data were consistent with those reported
in the literature.9b
(m), 155.3, 157.4; 31P NMR δ +93.6 (br m); MS (ESI) m/z 351.1
(100) [M+ − H]; HRMS (ESI) calcd for C20H21BO3P [M+ − H]
351.1321, found 351.1314.
(SP)-[(1R,2S)-N-Ephedrino][2-(2-methoxynaphth-1-yl)-
phenyl](phenyl)phosphine P-Borane ((SP)-1h). From 1-(2-
bromophenyl)-2-methoxynaphthalene (1.10 g, 3.51 mmol) following
the procedure as for 1a. Purification on silica gel eluting with toluene
then toluene/EtOAc 9:1 afforded a colorless solid foam (1.09 g, 90%).
The compound was obtained as a mixture of two atropo-diastereomers
(−)-(2′,6′-Dimethoxybiphenyl-2-yl)(phenyl)phosphine P-
Oxide: mp 166−168 °C; Rf 0.46 (EtOAc); [α]30 −5.5 (c 1.3,
D
1
CHCl3); H NMR δ 3.19 (s, 3H), 3.72, (s, 3H), 6.29 (d, J = 8 Hz,
1H), 6.59 (d, J = 8 Hz, 1H), 7.16−7.29 (m, 6H), 7.36−7.42 (m, 1H),
7.54−7.62 (m, 2H), 7.62 (d, JP−H = 492 Hz, 1H), 8.19 (m, 1H); 13C
NMR δ 54.8, 55.6, 103.2, 103.5, 115.3 (d, J = 6 Hz), 127.3−132.6 (m),
137.4 (d, J = 12 Hz), 156.9, 157.4; 31P NMR δ +20.1 (s); MS (ESI)
m/z 339.1 (100) [M+ + H]; HRMS (ESI) calcd for C20H20O3P [M+ +
H] 339.1150, found 339.1153.
1
in ∼1:1 ratio as revealed by H NMR: Rf 0.52 (toluene/EtOAc 9:1);
1
[α]25 +16.0 (c 1.1, CHCl3); H NMR δ 0.35−1.25 (br m, 3H), 0.62
D
(d, J = 7 Hz, 1.4H), 0.83 (d, J = 7 Hz, 1.6H), 1.66 (br s, 1H), 2.61 (d, J
= 8 Hz, 1.6H), 2.72 (d, J = 7 Hz, 1.4H), 3.69 (s, 1.3H), 3.75−3.76 (m,
1.8H), 3.89 (m, 0.5H), 4.66 (d, J = 4 Hz, 0.5H), 4.77 (d, J = 3 Hz,
0.5H), 6.94−7.69 (m, 20H); 13C NMR δ 9.8 (d, J = 5 Hz), 10.4 (d, J =
5 Hz), 32.0 (d, J = 2 Hz), 32.3 (d, J = 3 Hz), 55.2, 55.8, 57.5 (d, J = 10
Hz), 57.8 (d, J = 9 Hz), 78.5, 79.1, 112.2, 112.5, 122.5−134.6 (m),
141.3 (d, J = 10 Hz), 141.5 (d, J = 11 Hz), 142.5, 153.86, 153.90; 31P
NMR δ +72.0 (br m); MS (ESI) m/z 520.3 (100) [M+ + H]; HRMS
(ESI) calcd for C33H36BNO2P [M+ + H] 520.2577, found 520.2563.
Methyl (RP)-(Biphenyl-2-yl)(phenyl)phosphinite P-Borane
((RP)-2a). To a solution of ((SP)-1a (1.76 g, 4.00 mmol) in MeOH
(30 mL) was added H2SO4 (96%, 0.40 g, 3.96 mmol) at rt under
stirring. After being stirred for 1 day, the reaction mixture was filtered
through a pad of silica gel and concentrated. Extraction with CH2Cl2/
H2O and purification on silica gel eluting with toluene/hexane 9:1
then toluene (Rf 0.76) and recrystallization (CH2Cl2/hexane) afforded
Methyl (RP)-(Phenyl)(2′,4′,6′-trimethoxybiphenyl-2-yl)-
phosphinite P-Borane ((RP)-2d). From (SP)-1d (2.06 g, 3.89
mmol) following the procedure as for 2a. Purification on silica gel
eluting with toluene and then toluene/EtOAc 19:1 afforded 2d as
white crystals (0.92 g, 60%). Further elution with toluene/EtOAc 9:1
then toluene/EtOAc 4:1 afforded (hydroxy)(phenyl)(2′,4′,6′-trime-
thoxybiphenyl-2-yl)phosphine P-borane as white crystals (0.15 g,
10%). (RP)-2d: mp 136−138 °C; Rf 0.25 (toluene); [α]25 +46.6 (c
D
1.1, CHCl3); 1H NMR δ 0.30−1.50 (br m, 3H), 3.29 (s, 3H), 3.35 (s,
3H), 3.57 (d, J = 12 Hz, 3H), 3.79 (s, 3H), 5.81 (d, J = 2 Hz, 1H),
5.91 (d, J = 2 Hz, 1H), 7.10 (m, 1H), 7.19−7.25 (m, 2H), 7.30−7.36
(m, 3H), 7.45 (m, 1H), 7.53 (m, 1H), 8.16 (m, 1H); 13C NMR δ 53.5
(d, J = 2 Hz), 54.7, 54.8, 55.2, 89.3, 89.4, 109.9 (d, J = 3 Hz), 126.7−
133.8 (m), 139.2 (d, J = 8 Hz), 158.3 (d, J = 5 Hz), 161.3; 31P NMR δ
+107.8 (br m); MS (ESI) m/z 395.2 (100) [M+ − H]; HRMS (ESI)
calcd for C22H25BO4P [M+ − H] 395.1584, found 395.1592.
white crystals (0.87 g, 71%): mp 119−121 °C; [α]25 −21.0 (c 1.2,
D
CHCl3) ((SP)-enantiomer,8a [α]20D +17.4 (c 0.945, CH2Cl2), >99% ee
(HPLC)); 1H NMR δ 0.30−1.50 (br m, 3H), 3.56 (d, J = 12 Hz, 3H),
6.89−6.93 (m, 2H), 7.10 (m, 2H), 7.17−7.38 (m, 7H), 7.45−7.56 (m,
2H), 8.05 (m, 1H); 31P NMR δ +109.7 (br m). NMR data were
consistent with those reported in the literature.8a,b
(−)-(Hydroxy)(phenyl)(2′,4′,6′-trimethoxybiphenyl-2-yl)-
phosphine P-Borane: mp 151−154 °C; Rf 0.45 (toluene/EtOAc
1
4:1); [α]30 −6.9 (c 1.1, CHCl3); H NMR δ 0.40−1.60 (br m, 3H),
D
3.17 (s, 3H), 3.68 (s, 3H), 3.77 (s, 3H), 5.64 (d, J = 2 Hz, 1H), 6.16
(d, J = 2 Hz, 1H), 6.62 (br s, 1H), 7.05−7.25 (m, 6H), 7.53 (m, 2H),
8.46 (m, 1H); 13C NMR δ 54.7, 55.5, 57.2, 91.7, 92.0, 111.8 (d, J = 3.3
Hz), 127.2−135.1 (m), 137.3 (d, J = 2.0 Hz), 155.9, 158.0, 161.5; 31P
NMR δ +93.9 (br m); MS (ESI) m/z 381.1 (100) [M+ − H]; HRMS
(ESI) calcd for C21H23BO4P [M+ − H] 381.1427, found 381.1428.
