Intramolecular cationic cyclization of β-hydroxyalkylphosphine oxides—a route towards the benzophosphorinane core

Article abstract of DOI:10.1016/j.tet.2016.06.070

Intramolecular cationic cyclization of β-hydroxyalkylphosphine oxides in the presence of an acid lead to the formation of fused bicyclic compounds with an incorporated phosphorus atom. Depending on the structure of the starting compound the formation of e

Full text of DOI:10.1016/j.tet.2016.06.070

Accepted Manuscript
Intramolecular cationic cyclization of β-hydroxyalkylphosphine oxides—a route
towards the benzophosphorinane core
Katarzyna Włodarczyk, Marek Stankevič
PII:
S0040-4020(16)30602-0
10.1016/j.tet.2016.06.070
TET 27884
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 22 February 2016
Revised Date: 13 June 2016
Accepted Date: 27 June 2016
Please cite this article as: Włodarczyk K, Stankevič M, Intramolecular cationic cyclization of β-
hydroxyalkylphosphine oxides—a route towards the benzophosphorinane core, Tetrahedron (2016), doi:
10.1016/j.tet.2016.06.070.
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ACCEPTED MANUSCRIPT
Me
Me
Me
Me
O
P
Me
OH
R'
Me
H3PO4
170 oC
H3PO4
170 oC
P
R
P
O
O Me
R = Et, R' = Me
R, R' = Me
54%
74%

ACCEPTED MANUSCRIPT
Intramolecular cationic cyclization of β-hydroxyalkylphosphine oxides – a
route towards the benzophosphorinane core
Katarzyna Włodarczyk[a] and Marek Stankevič[a]*
[a] Department of Organic Chemistry, Faculty of Chemistry, Marie Curie-Sklodowska University,
Gliniana 33, 20-614 Lublin, Poland
* - Corresponding author. Tel.: +48 81 537-77-52; fax: +48 81 524-22-51;
email: marek.stankevic@poczta.umcs.lublin.pl
ABSTRACT
Intramolecular cationic cyclization of β-hydroxyalkylphosphine oxides in the presence of an acid lead
to the formation of fused bicyclic compounds with an incorporated phosphorus atom. Depending on
the structure of the starting compound the formation of either phosphaindane or benzophosphorinane
oxides has been observed. The key difference in the reactivity arises from the substitution pattern at
the carbinolic carbon atom of β-hydroxyalkylphosphine oxide.
KEYWORDS
β-Hydroxyalkylphosphine
oxide,
intramolecular,
cationic
cyclization,
phosphaindane,
benzophosphorinane
1. Introduction
The synthesis of organophosphorus compounds with a phosphorus atom incorporated into the cyclic
structure is always a synthetic challenge1 but, at the same time, these compounds have been found to
exhibit high selectivities as ligands in transition metal catalysis (Figure 1).2
Ph
t-Bu
t-Bu
H
P
H
H
P
P
H
H
P
P
P
H
t-Bu
H
t-Bu
TangPhos
H
Ph
3
2
ZhangPhos
1
t-Bu
t-Bu
H
P
P
P
H
P
t-Bu
H
P
i-Pr
i-Pr
H
P
t-Bu
BeePhos
DuanPhos
6
4
5
Figure 1. Examples of cyclic phosphine ligands
1

ACCEPTED MANUSCRIPT
The synthetic methods leading to cyclic phosphine precursors are mostly based on double
nucleophilic substitution of the phosphine dianion with the appropriate dielectrophile,2c-d,3 double
nucleophilic substitution with RPHal2-type compounds and bis-Grignard reagents,2a,4 McCormack
cyclization,5 ring-closing metathesis6 or intramolecular hydrophosphination.7 The synthesis of cyclic
organophosphorus compounds possessing a fused aromatic ring is much less is developed. Both
DuanPhos 4 and BeePhos 5 ligands were synthesized through double nucleophilic substitution
methodology of phosphine dianion PhP2- with the appropriate electrophile2d,e whereas ligand 6 was
prepared through double nucleophilic substitution at phosphorus using bis-Grignard reagent and
RPHal2-type compound.2f Other methods for the synthesis of these compounds include intramolecular
coupling reaction,8 ring-closing metathesis9 or electrophilic substitution at phosphorus.10 From a
synthetic point of view, the most useful approach is based on intramolecular electrophilic cyclization
of alkenylphosphine derivatives (Scheme 1)11 where the arylphosphine derivatives possessing an
alkenyl substituent undergo protonation upon treatment with a strong acid followed by an
intramolecular reaction of the formed cation with adjacent aryl substituent.
O
P
Polyphosphoric acid
180-200 oC, 4 h
Ph
P
Ph
O
7
8
37%
Scheme 1. Intramolecular cationic cyclization of 7.
This method is operationally simple and could potentially be used in the synthesis of a wide range of
fused organophosphorus ligand systems for use in catalysis. The above reaction must proceed through
the formation of a carbocation which undergoes a cyclization reaction (Scheme 2).
H
O
P
O
P
H+
cyclization
Ph
Ph
P
Ph
O
9
10
7
H+
- H+
1. Base
2. CH3CHO
O
O
OH
P
P
P
Ph
Ph
Ph
O
8
12
11
Scheme 2. Probable cyclization mechanism of 7 and 11.
If this mechanism is true, the carbocation 9 could be more conveniently obtained from the β-
hydroxyalkylphosphine oxide 11 (Scheme 2). A treatment of this molecule with a strong acid should
similarly lead to the cation 9. The oxide 11 is easily available from methylphosphine oxide 12 and
acetaldehyde. Regarding the availability of both carbonyl compounds and methylphosphine oxides it
2

ACCEPTED MANUSCRIPT
is easy to conclude that β-hydroxyalkylphosphine oxides could be regarded as very convenient
substrates for the synthesis of fused systems with incorporated phosphorus atoms. Herein, our results
concerning the use of β-hydroxyalkylphosphine oxides in the cationic cyclization are presented.
2. Results and discussion
The problem of acidic cyclization of β-hydroxyalkylphosphine oxides has never been a subject of a
detailed investigation although some precedent can be found in the literature.12 For test reactions, β-
hydroxyalkylphosphine oxides derived from dimethylphenylphosphine oxide 13 have been chosen
(Scheme 3, Table 1). The choice of 13 has been rationalized by the relatively easy access to the non-
racemic P-stereogenic adduct using sparteine chemistry13 although it should be pointed out that this
approach is effective only with phosphine-boranes and phosphine sulfides.
O
P
O
P
OH
R'
1. n-BuLi (1.0)
2. RCHO or RR'C(O) (1.5)
THF, -78 oC - rt, 110 min
Me
Me
Me
R
13
14-34
Scheme 3. Synthesis of substrates for cyclization
Table 1. Synthesis of substrates for cyclization
Substituents
Entry
Product Yields (%) (dr)
R
R'
1
2
Me
Ph
H
H
86 (53:47)
86 (54.4:45.5)
83 (52.5:47.5)
85 (58:42)
75 (54:46)
97 (53:47)
89
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
3
i-Pr
H
4
t-Bu
Et
H
5
H
6
c-Hex
Me
H
7
Me
Me
Me
Me
Me
Me
Me
Me
Ph
8
n-Bu
n-Pr
Ph
76 (56:44)
85 (52:48)
92 (66.5:33.5)
87 (55.5:44.5)
77 (53.5:46.5)
80 (60:40)
83 (91:9)
84
9
10
11
12
13
14
15
16
i-Pr
Et
t-Bu
t-BuCH2
Ph
n-Bu
n-Bu
82
3

ACCEPTED MANUSCRIPT
17
18
19
20
21
i-Pr
i-Pr
60
75
71
76
90
30
31
32
33
34
Et
Et
-(CH2)4-
-(CH2)5-
-(CH2)6-
A reaction of phosphine oxide 13 with carbonyl compounds in the presence of base afforded the
corresponding products 14-34 with high yields. In the case of aldehydes and unsymmetrical ketones a
mixtures of diastereomers have been obtained (Table 1, Entries 1-6, 8-14) but, generally, the
diastereoselectivity of the addition was low. At this point, the relative configuration of the major
diastereomers was not established.
In order to develop the mildest conditions for the cyclization reaction, an optimization of the
reaction conditions has been undertaken with 20 as the model compound (Scheme 4, Table 2).
O
P
Me
Me
Me
O
P
Me
Me
+
O
P
OH
Conditions
35
36
Me
Me Me
Me
Me
Me
+
20
P
O
20a
Scheme 4. Optimization of the reaction conditions
Table 2. Optimization of the reaction conditions
Entry
Conditions
Products
1
2
3
4
5
6
7
8
9
BF3-OEt2 (1.5), DCE, reflux, 4 h
AcOH, rt, 4 h
35 (20%), 36 (55%)
No reaction
AcOH, reflux, 4 h
No reaction
HBF4 (1.0), DCM, -78-0 oC, 4.5 h
HBF4 (1.0), DCM, rt, 4 h
HBF4 (3.0), DCE, reflux, 4 h
TFA, 45 oC, 4 h
H3PO4 (85%), 120 oC, 4 h
H3PO4 (85%), 170 oC, 5 h
No reaction
No reaction
35 (63%), 36 (23%)
36 (47%)
35 (65%), 36 (24%), 20a (5%)
20a (72%)
It appeared that conditions similar to those reported previously12 are optimal for cyclization of β-
hydroxyalkylphosphine oxides (Table 2, Entry 9). The use of other Brønstedt acids was either
inefficient (AcOH) or led to dehydration of substrate (HBF4, TFA).
4

ACCEPTED MANUSCRIPT
At first, β-hydroxyalkylphosphine oxides obtained from aldehydes have been subjected to cationic
cyclization (Scheme 5, Table 3).
O
P
Me
OH
R'
H3PO4 (85%)
170 oC, 5 h
Products
H
14-19
Scheme 5. Cyclization of 14-19.
Table 3. Cyclization of 14-19.
Entry
Substrate
Products
Me
O
P
O
P
1a
2
14 (R= Me, R‘= H)
15 (R= Ph, R‘= H)
+
+
Me
Me
P
O
Me
14a (81)b,e (34)d,e
14c (5)b
14b (8)b
Complex micture
Me
Me Me
Me
+
3
4
16 (R= i-Pr, R‘= H)
17 (R= t-Bu, R‘= H)
P
P
O
Me
O
Me
16b (12)b,e (12)c,e
16a (88)b (86)c
Me
Me
Me Me
Me
Me
+
P
P
O
Me
O
Me
17a (93)b,e (79)c,e
17b (7)b,e (7)c,e
Me
5
6
18 (R= Et, R‘= H)
P
O
Me
18a (100)b,e (40)d,e
19 (R= c-Hex, R‘= H)
Traces of the product
[a] The reaction took 72 h. After 5 h the product ratio was: 14a (15%), 14b (77%), 14c (8%). [b] Conversion based on 31P NMR spectrum of
the crude mixture. [c] Yields of the products isolated as mixtures with other compounds. [d] Yields of pure compounds. [e] Isolated as a
mixture of diastereomers.
Attempted cationic cyclization of compounds 14-19 revealed that the reaction pathway observed for
20 is followed only in the case of adduct 14. Phosphine oxide derived from acetaldehyde underwent
cyclization to a very limited extent under the developed reaction conditions and the main products
were 14b and 14c after heating the mixture for 5 h (Table 3, Entry 1). Prolonged heating of 14 in
phosphoric acid was needed to achieve the desired cyclization product as a mixture of two
diastereomers. This result might be the consequence of the lower stability of secondary carbocation
generated by removal of the water molecule.
5

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On the other hand, compounds 16-18 derived from isobutyraldehyde, pivalaldehyde or
propionaldehyde readily underwent cyclization reaction but the main or even only products were not
phosphaindane oxides but benzophosphorinane oxides 16b, 17a and 18b, all formed as mixtures of
diastereomers (Table 3, Entries 3-5). The formation of these products must therefore involve the
rearrangement of the initial carbocation. As it could be judged from the data presented in the Table 3,
the rearrangement might involve the transfer of either hydride (16b, 18a) or alkyl group (16c, 17a,
17b).
Following the research course, adducts 20-27 derived from methyl ketones have been subjected to
the cyclization reaction (Scheme 6, Table 4).
O
P
OH
H3PO4 (85%)
170 oC, 5 h
Products
R'
Me Me
20-27
Scheme 6. Cyclization of compounds 20-27.
Table 4. Cyclization of compounds 20-27.
Entry
1
Substrate
Products
Me
Me
20 (R= Me, R‘= Me)
P
Me
O
20a (100)a (74)c
n-Pr
n-Bu
Me
Me
P
P
Me
O
O
Me
21a (13)a,d
21b (45)a,d
2
21 (R= n-Bu, R‘= Me)
n-Pr Me
O
Me
P
Me
OH
P
O
Me
21c (10)a,d
21d (32)a,d
Et
n-Pr
Me
Me
Me
P
P
O
O
Me
22a (3)a,d
22b (36)a,d
3
4
22 (R= n-Pr, R‘= Me)
23 (R= Ph, R‘= Me)
Et Me
O
Me
P
Me
22d (58)a,d
OH
P
O
Me
22c (3)a,d
Complex reaction mixture
6

ACCEPTED MANUSCRIPT
Me Me
Me
5
6
7
8
24 (R= i-Pr, R‘= Me)
P
O
Me
17a (50)b,d
Me
P
Me Me
Et
Me
Me
Me
25 (R= Et, R‘= Me)
P
P
O
O
Me
O Me
25a (6)a (3)b
16a (10)a,d (6)b,d 16b (84)a,d (54)b,d
Me Me
Me
Me
26 (R= t-Bu, R‘= Me)
27 (R= t-BuCH2, R‘= Me)
P
Me
26a (45)c
O
Me
O
P
Me
Me
Me
Me
Me
P
O
35 (11)c
20a (31)c
[a] Conversion based on 31P NMR of the crude mixture. [b] Yields of the products isolated as mixtures with other compounds. [c] Yields of
pure compounds. [d] A mixture of diastereomers.
A screen of the products derived from methyl ketones revealed that only 20 undergoes cyclization
towards phosphaindane. The outcome in the case of compounds 21-27 depended on the structure of
the substrates around the carbinolic carbon atom. Compounds with long alkyl substituents at this atom
(21 and 22) afforded complex mixtures consisting of isomeric alcohols 21d and 22d as major products
along with some diastereomeric benzophosphorinane oxides (21b, 21c, 22b and 22c) and trace
amounts of phosphaindane oxides 21a and 22a. Adducts with shorter or branched alkyl groups at the
carbinolic carbon atom underwent preferentially or exclusively cyclization to benzophosphorinane
oxides (Table 4, Entries 5-7). Attempted cyclization of adduct 23 with a phenyl group at the carbinolic
atom afforded a complex reaction mixture (Table 4, Entry 4) whereas adduct 27 with a neopentyl
group at the same carbon atom underwent isobutene elimination prior to cyclization into the
phosphaindane core (Table 4, Entry 8).
Finally, a set of adducts 28-34 derived from symmetrical ketones other than acetone has been
subjected to cyclization reaction (Scheme 7, Table 5).
O
P
OH
H3PO4 (85%)
170 oC, 5 h
Products
R
Me
R
28-34
Scheme 7. Cyclization of compounds 28-34.
Table 5. Cyclization of compounds 28-34.
Entry
Substrate
Products
7

