One-pot conversions of olefins to cyclic carbonates and secondary allylic and homoallylic amines to cyclic carbamates

Article abstract of DOI:10.1021/jo101614f

Sequential treatment of a 1,2-disubstituted olefin with m-CPBA, Br ₃CCO₂H, and DBU results in the one-pot, stereospecific conversion of the olefin to the corresponding disubstituted cyclic carbonate (1,3-dioxolan-2-one). The reaction proceeds via an initial epoxidation followed by S_N2-type epoxide ring opening by Br₃CCO₂H and subsequent base-promoted carbonate formation upon elimination of bromoform. When a solution of a secondary allylic or homoallylic amine and Br ₃CCO₂H is sequentially treated with m-CPBA then DBU, the product of the reaction is a cyclic carbamate (1,3-oxazolidin-2-one or 1,3-oxazinan-2-one).

Full text of DOI:10.1021/jo101614f

pubs.acs.org/joc
One-Pot Conversions of Olefins to Cyclic Carbonates and Secondary
Allylic and Homoallylic Amines to Cyclic Carbamates
Stephen G. Davies,* Ai M. Fletcher, Wataru Kurosawa, James A. Lee, Giovanna Poce,
Paul M. Roberts, James E. Thomson, and David M. Williamson
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road,
Oxford OX1 3TA, U.K.
steve.davies@chem.ox.ac.uk
Received August 20, 2010
Sequential treatment of a 1,2-disubstituted olefin with m-CPBA, Br3CCO2H, and DBU results in the
one-pot, stereospecific conversion of the olefin to the corresponding disubstituted cyclic carbonate
(1,3-dioxolan-2-one). The reaction proceeds via an initial epoxidation followed by SN2-type epoxide
ring opening by Br3CCO2H and subsequent base-promoted carbonate formation upon elimination
of bromoform. When a solution of a secondary allylic or homoallylic amine and Br3CCO2H
is sequentially treated with m-CPBA then DBU, the product of the reaction is a cyclic carbamate
(1,3-oxazolidin-2-one or 1,3-oxazinan-2-one).
Introduction
gas into an epoxide ring has been developed into an efficient
synthetic route.4
Cyclic carbonates are useful intermediates within organic
synthesis1 and are often employed as protecting groups for
1,2-diols.2 Interest in their synthesis has increased recently as
they have been employed as polar aprotic solvents for a
variety of reactions and as electrolytes for lithium ion
batteries.3 Methods for their preparation often rely on the
treatment of a 1,2-diol with phosgene (or an equivalent),2
although more recently the metal-catalyzed insertion of CO2
As part of an ongoing research program directed toward
the chemo- and diastereoselective functionalization of allylic
and homoallylic amines at the olefin,5 we have previously
developed an ammonium-directed olefinic oxidation of allylic
(4) Coates, G. W.; Moore, D. R. Angew. Chem., Int. Ed. 2004, 43, 6618.
Zhou, C.-H.; Beltramini, J. N.; Fana, Y. X.; Lu, G. Q. Chem. Soc. Rev. 2008,
37, 527.
(5) For examples of chemo- and diastereoselective cyclopropanations of
allylic amines from this laboratory, see: (a) Davies, S. G.; Ling, K. B.;
Roberts, P. M.; Russell, A. J.; Thomson, J. E. Chem. Commun. 2007, 4029.
(1) Clements, J. H. Ind. Eng. Chem. Res. 2003, 42, 663.
(2) Shaikh, A.-A. G.; Sivaram, S. Chem. Rev. 1996, 96, 951.
€
€
(3) Schaffner, B.; Schaffner, F.; Verevkin, S. P.; Borner, A. Chem. Rev.
€
ꢀ
(b) Csatayova, K.; Davies, S. G.; Lee, J. A.; Ling, K. B.; Roberts, P. M.;
Russell, A. J.; Thomson, J. E.Tetrahedron 2010, 66, 8420.
2010, 110, 4554.
DOI: 10.1021/jo101614f
r
Published on Web 10/18/2010
J. Org. Chem. 2010, 75, 7745–7756 7745
2010 American Chemical Society

Davies et al.
JOCArticle
SCHEME 1a
SCHEME 3a
aReagents and conditions: (i) Cl3CCO2H, m-CPBA, CH2Cl2, rt, 21 h,
then NaHCO3 (0.1 M, aq); (ii) K2CO3, MeOH, rt, 16 h.
SCHEME 2a
aReagents and conditions: (i) Cl3CCO2H, m-CPBA, CH2Cl2, rt, 21 h,
then NaHCO3 (0.1 M, aq).
aReagents and conditions: (i) Cl3CCO2H, m-CPBA, CH2Cl2, rt, 21 h,
then NaHCO3 (0.1 M, aq); (ii) Et3N, CH2Cl2, rt, 2 h; (iii) acid, m-CPBA,
CH2Cl2, rt, 18 h, then base, 0 °C to rt, 2 h (see table).
and homoallylic amines6 to facilitate the synthesis of amino
diol units.7 For instance, treatment of 3-N,N-dibenzylami-
nocyclohex-1-ene 1 with Cl3CCO2H followed by m-CPBA
and basic aqueous workup using NaHCO3 gave trichlo-
roacetate ester 2 in 95:5 dr and quantitative yield. Tran-
sesterification of 2 upon treatment with K2CO3 in MeOH
gives amino diol 3 in 95:5 dr and quantitative yield7a
(Scheme 1).
Upon application of this protocol to bis- and trisho-
moallylic amines 4 and 5 we noted that cyclic carbonates 6
and 7 were produced as the major products, rather than the
expected trichloroacetate esters (Scheme 2).8 We were sur-
prised to note that this result represents only the second
reported example of the formation of a 1,3-dioxolan-2-one
upon treatment of an R-trichloroacetoxy alcohol with base9
(in contrast, treatment of an R-trichloroacetamido alcohol
with base to form a 1,3-oxazolidin-2-one has been well
documented).10 In this light, we proposed that the transfor-
mation could be developed into a one-pot protocol for the
conversion of an olefin to a cyclic carbonate and delineate
herein the results of our studies in this area.
(i.e., those employed for 1, 4, and 5), oxidation of 8 resulted
in a 56:35:9 mixture of the regioisomeric trichloroacetate
esters 9 and 10 and diol 11, with no trace of the correspond-
ing cyclic carbonate 12. The absence of any cyclization
suggested that the presence of the amine function within 4
and 5 may have been important in promoting carbonate
formation. Indeed, when the mixture of trichloroacetate
esters 9 and 10 (and diol 11) was treated with Et3N in
CH2Cl2, conversion of both 9 and 10 to carbonate 12
occurred, and 12 was isolated in 52% yield after purification.
This transformation was next developed into a one-pot
procedure for the formation of carbonate 12 from olefin 8:
the optimal protocol involved the treatment of allylbenzene 8
with m-CPBA followed by Br3CCO2H, followed finally by
the introduction of excess DBU to the reaction flask (as both
a base and sacrificial reducing agent to scavenge any remain-
ing peracid).11 These conditions proved more efficacious in
promoting carbonate formation than when employing either
F3CCO2H or Cl3CCO2H as the acid and/or than when
employing Et3N as both the reducing agent and base. No
trihaloacetate ester products were observed in any of these
optimization studies, presumably due to in situ hydrolysis
upon aqueous workup (Scheme 3).
The mechanism and course of the reaction was followed by
1H NMR spectroscopic analysis. Addition of m-CPBA to
allylbenzene 8 in CDCl3 promoted complete conversion of
starting material to epoxide 13 after 3 h. Subsequent addition
of Br3CCO2H produced a 65:35 mixture of tribromoacetate
esters 14 and 15 in quantitative conversion. When the
oxidation reaction was repeated using m-CPBA in the pres-
ence of Br3CCO2H, however, a reaction time of 7 h was
required before complete consumption of starting material
(to give a 65:35 mixture of tribromoacetate esters 14 and 15),
indicating that the epoxidation reaction occurs faster in
the absence of Br3CCO2H, presumably due to competitive
Results and Discussion
One-Pot Conversion of Olefins to Cyclic Carbonates. The
application of our oxidation protocol to allylbenzene 8 (as a
model substrate) was examined. Under our literature conditions7a
(6) We also developed a protocol for the diastereoselective oxidation of
the corresponding tertiary amine N-oxides; see: Aciro, C.; Davies, S. G.;
Kurosawa, W.; Roberts, P. M.; Russell, A. J.; Thomson, J. E. Org. Lett.
2009, 11, 1333.
(7) (a) Aciro, C.; Claridge, T. D. W.; Davies, S. G.; Roberts, P. M.;
Russell, A. J.; Thomson, J. E. Org. Biomol. Chem. 2008, 6, 3751. (b) Aciro, C.;
Davies, S. G.; Roberts, P. M.; Russell, A. J.; Smith, A. D.; Thomson, J. E.
Org. Biomol. Chem. 2008, 6, 3762. (c) Bond, C. W.; Cresswell, A. J.; Davies,
S. G.; Kurosawa, W.; Lee, J. A.; Fletcher, A. M.; Roberts, P. M.; Russell,
A. J.; Smith, A. D.; Thomson, J. E. J. Org. Chem. 2009, 74, 6735. (d) Bagal,
S. K.; Davies, S. G.; Lee, J. A.; Roberts, P. M.; Russell, A. J.; Scott, P. M.;
Thomson, J. E. Org. Lett. 2010, 12, 136.
(8) Although carbonate 7 could be isolated in pure form (84% yield), an
analytical sample of 6 could not be obtained even after exhaustive flash
column chromatography due to the presence of residual unidentified impu-
rities (∼10%).
(10) For instance, see: Oishi, T.; Ando, K.; Inomiya, K.; Sato, H.; Iida,
M.; Chida, N. Org. Lett. 2002, 4, 151. Sakaguchi, H.; Tokuyama, H.;
Fukuyama, T. Org. Lett. 2007, 9, 1635. Shih, T.-L.; Li, H.-Y.; Ke, M.-S.;
Kuo, W.-S. Synth. Commun. 2008, 38, 4139.
(9) Bailey, S.; Helliwell, M.; Teerawutgulrag, A.; Thomas, E. J. Org.
Biomol. Chem. 2005, 3, 3654.
(11) Wefelscheid, U. K.; Woodward, S. J. Org. Chem. 2009, 74, 2254.
7746 J. Org. Chem. Vol. 75, No. 22, 2010

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SCHEME 4a
SCHEME 6a
aReagents and conditions: (i) Br3CCO2H, m-CPBA, CDCl3, rt, 3 or
7 h; (ii) DBU, 0 °C to rt, 2 h.