Methyl (RP)-(2′,6′-Dimethoxy-4′-methylbiphenyl-2-yl)-
(phenyl)phosphinite P-Borane ((RP)-2e). From (SP)-1e (3.00 g,
5.8 mmol) following procedure as for 2a. Purification on silica gel
eluting with toluene then toluene/EtOAc 19:1 and recrystallization
(CH2Cl2/hexane) afforded white crystals (1.60 g, 73%): mp 121−123
°C; Rf 0.29 (toluene); [α]D30 +41.0 (c 1.1, CHCl3); 1H NMR δ 0.25−
1.40 (br m, 3H), 2.34 (s, 3H), 3.31 (s, 3H), 3.39 (s, 3H), 3.57 (d, J =
12 Hz, 3H), 6.06 (s, 1H), 6.19 (s, 1H), 7.12 (m, 1H), 7.19−7.37 (m,
5H), 7.47 (m, 1H), 7.55 (m, 1H), 8.16 (m, 1H); 13C NMR δ 22.1,
53.6 (d, J = 2 Hz), 54.7, 54.8, 103.3, 103.8, 114.2 (d, J = 3 Hz), 126.7−
133.9 (m), 139.4 (d, J = 7 Hz), 139.5, 157.4, 157.5; 31P NMR δ +107.7
(br m); MS (ESI) m/z 379.2 (100) [M+ − H]; HRMS (ESI) calcd for
C22H25BO3P [M+ − H] 379.1634, found 379.1625.
Methyl (RP)-(2′-Methoxybiphenyl-2-yl)(phenyl)phosphinite
P-Borane ((RP)-2b). From (SP)-1b (2.11 g, 4.50 mmol) following
the procedure as for 2a. Purification on silica gel eluting with toluene
(Rf 0.49) and then toluene/EtOAc 19:1 and recrystallization (MeOH/
hexane) afforded white crystals (1.25 g, 83%): mp 80−82 °C; [α]25
D
1
−2.2 (c 1.4, CHCl3); H NMR δ 0.30−1.50 (br m, 3H), 3.34 (s,
1.5H), 3.39 (s, 1.5H), 3.55 (d, J = 12 Hz, 1.5H), 3.57 (d, J = 12 Hz,
1.5H), 6.54 (m, 1H), 6.68−6.87 (m, 2H), 7.13−7.38 (m, 7H), 7.44−
7.56 (m, 2H), 8.03−8.19 (m, 1H); 13C NMR δ 53.4 (d, J = 2 Hz), 53.7
(d, J = 2 Hz), 54.5, 54.6, 109.3, 109.8, 118.9, 119.2, 126.8−134.0 (m),
142.6 (d, J = 9 Hz), 142.9 (d, J = 5 Hz), 156.2, 156.4; 31P NMR δ
+109.1 (br m); MS (ESI) m/z 335.1 (100) [M+ − H]; HRMS (ESI)
calcd for C20H21BO2P [M+ − H] 335.1372, found 335.1377.
Methyl (RP)-(2′,6′-Dimethoxybiphenyl-2-yl)(phenyl)-
phosphinite P-Borane ((RP)-2c). From (SP)-1c (8.00 g, 16.0
mmol) following the procedure as for 2a. Purification on silica gel
eluting with toluene and then toluene/EtOAc (19:1) and recrystalliza-
tion (CH2Cl2/hexane) afforded 2c as white crystals (4.63 g, 79%).
Further elution with toluene/EtOAc 4:1 and recrystallization
Methyl (RP)-(2′,6′-Diisopropoxybiphenyl-2-yl)(phenyl)-
phosphinite P-Borane ((RP)-2f). From (SP)-1f (1.97 g, 3.55
E
dx.doi.org/10.1021/jo400565b | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
mmol) following the procedure as for 2a. Purification on silica gel
eluting with toluene and then toluene/EtOAc 19:1 afforded 2f as white
crystals (0.51 g, 40%). Further elution with toluene/EtOAc 4:1 then
EtOAc afforded (−)-(2′,6′-diisopropoxybiphenyl-2-yl)(phenyl)-
phosphine P-oxide as white crystals (0.62 g, 45%).
0.30−1.50 (br m, 3H), 1.55 (d, J = 10 Hz, 3H), 3.19 (s, 3H), 3.56 (s,
3H), 3.83 (s, 3H), 5.83 (d, J = 2 Hz, 1H), 6.06 (d, J = 2 Hz, 1H), 7.07
(m, 1H), 7.22−7.51 (m, 8H) 8.08 (m, 1H); 13C NMR δ 10.5 (d, J =
41 Hz), 54.7, 55.1, 55.3, 89.6, 89.7, 110.4 (d, J = 3 Hz), 127.0−134.8
(m), 139.4 (d, J = 3 Hz), 158.3, 158.3, 161.5; 31P NMR δ +11.2 (br
m); MS (ESI) m/z 379.2 (100) [M+ − H]; HRMS (ESI) calcd for
C22H25BO3P [M+ − H] 379.1634, found 379.1628.
(SP)-(2′,6′-Dimethoxy-4′-methylbiphenyl-2-yl)(methyl)-
(phenyl)phosphine P-Borane ((SP)-3e). From (RP)-2e (0.71 g, 1.87
mmol) following the procedure as for 3b. Purification on silica gel
eluting with toluene and then toluene/EtOAc 19:1 afforded white
(RP)-2f: mp 84−86 °C; Rf 0.61 (toluene); [α]30 +17.1 (c 1.1,
D
CHCl3); 1H NMR δ 0.25−1.40 (m, 3H), 0.99 (d, J = 6 Hz, 3H), 1.01
(d, J = 6 Hz, 3H), 1.03 (d, J = 6 Hz, 3H), 1.10 (d, J = 6 Hz, 3H), 3.48
(d, J = 12 Hz, 3H), 4.17 (sep, J = 6 Hz, 1H), 4.30 (sep, J = 6 Hz, 1H),
6.30 (d, J = 8 Hz, 1H), 6.46 (d, J = 8 Hz, 1H), 7.07 (m, 1H), 7.13 (m,
1H), 7.21−7.28 (m, 2H), 7.31−7.40 (m, 2H), 7.43−7.51 (m, 3H),
7.90 (m, 1H); 13C NMR δ = 21.6, 21.9, 22.2, 22.3, 53.8 (d, J = 2 Hz),
69.6, 70.6, 105.4, 105.9, 120.6 (d, J = 3 Hz), 126.2−133.3 (m), 140.3
(d, J = 7 Hz), 156.6, 156.9; 31P NMR δ +109.3 (br m); MS (ESI) m/z
421.2 (100) [M+ − H]; HRMS (ESI) calcd for C25H31BO3P [M+ −
H] 421.2104, found 421.2089.