ACCEPTED MANUSCRIPT
O
P
1
28 (R= Ph, R‘= Ph)
Me
28a (22)c
n-Pr
n-Bu
n-Bu
n-Bu
P
P
Me
O
O Me
29a (9)a,d
29b (22)a,d
2
3
29 (R= n-Bu, R‘= n-Bu)
n-Pr n-Bu
O
n-Bu
P
Me
OH
P
O Me
29c (4)a,d
29d (65)a,d
i-Pr
Me Me
30 (R= i-Pr, R‘= i-Pr)
P
O Me
30a (18)c,d
Me
Et
Et
Et
P
P
Me
O
O Me
31a (1)a (1)b
31b (65)a,d (47)b,d
4
5
31 (R= Et, R‘= Et)
Me Et
O
P
Et
Me
OH
P
O Me
22c (24)a,d (22)b,d
31d (11)a,d (4)b,d
32 (R=R‘= -(CH2)4-)
32a (38)c,d
P
O Me
6
7
33 (R=R‘= -(CH2)5-)
34 (R=R‘= -(CH2)6-)
33a (27)c,d
P
Me
O
Traces of the product
[a] Conversion based on 31P NMR spectrum of the crude mixture. [b] Yields of the products isolated as mixtures with other compounds. [c]
Yields of pure compounds. [d] A mixture of diastereomers.
Under the standard reaction conditions compound 28 underwent intramolecular cyclization to the
corresponding fluorene 28a albeit with low yield (Table 5, Entry 1). The adduct derived from dibutyl
ketone afforded mainly the isomeric alcohol 29d but the one derived from 3-pentanone afforded
preferentially a mixture of two benzophosphorinanes 31b and 31c where the latter is formed through
ethyl group migration (Table 5, Entry 4). The adduct derived from diisopropyl ketone afforded
benzophosphorinane oxide 30a albeit in low yield (Table 4, Entry 3). Interestingly, adducts derived
8

ACCEPTED MANUSCRIPT
from cyclic ketones like cyclopentanone or cyclohexanone (but not cycloheptanone) afforded tricyclic
products as mixtures of isomers (Table 5, Entries 5 and 6).
The results presented so far show the general reactivity pathway for the transformation of β-
hydroxyalkyl(phenyl)phosphine oxides in acidic media. It was therefore interesting to find the
behaviour of other phosphine oxides possessing different substituents at phosphorus (Scheme 8).
Me
Me
O
P
OH
Me
H3PO4 (85%)
170 oC, 5h
R
P
Me
R
O
37 (R = Ph)
38 (R = t-Bu)
37a (79 %)
38a (61%)
Me Me
O
P
OH
H3PO4 (85 %)
170 oC, 24h
Me
R
P
Me
O
R
39 (R = Ph)
40 (R = t-Bu)
39a (62 %)
40a (93%)
O
P
Me
OH
Me
Me
H3PO4 (85%)
170 oC, 24 h
Me
Me
P
O
Me
41a 91% (76%)
41
Me
Et
Me
O
Me
O
O
P
Me
OH
P
P
H3PO4 (85%)
170 oC, 24 h
Me
+
Me
Me
Me
42
42b (14%)
42a (12%) (25% de)
Scheme 8. Cyclization of phosphine oxides 37-42.
It appeared that the developed method could be extended to other tertiary phosphine oxides
possessing at least one aryl substituent at phosphorus. Compounds 37 and 39 with two phenyl
substituents at phosphorus afforded either phosphaindane oxide 37a or benzophosphorinane oxide 39a
with good yields. Similarly, phosphine oxides 38 and 40 possessing a bulky t-butyl group underwent
clean formation of fused bicyclic systems 38a and 40a, respectively. An interesting issue was the
reaction of compounds 41 and 42 possessing a 1-naphthyl moiety. In the case of 41, the formation of
tricyclic phosphadihydrophenalene 41a as the sole product has been observed. This suggests, that the
carbocation tends to undergo cyclization with the distant naphthalene fragment instead of the adjacent
ortho carbon atom. Phosphine oxide 42, on the other hand, underwent competitive formation of
tricyclic 42a and 42b. Here, the competition between 6-endo-trig (processing through alkyl group
migration) and 7-endo-trig processes (processing through proton migration) is evidently seen.
Regarding the results presented above, the formation of phosphaindane core could be attributed to a 5-
endo-trig process and the formation of benzophosphorinane to a 6-endo-trig process. Unfortunately,
Baldwin’s rules14 cannot be applied to cationic cyclization reaction where no such generalization could
be made.15 Nevertheless, phosphaindane is the main product only in cases where the intermediary
9

ACCEPTED MANUSCRIPT
carbocation cannot undergo any rearrangement. In other cases the main or even the only product will
be benzophospholane. This is extremely well seen in the case of compound 25 (Scheme 9).
Me
Me
Me
Me
-H
H
P
P
Me
Me
O
O
25a
45
traces
cyclization
O
P
Me
OH2
O
P
OH
Me
O
P
Me
H3PO4
-H2O
Me
Me
Me
Me
Me
Me
Me
43
25
44
rearrangement
O
Me
P
Me
P
Me
Me
cyclization
-H
P
Me
H
Me
O
Me
O
Me
47
16b
48
main product
Scheme 8. Rearrangement-cyclization of 25.
Protonation of this substrate should afford cation 43 which loses water molecule yielding the cation
44. The most obvious step here would be cyclization to cation 45 followed by rearomatization which
should lead to phosphaindane 25a. This proces, however, is marginal and the main reaction pathway
leads through a rearrangement of tertiary cation 44 into secondary (!) cation 47 which then undergoes
cyclization into 48 which upon rearomatization provides benzophospholane 16b. There must
undoubtedly be an energy increase due to the formation of the less stable secondary carbocation but
this reaction pathway still prevails over the formation of 25a. A detailed mechanism of the cationic
cyclization is currently underway in our laboratory.
3. Conclusions
In conclusion, we have described the intramolecular cationic cyclization of a series of β-
hydroxyalkylphosphine oxides. Depending on the structure, the formation of either the phosphaindane
or the benzophosphorinane skeleton has been observed. The formation of the latter proceeds with
rearrangement of the initial tertiary carbocation prior to the cyclization step. The crucial element of the
selectivity of this transformation is the substitution pattern at the carbinolic carbon atom. The
formation of the benzophospholane core proceeds through a 6-endo-trig process, compared to a 5-
endo-trig cyclization observed for the phosphaindane framework. The parent carbocation would
preferentially undergo a rearrangement-cyclization sequence for compounds with branched or
moderately long (2-3 carbon atom chain) alkyl substituents at carbinolic carbon atom.
4. Experimental section
4.1. General informations
10

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All reactions were performed under an argon atmosphere using Schlenk techniques. Only dry solvents
were used, and the glassware was heated under vacuum prior to use. Solvents for chromatography
were distilled once before use, and solvents for extraction were used as received. Tetrahydrofurane
and diethyl ether were dried over sodium/benzophenone ketyl. n-BuLi was commercially available and
used as received.
Analytics and Instruments. The NMR spectra was recorded with Bruker Ascend (500 MHz)
spectrometer in CDCl3 as a solvent at room temperature unless otherwise noted. Chemical shifts (δ)
are reported in ppm relative to residual solvent peak. Mass spectra were recorded with Shimadzu GC-
MS QP2010S spectrometer working in electron ionization (EI) mode with Phenomenex Zebron ZB-
20HT INFERNO column using following parameters: pressure 65 kPa, total flow 33.9 mL/min,
column flow 1.0 mL/min, linear velocity 36.8 cm/s, split 30, temperature program (80 °C hold 0.5
min, 80−340 °C/19 °C/min hold 2 min, 300−340 °C/15 °C/min hold 3.26 min total 20 min). Thin layer
chromatography (TLC) was performed with precoated silica gel plates and visualized by UV light or
KMnO4 solution or iodide on silica gel. The reaction mixtures were purified by column
chromatography over silica gel (60−240 mesh). Melting points were determined in a capillary tube and
were uncorrected.
The starting compound dimethylphenylphosphine oxide (13),16 methyldiphenylphosphine oxide17 and
tert-butylmethylphenylphosphine oxide18 were prepared according to the literature procedures.
4.2. General Procedure A for the synthesis of β-hydroxyalkylphosphine oxides 14-34, 37-42.
In a flame-dried Schlenk tube (50 mL) equipped with magnetic stirrer and inert gas inlet was placed
methylphosphine oxide (1.0 mmol) in THF (5 mL). The mixture was cooled to −78 °C (dry ice-
acetone) and n-BuLi (1.0 mmol, 1.6 M in hexane) was added. After the orange mixture was stirred for
50 min at −78 °C, aldehyde or ketone (1.5 mmol) was added until no colour remained. Reaction was
allowed to warm to room temperature and was stirred for 1 hour. The reaction was quenched by
addition of saturated NH4Cl solution (10 mL) and extracted with DCM (3×20 mL). The combined
organic phases were dried over MgSO4, filtered, and evaporated under reduced pressure. The residue
was purified by flash column chromatography using AcOEt/MeOH (v/v = 9:1) or Hexane/CHCl3/i-
PrOH (v/v = 10:1:1) as eluent.
4.2.1. (2-Hydroxypropyl)methylphenylphosphine oxide (14). This compound was prepared according
to General Procedure A from dimethylphenylphosphine oxide 13 (0.300 g, 1.9 mmol) and
acetaldehyde (0.129 g, 2.9 mmol) as a pale yellow oil; yield 0.335 g (86%). Isolated as a mixture of
diastereomers (dr = 53:47).
Major diastereomer: Rf (AcOEt/MeOH 9:1) 0.29; δH (500 MHz, CDCl3) 1.20 (3H, dd, J 6.1 Hz, J 1.7
Hz), 1.77 (3H, d, J 13.2 Hz), 1.94−1.99 (1H, m), 2.15−2.20 (1H, m), 3.42 (1H, bs), 4.24−4.35 (1H, m),
7.44−7.56 (3H, m), 7.65−7.74 (2H, m); δC (126 MHz, CDCl3) 17.5 (d, J 69.9 Hz), 25.1 (d, J 9.1 Hz),
11

ACCEPTED MANUSCRIPT
40.3 (d, J 8.2 Hz), 62.8 (d, J 5.4 Hz), 128.7 (d, J 11.8 Hz), 129.8 (d, J 9.1 Hz), 131.8 (d, J 2.7 Hz),
133.1 (d, J 96.3 Hz); δP (202 MHz, CDCl3) 39.34; GC tR = 8.05 min; GC−MS (EI, 70 eV) m/z=183
(22), 180 (M−H2O) (3), 154 (66), 141 (14), 140 (32), 139 (100), 125 (23), 92 (20), 91 (80%).
Minor diastereomer: Rf (AcOEt/MeOH 9:1) 0.29; δH (500 MHz, CDCl3) 1.28 (3H, dd, J 6.0 Hz, J 1.6
Hz), 1.77 (3H, d, J 13.2 Hz), 2.01−2.08 (1H, m), 2.11−2.15 (1H, m), 4.13−4.24 (1H, m), 4.73 (1H, bs),
7.45−7.55 (3H, m), 7.66−7.73 (3H, m); δC (126 MHz, CDCl3) 16.5 (d, J 69.9 Hz), 24.9 (d, J 9.1 Hz),
39.9 (d, J 69.0 Hz), 63.3 (d, J 4.5 Hz), 128.7 (d, J 11.8 Hz), 129.6 (d, J 10.0 Hz), 131.8 (d, J 2.7 Hz),
133.6 (d, J 97.2 Hz); δC (202 MHz, CDCl3) 38.92; GC tR = 7.97 min; GC−MS (EI, 70 eV) m/z=183
(23), 180 (M−H2O) (3), 154 (66), 141 (15), 140 (36), 139 (100), 125 (26), 92 (20), 91 (80%);
ν max (ATR) for a mixture of diastereomers: 3296, 3050, 2964, 2897, 1652, 1436, 1294, 1148,
1109,1068, 1024, 936, 894, 809, 740, 693, 506, 486, 422.
4.2.2. (2-Hydroxy-2-phenylethyl)methylphenylphosphine oxide (15). This compound was prepared
according to General Procedure A from dimethylphenylphosphine oxide (13) (0.464 g, 3.0 mmol) and
benzaldehyde (0.479 g, 4.52 mmol) as a white solid; yield 0.672 g (86%). Isolated as a mixture of
diastereomers (dr = 54.5:45.5).
Major diastereomer: Rf (AcOEt/MeOH 9:1) 0.53; (500 MHz, CDCl3) 1.82 (3H, d, J 12.9 Hz),
2.19−2.31 (2H, m), 4.63 (1H, bs), 5.25−5.35 (1H, m), 7.22−7.27 (1H, m), 7.29−7.36 (3H, m),
7.37−7.41 (1H, m), 7.44−7.61 (3H, m), 7.66−7.79 (2H, m); δC (126 MHz, CDCl3) 16.4 (d, J 70.0 Hz),
41.1 (d, J 10.9 Hz), 69.5 (d, J 4.5 Hz), 125.5, 127.7, 128.5, 128.7 (d, J 11.8 Hz), 129.6 (d, J 9.1 Hz),
131.9 (d, J 2.7 Hz), 133.6 (d, J 98.1 Hz), 143.8 (d, J 11.8 Hz); δP (202 MHz, CDCl3) 38.42; GC tR =
12.99 min; GC−MS (EI, 70 eV) m/z=260 (M+) (1), 242 (M+−H2O) (14), 241 (13), 164 (12), 154 (100),
140 (57), 139 (64), 125 (36), 121 (12), 105 (19), 92 (21), 91 (80), 78 (20), 77 (66), 51 (33), 50 (11), 47
(21%).
Minor diastereomer: Rf (AcOEt/MeOH 9:1) 0.53; δH (500 MHz, CDCl3) 1.79 (3H, d, J 13.2 Hz),
2.42−2.52 (2H, m), 4.63 (1H, bs), 5.06−5.19 (1H, m), 7.22−7.27 (1H, m), 7.29−7.36 (3H, m),
7.37−7.41 (1H, m), 7.44−7.61 (3H, m), 7.66−7.79 (2H, m); δH (126 MHz, CDCl3) 17.7 (d, J 70.0 Hz),
40.6 (d, J 10.9 Hz), 69.0 (d, J 4.5 Hz), 125.4, 127.6, 128.5, 128.9 (d, J 11.8 Hz), 129.9 (d, J 10.0 Hz),
131.9 (d, J 2.7 Hz), 133.1 (d, J 96.3 Hz), 144.1 (d, J 13.6 Hz); δP (202 MHz, CDCl3) 39.02; GC tR =
12.88 min; GC−MS (EI, 70 eV) m/z=260 (M+) (1), 242 (M+−H2O) (7), 241 (11), 165 (11), 154 (100),
140 (55), 139 (54), 125 (34), 121 (10), 92 (21), 91 (81), 78 (16), 77 (47), 51 (22), 47 (21%);
ν max (ATR) for a mixture of diastereomers: 3241, 3055, 2903, 2854, 1588, 1487, 1435, 1347, 1294,
1228, 1160, 1114, 1080, 1059, 1025, 986, 882, 877, 825, 739, 694, 513, 481, 443.
12

