Effect of amino substituents on the stereochemical outcome of the photo-arbuzov rearrangements of 1-arylethyl phosphorodiamidites

Article abstract of DOI:10.1021/jo040297+

The essentially stereochemically pure 1-arylethyl phosphorodiamidites 8 and 9 were irradiated by UV light in acetonitrile, benzene, and cyclohexane (Tables 1-4). Reaction via singlet free-radical pairs, formed by carbon-oxygen bond scission (Scheme 1), wh

Full text of DOI:10.1021/jo040297+

Effect of Amino Substituents on the Stereochemical Outcome of
the Photo-Arbuzov Rearrangements of 1-Arylethyl
Phosphorodiamidites
Worawan Bhanthumnavin† and Wesley G. Bentrude*
Department of Chemistry, University of Utah, Salt Lake City, Utah 84112
bentrude@chem.utah.edu
Received December 31, 2004
The essentially stereochemically pure 1-arylethyl phosphorodiamidites 8 and 9 were irradiated by
UV light in acetonitrile, benzene, and cyclohexane (Tables 1-4). Reaction via singlet free-radical
pairs, formed by carbon-oxygen bond scission (Scheme 1), which are somewhat longer lived than
those from the analogous phosphites 5 and 6, is proposed. Tetramethyl 1-phenylethylphospho-
rodiamidite (8) gives the photo-Arbuzov rearrangement product 10 in 59% ( 2% GC yield, based
on percent 8 consumed (Tables 1 and 4), along with the free radical dimerization product 2,3-
diphenylbutane, 12a, in in amounts corresponding to ca. 19% of the potentially formed 1-phenylethyl
radicals. Similarly, from 9, the photorearrangement product 11 is generated in 64 ( 4% yield (Tables
2 and 4) along with a 18 ( 2% accountability of the 1-naphthylethyl radicals as 12b. The
photorearrangement of stereochemically enriched 8 (R/S ) 99:1) gives 10 in which an apparent 67
( 2% (100y, eq 3, Table 4) of the initial radical pairs [3,14] recombine with retention of configuration
at the stereogenic carbon (34 ( 3% net retention, eq 5). With TEMPO present, 70% (100y, eq 3) of
the initial 1-phenylethyl radicals, 14, from 8 combine with radicals 3 in the solvent cage with
retained configuration at carbon (40% percent net retention, eq 5). The yield of product 10 is reduced
to 54%, and 12a is absent. Similarly, the five-membered ring naphthylethyl analogue, phospho-
rodiamidite 9 (R/S ) 98:2), affords largely (R)-11 with apparent 34 ( 3% net retention. The degree
of stereorandomization observed in these systems is higher than was reported previously for
phosphites 5 and 6. The neglect of reconversion of pro-S 14 to pro-R 14 on the results of these
studies is addressed. Estimated maximum values (eq 4) of kcomb/krot (2.3) for the proximate radical
pairs [3,14] from 8 with TEMPO present appear to be at least 6-fold smaller than those of the
analogous phosphite (R)-5 (average kcomb/krot ) 13 with TEMPO present). Possible origins for this
effect are proposed.
Introduction
larization) studies of 1 (Ar ) Ph, p-MeCOC6H5, 1-naph-
thyl) are reasonably interpreted in terms of radical pair
intermediates [3,4]. In our recent report on the photolysis
The photo-Arbuzov rearrangements of arylmethyl phos-
phites 1 to the phosphonates 2 upon direct irradiation
with UV light, reported by this laboratory,1-3 have been
shown to be synthetically useful.4,5 Product,3 31P CIDNP,6
and CIDEP7 (chemically induced dynamic electron po-
† Present address: Department of Chemistry, Faculty of Science,
Chulalongkorn University, Phyathai Rd., Patumwan, Bangkok 10330,
Thailand.
(1) Omelanzcuk, J.; Sopchik, A. E.; Lee, S.-G.; Akutagawa, K.;
Cairns, S. M.; Bentrude, W. G. J. Am. Chem. Soc. 1988, 110, 6908-
6909.
(2) Cairns, S. M.; Bentrude, W. G. Tetrahedron Lett. 1989, 30, 1025-
1028.
(3) Ganapathy, S.; Soma Sekhar, B. B. V.; Cairns, S. M.; Akutagawa,
K.; Bentrude, W. G. J. Am. Chem. Soc. 1999, 121, 2085-2096.
(4) Bentrude, W. G.; Mullah, K. B. J. Org. Chem. 1991, 56, 7218-
7224.
of optically active phosphites, it was demonstrated that
the predominantly singlet or triplet nature of the radical
pair can be controlled by phosphite structure or use of
triplet sensitizers.8 In addition, the observed stereochem-
10.1021/jo040297+ CCC: $30.25 © 2005 American Chemical Society
Published on Web 05/13/2005
J. Org. Chem. 2005, 70, 4643-4651
4643

Bhanthumnavin and Bentrude
SCHEME 1
istry at the migratory carbon of stereochemically en-
riched, chiral phosphites was correlated with the multi-
plicity of the radical pair generated. Presumed proximate
chemical outcome. The photolysis of nearly stereochemi-
cally pure (R)-1-phenylethyl N,N,N′,N′-tetramethylphos-
phorodiamidite ((R)-8) and the 1-naphthylethyl analogue,
2-(1-naphthylethoxy)-1,3-dimethyl-1,3,2-diazaphospho-
lane ((R)-9), both of which have two amino substituents
on phosphorus, to give products 10 and 11 was carried
out. The stereochemical outcome and product yields
involving the presumed initial caged radical pair from 8
([3,14]S, Scheme 1) were determined in the presence of
the free-radical scavenger 2,2,6,6-tetramethylpiperidin-
1-oxyl radical (TEMPO). The extent of retention of
configuration at the stereogenic carbon was determined,
and estimates of the relative rate constants for cage
combination (kcomb) and rotation (krot) were made. These
systems are highly suitable for measurement of the
competition between cage combination and rotation
because we are able to show that the starting phospho-
rodiamidites, (R)-8 and (R)-9, and the products 10 and
11 are stereochemically stable under the photoreaction
conditions. Errors that result from not considering the
reversibility of the conversion of pro-R 14 to pro-S 14
(Scheme 1) are addressed in detail.
singlet radical pairs [3,14]S, analogous to those of Scheme
1, generated from direct irradiation of phosphites 5 and
6, give products with a high degree of retention of
configuration (80% net retention for 5 with TEMPO
present and 86% net retention for 6 without TEMPO).
By contrast, triplet radical pairs, produced from direct
irradiation of 7 or triplet sensitized photolysis of 6, yield
essentially racemic products.8
We report here the effect of changing the substituents
on phosphorus on the product distribution and stereo-
(5) Mullah, K. B.; Bentrude, W. G. Nucleosides Nucleotides 1994,
13, 127-153.
(6) Koptyug, I. V.; Sluggett, G. W.; Ghatlia, N. D.; Landis, M. S.;
Turro, N. J.; Ganapathy, S.; Bentrude, W. G. J. Phys. Chem. 1996,
100, 14581-14583.
Results
Preparation of 8 and 9. Isolation of Photorear-
ranged Products. Determination of Enantiopurity.
Phosphorodiamidites 8 and 9 were prepared from the
requisite phosphorus triamide and either the racemic
(7) Koptyug, I. V.; Ghatlia, N. D.; Sluggett, G. W.; Turro, N. J.;
Ganapathy, S.; Bentrude, W. G. J. Am. Chem. Soc. 1995, 117, 9486-
9491.
(8) Bhanthumnavin, W.; Bentrude, W. G. J. Org. Chem. 2001, 66,
980-990.