crystals (0.44 g, 64%): mp 106−109 °C; Rf 0.39 (hexane/EtOAc 4:1);
1
[α]30 +9.9 (c 1.2, CHCl3); H NMR δ 0.30−1.50 (br m, 3H), 1.52
D
(d, J = 10 Hz, 3H), 2.36 (s, 3H), 3.19 (s, 3H), 3.58 (s, 3H), 6.07 (s,
1H), 6.31 (s, 1H), 7.07 (m, 1H), 7.20−7.36 (m, 5H), 7.43 (m, 1H),
7.51 (m, 1H), 8.09 (m, 1H); 13C NMR δ 10.4 (d, J = 41 Hz), 22.2,
54.6, 55.0, 103.6, 103.9, 114.7 (d, J = 3 Hz), 126.9−134.8 (m), 139.5
(d, J = 3 Hz), 140.0, 157.3; 31P NMR δ +11.4 (br m); MS (ESI) m/z
363.2 (100) [M+ − H]; HRMS (ESI) calcd for C22H25BO2P [M+ −
H] 363.1685, found 363.1676.
(−)-(2′,6′-Diisopropoxybiphenyl-2-yl)(phenyl)phosphine P-
Oxide: mp 120−123 °C; Rf 0.58 (EtOAc); [α]25 −15.7 (c 1.1,
D
1
CHCl3); H NMR δ 0.81 (d, J = 6 Hz, 3H), 1.06 (d, J = 6 Hz, 3H),
1.09 (d, J = 6 Hz, 3H), 1.28 (d, J = 6 Hz, 3H), 4.06 (sep, J = 6 Hz,
1H), 4.42 (sep, J = 6 Hz, 1H), 6.34 (d, J = 8 Hz, 1H), 6.58 (d, J = 8
Hz, 1H), 7.12−7.39 (m, 7H), 7.50 (m, 2H), 7.75 (d, JP−H = 507 Hz,
1H), 8.09 (m, 1H); 13C NMR δ 21.4, 21.8, 21.9, 22.0, 69.5, 70.9,
105.5, 106.0, 117.9 (d, J = 6 Hz), 126.7−132.8 (m), 137.9 (d, J = 12
Hz), 155.7, 156.2; 31P NMR δ +19.4 (s); MS (ESI) m/z 395.2 (100)
[M+ + H]; HRMS (ESI) calcd for C24H28O3P [M+ + H] 395.1776,
found 395.1766.
(SP)-(2′,6′-Diisopropoxybiphenyl-2-yl)(methyl)(phenyl)-
phosphine P-Borane ((SP)-3f). From (RP)-2f (0.64 g, 1.52 mmol)
following procedure as for 3b. Purification on silica gel eluting with
toluene/hexane 9:1 then toluene afforded a colorless oil (0.42 g, 68%):
1
Rf 0.6 (hexane/EtOAc 4:1); [α]25 +58.8 (c 1.2, CHCl3); H NMR δ
D
0.40−1.55 (br m, 3H), 0.97 (d, J = 6 Hz, 3H), 1.02 (d, J = 6 Hz, 3H),
1.07 (d, J = 6 Hz, 3H), 1.22 (d, J = 6 Hz, 3H), 1.46 (d, J = 11 Hz, 3H),
4.17 (sep, J = 6 Hz, 1H), 4.40 (sep, J = 6 Hz, 1H), 6.31 (d, J = 8 Hz,
1H), 6.53 (d, J = 8 Hz, 1H), 7.01 (m, 1H), 7.14−7.49 (m, 8H), 7.93
(m, 1H); 13C NMR δ 11.1 (d, J = 40 Hz), 21.5, 21.8, 22.20, 22.22,
69.8, 70.5, 105.76, 105.80, 120.8 (d, J = 3 Hz), 126.6 −134.5 (m),
139.7 (d, J = 2 Hz), 156.6 (J = 11 Hz); 31P NMR δ +12.8 (br m); MS
(ESI) m/z 405.2 (100) [M+ − H]; HRMS (ESI) calcd for
C25H31BO2P [M+ − H] 405.2155, found 405.2157.
(M,SP)-4-Methoxy-9-phenyl-9,10-dihydro-9-phosphaphe-
nanthrene P-Borane ((M,SP)-4c) (Scheme 2, step iv). To a cold
solution (−20 °C) of (SP)-3c (0.10 g, 0.285 mmol) in THF (20 mL)
was added s-BuLi (1.4 M in cyclohexane, 225 μL) or MeLi (1.6 M in
Et2O, 250 μL), and the resulting mixture was allowed to warm to rt
overnight under stirring. Extraction with CH2Cl2/H2O, purification on
silica gel eluting with toluene/hexane 9:1 then toluene followed by
recrystallization (CH2Cl2/hexane) afforded white crystals (74 mg,
81%) possessing the same characteristics as described below.
(SP)-(Biphenyl-2-yl)(methyl)(phenyl)phosphine P-Borane
((SP)-3a). To a cold solution (−20 °C) of (RP)-2a (1.33 g, 4.34
mmol) in THF (15 mL) was added MeLi (1.6 M in Et2O, 4 mL, 1.5
equiv) and the resulting mixture allowed to warm to rt, stirred
overnight, and then quenched with H2O. Extraction with CH2Cl2 and
purification on silica gel eluting with hexane/EtOAc 19:1 and then
hexane/EtOAc 9:1 (Rf 0.40) and recrystallization from hexane/
CH2Cl2 afforded the title compound22 as white crystals (1.02 g, 81%):
mp 120−122 °C; [α]25 +50.7 (c 1.1, CHCl3) ((SP)-enantiomer,8c
D
[α]25 +54.8 (c 0.82, CHCl3); (RP)-enantiomer,8d [α]D −42.1 (c 1,
20
D
CHCl3), 99% ee (HPLC)); 1H NMR δ 0.30−1.45 (br m, 3H), 1.42 (d,
J = 10 Hz, 3H), 6.90 (d, J = 7 Hz, 2H), 7.13 (m, 2H), 7.19−7.40 (m,
7H), 7.48 (m, 2H), 7.98 (m, 1H); 13C NMR δ 11.9 (d, J = 41 Hz),
127.2 −132.3 (m), 134.3 (d, J = 15 Hz), 140.5 (d, J = 3 Hz), 146.9 (d,
J = 4 Hz); 31P NMR δ +13.7 (br m).