SCHEME 5a
aReagents and conditions: (i) Br3CCO2H, CDCl3, rt, 12 h; (ii) K2CO3,
MeOH rt, 2 h.
hydrogen bonding of the carboxylic acid to the peracid dis-
rupting the intramolecularly hydrogen-bonded, reactive confor-
mer of the latter.12 Subsequent addition of DBU promoted
complete conversion to carbonate 12, establishing that carbon-
ate formation occurs only upon basic workup. The obser-
vation that a 65:35 mixture of tribromoacetate esters 14 and
15 is formed in both of these reactions suggests that either the
intermediate epoxide 13 does not undergo regioselective ring
opening or regioselective ring opening occurs followed by an
equilibration process (Scheme 4). To determine which of these
mechanistic scenarios was in operation, enantiopure tetra-
dec-1-ene oxide (R)-16 (commercially available) was treated
with Br3CCO2H in CDCl3, which resulted in a 65:35 mixture
of tribromoacetate esters 17 and 18, respectively. Transes-
terification of this mixture upon treatment with K2CO3 in
MeOH gave the common diol 19 in 65:35 er,13 demonstrating
that the ring opening of epoxide 16 occurs in a nonregiose-
lective manner and hence results in erosion of the stereo-
chemical integrity of the final product 19 (Scheme 5); the
observation of a 65:35 mixture of tribromoacetate esters 14
and 15 from the epoxidation and ring opening of allylben-
zene 8 is therefore most likely also due to nonregioselective
ring opening of the intermediate epoxide 13 rather than an
equilibration process.
aReagents and conditions: (i) Br3CCO2H, m-CPBA, CH2Cl2, rt, 18 h,
then DBU, 0 °C to rt, 2 h.
The optimized reaction conditions were applied to a range
of mono- and disubstituted olefins bearing a variety of functional
groups. In these reactions, m-CPBA was added to a solution
of the olefin in CH2Cl2 followed by the addition of Br3CCO2H,
except in the cases of unsaturated amines 5, 33, and 42, in
which Br3CCO2H must be added first to prevent competing
N-oxidation.7a In each case, conversion to the corresponding
carbonate was observed. Carbonate formation from (Z)-olefins
30-33 resulted in the corresponding trans-configured carbon-
ates 34-37, while (E)-olefins 38-42 gave the corresponding
cis-configured carbonates 43-47, as single diastereoisomers.
These stereochemical assignments could be made confidently
on the basis of 1H NMR NOE analyses of 34-37 and 43-47:
cis-configured carbonates (1,3-dioxolan-2-ones) 43-47 gave
strong reciprocal enhancements between C(4)H and C(5)H
and between the C(4)- and C(5)-substituents (generally two
methylene groups), while in the trans-configured compounds
34-37 strong reciprocal enhancements were noted between
C(4)H and the C(5)-substituent and between the C(4)-sub-
stituentandC(5)H. The results from these experiments establish
that carbonate formation is a stereospecific (rather than
stereoselective) process, as would be expected for a mecha-
nism of formation involving epoxidation of the olefin, SN2-
type epoxide ring opening, and cyclization upon basification
via attack of the free hydroxyl group on the tribromoacetate
ester followed by loss of bromoform (Scheme 6).
(12) Poluektov, P. T.; Gonsovskaya, T. B.; Ponomarev, F. G.; Gusev,
Y. K. Polym. Sci. USSR 1973, 15, 686. Bach, R. D.; Dmitrenko, O.; Adam,
W.; Schambony, S. J. Am. Chem. Soc. 2003, 125, 924.
(13) The enantiomeric excess of diol 19 was determined by Chiral HPLC
analysis of the corresponding mono-p-nitrobenzoate derivative. For full
details see the Supporting Information.
J. Org. Chem. Vol. 75, No. 22, 2010 7747

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SCHEME 7a
of secondary bis- and trishomoallylic amines 4 and 5 which
gave carbonates 6 and 7, respectively, as the major products.
To investigate these observations further, secondary homo-
allylic amine 57 was sequentially treated with Cl3CCO2H
and m-CPBA followed by workup with aqueous NaHCO3
(i.e., under the conditions initially employed for oxidation of
4 and 5). This resulted in a mixture of products which
included carbamate 59 and carbonate 60 and as the major
components in an approximate 12:88 ratio, respectively.15
Purification via flash column chromatography gave carba-
mate 59 in 21% isolated yield and an impure sample of
carbonate 60 in ∼58% yield (the major impurity in this
sample was carbamate 59). The isolated yield of carbamate
59 (21%) was significantly higher than the proportion in-
dicated by analysis of the crude reaction mixture, suggesting
that carbonate 60 may undergo rearrangement to carbamate
59 during chromatography.16 Consistent with this hypothesis,
a sample of 60 in CDCl3 was observed by 1H NMR spectros-
copic analysis to rearrange to 59 over time; the rate of the
rearrangement process increased markedly in the presence of
triethylamine (Scheme 8).
aReagents and conditions: (i) Br3CCO2H, m-CPBA, CH2Cl2, rt, 18 h,
then DBU, 0 °C to rt, 2 h.
These results offer some insight into the mechanism of
formation of carbamate 59 upon sequential treatment with
Br3CCO2H, m-CPBA, and DBU, which was further investi-
gated by monitoring the reaction by 1H NMR spectroscopy.
Thus, a solution of homoallylic amine 57 and Br3CCO2H in
CDCl3 was treated with m-CPBA, which resulted in the
formation of an 87:13 mixture of tribromoacetate esters 62
and 63, respectively, with complete consumption of starting
material noted within 3 h. The appearance and disappear-
ance of an intermediate species was also observed; this
intermediate was tentatively assigned as being epoxide 61.
Addition of DBU to the reaction mixture resulted in the
immediate (<5 min) formation of a mixture of carbonate 60
(ca. 10%) and carbamate 59 (ca. 90%); within a further 2 h,
the major species present was carbamate 59 (>95%). A
general reaction pathway may therefore be proposed. Initial
epoxidation of homoallylic amine 57 gives epoxide 61. Ring
opening via an SN2-type process gives rise to a mixture of
regioisomeric tribromoacetate esters 62 and 63. Addition of
DBU to the reaction mixture results in deprotonation of
ammoniums 62 and 63 to reveal the nucleophilic nitrogen
atom within. Attack of the free amino group at the carbonyl
within the conjugate base of 63 leads directly to the corre-
sponding six-ring carbamate 59, although attack of the
hydroxyl group onto the carbonyl group results in formation
of the five-membered carbonate 60. Direct formation of
carbamate 59 from the conjugate base of 62 (the major
product of the oxidation reaction) is not possible and therefore
presumably proceeds via the initial formation of carbonate
60. Subsequent rearrangement of carbonate 60 to carbamate
59 is driven by formation of the more thermodynamically
favorable product (Scheme 9). Rearrangement of carbonates
6 and 7, derived from bis- and trishomoallylic amines 4 and 5
in this manner, is presumably disfavored (e.g., through kinetic
SCHEME 8a
aReagents and conditions: (i) Cl3CCO2H, m-CPBA, CH2Cl2, rt, 21 h,
then NaHCO3 (0.1 M, aq); (ii) stand in CDCl3.
One-Pot Conversion of Secondary Allylic and Homoallylic
Amines to Oxazolidinones and Oxazinanones. When this
procedure was applied to secondary allylic and homoallylic
amines 48 and 49, the corresponding carbamates (oxazolidi-
none 50 and oxazinanone 51, respectively) were produced as
the major products. Similarly, oxidation of secondary allylic
amines 52 and 56 gave the diastereoisomeric oxazolidinones
54 and 58, while oxidation of secondary homoallylic amines
53 and 57 gave the diastereoisomeric oxazinanones 55 and 59
in good isolated yield and as single diastereoisomers in each
case (Scheme 7). The relative configurations within 58 and 59
were unambiguously established by single-crystal X-ray
analyses.14 Therefore, given the diastereoisomeric nature of
54 and 58, and of 55 and 59, the relative configurations within
54 and 55 could confidently be assigned and are consistent
with the reaction proceeding via an anti-dihydroxylation
event with respect to the double bond in each case.
(15) The ratio of carbamate 59 to carbonate 60 was found to vary upon
several runs of this reaction, and a sample of carbonate 60 was not always
isolated upon purification: conversion to carbamate 59 during purification
was assumed to be complete in these cases.
The formation of carbamate products in these reactions is
in contrast to our initial observations concerning the oxidation
(16) O- to N-acyl migration has been previously reported. For instance,
see: Yakura, T.; Yoshimoto, Y.; Ishida, C.; Mabuchi, S. Tetrahedron 2007,
63, 4429. Yu, D.-S.; Xu, W.-X.; Liu, L.-X.; Huang, P.-Q. Synlett 2008, 1189.
Gonzalez-Gomez, J. C.; Foubelo, F.; Yus, M. J. Org. Chem. 2009, 74, 2547.
(14) Crystallographic data (excluding structure factors) have been depos-
ited with the Cambridge Crystallographic Data Centre as supplementary
publication numbers CCDC 784948 (58) and CCDC 784949 (59).
7748 J. Org. Chem. Vol. 75, No. 22, 2010

Davies et al.
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SCHEME 9
SCHEME 10
SCHEME 11a
retardation) due to the requirement to form a seven- or eight-
membered ring, respectively, thus accounting for the differ-
ences in reactivity in the oxidation reactions of unsaturated
amines 4, 5, and 57 carried out with m-CPBA in the presence
of Cl3CCO2H followed by workup with aqueous NaHCO3.
Analogous observations were made when the reaction of
1
allylic amine 52 was monitored by H NMR spectroscopy.
Addition of m-CPBA to a solution of 52 and Br3CCO2H in
CDCl3 resulted in the formation of epoxide 64 and tribro-
moacetate ester 65 as a single regioisomer;7 within 2 h
complete consumption of starting material was noted, and
within a further 4 h ring opening of the intermediate epoxide
64 to give tribromoacetate ester 65 had also reached comple-
tion. The observation of a single regioisomeric tribromoace-
tate ester 65 in this reaction is consistent with ring opening of
the intermediate epoxide 64 occurring at the carbon atom
distal to the protonated N-benzyl amino moiety,7 where its
destabilizing inductive electron-withdrawing influence on
the late transition state is less pronounced.17 Addition of
DBU to the reaction mixture gave a mixture of products,
although after 2 h the only species present was carbamate 54,
consistent with the conversion of tribromoacetate ester 65 to
carbamate 54 occurring via initial formation of carbonate 66
(Scheme 10).
Diastereoselective Synthesis of Carbonates from Chiral
Allylic Amines. We have recently shown that the substrate-
directed cyclopropanation of tertiary allylic amines 67 and
68 (having a stereogenic center at the allylic position) pro-
ceeds with very high levels of diastereoselectivity to give the
corresponding syn-cyclopropanes 70 and 71, consistent with
the directed reaction proceeding via transition state model 69
aReagents and conditions: (i) Et2Zn, CH2l2, F3CCO2H, CH2Cl2, rt, 1 h.
in which 1,3-allylic strain is minimized (Scheme 11).5b Given
the excellent levels of substrate control elicited in these systems,
it was envisaged that application of our oxidation method-
ology to chiral allylic amines such as 67 and 68 would result
in a diastereoselective version of this protocol that would be
applicable to the preparation of enantiopure carbonates:18
the protonated amino group has the capacity to effect hydrogen-
bonded delivery of the oxidant and promote ring opening of
the so-formed epoxide distal to itself.7
Oxidation of 67 and 68 with m-CPBA in the presence of
Cl3CCO2H at room temperature gave complete conversion
to the corresponding epoxides 73 and 74 in >99:1 dr in both
cases. The relative configuration within 74 was established
(18) The preparation of enantiopure tertiary allylic amines (with struc-
tures similar to 67 and 68) from R-amino acids has been demonstrated; see:
(17) Parker, R. E.; Isaacs, N. S. Chem. Rev. 1959, 59, 737. Addy, J. K.;
Parker, R. E. J. Chem. Soc. 1963, 915.
