Photochemical reactions of prop-2-enyl and prop-2-ynyl substituted 4-aminomethyl- and 4-oxymethyl-2(5H)-furanones

Article abstract of DOI:10.3987/COM-13-S(S)67

Compounds with a heterocyclic 9-oxatricyclo[5.3.0.01,5]decan-8-one skeleton were synthesized by intramolecular [2+2] photocycloaddition reactions of the title compounds (λ= 254 nm, Et2O or MeCN as the solvent). Starting from various substituted 4-(prop-2-enylaminomethyl)-2(5H)-furanones, products 5, 9, 18, 21, 23, 24 were obtained, which bear a nitrogen atom in position 3 of this skeleton within a pyrrolidine ring. The Boc or Cbz groups represent suitable nitrogen protecting groups, which were compatible with the irradiation conditions and which can be easily cleaved. In an analogous fashion an oxygen (product 22) and carbon substituent (product 25) could be implemented at position 3 of the product if the starting material was appropriately chosen. The prop-2-ynyl substituted substrates did not produce a [2+2] photocycloaddition product but rather underwent a cyclization to spiro products 11 and 13.

Full text of DOI:10.3987/COM-13-S(S)67

HETEROCYCLES, Vol. 88, No. 2, 2014
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HETEROCYCLES, Vol. 88, No. 2, 2014, pp. 1079 - 1100. © 2014 The Japan Institute of Heterocyclic Chemistry
Received, 29th June, 2013, Accepted, 1st August, 2013, Published online, 16th August, 2013
DOI: 10.3987/COM-13-S(S)67
PHOTOCHEMICAL REACTIONS OF PROP-2-ENYL AND
PROP-2-YNYL SUBSTITUTED 4-AMINOMETHYL- AND
4-OXYMETHYL-2(5H)-FURANONES
Diego A. Fort,a,b Thomas J. Woltering,b André M. Alker,c and Thorsten
Bacha*
a
Chair of Organic Chemistry I, Technische Universität München, D-85747
Garching, Germany, thorsten.bach@ch.tum.de
b Discovery Chemistry, PCMM, F. Hoffmann-La Roche Ltd., Grenzacherstrasse,
CH-4070 Basel, Switzerland
c
Biostructure Section, Molecular Design & Chemical Biology, Pharmaceuticals
Division, F. Hoffmann-La Roche Ltd., Grenzacherstrasse, CH-4070 Basel,
Switzerland
Dedicated to Professor Victor Snieckus on the occasion of his 77th birthday
Abstract – Compounds with a heterocyclic 9-oxatricyclo[5.3.0.01,5]decan-8-one
skeleton were synthesized by intramolecular [2+2] photocycloaddition reactions
of the title compounds (= 254 nm, Et2O or MeCN as the solvent). Starting from
various substituted 4-(prop-2-enylaminomethyl)-2(5H)-furanones, products 5, 9,
18, 21, 23, 24 were obtained, which bear a nitrogen atom in position 3 of this
skeleton within a pyrrolidine ring. The Boc or Cbz groups represent suitable
nitrogen protecting groups, which were compatible with the irradiation conditions
and which can be easily cleaved. In an analogous fashion an oxygen (product 22)
and carbon substituent (product 25) could be implemented at position 3 of the
product if the starting material was appropriately chosen. The prop-2-ynyl
substituted substrates did not produce a [2+2] photocycloaddition product but
rather underwent a cyclization to spiro products 11 and 13.

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INTRODUCTION
Although it has been discovered more than one hundred years ago,1,2 the [2+2] photocycloaddition
reaction of -unsaturated carbonyl compounds has remained to this date an actively studied synthetic
transformation. There are several reasons for the continuing interest in [2+2] photocycloaddition
chemistry. First of all, the quest for enantioselective [2+2] photocycloaddition reactions has not led to
satisfactory results. Although auxiliary-based approaches are known,3 there are no general concepts yet,
which allow for direct formation of enantiomerically enriched or enantiomerically pure [2+2] photocyclo-
addition products. Recent progress on this topic holds promise for catalytic enantioselective [2+2]
photocycloaddition reactions4 but further work is required. Secondly, [2+2] photocycloaddition reactions
offer the most concise access to cyclobutane skeletons, which are abundant structural motifs of natural
products5 and which can be used for a plethora of further transformations.6 For good reasons, the [2+2]
photocycloaddition is the most frequently used photochemical reaction in natural product synthesis.7 In a
significant number of recent studies8 the reaction has been applied to the synthesis of naturally occurring
cyclobutanes. The rigidity of the cyclobutane9 ring is a third reason why [2+2] photocycloaddition
reactions continue to attract the interest of synthetic chemists. The cyclobutane ring allows the positioning
of certain functional groups in a spatially defined way, which is increasingly appreciated by medicinal
and biological chemists.10 The introduction of these functional groups requires new types of substrates
being studied and in this context we have recently11 introduced the N-Boc (tert-butyloxycarbonyl)
protected 4-(allylaminomethyl)- and 4-(propargylaminomethyl)-2(5H)furanones A12,13 as new substrates
for photochemical transformations (Figure 1).
Figure 1. General structure of previously studied photo substrates A and general structure of the title
compounds B discussed in the present paper
Eight differently substituted 4-(allylaminomethyl)-2(5H)-furanones (vide infra) were shown to react to
the respective cyclobutanes in good yields (53-75%) and with perfect diastereoselectivity.11
N-Boc-4-(propargylaminomethyl)-2(5H)-furanone did not undergo a photocycloaddition but underwent
an interesting light-induced radical type cyclization reaction. We have now further expanded the substrate
scope of this reaction to general compound class B and we disclose in this full paper the details of our
work in this area.

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RESULTS AND DISCUSSION
4-(Prop-2-enylaminomethyl)-2(5H)-furanones. For the preparation of the photocycloaddition precursors
B with Y = H, 4-bromomethyl-2(5H)-furanone (4) was required as the starting material (Scheme 1).
Although the compound has been reported previously,14 we wanted to avoid radical conditions, which
require the use of CCl4 as solvent or the use of a transition metal salt (CuBr2). In addition, access to
4-hydroxymethyl-2(5H)-furanone (3) was straightforward starting from ketone 1 as key building block.
Scheme 1. Preparation of 4-(bromomethyl)-2(5H)-furanone (4) as precursor for the photocycloaddition
products 5 of N-Boc protected 4-(allylaminomethyl)-2(5H)-furanones
A Wittig reaction delivers the respective ester 2 in almost quantitative yield and subsequent mild ester
hydrolysis at elevated temperature induces the desired lactonization. This sequence has been previously
optimized to a fully reproducible multi-kilogram process15 and conditions for the conversion of alcohol 3
to bromide 4 were therefore examined. PBr3 in Et2O was the reagent of choice in the most practical
protocol. Although it delivered a moderate yield (52-58%) the ease of work-up and the high purity of
crude product made it superior to other procedures. Appel conditions16 delivered a better yield (67%) and
the protocol was amenable to large scale. However, extensive chromatography was necessary to remove
CHBr3 and PPh3O and to access a high quality product. Experiments on 5 g scale using a one-pot protocol
of mesylation (Ms2O, NEt3, THF) followed by direct substitution of the intermediate mesylate with LiBr
in THF suggest that this method is the highest yielding procedure (88%). It should be noted, though, that
the product is contaminated with some NEt3, which in the present case did not interfere with the
subsequent reactions (see Experimental). Indeed, as previously reported,11 displacement of the bromide
by allylic amines is facile and after immediate N-Boc protection the precursors for the photochemical
reactions are obtained. As mentioned above, the [2+2] photocycloaddition proceded smoothly delivering
products 5 in yields of 53-75% as single regio- and diastereoisomers.
Compounds 5 could be prepared on larger scale in a flow system.17 Processing amounts >50 g of
photoprecursor in the flow system, however, led to detrimental deposition of side products and a