(SP)-(2′-Methoxybiphenyl-2-yl)(methyl)(phenyl)phosphine
P-Borane ((SP)-3b). From (RP)-2b (1.30 g, 3.87 mmol) and MeLi
(1.6 M in Et2O, 2.9 mL, 1.2 equiv) at 0 °C. Workup as for 3a and
purification on silica gel eluting with toluene/hexane 4:1 (Rf 0.44) and
then toluene afforded white crystals (0.53 g, 43%): mp 93−96 °C;
[α]30D +34.3 (c 1.3, CHCl3); 1H NMR δ 0.30−1.50 (br m, 3H), 1.47−
1.54 (m, 3H), 3.39 (s, 1.3H), 3.55 (s, 1.7H), 6.56−6.68 (m, 2H), 6.88
(m, 0.5H), 7.00 (m, 0.5H), 7.14−7.55 (m, 9H), 7.89 (m, 0.5H), 8.10
(m, 0.5H); 13C NMR δ 11.0 (d, J = 42 Hz), 12.2 (d, J = 41 Hz), 54.7
(d, J = 9 Hz), 109.7, 110.1, 119.3, 119.5, 127.2−134.4 (m), 143.0 (d, J
= 3 Hz), 143.1 (d, J = 4 Hz), 156.2, 156.5; 31P NMR δ +12.8 (br m);
MS (ESI) m/z 319.1 (100) [M+ − H]; HRMS (ESI) calcd for
C20H21BOP [M+ − H] 319.1423, found 319.1414.
(SP)-(2′,6′-Dimethoxybiphenyl-2-yl)(methyl)(phenyl)-
phosphine P-Borane ((SP)-3c). From (RP)-2c (2.00 g, 5.50 mmol)
following the procedure as for 3b. Purification on silica gel eluting with
hexane/EtOAc (9:1) and then hexane/EtOAc 3:1 (Rf 0.30) afforded a
colorless foam (1.16 g, 60%): [α]25D −1.9 (c 1.2, CHCl3); 1H NMR δ
0.40−1.50 (br m, 3H), 1.52 (d, J = 10 Hz, 3H), 3.18 (s, 3H), 3.57 (s,
3H), 6.25 (dd, J = 8, 1 Hz, 1H), 6.48 (dd, J = 8, 1 Hz, 1H), 7.06−7.10
(m, 1H), 7.19−7.34 (m, 6H), 7.43 (tt, J = 8, 2 Hz, 1H), 7.51 (tt, J = 7,
2 Hz, 1H), 8.11 (ddd, J = 14, 8, 1 Hz, 1H); 31P NMR δ +11.3 (br m).
NMR data were in accordance with those reported in the literature.10b
(SP)-(Methyl)(phenyl)(2′,4′,6′-trimethoxybiphenyl-2-yl)-
phosphine P-Borane ((SP)-3d). From (RP)-2d (1.00 g, 2.52 mmol)
following the procedure as for 3b. Purification on silica gel eluting with
(P,SP)-9-Phenyl-9,10-dihydro-9-phosphaphenanthrene P-
Borane ((P,SP)-4b) (Scheme 2, Step v). To a cold solution (−20
°C) of (RP)-2b (0.56 g, 1.67 mmol) in THF (10 mL) was added MeLi
(1.6 M in Et2O, 4.2 mL), and the resulting mixture was allowed to
warm to rt overnight under stirring. Extraction with CH2Cl2/H2O,
purification on silica gel eluting with toluene/hexane 7:3 and then
toluene, and recrystallization (CH2Cl2/hexane) afforded white crystals
(0.35 g, 73%): mp 204−207 °C; Rf 0.51 (toluene/hexane 4:1); [α]25
D
+78.5 (c 1.0, CHCl3); 1H NMR δ 0.40−1.65 (br m, 3H), 3.31 (dd, J =
16, 8 Hz, 1H), 3.44 (dd, J = 16, 8 Hz, 1H), 7.10−7.35 (m, 8H), 7.45
(m, 1H), 7.65 (m, 1H), 7.75 (d, J = 8 Hz, 1H), 7.91 (m, 1H), 8.00 (m,
1H); 13C NMR δ = 29.3 (d, J = 38 Hz), 123.1−134.6 (m), 139.7; 31
P
NMR δ −1.9 (br m); MS (ESI) m/z 287.1 (100) [M+ − H]; HRMS
(ESI) calcd for C19H17BP [M+ − H] 287.1161, found 287.1158.
(M,SP)-4-Methoxy-9-phenyl-9,10-dihydro-9-phosphaphe-
nanthrene P-Borane ((M,SP)-4c). From (RP)-2c (3.54 g, 9.7 mmol)
following the procedure as for 4b. Purification on silica gel eluting with
toluene/hexane 9:1 (Rf 0.49) and then toluene afforded a white solid:
[α]25 −14.3 (c 1.1, CHCl3); 98% ee by HPLC on a Daicel Chiralsil
D
AD-H column, hexane/2-PrOH 95:5, 1 mL/min, UV detection (λ =
254 nm), tR 9.3 min (SP), 10.8 min (RP). White crystals (2.44 g, 79%)
from CH2Cl2/hexane in enantiopure form: mp 138−140 °C; [α]25
D
−14.6 (c 1.1, CHCl3); >99.9% ee (HPLC); 1H NMR δ 0.40−1.55 (br
m, 3H), 3.28 (m, 2H), 3.85 (s, 3H), 6.72 (d, J = 7 Hz, 1H), 6.88 (d, J
= 8 Hz, 1H), 7.11−7.44 (m, 7H), 7.61 (m, 1H), 8.01 (m, 1H), 8.29
(m, 1H); 13C NMR δ 30.3 (d, J = 38 Hz), 55.7, 111.4 (d, J = 1 Hz),
122.7−133.3 (m), 136.9, 156.8 (d, J = 2 Hz); 31P NMR δ −0.2 (br m);
hexane/EtOAc 9:1 afforded a yellow solid foam (0.777 g, 81%): Rf
1
0.27 (hexane/EtOAc 4:1); [α]25 +8.5 (c 1.1, CHCl3); H NMR δ
D
F
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Featured Article
MS (ESI) m/z 317.1 (100) [M+ − H]; HRMS (ESI) calcd for
Hz, 1H), 3.84 (s, 3H), 6.76 (d, J = 7 Hz, 1H), 6.91 (d, J = 8 Hz, 1H),
7.13−7.61 (m, 8H), 7.96 (m, 1H), 8.23 (m, 1H); 13C NMR δ 34.9 (d,
J = 69 Hz), 55.7, 111.6 (d, J = 2 Hz), 123.3, 123.5−131.7 (m), 137.3
(d, J = 7 Hz), 156.8 (d, J = 3 Hz); 31P NMR δ +23.5 (s); MS (ESI) m/
z 321.1 (100) [M+ + H]; HRMS (ESI) calcd for C20H18O2P 321.1044
[M+ + H], found 321.1050.