~
Barluenga, J.; Barangana, B.; Concellon, J. M. J. Org. Chem. 1995, 60, 6696.
ꢀ
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SCHEME 12a
SCHEME 13a
aReagents and conditions: (i) Cl3CCO2H, m-CPBA, CH2Cl2, rt, 1 h
(R = Ph) or 21 h (R = iPr); (ii) Br3CCO2H, CDCl3, rt, 12 h; (iii) DBU,
CDCl3, 0 °C to rt, 1 h; (iv) Br3CCO2H, m-CPBA CH2Cl2, rt, 18 h, then
DBU, 0 °C to rt, 2 h; (v) Cl3CCO2H, m-CPBA, CH2Cl2, 40 °C, 21 h;
(vi) K2CO3, MeOH, 60 °C 16 h.
aReagentsandconditions:(i)Br3CCO2H, m-CPBA, CH2Cl2, rt, 3 days,
then DBU, 0 °C to rt, 2 h.
unambiguously established by single-crystal X-ray analysis;21
diol 77 was also prepared directly from allylic amine 67 upon
treatment with m-CPBA in the presence of Cl3CCO2H at
40 °C followed by transesterification (K2CO3/MeOH), con-
sistent with a mechanism involving completely diastereose-
lective epoxidation followed by completely regioselective
ring opening (Scheme 12).
It is noteworthy that even in the absence of significant 1,3-
allylic strain it is possible to obtain modest levels of diastereo-
selectivity within systems similar in structure to tertiary
allylic amines 67 and 68. For example, under optimized
conditions, sequential treatment of tertiary allylic amine 78
with Br3CCO2H and m-CPBA at rt for 3 days followed by
DBU gave a chromatographically inseparable 85:15 mixture
of carbonates 82 and 83,22 which were isolated in 77%
combined yield. The relative configuration within the major
diastereoisomeric carbonate 82 was assigned upon the as-
sumption that the reaction proceeds by an analogous mech-
anism to that delineated for 67, via epoxidation transition
state model 79 that places the allylic C-H bond (i.e., C(1)H)
of 78 coplanar with the olefinic C-H bond (i.e., C(3)H) to
minimize allylic 1,3-strain (i.e., directly analogous to transi-
tion state model 72) to give the major epoxide diastereo-
isomer 80. Ring opening of the epoxide via an SN2-type
process at the carbon atom distal to the ammonium moiety
unambiguously by single-crystal X-ray analysis,19 and the
relative configuration within 73 was assigned by analogy.
The stereochemical outcomes of these oxidation reactions
are therefore consistent with an ammonium-directed process
proceeding via transition state model 72 in which 1,3-allylic
strain is minimized. Treatment of a sample of epoxide 73 in
CDCl3 with Br3CCO2H revealed quantitative conversion to
tribromoacetate ester 75 as a single regio- and diastereo-
isomer within 12 h. The connectivity within 75 was estab-
lished by 1H NMR COSY and HMBC analyses. Subsequent
treatment of 75 with DBU gave quantitative conversion to
carbonate 76 within 1 h. Interestingly, under analogous
conditions, epoxide 74 showed a distinct recalcitrance to
undergo ring opening upon treatment with Br3CCO2H, and
the use of more forcing conditions resulted only in starting
material degradation. In light of these results, application of
our previously optimized one-pot protocol for the formation
of carbonates from allylic amines was investigated for 67,
although this was found to give a 2:1 mixture of epoxide 73
(>99:1 dr) and carbonate 76 (>99:1 dr); when the reaction
was repeated using 10 equiv of Br3CCO2H to promote the
ring-opening reaction, complete conversion to carbonate 76
(>99:1 dr) was observed, and 76 was isolated in 90% yield as
a single diastereoisomer whose relative configuration was
unambiguously assigned by single-crystal X-ray analysis;20
this analysis also affirmed the regioselectivity of the epoxide
ring-opening reaction [i.e., that formation of tribromoace-
tate ester 75 from epoxide 73 occurs by preferential epoxide
ring opening distal to the ammonium moiety (as predicted)
rather than via a process involving ring opening proximal to
the ammonium moiety followed by migration of the tribro-
moacetate group]. Treatment of carbonate 76 with K2CO3
in MeOH gave diol 77 whose relative configuration was
(21) Crystallographic data (excluding structure factors) have been depos-
ited with the Cambridge Crystallographic Data Centre as supplementary
publication number CCDC 784952.
(22) The crude reaction mixture also contained an 85:15 mixture of diols
84 and 85 (the ratio of carbonates 82 and 83 to diols 84 and 85 was 88:12);
chromatography allowed isolation of the major diastereoisomeric diol 84 in
7% yield and >99:1 dr, in addition to the 85:15 mixture of carbonates 82 and
83. The production of diols 84 and 85 in this reaction is presumably a result of
competitive hydrolysis of the corresponding carbonates 82 and 83 or the
intermediate tribromoacetate esters. Treatment of an 85:15 mixture of
carbonates 82 and 83 with K2CO3 in MeOH gave an 85:15 mixture of diols
84 and 85.
(19) Crystallographic data (excluding structure factors) have been depos-
ited with the Cambridge Crystallographic Data Centre as supplementary
publication number CCDC 784950.
(20) Crystallographic data (excluding structure factors) have been depos-
ited with the Cambridge Crystallographic Data Centre as supplementary
publication number CCDC 784951.
7750 J. Org. Chem. Vol. 75, No. 22, 2010

Davies et al.
JOCArticle
gives tribromoacetate ester 81, which undergoes elimination
of bromoform upon treatment with base to give carbonate 82
as the major product (Scheme 13).
0.1 M aq NaHCO3 (4 ꢀ 100 mL), dried, and concentrated in
vacuo. Purification via flash column chromatography (eluent
EtOAc) gave 7 as a colorless oil (553 mg, 84%): νmax (film) 2937
(C-H), 1796 (CdO); δH (400 MHz, CDCl3) 1.36-1.45 (1H, m,
C(20)HA), 1.46-1.54 (1H, m, C(20)HB), 1.54-1.61 (2H, m, C(30)H2),
1.63-1.70 (1H, m, C(10)HA), 1.71-1.82 (1H, m, C(10)HB), 2.65
(2H, t, J 7.2, C(40)H2), 3.79 (2H, s, NCH2Ph), 4.03 (1H, dd,
J 8.3, 7.2, C(5)HA), 4.49 (1H, app t, J 8.3, C(5)HB), 4.63-4.71
(1H, m, C(4)H), 7.23-7.35 (5H, m, Ph); δC (100 MHz, CDCl3)
22.2 (C(20)), 29.0 (C(30)), 33.7 (C(10)), 48.5 (C(40)), 53.5 (NCH2Ph),
69.3 (C(5)), 77.0 (C(4)), 127.3, 128.3, 128.5 (o,m,p-Ph), 139.1
(i-Ph), 155.0 (C(2)); m/z (ESIþ) 250 ([M þ H]þ, 100%); HRMS
(ESIþ) C14H20NO3þ requires 250.1438; found 250.1439.
Method B. Following general procedure 2, 5 (189 mg, 1.00
mmol) in CH2Cl2 (6.7 mL) was treated with Br3CCO2H (1.48 g,
5.00 mmol) and m-CPBA (344 mg, 75%, 1.50 mmol) followed by
DBU (2.0 mL). Purification via flash column chromatography
(eluent EtOAc) gave 7 as a colorless oil (159 mg, 64%).
(RS)-4-Benzyl-1,3-dioxolan-2-one 12. Following general pro-
cedure 1, 8 (80.2 mg, 0.678 mmol) in CH2Cl2 (4.5 mL) was
treated with Br3CCO2H (1.00 g, 3.39 mmol) and m-CPBA (233 mg,
75%, 1.01 mmol) followed by DBU (1.0 mL). Purification via
flash column chromatography (eluent 40-60 °C petrol/EtOAc,
4:1) gave 12 as a colorless oil (101 mg, 84%):24 δH (400 MHz,
CDCl3) 2.99 (1H, dd, J 14.0, 6.5, CHACHBPh), 3.15 (1H, dd,
J 14.0, 6.1, CHACHBPh), 4.17 (1H, dd, J 8.5, 6.8, C(5)HA), 4.44
(1H, dd, J 8.5, 7.9, C(5)HB), 4.90-4.97 (1H, m, C(4)H),
7.21-7.38 (5H, m, Ph).
Tetradecane-1,2-diol 19. Br3CCO2H (147 mg, 0.50 mmol) was
added to a solution of (R)-1,2-epoxytetradecane 16 (21 mg, 0.10
mmol) in CDCl3 (0.6 mL). The reaction was monitored by 1H
NMR analysis for 12 h. The reaction mixture was then diluted
with CH2Cl2 (10 mL) and washed with satd aq Na2SO3 (10 mL),
followed by satd aq NH4Cl (10 mL). The organic layer was dried
and concentrated in vacuo. The residue was dissolved in MeOH
(2.0 mL). K2CO3 (138 mg, 1.0 mmol) was added, and the
mixture was stirred at rt for 16 h and then concentrated in
vacuo. The residue was dissolved in CH2Cl2 (10 mL) and washed
with satd aq NaHCO3 (10 mL) and brine (10 mL). The organic
layer was dried and concentrated in vacuo to give 19 as white
solid (20.0 mg, 87%, 65:35 er):25 mp 60-62 °C {lit.25 mp 62-
64 °C}; δH (400 MHz, CDCl3) 0.88 (3H, t, J 7.0, CH3), 1.19-
1.45 (22H, m, CH2), 3.25-3.35 (1H, m, C(1)HA), 3.65-3.78
(2H, m, C(1)HB, C(2)H).
The enantiomeric excess of 19 was determined by Chiral
HPLC of the corresponding mono-p-nitrobenzoate derivative,
giving resolution of both enantiomers: OD-H Daicel chiral
column, flow rate 1.5 mL/min (iso-propanol/hexane 3:97), (S)-
enantiomer tR = 17.1 min and (R)-enantiomer tR = 22.7 min.
