Addition of optically pure H-phosphinate to ketones: Selectivity, stereochemistry and mechanism

Article abstract of DOI:10.1039/c4ob01574f

Aromatic methyl ketones and cyclic asymmetric ketones underwent hydrophosphorylation with P-stereogenic H-P species in the presence of potassium carbonate to produce P,C-stereogenic tertiary α-hydroxyl phosphinates in excellent yields with up to 99 : 1 dr

Full text of DOI:10.1039/c4ob01574f

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: C. Zhao, Y. Sun,
N. Xin, Z. Xu, L. Liu, F. Meng, H. Zhang, B. Fu, Q. Liang, H. Zheng, L. Sun and L. Han, Org. Biomol. Chem.,
2014, DOI: 10.1039/C4OB01574F.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/obc

Organic & Biomolecular Chemistry
Page 1 ofJ8ournal Name
Dynamic Article Links ►
View Article Online
Cite this: DOI: 10.1039/c0xx00000x
www.rsc.org/xxxxxx
ARTDICOI: L10.1E039/TC4YOBP015E74F
Addition of Optically Pure H-Phosphinate to Ketones: the Selectivity,
Stereochemistry and Mechanism
Yong-Ming Suna, Nana Xina, Zhong-Yuan Xua, Li-Juan Liua, Fan-Jie Menga, He Zhanga, Bao-Ci Fua,
Qiu-Ju Lianga, Hong-Xing Zhenga, Li-Jun Suna, Chang-Qiu Zhao*a and Li-Biao Hanb
5
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
Aromatic methyl ketones and cyclic asymmetric ketones underwent hydrophosphorylation with P-
stereogenic H-P species in the presence of potassium carbonate to produce P,C-stereogenic tertiary α-
hydroxyl phosphinates in excellent yields and up to 99:1 dr. The diastereoselectivity was induced by
10 reversible conversion of less stable stereomer of product to more stable one via an equilibrium, which was
confirmed by aldehyde/ketone exchanging reaction. As attacking reagents to the exchanging, aliphatic or
aldehyde carbonyl showed more active than aromatic or ketone ones, respectively. The stabilities
difference between two diastereomers was controlled by the sizes of substituents linking to phosphorus or
α-carbon.
carbon and phosphorus chiral centers. The reported asymmetric
Pudovik reactions are usually committed the formation of C-
stereogenic α-hydroxyl phosphorus compounds via addition of
50 non-chiral P-H species to pre-chiral aldehydes. Addition of
phosphorus reagents that contained two or three chiral alkoxyl or
amino groups to aldehydes also afforded C-stereogenic α-
hydroxyl phosphorus compounds.[17b] The early synthesis of P- or
P,C-stereogenic these compounds via Pudovik reactions either
55 employed unseparated chiral P-H starting materials or affoded
diastereomeric mixtures of products. Owing to poor induction
effect of P-stereogenic centre to the formation of chiral
carbon,[9b,17] the simultaneous formations of carbon and
phosphorus chiral centers in excellent stereoselectivity are quite
60 limited. Zhao and co-workers prepared P,C-stereogenic α-
hydroxyl phosphinates,[14b] as a diastereomeric mixture derived
from R/S configuration on phosphorus. Recently, Montchamp’s
group reported the preparation of P,C-stereogenic α-hydroxyl
phosphinates in 94% de by means of Wittig rearrangement.[18]
15 Introduction
Because of potential applications as biological active substances[1]
and precursors of ligands for asymmetric catalysis,[2] the optically
active phosphorus compounds attracted extensive attention in
recent years. For example, α-hydroxyl phosphonic acid
20 derivatives have been used as the inhibitors of HIV protease,
polymerase,[3] and renin,[4] also these compounds have been
found to show anti-virus and anti-cancer activities.[5] The
optically enriched these compounds are mainly obtained through
enzymatic methods,[6] such as kinetic resolution of racemic
25 mixture by bacteria, fungi, or lapses,[7] or through asymmetric
reduction of α-keto phosphonate with baker’s yeast, fungi or
other catalysts.[6,8,9]
Another available chemical method[10] include asymmetric
oxidation of benzyl phosphonates.[11] The addition of P-H species
30 to carbon oxygen double bonds, known as Pudovik reaction,[12] is
frequently used for the formation of α-hydroxyl phosphorus
compounds, and the relevant asymmetric approaches are also
developed by several research groups. These reported methods
either use special reagents that are difficult to handle, or have
35 very limited substrate scope. Most catalyzed methods employ
asymmetric catalysts that involved in heavy metal or difficultly
accessible ligands.[13] Furthermore, the reported methods are only
suitable for the synthesis of optically active secondary α-hydroxyl
phosphonic acid derivatives. Acquirement of tertiary these
40 compounds in high stereoselectivity is still a challenging task for
organic chemists.[13a,14]
65
Thermodynamic-controlled reactions are frequently applied for
asymmetric synthesis to selectively obtain stable enantiomers. If
a chemical equilibrium between two stereomers can be readily
established, the less stable stereomer will be converted to the
more stable one, thereafter the latter was afforded in high
70 stereoselectivity. However, the stereoselective acquirement of
phosphorus-containing compounds utilizing stability-difference
of products was rather rare[19]
.
The importance of P-stereogenic compounds[9,20] and the
deficiency of satisfied method for acquiring them encourage us to
75 investigate the asymmetric Pudovik reaction employing P-
stereogenic RP-(L)-menthyl phenylphosphinate 1a.[15c,21] On the
basis of a reversible equilibrium,[19] the addition of P-H species to
aldehydes or ketones afford adducts in two diastereomers that
showed different thermodynamic stabilities and could be
P-stereogenic P-H species have attracted growing attention
because of their applications in construction of asymmetric P-C
bonds.[15] Theoretically, when these species are used in Pudovik
45 reaction, cleavage of P-H bond and formation of P-C bond were
involved,[16] and four stereomers were probably formed due to
This journal is © The Royal Society of Chemistry [year]
[journal], [year], [vol], 00–00 | 1

Organic & Biomolecular Chemistry
Page 2 of 8
converted. The reaction of 1a with aliphatic or aromatic ketones
was undertaken in the presence of potassium carbonate, affording
SPRC-stereomers of tertiary α-hydroxyl phosphinates
solution (entries 7-8). In the case of m-nitroacetophenone 2g, 3g’
was formed as major diastereomer, exhibited reversing drC to
View Article Online
DOI: 10.1039/C4OB01574F
other aromatic ketones.
predominantly, in moderate to excellent yields. The
aldehydes/ketones exchanging for α-hydroxyl phosphinates, as
well as their affinities to phosphorus, was explored. The
interactions between various substituents linking to phosphorus
or α-carbon of adducts, such as alkoxyl, aryl or methyl, were also
examined.