4644 J. Org. Chem., Vol. 70, No. 12, 2005

Photo-Arbuzov Rearrangements of 1-Arylethyl Phosphorodiamidites
TABLE 1. Yields and Stereochemical Results for the
TABLE 3. Photolysis of 8 (R/S ) 99:1) in the Presence of
Photorearrangement of 8 (R/S ) 99:1)a
Radical Trap TEMPOa
accountability yieldb (%)
accountability yieldb (%)
conversion
R/S ratio
conversion
R/S ratio
of 10d
solvent
of 8b (%)
10
12ac
of 10d,e
8/TEMPO
of 8b (%)
10
12ac
acetonitrile
acetonitrile
acetonitrile
cyclohexane
cyclohexane
cyclohexane
benzene
16
25
57
59
60
62
59
61
56
57
18
20
20
20
18
20
18
16
67:33
65:35
66:34
67:33
69:31
66:34
67:33
68:32
e
29
19
27
31
21
25
24
29
20
33
19
62
59
61
59
58
56
56
55
54
55
54
20
20
20
16
12
12
10
4
68:32
69:31
69:31
68:32
69:31
70:30
70:30
71:29
70:30
70:30
71:29
e
100
19
e
1:0.8
1:1.0
1:1.2
1:1.5
1:1.8
1:2.0
1:2.5
1:3.0
27
95
18
benzene
29
0
a Ca. 0.01 M 8 at 254 nm, 35-40 °C. b By GC analysis. Based
on the amount of consumed 8. c Yield of 12a doubled to account
for the stoichiometry of its formation from 8. d Determined by
chiral HPLC on a CHIRALCEL OD column. e Average 67/33.
0
0
a Ca. 0.01 M 8, cyclohexane solvent at 254 nm, 35-40 °C. b By
GC analysis. Based on the amount of consumed 8. c Yield of 12a
doubled to account for the stoichiometry of its formation from 8.
d Determined by chiral HPLC on a CHIRALCEL OD column. e No
TEMPO added.
TABLE 2. Product Yields and Stereochemical Results
Obtained from Direct Irradiation of 9 (R/S ) 98:2)a
accountability yieldb (%)
conversion
R/S ratio
of 11d,e
of 9b (%)
11
12bc
Photorearrangement of Stereochemically En-
riched Phosphorodiamidite 8 (R/S ) 99:1). Phospho-
rodiamidite 8 (ca. 0.01 M) of predominately R configu-
ration was irradiated at 254 nm through quartz in
acetonitrile, benzene, and cyclohexane solvents. Product
yields and stereochemical results are summarized in
Table 1. Rearrangement product 10 was formed in 59 (
2% yields (GC, Tables 1 and 4) along with an average
yield of 2,3-diphenylbutane (12a, two pairs of enanti-
omers separable by GC) corresponding to 19 ( 2% of the
potentially formed 1-phenylethyl radicals (Tables 1 and
4). Partial racemization was observed in product 10.
Starting with 8 of 99:1 R/S ratio, an average (R/S)
enantiomeric ratio of 67:33 was encountered in product
10 (34 ( 3% percent net retention, eq 5, Table 4). (R/S
ratios are based on percentages of total product, R plus
S.) The R/S ratios of the product 10 (Table 1) and 8
(Supporting Information) are largely constant regardless
of the percent conversion of (R)-8. In a control reaction
photoproduct (R)-10 (99% ee) was irradiated under
photoreaction conditions. Its enantiopurity remained
unchanged. Thus, both 8 and 10 are configurationally
stable.
Photorearrangement of Stereochemically En-
riched 2-(1-Naphthylethyl)diazaphospholane 9 (R/
S) ) 98:2. Phosphorodiamidite 9, the five-membered ring
1-naphthylethyl analogue of 8, was irradiated at 300 nm
through Pyrex in acetonitrile and cyclohexane solvents
(ca. 0.01 M). Product yields (64 ( 4%) and stereochemical
results for 9 are similar to those for phosphorodiamidite
8. Rearrangement product 11 was formed in 64 ( 4%
yield along with (12b) corrresponding to an 18 ( 2%
accountability of 1-naphthylethyl radicals (Tables 2 and
4). Other radical products such as 1-ethylnaphthalene
(or ethylbenzene from 8) were observed by GC in trace
amounts (GC and GC/MS) but were not quantified.
Starting with a 98:2 R/S ratio of 9, the R/S enantiomeric
ratios in the rearrangement product 11 (67:33) amount
to 34 ( 3% net retention at carbon (Table 4). Essentially
constant R/S ratios for phosphorodiamidite 9 (Supporting
Information) and the product 11 (Table 2) were observed
as a function of conversion. A solution of 70:30 (R/S) 11,
irradiated at a typical concentration of 9 in the stereo-
chemical studies, over the same period of time, had
unchanged R/S ratios (chiral HPLC). Furthermore, when
solvent
acetonitrile
acetonitrile
acetonitrile
cyclohexane
cyclohexane
cyclohexane
24
43
68
59
60
65
68
67
18
16
18
20
18
18
63:37
69:31
67:33
70:30
65:35
67:33
97
18
40
100
a Ca. 0.01 M 9 at 300 nm, 35-40 °C. b By GC analysis. Based
on the amount of consumed 9. c Yield of 12b doubled to account
for the stoichiometry of its formation from 9. d Determined by
chiral HPLC on a CHIRALCEL OD column. e Average 67/33.
alcohol or stereoisomer of R configuration and high
enantiomeric purity (97-98% ee). Photolysis of racemic
8 and 9 yielded the photorearranged products 10 and 11,
isolated by HPLC, and the radical dimer 12. The initial
enantiopurities of very largely R-form 8 and 9 were
determined, following their retentive conversion9 by
t-BuOOH to their oxides, HPLC purification, and chiral
HPLC analysis (baseline-resolved) on a CHIRALCEL OD
column as described in detail earlier for the phosphates
from oxidation of 5 and 6.8 The R/S ratios were the same
as those of the starting alcohols. Unreacted stereochemi-
cally enriched 8 and 9 were similarly oxidized and
analyzed by chiral HPLC at various photochemical
conversions as were the products 10 and 11. The R/S
ratios of the oxides remained unchanged (see the Sup-
porting Information.). Therefore, if the caged radical pairs
[3,14] recombine, they do so with retention of configura-
tion at carbon. As a result, any loss of configuration arises
during formation of 10 or 11.
Products 10 and 11 from optically enriched 8 or 9 were
purified by HPLC, and the enantiomeric ratios (Tables
1-3) were determined on a CHIRALCEL OD HPLC
column as described previously8 for the stereochemically
enriched phosphonates from 5 and 6. The predominant
enantiomer of 10 and 11 was assigned the R configura-
tion based on the known retentive stereochemistry of the
photo-Arbuzov rearrangement of phosphites determined
by X-ray crystallography and NMR spectroscopy.1,10
Product yields (Tables 1-3) were obtained by standard
quantitative GC measurements.
(9) Bentrude, W. G.; Hargis, J. H. J. Am. Chem. Soc. 1970, 92, 7136-
7144.
J. Org. Chem, Vol. 70, No. 12, 2005 4645

Bhanthumnavin and Bentrude
TABLE 4. Summary of Photochemical Results
accountability yield (%)
g
compd
conditions
product
dimera
cage yield product (%)
100yd
% net retentione
kcomb/krot
8
direct hν
with TEMPO
direct hν
direct hν
with TEMPO
direct hν
59 ( 2b
19 ( 2
0
c
54
c
67 ( 2b
34 ( 3(34)i
2.0
2.3
2.1
7.3
13
8
54h
70h
40h (40)
9
64 ( 4
67 ( 2
64h
18 ( 2
68 ( 3
88 ( 2
93h
34 ( 3 (36)
72 ( 2 (76)
80h (86)
5f
5f
6f
4h
0
3 ( 1
c
65
c
65 ( 4
95 ( 2
86 ( 3 (90)
19
a Yield of dimer doubled to account for the stoichiometry of its formation from starting materials. b Average deviation from average.
c TEMPO not added. Cage yield not applicable. d Equations 2 and 3. e Equation 5. f Data from ref 8. g Equation 4. h Average deviation
<1. i Numbers in parentheses are based on 100y values.
either 10 or 11 was subjected to the entire workup
procedure, their enantiomeric compositions were un-
changed.