Data for 2-hydroxytetradecyl 4-nitrobenzoate: p-Nitroben-
zoyl chloride (80 mg, 0.43 mmol) was added to a solution of diol
19 (20 mg, 0.09 mmol) in pyridine (1.0 mL) and CH2Cl2 (1.0
mL). The reaction mixture was stirred at rt for 8 h, diluted with
CH2Cl2 (10 mL), and washed with satd aq CuSO4 (10 mL) and
brine (10 mL). Purification via flash column chromatography
(eluent 40-60 °C petrol/EtOAc 8:1) gave 2-hydroxytetradecyl
4-nitrobenzoate as a white solid (17 mg, 53%): mp 63-65 °C;
νmax (KBr) 3475 (O-H), 2955 (C-H), 1697 (CdO), 1543; δH
(400 MHz, CDCl3) 0.88 (3H, t, J 7.0, CH3), 1.19-1.38 (20H, m,
CH2), 1.57-1.59 (2H, m, C(3)H2), 4.01-4.02 (1H, m, C(2)H),
4.28 (1H, dd, J 11.5, 7.1, C(1)HA), 4.43 (1H, dd, J 11.5, 3.0,
C(1)HB), 8.22 (2H, d, J 8.8, Ar), 8.30 (2H, d, J 8.8, Ar); δC (100
MHz, CDCl3) 14.1 (C(14)), 22.6, 25.4, 29.1, 29.3, 29.5, 29.6,
29.7, 31.9, 33.5 (C(3)-C(13)), 69.9 (C(2)), 70.0 (C(1)), 123.6,
Conclusion
In conclusion, sequential treatment of a 1,2-disubstituted
olefin with m-CPBA, Br3CCO2H, and DBU results in the
one-pot, stereospecific conversion of the olefin to the corre-
sponding disubstituted cyclic carbonate (1,3-dioxolan-2-
one). The reaction proceeds via an initial epoxidation fol-
lowed by SN2-type epoxide ring opening by Br3CCO2H and
subsequent base-promoted carbonate formation upon elim-
ination of bromoform. When a solution of a secondary
allylic or homoallylic amine and Br3CCO2H is sequentially
treated with m-CPBA then DBU, the product of the reaction
is a cyclic carbamate (1,3-oxazolidin-2-one or 1,3-oxazinan-
2-one).
Experimental Section
General Experimental Details. m-CPBA was supplied as a
70-77% slurry in water and titrated according to the procedure
of Swern23 immediately before use. Water was purified by an
Elix UV-10 system. Organic solvents were used as supplied
(analytical or HPLC grade) without prior purification. Organic
layers were dried over MgSO4. Thin layer chromatography was
performed on aluminum plates coated with 60 F254 silica. Plates
were visualized using UV light (254 nm), iodine, 1% aqueous
KMnO4, or 10% ethanolic phosphomolybdic acid. Flash col-
umn chromatography was performed either on Kieselgel 60
silica on a glass column or on an automated flash column
chromatography platform.
Melting points are uncorrected. IR spectra were recorded as
either a thin film on NaCl plates (film) or a KBr disk (KBr), as
stated. Selected characteristic peaks are reported in cm-1. NMR
spectra were recorded in the deuterated solvent stated. The field
was locked by external referencing to the relevant deuteron
1
1
resonance. H-1H COSY and H-13C HMQC analyses were
used to establish atom connectivity.
General Procedure 1 for Oxidation of Olefins. m-CPBA was
added to a stirred solution of olefin in CH2Cl2, and the resultant
mixture was stirred at rt for 10 min. Br3CCO2H was added in one
portion, and the reaction mixture was stirred at rt for 18 h. DBU
was added at 0 °C, and the resultant mixture was stirred at rt for
2 h. Satd aq NaHCO3 and CH2Cl2 were added, and the layers were
separated. The organic layer was washed with satd aq NaHCO3
and brine and then dried, filtered, and concentrated in vacuo.
General Procedure 2 for Oxidation of Unsaturated Amines.
Br3CCO2H was added to a stirred solution of olefin in CH2Cl2,
and the resultant mixture was stirred at rt for 10 min. m-CPBA
was added in one portion, and the reaction mixture was stirred
at rt for 18 h. DBU was added at 0 °C, and the resultant mixture
was stirred at rt for 2 h. Satd aq NaHCO3 and CH2Cl2 were
added, and the layers were separated. The organic layer was
washed with satd aq NaHCO3 and brine and then dried, filtered,
and concentrated in vacuo.
(RS)-4-(40-N-Benzylaminobutyl)-1,3-dioxolan-2-one 7. Method
A. Cl3CCO2H (2.13 g, 13.2 mmol) was added to 5 (500 mg,
2.64 mmol) in CH2Cl2 (5 mL) at rt, and the solution was stirred
for 30 min. m-CPBA (985 mg, 75%, 4.22 mmol) was added, and
the resultant solution was stirred at rt for 21 h. The mixture was
then diluted with CH2Cl2 (100 mL) and washed with satd aq
Na2SO3 (100 mL portions) until starch-iodide paper indicated that
no m-CPBA was present. The organic layer was then washed with
(24) Paddock, R. L.; Hiyama, Y.; McKay, J. M.; Nguyen, S. T. Tetra-
hedron Lett. 2004, 45, 2023.
(25) Kawashima, M.; Horikawa, Y. Biotechnol. Lett. 1993, 15, 1039.
(23) Swern, D. Org. React. 1953, VII, 392.
J. Org. Chem. Vol. 75, No. 22, 2010 7751

Davies et al.
JOCArticle
130.8, 135.3 (o,m,p-Ar), 150.6 (i-Ar), 164.8 (CdO); m/z (ESIþ)
402 ([M þ Na]þ, 90%); HRMS (ESIþ) C21H33NNaO5þ ([M þ
Na]þ) requires 402.2251; found 402.2252.
76.7 (C(40)), 155.0 (C(20)), 173.6 (C(1)); m/z (ESIþ) 225 ([M þ
Na]þ, 100%); HRMS (ESIþ) C9H14NaO5þ ([M þ Na]þ) requires
225.0733; found 225.0732.
(RS)-4-Phenyl-1,3-dioxolan-2-one 25. Following general
qprocedure 1, 20 (105 mg, 1.00 mmol) in CH2Cl2 (6.7 mL) was
treated with Br3CCO2H (1.48 g, 5.00 mmol) and m-CPBA (344
mg, 75%, 1.50 mmol), followed by DBU (1.0 mL). Purification
via flash column chromatography (eluent 40-60 °C petrol/
EtOAc, 4:1) gave 25 as a colorless oil (103 mg, 63%):26 δH
(400 MHz, CDCl3) 4.36 (1H, app t, J 8.4, C(5)HA), 4.81 (1H, app
t, J 8.4, C(5)HB), 5.69 (1H, app t, J 8.4, C(4)H), 7.21-7.38 (5H,
m, Ph).
(RS)-4-Decyl-1,3-dioxolan-2-one 26. Following general pro-
cedure 1, 21 (151 mg, 0.90 mmol) in CH2Cl2 (6 mL) was treated
with Br3CCO2H (1.33 g, 4.50 mmol) and mCPBA (309 mg, 75%,
1.35 mmol), followed by DBU (1.5 mL). Purification via flash
column chromatography (eluent 40-60 °C petrol/EtOAc 5:1)
gave 26 as a colorless oil (160 mg, 78%): νmax (film) 2925 (C-H),
1800 (CdO), 1065; δH (400 MHz, CDCl3) 0.86 (3H, t, J 6.9,
C(100)H3), 1.22-1.36 (15H, m, CH2), 1.42-1.50 (1H, m, C(20)-
HA), 1.67-1.69 (1H, m, C(10)HA), 1.77-1.89 (1H, m, C(10)HB),
4.07 (1H, t, J 8.5, C(5)HA), 4.52 (1H, t, J 8.5, C(5)HB), 4.67-4.72
(1H, m, C(4)H); δC (100 MHz, CDCl3) 14.1 (C(100)), 22.6, 24.3,
29.1, 29.2, 29.3, 29.4, 29.5, 31.8 (C(20)-C(90)), 33.9 (C(10)), 69.4
(C(4)), 76.7 (C(5)), 155.6 (C(2)); m/z þ(ESIþ) 251 ([M þ Na]þ,
100%); HRMS (ESIþ) C13H24NaO3 ([M þ Na]þ) requires
251.1618; found 251.1616.
(RS,RS)-4-Butyl-5-methyl-1,3-dioxolan-2-one 34. Following
general procedure 1, 30 (72 mg, 0.72 mmol) in CH2Cl2 (4.8 mL)
was treated with Br3CCO2H (1.06 g, 3.61 mmol) and m-CPBA
(250 mg, 75%, 1.08 mmol), followed by DBU (1.0 mL). Purifi-
cation via flash column chromatography (eluent 40-60 °C
petrol/EtOAc, 5:1) gave 34 asacolorlessoil(93mg,81%,>99:1dr):
νmax (film) 2959 (C-H), 1802 (CdO); δH (400 MHz, CDCl3)
0.89 (3H, t, J 6.5, C(40)H3), 1.30-1.40 (4H, m, C(20)H2, C(30)H2),
1.42 (3H, d, J 6.1, C(5)Me), 1.59-1.77 (2H, m, C(10)H2), 4.16
(1H, dt, J 6.9, 5.1, C(4)H), 4.36 (1H, dq, J 6.9, 6.1, C(5)H); δC
(100 MHz, CDCl3) 13.7 (C(40)), 19.0 (C(5)Me), 22.2 (C(20)), 26.7
(C(30)), 32.8 (C(10)), 78.4 (C(5)), 83.5 (C(4)), 154.6 (C(2)); m/þz
(ESIþ) 181 ([M þ Na]þ, 100%); HRMS (ESIþ) C8H14NaO3
([M þ Na]þ) requires 181.0835; found 181.0836.
(RS,RS)-4-(Benzyloxymethyl)-5-propyl-1,3-dioxolan-2-one 35.
Following general procedure 1, 31 (190 mg, 1.00 mmol) in CH2Cl2
(6.6 mL) was treated with Br3CCO2H (1.48 g, 5.00 mmol) and m-
CPBA (344 mg, 75%, 1.50 mmol), followed by DBU (1.5 mL).
Purification via flash column chromatography (eluent 40-60 °C
petrol/EtOAc, 4:1) gave 35 as a colorless oil (185 mg, 74%,
>99:1 dr): νmax (film) 2962 (C-H), 1797 (CdO); δH (500 MHz,
CDCl3) 0.96 (3H, t, J 7.0, C(300)H3), 1.38-1.44(1H, m, C(200)HA),
1.57-1.66 (2H, m, C(200)HB, C(100)HA), 1.79-1.85 (1H, m,
C(100)HB), 3.64-3.71 (2H, m, CH2OBn), 4.57-4.58 (2H, m,
OCH2Ph), 4.70-4.73 (2H, m, C(4)H, C(5)H), 7.30-7.45 (5H,
m, Ph); δC (125 MHz, CDCl3) 13.7 (C(300)H3), 19.2 (C(200)), 30.5
(C(100)), 66.7 (CH2OBn), 73.8 (CH2Ph), 76.7, 79.2 (C(4), C(5)),
127.7, 128.0, 128.5 (o,m,p-Ph), 137.0 (i-Ph), 154.5 (C(2)); m/þz
(ESIþ) 273 ([M þ Na]þ, 90%); HRMS (ESIþ) C14H18NaO4
([M þ Na]þ) requires 273.1097; found 273.1095.