60
5
Table 1. Hydrophosphorylation of 2b with 1a under various reaction
conditions.
10 Results and Discussion
1. Hydrophosphorylation of ketones with 1a.
entry
1
solvent
No
Base/(mol%)time/h yield % 3b/3b’[a]
Under neat condition, the hydrophosphorylation of aldehydes
with 1a afforded secondary α-hyderoxyphosphinate in high yield
but poor diastereoselectivity.[16b,22] Similar reaction of ketones 2
15 occurred sluggishly without catalyst. In the presence of potassium
carbonate, p-bromoacetophenone 2b reacted to 1a at room
temperature affording α-hydroxyl phosphinate 3b in high yield.
To our surprise, besides the stereochemistry at phosphorus kept
integral just as the reaction of aldehydes,[20,22] α-chiral carbon was
20 generated in some diastereoselectivity. For example, in DMF,
3b/3b’ were formed in 92% yield and 90:10 ratio (entry 2 of
Table 1). The two diastereomers 3b/3b’ were confirmed to have
SPRC and SPSC structures, respectively (vide infra). The
consequence encouraged us to further optimize the reaction
25 conditions, and the results were summarized in Table 1.
The solvents had significant influence on the yield and drC
(diastereomeric ratio on carbon, assigned as 3b:3b’). When
K2CO3 was used as catalyst, DMF and DMSO gave better yields
and drC than other solvents such as NMP, pyridine, acetonitrile
30 and THF (entries1-9, 13). In DMSO, 3b was afforded in 97%
yield and 98:2 drC. The mixed solvents containing DMSO also
improved the reaction results (entries 10 and 11). Base was
essential to the reaction. However, increasing amount of K2CO3
resulted in side reaction to afford O-phosphorylated product 4b
35 via Phospha-Brook rearrangement (entries 14 and 15).[20,23] At
elevated temperature, formation of 4b became significantly and
yield of 3b became poor (entry 17). When the reaction was
carried out under air, yield and drC of 4b wasn’t decreased
obviously (entry 16).
No
50
48
24
26
22
26
22
24
16
24
22
24
24
24
24
12
24
24
24
24
4
2
DMF
92 (90:10)
8 (44:56)
61 (44:56)
4 (40:60)
27 (43:57)
31 (52:48)
30 (60:40)[b]
16 (37:63)
85 (77:23)
88 (97:3)
NR
3
NMP
25
4
NMP
100
25
5
CH3CN
CH3CN
THF
6
100
25
7
8
THF
25
9
pyridine
pyridine/DMSO
DMF/DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
25
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
25
No
25
97 (98:2)
90 (97:3)
88 (98:2)
93 (97:3)[c]
55 (94:6)[d]
94 (95:5)[e]
99 (83:17)[f]
52 (49:51)
NR
50
100
25
25
25
40
Pyridine and calcium hydroxide also promoted the addition,
giving unsatisfied drC in DMSO. Other bases including sodium
bicarbonate, triethylamine didn’t show catalysis activities (entries
21-22). The stronger bases such as KOH or tetrabutylammonium
hydroxide resulted in predominately formation of 4b (entries 23-
25
Ca(OH)2/25 48
Et3N/100 24
NaHCO3/100 24
KOH/50 36
45 24).
The additions of 1a to various ketones 2 were examined. In
NR
Table 2, stereospecifically P-retention adduct 3 were obtained in
more than 99:1 drP. Most aryl methyl ketones having either
electron withdrawing or donating groups at para-position, gave
50 excellent yield and drC of 3. The results of p-fluoroacetophenone
2d were slight lower than others, affording 3d in 87% and 84:16
drC (entry 4). o-Chloroacetophenone formed 3 only in a trace
amount. At elevated temperature, O-phosphorylated product 4
was obtained as major product (entry 5). m-Bromoacetophenone
55 afforded 3e/3e’ in poor drC (entry 6). For nitro-substituted
acetophenones, drC can be improved significantly in concentrated
90 (45:55)[g]
Bu4NOH/25 13 98[g,h] (10:10:42:38)
[a] Typical procedure: 0.36 mmol 1a and 0.36 mmol 5b were stirred in 1
65 ml DMSO in the presence of base at room temperature. [b] To run the
reaction at 65oC. [c] To run the reaction under air. [d] To run the reaction
at 55oC. [e] To run the reaction in DMSO (2 ml). [f] To run the reaction in
DMSO (0.5 ml). [g] Two stereomers of 4b were formed, whose structures
weren’t confirmed. [h] 1a was partly epimerized to 1a/1a’ that afforded
70 four stereomers of 4b via reaction with 2b.
2
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 3 of 8
Organic & Biomolecular Chemistry
Some electron donating groups linking to acetophenones
15 resulted in formation of 3 took longer time, but inVigeowoAdrticdlerCO.nlpin-e
Table 2. Hydrophosphorylation of ketones with 1a.
DOI: 10.1039/C4OB01574F
entry
R1-CO-R2, 2
Ph, Me, 2a
time /h yield % drC (3/3’)[a]
Hydroxyacetophenone cannot afford
3 even at elevated
temperature or in the presence of stronger base such as KOH
(entry 12). In entry 13, m-aminoacetophenone 2k afforded 3k in
quite poor yield and drC. Under typical condition, trifluoro
20 acetophenone 2l afforded 4l predominantly. In the absence of
base, 3l/3l’ was obtained in 97% yield and 36:64 drC (entry 14).
Other aromatic ketones including α-tetralone, 2-acetyl furans, 1-
acetylnaphthalene, acetylferrocene and 1,1’-diacetylferrocene, as
seen in entries 15-19, gave poor results for formation of 3.