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precipitate covering the reactor wall, which in turn decreased the conversion of initially 89% to <5% over
a period of four days. Therefore we attempted a batch process and we found a full conversion of a 120
mM solution in MeCN (350 mL quartz flask) after 18 h delivering a crystalline crude product 5a. Overall,
an isolated purified product could be obtained in 70% yield (see Experimental). The tricyclic product 5a
could be separated in its enantiomers by chiral HPLC and the (racemic) compound was characterized also
by single crystal X-ray analysis.18 The three-dimensional structure (Figure 2) illustrates the rigidity
exerted by the central cyclobutane ring and confirms previous structure assignments.
Figure 2. Structure of 3-aza-9-oxatricyclo[5.3.0.01,5]decan-8-one 5a in the crystal
It could be shown that not only the Boc group is suitable for protection of 4-(allylamino-
methyl)-2(5H)-furanones in the photocycloaddition but also a benzyloxycarbonyl (Cbz) group. The Cbz
group is advantageous for the protection of bulkier substrates and offers alternative deprotection pathways
as compared to Boc. Starting from amine 6, the protection was readily achieved under Schotten-Baumann
conditions19 with CbzCl (Scheme 2). The [2+2] photocycloaddition of the resulting product 7 proceeded
smoothly and delivered the expected tricyclic product 8. Acetonitrile turned out to be the superior solvent
for the photoreaction. After two hours of irradiation (c = 5 mM) the yield was 69% in this solvent but
only 45% in Et2O.
O
O
O
CbzCl, NaHCO3
rt (CH2Cl2/H2O)
h ( = 254 nm)
rt (MeCN)
Cbz
N
O
O
H
H
O
N
N
92%
69%
6
7
8
Cbz
Scheme 2. Synthesis of the N-Cbz protected photocycloaddition product 8
Irradiation of the free amine 6 and its N-acetyl or N-tosyl (Ts) derivatives resulted only in little or no
conversion. For reasons of product scope and for NMR-spectroscopic characterization it was desirable,
however, to convert the Boc- or Cbz-protected 3-aza-9-oxatricyclo[5.3.0.01,5]decan-8-ones into
compounds with a non-amidic protecting group. Indeed, due to the formation of rotamers, products 5
gave only broad NMR signals and decomposed at the relatively high temperature (120 °C) required to

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record well resolved NMR spectra. Conversion to the N-Ts derivatives was achieved by acidic
deprotection (Scheme 3) and subsequent tosylation. Compounds 9b and 9c were readily available from
the respective precursors 5b and 5c. Product 9b was crystalline and was subjected to X-ray
crystallographic analysis.20 The crystal structure allowed nicely correlating the NMR information
(coupling constants, NOE contacts) with the crystallographic data.
Scheme 3. Preparation of the N-Ts protected 3-aza-9-oxatricyclo[5.3.0.01,5]decan-8-ones 9 and crystal
structure of racemic product 9b
4-(Prop-2-ynyloxymethyl)- and 4-(prop-2-ynylaminomethyl)-2(5H)-furanones. Propargylic amine 10a
was obtained from bromide 4 and subsequent N-Boc protection. Its oxygen analogue 10b was prepared
from primary alcohol 3, which acted as a nucleophile displacing the triflate leaving group in propargyl
triflate. Like the former amine 10a, the latter ether 10b did not form the respective cyclobutene under
typical irradiation conditions. Rather the respective spiro compound 11b was isolated in a yield, which
was comparable to the yield previously reported11 for product 11a.
Scheme 4. Synthesis of spiro compounds 11 from 2(5H)-furanones 10
Mechanistically it is likely that the photoexcited -unsaturated lactone undergoes via its triplet state a
hydrogen abstraction from the solvent rather than cyclization. Addition to the triple bond leads to a
vinylic radical, which abstracts another hydrogen atom from the solvent. The mechanistic hypothesis was
supported by deuterium incorporation at the vinylic double bond when performing the reaction in
d10-Et2O.11 With the silylated acetylene 12, which was obtained from bromide 4 in two steps, as substrate,
an analogous cyclization was observed, which led to products 13 as a mixture of diastereoisomers.

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According to NOESY spectra the major diastereoisomer was (Z)-13, which showed NOE contacts
between the vinylic hydrogen atom and the - and -hydrogen atoms of the -lactone ring. In the minor
diastereoisomer the vinylic hydrogen atom showed a NOE contact to the pyrrolidine methylene group in
-position to the nitrogen atom. The result is in line with a related radical cyclization reaction to a
silylated alkyne, which also led predominantly to a spiro compound with an exocyclic double bond of the
same relative configuration.21
Scheme 5. Diastereoselectivity in the synthesis of spiro compounds 13 from 2(5H)-furanone 12
3-Substituted 4-(prop-2-enylaminomethyl)-2(5H)-furanones. In order to access 3-substituted
2(5H)-furanones, it was tried to perform the previously described Wittig reaction (Scheme 1) with sub-
stituted ylides. There was no conversion, however, even in toluene at reflux temperature. Attempts to
perform the olefination with phosphonates 14 (Scheme 6) did not look very promising, either, as the
attempted transformation with NaH gave only traces of products. Gratifyingly, we found that generation
of the enolate with isopropylmagnesium chloride22 led to very good product yields in the desired
Horner-Wadsworth-Emmons reaction with ketone 1. The subsequent conversion of -unsaturated esters
15 to the respective 3-substituted 4-(bromomethyl)-2(5H)-furanones 17 followed the standard protocol of
acidic hydrolysis/lactone formation and bromination of alcohols 16 using PBr3.
Y
CO2Et
O
Y = Me 14a
Y = F 14b
Y
PO(OEt)2
OEt
O
AcO
OAc
i PrMgCl (THF), rt
AcO
OAc
80%
84%
Y = Me 15a
Y = F 15b
1
O
O
Y
Y
AcCl (MeOH)
rt, then 50 °C
PBr3 (Et2O)
O
O
HO
Br
78 °C, then rt
99%
Y = Me 16a
Y = F 16b
90%
97%
Y = Me 17a
Y = F 17b
quant.
Scheme 6. Preparation of 4-(bromomethyl)-2(5H)-furanones 17a and 17b