Arbuzov rearrangements of phosphites 5 and 6 are
consistent with the key reaction step being homolysis of
the ArCHMe-OPX2 bond to give the radical pair analo-
gous to [3,14]S. Analogously, photochemical excitation of
8 or 9 is proposed (Scheme 1) to produce a singlet excited
state, 13S, which undergoes homolytic C-O bond dis-
sociation to the corresponding singlet geminate radical
pair [3,14]S On cage recombination, the initial geminate
radical pair [3,14]S involving pro-R 14 yields the rear-
ranged product, (R)-10 or (R)-11, with retention of con-
figuration at the prochiral carbon. Rotation of pro-R 14
to give pro-S 14 prior to combination with 3 affords 10
and 11 with inverted carbon configuration. Singlet gemi-
nate radical pairs are typically short-lived and predomi-
nantly undergo recombination within the solvent cage.
Indeed, with the phosphites a relatively high degree of
retention of configuration at stereogenic carbon is seen
(Table 4).8 Diffusion of the radical pair from the solvent
cage leads to dimer 12 and racemized 10 or 11. For
phosphites 5 and 6, only 3-4% of 12 is found. Scheme 1
also provides for intersystem crossing of the initially
formed singlet excited starting material, 13S, to its triplet
excited state to generate triplet radical pairs. The pos-
sibility that radical pair [3,14]S is converted to the more
long-lived triplet pair, [3,14]T, also is depicted. The data
from Tables 1-3 are condensed and summarized in Table
4 for ease of comparison, along with the earlier results
for phosphites 5 and 68 to facilitate discussion.
When the reconversion of pro-S 14 to pro-R 14 and
radical pair diffusion are negligible, as for 5 and 6, the
stereochemical results can be readily analyzed in terms
of Scheme 1 to provide an estimate of the ratio kcomb/krot
for the radical pair [3,14]. Let RSM and SSM represent the
percentages of starting phosphorodiamidite in the R and
S configurations, respectively, and Robsd and Sobsd be the
percentages of observed product in the R and S configu-
rations. The total yields of 10 and 11 are not 100 percent.
However, calculation of Robsd and Sobsd based on total 10
or 11 formed is reasonable since the formation of products
other than 10 or 11 will not be affected by the R or S
configuration at the stereogenic carbon; i.e., inefficiencies
in formation of R and S products are proportionately the
same.
Photorearrangement of Stereochemically En-
riched 8 in the Presence of Nitroxide Radical
Scavenger. The stable radical TEMPO is commonly
employed to trap free radicals that escape the initial
solvent cage and is applicable to both phosphorus- and
carbon-centered radicals. Photoexcited TEMPO can ex-
tract hydrogen resulting in depletion of radical scavenger
concentration. Therefore, the trapping experiment was
done in cyclohexane where this side reaction occurs to a
lesser extent than in acetonitrile.11 The concentrations
of TEMPO used were below those known to trigger the
anti-scavenging effect noted by Turro and co-workers.12
Detailed analysis of other products, formed from reac-
tions with TEMPO, was published earlier,3,8 including
the product of trapping of radical 3 for phosphite 1 with
R ) Me, Ar ) p-acetylphenyl.
Irradiation of phosphorodiamidite (R)-8 (R/S ) 99:1,
ca. 0.01 M) in the presence of increasing amounts of
TEMPO (0.002-0.030 M) was carried out (Table 3). The
first 3 entries in Table 3 without added TEMPO are
included for comparison. The yield of 10 decreases from
59 ( 2% and levels off at about 54% when the TEMPO
concentration exceeds 0.02 M (Tables 3 and 4). Simulta-
neously, the yields of dimer 12a decrease until no dimer
is found when 2 equivalents or more of the trap are used.
Concurrently, a small increase in retention of configu-
ration in product 10 is observed. The initial 67:33
enantiomeric composition (R/S) of 10 becomes constant
at 70:30 (40% net retention, Tables 3 and 4), presumably
corresponding to 10 formed exclusively from [3,14]S in
the solvent cage.
Discussion
Analysis of Stereochemical Results. It is clear from
the lack of effect (Tables 1-3) of change to a polar solvent,
acetonitrile, that polar effects including ion-pair forma-
tion do not influence these reactions. As noted, Scheme
1 summarizes possible pathways for product formation
in the photorearrangements of 8 and 9 by a free-radical
pair mechanism. The results obtained previously8 from
the product and stereochemical studies of the photo-
By the approach used previously,8 let y equal the
fraction of initially formed reaction pairs [3,14]S from RSM
or SSM that combines before rotation with retention of
configuration at the prochiral center of pro-R 14. Then
1-y is the fraction of initial RSM or SSM that yields product
with inverted configuration after conversion of pro-R 14
to pro-S 14. The quantity y can be readily obtained.8
(10) Bhanthumnavin, W.; Bentrude, W. G.; Arif, A. M. J. Org. Chem.
1998, 63, 7753-7758.
(11) Johnston, L. J.; Tencer, M.; Scaiano, J. C. J. Org. Chem. 1986,
51, 2806-2808.
(12) Step, E. N.; Buchachenko, A. L.; Turro, N. J. J. Am. Chem. Soc.
1994, 116, 5462-5466.
4646 J. Org. Chem., Vol. 70, No. 12, 2005

Photo-Arbuzov Rearrangements of 1-Arylethyl Phosphorodiamidites
Based on the R enantiomer:
The assumptions that kcomb . krot and (kcomb and krot)
. kdiff apply well to phosphites 5 and 6 (Table 1) studied
earlier.8 Only a small amount of radical dimer 12 (ca.
4% accountability of potentially formed cage-free 14) is
found, and a high degree of retention at carbon is
observed (Table 4). Neither 31P CIDNP nor ESR signals
can be observed on direct UV irradiation of the achiral,
1-naphthylmethyl analogue of phosphite 6.13 These re-
sults are consistent with photo reaction via rather short-
lived, singlet radical pairs [3,14]. By contrast, in the
photorearrangements of 8 and 9 relatively large amounts
of dimer 12 are formed, and considerable loss of config-
uration at the stereogenic carbon of products 10 and 11
(Tables 1-4) is noted. Consequently, for 8 and 9 both
radical pair diffusion and reversibility of the conversion
of pro-R 14 to pro-S 14 are significant; and the conse-
quent errors in application of eqs 2-5 must be consid-
ered.
Robsd ) RSM y + SSM(1 - y)
(1)
(2)
(3)
and
y ) (Robsd - SSM)/(RSM - SSM
)
When SSM is negligible
y ) Robsd/RSM ) Robsd/100
Values for y, based on the R/S product ratios of Tables
1-3, are given in Table 4 for phosphorodiamidite 8 and
9 on a percentage basis, 100y. When the percentage of S
enantiomer, SSM, is only 1% (as for 8), eqs 2 and 3 give
the same value for y. For 5, 6, and 9, SSM is 2-3%, and
eq 2 was used to give a slightly higher number for y (e.g.,
for 0.93 vs 0.90 for 5 with added TEMPO) which,
however, is surely within experimental error of that
calculated from eq 3.
The relationship between the rate constant for rotation
(krot) and the rate constant for recombination (kcomb
simply corresponds (eq 4) to the fraction (y) of radical
pairs initially formed within the initial solvent cage that
undergoes recombination with 3 before rotation of pro-R
14 divided by the fraction that undergoes recombination
after one rotation:
Singer and co-workers14 carried out a steady-state
treatment of the thermal rearrangement via singlet
radical pairs of optically pure (S)-MePhCHNdCdCPh2.