1
40
24
68
54
24
60
40
72
90
96
88
72
24
76
48
107
48
24
40
24
44
24
96
65
24
100
16
24
3a, 75 (90:10)
3b, 97 (98:2)
3c, 90 (99:1)
3d, 87 (84:16)
Trace[b]
2
p-BrC6H4, Me, 2b
p-ClC6H4, Me, 2c
p-FC6H4, Me, 2d
o-ClC6H4, Me
3
4
5
25
Some aliphatic ketones also showed excellent activities to the
reaction. As expected, symmetric ketones gave only one
diastereomer because no chiral carbon was generated (entries 20
to 23). The addition of 1a to acyclic asymmetric ketones showed
weak selectivity (entries 24 and 26). For cyclic asymmetric
6
m-BrC6H4, Me, 2e
p-NO2C6H4, Me, 2f
m-NO2C6H4, Me, 2g
p-CH3C6H4, Me, 2h
p-CH3OC6H4, Me, 2i
p-PhC6H4, Me, 2j
p-HOC6H4, Me
m-NH2C6H4, Me, 2k
Ph, CF3, 2l
3e, 70 (67:33)
3f, 48 (94:6)[c]
3g’, 71 (12:88)[c]
3h, 93 (99:1)
3i, 94 (99:1)
3j, 87 (97:3)
NR
7
8
30 ketones, racemic 2-methyl cyclohexanone 2w afforded four
stereomers of 3w in the ratio of 5:50:7:38. Two enantiomers of
2w reacted to 1a respectively, forming two pairs of diastereomers,
either in more than 20:80 drC (entry 27). More bulky 2-
cyclopentylcyclopentanone 2x cannot react to 1a in the presence
35 of K2CO3. When catalyzed by tBuOK, two stereomers of 3x were
stereospecifically obtained from the two enantiomers of racemic
2x, in 42:58 ratio and 24% yield.
Significant epimerization of 1a to 1a/1a’ wasn’t detected
during the above addition. We believed that 1a was stable toward
40 K2CO3 or KOH in the presence of active ketone. However, when
1a was excess or inactive ketone was used, epimerization of 1a
was observed. As seen in Table 2, low conversion for inactive
ketones always accompanied by poor drC (or increasing formation
of 4), which might be partly ascribed to the epimerization of 1a.
45
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
3k, 35 (63: 37)
3l, 97 (36:64)[d,e]
Trace
α-Tetralone
2-Furyl, Me, 2m
1-Naphyl, Me, 2n
1,1'-Diacetylferrocene, 2o
Acetylferrocene
(CH2)5, 2p
3m, 47 (53:47)[e]
3n, 19 (46:54)[e]
3o, 24 (50:50)[e,f]
Trace
A
3p, 99
(CH2)4, 2q
3q, 98
Me, Me, 2r
3r, 99
Et, Et, 2s
3s, 54
Et, Me, 2t
3t, 98 (27:73)[e]
3u, 83 (68:32)
3v, 54 (51:49)[e]
3w, 90 (5:50:7:38)[e]
3x, 24 (42:58)[e,f]
iBu, Me, 2u
iPr, Me, 2v
2-Me-cyclohexanone, 2w
2-cycloPentyl-cyclopentanone,2x
B
[a] Typical procedure: 0.36 mmol (RP)-1a and 0.36 mmol 2b were stirred
in 1 ml DMSO in the presence of K2CO3 (25 % molar) at rt. Yield and drC
were estimated by 31P-NMR spectroscopy. DrC were assigned as 3/3’
except for unconfirmed stereomers. [b] When the reaction was carried out
at 60oC, only 4 was detected. [c] DMSO was used in 0.5 ml. When 1 ml
of DMSO was used, 3f and 3g’ were formed in 86% (84:16) and 82%
(15:85), respectively. [d] The reaction was carried out in diethyl ether
5
10 without base. Under typical condition, only 4l was formed. [e] The
Figure 1. ORTEP drawing for SPRC-3b (A) and SPSC-3g’ (B).
structures of stereomers weren’t confirmed. [f] tBuOK was used as base
.
The structure of 3 was determined based on crystallography
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 3

Organic & Biomolecular Chemistry
Page 4 of 8
and 31P-NMR spectroscopy. Formation of sole diastereomer from
symmetric ketone and 1a exhibited integral stereochemistry on 55 As leaving moieties, the above orders of carbonyl were reversed.
carbonyl. The orders also indicated their affinities to phosphorus.
View Article Online
DOI: 10.1039/C4OB01574F
Table 3. Ketone or aldehyde exchanging reaction for 3 or 6.
phosphorus, and the SP configuration of 3p[24] indicated P-
retention mechanism. The R configuration on α-carbon was
confirmed by X-ray diffraction of 3b, 3i and 3j (Figure 1). 3g’
was similarly confirmed to have SPSα-C structure (Part B of Figure
1). On 31P-NMR spectroscopy, the peaks of SPRC-3 located at
lower field than SPSC-3’. For asymmetric aliphatic ketones,
except for SPRC-3u (entry 25), the structures of other adducts
5
10 were not confirmed.
entry 3 or 6
aldehyde or base/time(h) Yield % (drP)(drC)[a]
ketone
2. Aldehyde/ketone Exchanging Reaction and Proposed
Mechanism.
1
p-BrC6H4, p-MeOC6H4, Me, K2CO3/48 3i, 13 (>99:1) (>99:1)
In some cases of Table 2, a trace amount of unconsumed 1a was
15 detected during addition to 2, even if excess 2 was used. The
consequence exhibited reversible reaction.[21] For to further
confirm the mechanism, aldehydes or ketones-exchanging
reaction was examined. When 3b was stirred with ketone 2 in the
presence of K2CO3, phosphorus moiety was combined to 2 to
20 form new kind of 3. As seen in entries 1-2 of Table 3, both
aromatic and aliphatic ketones can accept transferring phosphorus
from 3. The ketone-exchanging depended on the structure and
concentration of additional ketone. For example, cyclohexanone
2p was more active than p-methoxyacetophenone 2i. Two equiv
25 2p formed more exchanged adduct 3p (entries 2-3). The reaction
of a mixture of 3b/3b’ to 2p afforded 3p, which also confirmed
the different configuration on α-carbons of 3b and 3b’.