C20H19BOP [M+ − H] 317.1267, found 317.1265.
(M,SP)-2,4-Dimethoxy-9-phenyl-9,10-dihydro-9-phospha-
phenanthrene P-Borane ((M,SP)-4d). From (RP)-2d (0.89 g, 2.25
mmol) following the procedure as for 4b. Purification on silica gel
eluting with toluene then toluene/EtOAc 50:1 afforded off-white
crystals (0.08 g, 10%). Further elution with toluene/EtOAc 19:1 and
then 9:1 (Rf 0.38) afforded (SP)-3d (0.67 g, 78%; its characteristics are
as described above). (M,SP)-4d: mp 105−107 °C; [α]25D +34.3 (c 1.0,
CHCl3); 1H NMR δ 0.45−1.60 (br m, 3H), 3.19 (dd, J = 16 and 8 Hz,
1H), 3.29 (dd, J = 16 and 8 Hz, 1H), 3.74 (s, 3H), 3.82 (s, 3H), 6.25
(d, J = 2 Hz, 1H), 6.43 (d, J = 2 Hz, 1H), 7.17−7.40 (m, 6H), 7.57 (m,
1H), 7.97 (m, 1H), 8.22 (m, 1H); 13C NMR δ 30.8 (d, J = 38 Hz),
55.2, 55.7, 98.5 (d, J = 1 Hz), 107.3 (d, J = 6 Hz), 117.0 (d, J = 7 Hz),
123.5−133.2 (m), 137.2, 158.3 (d, J = 2 Hz), 160.0; 31P NMR δ −1.3
(br m); MS (ESI) m/z 347.1 (100) [M+ − H]; HRMS (ESI) calcd for
C21H21BO2P [M+ − H] 347.1372, found 347.1378.
(M,9SP,10S)-4-Methoxy-9-phenyl-10-[(2S)-2-phenyl-2-hy-
droxyethyl]-9,10-dihydro-9-phosphaphenanthrene P-Borane.
To a cold solution (−78 °C) of (SP)-4c (0.66 g, 2.1 mmol) in THF
(20 mL) was added s-BuLi (1.3 M in hexane, 1.6 mL). After the
solution was stirred at −78 °C for 1 h, a solution of (R)-(+)-styrene
oxide (0.13 g, 1.1 mmol) in THF (4 mL) was slowly added, and the
resulting mixture was allowed to warm to rt and stirred for 24 h before
quenching with H2O. Extraction with CH2Cl2/H2O and purification
on silica gel eluting with CH2Cl2/hexane 9:1 then CH2Cl2 afforded the
title compound (0.34 g, 70%): Rf 0.32 (toluene/EtOAc 19:1); [α]25
+41.4 (c 1.2, CHCl3); H NMR δ 0.50−1.60 (br m, 3H), 1.76 (m,
D
1
1H), 1.85 (br s, 1H), 2.33 (m, 1H), 3.23 (m, 1H), 3.82 (s, 3H), 4.90
(m, 1H), 6.51 (d, J = 7 Hz, 1H), 6.82 (d, J = 8 Hz, 1H), 7.03 (m, 1H),
7.08−7.37 (m, 10H), 7.46 (m, 1H), 7.63 (m, 1H), 8.08 (m, 1H), 8.26
(m, 1H); 13C NMR δ 36.4 (d, J = 36 Hz), 38.5 (d, J = 4 Hz), 55.7,
72.9 (d, J = 9 Hz), 111.4, 121.2−131.7 (m), 134.9 (d, J = 16 Hz),
136.7, 137.2 (d, J = 9 Hz), 143.1, 156.9 (d, J = 1 Hz); 31P NMR δ +9.2
(br m); MS (ESI) m/z 437.2 (100) [M+ − H]; HRMS (ESI) calcd for
C28H27BO2P 437.1842 [M+ − H], found 437.1841.
(M,9RP,10S)-4-Methoxy-9-phenyl-10-[(2S)-2-phenyl-2-hy-
droxyethyl]-9,10-dihydro-9-phosphaphenanthrene P-Oxide
(7). A solution of the previous compound (65 mg, 0.15 mmol) in
Et2NH (1.5 mL) was refluxed for 2 h under the inert atmosphere then
allowed to cool to rt and concentrated. Rapid purification of the
concentrated residue on silica gel eluting with toluene/EtOAc 4:1
under the inert atmosphere afforded the free phosphine as pale yellow
oil (64 mg, 0.15 mmol). To this compound in acetone (2 mL) was
added H2O2 (50 wt % in H2O, 50 μL). After stirring at 0 °C for 3 h,
the reaction mixture was partitioned between EtOAc and H2O.
Purification on silica gel eluting with EtOAc and recrystallization (i-
(M,SP)-4-Methoxy-2-methyl-9-phenyl-9,10-dihydro-9-phos-
phaphenanthrene P-Borane ((M,SP)-4e). From (RP)-2e (0.71 g,
1.9 mmol) following the procedure as for 4b. Purification on silica gel
eluting with toluene/hexane 9:1 (Rf 0.53) and then toluene and
recrystallization (CH2Cl2/hexane) afforded white crystals (0.49 g,
1
77%): mp 140−142 °C; [α]25 +10.9 (c 1.1, CHCl3); H NMR δ
D
0.45−1.50 (br m, 3H), 2.25 (s, 3H), 3.24 (m, 2H), 3.82 (s, 3H), 6.54
(s, 1H), 6.68 (s, 1H), 7.16−7.42 (m, 6H), 7.58 (m, 1H), 7.98 (m, 1H),
8.27 (m, 1H); 13C NMR δ 21.3, 30.2 (d, J = 38 Hz), 55.6, 112.4 (d, J =
1 Hz), 120.8−133.1 (m), 137.1, 139.5, 157.3 (d, J = 2 Hz); 31P NMR δ
−0.4 (br m); MS (ESI) m/z 331.1 (100) [M+ − H]; HRMS (ESI)
calcd for C21H21BOP [M+ − H] 331.1423, found 331.1425.