Based on a scheme completely parallel to Scheme 1, but
including reversible rotation of 14 and diffusion of the
radical pairs analogous to [pro-R 14,3]S and [pro-S, 14,3]-
)
S, they obtained relative values of krot, kcomb, and kdiff
.
However, this treatment requires accurate measurement
of the fraction of radicals (f) that escape the solvent cage,
f ) kdiff/(kdiff + kcomb), which is not available from our data.
Nonetheless, the effects of rotation of 14 and radical
diffusion on measured or apparent y, krot/kcomb, and
percent net retention can be illustrated semiquantita-
tively with a simple model.
Model for the Effects of Reversibility of pro-R 14
Rotation and Radical Diffusion. Start with 13 (Scheme
1) that is 100% the R enantiomer and gives 100 [3, pro-R
14]S radical pairs. In the simplest case, assume that no
radical diffusion occurs, but 40 of the initial 100 pro-R
kcomb/krot ) y/(1-y)
(4)
Percent net retention, also recorded in Table 4, is the
mechanism-independent quantity calculated from the
average Robsd/Sobsd ratios of Tables 1-3 via eq 5.
% net retention ) [(Robsd - Sobsd)/(Robsd + Sobsd)] ×
100 ) Robsd - Sobsd (5)
14 are converted to 40 pro-S 14 (i.e., actual kcomb/krot
)
Equation 5 assumes that the starting material is 100%
in the R configuration. There are very small errors in
Robsd and Sobsd as 1-3% of SSM is present in each case. In
parentheses in Table 4 are the slightly higher percent net
retention values based on 100y whose calculation via eq
2 accounts for SSM in 5, 6 and 9; for example, for 9 this
number is (68-32) or 36%.
60:40 ) 1.5) which combine with 3 to afford S product
(Sobsd ) 40). The remaining 60 pro-R 14 couple with 3 to
give R product; thus, Robsd ) 60; Robsd/Sobsd ) 60:40; 100y
) 60 (eq 3); percent net retention ) 20% (eq 5).
Then, allow the 40 pro-S 14 formed from pro-R 14 to
be apportioned 60:40 between coupling to afford 24 S
product and reconversion to 16 pro-R 14 (again, kcomb
/
When the rotation of radical 14 (Scheme 1) is revers-
ible, i.e., conversion of pro-S 14 back to pro-R 14 competes
with kcomb to give product of S configuration, eqs 1-4 are
only approximations, since they are based on the as-
sumption that kcomb . krot rotation. (The reversible
rotation of pro-R 14 and the potential for the diffusion
of the radical pair [pro-S 14,3] from the solvent cage are
not shown in Scheme 1, but their inclusion can be readily
visualized.) Obviously, if pro-R 14 is regenerated from
pro-S 14 (krot) in competition with recombination (kcomb),
the measured or apparent value of Robsd will be increased.
Consequently, the apparent or measured y value in Table
4 is larger than it actually is. As a result, the value of
kcomb/krot based on eq 4 will increased. In addition the
apparent or measured percent net retention (eq 5) also
will be increased. Moreover, diffusion of the radical pair
[3,14] from the solvent cage will have an affect on the
stereochemical outcome of the processes depicted in
Scheme 1. These effects will be discussed below in more
detail.
krot ) 1.5), which is subsequently split 60:40 between 10
R product and reformation of 6 pro-S 14. The latter
divides 60:40 between coupling to yield 4 S product and
reversion to 2 pro-R 14 which combine with 3 to form 2
R product. The combined yield of R product (Robsd) is 72%
(60 + 10 + 2). Sobsd is 28, and Robsd/Sobsd is 72:28. The
actual fraction of initial pro-R 14 that couple before
rotation, y, is [(1.5/(1.0 + 1.5)] or 0.6. However, the
apparent or measured value of y, calculated from Robsd
,
is 72:100 or 0.72 (eq 3, 100y ) 72). From eq 4 the
apparent kcomb/krot is [0.72/(1 - 0.72)] or 2.6 which is (2.6/
1.5) or 1.7 times the actual kcomb/krot. This is a small but
significant increase in measured or apparent kcomb/krot
that results from the reversibility of the conversion of
pro-R 14 to pro-S 14. As noted above, were the formation
(13) Sluggett, G. W.; Landis, M. S.; Ghatlia, N.; Turro, N. J.;
Bhanthumnavin, W. unpublished results.
(14) Lee, K.-W.; Horowitz, N.; Ware, J.; Singer, L. A. J. Am. Chem.
Soc. 1977, 99, 2622-2627.
J. Org. Chem, Vol. 70, No. 12, 2005 4647

Bhanthumnavin and Bentrude
of initial pro-S 14 irreversible, the ratio Robsd/Sobsd would
be 60:40 corresponding to a percent net retention of (60
- 40) or 20, eq 5. For the calculated ratio of enantiomers,
Robsd/Sobsd of 72:28, the measured percent net retention
is expected to be (72-28) or 44, a larger percentage than
in the absence of rotation of radical 14 from the pro-S
configuration back to the pro-R form. It is clear that the
reversible interconversion of pro-R 14 and pro-S 14
increases both apparent kcomb/krot and percent net reten-
tion.
Inclusion of diffusion in this model with kcomb/krot still
1.5, and kdiff accounting for 20% of the initial radical pair,
decreases the overall rearrangement product yield,
changes Robsd and Sobsd, increases y and, therefore, the
measured kcomb/krot. Assume again that 100 pro-R [14,3]-
S are generated, but now 20 (20%) undergo diffusion. The
other 80 pairs are apportioned according to the assumed
ratio kcomb/krot ) 1.5 so that 32 pro-S 14 are generated by
rotation. The remaining 48 pro-R 14 (48% of the initial
pairs) combine with radical 3 to give R product. The
relative rate constants are then kdiff/krot/kcomb ) 1:1.6:2.4.
Of the 32 pro-S 14 generated, 20% or 6 undergo diffusion,
48% or 15 combine with radical 3 to generate S product
(15%), and 32% or 10 undergo rotation to reform R-14
(kcomb/krot )1.5). The 10 R-14 are then apportioned
between diffusion (2), combination with 3 to yield R
product (5), and reformation of S-14 (3), 2 of which afford
S product along with diffusion (<1) and regeneration of
pro-R 14 (1). Consideration of the fractional distribution
of products of the one pro-R 14 does not refine the results
beyond the experimental error in the measurement of R
and S products. Total accountabilities are thus as fol-
lows: R product, 53% (48 + 5); S product, 18% (16 + 2);
radical diffusion products 29% (20 + 6 + 2 +1).
As noted above, since the total yield of R- and S-
product is not 100%, the percentages Robsd and Sobsd must
be based on total rearrangement product formed. Thus,
Robsd is [53/(53 + 18)] × 100 ) 75, and Sobsd is 25. The
apparent value of y (eq 3) is 0.75 (Robsd/RSM ) 75/100) and
from eq 4 kcomb/krot ) 3.0, [0.75/(1 - 0.75)]. Actual y is
still 0.6 with kcomb/krot ) 1.5. The apparent or measured
kcomb/krot is 2.0 times the actual value (3.0/1.5). On a
percent net retention basis, the experimental value is 50%
(75 - 25) vs the actual value of 20. It may be surprising
that inclusion of 20% diffusion of the pairs [3,14]S in
Scheme 1 has a relatively small, though not negligible,
effect on measured or apparent y and kcomb/krot when
compared to the actual values.
If one assumes 30% diffusion of each radical pairs
[3,14]S set formed, the same model shows that the
combined yield of R and S products is reduced to 60%
(diffusion total 40%) with Robsd/Sobsd increased to 78:22.
Apparent y is increased to 0.78 and kcomb/krot to 3.5. This
ratio is 2.3 times (3.5:1.5) the actual number. Percent net
retention is 56.