Exchanging also occurred for aldehydes. RPRC-6a was
obtained from addition of SP-1a’ to benzaldehydes 5a.[22] When
30 reacted with 2p, its R-phosphorus moved to cyclohexanone and
kept retention, affording RP-3p (entry 4). In a similar reaction to
o-anisaldehyde 5b, four peaks from 35.0 to 36.2 ppm were
observed on 31P-NMR spectroscopy, two of the them were
assigned as unconsumed RPRC-6a and its epimerized partner
35 RPSC-6a, and the two others, in 29% yield and 24:76 ratio, were
assigned as newly formed RPRC-6b and RPSC-6b via aldehyde
exchanging (entry 6). However, as shown in entry 7, aromatic
ketone cannot accept phosphorus from RPRC-6a.
Me, 3b
2i (2 eq)
2
3
3b
(CH2)5, 2p (2 eq) K2CO3/24
3p, 70 (>99:1)
3p, 31 (>99:1)
3b/3b’
2p (1 eq)
K2CO3/24
(59:41)
4
5
6
Ph, H
(CH2)5, 2p (5 eq) K2CO3/48
RP-3p, 15 (<1:99)
RPRC-6a
Ph, H
RPRC-6a
o-MeOC6H4, H, none/24
5b (1 eq)
NR[b]
Ph, H
RPRC-6a
5b (2 eq)
2a (3 eq)
K2CO3/24 RPRC-6b/RPSC-6b, 29
(<1:99)(24:76)
7
8
Ph, H 6a[c]
K2CO3/24
NR
(CH2)5 3p Me, Me, 2r, (2 K2CO3/24
3r, 10 (>99:1)
eq)
9
(CH2)5 3p
2r, (2 eq)
5b (2 eq)
5b (2 eq)
KOH/24
K2CO3/24
KOH/13
3r, 13 (>99:1)
4ald (trace)
4ald, 91
10 (CH2)5 3p
11 (CH2)5 3p
60 [a] Typical procedure: the mixture of optically pure 3b and 2i was stirred
in DMSO in the presence of K2CO3 (25% mol) for 48 h at room
temperature. The yield, drP (in first parentheses, the ratio of SP/RP) and drC
(in second parentheses, if applicable, the ratio of RC/SC) were estimated by
31P-NMR spectroscopy. [b] The two reactants were heated in neat state at
65 80oC. [c] The mixture of four stereomers was used.
Catalyzed by either K2CO3 or KOH, aliphatic ketones can also
40 be exchanged (entries 8-11). For example, 3p and acetone 2r
afforded 3r in 10-13% yield. However, aromatic aldehydes
difficultly accepted phosphorus combined to aliphatic ketones.
When o-anisaldehyde 5b was stirred with 3p in the presence of
K2CO3, expected 6b wasn’t detected. In the presence of stronger
45 base KOH, O-phosphorylated aldehyde 4ald was obtained,
probably via irreversibly Phospha-Brook rearrangement of 6b
(entries 10- 11 and Scheme 1).
When a mixture of SPSC-6a and RPSC-6c (Ar=p-tolyl) was
stirred in the presence of K2CO3, eight peaks on 31P-NMR
spectroscopy were observed from 34.9 to 36.4 ppm, which
70 indicated facile exchange between aromatic aldehydes. The
phosphorus having RP and SP configuration, respectively, added
to two kinds of aromatic aldehydes, forming two kinds of adducts
6a and 6c, both in four stereomers (Scheme 2).
Scheme 1. Formatio of 4ald in the presence of KOH.
50
These results exhibited aliphatic ketones combined to
phosphorus more firmly than aromatic ketones. As attacking
reagents, aliphatic carbonyl exhibited more active than aromatic
carbonyl, and aldehyde carbonyl more active than ketone
75 Scheme 2. Cross-exchanging reaction of aldehydes between 6a and 6c.
In the absence of base, no exchanging occurred between RPRC-
4
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 5 of 8
Organic & Biomolecular Chemistry
6a and 2b (entry 5), which indicated the addition of 1a to
to phosphorus as electrophilic reagent, meanwhile P-C bond was
aldehydes or ketones was reversible under alkali condition. The
variation of drC over time also confirmed this mechanism. When
the mixture of 3b/3b’, which was isolated from the reaction of 1a
broken and original aldehyde was replaced as leaving group. In a
View Article Online
possible six-member intermediate 9, the crowded groups around
DOI: 10.1039/C4OB01574F
phosphorus resulted in enhanced induction of (-)-menthyl to
5
to 3b for 30 minutes, was stirred with K2CO3 for 1.5 and 5 hours, 45 formation of chiral α-carbon in 6a. To the best of our knowledge,
the initial 59:41 drC was improved to 94:6 and 97:3, respectively.
At the same time, a trace amount of 1a was detected by 31P NMR
spectroscopy. In fact, the reaction of 1a to 2b was completed
within 1 hour, and prolonged reaction time only improved the
although the bimolecular electrophilic substitution (SE2) on
phosphorus hasn’t been reported, it can be explained by
traditional SN2 reaction except the electronic properties for
attacking and accepting roles were reversed. During this process,
10 ratio of 3b/3b’. As seen in Scheme 3, drC of 3b/3b’ was observed 50 the configuration on phosphorus kept retention, which was
in as 60:40, 90:10, and 97:3 when 1a and 3b were stirred for 0.25,
different to SN2 reaction occurred at carbon atom.
10, and 24 hours, respectively.[25]
Scheme 5. Supposed bimolecular electrophilic substitution (SE2)
mechanism for aldehyde-exchanging..
55
3. Diastereoselectivity of the Hydrophosphorylation.
15
Scheme 3. Improvement for drC of 3a/3a’ with reaction time.