ACCEPTED MANUSCRIPT
4.2.3. (2-Hydroxy-3-methylbutyl)methylphenylphosphine oxide (16). This compound was prepared
according to General Procedure A from dimethylphenylphosphine oxide (13) (0.326 g, 2.1 mmol) and
isobutyraldehyde (0.228 g, 3.17 mmol); yield of two diastereomers 0.395 g, (83%), (dr = 52.5:47.5).
Major diastereomer: Yield 45% (0.182 g, 38% isolated as a pure compound); white solid; mp 90.3–
92.1 °C; [Found C, 63.68; H, 8.50. C12H19O2P requires C, 63.70; H, 8.46%]; Rf (Hexane/CHCl3/i-
PrOH 5:1:1) 0.52; ν max (ATR) 3236, 2948, 2910, 2866, 1436, 1382, 1326, 1286, 1221, 1169, 1114,
1093, 1036, 887, 694, 689, 553, 507, 477, 418; δH (500 MHz, CDCl3) 0.86 (3H, d, J 6.6 Hz), 0.87 (6H,
d, J 3.8 Hz), 1.59−1.70 (1H, m), 1.78 (3H, d, J 13.6 Hz), 1.88−1.97 (1H, m), 2.00−2.11 (1H, m),
3.75−3.83 (1H, m), 4.52 (1H, bs), 7.43−7.53 (3H, m), 7.66−7.73 (2H, m); δC (126 MHz, CDCl3) 17.3,
17.6 (d, J 69.9 Hz), 17.8, 34.6 (d, J 11.8 Hz), 34.9 (d, J 70.8 Hz), 70.8 (d, J 5.4 Hz), 128.6 (d, J 11.8
Hz), 129.7 (d, J 9.1 Hz), 131.6 (d, J 2.7 Hz), 133.5 (d, J 96.3 Hz); δP (202 MHz, CDCl3) 40.27; GC tR
= 9.89 min; GC−MS (EI, 70 eV) m/z=208 (M+−H2O) (3), 183 (72), 154 (12), 140 (37), 139 (100), 125
(18), 91 (29), 77 (26), 47 (16%).
Minor diastereomer: Yield 37% (0.140 g, 29% isolated as a pure compound); colorless oil; Rf
(Hexane/CHCl3/i-PrOH 5:1:1) 0.42; [Found C, 63.92; H, 8.71. C12H19O2P requires C, 63.70; H,
8.46%]; ν max (ATR) 3308, 2969, 2902, 2859,1437, 1359, 1291, 1237, 1158, 1118, 1071, 1019, 965,
890, 740, 693, 668, 519, 490, 460, 437; δH (500 MHz, CDCl3) 0.90 (3H, d, J 6.9 Hz), 0.94 (6H, d, J
6.9 Hz), 1.69−1.76 (1H, m), 1.78 (3H, d, J 12.9 Hz), 1.94−2.12 (2H, m), 3.87−3.96 (1H, m), 4.06 (1H,
bs), 7.46−7.56 (3H, m), 7.67−7.75 (2H, m); δC (126 MHz, CDCl3) 16.1 (d, J 69.9 Hz), 17.5, 17.9, 34.6
(d, J 11.8 Hz), 34.9 (d, J 69.9 Hz), 71.6 (d, J 5.4 Hz), 128.7 (d, J 11.8 Hz), 129.6 (d, J 10.0 Hz), 131.8
(d, J 2.7 Hz), 133.8 (d, J 97.2 Hz); δP (202 MHz, CDCl3) 40.14; GC tR = 10.04 min; GC−MS (EI, 70
eV) m/z=208 (M+−H2O) (4), 183 (75), 154 (12), 140 (32), 139 (100), 125 (14), 91 (28), 77 (23), 47
(14%). Analytical data are in accordance with those reported in the literature.19
4.2.4. (2-Hydroxy-3,3-dimethylbutyl)methylphenylphosphine oxide (17). This compound was prepared
according to General Procedure A from dimethylphenylphosphine oxide (13) (0.295 g, 1.92 mmol)
and pivalaldehyde (0.247 g, 2.87 mmol); yield of two diastereomers 0.388 g (84%), (dr = 58:42).
Major diastereomer: Yield 53% (0.215 g, 47% isolated as a pure compound); white solid; mp 137–
138.1 °C; Rf (Hexane/CHCl3/i-PrOH 5:1:1) 0.58; [Found C, 65.01; H, 8.84. C13H21O2P requires C,
64.98; H, 8.81%]; ν max (ATR) 3277, 2952, 2867, 1476, 1438, 1361, 1323, 1286, 1229, 1168, 1114,
1069, 1013, 884, 823, 743, 695, 654, 493, 431; δH (500 MHz, CDCl3) 0.83 (9H, s), 1.78 (3H, d, J 13.2
Hz), 1.95−2.07 (2H, m), 3.58−3.64 (1H, m), 4.30 (1H, bs), 7.46−7.55 (3H, m), 7.68−7.73 (2H, m); δC
(126 MHz, CDCl3) 17.9 (d, J 69.9 Hz), 25.3, 32.9 (d, J 70.8 Hz), 35.1 (d J 11.8 Hz), 73.9 (d, J 5.5 Hz),
128.7 (d, J 10.9 Hz), 129.9 (d, J 9.1 Hz), 131.7 (d, J 2.7 Hz), 133.4 (d, J 95.4 Hz); δP (202 MHz,
CDCl3) 40.67; GC tR = 9.92 min; GC−MS (EI, 70 eV) m/z=183 (93), 140 (32), 139 (100), 125 (13), 91
(23), 77 (20), 47 (14%).
13

ACCEPTED MANUSCRIPT
Minor diastereomer: Yield 32% (0.077 g, 17% isolated as a pure compound); white solid; mp 123.4–
124.4 °C; Rf (Hexane/CHCl3/i-PrOH 5:1:1) 0.50; [Found C, 64.95; H, 8.77. C13H21O2P requires C,
64.98; H, 8.81%]; ν max (ATR) 3244, 2953, 2866, 1477, 1434, 1361, 1297, 1238, 1149, 1139, 1108,
1066, 1013, 906, 873, 827, 740, 691, 554, 493, 427; δH (500 MHz, CDCl3) 0.91 (9H, s), 1.79 (3H, d, J
12.6 Hz), 1.97−2.03 (2H, m), 3.79−3.85 (1H, m), 4.01 (1H, bs), 7.47−7.56 (3H, m), 7.69−7.75 (2H,
m); δC (126 MHz, CDCl3) 15.8 (d, J 70.8 Hz), 25.34, 33.2 (d, J 70.8 Hz), 35.2 (d, J 11.8 Hz), 74.5 (d,
J 5.4 Hz), 128.7 (d, J 11.8 Hz), 129.6 (d, J 10.0 Hz), 131.8 (d, J 2.7 Hz), 133.9 (d, J 97.2 Hz); δP (202
MHz, CDCl3) 40.42; GC tR = 10.11 min; GC−MS (EI, 70 eV) m/z=183 (95), 140 (32), 139 (100), 125
(13), 91 (22), 77 (20), 47 (13%).
4.2.5. (2-Hydroxybutyl)methylphenylphosphine oxide (18). This compound was prepared according to
General Procedure A from dimethylphenylphosphine oxide (13) (0.335 g, 2.17 mmol) and
propionaldehyde (0.189 g, 3.26 mmol); yield of two diastereomers 0.346 g (75%), (dr = 54:46).
Major diastereomer: Yield 46% (0.187 g, 41% isolated as a pure compound); colorless oil; Rf
(AcOEt/MeOH 9:1) 0.32; [Found C, 62.48; H, 8.31. C11H17O2P requires C, 62.25; H, 8.31%]; δH (500
MHz, CDCl3) 0.87 (3H, t, J 7.4 Hz), 1.37−1.50 (1H, m), 1.50-1.61 (1H, m), 1.79 (3H, d, J 12.3 Hz),
1.92−2.03 (1H, m), 2.05−2.17 (1H, m), 3.86−3.98 (1H, m), 4.54 (1H, bs), 7.42−7.58 (3H, m),
7.64−7.77 (2H, m); δC (126 MHz, CDCl3) 9.5, 17.7 (d, J 69.0 Hz), 31.6 (d, J 13.6 Hz), 37.8 (d, J 67.2
Hz), 67.7 (d, J 5.4 Hz), 128.7 (d, J 10.9 Hz), 129.9 (d, J 9.1 Hz), 131.7 (d, J 2.7 Hz), 133.4 (d, J 96.3
Hz); δP (202 MHz, CDCl3) 39.53; GC tR = 9.70 min; GC−MS (EI, 70 eV) m/z=194 (M+−H2O) (4), 183
(58), 154 (23), 140 (36), 139 (100), 125 (18), 92 (10), 91 (45%).
Minor diastereomer: Yield 30% (0.109 g, 24% isolated as a pure compound); white solid; mp 106.4–
108.2 °C; Rf (AcOEt/MeOH 9:1) 0.26; [Found C, 62.28; H, 9.01. C11H17O2P requires C, 62.25; H,
8.31%]; ν max (ATR) 3307, 2968, 2923, 1437, 1358, 1291, 1237, 1158, 1117, 1071, 1025, 1018, 965,
890, 739, 693, 667, 518, 491, 460, 436; δH (500 MHz, CDCl3) 0.90 (3H, t, J 7.6 Hz), 1.43−1.65 (2H,
m), 1.76 (3H, d, J 12.9 Hz), 1.95−2.16 (2H, m), 3.96−4.09 (1H, m), 4.21 (1H, bs), 7.42−7.56 (3H, m),
7.62−7.76 (2H, m); δC (126 MHz, CDCl3) 9.6, 16.4 (d, J 69.9 Hz), 31.5 (d, J 12.7 Hz), 37.8 (d, J 69.9
Hz), 68.4 (d, J 5.4 Hz), 128.7 (d, J 11.8 Hz), 129.6 (d, J 10.0 Hz), 131.8 (d, J 2.7 Hz), 133.8 (d, J 97.2
Hz); δP (202 MHz, CDCl3) 39.16; GC tR = 9.84 min; GC−MS (EI, 70 eV) m/z=194 (M+−H2O) (7), 183
(54), 154 (26), 140 (35), 139 (100), 125 (16), 92 (11), 91 (46) 77 (29), 51 (12), 47 (17%).
4.2.6. (2-Cyclohexyl-2-hydroxyethyl)methylphenylphosphine oxide (19). This compound was prepared
according to General Procedure A from dimethylphenylphosphine oxide (13) (0.317 g, 2.1 mmol) and
cyclohexanal (0.346 g, 3.09 mmol); yield of two diastereomers 0.530 g (97%), (dr = 53:47).
Major diastereomer: Yield 50% (0.105 g, 19% isolated as a pure compound); white solid; mp 102.8–
104.2 °C; Rf (Hexane/CHCl3/i-PrOH 5:1:1) 0.62; [Found C, 67.78; H, 8.81. C15H23O2P requires C,
14