14 should be minimal. The importance of these consid-
erations in the still-instructive comparison of the values
of kcomb/krot for 8 and 9 with those for 5 and 6 will be
addressed below.
Photorearrangements of Phosphorodiamidite 8
and 9. Comparison to 5 and 6. In summary, the
photoreactions of 8 and 9 give the corresponding rear-
ranged products, 10 and 11, in fair to good accountability
yields (Tables 1-4). Significantly, these photoprocesses
are accompanied by the formation of about 9-10% of the
corresponding 2,3-diarylbutanes (18-20% of potentially
formed radicals 14) which obviously arise from dimer-
ization of free 1-arylethyl radicals that diffuse from the
initial solvent cage.
In addition, the stereochemical results (Tables 1-4)
reveal that for 8 and 9 a considerable amount of stereo-
randomization has occurred. Starting with a 99:1 (R/S)
ratio enantiomeric mixture of phosphorodiamidite 8 and
98:1 (R/S) 9, only about 34% net retention (eq 5) is
observed in products 10 and 11. This number increases
to 40% for 8 when the free radical scavenger TEMPO is
present, and the radicals that give dimer 12 are trapped
completely. Of the radicals 14 formed, 65-70% combine
with 3 with retention of configuration. Very significantly,
for 8 and 9 the percent retention of configuration of the
stereogenic carbon (34%) is considerably lower than is
observed (Table 4) in the direct photolysis of the phosphite
analog 5 (80% net retention with TEMPO added) and 6
(86%, no TEMPO). The same is true for the values of 100y
with TEMPO present; i.e., 93 for 5 versus only 70 for 8.
That rotation of geminate, pro-R 1-phenylethyl radical,
14, from 8 (Scheme 1) competes well with combination
with its phosphinoyl radical partner, 3, is confirmed by
the ratio kcomb/krot (2.3, TEMPO added, Table 4) for the
1-phenylethyl radical from 8 (eqn 4). This is much lower
than what is seen for the caged pair from phosphite 5
(kcomb/krot ) 13, TEMPO added, Table 4) or for photolysis
of 6 without added TEMPO (kcomb/krot ) 19, Table 4).8
These results, along with the relatively high yield of
dimers 12a and 12b and reduced degree of retention of
stereochemistry at carbon with both 8 and 9, compared
to those from direct photolysis of 5 and 6, indicate that
irradiation of 8 and 9 yields comparatively long-lived
radical pair intermediates. It seems quite certain that
reversal of the conversion of pro-R 14 to pro-S 14 occurs
in the photorearrangements of 8 and 9.
The possibility that the relatively high degree of
stereorandomization seen for 8 and 9 results from
random combination of radicals 3 and 14 that have
escaped the solvent cage is excluded by the results for 8
with added TEMPO. The lack of 2,3-diphenylbutane
formation above 0.02 M TEMPO concentration shows
that none of the 2-phenylethyl radicals are available for
cross combination. Based on the reduction in yield of 10
on addition of TEMPO, cross combination of cage-free
radicals 3 and 14 evidently contributes no more than
5-6% to the total yield of 10 in the absence of TEMPO.
Notably, based on the extent of diffusion and loss of
configuration at carbon with 8 and 9, the radical pairs
from these compounds, though evidently relatively long-
lived, do not live as long as the triplet pairs formed on
direct irradiation (ESR study6) of the p-acetyl analogue
of phosphite 7 (1, R ) Me, Ar ) p-MeCOC6H4) or on
triplet sensitized photolysis (31P CIDNP and ESR stud-
The important conclusion from the above consider-
ations is that the values of y in Table 4 are larger than
the actual ones so that the numbers for kcomb/krot (Table
4) are also higher. As a result, the experimental values
for kcomb/krot of Table 4 for 8 and 9 are maximum ones.
The ratio kcomb/krot is expected to be reasonably accurate
for 5 with TEMPO present, because as noted earlier,
there is little radical pair diffusion, and the high values
of 100y (Table 4) indicate that return of pro-S 14 to pro-R
4648 J. Org. Chem., Vol. 70, No. 12, 2005

Photo-Arbuzov Rearrangements of 1-Arylethyl Phosphorodiamidites
ies7) of the chiral 1-naphthylmethyl analogue of 6 (1, R
) Me, Ar ) 1-naphthyl). In the triplet-sensitized reaction
of 6 itself, about 40% of potentially formed 14 radicals
yield dimer 12b, along with a relatively low yield (20%)
of rearranged product, the 1-(1-naphthyl)ethylphospho-
nate.8 Similarly, direct irradiation of 7 itself yields only
20% of the rearrangement product, the 2-(p-acetyl)-
ethylphosphonate, again with a 36-42% accountability
yield of dimer (12, Ar ) p-MeCOC6H4CH2).8 These
systems have not been examined with TEMPO present.
Both reactions occur with near-total loss of configuration
at carbon.8 These results are directly opposite to the
rearrangement yields, largely retentive stereochemistry
at stereogenic carbon, and minor amounts of dimer
observed on direct irradiation of phosphites 5 and 6
(Table 4).8 The photoreactions of 5 and 6, as noted earlier,
likely occur via singlet radical pairs.
Before considering the possible origins of the differ-
ences in kcomb/krot, it must be reemphasized that applica-
tion of eqs 1-4 to the photorearrangements of 5 and 6
likely is valid. However, the modeling approach shows
clearly that when diffusion of [3,14]S and reversible
rotation of 14 occur, as must be true for 8 and 9, the
apparent or measured values of Robsd, y (eqs 2 and 3),
kcomb/krot (eq 4), and percent net retention (eq 5) of Table
or of the reversibility of the conversion of pro-R 14 to
pro-S 14. The decrease in the value for kcomb for [3,14]
from 8 (and presumably 9), compared to the correspond-
ing radical pair from 5 (and presumably 6), must be an
inherent property of the reaction system.
Interestingly, the results for the model system for
Scheme 1 (which is only an approximation) with revers-
ible rotation of pro-R 14, 20% radical diffusion, and actual
kcomb/krot ) 1.5 are similar to those for photorearrange-
ment of 8. The predicted measured value for kcomb/krot is
3.0 (Robsd, 75) compared to the actual value of 1.5 (Robsd
,
60).
The large apparent decrease in kcomb could be at least
in part a result of the differences in s-character of the
SOMO of 14, X2P(O)•. This effect has been seen in the
influence of substituents X and Y on the rate constants
for addition of XYP(O)• to oxygen and n-butylacrylate and
for the abstraction of bromine from BrCCl3 and hydrogen
from PhSH.15,16 Rates of reaction were increased by
increased hyperfine splittings to phosphorus (five radi-
cals, aP 255-369 G) and consequent increase in s char-
acter in the SOMO. The range of rate constants at 23 K
was 1.7-fold for addition to oxygen; 7-fold for addition to
n-butyl acrylate; 13-fold for abstraction of hydrogen from
PhSH; and 9-fold for abstraction of bromine from BrCCl3.
The phosphorus hyperfine splitting for (MeO)2P(O)• (aP,
697 G at 251 °K) is larger than that for (Me2N)2P(O)• (aP,
524 G at 276 °K).17 Based on the greater s-character of
its SOMO, (MeO)2P(O)• from 6 should recombine with 14
more rapidly within the solvent cage than (Me2N)2P(O)•
from 8. As a result, the pair [(MeO)2P(O)•/3] would exhibit
less diffusion from the solvent cage and greater retention
of configuration at the stereogenic carbon of 14.
However, since the rate constant (kcomb) for coupling
of [3,14] will be very large, its perturbation by change of
substituents on 14 from alkoxy to amino may not be great
enough to account entirely for the change in kcomb. Steric
factors also may be associated with the increased diffu-
sion (decreased kcomb) of the amino-substituted radicals
which will be less pyramidal (smaller aP) and also feature
comparatively bulky amino substituents on phosphorus.