HETEROCYCLES, Vol. 88, No. 2, 2014
1085
Bromide 17a was converted into the 4-(allylamino)- and 4-(methallylamino)-2(5H)-furanones by
treatment with the commercially available primary amines allylamine and methallylamine (Scheme 7).
N-Boc protection could be performed without prior purification of the resulting secondary amines
employing Boc2O in the absence of additional base and THF as solvent. The overall yields for the
transformations were high and the resulting 2(5H)-furanones 18 were subsequently subjected to typical
irradiation conditions (= 254 nm). Acetonitrile was a superior solvent as compared to Et2O, which had
been used in previous reactions. To our pleasant surprise, the product yields for the intramolecular [2+2]
photocycloaddition products 19 were even higher than those obtained from the 3-unsubstituted
2(5H)-furanones. Other regio- and diastereoisomers were not detectable and products 19 were obtained as
spectroscopically homogeneous compounds.
Scheme 7. Preparation of 3-methyl-4-(prop-2-enylaminomethyl)-2(5H)-furanones 18 and their
intramolecular [2+2] photocycloaddition
Although we had previously shown that the enone [2+2] photocycloaddition reactions proceed well with
fluorinated olefins,23 we had so far not tested an -fluorinated enone as substrate. The required starting
material 20 was prepared from 4-(bromomethyl)-2(5H)-furanone 17b employing the same sequence
already applied to 17a (Scheme 8). The N-Boc-proteced allylic amine 20 underwent a clean and
high-yielding [2+2] photocycloaddition to a 3-aza-9-oxatricyclo[5.3.0.01,5]decan-8-one with a fluorine
substituent at carbon atom C-7.
Scheme 8. Preparation of 3-fluoro-4-(prop-2-enylaminomethyl)-2(5H)-furanone 20 and its intramolecular
[2+2] photocycloaddition
Related [2+2] photocycloaddition products. In our preliminary studies we had synthesized – in addition
to the products 5 described above (Scheme 1) – the related photocycloaddition products 22-24. Product
22 is derived from the respective allylic ether (55% yield), product 23 from an allenylmethylamine (71%

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yield) and product 24 from a difluorinated allylic amine (63% yield). In addition, we could in the present
work show, that it is also possible to install a carbon group at position 3 of the 9-oxa-
tricyclo[5.3.0.01,5]decan-8-one skeleton readily generated by intramolecular [2+2] photocycloaddition.
Product 25 was obtained in 45% yield upon irradiation of the respective diester in acetonitrile (= 254
nm). The starting material for the [2+2] photocycloaddition was obtained from bromide 4 upon
nucleophilic displacement with the respective malonate (see Experimental). Product 25 was  as all other
products  isolated as a single regio- and diastereoisomer.
Figure 3. Structure of various 9-oxatricyclo[5.3.0.01,5]decan-8-one 22-25 obtained by intramolecular
[2+2] photocycloaddition
CONCLUSION
In summary, a total number of 14 different 9-oxatricyclo[5.3.0.01,5]decan-8-ones were obtained by
intramolecular [2+2] photocycloaddition reactions (53-92% yield) from substrates with the general
structure B. Two additional products were prepared by protective group manipulations in the 3-aza-series.
The preferred solvents for the irradiation were Et2O and acetonitrile at = 254 nm. The reaction could be
performed on preparative scale (up to 50 g) either in a batch mode or using a continuous flow system. The
products contain either a nitrogen, an oxygen or a carbon atom in position C-3. By choosing appropriate
starting materials, they can be substituted at all positions of the central cyclobutane ring. All products
have at least two exit vectors for further functionalization based on lactone ring opening. In addition, the
3-aza-products can be further functionalized at the nitrogen atom. Consecutive reactions of the
photocycloaddition products are currently being studied in our laboratories and will be reported in due
course.
EXPERIMENTAL
General: All reactions, sensitive to air or moisture, were carried out in flame-dried glassware under
positive pressure of argon using standard techniques. For the photoreactions, the compounds were
dissolved in the corresponding solvent, degassed by purging with Ar in an ultrasonicator for 15 minutes
and irradiated in a Rayonet RPR 200 merry-go-round reactor, equipped with 16 Rayonet RPR-2537 Å
lamps (λ = 254 nm). Unless otherwise stated, the reactions were stopped when the starting material was

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fully consumed according to thin layer chromatography (TLC) and/or LC-MS analysis. The solvent was
then removed and the residue was purified by column chromatography. Unless otherwise noted only one
reaction product could be determined. Typically, an immobile spot could be seen on TLC, which we
tentatively attribute to polymeric side-products. Flash chromatography was performed on silica gel 60
(Merck, 230-400 mesh) with the eluent mixtures given for the corresponding procedures. TLC was
performed on silica coated glass plates (silica gel 60 F254). Compounds were detected by UV (λ = 254
nm), CAM (cerium ammonium molybdate solution) or KMnO4. IR: JASCO IR-4100. MS /HRMS:
1
13
Finnigan MAT 8200. H and C NMR: Bruker AV-300, AV-400 and AV-600 recorded at 300 K unless
otherwise indicated. Chemical shifts are reported relative to the solvent [CHCl3: δ (1H) = 7.26 ppm, δ
(13C) = 77.0 ppm, DMSO: δ (1H) = 2.50 ppm, δ (13C) = 39.5 ppm] as reference. Apparent multiplets
which occur as a result of accidental equality of coupling constants to those of magnetically
non-equivalent protons are marked as virtual (virt.). The relative configuration of the products and the
multiplicity of the 13C-NMR signals were determined by two-dimensional NMR spectra (COSY, NOESY,
HSQC, HMBC). Melting points were measured on a Büchi B-540 and are not corrected.
4-(Bromomethyl)-2(5H)-furanone (4) Appel procedure: A 750-mL four-necked flat bottom flask
equipped with overhead stirrer, thermometer, reflux condenser and nitrogen bubbler was charged with
4-(hydroxymethyl)-2(5H)-furanone (3)15 (90.0 g, 789 mmol, 1.0 eq) in MeCN (250 mL), cooled to 5 °C,
PPh3 (207 g, 789 mmol, 1.0 eq) and then solid CBr4 (262 g, 789 mmol, 1.0 eq) was added portionwise
keeping the internal temperature below 30 °C, the cooling bath was removed and the resulting solution
was stirred at 25 °C for 1 h. The reaction mixture was evaporated to dryness to give a green semisolid. All
crude material was purified by flash chromatography (silica gel, ca. 1200 g, loaded with toluene, 0% to
30% EtOAc in heptane; not full separation, CHBr3 nicely removed, but some TPPO leaked through in the
end, impure fractions 4.5 g obtained) to give the 4-(bromomethyl)-2(5H)-furanone (4) (83.4 g, 67%) as a
light brown oil.
Mesylation/substitution protocol: To a solution of 4-(hydroxymethyl)-2(5H)-furanone (3)15 (3.42 g, 30
mmol, 1.0 eq) in THF (300 mL) at –78 °C was added methanesulfonic anhydride (7.32 g, 42.0 mmol, 1.4
eq) followed by dropwise addition of a solution of Et3N (4.86 g, 6.69 mL, 48.0 mmol, 1.6 eq) in THF
(100 mL) and the mixture was stirred at –78 °C for 1 h, then at 0 °C for 90 min. Methanesulfonic acid
(577 mg, 390 µL, 6.00 mmol, 0.2 eq) was added, stirred for another 5 min, then a 2 M solution of lithium
bromide in THF (52.5 mL, 105 mmol, 3.5 eq) was added, the cooling bath was removed and when the
internal temperature reached 15 °C the reaction was finished. All solids were filtered off and washed with
tert-butyl methyl ether (TBME). The filtrate was washed with water and brine, dried over Na2SO4.
Removal of the solvent in vacuum left a dark brown oil, which was purified by silica gel column