ACCEPTED MANUSCRIPT
67.65; H, 8.70%]; ν max (ATR) 3266, 2912, 2850, 1436, 1286, 1165, 1111, 1061, 989, 882, 742, 689,
580, 487, 430; δH (500 MHz, CDCl3) 0.87−1.01 (2H, m), 1.02−1.16 (3H, m), 1.27−1.36 (1H, m),
1.56−1.65 (2H, m), 1.66−1.76 (3H, m), 1.78 (3H, d, J 13.2 Hz), 1.94−2.01 (1H, m), 2.05−2.15 (1H,
m), 3.72−3.81 (1H, m), 4.35 (1H, bs), 7.43−7.55 (3H, m), 7.66−7.73 (2H, m); δC (126 MHz, CDCl3)
17.8 (d, J 69.9 Hz), 25.6 (d, J 89.0 Hz), 26.2 (d, J 39.1 Hz), 28.1 (d, J 70.8 Hz), 35.2 (d, J 70.8 Hz),
44.6 (d, J 11.8 Hz), 70.3 (d, J 5.5 Hz), 128.7 (d, J 11.8 Hz), 129.8 (d, J 9.1 Hz), 131.7 (d, J 1.8 Hz),
133.4 (d, J 96.3 Hz); δP (202 MHz, CDCl3) 40.32; GC tR = 12.47 min; GC−MS (EI, 70 eV) m/z=248
(M+−H2O) (1), 183 (100), 154 (13), 140 (33), 139 (68), 125 (13), 91 (22), 77 (40), 51 (12), 47 (11%).
Minor diastereomer: Yield 47% (0.051 g, 9% isolated as a pure compound); white solid; mp 113.8–
115.1 °C; Rf (Hexane/CHCl3/i-PrOH 5:1:1) 0.51; [Found C, 67.82; H, 8.79. C15H23O2P requires C,
67.65; H, 8.70%]; ν max (ATR) 3233, 2916, 2847, 1434, 1297, 1136, 1102, 989, 908, 823, 744, 691,
502, 424; δH (500 MHz, CDCl3) 0.86−1.04 (2H, m), 1.05−1.17 (3H, m), 1.19−1.25 (1H, m), 1.32−1.45
(1H, m), 1.58−1.68 (2H, m), 1.68−1.74 (1H, m), 1.77 (3H, d, J 12.9 Hz), 1.80−1.87 (1H, m),
1.95−2.14 (2H, m), 3.87−3.96 (1H, m), 4.05 (1H, bs), 7.43−7.56 (3H, m), 7.65−7.74 (2H, m); δC (126
MHz, CDCl3) 16.2 (d, J 69.9 Hz), 25.6 (d, J 87.2 Hz), 26.2 (d, J 41.8 Hz), 28.3 (d, J 62.7 Hz), 35.2 (d,
J 70.8 Hz), 44.5 (d, J 11.8 Hz), 71.2 (d, J 6.4 Hz), 128.7 (d, J 10.9 Hz), 129.6 (d, J 10.0 Hz), 131.8 (d,
J 2.7 Hz), 133.9 (d, J 97.2 Hz); δP (202 MHz, CDCl3) 40.05; GC tR = 12.59 min; GC−MS (EI, 70 eV)
m/z=248 (M+−H2O) (2), 184 (10), 183 (100), 154 (17), 140 (40), 139 (73), 125 (15), 91 (24), 77 (18),
55 (11), 47 (12%).
4.2.7. (2-Hydroxy-2-methylpropyl)methylphenylphosphine oxide (20). This compound was prepared
according to General Procedure A from dimethylphenylphosphine oxide (13) (0.077 g, 0.5 mmol)
acetone (0.043 g, 0.75 mmol) as a white solid; yield 0.094 g (89%); mp 92.4–93.1 °C; Rf
(AcOEt/MeOH 9:1) 0.34; [Found C, 62.33; H, 8.13. C11H17O2P requires C, 62.25; H, 8.07%]; ν max
(ATR) 3312, 3063, 2966, 2963, 2920, 2885, 1443, 1376, 1273, 1227, 1158, 1111, 971, 892, 875, 823,
743, 695, 547, 495, 437; δH (500 MHz, CDCl3) 1.22 (3H, s), 1.38 (3H, s), 1.76 (3H, d, J 12.9 Hz),
2.17−2.35 (2H, m), 4.31 (1H, bs), 7.41−7.59 (3H, m), 7.63−7.78 (2H, m); δC (126 MHz, CDCl3) 19.3
(d, J 69.9 Hz), 30.9 (d, J 6.4 Hz), 31.9 (d, J 9.1 Hz), 43.0 (d, J 69.0 Hz), 70.6 (d, J 5.5 Hz), 128.7 (d, J
11.8 Hz), 129.6 (d, J 10.0 Hz), 131.7 (d, J 2.7 Hz), 134.8 (d, J 96.3 Hz); δP (202 MHz, CDCl3) 38.10;
GC tR = 9.16 min; GC−MS (EI, 70 eV) m/z=194 (M+−H2O) (13), 197 (46), 194 (14), 154 (56), 139
(100), 92 (18), 91 (73), 77 (30), 51 (12), 47 (16%). Analytical data are in accordance with those
reported in the literature.20
4.2.8. (2-Hydroxy-2-methylhexyl)methylphenylphosphine oxide (21). This compound was prepared
according to General Procedure A from dimethylphenylphosphine oxide (13) (0.201 g, 1.30 mmol)
and 2-hexanone (0.196 g, 1.95 mmol) as a white solid; yield 0.251 g (75%). Isolated as a mixture of
diastereomers (dr = 56:44).
15

ACCEPTED MANUSCRIPT
Major diastereomer: Rf (AcOEt/MeOH 9:1) 0.54; δH (500 MHz, CDCl3) 0.71 (3H, t, J 7.3 Hz),
0.86−0.99 (1H, m), 1.01−1.13 (1H, m), 1.17 (3H, s), 1.29−1.33 (2H, m), 1.55−1.63 (2H, m), 1.76 (3H,
d, J 12.9 Hz), 2.12−2.35 (2H, m), 4.56 (1H, bs), 7.47−7.60 (3H, m), 7.68−7.79 (2H, m); δC (126 MHz,
CDCl3) 14.0, 19.4 (d, J 69.9 Hz), 23.0, 26.2, 28.7 (d, J 79.0 Hz), 41.3 (d, J 69.0 Hz), 44.5 (d, J 10.0
Hz), 72.7 (d, J 5.4 Hz), 128.8 (d, J 11.8 Hz), 129.7 (d, J 10.0 Hz), 131.6 (d, J 2.7 Hz), 134.9 (d, J 95.4
Hz); δP (202 MHz, CDCl3) 38.58; GC tR = 10.66 min; GC−MS (EI, 70 eV) m/z=236 (M+−H2O) (6),
197 (80), 157 (12), 154 (38), 140 (49), 139 (100), 125 (13), 92 (11), 91 (48), 77 (29), 47 (17%).
Minor diastereomer: Rf (AcOEt/MeOH 9:1) 0.54; δH (500 MHz, CDCl3) 0.87−0.97 (m, 1H), 0.91 (3H,
t, J 6.9 Hz), 1.18−1.22 (1H, m), 1.29−1.34 (2H, m), 1.34 (3H, d, J 1.6 Hz), 1.42−1.56 (2H, m), 1.78
(3H, d, J 12.9 Hz), 2.13−2.34 (2H, m), 4.72 (1H, bs), 7.48−7.58 (3H, m), 7.68−7.77 (2H, m); δC (126
MHz, CDCl3) 13.9, 19.3 (d, J 69.9 Hz), 22.8, 26.6, 28.6 (d, J 75.4 Hz), 41.3 (d, J 69.0 Hz), 43.3 (d, J
6.4 Hz), 72.9 (d, J 6.4 Hz), 128.7 (d, J 11.8 Hz), 129.7 (d, J 10.0 Hz), 131.7 (d, J 2.7 Hz), 135.0 (d, J
95.4 Hz); δP (202 MHz, CDCl3) 38.42; GC tR = 10.57 min; GC−MS (EI, 70 eV) m/z=236 (M+−H2O)
(7), 197 (74), 154 (33), 140 (55), 139 (100), 125 (15), 92 (11), 91 (48), 77 (29), 58 (11), 47 (17%);
ν max (ATR) for a mixture of diastereomers: 3723, 3623, 3358, 3291, 3058, 2932, 2858, 1440, 1373,
1291, 1237, 1150, 1105, 1028, 941, 879, 822, 738, 693, 538, 499, 434.
4.2.9. (2-Hydroxy-2-methylpentyl)methylphenylphosphine oxide (22). This compound was prepared
according to General Procedure A from dimethylphenylphosphine oxide (13) (0.373 g, 2.42 mmol)
and 2-pentanone (0.312 g, 3.63 mmol) as a colorless oil; yield 0.495 g (85%). Isolated as a mixture of
diastereomers (dr = 52:48).
Major diastereomer: Rf (AcOEt/MeOH 9:1) 0.50; δH (500 MHz, CDCl3) 0.94 (3H, t, J 7.3 Hz), 1.19
(3H, s), 1.37−1.45 (2H, m), 1.55−1.62 (2H, m), 1.78 (3H, d, J 13.2 Hz), 2.12−2.37 (2H, m), 4.59 (1H,
bs), 7.48−7.59 (3H, m), 7.69−7.80 (2H, m); δC (126 MHz, CDCl3) 14.4, 17.2, 19.4 (d, J 69.9 Hz), 28.6
(d, J 71.8 Hz), 41.7 (d, J 2.7 Hz), 47.1 (d, J 9.1 Hz), 72.7 (d, J 6.4 Hz), 128.8 (d, J 11.8 Hz), 129.7 (d,
J 2.7 Hz), 131.7 (d, J 5.4 Hz), 135.0 (d, J 96.3 Hz); δC (202 MHz, CDCl3) 38.63; GC tR = 10.16 min;
GC−MS (EI, 70 eV) m/z=225 (M+−CH3) (11), 223 (M+−H2O) (2), 197 (84), 157 (14), 154 (37), 140
(40), 139 (100), 125 (10), 92 (12), 91 (55), 77 (29), 47 (16%).
Minor diastereomer: Rf (AcOEt/MeOH 9:1) 0.50; δH (500 MHz, CDCl3) 0.66 (3H, t, J 7.3 Hz),
0.97−1.06 (1H, m), 1.22−1.27 (1H, m), 1.36 (3H, d, J 1.3 Hz), 1.45−1.54 (2H, m), 1.80 (3H, d, J 12.9
Hz), 2.13−2.36 (2H, m), 4.59 (1H, bs), 7.49−7.59 (3H, m), 7.70−7.78 (2H, m); δC (126 MHz, CDCl3)
14.1, 17.7, 19.3 (d, J 69.9 Hz), 28.7 (d, J 75.4 Hz), 41.1 (d, J 2.7 Hz), 45.8 (d, J 6.4 Hz), 72.9 (d, J 5.4
Hz), 128.8 (d, J 10.9 Hz), 129.6 (d, J 2.7 Hz), 131.7 (d, J 5.4 Hz), 134.9 (d, J 96.3 Hz); δP (202 MHz,
CDCl3) 38.44; GC tR = 10.11 min; GC−MS (EI, 70 eV) m/z=225 (M+−CH3) (9), 222 (M+−H2O) (9),
197 (86), 157 (13), 154 (34), 140 (45), 139 (100), 125 (11), 92 (12), 91 (55), 77 (29), 47 (17%);
16

ACCEPTED MANUSCRIPT
ν max (ATR) for a mixture of diastereomers: 3329, 2957, 2869, 1436, 1372, 1294, 1151, 1112, 1015,
892, 822, 738, 694, 489, 437;
4.2.10. (2-Hydroxy-2-phenylpropyl)methylphenylphosphine oxide (23). This compound was prepared
according to General Procedure A from dimethylphenylphosphine oxide (13) (0.211 g, 1.37 mmol)
and acetophenone (0.247 g, 2.05 mmol) as a white solid; yield 0.345 g (93%). Isolated as a mixture of
diastereomers (dr = 66.5:33.5).
Major diastereomer: Rf (AcOEt/MeOH 9:1) 0.68; δH (500 MHz, CDCl3) 1.68 (3H, d, J 1.9 Hz), 1.78
(3H, d, J 12.9 Hz), 2.68 (2H, d, J 8.5 Hz), 5.90 (1H, bs), 6.98-7.08 (3H, m), 7.23−7.27 (2H, m),
7.34−7.42 (2H, m), 7.53−7.66 (3H, m); δC (126 MHz, CDCl3) 18.7 (d, J 70.8 Hz), 33.4 (d, J 10.9 Hz),
43.8 (d, J 68.1 Hz), 74.0 (d, J 5.4 Hz), 124.8, 126.5, 127.6, 128.2 (d, J 12.7 Hz), 129.4 (d, J 9.1 Hz),
129.6 (d, J 10.0 Hz), 131.0 (d, J 2.7 Hz), 133.1 (d, J 98.1 Hz), 146.0 (d, J 4.5 Hz); δC (202 MHz,
CDCl3) 38.91; GC tR = 12.20 min; GC−MS (EI, 70 eV) m/z=259 (M+−CH3) (49), 241 (M+−H2O) (1),
157 (29), 154 (100), 139 (80), 121 (10), 105 (17), 103 (12), 92 (20), 91 (83), 78 (10), 77 (50), 51 (20),
47 (14%).
Minor diastereomer: Rf (AcOEt/MeOH 9:1) 0.74; δH (500 MHz, CDCl3) 1.67 (3H, d, J 1.9 Hz), 1.81
(3H, d, J 12.9 Hz), 2.57 (2H, d, J 10.1 Hz), 6.05 (1H, bs), 7.21−7.27 (1H, m), 7.28−7.32 (1H, m),
7.34−7.42 (3H, m), 7.43−7.49 (1H, m), 7.52−7.67 (3H, m), 7.69−7.76 (1H, m); δC (126 MHz, CDCl3)
16.9 (d, J 68.1 Hz), 32.9 (d, J 10.9 Hz), 44.2 (d, J 67.2 Hz), 74.1 (d, J 6.4 Hz), 125.0, 127.0, 128.4,
128.7 (d, J 11.8 Hz), 128.8 (d, J 11.8 Hz), 129.3 (d, J 9.1 Hz), 131.9 (d, J 2.7 Hz), 134.8 (d, J 96.3
Hz), 147.3 (d, J 4.5 Hz); δP (202 MHz, CDCl3) 39.96; GC tR = 12.48 min; GC−MS (EI, 70 eV)
m/z=259 (M+−CH3) (50), 241 (M+−H2O) (1), 157 (29), 154 (100), 140 (10), 139 (68), 103 (13), 92
(20), 91 (83), 78 (10), 77 (35), 51 (12), 47 (11%);
ν max (ATR) for a mixture of diastereomers: 3231, 3054, 3023, 2965, 1591, 1490, 1436, 1369, 1292,
1256, 1142, 1114, 1068, 1024, 919, 893, 824, 737, 685, 501, 425.
4.2.11. (2-Hydroxy-2,3-dimethylbutyl)methylphenylphosphine oxide (24). This compound was
prepared according to General Procedure A from dimethylphenylphosphine oxide (13) (0.204 g, 1.32
mmol) and 3-methyl-2-butanone (0.171 g, 1.99 mmol) as a white sticky solid; yield 0.275 g (87%).
Isolated as a mixture of diastereomers (dr = 55.5:45.5).
Major diastereomer: Rf (AcOEt/MeOH 9:1) 0.55; δH (500 MHz, CDCl3) 0.91 (6H, d, J 6.3 Hz), 1.10
(3H, d, J 6.6 Hz), 1.81 (3H, d, J 12.9 Hz), 1.83−1.88 (1H, m), 2.06−2.18 (1H, m), 2.23−2.34 (1H, m),
4.61 (1H, bs), 7.46−7.58 (3H, m), 7.68−7.78 (2H, m); δC (126 MHz, CDCl3) 16.9, 17.5, 19.5 (d, J 70.8
Hz), 25.1 (d, J 4.5 Hz), 38.2 (d, J 69.9 Hz), 39.6 (d, J 10.0 Hz), 75.0 (d, J 6.4 Hz), 128.8 (d, J 11.8
Hz), 129.6 (d, J 11.8 Hz), 131.6 (d, J 2.7 Hz), 135.1 (d, J 95.4 Hz); δP (202 MHz, CDCl3) 39.40; GC tR
17