Large steric effects on the combination rates of carbon
radicals are well-known.18 The difference in steric size
between (Me2N)2P(O)• and (MeO)2P(O)•, along with re-
combination rate constant differences based on variation
in the s-character of the SOMO of the two radicals may
account for the apparently larger value of kcomb for
(MeO)2P(O)•.
4 are larger than the actual ones. Consequently, y, kcomb
/
krot, and percent net retention for 8 and 9 are maximum
values. The effects of changing substituents on phospho-
rus from alkoxy to amino are in fact larger than what is
indicated by the parameters of Table 4 taken at face
value.
Possible Origins of Substituent Effects on the
Degree of Retention of Configuration at Carbon
and kcomb/krot. First, one could attempt to account for
the decrease in kcomb/krot with 8 and 9 by an increase in
krot. However, it seems intuitively obvious that the amino
groups of the pair [3, 14] must be sterically larger than
MeO and would decrease krot for radical 14 of the pair
[3,14]. Furthermore, an increase in krot cannot account
for the sizable increase seen in the products of radical
diffusion from the solvent cage for 8 and 9 (Table 4).
A second approach is to assume that krot for the pairs
[3,14] from 5 and 8 is essentially the same, and kcomb is
somehow decreased for 14 from 8 and 9. Thus, with the
numbers of Table 4 taken at face value, kcomb for the
radical pair from 8 is about 6-fold slower than it is for
the pair generated by 5 ([kcomb/krot (5)/kcomb/krot(8)] ) kcomb
-
(5)/kcomb(8) ) 13/2.3 ) 5.7 (both cases with TEMPO
present). From the data of Table 4, the value of kcomb(6)/
kcomb(8) also must be quite high; however, experiments
for 6 with TEMPO present were not done in which case
the ratio would be reduced.
Third, a reaction component composed of long-lived
triplet radical pairs, generated by one of the pathways
shown in Scheme 1, could be responsible in part for the
configuration loss and enhanced diffusion of radicals
formed on photolysis of 8 and 9. As noted earlier, based
on the extent of diffusion and loss of configuration at
carbon with 8 and 9, the radical pairs from these
compounds on average do not live as long as the distinctly
As shown in the model approach, neglect of the
reversibility of the conversion of pro-R 14 to pro-S 14 in
the use of eqs 1-4 leads to an increased apparent or
measured value of y. For example, if the actual value of
y for 8 with added TEMPO is 0.6 (i.e., Robsd, 60) instead
of the apparent or measured 0.70 of Table 4, kcomb/krot
becomes 1.5 instead of 2.3. This reduction would increase
the value of kcomb(5)/kcomb(8) from 5.7 to 13/1.5 or 8.7.
Therefore the estimate for kcomb(5)/kcomb(8) of 5.7, based
in Table 4, is a minimum value. Evidently, the large
apparent value of approximately six for kcomb(5)/kcomb(8)
is not an artifact of neglect of diffusion of the pair [3,14]
(15) Sluggett, G. W.; McGarry, P. F.; Koptyug, I. V.; Turro, N. J. J.
Am. Chem. Soc. 1996, 118, 7367-7372.
(16) Jockusch, S.; Turro, N. J. J. Am. Chem. Soc. 1998, 120, 11773-
11777.
(17) Roberts, B. P.; Singh, K. J. Organomet. Chem. 1978, 159, 31-
35.
(18) Leffler, J. E. An Introduction to Free Radicals; John Wiley &
Sons: New York, 1993.
J. Org. Chem, Vol. 70, No. 12, 2005 4649

Bhanthumnavin and Bentrude
triplet pairs formed on direct irradiation of phosphite 7
or from triplet sensitized photolysis of the l-naphthyl-
methyl analogue of 6 reported previously. However, as
illustrated in Scheme 1, a fraction of a singlet species,
either electronically excited starting material, 13, or
radical pair [3,14]S might undergo intersystem crossing
to the corresponding triplet.19,20 These possibilities cannot
be evaluated at this time.
values for the radicals from 8 and 9 most likely results
from a decrease in kcomb for the phosphinoyl radicals,
(Me2N)2P(O)•, from 8 and 9 which also accounts for
increased radical pair diffusion and loss of configuration
through rotation of radical 14 within the solvent cage. A
ratio of kcomb for the two systems is calculated from the
data of Table 4, assuming krot to be the same. A minimum
value of 5-6 for kcomb(5)/kcomb(8) in favor of the pair from
6 is estimated. The decrease in kcomb may arise at least
in part from the known lower degree of s-character in
the SOMO of diaminophosphinoyl radicals [X2P(O)•; X,
) amino], indicated by ESR hyperfine splittings, and
consequent reduced reactivity toward the 1-arylethyl
radical, 14, in the solvent cage. Steric factors may also
play a part in making the more nearly planar, amino-
substituted radicals (decreased SOMO s-character) less
prone to cage recombination. In addition the apparent
reduced kcomb/krot and increased radical diffusion observed
for 8 and 9 might not be totally a function of singlet pair
lifetimes if a triplet radical pair component (Scheme 1)
is present. Further insight will be sought in future
investigations of 8 and 9 using triplet quenchers as well
as31P CIDNP and ESR magnetic resonance techniques.
Further Studies. The presence of triplet radical pairs
[3,14] from the direct irradiation of the achiral p-
acetylbenzyl analogue of 7 (1, Ar ) p-acetylphenyl) and
triplet sensitized photoreactions of the achiral 1-naphthyl
analogue of 6 (1, Ar ) 1-naphthyl) was demonstrated by
ESR-based CIDEP techniques.7 31P CIDNP measure-
ments were used to define the presence of triplet [3,14]
from the analogue of 7 (1, Ar ) p-acetylphenyl).6 It is
clear that the major pathway for photoreactions of 8 and
9 described in the present paper does not involve triplet
[3,14]. Nonetheless, further studies of the photoreactions
of 8 and 9 will be carried out using triplet quenchers as
well as 31P CIDNP and time-resolved ESR methods.
These magnetic resonance techniques offer the possibility
of differentiating the singlet or triplet spin characteristics
of radical pairs involved in the photochemistry from the
phase of spin polarization observed. The presence of a
triplet component might account for or at least contribute
to the loss of stereochemistry and increased extent of
radical diffusion encountered with these phosphorodia-
midite.
Photo-Arbuzov rearrangements of phosphites related
to 1-6 are synthetically useful.4,5 However, the synthetic
utility of the photorearrangements of phosphodiamidites
analogous to 8 and 9 remains to be evaluated.
Experimental Section
Steric effects on the diffusive separation of the radicals
[3,14]S should be amenable to study by use of more
sterically bulky amino groups, i.e., i-Pr2N instead of
Me2N.
Spectroscopic Data. J for the 1H NMR data refer to
proton-proton coupling unless otherwise stated. Ultraviolet
(UV) spectra were obtained in acetonitrile and cyclohexane on
a diode array spectrophotometer. Wavelength maxima (λmax
)
are reported in nm with extinction coefficients, ꢀ, in M-1 cm-1
.