(RS)-4-(Benzyloxymethyl)-1,3-dioxolan-2-one 27. Following
general procedure 1, 22 (107 mg, 0.72 mmol) in CH2Cl2 (4.8 mL)
was treated with Br3CCO2H (1.06 g, 3.60 mmol) and m-CPBA
(506 mg, 75%, 2.19 mmol), followedby DBU (1.0mL). Purification
via flash column chromatography (eluent 40-60 °C petrol/EtOAc,
4:1) gave 27 as a colorless oil (94 mg, 63%):27 δH (400 MHz,
CDCl3) 3.62 (1H, dd, J 11.0, 3.7, CHAHBOBn), 3.71 (1H, dd, J
11.0, 3.7, CHAHBOBn), 4.38 (1H, dd, J 8.6, 6.2, C(5)HA), 4.48
(1H, app t, J 8.6, C(5)HB), 4.58 (2H, AB system, J 12.2, OCH2Ph),
4.79-4.84 (1H, m, C(4)H), 7.30-7.40 (5H, m, Ph).
(RS,RS)-5-(20-Hydroxyethyl)-4-ethyl-1,3-dioxolan-2-one 36.
Following general procedure 1, 32 (100 mg, 1.00 mmol) in
CH2Cl2 (6.6 mL) was treated with Br3CCO2H (1.48 g, 5.00
mmol) and m-CPBA (344 mg, 75%, 1.50 mmol), followed by
DBU (1.0 mL). Purification via flash column chromatography
(eluent 40-60 °C petrol/EtOAc, 1:1) gave 36 as a pale yellow oil
(83 mg, 65%, >99:1 dr): νmax (film) 3424 (O-H), 2972 (C-H),
1790 (CdO); δH (400 MHz, CDCl3) 1.02 (3H, t, J 7.5, Me), 1.74
(2H, q, J 7.5, C(100)H2), 1.91-1.98 (2H, m, C(10)H2), 3.78-3.81
(2H, m, C(20)H2), 4.30 (1H, dd, J 12.6, 7.5, C(5)H), 4.47-4.52
(1H, m, C(4)H); δC (100 MHz, CDCl3) 8.8 (C(200)), 26.5 (C(100)),
36.2 (C(10)), 57.9 (C(20)), 79.1 (C(4)), 83.4 (C(5)), 155.0 (C(2));
(RS)-4-(40-Acetoxybutyl)-1,3-dioxolan-2-one 28. Following
general procedure 1, 23 (70 mg, 0.50 mmol) in CH2Cl2 (3.3 mL)
was treated with Br3CCO2H (740 mg, 2.5 mmol) and m-CPBA
(172 mg, 75%, 0.75 mmol), followed by DBU (1.0 mL). Purifi-
cation via flash column chromatography (eluent 40-60 °C
petrol/EtOAc, 1:1) gave 28 as an opaque oil (85 mg, 84%): νmax
(film) 2917 (C-H), 1793 (CdO, carbonate), 1731 (CdO, ester);
δ
H (400 MHz, CDCl3) 1.41-1.50 (1H, m, CH2), 1.53-1.61 (1H,
m/z (ESIþ) 183 ([M þ Na]þ, 100%); HRMS (ESIþ) C7H12NaO4
þ
m, CH2), 1.66-1.76 (4H, m, CH2), 2.04 (3H, s, COMe), 4.05-
4.08 (3H, m, C(5)HA, C(40)H2), 4.53 (1H, t, J 9.4, C(5)HB),
4.47-4.74 (1H, m, C(4)H); δC (100 MHz, CDCl3) 20.9 (Me),
21.1, 28.1, 33.5 (C(10)-C(30)), 63.7 (C(40)), 69.3 (C(5)), 76.8
(C(4)), 154.9 (C(2)), 171.1 (COMe); mþ/z (ESIþ) 225 ([M þ Na]þ,
100%); HRMS (ESIþ) C9H14NaO5 ([M þ Na]þ) requires
225.0733; found 225.0732.
([M þ Na]þ) requires 180.0628; found 180.0636.
(RS,RS)-4-(20-Dibenzylaminoethyl)-5-ethyl-1,3-dioxolan-2-one
37. Following general procedure 2, 33 (279 mg, 1.00 mmol) in
CH2Cl2 (6.6 mL) was treated with Br3CCO2H (1.48 g, 5.00 mmol)
and m-CPBA(344mg, 75%, 1.5mmol), followedbyDBU(1.0mL).
Purification via flash column chromatography (eluent 40-60 °C
petrol/EtOAc, 6:1) gave 37 as a colorless oil (252 mg, 74%,
>99:1 dr): νmax (film) 2969 (C-H), 1801 (CdO); δH (500 MHz,
CDCl3) 0.98 (3H, t, J 7.4, C(200)H3), 1.46-1.58 (2H, m, C(100)H2),
1.71-1.86 (1H, m, C(10)HA), 1.88-1.94 (1H, m, C(10)HB), 2.59-
2.63 (2H, m, C(20)H2), 3.61 (4H, AB system, JAB 13.5, N(CH2-
Ph)2), 4.05-4.09 (1H, m, C(5)H), 4.28-4.32 (1H, m, C(4)H),
7.26-7.34 (10H, m, Ph); δC (125 MHz, CDCl3) 8.9 (C(200)H3),
26.5 (C(100)H2), 31.9 (C(10)), 49.0 (C(20)), 58.8 (N(CH2Ph)2), 79.8
(C(5)), 82.8 (C(4)), 127.1, 128.4, 128.8 (o,m,p-Ph), 139.0 (i-Ph),
154.7 (C(2)); m/z (ESIþ) 362 ([M þ Na]þ, 100%); HRMS (ESIþ)
C21H26NO3þ ([M þ H]þ) requires 340.1907; found 340.1911.
(RS,SR)-4-Butyl-5-methyl-1,3-dioxolan-2-one 43. Following
general procedure 1, 38 (71 mg, 0.72 mmol) in CH2Cl2 (4.8 mL)
was treated with Br3CCO2H (1.06 g, 3.61 mmol) and m-CPBA
(250 mg, 75%, 1.08 mmol), followed by DBU (1.0 mL).
Purification via flash column chromatography (eluent 40-60 °C
(RS)-Methyl 5-(10,30-dioxolan-20-one-40-yl)pentanoate 29.
Following general procedure 1, 24 (142 mg, 1.00 mmol) in CH2Cl2
(6.6 mL) was treated with Br3CCO2H (1.48 g, 5.00 mmol) and m-
CPBA (344 mg, 75%, 1.50 mmol), followed by DBU (1.0 mL).
Purification via flash column chromatography (eluent 40-60 °C
petrol/EtOAc, 2:1) gave 29 as a yellow oil (143 mg, 71%): νmax
(film) 2917 (C-H), 1793 (CdO, carbonate), 1731 (CdO, ester);
δH (400 MHz, CDCl3) 1.38-1.59 (2H, m, C(4)H2), 1.64-1.86
(4H, m, C(3)H2, C(5)H2), 2.32 (2H, t, J 7.2, C(2)H2), 3.65 (3H, s,
OMe), 4.05 (1H, dd, J 10.8, 7.2, C(50)HA), 4.52 (1H, dd, J 10.8,
8.4, C(50)HB), 4.66-4.73 (1H, m, C(40)H); δC (100 MHz, CDCl3)
23.9, 24.3 (C(3), C(4), C(5)), 33.5 (C(2)), 51.6 (OMe), 69.3 (C(50)),
(26) Kim, Y. J.; Barma, R. S. J. Org. Chem. 2005, 70, 7882.
(27) Matsumoto, K.; Fuwa, S.; Shimojo, M.; Kitajima, H. J. Chem. Soc.
Jpn. 1996, 69, 2977.
7752 J. Org. Chem. Vol. 75, No. 22, 2010

Davies et al.
JOCArticle
petrol/EtOAc, 5:1) gave 43 as a colorless oil (105 mg, 92%,
>99:1 dr): νmax (film) 2959 (C-H), 1799 (CdO); δH (400 MHz,
CDCl3) 0.93 (3H, t, J 7.2, C(40)H3), 1.36 (3H, d, J 6.7, C(5)Me),
1.35-1.44 (4H, m, C(20)H2, C(30)H2), 1.51-1.57 (1H, m,
C(10)HA), 1.67-1.77 (1H, m, C(10)HB), 4.63 (1H, ddd, J 10.2,
7.0, 3.4, C(4)H), 4.83 (1H, dq, 7.0, 6.7, C(5)H); δC (100 MHz,
CDCl3) 13.8 (C(40)), 14.5 (C(5)Me), 22.3 (C(20)), 27.6 (C(30)),
28.5 (C(10)), 76.0 (C(5)), 80.0 (C(4)), 154.7 (C(2)); m/z (ESIþ) 181
([M þ Na]þ, 100%); HRMS (ESIþ) C8H14NaO3þ ([M þ Na]þ)
requires 181.0835; found 181.0831.
49.7 (C(20)), 58.9 (N(CH2Ph)2), 77.8 (C(5)), 80.3 (C(4)), 127.3,
128.2, 129.7 (o,m,p-Ph), 139.0 (i-Ph), 154.6 (C(2)); m/z (ESIþ)
362 ([M þ Na]þ, 100%);HRMS(ESIþ) C21H26NO3þ ([M þ H]þ)
requires 340.1907; found 340.1911.
(RS)-N(3)-Benzyl-5-(hydroxymethyl)-1,3-oxazolidin-2-one 50.
Following general procedure 2, 48 (147 mg, 1.00 mmol) in CH2Cl2
(6.6 mL) was treated with Br3CCO2H (1.48 g, 5.00 mmol) and
m-CPBA (344 mg, 75%, 1.50 mmol), followed by DBU (2.0 mL).
Purification via flash column chromatography (gradient elution,
50%f100% EtOAc in 30-40 °C petrol) gave 50 as a colorless
oil (157 mg, 88%): νmax (film) 3408 (O-H), 2924, 2874 (C-H),
1731 (CdO); δH (400 MHz, CDCl3) 3.35 (1H, app t, J 8.6,
C(4)HA), 3.42 (1H, app t, J 8.6, C(4)HB), 3.57 (1H, dd, J 12.5,
4.3, C(10)HA), 3.78 (1H, dd, J 12.5, 3.2, C(10)HB), 4.36 (2H, AB
system, JAB 15.0, NCH2Ph), 4.53-4.57 (1H, m, C(5)H), 7.25-
7.33 (5H, m, Ph); δC (100 MHz, CDCl3) 45.2 (C(4)), 48.2
(NCH2Ph), 62.8 (C(10)), 73.8 (C(5)), 127.9, 128.0, 128.8 (o,m,
p-Ph), 135.6 (i-Ph), 158.3 (C(2)); m/z (þESIþ) 230 ([M þ Na]þ,
100%); HRMS (ESIþ) C11H13NNaO3 ([M þ Na]þ) requires
230.0788; found 230.0788.