The H-phosphinates 1b to 1e containing various alkoxyl groups
were prepared and employed to further explore the selctivity of
hydrophosphorylation (Scheme 6). When 1d was used to react
On the basis of these consequences, we believed the different
thermodynamic stabilities between 3 and 3’. As seen in Scheme 4,
1a was converted to anion 7 by base,[26] which added to
electropositive carbonyl carbon from two sides to afford adducts
60 with 2b under the above optimized condition, two peaks at 39.4
and 39.7 ppm were observed on 31P-NMR spectroscopy. The
former one was confirmed as (l)-3db[27] by X-ray diffraction
results (Figure 2). The ratio of (u/l)-stereomers also was
improved with prolonged time, reaching 28:72 after 72 h. For the
65 reactions of 1b-1e, (l)-stereomers were also dominatly formed,
whose peaks located at upfield on 31P-NMR spectroscopy, and dr
(ratio of u/l) were improved to 30:70-20:80 with time.
20 8 and 8’. Protonation of 8 and 8’ afforded 3 and 3’, respectively.
In the presence of base, more unstable 3’ would have stronger
tendency to become back to 1a and 2 through alkoxyl anion 8’,
which then was further converted to 3 through 8 after enough
time.
The predominantly formation of (l)-stereomers of 3bb-3eb
from 1b-1e, to our surprise, was contrary to the formation of SPRC
70 or (u)-3b in 98:2 drC (Table 2, entry 2). When the mixture of
1a/1a’ reacted to 2b, four stereomers of product gave peaks at
37.8, 38.3, 38.4, and 38.7 ppm on 31P-NMR spectroscopy, in the
ratio of 54:25:1:20. Among those, the ratio of 54:1 for the peaks
at 37.8 and 38.4 ppm, ascribed to 3b/3b’, were quite coherent to
75 98:2 in Table 2. Meanwhile, (SP)-1a’ gave 3b’’/3b’’’ in even
poorer ratio (25:20 or 20:25, did not confirmed) than reactions of
1b-1e.
25
Scheme 4. Supposed reversible mechanism for addition of 1 to ketones 2.
During the exchanging of RPRC-6a with o-aisaldehyde 5b, we
noticed the formation of adduct 6b showed 24:76 drC. As contrast,
30 when 1a and 5b were stirred under similar condition
(K2CO3/DMSO), 6b was formed only in 50:50 drC.[22] In a
separated experiment, the alkoxyl lithium salt of 6d (Ar=p-
chlorophenyl, mixture of two diastereomers) and benzaldehydes
(2 equiv) afforded exchanging product 6a in 73% yield and 29:71
35 drC.
80
The obvious selectivities for formation of 6a and 6b promoted
us to suppose a possible alternative route for the exchanging
reaction. As seen in Scheme 5, except for the above exchanging
via reversible addition, directly substitution of aldehydes from
40 phosphorus might take place. The attacking aldehyde approached
Scheme 6. Additions to 2b by various H-phosphinates 1.
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 5

Organic & Biomolecular Chemistry
Page 6 of 8
View Article Online
DOI: 10.1039/C4OB01574F
Figure 2. ORTEP drawing for (l)-3db.
The time-dependences of dr for reactions of 1a-1e were
presented in Figure 3. In the case of 1b, yield of 3bb became
worse after reached a top, owing to the formation of O-
phosphorylated product 4bb via Phospha-Brook rearrangement,
which lead the calculation of dr was not quite accurate. 1b-1e
showed distinctly reversed selectivity to 1a. It seemed that dr
became worse with increasing volume of alkoxyl. For (SP)-1a’,
Figure 5. Supposed conformation of 3b/3b’ (A) and 3b’’/3b’’’ (B).
The unusual consequences of Figure
3 indicated the
5
20 diastereoselectivities greatly depended on alkoxyl groups of 1. As
shown in Figure 4, intermolecular hydrogen bond between α-
hydroxyl and P=O consisted one-dimensional chain structure of
3b, in which the two oxygen atoms located at against positions of
a cross conformation. Because of the restriction of six-member
25 ring of menthyl, ortho-isopropyl located near to α-carbon of 3. In
the ORTEP drawing for 3b (Part A of Figure 1), benzene ring of
acetophenone moiety faced to the isopropyl with its plane, and
two methyl of isopropyl oriented far to benzene ring. In this
manner, the spatial repulsion between isopropyl to aryl might be
30 weaker than that to methyl (Figure 5).
10 the worst ratio of 3b’’/3b’’’ kept around 50:50, and was not
improved with time.
We supposed approaching of ortho-isopropyl to α-methyl lead
lower stability of 3b’. In the adduct 6 obtained from 1a and
aldehydes, the spatial interaction between isopropyl to α-
hydrogen was not significant, therefore formation of 6 showed
35 poor drC.[22] For 1b-1e, the similar ortho-effect of isopropyl
wasn’t existed. Weakened repulsion between alkoxyl to α-methyl
resulted in (l) or RPRC+SPSC stereomers 3bb-3eb were more
stable. Big alkxoyl such as in 1e, tended to form more (u)-
stereomer and give poor u/l ratio.
40
The even poorer dr for formation of 3b’’/3b’’’ from (SP)-1a’
might also be ascribed to the size of menthoxyl. As shown in Part
B of Figure 5, the long distance between isopropyl to α-aryl or α-
methyl in 3b’’ and 3b’’’ lead weak or negligible interaction
between them. We believed menthoxyl in 1a’ has similar size to
45 phenyl, so that the stabilities difference between 3b’’ and 3b’’’
was insignificant.
Figure 3. Time-dependences of dr for hydrophosphorylation of 2b with
1a-1e.
Aryl groups of 2 also influenced drC of 3/3’. For big aryl, the
planar orientation of benzene ring toward isopropyl might be
hindered. The increased repulsion of isopropyl to aryl lead
50 decreased stability-difference between two diastereomers 3/3’.
For example, meta-substituted acetophenones afforded 3e and 3k,
respectively, in less than 70:30 drC (entries 6 and 13 of Table 2).
ortho-Chloroacetophenone cannot form corresponding C-
phosphorylated product 3 (entry 5 of Table 2). In the reaction of
55 m-nitroacetophenone 2g with 1a, 3g’ even was afforded as major
product, in reversed drC 12:88 (entry 8 of Table 2).
Density functional calculations of 3b/3b’ and 3g/3g’ supported
the above assumption. As shown in Table 4, the single point
energy of 3b was lower than 3b’ by 14.25 kcal/mol, and 3g’ was
60 lower than 3g by 0.15 kcal/mol (for details, please see SI). Theses
results were consistent with the observation of drC for the two
compounds, as shown in Table 2.