(P,SP)-9-Phenyl-9,10-dihydro-9-phosphaphenanthrene
((P,SP)-5b). A solution of (P,SP)-4b (0.10 g, 0.35 mmol) in Et2NH
(3.5 mL) was refluxed for 2 h. Purification on silica gel eluting with
toluene/hexane 3:2 under an inert atmosphere afforded a pale yellow
oil (0.09 g, 93%): Rf 0.63 (toluene/hexane 1:1); [α]25D −203.0 (c 1.1,
CHCl3); 1H NMR δ 3.07 (dd, J = 15, 10 Hz, 1H), 3.22 (dd, J = 15, 3
Hz, 1H), 6.99−7.18 (m, 8H), 7.28 (m, 1H), 7.45 (m, 1H), 7.55−7.67
(m, 2H), 7.82 (d, J = 8 Hz, 1H); 13C NMR δ 29.5 (d, J = 11 Hz),
125.8−136.6 (m), 139.2; 31P NMR δ −41.7 (s); MS (ESI) m/z 275.2
(100) [M+ + H]; HRMS (ESI) calcd for C19H16P [M+ + H] 275.0990,
found 275.0996.
Pr2O/CH2Cl2) afforded yellowish crystals (65 mg, 99%): mp 179−181
1
°C; Rf 0.60 (EtOAc); [α]25 +94.5 (c 1.0, CHCl3); H NMR δ 2.15
D
(m, 1H), 2.47 (m, 1H), 3.21 (m, 1H), 3.83 (s, 3H), 5.03 (m, 1H), 5.17
(m, 1H), 6.26 (d, J = 8 Hz, 1H), 6.82 (d, J = 8 Hz, 1H), 7.00 (m, 1H),
7.16−7.44 (m, 10H), 7.52 (m, 1H), 7.66 (m, 1H), 8.09−8.21 (m, 2H);
13C NMR δ 39.3 (d, J = 61 Hz), 39.7 (d, J = 10 Hz), 55.7, 71.4 (d, J =
4 Hz), 111.7 (d, J = 1 Hz), 123.0−132.2 (m), 137.0 (d, J = 6 Hz),
137.1 (d, J = 10 Hz), 143.9, 156.8 (d, J = 2 Hz); 31P NMR δ +31.1 (s);
MS (ESI) m/z 441.2 (100) [M+ + H]; HRMS (ESI) calcd for
C28H26O3P 441.1620 [M+ + H], found 441.1613.
(SP)-Spiro[(2,6-dimethoxy-2,5-cyclohexadiene)-1,1′-(3-phe-
nyl-3-phosphindane-P-Borane)] ((SP)-8c). To a cold solution (−20
°C) of (SP)-3c (1.00 g, 2.86 mmol) in THF (15 mL) was added s-BuLi
(1.3 M in cyclohexane/hexane, 2.20 mL). After the solution was
stirred at −30 °C for 1 h, CuCl2 (0.42 g, 3.15 mmol) was added and
the reaction mixture allowed to stir for 2 h at −20 °C. The reaction
mixture was quenched with H2O at −20 °C, brought to rt, and then
diluted with EtOAc, aq NH4OH, and brine. The organic phase was
washed twice with aq NH4OH and once with brine. Purification on
silica gel eluting with toluene/hexane 3:2 containing 1% of Et3N
(M,SP)-4-Methoxy-9-phenyl-9,10-dihydro-9-phosphaphe-
nanthrene ((M,SP)-5c). From (M,SP)-4c (0.34 g, 1.10 mmol)
following the procedure as for 5b. Purification on silica gel eluting
with toluene afforded a pale yellow oil (0.32 g, 99%): Rf 0.66 (toluene/
1
hexane 4:1); [α]30 −244.0 (c 1.3, CHCl3); H NMR δ 2.95 (dd, J =
D
15, 9 Hz, 1H), 3.21 (dd, J = 15, 4 Hz, 1H), 3.77 (s, 3H), 6.68 (d, J = 7
Hz, 1H), 6.76 (d, J = 8 Hz, 1H), 7.03 (m, 1H), 7.09−7.19 (m, 5H),
7.26 (m, 1H), 7.44 (m, 1H), 7.61 (m, 1H), 8.20 (d, J = 8 Hz, 1H); 13C
NMR δ 30.9 (d, J = 11 Hz), 55.8, 110.5, 122.2−136.5 (m), 156.7 (d, J
= 4 Hz); 31P NMR δ −39.9 (s); MS (ESI) m/z 305.1 (100) [M+ + H];
HRMS (ESI) calcd for C20H18OP [M+ + H] 305.1095, found
305.1102.
(M,SP)-4-Methoxy-2-methyl-9-phenyl-9,10-dihydro-9-phos-
phaphenanthrene ((M,SP)-5e). From (M,SP)-4e (0.19 g, 0.58
mmol) following the procedure as for 5b. Purification on silica gel
eluting with toluene afforded a pale yellow oil (0.18 g, 99%): Rf 0.68
(toluene/hexane 4:1); [α]30D −176.1 (c 1.7, CHCl3); 1H NMR δ 2.22
(s, 3H), 2.90 (dd, J = 15, 9 Hz, 1H), 3.18 (dd, J = 15, 3 Hz, 1H), 3.74
(s, 3H), 6.52 (s, 1H), 6.58 (s, 1H), 7.10−7.24 (m, 6H), 7.40 (dt, J = 8,
2 Hz, 1H), 7.54 (m, 1H), 8.17 (d, J = 8 Hz, 1H); 13C NMR δ 21.3,
30.8 (d, J = 11 Hz), 55.7, 111.4, 121.9−138.3 (m), 156.7 (d, J = 1 Hz);
31P NMR δ −39.3 (s); MS (ESI) m/z 319.1 (100) [M+ + H]; HRMS
afforded a pale yellow oil (0.43 g, 43%): Rf 0.28 (hexane/EtOAc 9:1);
1
[α]25 +69.3 (c 1.2, CHCl3); H NMR δ 0.50−1.70 (br m, 3H), 2.66
D
(dd, J = 15, 12 Hz, 1H), 2.81 (dd, J = 15, 2 Hz, 1H), 2.94 (m, 1H),
3.06 (m, 1H), 3.31 (s, 3H), 3.44 (s, 3H), 4.80 (app t, J = 4 Hz, 1H),
4.87 (app t, J = 4 Hz, 1H), 7.20−7.26 (m, 1H), 7.29−7.47 (m, 6H),
7.69−7.76 (m, 2H); 13C NMR δ 24.2, 34.4 (d, J = 37 Hz), 54.3, 54.6,
56.4 (d, J = 3 Hz), 90.7, 92.1, 124.7 (d, J = 9 Hz), 128.1−133.1 (m),
152.6 (d, J = 14 Hz), 155.0 (d, J = 2 Hz), 155.7 (d, J = 3 Hz); 31P
NMR δ +36.6 (br m); MS (ESI) m/z 349.2 (100) [M+ − H]; HRMS
(ESI) calcd for C21H23BO2P 349.1529 [M+ − H], found 349.1535.
(SP)-Spiro[(2,6-dimethoxy-4-oxo-2,5-cyclohexadiene)-1,1′-
(3-phenyl-3-phosphindane P-borane)] ((SP)-8d). From (SP)-3d
(0.67 g, 1.76 mmol) following the procedure as for 8c. Purification on
silica gel eluting with CH2Cl2 and then hexane/EtOAc (gradient
(ESI) calcd for C21H20OP [M+ + H] 319.1252, found 319.1254.