(RS,SR)-4-Phenyl-4-methyl-1,3-dioxolan-2-one 44. Following
general procedure 1, 39 (118 mg, 1.00 mmol) in CH2Cl2 (6.6 mL)
was treated with Br3CCO2H (1.48 g, 5.00 mmol) and m-CPBA
(344 mg, 75%, 1.50 mmol), followed by DBU (1.2 mL). Purifica-
tion via flash column chromatography (eluent 40-60 °C petrol/
EtOAc, 5:1) gave 44 as a colorless oil (157 mg, 88%, >99:1 dr):
νmax (film) 2984, 2936 (C-H), 1806 (CdO); δH (400 MHz,
CDCl3) 1.54 (3H, dt, J 6.1, 1.5, C(5)Me), 4.56-4.64 (1H, m,
C(5)H), 5.14 (1H, d, J 8.1, C(4)H), 7.34-7.37 (2H, m, Ph),
7.41-7.44 (3H, m, Ph); δC (100 MHz, CDCl3) 18.3 (C(5)Me),
80.8 (C(5)), 84.9 (C(4)), 126.0, 129.1, 129.7 (o,m,p-Ph), 135.0
(i-Ph), 154.3 (C(2)); m/z (ESIþ) 201 ([M þ Na]þ, 100%); HRMS
(RS)-N(3)-Benzyl-6-(hydroxymethyl)-1,3-oxazinan-2-one 51.
Following general procedure 2, 49 (100 mg, 0.620 mmol) in
CH2Cl2 (4.1 mL) was treated with Br3CCO2H (917 mg, 3.10
mmol) and m-CPBA (213 mg, 75%, 0.93 mmol), followed by
DBU (1.0 mL). Purification via flash column chromatography
(gradient elution, 50%f100% EtOAc in 30-40 °C petrol)
gave 51 as a pale yellow solid (83 mg, 61%): mp 95-97 °C;
(ESIþ) C10H10NaO3 ([M þ Na]þ) requires 201.0522; found
þ
201.0524.
(RS,SR)-4-(Benzyloxymethyl)-5-propyl-1,3-dioxolan-2-one 45.
Following general procedure 1, 40 (190 mg, 1.00 mmol) in CH2Cl2
(6.6 mL) was treated with Br3CCO2H (1.48 g, 5.00 mmol) and
m-CPBA (344 mg, 75%, 1.50 mmol), followed by DBU (1.5 mL).
Purification via flash column chromatography (eluent 40-60 °C
petrol/EtOAc, 4:1) gave 45 as a colorless oil (178 mg, 71%,
>99:1 dr): νmax (film) 2959 (C-H), 1793 (CdO), 1051; δH (500
MHz, CDCl3) 0.97 (3H, t, J 7.0, C(300)H3), 1.38-1.44 (2H, m,
C(200)H2), 1.60-1.70 (1H, m, C(100)HA), 1.70-1.80 (1H, m,
C(100)HB), 3.60 (1H, dd, J 10.9, 1.9, C(10)HA), 3.68 (1H, dd,
J 10.9, 1.9, C(10)HB), 4.34-4.37 (1H, m, C(4)H), 4.52-4.61 (3H,
m, OCH2Ph, C(5)H), 7.30-7.44 (5H, m, Ph); δC (125 MHz,
CDCl3) 13.6 (C(300)), 17.8 (C(200)), 36.0 (C(100)), 68.7 (CH2OBn),
73.7 (OCH2Ph), 78.6 (C(5)), 79.9 (C(4)), 127.7, 128.0, 128.6 (o,
m,p-Ph), 137.0 (i-Ph), 154.5 (C(2)); m/z (ESIþ) 273 ([M þ Na]þ,
ν
max (KBr) 3384 (O-H), 2928, 2872 (C-H), 1672 (CdO); δH
(400 MHz, CDCl3) 1.89-2.17 (2H, m, C(5)H2), 3.20-3.23
(1H, m, C(4)HA), 3.28-3.31 (1H, ddd, J 16.7, 11.5, 5.3,
C(4)HB), 3.67 (1H, dd, J 12.3, 5.2, C(10)HA), 3.83 (1H, dd, J
12.3, 3.4, C(10)HB), 4.34-4.38 (1H, m, C(6)H), 4.55 (2H, AB
system, JAB 14.9, NCH2Ph), 7.26-7.50 (5H, m, Ph); δC (100
MHz, CDCl3) 23.4 (C(5)), 43.6 (C(4)), 52.6 (NCH2Ph), 64.3
(CH2OH), 77.7 (C(6)), 127.7, 128.0, 128.7 (o,m,p-Ph), 136.4
(i-Ph), 153.8 (C(2)); m/z (ESIþ) 244 ([M þ Na]þ, 100%); HRMS
(ESIþ) C12H15NNaO3þ ([M þ Na]þ) requires 244.0944; found
244.0943.
(RS,SR)-N(3)-Benzyl-5-(10-hydroxybutyl)-1,3-oxazolidin-2-one
54. Following general procedure 2, 52 (100 mg, 0.528 mmol) in
CH2Cl2 (3.5 mL) was treated with Br3CCO2H (778 mg, 2.64 mmol)
and m-CPBA (181 mg, 75%, 0.79 mmol), followed by DBU (1.0
mL). Purification via flash column chromatography (gradient
elution, 50%f100% EtOAc in 30-40 °C petrol) gave 54 as a
colorless oil (113 mg, 86%, >99:1 dr): νmax (film) 3418 (O-H),
2957 (C-H), 1726 (CdO); δH (400 MHz, CDCl3) 0.91 (3H, app
t, J 7.0, C(40)H3), 1.31-1.38 (3H, m, C(20)H2, C(30)HA), 1.51-
1.55 (1H, m, C(30)HB), 3.32 (1H, t, J 8.7, C(4)HA), 3.45-3.47
(1H, m, C(4)HB), 3.86-3.89 (1H, m, C(10)H), 4.33 (1H, d, J 14.9,
NCHAHBPh), 4.40 (1H, ddd, J 16.3, 8.7, 3.7, C(5)H), 4.52 (1H,
d, J 14.9, NCHAHBPh), 7.23-7.50 (5H, m, Ph); δC (100 MHz,
CDCl3) 13.9 (C(40)), 18.6 (C(30)), 33.5 (C(20)), 44.0 (C(4)), 48.3
(NCH2Ph), 70.4 (C(10)), 75.7 (C(5)), 127.9, 128.1, 128.8 (o,m,p-
Ph), 135.6 (i-Ph), 158.0 (C(2)); m/z (ESIþ) 272 ([M þ Na]þ,
100%); HRMS (ESIþ) C14H18NaO4 ([M þ Na]þ) requires
þ
273.1097; found 273.1095.
(RS,SR)-4-(20-Hydroxyethyl)-5-ethyl-1,3-dioxolan-2-one 46.
Following general procedure 1, 41 (100 mg, 1.00 mmol) in CH2Cl2
(6.6 mL) was treated with Br3CCO2H (1.48 g, 5.00 mmol) and m-
CPBA (344 mg, 75%, 1.50 mmol), followed by DBU (1.5 mL).
Purification via flash column chromatography (eluent 40-60 °C
petrol/EtOAc, 1:1) gave 46 as a colorless oil (88 mg, 55%, >99:1
dr): νmax (film) 3417 (O-H), 2974 (C-H), 1792 (CdO); δH (400
MHz, CDCl3) 1.08 (3H, t, J 7.6, C(200)H3), 162-1.72 (2H, m,
C(100)H2), 1.73-1.92 (2H, m, C(10)H2), 3.79-3.87 (2H, m,
C(20)H2), 4.59-4.65 (1H, m, C(4)H), 4.90-4.96 (1H, m, C(5)H);
δC (100 MHz, CDCl3) 10.0 (C(200)), 22.4 (C(100)), 31.3 (C(10)),
58.4 (C(20)), 76.7 (C(4)), 81.2 (C(5)), 154.7 (C(2)); m/z (ESIþ) 183
([M þ Na]þ, 100%); HRMS (ESIþ) C7H12NaO4þ ([M þ Na]þ)
requires 183.0628; found 183.0629.
þ
100%); HRMS (ESIþ) C14H19NNaO3 ([M þ Na]þ) requires
(RS,SR)-4-(20-Dibenzylaminoethyl)-5-ethyl-1,3-dioxolan-2-one
47. Following general procedure 2, 42 (279 mg, 1.00 mmol) in
CH2Cl2 (6.6 mL) was treated with Br3CCO2H (1.48 g, 5.00
mmol) and m-CPBA (344 mg, 75%, 1.5 mmol), followed by
DBU (1.5 mL). Purification via flash column chromatography
(eluent 40-60 °C petrol/EtOAc, 6:1) gave 47 as a colorless oil
(270 mg, 79%, >99:1 dr): νmax (film) 2971, 2803 (C-H), 1798
(CdO); δH (500 MHz, CDCl3) 0.95 (3H, t, J 7.3, C(200)H3),
1.30-1.35 (1H, m, C(100)HA), 1.50-1.57 (1H, m, C(100)HB), 1.67-
1.69 (1H, m, C(10)HA), 1.80-1.85 (1H, m, C(10)HB), 2.57-2.68
(2H, m, C(20)H2), 3.61 (4H, br s, N(CH2Ph)2), 4.26-4.30 (1H,
m, C(5)H), 4.72-4.76 (1H, m, C(4)H), 7.26-7.34 (10H, m, Ph);
δC (125 MHz, CDCl3) 9.96 (C(200)), 22.2 (C(100)), 27.0 (C(10)),
272.1257; found 272.1254.
(RS,SR)-N(3)-Benzyl-6-(10-hydroxypropyl)-1,3-oxazinan-2-one
55. Following general procedure 2, 53 (120 mg, 0.630 mmol) in
CH2Cl2 (4.1 mL) was treated with Br3CCO2H (932 mg, 3.15
mmol) and m-CPBA (216 mg, 75%, 0.95 mmol), followed by
DBU (1.0 mL). Purification via flash column chromatography
(gradient elution, 50%f100% EtOAc in 30-40 °C petrol) gave
55 as a colorless oil (138 mg, 88%, >99:1 dr): C14H19NO3
requires C, 67.45; H, 7.7; N, 5.6%; found C, 67.5; H, 7.6; N,
5.4%; νmax (film) 3392 (O-H), 3030 (C-H), 2966 (C-H), 1672
(CdO); δH (400 MHz, CDCl3) 1.02 (3H, t, J 5.5, C(30)H3),
1.45-1.56 (2H, m, C(20)H2), 1.89-2.05 (2H, m, C(5)H2),
3.18-3.25 (2H, m, C(4)H2), 3.73 (1H, app quintet, J 3.8, C(10)H),
J. Org. Chem. Vol. 75, No. 22, 2010 7753

Davies et al.
JOCArticle
4.15 (1H, dt, J 10.8, 3.8, C(6)H), 4.53 (2H, AB system, JAB 14.9,
NCH2Ph), 7.27-7.35 (5H, m, Ph); δC (100 MHz, CDCl3) 10.2
(C(30)), 21.2 (C(20)), 24.9 (C(5)), 43.6 (C(4)), 52.5 (NCH2Ph),
73.2 (C(10)), 79.9 (C(6)), 127.7, 128.0, 128.7 (o,m,p-Ph), 136.5
(i-Ph), 154.1 (CdO); m/z (ESI-) 248 ([M - H]-, 100%); HRMS
X-ray Crystal Structure Determination for 59. Data were collect-
ed using an Enraf-Nonius κ-CCD diffractometer with graphite
monochromated Mo KR radiation using standard procedures at
150 K. The structure was solved by direct methods (SIR92); all
non-hydrogen atoms were refined with anisotropic thermal
parameters. Hydrogen atoms were added at idealized positions.