15
Figure 4. One-dimensional chain structure of 3b.
6
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 7 of 8
Organic & Biomolecular Chemistry
Table 4. Density functional calculations of 3b/3b’ and 3g/3g’.[a]
Although thermodynamic controlled reactions are widely
applied in asymmetric synthesis, the similar P-involved reversible
equilibrium, to the best of our knowledgeD, OhIa:s1n0’.1t0b3e9e/Cn4rOepBo01rt5e7d4.F
View Article Online
Compounds
ESpRc-opt
ESpSc-opt
ESpRc-opt - ESpSc-opt
(kcal/mol)
55 Our research employed simple catalysts to realize
diastereoselective hydrophosphorylation of ketones and
preparation of P,C-stereogenic α-hydroxyphosphinates. The
consequences of the stereochemistry on both phosphorus and
carbon atoms are hoped to deeply reveal the mechanism of P-
60 involved asymmetric reactions.
3b/3b’ [b]
3g/3g’[b]
-4075.3727 a.u. -4075.3500 a.u.
-1706.0739 a.u. -1706.0742 a.u.
-14.25
0.15
[a] The whole calculations were performed in Gaussian 09 using the
B3LYP density functional. [b] Structures of 3b and 3g’ were referred
from X-ray diffraction results.
5
Notes and references
Additionlly, drC were also influenced by solubility-difference
between two stereomers 3/3’. When the mixture of 3b/3b’ (59:41)
was stirred in DMSO, according the concentration of typical
procedure of Table 2, the ratio of 3b/3b’ was detected as 22:78
10 and 62:38 in solution and unsolvable solid, respectively. These
results indicated 3b’ was more solvable than 3b, and have more
chance being converted back to 1a and 2b. The drC for formations
of 3f/3f’ and 3g/3g’ were obviously improved when reactions
were carried out in concentrated solution (entries 7-8 of Table 2).
15 However, in some cases such as entry 6, 1a and 2e in DMSO
formed a clear solution, 3e/3e’ was generated still in 67:33 drC.
We believed thermodynamic stability took more important role
than solubility to the diastereoselectivity.
a Prof. Dr. C.-Q. Zhao, College of Chemistry and Chemical Engineering,
Liaocheng University, Liaocheng, Shandong 252059, China, Fax:
65 (+86)6358239121, E-mail: literabc@hotmail.com
b National Institute of Advanced Industrial Science and Technology
(AIST), Tsukuba, Ibaraki 305-8565, Japan
† Electronic Supplementary Information (ESI) available: [Experimental
procedures, spectral data for products, and crystallographic information
70 are included]. See DOI: 10.1039/b000000x/
‡ The authors acknowledge the financial support of the Natural Science
Foundation of China (grant no. 20772055).
1
a) L. D. Quin, A Guide to Organophosphorus Chemistry; Wiley-
Interscience: New York, 2000; b) M. Sasaki, In Chirality in
Agrochemicals; N. Kurihara, J. Miyamoto, Eds. Wiley & Sons:
Chichester, 1998, pp 85-139; c) T. Imamoto, In Handbook of
OrganophosphorusChemistry; R. Engel, Eds. Marcel Dekker: New
York, 1992, Chapter 1; d) H. B. Kagan, M. Sasaki, In Chemistry of
Organophosphorus Compounds; F. R. Hartley, Ed. Wiley & Sons:
New York, 1990, Vol. 1, Chapter 3; e) N. V. Dubrovina, A. Börner,
Angew. Chem., Int. Ed. 2004, 43, 5883-5886.
75
80
20 Conclusions
The hydrophosphorylation of ketones 2 with optically pure H-
phosphinate 1a was catalyzed by potassium carbonate, affording
P,C-stereogenic tertiary α-hydroxyphosphinates 3. During the
reaction, the configuration on phosphorus stereospecifically kept
25 retention, and the diastereoselectivities for formation of chiral α-
carbon depended on the structures of ketones 2. Excellent drC and
yields were realized for most aryl methyl ketones and cyclic
asymmetric ketones. Acyclic aliphatic ketones showed weak
selectivities.
Reversible addition and stabilities-differences between two
diastereomers of adducts were contributed to the selectivities.
Aldehydes/ketones exchanging reaction only took place in the
presence of base, which confirmed the reversible mechanism.
During the exchanging, phosphorus was stereospecifically
35 transferred in retention configuration. As attacking reagents,
aliphatic or aldehyde carbonyl was more active than aromatic or
ketone carbonyl. The two diastereomers 3/3’ showed different
stabilities, the more stable stereomer was converted to less stable
one via the reversible addition, so that drC were obviously
40 improved over reaction time.
The thermodynamic stabilities of two diastereomers of adducts
were examined. For most adducts obtained from 1a, SPRC
stereomers were more stable than SPSC ones. For 1b to 1e, (l) or
RPRC+SPSC adducts were stable. Addition by 1a showed excellent
45 drC that was attributed to ortho-isopropyl on menthyl. The
approaching and repulsion between ortho-isopropyl to α-methyl
within 3 resulted in the lower stabilities of SPSC diastereomers.
Alkoxyl in 1b-1e were thought as smaller than phenyl, so that
these compounds exhibited reversed drC to 1a. The worst
50 selectivity for 1a’ was explained by the similar sizes of
menthoxyl to phenyl.
2
a) C. Darcel, J. Uziel and S. Jugé, In Phosphorous Ligands in
Asymmetric Catalysis; A. Börner, Ed. Wiley-VCH: Weinheim, 2008,
Vol. 3, pp 1211-1233; b) P. C. J. Kamer and P. N. M. C. V. Leeuwen,
Phosphours (III) Ligands in Homogeneous Catalysis: Design and
Synthesis, Wiley & Sons: Ltd, 2012; c) T. Nemoto, Chem. Pharm.
Bull. 2008, 56 (9), 1213-1228; d) Y. H. Huang, R. J. Chew, Y. X. Li,
S. A. Puallarkat and P. –H. Leung, Org. Lett. 2011, 13, 5862-5865; e)
B. Zupančič, B. Mohar and M. Stephan, Tetrahedron Lett. 2009, 50,
7382-7384; f) Y.–L. Zhao, G.–J. Wu and F.–S. Han, Chem. Commun.