(M,RP)-4-Methoxy-9-phenyl-9,10-dihydro-9-phosphaphe-
nanthrene P-Oxide ((M,RP)-6c). To a cold solution (0 °C) of (SP)-
5c (94 mg, 0.309 mmol) in acetone (3 mL) was added H2O2 (50 wt %
in H2O, 90 μL) and the mixture stirred for 3 h at 0 °C. Extraction with
EtOAc/H2O and purification on silica gel eluting with EtOAc (Rf
0.36) afforded a white foam (97 mg, 98%): [α]25 +37.5 (c 1.2,
D
CHCl3); 1H NMR δ 3.36 (dd, J = 15, 14 Hz, 1H), 3.60 (dd, J = 21, 15
G
dx.doi.org/10.1021/jo400565b | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
elution from 80:20 to 20:80) and recrystallization (CH2Cl2/EtOAc)
afforded yellow crystals (0.19 g, 30%): mp 188−192 °C; Rf 0.50
(EtOAc); [α]25D +110.5 (c 1.1, CHCl3); 1H NMR δ 0.50−1.70 (br m,
3H), 2.75 (dd, J = 15, 12 Hz, 1H), 2.91 (dd, J = 15, 1.4 Hz, 1H), 3.45
(s, 3H), 3.64 (s, 3H), 5.54 (d, J = 1 Hz, 1H), 5.58 (d, J = 1 Hz, 1H),
7.12 (m, 1H), 7.39−7.60 (m, 6H), 7.69 (m, 2H); 13C NMR δ 34.1 (d,
J = 35 Hz), 55.9, 56.2, 58.0 (d, J = 3 Hz), 99.8, 100.7, 123.9 (d, J = 8
Hz), 128.4−133.6 (m), 147.8 (d, J = 13 Hz), 172.1 (d, J = 2 Hz),
173.3 (d, J = 3 Hz), 187.6; 31P NMR δ +41.8 (br m); MS (ESI) m/z
365.1 (25) [M+ + H]; HRMS (ESI) calcd for C21H23BO3P [M+ + H]
365.1478, found 365.1479.
Angew. Chem., Int. Ed. 2002, 41, 612−614. (c) Harvey, J. S.;
Malcolmson, S. J.; Dunne, K. S.; Meek, S. J.; Thompson, A. L.;
Schrock, R. R.; Hoveyda, A. H.; Gouverneur, V. Angew. Chem., Int. Ed.
2009, 48, 762−766. (d) Yan, Y.; Zhang, X. Tetrahedron: Asymmetry
2006, 47, 1567−1569. (e) Doro, F.; Lutz, M.; Reek, J. N. H.; Spek, A.
L.; van Leeuwen, P. W. N. M. Eur. J. Inorg. Chem. 2008, 1309−1317.
̌
(6) (a) Stephan, M.; Sterk, D.; Mohar, B. Adv. Synth. Catal. 2009,
351, 2779−2786. (b) Zupanci
̌ ̌
c, B.; Mohar, B.; Stephan, M. Org. Lett.
2010, 12, 1296−1299. (c) Zupanci
̌
c,
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B.; Mohar, B.; Stephan, M. Org.
̌
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ASSOCIATED CONTENT
* Supporting Information
(7) (SP,SP)-1,2-Bis[(o-biphenylyl)(phenyl)phosphino]ethane (Cel-
PHOS-P*) was prepared from (RP)-(o-biphenylyl)(methyl)(phenyl)
phosphine P-oxide by sequential addition of n-BuLi, CuCl and CuCl2,
followed by a reduction step. For this, see: Gilheany, D.; Cumming, G.
R.; King, G.; Voegler, M.; Larichev, V. WO 2008117054; CAN
149:426084.
■
S
HPLC chromatograms of 4c. X-ray crystallographic data for 1b,
4c, 7, and 8d (CIF). 1H and 13C NMR spectra. This material is
available free of charge via the Internet at http://pubs.acs.org.
(8) For the preparation of (o-biphenylyl)-P-Eph 1a and (o-
biphenylyl)-P-OMe 2a enantiomers, see: (a) Nettekoven, U.; Kamer,
P. C. J.; van Leeuwen, P. W. N. M.; Widhalm, M.; Spek, A. L.; Lutz, M.
J. Org. Chem. 1999, 64, 3996−4004. (b) Colby, E. A.; Jamison, T. F. J.
Org. Chem. 2003, 68, 156−166. For the preparation of (RP)- or (SP)-
(o-biphenylyl)(methyl)(phenyl)phosphine P-borane (3a) and their
use, see, for example: (c) Tsuruta, H.; Imamoto, T. Synlett 2001, 999−
AUTHOR INFORMATION
Corresponding Author
*E-mail: barbara.mohar@ki.si, mstephan@phosphoenix.com.
■
Present Address
∥(M.S.) PhosPhoenix SARL, 115, rue de l′Abbe
́
Groult, 75015
Paris, France.
́
1002. (d) Bauduin, C.; Moulin, D.; Kaloun, E. B.; Darcel, C.; Juge, S. J.
Org. Chem. 2003, 68, 4293−4301. (e) Grabulosa, A.; Muller, G.;
Notes
́
Ordinas, J. I.; Mezzetti, A.; Maestro, M. A.; Font-Bardia, M.; Solans, X.
The authors declare no competing financial interest.
Organometallics 2005, 24, 4961−4973.
(9) (a) The corresponding 2-bromobiaryls were prepared from o-
bromohalobenzenes either by SNAr using O,O′-doubly stabilized 2,6-
dialkoxyaryllithiums or by Suzuki cross-coupling. (b) OxazaPB ring-
opening with the bulky g-Li reagent gave rise to 1g in low yield (22%)
accompanied by (RP)-trans-(N-methylamino)(phenyl)(1-phenyl-1-
propenyloxy)phosphine P-borane (73%) resulting from a competitive
attack on the ephedrino moiety. Therefore, reactions with 1g were not
pursued further. For reaction of oxazaPB with bulky aryllithiums, see:
ACKNOWLEDGMENTS
■
This work was supported by the Ministry of Higher Education,
Science, and Technology of the Republic of Slovenia (Grant
No. P1-242). We thank Eva Jeretin for assistance.
REFERENCES
■
(1) For recent literature surveys, see: (a) Grabulosa, A. P-Stereogenic
Ligands in Enantioselective Catalysis, 1st ed.; RSC Publishing:
Cambridge, UK, 2011. (b) Phosphorous(III) Ligands in Homogeneous
Catalysis: Design and Synthesis, Kamer, P. C. J., van Leeuwen, P. W. N.