ACCEPTED MANUSCRIPT
= 10.06 min; GC−MS (EI, 70 eV) m/z=225 (M+−CH3) (7), 198 (11), 197 (98), 157 (15), 154 (20), 140
(24), 139 (100), 91 (38), 77 (25), 47 (15%).
Minor diastereomer: Rf (AcOEt/MeOH 9:1) 0.55; δH (500 MHz, CDCl3) 0.66 (3H, d, J 6.6 Hz), 0.94
(3H, d, J 6.6 Hz), 1.33 (3H, s), 1.76 (3H, d, J 12.9 Hz), 1.80−1.82 (1H, m), 2.06−2.18 (1H, m),
2.22−2.33 (1H, m), 4.55 (1H, bs), 7.46−7.60 (3H, m), 7.68−7.78 (2H, m); δC (126 MHz, CDCl3) 16.8,
17.7, 19.3 (d, J 69.0 Hz), 24.6 (d, J 7.3 Hz), 38.5 (d, J 8.2 Hz), 38.8 (d, J 70.8 Hz), 75.3 (d, J 6.4 Hz),
128.7 (d, J 11.8 Hz), 129.7 (d, J 12.7 Hz), 131.7 (d, J 2.7 Hz), 135.1 (d, J 96.3 Hz); δP (202 MHz,
CDCl3) 39.03; GC tR = 10.09 min; GC−MS (EI, 70 eV) m/z=225 (M+−CH3) (5), 198 (10), 197 (97),
157 (14), 154 (20), 140 (28), 139 (100), 125 (11), 91 (40), 77 (26), 47 (16%);
ν max (ATR) for a mixture of diastereomers: 3344, 3051, 2959, 2874, 1466, 1437, 1409, 1383, 1294,
1155, 1110, 1011, 923,894, 817, 737, 693, 576, 530, 493, 436.
4.2.12. (2-Hydroxy-2-methylbutyl)methylphenylphosphine oxide (25). This compound was prepared
according to General Procedure A from dimethylphenylphosphine oxide (13) (0.223 g, 1.45 mmol)
and 2-butanone (0.157 g, 2.17 mmol) as a colorless oil; yield 0.253 g (77%). Isolated as a mixture of
diastereomers (dr = 53.5:46.5).
Major diastereomer: Rf (AcOEt/MeOH 9:1) 0.42; δH (500 MHz, CDCl3) 0.86 (3H, t, J 7.6 Hz), 1.14
(3H, s), 1.42−1.51 (1H, m), 1.51−1.58 (1H, m), 1.73 (3H, d, J 12.9 Hz), 2.06−2.14 (1H, m), 2.15-2.27
(1H, m), 5.25 (1H, bs), 7.40−7.51 (3H, m), 7.62−7.73 (2H, m); δC (126 MHz, CDCl3) 8.1, 18.9 (d, J
69.9 Hz), 27.4 (d, J 4.5 Hz), 37.1 (d, J 9.1 Hz), 41.0 (d, J 69.9 Hz), 72.6 (d, J 6.4 Hz), 128.6 (d, J 11.8
Hz), 129.5 (d, J 10.0 Hz), 131.5 (d, J 2.7 Hz), 134.5 (d, J 96.3 Hz); δP (202 MHz, CDCl3) 39.35; GC tR
= 9.74 min; GC−MS (EI, 70 eV) m/z=208 (M+−H2O) (11), 197 (67), 157 (13), 154 (32), 140 (34), 139
(100), 92 (13), 91 (55), 77 (28), 47 (16%).
Minor diastereomer: Rf (AcOEt/MeOH 9:1) 0.42; δH (500 MHz, CDCl3) 0.68 (3H, t, J 7.4 Hz), 1.27
(3H, s), 1.52−1.59 (2H, m), 1.74 (3H, d, J 12.9 Hz), 2.15−2.26 (2H, m), 5.17 (1H, bs), 7.39−7.52 (3H,
m), 7.62−7.72 (2H, m); δC (126 MHz, CDCl3) 8.2, 18.6 (d, J 7.3 Hz), 28.1 (d, J 8.2 Hz), 35.9 (d, J 6.4
Hz), 41.2 (d, J 69.0 Hz), 72.9 (d, J 5.4 Hz), 128.6 (d, J 11.8 Hz), 129.4 (d, J 10.0 Hz), 131.6 (d, J 2.7
Hz), 134.6 (d, J 96.3 Hz); δP (202 MHz, CDCl3) 39.08; GC tR = 9.74 min; GC−MS (EI, 70 eV)
m/z=208 (M+−H2O) (11), 197 (67), 157 (13), 154 (32), 140 (34), 139 (100), 92 (13), 91 (55), 77 (28),
47 (16%);
ν max (ATR) for a mixture of diastereomers: 3324, 3053, 2966, 2927, 2879, 1442, 1436, 1408, 1372,
1294, 1151, 1112, 995, 904, 892, 823, 737, 694, 536, 492, 436.
4.2.13. (2-Hydroxy-2,3,3-trimethylbutyl)methylphenylphosphine oxide (26). This was prepared
according to General Procedure A from dimethylphenylphosphine oxide (13) (0.354 g, 2.29 mmol)
18

ACCEPTED MANUSCRIPT
and 3,3-dimethyl-2-butanone (0.345 g, 3.35 mmol) as a white solid; yield 0.469 g (80%). Isolated as a
mixture of diastereomers (dr = 60:40).
Major diastereomer: Rf (AcOEt/MeOH 9:1) 0.62; δH (500 MHz, CDCl3) 0.95 (9H, s), 1.17 (3H, d, J
0.9 Hz), 1.75 (3H, d, J 12.9 Hz), 1.99−2.14 (1H, m), 2.37−2.47 (1H, m), 4.27 (1H, bs), 7.46−7.57 (3H
m), 7.66−7.79 (2H, m); δC (126 MHz, CDCl3) 19.3, 24.0 (d, J 3.6 Hz), 24.9, 36.8 (d, J 70.8 Hz), 38.6
(d, J 10.0 Hz), 76.5 (d, J 6.4 Hz), 128.8 (d, J 10.9 Hz), 129.7 (d, J 10.0 Hz), 131.5 (d, J 2.7 Hz), 135.2
(d, J 94.5 Hz); δP (202 MHz, CDCl3) 39.77; GC tR = 10.27 min; GC−MS (EI, 70 eV) m/z= 198 (11),
197 (100), 157 (14), 154 (12), 140 (11), 139 (87), 91 (24), 77 (19), 47 (11%).
Minor diastereomer: Rf (AcOEt/MeOH 9:1) 0.62; δH (500 MHz, CDCl3) 0.93 (9H, s), 1.55 (3H, d, J
0.6 Hz), 1.85 (3H, d, J 12.9 Hz), 1.97−2.14 (1H, m), 2.36−2.49 (1H, m), 4.25 (1H, bs), 7.46−7.58 (3H,
m), 7.65−7.80 (2H, m); δC (126 MHz, CDCl3) 19.8, 24.4 (d, J 2.7 Hz), 24.9, 37.4 (d, J 69.9 Hz), 38.7
(d, J 9.1 Hz), 76.4 (d, J 6.4 Hz), 128.7 (d, J 11.8 Hz), 129.4 (d, J 9.1 Hz), 131.6 (d, J 2.7 Hz), 135.6 (d,
J 98.1 Hz); δP (202 MHz, CDCl3) 39.62; GC tR = 10.37 min; GC−MS (EI, 70 eV) m/z=198 (11), 197
(100), 157 (12), 154 (11), 140 (13), 139 (84), 91 (24), 77 (19), 47 (11%);
ν max (ATR) for a mixture of diastereomers: 3421, 3271, 2957, 2909, 2871, 1477, 1438, 1370, 1298,
1142, 1112, 1001, 895, 831, 743, 697, 493, 447.
4.2.14. (2-Hydroxy-2,4,4-trimethylpentyl)methylphenylphosphine oxide (27). This compound was
prepared according to General Procedure A from dimethylphenylphosphine oxide (13) (0.226 g, 1.47
mmol) and 4,4-dimethyl-2-pentanone (0.251 g, 2.20 mmol) as a white solid; yield 0.325 g (83%).
Isolated as a mixture of diastereomers (dr = 91:9).
Major diastereomer: Rf (AcOEt/MeOH 9:1) 0.73; δH (500 MHz, CDCl3) 0.92 (9H, s), 1.24−1.35 (2H,
m), 1.49 (3H, d, J 1.6 Hz), 1.77 (3H, d, J 12.9 Hz), 2.17−2.24 (1H, m), 2.26−2.35 (1H, m), 4.54 (1H,
bs), 7.46−7.57 (3H, m), 7.66−7.76 (2H, m); δC (126 MHz, CDCl3) 19.4 (d, J 69.0 Hz), 30.6 (d, J 8.2
Hz), 31.3, 31.4, 44.8 (d, J 68.1 Hz), 55.2 (d, J 7.3 Hz), 74.3 (d, J 6.4 Hz), 128.7 (d, J 11.8 Hz), 129.6
(d, J 10.0 Hz), 131.6 (d, J 2.7 Hz), 135.2 (d, J 96.3 Hz); δP (202 MHz, CDCl3) 38.17; GC tR = 10.57
min; GC−MS (EI, 70 eV) m/z=253 (M+−CH3) (6), 198 (11), 197 (100), 154 (39), 140 (12), 139 (90),
92 (11), 91 (43), 77 (22), 57 (14), 47 (12%).
Minor diastereomer: Rf (AcOEt/MeOH 9:1) 0.73; δH (500 MHz, CDCl3) 1.03 (9H, s), 1.25 (3H, s),
1.32−1.33 (2H, m), 1.75 (3H, d, J 12.8 Hz), 2.17−2.22 (1H, m), 2.36−2.44 (1H, m), 4.47 (1H, bs),
7.47−7.57 (3H, m), 7.67−7.76 (2H, m); δC (126 MHz, CDCl3) 19.7 (d, J 69.9 Hz), 30.0 (d, J 5.4 Hz),
31.4, 31.6, 43.9 (d, J 68.1 Hz), 56.6 (d, J 10.0 Hz), 74.2 (d, J 6.4 Hz), 128.8 (d, J 11.8 Hz), 129.6 (d, J
9.3 Hz), 131.6 (d, J 2.7 Hz), 136.6 (d, J 95.4 Hz); δP (202 MHz, CDCl3) 38.17; GC tR = 10.37 min;
GC−MS (EI, 70 eV) m/z=253 (M+−CH3) (8), 198 (11), 197 (95), 193 (11), 157 (10), 154 (45), 140
(13), 139 (100), 92 (11), 91 (48), 77 (27), 57 (21), 47 (14%);
19

ACCEPTED MANUSCRIPT
ν max (ATR) for a mixture of diastereomers: 3296, 2953, 2904, 2866, 1448, 1435, 1375, 1361, 1296,
1239, 1154, 1098, 918, 899, 894, 857, 795, 741, 733, 691, 597, 512, 441.
4.2.15. (2-Hydroxy-2,2-diphenylethyl)methylphenylphosphine oxide (28). This compound was
prepared according to General Procedure A from dimethylphenylphosphine oxide (13) (0.105 g, 0.68
mmol) and benzophenone (0.185 g, 1.0 mmol) as a white solid; yield 0.191 g (84%); mp 144.8–146.2
°C; Rf (AcOEt/MeOH 9:1) 0.77; [Found C, 75.15; H, 6.46. C21H21O2P requires C, 74.99; H, 6.29%]; ν
max (ATR) 3207, 3054, 2914, 1591, 1440, 1438, 1296, 1223, 1146, 1112, 982, 930, 874, 826, 741,
689, 599, 531, 485, 464; δH (500 MHz, CDCl3) 1.36 (3H, d, J 12.9 Hz), 1.65 (1H, bs), 2.90−3.09 (2H,
m), 7.02−7.15 (3H, mH), 7.21−7.27 (1H, m), 7.29−7.37 (4H, m), 7.36−7.42 (2H, m), 7.44−7.52 (3H,
m), 7.52−7.58 (2H, m); δC (126 MHz, CDCl3) 17.5 (d, J 69.0 Hz), 42.4 (d, J 68.1 Hz), 125.7, 125.9,
126.9, 127.1, 127.9, 128.3, 128.6 (d, J 11.8 Hz), 129.4 (d, J 9.1 Hz), 131.6 (d, J 2.7 Hz), 134.0 (d, J
99.0 Hz), 146.0 (d, J 8.2 Hz), 146.7 (d, J 6.4 Hz); δP (202 MHz, CDCl3) 40.40; GC tR = 19.71 min;
GC−MS (EI, 70 eV) m/z=182 (33), 154 (34), 139 (50), 105 (100%).
4.2.16. (2-Butyl-2-hydroxyhexyl)methylphenylphosphine oxide (29). This compound was prepared
according to General Procedure A from dimethylphenylphosphine oxide (13) (0.366 g, 2.4 mmol) )
and 5-nonanone (0.506g, 3.56 mmol) as a white solid; yield 0.557 g (82%); mp 106.3–108 °C; Rf
(AcOEt/MeOH 9:1) 0.73; [Found C, 68.94; H, 9.93. C17H29O2P requires C, 68.89; H, 9.86%]; ν max
(ATR) 3311, 3061, 2951, 2917, 2867, 1462, 1436, 1375, 1290, 1267, 1143, 1107, 996, 897, 879, 831,
744, 694, 606, 495, 488, 432, 428; δH (500 MHz, CDCl3) 0.62 (3H, t, J 7.9 Hz), 0.70−0.83 (2H, m),
0.86 (3H, t, J 6.9 Hz), 0.91−1.01 (1H, m), 1.03−1.14 (1H, m), 1.19−1.31 (4H, m), 1.31−1.42 (1H, m),
1.43−1.55 (3H, m), 1.70 (3H, d, J 12.9 Hz), 2.09−2.25 (2H, m), 4.66 (1H, s), 7.41−7.52 (3H, m),
7.65−7.73 (2H, m); δC (126 MHz, CDCl3) 13.8, 14.0, 19.4 (d, J 69.0 Hz), 22.7, 23.1, 25.5, 26.3, 39.5
(d, J 68.1 Hz), 40.1 (d, J 5.4 Hz), 40.7 (d, J 9.1 Hz), 74.8 (d, J 5.4 Hz), 128.7 (d, J 10.9 Hz), 129.7 (d,
J 9.1 Hz), 131.6 (d, J 2.7 Hz), 135.0 (d, J 95.4 Hz); δP (202 MHz, CDCl3) 38.70; GC tR = 11.58 min;
GC−MS (EI, 70 eV) m/z=278 (M+−H2O) (5), 240 (14), 239 (100), 157 (21), 154 (32), 140 (41), 139
(68), 125 (11), 91 (35), 77 (21), 57 (15), 55 (10), 47 (11%).
4.2.17. (2-Hydroxy-2-i-propyl-3-methylbutyl)methylphenylphosphine oxide (30). This compound was
prepared according to General Procedure A from dimethylphenylphosphine oxide (13) (0.198 g, 1.3
mmol) ) and 2,4-dimethyl-3-pentanone (0.220g, 1.93 mmol) as a colorless oil; yield 0.204 g (60%); Rf
(AcOEt/MeOH 9:1) 0.71; [Found C, 67.28; H, 9.57. C15H25O2P requires C, 67.14; H, 9.39%]; ν max
(ATR) 3361, 2960, 2914, 2876, 1467, 1436, 1411, 1384, 1292, 1145, 1110, 990, 894, 741, 694, 530,
488, 434; δH (500 MHz, CDCl3) 0.72 (3H, d, J 6.9 Hz), 0.88 (3H, d, J 6.9 Hz), 0.92 (3H, d, J 6.9 Hz),
1.01 (3H, d, J 6.6 Hz), 1.81 (3H, d, J 12.9 Hz), 1.82−1.87 (1H, m), 1.90−1.98 (1H, m), 2.03−2.20 (2H,
m), 4.32 (1H, bs), 7.43−7.54 (3H, m), 7.64−7.75 (2H, m); δC (126 MHz, CDCl3) 17.1, 17.3, 17.4, 17.5,
18.8 (d, J 70.8 Hz), 34.1 (d, J 69.0 Hz), 35.4 (d, J 4.5 Hz), 36.3 (d, J 2.7 Hz), 78.7 (d, J 6.4 Hz), 128.6
20