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chromatography (heptane:EtOAc 0% to 60% EtOAc) to give the 4-(bromomethyl)-2(5H)-furanone (4)
1
(5.16 g, 88%) as a light brown liquid (contains some NEt3 impurity). Rf: 0.32 (pentane:EtOAc 7:3). H
13
NMR (600 MHz, CDCl3): δ (ppm) 6.16 (s, 1 H3), 4.96 (s, 2 H5), 4.25 (s, 2 H, CH2Br). C NMR (151
MHz, CDCl3): δ (ppm) 172.5 (C2), 163.2 (C4), 118.9 (C3), 71.9 (C5), 22.5 (CH2Br). The analytical data
obtained matched those reported in the literature.14
N-tert-Butoxycarbonyl-3-aza-9-oxatricyclo[5.3.0.01,5]decan-8-one (5a) Large scale preparation: A
solution of tert-butyl allyl[(5-oxo-2,5-dihydrofuran-3-yl)methyl]carbamate11 (53.6 g, 212 mmol) in
MeCN (1.73 L) (concentration: 3%) was deoxygenated by bubbling argon through the solution under
sonication for 30 min and then irradiated at 254 nm in batches of ca. 350 mL in a quartz flask in a
Rayonet RPR-200 photoreactor (16 lamps, 8 W each) for 18 h per batch. After full conversion (crude GC
76%) the combined yellow solution was evaporated whereupon the crude material already crystallized.
The crude material was purified by flash chromatography (silica gel, 500 g, 30% to 50% EtOAc in
heptane) to give a light yellow solid which was vigorously stirred with a large magnetic stir bar in
n-heptane (~300 mL) and very little EtOAc (~20 mL) at 23 °C for 1 h to give the pure
N-tert-butoxycarbonyl-3-aza-9-oxatricyclo[5.3.0.01, 5]decan-8-one (5a) (37.5 g, 70%) as a white solid. mp
97-99 °C. Rf = 0.57 (pentane:EtOAc 1:1). IR (ATR): υ (cm-1) = 1755 (vs, C=O), 1692 (w), 1471 (m),
1
1397 (s), 1229 (m), 1161 (s), 1135 (m), 1011 (vs), 970 (m), 875 (m). H NMR (500 MHz, CDCl3): δ
(ppm) 4.39 (d, 2J = 9.8 Hz, 1 H10), 4.16 (d, 2J = 9.8 Hz, 1 H10), 3.95-3.92 (br. s, 1 H2), 3.73-3.58 (br. s, 1
2
3
2
H4), 3.30 (dd, J = 11.8 Hz, J = 6.5 Hz, 1 H4), 3.07 (d, J = 12.2 Hz, 1 H2), 2.97-2.86 (m, 1 H7, 1 H5),
2.36 (ddd, 2J = 12.9 Hz, 3J = 8.5 Hz, 3J = 6.7 Hz, 1 H6), 2.22 (ddd, 2J = 12.9 Hz, 3J = 8.5 Hz, 3J = 3.5 Hz,
1 H6), 1.49 [s, 9 C(CH3)3]. 13C NMR (151 MHz, CDCl3): δ (ppm) 179.3 (C8), 155.0 (COOtBu), 80.1
[C(CH3)3], 72.5 (C10), 52.2 (C4), 50.8 (C2), 39.9 (C7, C5), 28.4 [C(CH3)3], 27.6 (C6), (C1 not observed).
MS (EI, 70 eV): m/z (%) = 198 (31) [(M-C3H3O)+], 153 (26) [(M-C5H9O)+], 57 (100) [(M-C11H18NO2)+].
+
HRMS (ESI): Calculated for C13H20NO4 [(M+H)]+= 254.1387. Found = 254.1390. The analytical data
obtained matched those reported in the literature.11
Benzyl allyl[(5-oxo-2,5-dihydrofuran-3-yl)methyl]carbamate (7) To a mixture of 4-(allylamino-
methyl)-2(5H)-furanone (6) (1.00 g, 6.53 mmol, 1.0 eq) and sodium bicarbonate (8.77 g, 104 mmol, 16
eq) in CH2Cl2 (4.0 mL) and water (4.0 mL) at room temperature was added dropwise CbzCl (2.80 mL,
19.6 mmol, 3.0 eq) and the mixture was stirred at room temperature for 16 h. After that time, the reaction
mixture was poured into water and extracted with CH2Cl2. The organic layer was dried over Na2SO4.
Removal of the solvent in vacuum left a light yellow oil that was purified by column chromatography
(heptane:EtOAc 1:1) to give benzyl allyl[(5-oxo-2,5-dihydrofuran-3-yl)methyl]carbamate (7) (1.72 g,