M., Eds.; John Wiley & Sons, Ltd.: West Sussex, UK, 2012. (c)
̌
Stephan, M.; Sterk, D.; Modec, B.; Mohar, B. J. Org. Chem. 2007, 72,
8010−8018. (c) The unsymmetrical h-Li led to a 1:1 atropo-
diastereomeric mixture 1h.
(10) (a) A patent application was filed for this work: Cusak, A.;
̌
Jeretin, E.; Mohar, B.; Stephan, M. SI23833, 2011. (b) During the
preparation of this manuscript, the following article appeared wherein
compounds 1c, 2c, and 3c were prepared: Grabulosa, A.; Mannu, A.;
Muller, G.; Calvet, T.; Font-Bardia, M. J. Organomet. Chem. 2011, 696,
2338−2345.
Phosphorus Ligands in Asymmetric Catalysis, Borner, A., Ed.; Wiley-
̈
VCH: Weinheim, 2008; Vols. 1−3.
(2) For significant general accesses to P-stereogenic phosphines in
particular, see: (a) Imamoto, T.; Oshiki, T.; Onozawa, T.; Kusumoto,
T.; Sato, K. J. Am. Chem. Soc. 1990, 112, 5244−5252. (b) Juge,
́
S.;
(11) 1H and 13C NMRs showed rotational isomers for (SP)-1b but its
X-ray structure analysis revealed only P-atropisomery (or Sa). “P” here
denotes the stereodescriptor “plus”.
Stephan, M.; Laffitte, J. A.; Genet, J.-P. Tetrahedron Lett. 1990, 31,
̂
6357−6360. (c) Muci, A. R.; Campos, K. R.; Evans, D. A. J. Am. Chem.
Soc. 1995, 117, 9075−9076. (d) Ohashi, A.; Kikuchi, S.; Yasutake, M.;
Imamoto, T. Eur. J. Org. Chem. 2002, 15, 2535−2546. (e) Stephan, M.;
Modec, B.; Mohar, B. Tetrahedron Lett. 2011, 52, 1086−1089. For
enantioselective cyclization to 5-membered cyclic phosphines, see:
(f) Brunker, T. J.; Anderson, B. J.; Blank, N. F.; Glueck, D. S.;
Rheingold, A. L. Org. Lett. 2007, 9, 1109−1112.
(12) (a) The P-stereochemistry was assigned according to the
general stereochemical course of the Juge−
́
Stephan route,2b,e X-ray
structure analyses of (SP)-3a (derived from (−)-ephedrine),8e and 4c
(this work). (b) Ee’s of 2a8a and 3a8d were determined by chiral
HPLC.
(13) Partial P-OMe hydrolysis arose following an unoptimized
workup procedure. For example, (−)-(2′,6′-dimethoxybiphenyl-2-yl)
(hydroxy)(phenyl)phosphine P-borane (6%) and (−)-(2′,6′-dime-
thoxybiphenyl-2-yl)(phenyl)phosphine P-oxide (10%) ensuing from
its slow BH3 loss were formed with compound 2c. (−)-(Hydroxy)
(phenyl)(2′,4′,6′-trimethoxybiphenyl-2-yl)phosphine P-borane (10%)
formed with 2d. (−)-(2′,6′-Diisopropoxybiphenyl-2-yl)(phenyl)phos-
phine P-oxide (45%) formed with 2f.
(3) For selected compilation of phosphacyclic ligands’ application
(ligands’ acronyms: DiSquareP*, R-FerroTANE, R-CnrPHOS,
TangPhos, DuanPhos, ZhangPhos, R-DuPHOS, R-BPE, RoPHOS,
BASPHOS, R-BeePHOS, BINAPHANE, BINEPINEs, BINAPINE,
SITCPs, etc.) in asymmetric transformations, see the Supporting
Information and: (a) Reference 1. (b) Tang, W.; Zhang, X. Chem. Rev.
2003, 103, 3029−3069. (c) Handbook of Homogeneous Hydrogenation;
de Vries, J. G., Elsevier, C. J., Eds.; Wiley-VCH: Weinheim, 2006; Vols.
1−3.
(14) (a) 1H and 13C NMRs showed a single atropisomer for 4, 5,
and 6. (b) Ee (>99.9%) of 4c was determined by chiral HPLC.
(15) (a) P-α-Alkylation at the bridge-junction occurred with high
trans-stereoselectivity, and the results of an ongoing broader study will
be presented elsewhere. (b) Due to CIP stereochemistry rules, (R)-
styrene oxide ring-opening at the terminal position leads in this case to
reversal of configuration at the resulting Cα-OH.
(4) (a) Holz, J.; Genson, M.-N.; Zayas, O.; Borner, A. Curr. Org.
̈
Chem. 2007, 11, 61−106. (b) Erre, G.; Enthaler, S.; Junge, K.; Gladiali,
S.; Beller, M. Coord. Chem. Rev. 2008, 252, 471−491.
(5) For selected recent works on nonracemic phosphorinanes, see:
(a) Kobayashi, S.; Shiraishi, N.; Lam, W.; Manabe, K. Tetrahedron Lett.
2001, 42, 7303−7306. (b) Ostermeier, M.; Prieβ, J.; Helmchen, G.
H
dx.doi.org/10.1021/jo400565b | J. Org. Chem. XXXX, XXX, XXX−XXX

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(16) Phosphine-P-borane deprotection with Et2NH or phosphine P-
oxidation with H2O2 proceeds with retention of P-stereochemistry.2a
Because of CIP stereochemistry rules, the switch from “BH3” (small)
to ”O” (big) reverses the P-configuration.
(17) (a) On this basis, only compounds 4b and 5b of the prepared
phosphacyclic series would have P-atropisomery (CIP rules). (b) The
biaryl dihedral angles found in (M,SP)-4c are 33.6 (1)° and 34.8(1)°
and in (M,9RP,10S)-7 is 33.52(8)°.
(18) No cyclization took place when (SP)-3c was left for 24 h in
presence of anhydrous CuCl2 in THF at rt.
(19) For N-Me-N-Bn-anilines, a 5-exo-trig radical carbocyclization
followed by a ring-strain transposition to a 6-membered ring has been
proposed. For this, see: Roman, D. S.; Takahashi, Y.; Charette, A. B.
Org. Lett. 2011, 13, 3242−3245.
(20) Cheng, X.; Zhu, S.-F.; Qiao, X.-C.; Yan, P.-C.; Zhou, Q.-L.
Tetrahedron 2006, 62, 8077−8082.
(21) Becht, J.-M.; Ngouela, S.; Wagner, A.; Mioskowski, C.
Tetrahedron 2004, 60, 6853−6857.
(22) The X-ray crystal-structure of (SP)-3a has been determined. For
this, see ref 8e.
I
dx.doi.org/10.1021/jo400565b | J. Org. Chem. XXXX, XXX, XXX−XXX