The structure was refined using CRYSTALS.28
-
(ESI-) C14H18NO3 ([M - H]-) requires 248.1292; found
248.1291.
(RS,RS)-N(3)-Benzyl-5-(10-hydroxybutyl)-1,3-oxazolidin-2-one
58. Following general procedure 2, 56 (100 mg, 0.528 mmol) in
CH2Cl2 (3.5 mL) was treated with Br3CCO2H (778 mg, 2.64 mmol)
and m-CPBA (181 mg, 75%, 0.79 mmol), followed by DBU
(1.0 mL). Purification via flash column chromatography (gradient
elution, 50%f100% EtOAc in 30-40 °C petrol) gave 58 as a
colorless oil (117 mg, 89%, >99:1 dr): νmax (film) 3418 (O-H), 2957
(C-H), 1726 (CdO); δH (400 MHz, CDCl3) 0.92 (3H, t, J 7.1,
C(40)H3), 1.39-1.54 (4H, m, C(20)H2, C(30)H2), 3.30 (1H, app t, J
7.5, C(4)HA), 3.41 (1H, app t, J 7.5, C(4)HB), 3.53-3.56 (1H, m,
C(10)H), 4.36 (1H, d, J 15.0, NCHAHBPh), 4.36-4.38 (1H, m,
C(5)H), 4.49 (1H, d, J 15.0, NCHAHBPh), 7.26-7.38 (5H, m, Ph);
δC (100 MHz, CDCl3) 13.8 (C(40)), 18.7 (C(30)), 34.5 (C(20)), 45.7
(C(4)), 48.3 (NCH2Ph), 72.1 (C(10)), 75.7 (C(5)), 127.9, 128.0, 128.8
(o,m,p-Ph), 135.6 (i-Ph), 157.7 (C(2)); m/z (ESIþ) 250 ([M þ H]þ,
100%); HRMS (ESIþ) C14H20NO3þ ([M þ H]þ) requires 250.1438;
found 250.1436.
X-ray crystal structure data for 61 [C14H19NO3]: M = 249.31,
˚
monoclinic, space group P21/n, a = 12.0044(4) A, b = 9.1663(4) A,
˚
3
˚
˚
c = 12.0881(5) A, β = 92.7130(18)°, V = 1328.63(9) A , Z = 4,
μ = 0.087 mm-1, colorless plate, crystal dimensions = 0.13 ꢀ
0.18 ꢀ 0.21 mm3. A total of 3016 unique reflections were
measured for 5 < θ < 27, and 3016 reflections were used in
the refinement. The final parameters were wR2 = 0.141 and
R1 = 0.065 [I > -3.0σ(I)].
Crystallographic data (excluding structure factors) have been
deposited with the Cambridge Crystallographic Data Centre as
supplementary publication number CCDC 784949. Copies of
the data can be obtained, free of charge, on application to CCDC,
12 Union Road, Cambridge, CB2 1EZ, UK [fax: þ44(0)-1223-
336033 or e-mail: deposit@ccdc.cam.ac.uk].
(RS,SR)-1-N,N-Dibenzylamino-1-phenyl-2,3-epoxy-3-methyl-
butane 73. Cl3CCO2H (1.20 g, 7.33 mmol) was added to a solution
of 67 (500 mg, 1.47 mmol) in CH2Cl2 (10 mL) at rt, and the
solution was stirred for 30 min. m-CPBA (1.08 g, 70%, 4.40
mmol) was added, and the solution was stirred at rt for 1 h. The
mixture was then diluted with CH2Cl2 (20 mL) and washed with
satd aq Na2SO3 (50 mL portions) until starch-iodide paper
indicated that no m-CPBA was present. The organic layer was
washed with satd aq NaHCO3 (4 ꢀ 50 mL), dried, and con-
centrated in vacuo. Purification via flash column chromatogra-
phy (gradient elution, 1%f5% Et2O in 30-40 °C petrol) gave
73 as a colorless oil (516 mg, 98%, >99:1 dr): νmax (film) 3041
(C-H), 2961 (C-H), 1493; δH (400 MHz, CDCl3) 0.91 (3H, s,
Me), 1.45 (3H, s, Me), 3.34 (1H, d, J 9.0, C(2)H), 3.65 (1H, d, J
9.0, C(1)H), 3.80 (4H, AB system, JAB 13.5, N(CH2Ph)2), 7.14-
7.49 (15H, m, Ph); δC (100 MHz, CDCl3) 18.8 (Me), 24.8 (Me),
53.9 (N(CH2Ph)2), 56.2 (C(3)), 60.3 (C(1)), 63.2 (C(2)), 126.7,
127.2, 127.8, 128.1, 128.3, 129.0 (o,m,p-Ph), 139.9, 140.0 (i-Ph);
m/z (ESIþ) 358 ([M þ H]þ, 100%); HRMS (ESIþ) C25H28NOþ
([M þ H]þ) requires 358.2165; found 358.2167.
X-ray Crystal Structure Determination for 58. Data were
collected using an Enraf-Nonius κ-CCD diffractometer with
graphite monochromated Mo KR radiation using standard proce-
dures at 150 K. The structure was solved by direct methods (SIR92);
all non-hydrogen atoms were refined with anisotropic thermal
parameters. Hydrogen atoms were added at idealized positions.
The structure was refined using CRYSTALS.28
X-ray crystal structure data for 58 [C14H19NO3]: M = 498.62,
˚
triclinic, space group P1, a = 9.6645(4) A, b = 11.3513(4) A,
˚
˚
c = 12.7583(5) A, R = 101.4022(16)°, β = 104.9826(16)°, γ =
3
-1
˚
90.623(2)°, V = 1322.54(9) A , Z = 4, μ = 0.088 mm
,
colorless block, crystal dimensions = 0.12 ꢀ 0.16 ꢀ 0.24 mm3.
A total of 5982 unique reflections were measured for 5 < θ < 27,
and 2904 reflections were used in the refinement. The final param-
eters were wR2 = 0.134 and R1 = 0.127 [I > 2.5σ(I)].
Crystallographic data (excluding structure factors) have been
deposited with the Cambridge Crystallographic Data Centre as
supplementary publication number CCDC 784948. Copies of
the data can be obtained, free of charge, on application to CCDC,
12 Union Road, Cambridge, CB2 1EZ, UK [fax: þ44(0)-1223-
336033 or e-mail: deposit@ccdc.cam.ac.uk].
(RS,SR)-1-N,N-Dibenzylamino-1-isopropyl-2,3-epoxy-3-methyl-
butane 74. Cl3CCO2H (265 mg, 1.63 mmol) was added to a solu-
tion of 68 (100 mg, 0.33 mmol) in CH2Cl2 (2 mL) at rt, and the
solution was stirred for 30 min. m-CPBA (120 mg, 70%, 0.48
mmol) was added, and the solution was stirred at rt for 21 h. The
mixture was then diluted with CH2Cl2 (10 mL) and washed with
satd aq Na2SO3 (20 mL portions) until starch-iodide paper
indicated that no m-CPBA was present. The organic layer was
washed with satd aq NaHCO3 (4 ꢀ 20 mL), dried, and concen-
trated in vacuo. Purification via flash column chromatography
(gradient elution, 1%f5% Et2O in 30-40 °C petrol) gave 73 as
a white solid (105 mg, 99%, >99:1 dr): mp 74-77 °C; νmax (film)
2958 (C-H), 2927 (C-H), 1493; δH (400 MHz, CDCl3) 0.78
(3H, d, J 6.7, MeCHMe), 1.02 (3H, d, J 6.7, MeCHMe), 1.15
(3H, s, C(3)Me), 1.36 (3H, s, C(3)Me), 1.80-1.89 (1H, m,
CHMe2), 2.11 (1H, app t, J 9.8, C(1)H), 2.92 (1H, d, J 9.8,
C(2)H), 3.90 (4H, AB system, JAB 13.1, N(CH2Ph)2), 7.20-7.49
(10H, m, Ph); δC (100 MHz, CDCl3) 19.5 (Me), 19.8 (Me), 20.9
(Me), 24.5 (Me), 28.8 (CHMe2), 54.7 (N(CH2Ph)2), 56.6 (C(3)),
60.8 (C(1)), 66.3 (C(2)), 126.6, 128.0, 129.2 (o,m,p-Ph), 140.6
(i-Ph); m/z (ESIþ) 346 ([M þ Na]þ, 100%); HRMS (ESIþ)
C22H30NOþ ([M þ H]þ) requires 324.2322; found 324.2325.
X-ray Crystal Structure Determination for 74. Data were
collected using an Enraf-Nonius κ-CCD diffractometer with
graphite monochromated Mo KR radiation using standard
procedures at 150 K. The structure was solved by direct
methods (SIR92); all non-hydrogen atoms were refined with
(RS,RS)-N(3)-Benzyl-6-(10-hydroxypropyl)-1,3-oxazinan-2-one
59. Following general procedure 2, 57 (120 mg, 0.630 mmol) in
CH2Cl2 (4.2 mL) was treated with Br3CCO2H (932 mg, 3.15
mmol) and m-CPBA (216 mg, 75%, 0.95 mmol), followed by
DBU (1.0 mL). Purification via flash column chromatography
(gradient elution, 50%f100% EtOAc in 30-40 °C petrol) gave
59 as a colorless oil (132 mg, 84%, >99:1 dr): C14H19NO3
requires C, 67.45; H, 7.7; N, 5.6%; found C, 67.4; H, 7.6; N,
5.6%; νmax (film) 3390 (O-H), 3031 (C-H), 2934 (C-H), 1681
(CdO); δH (400 MHz, CDCl3) 0.99 (3H, t, J 7.0, C(30)H3),
1.53-1.64 (2H, m, C(20)H2), 1.87-1.91 (2H, m, C(5)H2), 3.17-
3.22 (1H, m, C(4)HA), 3.21-3.30 (1H, m, C(4)HB), 3.49-3.53
(1H, m, C(10)H), 4.11-4.16 (1H, m, C(6)H), 4.54 (2H, AB
system, JAB 15.0, NCH2Ph), 7.26-7.35 (5H, m, Ph); δC (100
MHz, CDCl3) 9.9 (C(30)), 23.8 (C(20)), 25.5 (C(5)), 43.7 (C(4)),
52.5 (NCH2Ph), 74.2 (C(10)), 79.8 (C(6)), 127.6, 128.1, 128.7
(o,m,p-Ph), 136.5 (i-Ph), 153.8 (C(2)); m/z (ESI-) 248 ([M-H]-,
100%); HRMS (ESI-) C14H18NO3- ([M-H]-) requires 248.1292;
found 248.1292.
(28) Betteridge, P. W.; Carruthers, J. R.; Cooper, R. I.; Prout, C. K.;
Watkin, D. J. CRYSTALS; Chemical Crystallography Laboratory, Uni-
versity of Oxford: U.K., 2010; Issue 14.
7754 J. Org. Chem. Vol. 75, No. 22, 2010

Davies et al.