HETEROCYCLES, Vol. 88, No. 2, 2014
1089
92%) as a yellow oil. Rf = 0.31 (heptane:EtOAc 1:1). IR (ATR): υ (cm-1) = 2954 (w, CH2N), 2925 (w,
CH2N), 1778 (m, C=O), 1746 (s, O-C=O), 1696 (s, C=O), 1643 (w, C=C), 1497 (w, CAr), 1239 (s, C-O),
1
1028 (m, C=C), 885 (m, C=C), 770 (w, CAr), 698 (m, CAr). H NMR (600 MHz, CDCl3): δ (ppm)
7.39-7.33 (m, 5 Har), 5.92 (br. s, 1 H4), 5.76 (br. s, 1 H2’), 5.21 (br. s, 2 H3’), 5.17 (br. s, 2 H, OCH2), 4.77
(br. s, 2 H2), 4.25 (br. s, 2 H, NCH2), 3.93 (br. s, 2 H1’). 13C NMR (151 MHz, CDCl3): δ (ppm) 173.0 (C5),
165.8 (C3), 156.1 (CO), 135.8 (Cipso), 132.5 (C2’), 128.6 (Car), 128.4 (Car), 127.9 (Car), 118.9 (C4), 117.0
(C3’), 71.9 (C2), 67.9 (OCH2), 50.0 (C1’), 44.9 (CH2). MS (EI, 70 eV): m/z (%): 288 (100) [(M+H)+].
HRMS (ESI): Calculated for C16H17NO4 [(M)+] = 287.1158. Found = 287.1163.
Benzyl (3-aza-9-oxatricyclo[5.3.0.01,5]decan-8-one)carbamate (8) The compound was prepared from
benzyl allyl[(5-oxo-2,5-dihydrofuran-3-yl)methyl]carbamate (7) (1.40 g, 4.87 mmol) in 962 mL of MeCN
by irradiation for 6 h (5 mM). Purification of the crude material by column chromatography
(heptane:EtOAc 1:1) afforded photoproduct (8) as a yellow oil (962 mg, 69%). Rf = 0.18 (heptane:EtOAc
1:1). IR (ATR): υ (cm-1) = 3032 (w, CAr), 1764 (m, O-C=O), 1694 (s, C=O), 1497 (w, CAr), 1013 (s, C-O).
2
1H NMR (600 MHz, CDCl3): δ (ppm) 7.38-7.34 (m, 5 Har), 5.18 (s, CH2), 4.40 (d, J = 9.9 Hz, 1 H10),
4.12 (d, 2J = 9.9 Hz, 1 H10), 4.03 (d, 2J = 12.1 Hz, 1 H2), 3.74 (d, 2J = 11.8 Hz, 1 H4), 3.38 (dd, 2J = 11.8
Hz, 3J = 6.6 Hz, 1 H4), 3.14 (d, 2J = 12.1 Hz, 1 H2), 2.97-2.93 (m, 1 H7, 1 H5), 2.38 (ddd, 2J = 12.9 Hz, 3J
3
13
= 8.3 Hz, J = 3.6 Hz, 1 H6), 2.23-2.20 (m, 1 H6). C NMR (151 MHz, CDCl3): δ (ppm) 179.1 (C8),
155.2 (NCOO), 136.4 (Car), 128.6 (Cipso), 128.2 (Car), 128.0 (Car), 72.3 (C10), 67.3 (CH2), 52.4 (C4), 50.9
(C2), 41.8 (C5), 39.9 (C7), 27.6 (C6), C1 not detected. MS (EI, 70 eV): m/z (%) = 287 (20) [(M)+], 91 (100).
HRMS (ESI): Calculated for C16H17NO4 [(M)+] = 287.1158. Found = 287.1154.
N-(p-Methylbenzenesulfonamide)-5-methyl-3-aza-9-oxatricyclo[5.3.0.01,5]decan-8-one (9b) To a
solution of N-tert-butoxycarbonyl-5-methyl-2-aza-9-oxa-tricyclo[5.3.0.01,5]decan-8-one (5b) (315 mg,
1.18 mmol, 1.0 eq) in CH2Cl2 (6 mL) at 0 °C was added trifluoroacetic acid (1.83 mL, 23.6 mmol, 20 eq).
The resulting solution was allowed to warm to room temperature and stirred for 1 h. Evaporation of
volatiles at reduced pressure afforded a crude product that was dissolved in CH2Cl2 (4 mL) and cooled to
0 °C. A solution of tosyl chloride (270 mg, 1.42 mmol, 1.2 eq) and Et3N (1.2 mL, 7.1 mmol, 6.0 eq) in
CH2Cl2 (2 mL) was added and the mixture stirred for 12 h at room temperature. After this time, CH2Cl2
and water were added. The aqueous layer was extracted with CH2Cl2 and the combined organic phases
were dried (Na2SO4), filtered and the solvent removed. Purification of the crude by column
chromatography (heptane:EtOAc 1:1) afforded the tosylated product 9b as a white solid (315 mg, 83%).
mp 189 °C. Rf = 0.16 (heptane:EtOAc 1:1). IR (ATR): υ (cm-1) = 1787 (m, CO), 1599 (w, Car), 1492 (w,
1
Car), 1455 (m), 1344 (m, SO2), 1173 (s, SO2), 1024 (s, O-C=O). H NMR (600 MHz, CDCl3): δ (ppm)

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HETEROCYCLES, Vol. 88, No. 2, 2014
7.69 (d, 3J = 8.3 Hz, 2 Har), 7.36 (d, 3J = 8.3 Hz, 2 Har), 4.22 (d, 2J = 10.3 Hz, 1 H10), 3.99 (d, 2J = 10.3 Hz,
1 H10), 3.72 (d, 2J = 10.2 Hz, 1 H4), 3.51 (d, 2J = 9.8 Hz, 1 H2), 2.94 (dd, 3J = 10.2 Hz, 3J = 3.7 Hz, 1 H7),
2.58 (dd, 2J = 12.8 Hz, 3J = 10.2 Hz, 1 H6), 2.48-2.45 (m, Me, 1 H4), 2.28 (d, 2J = 9.8 Hz, 1 H2), 1.96 (dd,
2J = 12.8 Hz, 3J = 3.6 Hz, 1 H6), 1.16 (s, CH3). 13C NMR (151 MHz, CDCl3): δ (ppm) 179.1 (C8), 144.3
(Cipso), 131.2 (Cipso), 129.8 (Car), 128.1 (Car), 67.6 (C10), 60.2 (C2), 52.8 (C4), 51.6 (C5), 44.9 (C1), 37.7
(C7), 33.8 (C6), 21.6 (ArCH3), 18.7 (CH3). MS (EI, 70 eV): m/z (%) = 322 (100) [(M+H)+]. HRMS (ESI):
Calculated for C16H19NO4S [(M)+] = 321.1035. Found = 321.1036.
N-(p-Methylbenzenesulfonamide)-5-phenyl-3-aza-9-oxatricyclo[5.3.0.01,5]decan-8-one (9c) To a
solution of N-tert-butoxycarbonyl-5-phenyl-2-aza-9-oxa-tricyclo[5.3.0.01,5]decan-8-one (5c) (294 mg,
0.856 mmol, 1.0 eq) in CH2Cl2 (5 mL) at 0 °C was added trifluoroacetic acid (1.33 mL, 17.3 mmol, 20
eq). The resulting solution was allowed to warm to room temperature and stirred for 1 h. Evaporation of
volatiles at reduced pressure afforded a crude product that was dissolved in CH2Cl2 (4 mL) and cooled to
0 °C. A solution of tosyl chloride (196 mg, 1.3 mmol, 1.2 eq) and Et3N (0.72 mL, 5.14 mmol, 6 eq) in
CH2Cl2 (2 mL) was added and the mixture stirred for 12 h at room temperature. After this time, CH2Cl2
and water were added. The aqueous layer was extracted with CH2Cl2 and the combined organic phases
were dried (Na2SO4), filtered and the solvent removed. Purification of the crude material by column
chromatography (heptane:EtOAc 1:1) afforded the tosylated product (9c) as a white solid (200 mg, 61%).
mp 106 °C. Rf = 0.31 (heptane:EtOAc 1:1). IR (ATR): υ (cm-1) = 3058 (w, Car), 3027 (w, Car), 2952 (w,
1
CH), 1767 (m, CO), 1598 (w, Car), 1496 (w, Car), 1340 (m, SO2), 1161 (s, SO2), 1013 (s, O-C=O). H
3
3
NMR (600 MHz, CDCl3): δ (ppm) 7.73 (virt. dt, J = 8.3 Hz, J = 1.9 Hz, 2 Har), 7.40-7.33 (m, 4 Har),
7.28 (dt, 3J = 7.4 Hz, 3J = 1.2 Hz, 1 Har), 6.99-6.93 (m, 2 Har), 4.06 (d, 2J = 10.5 Hz, 1 H10), 3.98 (d, 2J =
10.5 Hz, 1 H10), 3.83 (d, 2J = 10.2 Hz, 1 H4), 3.78 (d, 2J = 10.3 Hz, 1 H2), 3.08 (dd, 3J = 10.3 Hz, 3J = 4.2
13
Hz, 1 H7), 2.94- 2.86 (m, 1 H6, 1 H2), 2.80-2.74 (m, 1 H6, 1 H4), 2.48 (s, CH3). C NMR (151 MHz,
CDCl3): δ (ppm) 178.2 (C8), 144.5 (Ce), 137.6 (Ca), 131.5 (Ch), 129.9, 129.1, 128.1, 127.7 (Cd), 126.8,
67.7 (C10), 62.9 (C2), 55.2 (C5), 54.2 (C4), 52.6 (C1), 37.9 (C7), 31.2 (C6), 21.7 (CH3). MS (EI, 70 eV):
m/z (%) = 383 (35) [(M)+], 228 (95) [(M-C7H7SO2)+], 155 (100), 118 (80), 91 (92). HRMS (ESI):
Calculated for C21H21NO4S [(M)+] = 383.1192. Found = 383.1193.
4-(Prop-2-ynoxymethyl)-2(5H)-furanone (10b) 4-(Hydroxymethyl)-2(5H)-furanone (3) (413 mg, 3.62
mmol, 1.0 eq) and K2CO3 (8.0 g, 57.9 mmol, 16 eq) were dissolved in dry CH2Cl2 (20 mL) and cooled to
–35 °C. A solution of propynyl triflate (3.40 g, 18 mmol, 5 eq) in dry CH2Cl2 (20 mL) was added slowly.
The mixture was allowed to warm to room temperature and stirred for 72 h. Evaporation to dryness and
purification by column chromatography (heptane:EtOAc 1:1) afforded the expected product 10b (158 mg,