2012, 48, 5868-5870; g) Z. P. Zeng, Y. Jiang, Y. Liu, G. Tang, P. X.
Xu, Y. F. Zhao and G. M. Blackburn, Org. Biomol. Chem. 2011, 9,
6973-6979.
85
90
30
95
3
a) V. P. Kukhar, H. R. Hudson, et al. Aminophosphonic and
Aminophosphinic acids Chemistry and Biological Activity; Wiley &
Sons: Chichester, U.K., 2000; b) M. Sawa, T. Tsukamoto, T. Kiyoi,
K. Kurokawa, F. Nakajima, Y. Nakada, K. Yokota, Y. Inoue, H.
Kondo and K. Yoshino, J. Med. Chem. 2002, 45, 930-936; c) N. P.
Camp, P. C. D. Hawkins, P. B. Hitchcock and D. Gani, Bioorg. Med.
Chem. Lett. 1992, 2, 1047-1052; d) N. P. Camp, D. A. Perry, D.
Kinchington, P. C. D. Hawkins, P. B. Hitchcock and D. Gani, Bioorg.
Med. Chem. 1995, 3, 297-312; e) D. A. McLeod R. I. Brinkworth, J.
A. Ashley, K. D. Janada and P. Wirsching, Bioorg. Med. Chem. Lett.
1991, 1, 653-658; f) B. Stowasser, K.-H. Budt, J.-Q. Li, A. Peyman
and D. Ruppert, Tetrahedron Lett. 1992, 33, 6625–6628.
100
105
110
115
4
5
a) Dellaria, Jr. J. F., R. G. Maki, H. H. Stein, J. Cohen, D. Whittern,
K. Marsh, D. J. Hoffman, J. J. Plattner and T. J. Perun, J. Med. Chem.
1990, 33, 534-542; b) M. Tao, R. Bihovsky, G. J. Wells and J. P.
Mallamo, J. Med. Chem. 1998, 41, 3912-3916.
a) M. L. Peters, M. Leonard and A. A. Licata, CleV. Clin. J. Med.
2001, 68, 945-951; b) B. Z. Leder and H. M. Kronenberg,
Gastroenterology 2000, 119, 866-869; c) R. Snoeck, A. Holy, C.
Dewolf-Peeters, J. Van Den Oord, E. De Clercq and G. Andrei,
Antimicrob. Agents Chemother. 2002, 46, 3356-3361.
6
For review, see: P. Kafarski and B. J. Lejczak, Mol. Catal. B:
Enzymol. 2004, 29, 99-104.
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 7

Organic & Biomolecular Chemistry
Page 8 of 8
7
a) Y.-F. Li, Tetrahedron: Asymmetry 1993, 4, 109-120; b) M.
18 O. Berger and J.-L. Montchamp, Angew. Chem., Int. Ed. 2013, 52,
11377-11380.
19 a) E. Öhler and E. Zbiral, Liebigs Ann. Chem. 1991, 229-236; b) F. A.
Drescher, Y.-F. Li and F. Hammerschmidt, Tetrahedron 1995, 51,
4933-4946; c) M. Drescher, F. Hammerschmidt and H. Kahling,
Synthesis 1995, 1267- 1272; d) F. Wuggenig and F. Hammerschmidt,
Monatsh. Chem. 1998, 129, 423-436; e) T. Khushi, K. J. O’Toole and
J. T. Sime, Tetrahedron Lett. 1993, 34, 2375-2378.
a) M. Brzezinska-Rodak, E. Zymanczyk-Duda, P. Kafarski and B.
Lejczak, Biotechnol. Prog. 2002, 18, 1287-1291; b) A. Maly, B.
Lejczak and P. Kafarski, Tetrahedron: Asymmetry 2003, 14, 1019-
1024.
a) C. Meier and W. H. G. Laux, Tetrahedron: Asymmetry 1996, 7,
89-94; b) C. Meier and W. H. G. Laux, Tetrahedron: Asymmetry
1995, 6, 1089- 1092; c) C. Meier and W. H. G. Laux, Tetrahedron
1996, 52, 589-598; d) T. Gajda, Tetrahedron: Asymmetry 1994, 5,
1965-1972; e) V. Nesterov and O. I. Kolodyazhnyi, Russ. J. Gen.
Chem. 2005, 75, 1161-1162.
View Article Online
DOI: 10.1039/C4OB01574F
Kortmann, M.-C. Chang, E. Otten, E. P. A. Couzijn, M. Lutz and A. J.
Minnaard, Chem. Sci., 2013, 2014, 5, 1322-1327.
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
20 For selected examples of synthesis chiral phosphine, please see: a) T.
Miura, H. Yamada, S. Kikuchi and T. Imamoto, J. Org. Chem. 2000,
65, 1877–1880; b) J. S. Harvey and V. Gouverneur, Chem. Commun.
2010, 46, 7477–7485; c) J. J. Gammon, P. O’Brien and B. Kelly, Org.
Lett. 2009, 11, 5022–5025; d) J. J. Gammon, V. H. Gessner, G. R.
Barker, J. Granander, A. C. Whitwood, C. Strohmann, P. O’Brien
and B. Kelly, J. Am. Chem. Soc. 2010, 132, 13922–13927; e) D.
Wiktelius, M. J. Johansson, K. Luthman and N. Kann, Org. Lett.
2005, 7, 4991–4994; f) V. S. Chan, M. Chiu, R. G. Bergman and F. D.
Toste, J. Am. Chem. Soc. 2009, 131, 6021–6032; g) K. V. Rajendran,
L. Kennedy and D. G. Gilheany, Eur. J. Org. Chem. 2010, 5642–
5649.
8
9
10 For reviews, see: (a) D. F. Wiemer, Tetrahedron 1997, 53, 16609-
16644. b) H. Gröger and B. Hammer, Chem. Eur. J. 2000, 6, 943-948.
11 a) D. M. Pogatchnik and D. F. Wiemer, Tetrahedron Lett. 1997, 38,
21 H. Zhang, Y.-M. Sun, L. Yao, S.-Y. Ji, C.-Q. Zhao and L.-B. Han,
Chem. Asian J. 2014. 9, 1329-1333.