ACCEPTED MANUSCRIPT
(d, J 10.9 Hz), 129.7 (d, J 9.1 Hz), 131.5 (d, J 2.7 Hz), 135.2 (d, J 96.3 Hz); δP (202 MHz, CDCl3)
39.03; GC tR = 10.79 min; GC−MS (EI, 70 eV) m/z=250 (M+−H2O) (2), 226 (14), 225 (100), 157 (28),
154 (22), 140 (30), 139 (78), 125 (12), 91 (36), 77 (24), 71 (12), 69 (14), 47 (16%).
4.2.18. (2-Ethyl-2-hydroxybutyl)methylphenylphosphine oxide (31). This compound was prepared
according to General Procedure A from dimethylphenylphosphine oxide (13) (0.205 g, 1.3 mmol) )
and pentan-3-one (0.172g, 1.99 mmol) as a colorless oil; yield 0.240 g (75%); Rf (AcOEt/MeOH 9:1)
0.56; [Found C, 65.15; H, 9.08. C13H21O2P requires C, 64.98; H, 8.81%]; ν max (ATR) 3302, 2967,
2960, 2934, 2873, 1440, 1296, 1254, 1210, 1152, 1111, 1023, 978, 961, 899, 890, 825, 745, 693, 582,
500, 430; δH (500 MHz, CDCl3) 0.66 (3H, t, J 7.6 Hz), 0.88 (3H, t, J 7.6 Hz), 1.39−1.52 (1H, m),
1.53−1.70 (3H, m), 1.78 (3H, d, J 12.9 Hz), 2.12−2.27 (2H, m), 4.40 (1H, bs), 7.46−7.56 (3H, m),
7.67−7.75 (2H, m); δC (126 MHz, CDCl3) 7.8, 7.9, 19.3 (d, J 69.9 Hz), 32.1 (d, J 5.4 Hz), 32.6 (d, J
9.1 Hz), 38.9 (d, J 69.0 Hz), 75.2 (d, J 5.5 Hz), 128.7 (d, J 11.8 Hz), 129.5 (d, J 10.0 Hz), 131.6 (d, J
2.7 Hz), 135.0 (d, J 96.3 Hz); δP (202 MHz, CDCl3) 38.95; GC tR = 10.20 min; GC−MS (EI, 70 eV)
m/z=222 (M+−H2O) (12), 212 (10), 211 (89), 157 (25), 154 (35), 140 (48), 139 (100), 125 (15), 92
(13), 91 (57), 77 (33), 57 (16), 55 (13), 51 (11), 47 (21%).
4.2.19. [(1-Hydroxy)cyclopentylmethyl)]methylphenylphosphine oxide (32). This compound was
prepared according to General Procedure A from dimethylphenylphosphine oxide (13) (0.118 g, 0.7
mmol) ) and pentanone (0.097g, 1.15 mmol) as a white solid; yield 0.129 g (71%); mp 80.7–81.4 °C;
Rf (AcOEt/MeOH 9:1) 0.43; [Found C, 65.59; H, 8.14. C13H21O2P requires C, 65.53; H, 8.04%]; ν max
(ATR) 3301, 3057, 2957, 2885, 2841, 1424, 1402, 1378, 1299, 1296, 1262, 1224, 1162, 1144, 1110,
1002, 892, 873, 829, 746, 697, 499, 447; δH (500 MHz, CDCl3) 1.16−1.30 (1H, m), 1.42−1.60 (3H,
m), 1.67−1.77 (2H, m), 1.74 (3H, d, J 12.9 Hz), 1.78−1.85 (1H, m), 1.87−1.96 (1H, m), 2.20−2.30
(1H, m), 2.37−2.47 (1H, m), 4.29 (1H, bs), 7.41−7.54 (3H, m), 7.64−7.76 (2H, m); δC (126 MHz,
CDCl3) 19.0 (d, J 69.0 Hz), 23.1, 23.5, 40.7 (d, J 6.4 Hz), 41.2 (d, J 69.0 Hz), 41.8 (d, J 8.2 Hz), 80.4
(d, J 6.4 Hz), 128.7 (d, J 11.8 Hz), 129.7 (d, J 9.1 Hz), 131.7 (d, J 2.7 Hz), 134.6 (d, J 96.3 Hz); δP
(202 MHz, CDCl3) 38.53; GC tR = 9.30 min; GC−MS (EI, 70 eV) m/z=238 (M+) (1), 220 (M+−H2O)
(17), 219 (12), 209 (36), 196 (50), 181 (36), 157 (11), 154 (60), 140 (56), 139 (100), 125 (29), 99 (10),
92 (19), 91 (86%).
4.2.20. [(1-Hydroxy)cyclohexylmethyl)]methylphenylphosphine oxide (33). This compound was
prepared according to General Procedure A from dimethylphenylphosphine oxide (13) (0.101 g, 0.65
mmol) and hexanone (0.097g, 0.98 mmol) as a white solid; yield 0.126 g (76%); mp 108.8–110.4 °C;
Rf (AcOEt/MeOH 9:1) 0.55; [Found C, 66.48; H, 8.23. C14H21O2P requires C, 66.65; H, 8.39%]; ν max
(ATR) 3306, 2929, 2888, 2844, 1438, 1261, 1175, 1153, 1109, 981, 892, 819, 747, 695, 511, 487, 446;
δH (500 MHz, CDCl3) 1.10−1.25 (2H, m), 1.26−1.35 (1H, m), 1.35−1.47 (2H, m), 1.48−1.58 (2H, m),
1.60−1.71 (2H, m), 1.75 (3H, d, J 12.9 Hz), 1.76−1.80 (1H, m), 2.14−2.28 (2H, m), 4.53 (1H, bs),
21

ACCEPTED MANUSCRIPT
7.43−7.55 (3H, m), 7.65−7.74 (2H, m); δC (126 MHz, CDCl3) 19.5 (d, J 69.9 Hz), 22.0, 22.2, 25.4,
39.0 (d, J 6.4 Hz), 40.1 (d, J 10.0 Hz), 41.8 (d, J 70.8 Hz), 71.9 (d, J 6.4 Hz), 128.7 (d, J 11.8 Hz),
129.6 (d, J 10.0 Hz), 131.6 (d, J 2.7 Hz), 135.1 (d, J 95.4 Hz); δP (202 MHz, CDCl3) 38.65; GC tR =
11.64 min; GC−MS (EI, 70 eV) m/z=252 (M+) (3), 234 (M+−H2O) (26), 233 (11), 210 (16), 209 (68),
196 (30), 181 (17), 157 (15), 154 (70), 141 (18), 140 (75), 139 (100), 125 (30), 121 (10), 95 (10), 92
(22), 91 (97), 77 (41), 65 (10), 55 (19), 51 (14), 47 (30%).
4.2.21. [(1-Hydroxy)cycloheptylmethyl)]methylphenylphosphine oxide (34). This compound was
prepared according to General Procedure A from dimethylphenylphosphine oxide (13) (0.204 g, 1.33
mmol) and heptanone (0.233g, 1.99 mmol) as a white solid; yield 0.319 g (90%); mp 80.6–82.6 °C; Rf
(AcOEt/MeOH 9:1) 0.50; [Found C, 67.49; H, 8.61. C15H23O2P requires C, 67.65; H, 8.70%]; ν max
(ATR) 3350, 2923, 2858, 1436, 1290, 1246, 1155, 1146, 1103, 1033, 901, 879, 801, 745, 736, 690,
571, 494, 445; δH (500 MHz, CDCl3) 1.04−1.17 (1H, m), 1.24−1.37 (2H, m), 1.38−1.46 (2H, m),
1.46−1.56 (3H, m), 1.59−1.63 (2H, m), 1.72 (3H, d, J 12.9 Hz), 1.75−1.82 (1H, m), 1.87−1.95 (1H,
m), 2.16−2.28 (2H, m), 4.54 (1H, bs), 7.41−7.53 (3H, m), 7.64−7.71 (2H, m); δC (126 MHz, CDCl3)
19.3 (d, J 69.9 Hz), 21.8, 21.8, 24.2, 29.4 (d, J 16.3 Hz), 42.2 (d, J 6.4 Hz), 42.9 (d, J 69.0 Hz), 43.7
(d, J 9.1 Hz), 75.8 (d, J 6.4 Hz), 128.6 (d, J 10.9 Hz), 129.5 (d, J 10.0 Hz), 131.5 (d, J 3.6 Hz), 135.0
(d, J 95.4 Hz); δP (202 MHz, CDCl3) 38.54; GC tR = 12.38 min; GC−MS (EI, 70 eV) m/z=266 (M+)
(2), 248 (M+−H2O) (17), 209 (50), 196 (32), 181 (23), 157 (15), 155 (11), 154 (92), 141 (20), 140
(100), 139 (98), 125 (35), 109 (12), 95 (10), 92 (22), 91 (96), 79 (11), 77 (43), 68 (14), 67 (14), 55
(24), 51 (14), 47 (31%).
4.2.22. (2-Hydroxy-2-methylpropyl)diphenylphosphine oxide (37). This compound was prepared
according to General Procedure A from diphenylmethylphosphine oxide (0.302 g, 1.4 mmol) and
acetone (0.122 g, 2.1 mmol) as a white solid; yield 0.278 g (73%); mp 103.8–105.7 °C; Rf
(AcOEt/MeOH 9:1) 0.64; [Found C, 69.96; H, 6.85. C16H19O2P requires C, 70.06; H, 6.98%]; ν max
(ATR) 3321, 3055, 2977, 2924, 2878, 1477, 1435, 1376, 1232, 1163, 1098, 972, 902, 804, 748, 711,
667, 567, 511, 487; δH (500 MHz, CDCl3) 1.28 (6H, s), 2.60 (2H, d, J 9.5 Hz), 4.41 (1H, bs),
7.45−7.54 (6H, m), 7.72−7.78 (4H, m); δC (126 MHz, CDCl3) 31.5, 31.6, 41.2 (d, J 69.9 Hz), 70.8 (d,
J 6.4 Hz), 128.7 (d, J 11.8 Hz), 130.4 (d, J 9.1 Hz), 131.8 (d, J 2.7 Hz), 133.9 (d, J 99.0 Hz); δC (202
MHz, CDCl3) 32.45; GC tR = 12.18 min; GC−MS (EI, 70 eV) m/z=256 (M+−H2O) (21), 255 (31), 216
(27), 215 (87), 202 (14), 201 (100), 152 (12), 131 (14), 125 (17), 91 (24), 78 (13), 77 (71), 51 (41), 47
(45%). Analytical data are in accordance with those reported in the literature.21
4.2.23. (2-Hydroxy-2-methylpropyl)-t-butylphenylphosphine oxide (38). This compound was prepared
according to General Procedure A from tert-butylmethylphenylphosphine oxide (0.142 g, 0.7 mmol)
and acetone (0.063 g, 1.1 mmol) as a white solid; yield 0.116 g (63%); mp 114.8–115.9 °C; Rf
(AcOEt/MeOH 9:1) 0.60; [Found C, 66.01; H, 9.08. C14H23O2P requires C, 66.12; H, 9.12%]; ν max
22