HETEROCYCLES, Vol. 88, No. 2, 2014
1091
30%) as a colorless oil. Rf = 0.26 (heptane:EtOAc 1:1). IR (ATR): υ (cm-1) = 2923 (s, C-H), 2117 (w,
C≡C), 1742 (s, C=O), 1647 (m, C=CH), 1094 (m, C-O), 1030 (m, C-O). 1H NMR (600 MHz, CDCl3): δ
(ppm) 6.04 (virt. q, 4J = 4J = 1.8 Hz, 1 H3), 4.86 (dt, 4J = 1.8 Hz, 4J = 0.8 Hz, 2 H5), 4.49 (dt, 4J = 1.8 Hz,
4J = 0.8 Hz, CH2), 4.25 (d, 4J = 2.3 Hz, 2 H1’), 2.52 (t, 4J = 2.4 Hz, 1 H3’). 13C NMR (151 MHz, CDCl3): δ
(ppm) 173.2 (C2), 165.5 (C4), 116.2 (C3), 78.3 (C3’), 75.9 (C2’), 71.4 (C5), 65.1 (CH2), 58.5 (C1’). MS (EI,
70 eV): m/z (%) = 153 (100) [(M+H)+], 123 (25) [(M-CHO)+], 108 (39), 95 (60), 39 (100).
9-Methylene-2,7-dioxaspiro[4.4]nonan-3-one (11b) The compound was prepared from photoprecursor
10b (60 mg, 0.394 mmol) in 80 mL of Et2O by irradiation for 90 min (5 mM). Purification of the crude
product by column chromatography (heptane:EtOAc 1:1) afforded 9-methylene-2,7-dioxa-
spiro[4.4]nonan-3-one (11b) as an oil (37.0 mg, 60%). Rf = 0.28 (heptane:EtOAc 1:1). IR (ATR): υ (cm-1)
1
= 2973 (s, C-H), 2117 (w, C≡C), 1776 (s, C=O), 1695 (w, C=CH2), 1017 (s, C-O), 930 (m). H NMR
(600 MHz, CDCl3): δ (ppm) 5.15 (dd, 2J = 3.2 Hz, 4J = 2.0 Hz, 1 H6), 5.13 (dt, 2J = 3.2 Hz, 4J = 1.2 Hz, 1
2
H6), 4.46 (dd, 2J = 13.8 Hz, 4J = 2.0 Hz, 1 H4), 4.40 (ddd, J = 13.7 Hz, 4J = 1.2 Hz, 4J = 0.5 Hz, 1 H4),
4.31 (d, 2J = 9.2 Hz, 1 H2), 4.17 (dd, 2J = 9.2 Hz, 4J = 0.9 Hz, 1 H2), 3.96 (d, 2J = 9.0 Hz, 1 H10), 3.76 (d,
2
2
13
2J = 9.0 Hz, 1 H10), 2.70 (d, J = 17.6 Hz, 1 H7), 2.59 (d, J = 17.6 Hz, 1 H7). C NMR (151 MHz,
CDCl3): δ (ppm) 175.1 (C8), 150.3 (C5), 105.3 (C6), 77.6 (C2), 76.9 (C4), 71.6 (C10), 50.2 (C1), 38.4 (C7).
MS (EI, 70 eV): m/z (%) = 152 (5) [(M)+], 124 (10), 110 (35), 96 (100), 67 (96), 39 (50).
tert-Butyl N-[(5-oxo-2H-furan-3-yl)methyl]-N-(3-trimethylsilylprop-2-ynyl)carbamate (12) To a
solution of bromide 4 (720 mg, 4.07 mmol, 1.0 eq) in THF (6 mL) at 0 °C was dropwise added a solution
of Et3N (2.27 mL, 16.3 mmol, 3.0 eq) and 3-(trimethylsilyl)prop-2-yn-1-amine (666 mg, 4.07 mmol, 1.0
eq) in THF (5 mL). The resulting solution was stirred at room temperature for 12 h. The precipitate was
filtered off, washed with THF, and the solvent was removed in vacuum. The crude material was purified
by column chromatography (heptane:EtOAc 1:3) and the product was used for protection reactions
without further purification. The amine (406 mg, 1.82 mmol, 1.0 eq) was dissolved in THF (5.0 mL) and
Boc2O (436 mg, 464 µL, 2.00 mmol, 1.1 eq) was added. The reaction mixture was heated at 40 °C for 2 h,
then the solvent was evaporated and the residue purified by column chromatography (heptane:EtOAc 1:1)
to afford the Boc-protected product 12 as a light orange solid (406 mg, 69%). mp 78 °C. Rf = 0.45
1
(heptane:EtOAc 1:1). H NMR (600 MHz, DMSO-d6): δ (ppm) 5.88 (t, 4J = 1.6 Hz, 1 H4), 4.73 (br. s, 2
H2), 4.16 (br. s, CH2), 4.04-3.85 (br. s, 2 H1’), 1.31 [s, C(CH3)3], 0.00 [s, Si(CH3)3]. 13C NMR (151 MHz,
DMSO-d6): δ (ppm) 178.8 (C5), 168.3 (COOtBu), 154.1 (C3), 115.1 (C4), 102.50 (C2’), 88.0 (C3’), 80.0
[C(CH3)3], 71.6 (C2), 44.9 (C1’), 37.3 (CH2), 27.7 [C(CH3)3], 0.00 [Si(CH3)3]. MS (EI, 70 eV): m/z (%) =
308 [(M-CH3)+], 267 [(M-C4H8)+], 252 [(M-C5H11)+], 178, 112, 57. HRMS (ESI): Calculated for