3495-3498; b) D. M. Cermak, Y. Du and D. F. Wiemer, J. Org. 90 22 TMSCl-promoted addition of diastereomeric mixture 1a/1a’ to
Chem. 1999, 64, 388-393; c) D. Skropeta and R. R. Schmidt,
Tetrahedron: Asymmetry 2003, 14, 265-273.
aldehydes was reported in reference 16b. We have undertaken the
hydrophosphorylation of aldehydes with 1a catalyzed by base, and
the results will be published elsewhere.
12 a) A. N. Pudovik and I. V. Konovalova, Synthesis. 1979, 81-96; b) Q.
M. Wu, J. Zhou, Z. G. Yao, F. Xu and Q. Shen, J. Org. Chem. 2010,
75, 7498-7501; c) J P. A. oshua and Y. Hisashi, J. Am. Chem. Soc.
2008, 130, 10521-10523; d) A. E. Wroblewski and K. B. Balcerzak,
Tetrahedron: Asymmetry 2001, 12, 427-431; e) T. Yokomatsu, T.
Yamagishi and S. Shibuya, Tetrahedron: Asymmetry 1993, 4, 1401-
1404; f) B. J. Rowe and C. D. Spilling, Tetrahedron: Asymmetry
23 a) L. El Kaïm, L. Gaultier, L. Grimaud and A. Dos Santos, Synlett
2005, 2335-2336; b) M. T. Corbett, D. Uraguchi, T. Ooi and J. S.
Johnson, Angew. Chem., Int. Ed. 2012, 51, 4685-4689.
24 B. C. Fu and C.-Q. Zhao, Acta Cryst. 2010. E66, o859.
25 Similar addition of P-stereogenic secondary phosphine oxide to
aldehydes also showed time dependence of dr, it was believed as
reversible, as seen in reference 20.
95
2001, 12, 1701-1708; d) T. Arai, M. Bougauchi, H. Sasai and M. 100
Shibasaki, J. Org. Chem. 1996, 61, 2926-2927.
26 D. Uraguchi, T. Ito and T. Ooi, J. Am. Chem. Soc. 2009, 131, 3836-
3837.
13 For some recent examples of asymmetric synthesis of α-
hydroxyphosphonates, see: a) S. Samanta and C.-G. Zhao, J. Am.
Chem. Soc. 2006, 128, 7442–7443; b) R. Dodda and C.-G. Zhao, Org.
Lett. 2006, 8, 4911–4914; c) J. Liu, Z. Yang, Z. Wang, F. Wang, X. 105
Chen, X. Liu, X. Feng, Z. Su and C. Hu, J. Am. Chem. Soc. 2008,
130, 5654–5655; d) V. D. Pawar, S. Bettigeri, S.-S. Weng, J.-Q. Kao
and C.-T. Chen, J. Am. Chem. Soc. 2006, 128, 6308–6309; e) V. B.
Gondi, K. Hagihara and V. H. Rawal, Angew. Chem., Int. Ed. 2009,
48, 776–779; f) D. M. Pogatchnik and D. F. Wiemer, Tetrahedron
Lett. 1997, 38, 3495–3498; g) D. M. Cermak, Y. Du and D. F.
Wiemer, J. Org. Chem. 1999, 64, 388–393; h) D. Skropeta and R. R.
Schmidt, Tetrahedron: Asymmetry. 2003, 14, 265–273; i) A. E.
Wroblewski and K. B. Balcerzak, Tetrahedron: Asymmetry. 2001, 12,
427–431; j) T. Yokomatsu, T. Yamagishi and S. Shibuya,
Tetrahedron: Asymmetry. 1993, 4, 1401–1404; k) B. J. Rowe and C.
D. Spilling, Tetrahedron: Asymmetry. 2001, 12, 1701–1708; l) T.
Arai, M. Bougauchi, H. Sasai and M. Shibasaki, J. Org. Chem. 1996,
61, 2926–2927; m) H. Sasai, M. Bougauchi, T. Arai and M.
Shibasaki, Tetrahedron Lett. 1997, 38, 2717–2720; n) B. Saito and T.
Katsuki, Angew. Chem. Int. Ed. 2005, 44, 4600–4602; o) M. D.
Groaning, B. J. Rowe and C. D. Spilling, Tetrahedron Lett. 1998, 39,
5485–5488.
27 V. Prelog and D. Seebach, Angew. Chem., Int. Ed. Engl. 1982, 21,
654-660.
14 For examples of the synthesis of racemic tertiary α-hydroxy
phosphonates via allylation, see: (a) D. F. Wiemer and D. Y. Kim,
Tetrahedron Lett. 2003, 44, 2803-2805; b) S. Samanta, S. Perera, and
C.-G. Zhao, J. Org. Chem. 2010, 75, 1101–1106
15 a) L.-B. Han, C.-Q. Zhao, S. Onozawa, M. Goto and M. Tanaka, J.
Am. Chem. Soc. 2002, 124, 3842-3843; b) L.-B. Han and C.-Q. Zhao,
J. Org. Chem. 2005, 70, 10121-10123; c) Q. Xu, C. -Q. Zhao and L.-
B. Han, J. Am. Chem. Soc. 2008, 130, 12648-12655; d) X. H. Zhang,
H. Z. Liu, X. M. Hu, G. Tang, J. Zhu and Y. F. Zhao, Org. Lett. 2011,
13, 3478-3481.
16 a) J. -L. Pirat, M. Jérôme, V. David, J. –N. Volle, T. Monique and H.
–J. Cristau, J. Org. Chem. 2005, 70, 7035-7041; b) J. X. Zhou. Z. H.
Cai, G. F. Zhao and C. C. Tang, Heteroatom Chem. 2003, 14, 312-
315.
17 M. P. Sibi, S. Manyem and J. Zimmerman, Chem. Rev. 2003, 103,
3263-3295; b) O. I. Kolodiazhnyi, Tetrahedron: Asymmetry 1998, 9,
1279–1332; c) O. I. Kolodiazhnyi, Tetrahedron 2003, 59, 5953–6018.
8
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]