ACCEPTED MANUSCRIPT
(ATR) 3258, 3063, 2970, 2903, 2868, 1461, 1435, 1364, 1246, 1208, 1147, 1104, 903, 813, 745, 695,
627, 527, 491, 461; δH (500 MHz, CDCl3) 1.06 (3H, s), 1.10 (9H, d, J 14.8 Hz), 1.33 (3H, d, J 2.5 Hz),
2.15−2.21 (1H, m), 2.35−2.44 (1H, m), 4.48 (1H, bs), 7.45−7.58 (3H, m), 7.68−7.82 (2H, m); δC (126
MHz, CDCl3) 23.7, 30.1 (d, J 3.6 Hz), 32.91 (d, J 69.0 Hz), 32.92 (d, J 11.8 Hz), 34.1 (d, J 62.7 Hz),
70.4 (d, J 5.4 Hz), 128.3 (d, J 10.9 Hz), 131.3 (d, J 86.3 Hz), 131.4 (d, J 7.3 Hz), 131.6 (d, J 2.7 Hz);
δP (202 MHz, CDCl3) 50.17; GC tR = 9.63 min; GC−MS (EI, 70 eV) m/z=236 (M+−H2O) (3), 239
(16), 197 (25), 180 (16), 179 (10), 142 (27), 141 (33), 140 (46), 125 (100), 91 (15), 78 (13), 78 (16),
77 (26), 57 (67) 47 (49%).
4.2.24. (2-Hydroxy-3-methylbutyl)diphenylphosphine oxide (39). This compound was prepared
according to General Procedure A from diphenylmethylphosphine oxide (0.282 g, 1.3 mmol) and
isobutyraldehyde (0.141 g, 2.0 mmol) as a colorless oil; yield 0.295 g (78%); Rf (AcOEt/MeOH 9:1)
0.72; [Found C, 70.98; H, 7.52. C17H21O2P requires C, 70.82; H, 7.34%]; ν max (ATR) 3333, 3053,
2957, 2870, 1436, 1154, 1118, 994, 742, 699, 692, 539; δH (500 MHz, CDCl3) 0.90 (3H, d, J 2.2 Hz),
0.91 (3H, d, J 2.2 Hz), 1.72−1.81 (1H, m), 2.32−2.44 (2H, m), 3.78−3.89 (1H, m), 4.43 (1H, bs),
7.42−7.55 (6H, m), 7.69−7.80 (4H, m); δC (126 MHz, CDCl3) 17.5, 17.8, 32.9 (d, J 72.7 Hz), 34.4 (d,
J 12.7 Hz), 71.3 (d, J 5.4 Hz), 128.7 (d, J 6.4 Hz), 128.8 (d, J 6.4 Hz), 130.4 (d, J 10.0 Hz), 130.9 (d, J
10.0 Hz), 131.7 (d, J 98.1 Hz), 131.98 (d, J 2.7 Hz), 132.0 (d, J 2.7 Hz), 133.5 (d, J 99.9 Hz); δP (202
MHz, CDCl3) 35.29; GC tR = 11.12 min; GC−MS (EI, 70 eV) m/z=270 (M+−H2O) (5), 246 (13), 245
(86), 215 (26), 202 (44), 201 (100), 77 (41); 51 (16), 47 (27%). Analytical data are in accordance with
those reported in the literature.22
4.2.25. (2-Hydroxy-3-methylbutyl)-t-butylphenylphosphine oxide (40). This compound was prepared
according to General Procedure A from tert-butylmethylphenylphosphine oxide (0.142 g, 0.7 mmol)
and isobutyraldehyde (0.078 g, 1.1 mmol) as a white solid; yield 0.126 g (65%). Isolated as a mixture
of diastereomers (dr = 52:48).
Major diastereomer: Rf (AcOEt/MeOH 9:1) 0.65; ν max (ATR) 3284, 2955, 2871, 1477, 1434, 1364,
1138, 1105, 997, 844, 816, 779, 695, 632, 599, 476; δH (500 MHz, CDCl3) 0.88 (3H, d, J 6.6 Hz), 0.92
(3H, d, J 6.6 Hz), 1.10 (9H, d, J 14.8 Hz), 1.62−1.77 (1H, m), 2.06−2.14 (2H, m), 3.47−3.59 (1H, m),
4.82 (1H, bs), 7.37−7.55 (3H, m), 7.59−7.72 (2H, m); δC (126 MHz, CDCl3) 17.60, 17.62, 23.8, 25.5
(d, J 64.5 Hz), 32.6 (d, J 68.1 Hz), 34.3 (d, J 11.8 Hz), 71.3 (d, J 5.5 Hz), 128.0 (d, J 10.9 Hz), 129.0
(d, J 86.3 Hz), 131.68 (d, J 8.2 Hz), 131.70 (d, J 2.7 Hz); δP (202 MHz, CDCl3) 54.46; GC tR = 10.26
min; GC−MS (EI, 70 eV) m/z=250 (M+−H2O) (2), 225 (74), 211 (25), 193 (13), 142 (20), 141 (29);
140 (32), 126 (24) 125 (100) 91 (12%).
Minor diastereomer: Rf (AcOEt/MeOH 9:1) 0.65; ν max (ATR) 3276, 2955, 2869, 1463, 1436, 1364,
1139, 1106, 998, 844, 817, 778, 696, 633, 508, 473; δH (500 MHz, CDCl3) 0.86 (6H, d, J 6.6 Hz), 1.09
23

ACCEPTED MANUSCRIPT
(9H, d, J 15.1 Hz), 1.64−1.77 (1H, m), 2.09−2.13 (1H, m), 2.30−2.37 (1H, m), 3.92−4.04 (1H, m),
4.31 (1H, bs), 7.39−7.55 (3H, m), 7.62−7.69 (2H, m); δC (126 MHz, CDCl3) 17.7, 18.1, 24.2, 27.8 (d,
J 64.5 Hz), 33.2 (d, J 68.1 Hz), 34.5 (d, J 10.0 Hz), 72.5 (d, J 6.4 Hz), 128.3 (d, J 10.0 Hz), 131.1 (d, J
8.2 Hz), 131.6 (d, J 88.1 Hz), 131.4 (d, J 2.7 Hz); δP (202 MHz, CDCl3) 49.99; GC tR = 10.53 min;
GC−MS (EI, 70 eV) m/z=250 (M+−H2O) (3), 225 (56), 211 (31), 193 (16), 142 (27), 141 (35); 140
(34), 126 (31) 125 (100) 91 (13%).
4.2.26. (2-Hydroxy-2-methylpropyl)methyl-1-naphthylphosphine oxide (41). This compound was
prepared according to General Procedure A from dimethyl-1-naphthylphosphine oxide (0.123 g, 0.6
mmol) and acetone (0.052 g, 0.9 mmol) as a white solid; yield 0.154 g (98%); mp 95.8–97.4 °C; Rf
(AcOEt/MeOH 9:1) 0.43; [Found C, 68.75; H, 7.38. C15H19O2P requires C, 68.69; H, 7.30%]; ν max
(ATR) 3364, 3298, 2966, 2919, 1505, 1459, 1377, 1296, 1270, 1204, 1132, 1096, 1024, 984, 961, 907,
889, 834, 802, 774, 741, 550, 440; δH (500 MHz, CDCl3) 1.26 (3H, s), 1.46 (3H, s), 2.00 (3H, d, J 12.9
Hz), 2.35−2.42 (1H, m), 2.49−2.58 (1H, m), 5.09 (1H, bs), 7.55 (2H, ddd, J 8.4 Hz, 7.3 Hz, 1.7 Hz),
7.58−7.64 (1H, m), 7.92 (1H, d, J 8.2 Hz), 8.01 (1H, d, J 8.2 Hz), 8.06 (1H, ddd, J 14.6 Hz, 7.0 Hz,
1.1 Hz), 8.38 (1H, d, J 8.5 Hz); δC (126 MHz, CDCl3) 19.9 (d, J 69.9 Hz), 31.1 (d, J 7.3 Hz), 31.7 (d, J
8.2 Hz), 43.3 (d, J 68.1 Hz), 70.8 (d, J 6.4 Hz), 124.7 (d, J 12.7 Hz), 125.1 (d, J 4.5 Hz), 126.2, 127.4,
129.5, 130.6 (d, J 93.6 Hz), 131.5 (d, J 8.2 Hz), 132.0 (d, J 10.0 Hz), 132.9 (d, J 2.7 Hz), 133.7 (d, J
9.1 Hz); δP (202 MHz, CDCl3) 39.38; GC tR = 12.31 min; GC−MS (EI, 70 eV) m/z=262 (M+) (10),
247 (50), 245 (14), 244 (25), 243 (23), 229 (57) 204 (26), 203 (98), 190 (13), 189 (100), 181 (11), 180
(15); 174 (13), 173 (36) 171 (19), 170 (12), 165 (12), 142 (17), 141 (75), 128 (47); 127 (48), 126 (18)
(100), 119 (31); 115 (35), 101 (11), 77 (23); 63 (11%).
4.2.27. (2-Hydroxy-3-methylpropyl)methyl-1-naphthylphosphine oxide (42). This compound was
prepared according to General Procedure A from dimethyl-1-naphthylphosphine oxide (0.216 g, 1.1
mmol) and isobutyraldehyde (0.114 g, 1.6 mmol); yield of two diastereomers 0.273 g (94%), (dr =
50.5:49.5).
Major diastereomer: Yield 0.127 g (44% isolated as a pure compound); white solid; mp 97.7–99.7 °C;
Rf (Hexane/CHCl3/i-PrOH 5:1:1) 0.38; [Found C, 69.63; H, 7.69. C16H21O2P requires C, 69.55; H,
7.66%]; ν max (ATR) 3249, 2958, 2906, 2874, 1505, 1460, 1299, 1111, 1024, 1000, 904, 823, 795,
769, 715, 509, 439; δH (500 MHz, CDCl3) 0.93 (3H, d, J 6.9 Hz), 0.97 (3H, d, J 6.3 Hz), 1.74−1.85
(1H, m), 2.02 (3H, d, J 12.6 Hz), 2.09−2.20 (1H, m), 2.28−2.44 (1H, m), 4.00-4.15 (1H, m), 4.52 (1H,
bs), 7.49−7.62 (2H, m), 7.62−7.67 (1H, m), 7.88−7.98 (2H, m), 8.04 (1H, d, J 8.2 Hz), 8.60 (1H, d, J
8.5 Hz); δC (126 MHz, CDCl3) 16.7 (d, J 70.8 Hz), 17.7, 18.1, 34.6 (d, J 6.4 Hz), 34.9 (d, J 63.6 Hz),
72.1 (d, J 5.4 Hz), 124.6 (d, J 12.7 Hz), 125.6 (d, J 4.5 Hz), 126.5, 127.6, 129.4, 129.9 (d, J 94.5 Hz),
130.8 (d, J 9.1 Hz), 132.6 (d, J 8.2 Hz), 133.2 (d, J 2.7 Hz), 133.8 (d, J 9.1 Hz); δP (202 MHz, CDCl3)
42.11; GC tR = 12.89 min; GC−MS (EI, 70 eV) m/z=276 (M+) (14), 234 (11), 233 (80), 214 (30), 203
24

ACCEPTED MANUSCRIPT
(32), 190 (52) 189 (100), 175 (30), 173 (27), 171 (14), 141 (36), 128 (47); 127 (34), 126 (10) 115 (18),
77 (16%).
Minor diastereomer: Yield 0.146 g (50% isolated as a pure compound); white sticky solid; Rf
(Hexane/CHCl3/i-PrOH 5:1:1) 0.56; [Found C, 69.68; H, 7.66. C16H21O2P requires C, 69.55; H,
7.66%]; ν max (ATR) 3236, 2957, 2922, 2871, 1507, 1461, 1294, 1142, 1135, 1025, 987, 890, 801,
773, 451, 428; δH (500 MHz, CDCl3) 0.88 (3H, d, J 6.6 Hz), 0.88 (3H, d, J 6.9 Hz), 1.62−1.78 (1H,
m), 2.04 (3H, d, J 12.9 Hz), 2.20−2.41 (2H, m), 3.84−3.97 (1H, m), 4.23 (1H, bs), 7.52−7.67 (3H, m),
7.96 (1H, d, J 7.9 Hz), 8.00−8.16 (2H, m), 8.42 (1H, d, J 8.5 Hz); δC (126 MHz, CDCl3) 17.4, 18.0,
19.1 (d, J 69.9 Hz), 34.6 (d, J 12.7 Hz), 35.3 (d, J 69.9 Hz), 71.6 (d, J 5.4 Hz), 124.8 (d, J 12.7 Hz),
125.2 (d, J 3.6 Hz), 126.3, 127.4, 129.4 (d, J 91.7 Hz), 129.5, 132.1 (d, J 8.2 Hz), 132.5 (d, J 9.1 Hz),
133.1 (d, J 2.7 Hz), 133.8 (d, J 9.1 Hz); δP (202 MHz, CDCl3) 40.79; GC tR = 12.88 min; GC−MS (EI,
70 eV) m/z= 276 (M+) (14), 234 (11), 233 (77), 214 (18), 203 (37), 190 (49) 189 (100), 175 (26), 174
(10), 171 (12), 141 (40), 128 (48); 127 (36), 126 (12) 115 (19), 77 (20%).
4.3. General Procedure B. Attempted synthesis of Cyclic Phosphine Oxides.
Method 1. In a flame-dried Schlenk tube (20 mL) equipped with magnetic stirrer and inert gas inlet
was placed (2-hydroxy-2-methylpropyl)methylphenylphosphine oxide (20) (0.076g, 0.36 mmol) in
DCE (3 mL) and BF3-OEt2 (0.132 g 0.54 mmol) was added. Reaction was stirred of reflux for 4 hours.
After that time the reaction was cooled to room temperature and quenched by addition of H2O (10 mL)
and extracted with DCM (3×20 mL). The combined organic phases were dried over MgSO4, filtered,
and evaporated under reduced pressure. The residue was purified by column chromatography using
AcOEt/MeOH (v/v = 9:1) as eluent.
Method 2. In a flame-dried Schlenk tube (20 mL) equipped with magnetic stirrer and inert gas inlet
was placed (2-hydroxy-2-methylpropyl)methylphenylphosphine oxide (20) (0.053g, 0.25 mmol) and
AcOH (1 mL) was added. Reaction was stirred of room temperature or reflux for 4 hours. The reaction
was quenched by addition of H2O (10 mL) and extracted with DCM (3×20 mL). The combined
organic phases were dried over MgSO4, filtered and evaporated under reduced pressure. The residue
was purified by column chromatography using AcOEt/MeOH (v/v = 9:1) as eluent.
Method 3. In a flame-dried Schlenk tube (20 mL) equipped with magnetic stirrer and inert gas inlet
was placed (2-hydroxy-2-methylpropyl)methylphenylphosphine oxide (20) (0.072g, 0.33 mmol) and
HBF4-OEt2 (0.164 g 1.0 mmol) was added. Reaction was stirred of reflux for 4 hours. The reaction
was quenched by addition of H2O (10 mL) and extracted with DCM (3×20 mL). The combined
organic phases were dried over MgSO4, filtered, and evaporated under reduced pressure. The residue
was purified by column chromatography using AcOEt/MeOH (v/v = 9:1) as eluent.
25