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HETEROCYCLES, Vol. 88, No. 2, 2014
C16H27NO4Si+ = 325.1709. Found = 325.1708.
tert-Butyl-3-oxo-9-(silylmethylene)-2-oxa-7-azaspiro[4.4]nonane-7-carboxylate (13) The compound
was prepared from photoprecursor 12 (79.0 mg, 0.24 mmol) in 49 mL of Et2O by irradiation for 2 h (5
mM). Purification of the crude by column chromatography (heptane:EtOAc 1:1) afforded the
photoproduct 13 as a white solid (43.1 mg, 59%). The product purified was a mixture of (Z)- and
(E)-product in a 85:15 ratio. The relative configuration was assigned by extensive one- and
two-dimensional NMR experiments. Rf = 0.52 (heptane:EtOAc 1:1). 1H NMR (300 MHz, CDCl3) of the
(Z)-isomer: δ (ppm) 5.45 (br. s, 1 H6), 4.08 (d, 2J = 9.1 Hz, 1 H10), 4.02 (d, 2J = 9.1 Hz, 1 H10), 3.95 (br. s,
2 H2), 3.49 (d, 2J = 11.0 Hz, 1 H4), 3.28 (d, 2J =11.0 Hz, 1 H4), 2.57 (d, 2J = 18.0 Hz, 1 H7), 2.38 (d, 2J =
13
18.0 Hz, 1 H7), 1.35 [s, C(CH3)3], 0.03 [s, Si(CH3)3]. C NMR (151 MHz, CDCl3): δ (ppm) 175.8 (C8),
153.6 (COOtBu), 150.1 (C5), 124.4 (C6), 79.4 [C(CH3)3], 76.2 (C10), 74.0 (C1), 58.4 (C4), 49.7 (C2), 38.4
(C7), 28.3 [C(CH3)3], 0.03 [Si(CH3)3]. MS (EI, 70 eV): m/z (%) = 325 (5) [(M)+], 310 (2) [(M-CH3)+], 269
(10) [(M-C3H8)+], 73 (30) [(M-C3H9Si)+], 57 (100). HRMS (ESI): Calculated for C16H27NO4Si+ =
325.1709. Found = 325.1715.
Ethyl 4-acetoxy-3-(acetoxymethyl)-2-methylbut-2-enoate (15a) A 2000-mL four-necked flat bottom
flask equipped with overhead stirrer, thermometer, reflux condenser and nitrogen bubbler was charged
with triethyl 2-phosphonopropionate (14a) (94.9 mL, 442 mmol, 1.1 eq) in THF (1000 mL), cooled to
0 °C, added dropwise isopropylmagnesium chloride (2 M in THF) (221 mL, 442 mmol, 1.1 eq) and the
mixture was stirred at 23 °C for 1 h. Then 2-oxopropane-1,3-diyl diacetate (1) (70 g, 402 mmol, 1.0 eq)
was added in one portion, the light yellow mixture was stirred at 23 °C for 18 h, then poured into NH4Cl
(sat.), extracted with TBME, washed with brine, dried over Na2SO4 and filtered. Removal of the solvent
in vacuum left a dark brown liquid which was purified by column chromatography (heptane:EtOAc 3:1)
to give the ethyl 4-acetoxy-3-(acetoxymethyl)-2-methylbut-2-enoate (15a) (83.1 g, 80%) as a light yellow
liquid. Rf = 0.58 (heptane:EtOAc 1:1). 1H NMR (600 MHz, CDCl3): δ (ppm) 4.86 (d, 4J =1.0 Hz, OCH2),
4.77-4.69 (m, OCH2), 4.25 (q, 3J = 7.1 Hz, OCH2), 2.07 (s, CH3), 2.05 (s, CH3), 2.02 (s, CH3), 1.32 (t, 3J
= 7.2 Hz, CH3). 13C NMR (151 MHz, CDCl3): δ (ppm) 170.7, 170.6, 168.4 (C9, C10, C3), 134.3, 133.9 (C6,
C4), 62.3, 61.2, 61.1 (C2, C7, C8), 20.8, 20.7 (C11, C12), 15.9 (C5), 14.1 (C1). MS (EI, 70 eV): m/z (%) =
+
258 (100) [(M)+]. HRMS (ESI): Calculated for C12H18O6 [(M)]+ = 258.1103. Found = 258.1103.
4-(Hydroxymethyl)-3-methyl-2(5H)-furanone
(16a)
To
a
solution
of
ethyl
4-acetoxy-3-(acetoxymethyl)-2-methylbut-2-enoate (15a) (86.2 g, 334 mmol, 1.0 eq) in MeOH (374 mL)
at room temperature was dropwise added acetyl chloride (2.37 mL, 33.4 mmol, 0.1 eq) and the mixture
was stirred at room temperature for 18 h. Then the mixture was stirred for 2 h at 50 °C. The solvent was

HETEROCYCLES, Vol. 88, No. 2, 2014
1093
evaporated and azeotroped three times with toluene to give the 4-(hydroxy-
methyl)-3-methyl-2(5H)-furanone (16a) (43.4 g, 99%) as a brown liquid which was used without further
1
purification. Rf = 0.22 (heptane:EtOAc 1:1). H NMR (600 MHz, CDCl3): δ (ppm) 4.89-4.86 (m, 2 H5),
4.61 (br. s, 2 H6) 1.83 (s, CH3). 13C NMR (151 MHz, CDCl3): δ (ppm) 176.1 (C2), 159.8 (C4), 122.5 (C3),
70.9 (C5), 57.4 (C6), 8.5 (CH3). MS (EI, 70 eV): m/z (%) = 129 (100) [(M+H)+]. HRMS (ESI): Calculated
+
for C6H8O3 [(M)]+ = 128.0473. Found = 128.0473.
4-(Bromomethyl)-3-methyl-2(5H)-furanone
(17a)
To
a
solution
of
4-(hydroxy-
methyl)-3-methyl-2(5H)-furanone (16a) (2.00 g, 15.6 mmol, 1.0 eq) in Et2O (162 mL) at –78 °C was
added phosphorus tribromide (736 µL, 7.8 mmol, 0.5 eq) in Et2O (18.0 mL) and the mixture was stirred at
–78 °C to 23 °C over night, then poured onto ice water, diluted with Et2O and the phases were separated.
The organic layer was washed with NaHCO3 (sat.) and brine, dried over Na2SO4 and the solvent was
removed to obtain 4-(bromomethyl)-3-methyl-2(5H)-furanone (17a) (2.68 g, 90%) as a light yellow oil.
Rf = 0.41 (heptane:EtOAc 1:1). 1H NMR (600 MHz, CDCl3): δ (ppm) 4.87-4.86 (m, 2 H5), 4.22 (s, 2 H6),
1.91 (t, 5J = 2.1 Hz, CH3). 13C NMR (151 MHz, CDCl3): δ (ppm) 174.2 (C2), 153.1 (C4), 126.6 (C3), 70.5
(C5), 21.6 (C6), 8.9 (CH3). MS (EI, 70 eV): m/z (%) = 191,193 (100) [M+]. HRMS (ESI): Calculated for
+
C6H7BrO2NH4 [(M+NH4)]+ = 207.9622. Found = 207.9629.
Ethyl 4-acetoxy-3-(acetoxymethyl)-2-fluorobut-2-enoate (15b) To
a
solution of triethyl
2-fluoro-2-phosphonoacetate (14b) (111 mL, 550 mmol, 1.0 eq) in THF (1.43 L) at 0 °C was dropwise
added isopropylmagnesium chloride (2 M in THF) (289 mL, 577 mmol, 1.05 eq) and the mixture was
stirred at 0 °C for 2 h. 2-Oxopropane-1,3-diyl diacetate (1) (95.7 g, 550 mmol, 1.0 eq) was dissolved in
100 mL of THF and was added slowly in a dropping funnel. The reaction mixture was stirred at room
temperature over night and then poured into NH4Cl (sat.) and extracted with TBME. The organic layer
was dried over Na2SO4, filtered and the solvent removed. The crude material was purified by column
chromatography (heptane:EtOAc 3:1) to give ethyl 4-acetoxy-3-(acetoxymethyl)-2-fluorobut-2-enoate
(15b) (121 g, 84%) as a light yellow liquid. Rf = 0.49 (heptane:EtOAc 1:1). 1H NMR (600 MHz, CDCl3):
δ (ppm) 5.15 (d, 4JF = 2.2 Hz, OCH2), 4.85 (d, 4JF = 3.5 Hz, OCH2), 4.34 (q, 3J = 7.1 Hz, OCH2), 2.08 (s,
CH3), 2.07 (s, CH3), 1.36 (t, 3J = 7.1 Hz, CH3). 13C NMR (151 MHz, CDCl3): δ (ppm) 170.4 (d, 2JF = 5.5
Hz, C3), 159.9 (s, C8), 159.7 (s, C9), 147.8 (d, 1JF = 267.7 Hz, C4), 123.4 (d, 2JF = 5.5 Hz, C5), 62.9 (s, C2),
58.7 (d, 3JF = 5.8 Hz, C7), 57.9 (d, 3JF = 10.2 Hz, C6), 20.7 (s, C10), 20.7 (s, C11), 14.0 (s, C1). MS (EI, 70
+
eV): m/z (%) = 263 (38) [(M+H)+], 199 (100) [(M-OAc)+]. HRMS (ESI): Calculated for C11H15FO6
[(M)]+ = 262.0856. Found = 262.0848.