Conclusions
Irradiation Experiments. Procedures for the preparation
under argon of 0.01 M solutions of 8 and 9 with an appropriate
amount of tri-n-propyl phosphate for quantitative studies and
for the ensuing analyses by GLC of the photoreactions of 8
and 9, were described earlier for the phosphites 5-7.8 Phos-
phoramidite 8 was irradiated in a Rayonet reactor though
quartz at 254 nm while 9 was irradiated with the Rayonet
apparatus through Pyrex at 300 nm at the concentrations
recorded in Tables 1-3. Quantitative gas chromatographic
analyses for 8-11 and 12 were done with a flame ionization
detector (FID) and a DB-1 (1% methyl silicone) capillary
column (10 or 30 m × 0.25 mm × 0.25 mm) with tri-n-propyl
phosphate as internal standard. LRMS and HRMS were
performed in the EI (70 ev) or CI mode as were GC/MS
analyses (15 or 30 m × 0.25 mm × 0.25 mm DB-1 capillary
column). The techniques recorded below for purification of the
enantiomeric phosphoroamidates 10 and 11 and determination
of their enantiomeric composition by chiral HPLC are com-
pletely analogous to the methods described in detail for the
phosphonates from photorearrangement of 5 and 6.8
Determinations of Enantiomeric Compositions of
Products. Column chromatography (silica gel, chloroform)
prepurification was done on all mixtures (10, 11 and oxides of
8 and 9) to be purified or analyzed by HPLC. The prepurified
material was dissolved in 1-2 mL of the intended HPLC
eluent, and the solution was filtered through a Millex-HV13
(0.45 mm, 13 mm diameter) filter unit. The commonly used
solvent system was 1.3-1.7% methanol in chloroform. Separa-
tions and analyses by HPLC were done under isocratic
conditions (UV detector) on 4.6 mm i.d. analytical, 10 mm i.d.
semipreparative, and 21.4 mm i.d. preparative Dynamax
HPLC columns (100 Å spherical Microsorb packings in 5 mm
particle size).
On irradiation, phosphorodiamidites 8 and 9 undergo
the photo-Arbuzov rearrangement reaction to give 10 and
11, respectively, as major products. Also formed are the
products of radical pair diffusion and dimerization, the
2,3-diarylbutanes 12a and 12b. Like the previously
studied phosphites 5 and 6, the photoreactions of the
phosphorodiamidite are most simply understood as pro-
ceeding primarily via singlet radical pairs [3,14]S (Scheme
1). Notably, 8 and 9 give significantly increased amounts
of dimer 12 compared to 5 and 6. Furthermore, the loss
of configuration at the stereogenic carbon in products 10
and 11 is considerably increased over what is observed
with phosphites 5 and 6. The radical pairs from 8 and 9
must be relatively long-lived compared to those from 5
and 6. As measured by eq 5, kcomb/krot is reduced for the
radical pair [3,14] from 8 (TEMPO present) and 9
compared to the same parameters for phosphites 5
(TEMPO present) and 6 (Table 4). Arguments that
include use of a simple model system are made to show
that the reduced kcomb/krot is not the result of the neglect
in the application of eqs 1-5 of the reversal of the
rotation of radical 14 and of diffusion of the pair [3,14]S.
Evidently, the measured kcomb/krot of 2.3 is in fact a
maximum value. It proposed that the reduced kcomb/krot
(19) Gilbert, A.; Baggott, J. Essentials of Molecular Photochemistry;
Blackwell Scientific: London, 1991.
(20) Turro, N. J.; Buchachenko, A. L.; Tarasov, V. F. Acc. Chem.
Res. 1995, 28, 69-80.
4650 J. Org. Chem., Vol. 70, No. 12, 2005

Photo-Arbuzov Rearrangements of 1-Arylethyl Phosphorodiamidites
Chiral HPLC analyses employed a CHIRALCEL OD HPLC
column (250 mm × 4.6 mm i.d.), equipped with a 50 mm ×
4.6 mm i.d. guard column. Mobile phases used were 95:5-90:
10 of hexanes/2-propanol. Optimum flow rate was 1.0 mL/min.
Initial (Tables 1-3) and subsequent R/S ratios (Supporting
Information) for 8 and 9 (Tables 1-3) were determined by
chiral HPLC analysis on their oxides formed on oxidation by
tert-butyl hydroperoxide.8,9 The enantiomeric ratios for 10 and
11 recorded in Tables 1-3 as a function of conversion of 8 and
9 were also determined by chiral HPLC analysis following the
separation of the oxide and phosphorodiamidate rearrange-
ment product.
Preparation of 1-Phenylethyl N,N,N′,N′-Tetrameth-
ylphosphorodiamidite (8). At room temperature under
argon atmosphere, a solution of 1-phenylethanol (3.0 g, 25
mol.) in 10 mL of acetonitrile was added dropwise to a solution
of hexamethylphosphourus triamide (4.4 g, 27 mol.) and a
catalytic amount of 1-H-tetrazole (18 mg, 0.28 mmol) in 20
mL of acetonitrile. The solution was stirred at room temper-
ature for an additional 1 h. The solvent was removed in vacuo.
A 15 mL portion of a 1:1 mixture of dry ether and ethyl acetate
was added to the residue. The solid was filtered off in a Schlenk
apparatus under argon. Solvent removal in vacuo followed by
vacuum distillation gave 8 (4.0 g, 17 mmol, 63%) as a colorless
liquid: bp 55-56 °C (0.05 mmHg) (99% purity by GC); 31P
NMR (121 MHz, CDCl3, {1H}) δ 140.4; 1H NMR (300 MHz,
5.72 (dq, 1 H, 3JHP ) 8.6 Hz, 3J ) 6.6 Hz), 7.39-7.50 (m, 3 H),
7.63-7.83 (m, 3 H), 8.13 (d, 1 H, J ) 8.3); 13C NMR (75 MHz,
2
2
CDCl3, {1H}) δ 25.4 (d, JCP ) 3.1 Hz), 33.88 (d, JCP ) 23.4
Hz), 33.93 (d, 2JCP ) 23.9 Hz), 52.6 (d, 2JCP ) 9.9 Hz), 52.8 (d,
2
2JCP ) 9.9 Hz), 68.4 (d, JCP ) 11.4 Hz), 123.1, 123.2, 125.1,
125.33, 125.5, 127.2, 128.7, 129.9, 133.4, 141.3, (d, JCP ) 1.6
Hz); UV (CH3CN): 262 (ꢀ 5.3 × 103), 272 (ꢀ 7.9 × 103), 282 (ꢀ
9.3 × 103), 294 (ꢀ 6.7 × 103); GC-EIMS (70 eV) m/z (relative
intensity) 288 [M]+ (5), 155 (26), 133 (100), 127 (9); HRMS [M]+
calcd for C16H21N2OP 288.1392, found 288.1392. By the same
procedure, (R)-2-(1-(1-Naphthyl)ethoxy)-1,3-dimethyl-1,3,2-
diazaphospholane (9) (R/S ) 98:2) was prepared in sufficient
quantities for the stereochemical studies.
2-(1-(1-Naphthyl)ethoxy)-2-oxo-1,3-dimethyl-1,3,2-di-
azaphospholane (10-O) was isolated from oxidation of a 0.3-
0.5 g sample of 9 with 3 M tert-butyl hydroperoxide9 by the
procedure established previously for phosphites followed by
HPLC purification of a portion of the product (1.1% methanol
1
in chloroform): 31P NMR (121 MHz, CDCl3, {1H}) δ 0.84; H
3
NMR (300 MHz, CDCl3) δ 1.74 (d, 3 H, J ) 6.4 Hz), 2.36 (d,
6 H, 3JHP ) 9.8 Hz), 2.98-3.15 (m, 4 H), 6.03 (dq, 1 H, 3JHP
)
9.7 Hz, 3J ) 6.7 Hz), 7.45-7.56 (m, 3 H), 7.69 (d, 1 H, J ) 6.6
Hz), 7.78 (d, 1 H, J ) 8.3 Hz), 7.85-7.88 (m, 1 H), 8.15-8.18
3
(m, 1 H); 13C NMR (75 MHz, CDCl3, {1H}) δ 24.5 (d, JCP
)
2
2
5.7 Hz), 31.5 (d, JCP ) 4.2 Hz), 31.7 (d, JCP ) 4.2 Hz), 46.7
2
2
2
(d, JCP ) 14.5 Hz), 46.9 (d, JCP ) 13.5 Hz), 72.6 (d, JCP
)
3
3
CDCl3) δ 1.18 (d, 6 H, J ) 6.6 Hz), 2.11 (d, 6 H, JHP ) 8.8
Hz), 2.27 (d, 3 H, 3JHP ) 9.0 Hz), 4.66 (dq, 1 H, 3JHP ) 9.4 Hz,
3J ) 6.5 Hz), 6.77-7.07 (m, 5 H); 13C NMR (75 MHz, CDCl3,
7.3 Hz), 123.2, 123.3, 125.3, 125.5, 126.0, 128.1, 128.8, 129.79,
133.7, 138.9 (d, JCP ) 3.6 Hz); GC-EIMS (70 eV) m/z (relative
intensity) 304 [M]+ (24), 155 (39), 154 (100), 127 (11); HRMS
[M]+ calcd for C16H21N2O2P 304.1341, found 304.1355.