ACCEPTED MANUSCRIPT
Method 4. In a flame-dried Schlenk tube (20 mL) equipped with magnetic stirrer and inert gas inlet
was placed (2-hydroxy-2-methylpropyl)methylphenylphosphine oxide (20) (0.072g, 0.34 mmol) and
o
TFA (1 mL) was added. Reaction was warmed to 45 C and stirred for 4 hours. The reaction was
quenched by addition of H2O (10 mL) with NaHCO3 and extracted with CHCl3 (3×20 mL). The
combined organic phases were dried over MgSO4, filtered, and evaporated under reduced pressure.
The residue was purified by column chromatography using AcOEt/MeOH (v/v = 9:1) as eluent.
4.3.1. (2-Methylprop-1-enyl)(methylphenyl)phosphine oxide (35). This compound was prepared
according
to
General
Procedure
B,
Method
3
from
(2-hydroxy-2-
methylpropyl)methylphenylphosphine oxide (20) (0.072 g, 0.33 mmol) as a white sticky solid; yield
0.041 g (63%); Rf (AcOEt/MeOH 9:1) 0.36; [Found C, 68.09; H, 7.86. C11H15OP requires C, 68.03; H,
7.78%]; δH (500 MHz, CDCl3) 1.69 (3H, d, J 13.2 Hz), 1.91 (3H, s), 1.98 (3H, dd, J 2.5 Hz, J 0.9 Hz),
5.67 (1H, d, J 26.2 Hz), 7.41−7.51 (3H, m), 7.68−7.76 (2H, m); δC (126 MHz, CDCl3) 18.8 (d, J 74.5
Hz), 21.3 (d, J 8.2 Hz), 28.4 (d, J 17.3 Hz), 117.9 (d, J 102.6 Hz), 128.4 (d J 11.8 Hz), 129.9 (d, J 10.0
Hz), 131.1 (d, J 2.7 Hz), 135.6 (d, J 101.7 Hz), 158.7; δP (202 MHz, CDCl3) 24.52; GC tR = 10.19
min; GC−MS (EI, 70 eV) m/z=194 (M+) (32), 193 (100), 179 (19), 139 (59), 131 (16), 130 (18), 129
(26), 125 (15), 121 (12), 117 (13), 115 (26), 91 (41), 78 (17), 77 (62), 69 (11), 65 (17), 63 (28), 55
(10), 53 (19), 51 (60), 50 (19), 47 (66%).
4.3.2. (2-Methylprop-2-enyl)(methylphenyl)phosphine oxide (36). This compound was prepared
according
to
General
Procedure
B,
Method
3
from
(2-hydroxy-2-
methylpropyl)methylphenylphosphine oxide (20) (0.072 g, 0.33 mmol) as a white solid; yield 0.015 g
(23%); mp 56.3–58.4 °C; Rf (AcOEt/MeOH 9:1) 0.45; [Found C, 68.11; H, 7.84. C11H15OP requires C,
68.03; H, 7.78%]; ν max (ATR) 3409, 3061, 3054, 2939, 2912, 1712, 1642, 1437, 1293, 1169, 1111,
894, 740, 695, 530, 485, 435; δH (500 MHz, CDCl3) 1.75 (3H, d, J 12.6 Hz), 1.78−1.82 (3H, m), 2.76
(2H, d, J 14.8 Hz), 4.70−4.75 (1H, m), 4.90−4.95 (1H, m), 7.45−7.57 (3H, m), 7.69−7.77 (2H, m); δC
(126 MHz, CDCl3) 15.3 (d, J 71.8 Hz), 24.3, 41.9 (d, J 65.4 Hz), 115.5 (d, J 10.0 Hz), 128.5 (d, J 10.9
Hz), 130.2 (d, J 9.1 Hz), 131.6 (d, J 2.7 Hz), 133.6 (d, J 95.4 Hz), 137.0 (d, J 10.0 Hz); δP (202 MHz,
CDCl3) 35.03; GC tR = 10.00 min; GC−MS (EI, 70 eV) m/z=194 (M+) (16), 193 (37), 139 (100), 131
(13), 91 (37), 78 (11), 77 (53), 63 (11), 51 (38), 50 (11), 47 (30%).
4.4. General Procedure C for the Synthesis of Cyclic Phosphine Oxides from β-
hydroxyalkylphosphine oxides 14-34, 37-42.
o
The alcohol 14-34, 37-42 (0.1mmol) was stirred at 170 C with 85% H3PO4 (6.3mmol) for 5 h. The
o
mixture was cooled below 100 C and poured on to ice-water (10 mL). The solution was extracted
with dichloromethane or chloroform (4x10 ml). The aqueous solution was washed with sodium
hydrogen carbonate solution (10 mL) and water (10 mL). The extracts were dried over MgSO4,
filtered, and evaporated under reduced pressure. The residue was purified by column chromatography
26

ACCEPTED MANUSCRIPT
using CHCl3/MeOH (v/v = 15:1), AcOEt/MeOH (v/v = 9:1) or hexane/CHCl3/i-PrOH (v/v = 5:1:1) as
eluent.
4.4.1. 1,3-Dimethylphosphindoline-1-oxide (14a). This compound was prepared according to General
Procedure C from (2-hydroxypropyl)methylphenylphosphine oxide (14) (0.083 g, 0.42 mmol) as a
colorless oil; yield 81% (0.03 g, 34% isolated as a pure compound). Isolated as a mixture of
diastereomers (dr = 56:44).
Major diastereomer: Rf (EtOAc/MeOH 9:1) 0.34; δH (500 MHz, CDCl3) 1.47 (3H, d, J 6.9 Hz), 1.67
(3H, d, J 12.9 Hz), 1.75−1.82 (2H, m), 3.16−3.29 (1H, m), 7.32−7.41 (2H, m), 7.48−7.55 (1H, m),
7.67−7.78 (1H, m); δC (126 MHz, CDCl3) 16.7 (d, J 67.2 Hz), 21.8 (d, J 9.1 Hz), 34.5 (d, J 4.5 Hz),
36.5 (d, J 69.0 Hz), 124.8 (d, J 11.8 Hz), 127.5 (d, J 3.6 Hz), 127.8 (d, J 9.1 Hz), 132.5 (d, J 2.7 Hz),
133.6 (d, J 99.9 Hz), 150.1 (d, J 28.2 Hz); δP (202 MHz, CDCl3) 53.50; GC tR = 9.72 min; GC−MS
(EI, 70 eV) m/z=181 (M++1) (7), 180 (M+) (55), 179 (39), 166 (10), 165 (100), 147 (39), 117 (16), 116
(12), 115 (29) 91 (12%).
Minor diastereomer: Rf (EtOAc/MeOH 9:1) 0.34; δH (500 MHz, CDCl3) 1.38 (3H, d, J 6.9 Hz), 1.82
(3H, d, J 13.6 Hz), 2.44−2.59 (2H, m), 3.59−3.73 (1H, m), 7.32−7.40 (2H, m), 7.47−7.55 (1H, m),
7.67−7.78 (1H, m); δC (126 MHz, CDCl3) 18.8 (d, J 67.2 Hz), 22.5 (d, J 7.3 Hz), 35.5 (d, J 69.0 Hz),
35.3 (d, J 4.5 Hz), 125.3 (d, J 11.8 Hz), 127.6 (d, J 4.5 Hz), 127.7 (d, J 10.9 Hz), 132.7 (d, J 1.8 Hz),
133.4 (d, J 99.0 Hz), 151.3 (d, J 28.2 Hz); δP (202 MHz, CDCl3) 55.60; GC tR = 9.50 min; GC−MS
(EI, 70 eV) m/z=181 (M++1) (14), 180 (M+) (94), 179 (99), 166 (11), 165 (100), 149 (13), 147 (53),
145 (10), 117 (27), 116 (16), 115 (39) 91 (19%);
ν max (ATR) for a mixture of diastereomers: 3238, 2972, 2910, 2835, 1445, 1400, 1369, 1174, 1118,
1059, 884, 823, 764, 482, 442.
4.4.2. (Methylprop-1-enyl)(methylphenyl)phosphine oxide (14b). This compound was prepared
according to General Procedure C from (2-hydroxypropyl)methylphenylphosphine oxide (14) (0.083
g, 0.42 mmol) afforded the product 14b; conversion 8% (based on 31P NMR spectra of the mixture); Rf
(EtOAc/MeOH 9:1) 0.34; δP (202 MHz, CDCl3) 26.12; GC tR = 8.39 min; GC−MS (EI, 70 eV)
m/z=180 (M+) (67), 179 (100), 165 (29), 147 (24), 139 (24), 125 (26), 117 (40), 116 (25), 115 (31), 91
(22), 77 (41), 65 (10), 63 (11), 51 (31), 47 (49%).
4.4.3. (Methylprop-2-enyl)(methylphenyl)phosphine oxide (14c). This compound was prepared
according to General Procedure C from (2-hydroxypropyl)methylphenylphosphine oxide (14) (0.083
g, 0.42 mmol) afforded the product 14c; conversion 5% (based on 31P NMR spectra of the mixture); Rf
(EtOAc/MeOH 9:1) 0.34; δP (202 MHz, CDCl3) 34.11; GC tR = 8.57 min; GC−MS (EI, 70 eV)
m/z=180 (M+) (6), 179 (14), 139 (100), 77 (23), 51 (13%).
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ACCEPTED MANUSCRIPT
4.4.4. 1,4,4-Trimethyl-1,2,3,4-tetrahydrophosphinoline-1-oxide (16a). This compound was prepared
according to General Procedure C from (2-hydroxy-3-methylbutyl)methylphenylphosphine oxide (16)
(0.432 g, 1.91 mmol) as a pale yellow oil; yield 0.430 g (86%) of title compound containing 12% of
16b; Rf (AcOEt/MeOH 9:1) 0.26; δH (500 MHz, CDCl3) 1.36 (3H, s), 1.37 (3H, s), 1.70 (3H, d, J 12.0
Hz), 1.91−2.04 (1H, m), 2.07−2.21 (2H, m), 2.26−2.39 (1H, m), 7.31−7.37 (1H, m), 7.40−7.50 (2H,
m), 7.79−7.89 (1H, m); δC (126 MHz, CDCl3) 17.4 (d, J 71.8 Hz), 23.5 (d, J 67.2 Hz), 30.9, 31.0, 34.9
(d, J 3.6 Hz), 35.5 (d, J 4.5 Hz), 126.6 (d, J 10.9 Hz), 126.6 (d, J 9.1 Hz), 129.1 (d, J 93.5 Hz), 130.5
(d, J 6.4 Hz), 131.9 (d, J 2.7 Hz), 150.7 (d, J 7.3 Hz); δP (202 MHz, CDCl3) 29.52; GC tR = 10.63 min;
GC−MS (EI, 70 eV) m/z=208 (M+) (29), 207 (14), 194 (12), 193 (100), 179 (13), 178 (20), 165 (23),
131 (15), 130 (24), 129 (21), 128 (13), 116 (12), 115 (22), 91 (16), 78 (30), 77 (13), 63 (11%).
Analytical data are in accordance with those reported in the literature.18
4.4.5. 1,4,4-Trimethyl-1,2,3,4-tetrahydrophosphinoline-1-oxide (16b). This compound was prepared
according to General Procedure C from (2-hydroxy-2-methylbutyl)methylphenylphosphine oxide (25);
yield 54%, (isolated as a mixture of diastereomers contaminated with 16a). Rf (AcOEt/MeOH 9:1)
0.26; δH (500 MHz, CDCl3) (due to overlapping only selected peaks of epimers are described) 1.08
(3H, d, J 7.6 Hz) and 1.14 (3H, d, J 6.9 Hz) and 1.17 (3H, d, J 6.8 Hz) and 1.17 (3H, d, J 6.8 Hz) and
1.20 (3H, d, J 7.3 Hz) and 1.22 (3H, d, J 6.9 Hz) and 1.28 (3H, d, J 7.3 Hz) and 1.41 (3H, d, J 7.3 Hz),
1.65 (3H, d, J 12.4 Hz) and 1.65 (3H, d, J 12.0 Hz) and 1.69 (3H, d, J 12.8 Hz) and 1.71 (3H, d, J 12.6
Hz), 2.12−2.25 (7H, m), 2.25−2.38 (3H, m), 2.38−2.50 (1H, m), 2.56−2.66 (1H, m), 2.66−2.73 (1H,
m), 2.79−2.89 (2H, m), 2.89−2.99 (1H, m), 7.13−7.18 (1H, m), 7.19−7.23 (1H, m), 7.23−7.30 (2H,
m), 7.31−7.38 (4H, m), 7.39−7.48 (4H, m), 7.74−7.91 (4H, m); δP (202 MHz, CDCl3) 24.82 and 26.00
and 27.86 and 31.53; GC peak 1; tR = 10.45 min; GC−MS (EI, 70 eV) m/z=208 (M+) (21), 194 (12),
193 (100), 165 (22), 151 (11), 133 (23), 129 (14), 115 (14), 91 (10); GC peak 2; tR = 10.64 min;
GC−MS (EI, 70 eV) m/z=208 (M+) (42), 207 (12), 194 (12), 193 (100), 179 (27), 178 (15), 166 (25);
165 (72), 151 (17), 147 (15); 133 (35), 131 (17), 130 (20), 129 (25), 128 (17), 116 (14), 115 (28), 91
(21); GC peak 3; tR = 10.69 min; GC−MS (EI, 70 eV) m/z=208 (M+) (38), 194 (12), 193 (100), 179
(26), 178 (10), 166 (35); 165 (90), 151 (20), 147 (13); 133 (41), 131 (14), 130 (20), 129 (25), 128 (16),
116 (10), 115 (23), 91 (18); GC peak 4; tR = 10.77 min; GC−MS (EI, 70 eV) m/z=208 (M+) (19), 194
(12), 193 (100), 165 (18), 133 (19), 129 (14), 115 (12%).
4.4.6. 1,3,4,4-Tetramethyl-1,2,3,4-tetrahydrophosphinoline-1-oxide (17a). This compound was
prepared
according
to
General
Procedure
C
from
(2-hydroxy-3,3-
dimethylbutyl)methylphenylphosphine oxide (17) (0.099 g, 0.41 mmol) as a colorless oil; yield 79%
(isolated as a mixture containing 7% of 17b). Isolated as a mixture of diastereomers (dr = 56:44).
Major diastereomer: Rf (AcOEt/MeOH 9:1) 0.21; δH (500 MHz, CDCl3) 1.10 (3H, dd, J 6.9 Hz, J 1.3
Hz), 1.20 (3H, s), 1.41 (3H, s), 1.68 (3H, d, J 12.6 Hz), 1.91−2.00 (1H, m), 2.02−2.14 (1H, m),
28