JOCArticle
anisotropic thermal parameters. Hydrogen atoms were
added at idealized positions. The structure was refined using
CRYSTALS.28
X-ray crystal structure data for 74 [C22H29NO]: M = 323.48,
˚
monoclinic, space group P21/c, a = 12.1182(2) A, b =
(10 mL) and washed with satd aq NaHCO3 (10 mL) and brine
(10 mL). The organic layer was dried and concentrated in
vacuo. Purification via flash column chromatography (eluent
40-60 °C petrol/EtOAc, 5:1) gave 77 as a white solid (72 mg,
62%, >99:1 dr): mp 90-94 °C; νmax (film) 3315 (O-H), 2971
(C-H); δH (400 MHz, CDCl3) 0.64 (3H, s, C(3)MeA), 0.98
(3H, s, C(3)MeB), 2.99-3.02 (2H, m, N(CHAHBPh)2), 3.84
(1H, d, J 9.4, C(1)H), 3.87-3.91 (2H, m, N(CHAHBPh)2), 4.07
(1H, J 9.4, C(2)H), 7.25-7.47 (15H, m, Ph); δC (100 MHz,
CDCl3) 24.7(Me),27.9(Me),52.9(N(CH2Ph)2),53.6(N(CH2Ph)2),
60.0 (C(1)), 73.3 (C(2)), 127.2, 127.5, 128.0, 128.3, 128.6, 130.3
(o,m,p-Ph), 138.2, 139.8 (i-Ph); m/z þ(ESIþ) 376 ([M þ H]þ,
100%); HRMS (ESIþ) C25H30NO2 ([M þ H]þ) requires
376.2271; found 376.2270.
Method B. K2CO3 (127 mg, 0.92 mmol) was added to a solu-
tion of 76 (37 mg, 0.09 mmol) in MeOH (2.0 mL). The mixture
was heated to 60 °C for 16 h and then concentrated in vacuo. The
residue was dissolved in CH2Cl2 (10 mL) and washed with satd
aq NaHCO3 (10 mL) and brine (10 mL). The organic layer was
dried and concentrated in vacuo. Purification via flash column
chromatography (eluent 40-60 °C petrol/EtOAc, 5:1) gave 77
as a white solid (34 mg, 98%, >99:1 dr).
˚
˚
10.2863(2) A, c = 15.4746(3) A, β = 97.3039(8)°, V =
1913.28(6) A , Z = 4, μ = 0.068 mm-1, colorless plate, crystal
3
˚
dimensions = 0.18 ꢀ 0.21 ꢀ 0.28 mm3. A total of 4354 unique
reflections were measured for 5 < θ < 27, and 2864 reflections
were used in the refinement. The final parameters were wR2 =
0.090 and R1 = 0.043 [I > -3.0σ(I)].
Crystallographic data (excluding structure factors) have been
deposited with the Cambridge Crystallographic Data Centre as
supplementary publication number CCDC 784950. Copies of
the data can be obtained, free of charge, on application to CCDC,
12 Union Road, Cambridge, CB2 1EZ, UK [fax: þ44(0)-1223-
336033 or e-mail: deposit@ccdc.cam.ac.uk].
(RS,SR)-4,4-Dimethyl-5-[(N,N-dibenzylamino)(phenyl)methyl]-
1,3-dioxolan-2-one 76. Following general procedure 2, 67 (170 mg,
0.500 mmol) in CH2Cl2 (3.3 mL) was treated with Br3CCO2H
(1.48 g, 5.00 mmol) and m-CPBA (184 mg, 70%, 0.75 mmol),
followed by DBU (1.0 mL). Purification via flash column chroma-
tography (eluent 40-60 °C petrol/EtOAc, 5:1) gave 43 as a white
solid (180 mg, 90%, >99:1 dr): mp 126-128 °C; νmax (KBr)
2981 (C-H), 1797 (CdO); δH (400 MHz, CDCl3) 0.97 (3H, s,
C(5)MeA), 1.13 (3H, s, C(5)MeB), 3.19 (2H, d, J 13.7, N-
(CHAHBPh)2), 3.99 (2H, d, J 13.7, N(CHAHBPh)2), 4.07 (1H,
d, J 11.1, C(10)H), 5.11 (1H, d, J 11.1, C(5)H), 7.10-7.49 (15H,
m, Ph); δC (100 MHz, CDCl3) 21.4 (Me), 26.8 (Me), 53.5
(N(CH2Ph)2), 60.2 (C(10)), 84.1 (C(4)), 84.2 (C(5)), 127.2, 127.5,
128.4, 128.8, 129.3, 130.3 (o,m,p-Ph), 138.1, 139.0 (i-Ph), 153.9
(C(2)); m/z (ESIþ) 424 ([M þ Na]þ, 70%); HRMS (ESIþ)
C26H28NO3þ ([M þ H]þ) requires 402.2064; found 402.2067.
X-ray Crystal Structure Determination for 76. Data were
collected using an Enraf-Nonius κ-CCD diffractometer with graphite
monochromated Mo KR radiation using standard procedures at
150 K. The structure was solved by direct methods (SIR92); all
non-hydrogen atoms were refined with anisotropic thermal
parameters. Hydrogen atoms were added at idealized positions.
The structure was refined using CRYSTALS.28
X-ray Crystal Structure Determination for 77. Data were
collected using an Enraf-Nonius κ-CCD diffractometer with
graphite monochromated Mo KR radiation using standard
procedures at 150 K. The structure was solved by direct
methods (SIR92); all non-hydrogen atoms were refined with
anisotropic thermal parameters. Hydrogen atoms were
added at idealized positions. The structure was refined using
CRYSTALS.28
X-ray crystal structure data for 77 [C25H29NO2]: M = 375.51,
˚
monoclinic, space group P21/c, a = 10.14550(10) A, b =
˚
˚
8.47320(10) A, c = 24.9311(4) A, β = 97.0646(6)°, V =
2126.93(5) A , Z = 4, μ = 0.073 mm-1, colorless block, crystal
3
˚
dimensions = 0.20 ꢀ 0.20 ꢀ 0.20 mm3. A total of 4820 unique
reflections were measured for 5 < θ < 27, and 2564 reflections
were used in the refinement. The final parameters were wR2 =
0.046 and R1 = 0.040 [I > 3.0σ(I)].
Crystallographic data (excluding structure factors) have
been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication number CCDC 784952.
Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge, CB2
1EZ, UK [fax: þ44(0)-1223-336033 or e-mail: deposit@ccdc.
cam.ac.uk].
X-ray crystal structure data for 76 [C26H27NO3]: M = 401.51,
˚
triclinic, space group P1, a = 8.7549(2) A, b = 9.8380(3) A,
˚
˚
c = 14.0722(5) A, R = 85.2408(11)°, β = 83.4949(12)°, γ =
3
-1
˚
66.4693(13)°, V = 1103.16(6) A , Z = 2, μ = 0.078 mm
,
colorless block, crystal dimensions = 0.21 ꢀ 0.24 ꢀ 0.27 mm3. A
total of 4962 unique reflections were measured for 5 < θ < 27,
and 4962 reflections were used in the refinement. The final
parameters were wR2 = 0.100 and R1 = 0.063 [I > -3.0σ(I)].
Crystallographic data (excluding structure factors) have
been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication number CCDC 784951.
Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge, CB2
1EZ, UK [fax: þ44(0)-1223-336033 or e-mail: deposit@ccdc.
cam.ac.uk].
(4RS,5SR,10SR)-4-[(N,N-Dibenzylamino)(phenyl)methyl]-5-
methyl-1,3-dioxolan-2-one 82. Br3CCO2H (2.96 g, 10.0 mmol)
was added to a stirred solution of 78 (265 mg, 1.00 mmol) in
CH2Cl2 (6.6 mL), and the resultant mixture was stirred at rt for
10 min. m-CPBA (367 mg, 70%, 1.50 mmol) was added in one
portion, and the reaction mixture was stirred at rt for 3 days.
DBU was added at 0 °C, and the resultant mixture was stirred at
rt for 2 h. Satd aq NaHCO3 (10 mL) was added, and the layers
were separated. The organic layer was washed with satd aq
NaHCO3 (2 ꢀ 10 mL) and brine (10 mL) and then dried and
concentrated in vacuo to give an 85:15 mixture of 82 and 83 as a
colorless oil (298 mg, 77%, 82:83, 85:15). An analytical sample
of 82 (>95:5 dr) was obtained after exhaustive flash column
chromatography: νmax (film) 2986 (C-H), 1803 (CdO); δH (400
MHz, CDCl3) 0.94 (3H, d, J 9.3, C(5)Me), 3.29 (2H, d, J 13.5,
N(CHAHBPh)2), 3.95 (2H, d, J 13.5, N(CHAHBPh)2), 4.07 (1H,
app d, J 9.3, C(10)H), 5.11 (1H, q, J 9.3, C(5)H), 5.43-5.55 (1H,
m, C(4)H), 7.10-7.49 (15H, m, Ph); δC (100 MHz, CDCl3) 14.5
(Me), 53.6 (N(CH2Ph)2), 59.3 (C(10)), 75.6 (C(5)), 77.7 (C(4)),
127.1, 128.4, 128.5, 128.8, 128.9, 133.5 (o,m,p-Ph), 138.9, 139.0
(i-Ph), 154.6 (C(2));þm/z (ESIþ) 388 ([M þ H]þ, 100%); HRMS
(ESIþ) C25H26NO3 ([M þ H]þ) requires 388.1907; found
388.1904.
(RS,SR)-1-N,N-Dibenzylamino-1-phenyl-3-methyl-butane-2,
3-diol 77. Method A. Cl3CCO2H (253 mg, 1.55 mmol) was added
to 67 (106 mg, 0.310 mmol) in CH2Cl2 (2 mL) at rt, and the
resultant solution was stirred for 30 min. m-CPBA (80 mg, 73%,
0.34 mmol) was added, and the reaction mixture was stirred at
40 °C for 21 h. The mixture was then cooled to rt, diluted with
CH2Cl2 (10 mL), and washed with satd aq Na2SO3 (10 mL
portions) until starch-iodide paper indicated that no m-CPBA
was present. The organic layer was washed with satd aq
NaHCO3 (4 ꢀ 10 mL), dried, and concentrated in vacuo. The resi-
due was dissolved in MeOH (4.0 mL); K2CO3 (428 mg, 3.1 mmol)
was added; and the mixture was stirred at rt for 16 h and then
concentrated in vacuo. The residue was dissolved in CH2Cl2
J. Org. Chem. Vol. 75, No. 22, 2010 7755

Davies et al.
JOCArticle
Acknowledgment. The authors would like to thank Aji-
nomoto Co., Inc. for funding (W.K.), the Oxford Chemical
Crystallography Service for the use of their X-ray diffrac-
tometers, Helen R. Storr for assistance with NMR experi-
ments, and Michael C. Willis and Robert H. Snell for
assistance with Chiral HPLC analysis.
Supporting Information Available: Full details of all
experimental procedures, characterization data, copies of
1H and 13C NMR spectra, and crystallographic information
files (for structures CCDC 784948-784952). This material
is available free of charge via the Internet at http://pubs.
acs.org.
7756 J. Org. Chem. Vol. 75, No. 22, 2010