1-Phenylethyl N,N,N′,N′-tetramethylphosphorodiam-
idite oxide (8-O) was formed by the same procedure8,9 used
to obtain 10-O and isolated by HPLC purification. The thick
oil was shown to be >99% pure by GC analysis.
{1H}) δ 25.0 (d, JCP ) 5.8 Hz), 36.5 (d, JCP ) 18.2 Hz), 36.8
(d, 2JCP ) 17.9 Hz), 72.7 (d, 2JCP ) 19.8 Hz), 125.8, 127.0, 128.1,
145.0 (d, 3JCP ) 3.2 Hz); UV (CH3CN) 258 (ꢀ 866); GC-EIMS
(70 eV) m/z (relative intensity) 240 [M]+ (12), 226 (12), 135
(100), 105(10). Anal. Calcd for C12H21N2OP: C, 59.98; H, 8.81;
N, 11.66. Found: C, 60.09; H, 8.88; N, 11.65.
2
2
2-(1-(1-Naphthyl)ethyl)-2-oxo-1,3-dimethyl-1,3,2-diaza-
phospholane (11) was isolated in 99% GC purity by HPLC
(1% methanol in chloroform) from the mixture obtained by
irradiation to partial conversion of diazaphospholane 9 at 300
nm in benzene on an approximately 0.5 g scale: 31P NMR (121
MHz, CDCl3, {1H}) δ 129.3; 1H NMR (300 MHz, CDCl3) δ 1.73
(dd, 3 H, 3JHP ) 17.0 Hz, 3J ) 7.2 Hz), 2.43 (d, 3 H, 3JHP ) 9.0
Hz), 2.46 (d, 3 H, 3JHP ) 8.8 Hz), 2.77-3.03 (m, 4 H), 4.20 (dq,
(R)-1-Phenylethyl N,N,N′,N′-Tetramethylphosphorodi-
amidite ((R)-8). By the procedure used for the preparation
of racemic 8, reaction of hexamethylphosphorus triamide (1.1
g, 6.7 mmol), 0.80 g (6.5 mmol) of (R)-1-phenylethanol (99:1
R/S), and 1H-tetrazole (4.3 mg, 0.6 mmol) followed by distil-
lation gave 0.99 g (4.1 mmol, 62%) of (R)-8; 99% purity by GC,
99:1 R/S ratio determined on the corresponding oxide from
oxidation by tert-butyl hydroperoxide.8,9
2
3
1 H, JHP ) 19.3 Hz, J ) 7.3 Hz), 7.43-7.55 (m, 3 H), 7.60-
7.64 (m, 1 H), 7.71-7.74 (m, 1 H), 7.82-7.85 (m, 1 H), 8.14 (d,
1 H, J ) 8.3 Hz); 13C NMR (75 MHz, CDCl3, {1H}) δ 17.0 (d,
3JCP ) 4.2 Hz), 32.5 (d, 2JCP ) 4.9 Hz), 32.6 (d, 2JCP ) 5.2 Hz),
34.8 (d, 1JCP ) 117.8 Hz), 47.4 (d, 2JCP ) 8.3 Hz), 47.6 (d, 2JCP
) 8.3 Hz), 123.0, 124.9, 125.0, 125.1 (d, JCP ) 18.2 Hz), 125.6,
126.8 (d, JCP ) 3.6 Hz), 128.7, 131.4 (d, JCP ) 5.7 Hz), 133.6
(d, JCP ) 2.1 Hz), 136.0 (d, JCP ) 6.2); UV (CH3CN): 266 (ꢀ
4.7 × 104), 276 (ꢀ 7.4 × 104), 286 (ꢀ 8.9 × 104), 298 (ꢀ 6.1 ×
104); GC-EIMS (70 eV) m/z (relative intensity) 288 [M]+ (14),
155 (10), 133 (100). Anal. Calcd for C16H21N2OP: C, 66.65; H,
7.34; N, 9.72. Found: C, 66.66; H, 7.31; N, 9.70.
1-Phenylethyl N,N,N′,N′-Tetramethylphosphonic Acid
Diamide (10). On irradiation at 254 nm approximately 0.3 g
of phosphorodiamidite 8 in benzene was partially converted
to 10 which was isolated from the product mixture in 99% GC
purity by HPLC (1.5% methanol in chloroform): 31P NMR (121
1
MHz, CDCl3, {1H}) δ 37.5; H NMR (300 MHz, CDCl3) δ 1.55
(dd, 3 H, 3JHP ) 16.4 Hz, 3J ) 7.3 Hz), 2.31 (d, 6 H, 3JHP ) 9.0
Hz), 2.7 (d, 6 H, 3JHP ) 8.6 Hz), 3.30 (dq, 1 H, 2JHP ) 14.3 Hz,
3J ) 7.2 Hz), 7.20-7.43 (m, 5 H); 13C NMR (75 MHz, CDCl3,
{1H}) δ 17.1 (d, 2JCP ) 4.2 Hz), 36.3 (d, 2JCP ) 3.1 Hz), 36.6 (d,
1
2JCP ) 3.1 Hz), 75.1 (d, JCP ) 109.5 Hz), 126.6 (d, JCP ) 2.6
Hz), 128.3 (d, JCP ) 2.1 Hz), 128.8 (d, JCP ) 6.2 Hz), 139.9 (d,
2JCP ) 5.7 Hz); UV (CH3CN): 248 (ꢀ 123), 254 (ꢀ 165), 260 (ꢀ
194), 266 (ꢀ 143); GC-EIMS (70 eV) m/z (relative intensity)
240 [M]+, 226, 135 (100), 105(6). Anal. Calcd for C12H21N2OP:
C, 59.98; H, 8.81; N, 11.66. Found: C, 59.96; H, 8.83; N, 11.73.
2-(1-(1-Naphthyl)ethoxy)-1,3-dimethyl-1,3,2-diazaphos-
pholane (9) was prepared by the reaction of 2-diethylamino-
1,3-dimethyl-1,3,2-diazaphospholane (1.2 g, 0.059 mmol) and
1-(1-naphthyl) ethanol (1.1 g, 0.064 mmol) following the
procedure for preparation of phosphoramidite 8. Flash chro-
matography gave 9 as a colorless thick oil (1.2 g, 0.042 mmol,
71%): 31P NMR (121 MHz, CDCl3, {1H}) δ 128.9; 1H NMR (300
Acknowledgment. This research was supported by
grants from the National Science Foundation and the
National Institutes of Health.
Supporting Information Available: General experimen-
tal information; preparations and spectral data for the precur-
sors to phosphorodiamidite 9; tables showing the configura-
tional stabilities of unreacted 8 and 9 over the course of
irradiation. This material is available free of charge via the
Internet at http://pubs.acs.org.
MHz, CDCl3) δ 1.60 (d, 3 H, 3J ) 6.4 Hz), 2.46 (d, 3 H, 3JHP
)
3
12.5 Hz), 2.47 (d, 3 H, JHP ) 12.5 Hz), 2.88-3.29 (m, 4 H),
JO040297+
J. Org. Chem, Vol. 70, No. 12, 2005 4651