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HETEROCYCLES, Vol. 88, No. 2, 2014
3-Fluoro-4-(hydroxymethyl)-2(5H)-furanone (16b) To a solution of 2-(2-ethoxy-1-fluoro-2-oxo-
ethylidene)propane-1,3-diyl diacetate (15b) (121 g, 461 mmol, 1.0 eq) in MeOH (604 mL) at room
temperature was dropwise added acetyl chloride (3.28 mL, 46.1 mmol, 0.1 eq) and the mixture was stirred
at room temperature for 18 h and then stirred for 2 h at 50 °C. The solvent was evaporated and azeotroped
three times with toluene to give the 3-fluoro-4-(hydroxymethyl)-2(5H)-furanone (16b) (61.0 g, 100%) as
1
4
light brown liquid. Rf = 0.28 (heptane:EtOAc 1:1). H NMR (600 MHz, CDCl3): δ (ppm) 4.92 (dt, JF =
4
13
5.6 Hz, J = 1.1 Hz, 2 H5), 4.64 (br. s, 2 H6), 3.08 (br. s, 1 OH). C NMR (151 MHz, CDCl3): δ (ppm)
166.0 (d, 2JF = 30.8 Hz, C2), 142.3 (d, 1JF = 270.4 Hz, C3), 138.4 (d, 2JF = 5.5 Hz, C4), 67.2 (d, 3JF = 6.6
3
Hz, C5), 54.9 (d, JF = 2.5 Hz, C6). MS (EI, 70 eV): m/z (%) = 133 (30) [(M+H)+], 119 (42) 115 (43)
+
[(M-OH)+], 83 (100) [(M-CH2FO)+]. HRMS (ESI): Calculated for C5H5FO3 [(M)]+ = 132.0222. Found =
132.0220.
4-(Bromomethyl)-3-fluoro-2(5H)-furanone (17b) To a solution of 3-fluoro-4-(hydroxymethyl)-2(5H)-
furanone (16b) (12.0 g, 90.8 mmol, 1.0 eq) in Et2O (162 mL) at –78 °C was added phosphorus tribromide
(4.28 mL, 45.4 mmol, 0.5 eq) in Et2O (18.0 mL) and the mixture was stirred at –78 °C to 23 °C over night.
Then it was poured onto ice water and diluted with Et2O. The organic layer was washed with NaHCO3
(sat.) and brine. The solvent was dried over Na2SO4. Removal of the solvent in vacuum left the
4-(bromomethyl)-3-fluoro-2(5H)-furanone (17b) (17.1 g, 97%) as a light yellow oil. Rf = 0.47
1
4
4
(heptane:EtOAc 1:1). H NMR (600 MHz, CDCl3): δ (ppm) 4.85 (dt, JF = 5.8 Hz, J = 0.8 Hz, 2 H5),
4.23 (dt, 4JF = 1.9 Hz, 4J = 0.8 Hz, 2 H6). 13C NMR (151 MHz, CDCl3): δ (ppm) 164.0 (d, 2JF = 30.0 Hz,
C2), 144.2 (d, 1JF = 280.6 Hz, C3), 132.9 (d, 2JF = 5.8 Hz, C4), 67.2 (d, 3JF = 5.8 Hz, C5), 17.4 (d, 3JF = 2.5
Hz, C6). MS (EI, 70 eV): m/z (%) = 194,196 (20) [(M+H)+], 165,167 (20), 137,139 (10), 115 (100)
+
[(M-Br)+]. HRMS (ESI): Calculated for C6H6FBrO2 [(M)]+ = 193.9377. Found = 193.9378.
tert-Butyl N-allyl-N-[(4-methyl-5-oxo-2H-furan-3-yl)methyl]carbamate (18a) To a solution of
bromide 17a (1.00 g, 5.25 mmol, 1.0 eq) in THF (10 mL) at 0 °C was dropwise added a solution of
triethylamine (2.20 mL, 15.8 mmol, 3 eq) and prop-2-en-1-amine (0.40 mL, 5.25 mmol, 1.0 eq) in THF
(10 mL). The resulting solution was stirred at room temperature for 12 h. The precipitate was filtered off,
washed with THF, and the solvent was removed in vacuum. The crude material was purified by column
chromatography (heptane:EtOAc 1:3) and the amine was used for protection reactions without further
purification. To a solution of the amine (822 mg, 4.92 mmol, 1 eq) in dry THF (12 mL) was added Boc2O
(1.07 g, 4.92 mmol, 1.0 eq). The resulting solution was stirred at 40 °C for 2 h. After that time, the
solvent was removed under reduced pressure and the residue purified by column chromatography
(heptane:EtOAc 1:1) to afford the Boc-protected product (18a) as a colorless oil (1.30 g, 92%). Rf = 0.44

HETEROCYCLES, Vol. 88, No. 2, 2014
1095
(heptane:EtOAc 1:1). IR (ATR): υ (cm-1) = 3083 (w, C=C), 2976 (s, C-H), 1752 (s, C=O), 1689 (s,
O-C=O), 1356 (m, tBu), 866 (m, C=C). 1H NMR (300 MHz, CDCl3): δ (ppm) 5.74 (ddt, 3J = 16.8 Hz, 3J
= 10.5 Hz, 3J = 5.9 Hz, 1 H2’), 5.21-5.12 (m, 2 H3’), 4.68 (t, 4J = 1.0 Hz, 2 H2), 4.18 (br. s, CH2), 3.80 (br.
13
s, 2 H1’), 1.85 (s, CH3), 1.47 [(s, C(CH3)3)]. C NMR (151 MHz, CDCl3): δ (ppm) 174.7 (C5), 156.2
(COOtBu), 133.1 (C2’), 123.5 (C4), 117.5 (C3’), 80.9 [C(CH3)3], 71.1 (C2), 50.4 (C1’), 42.4 (CH2), 28.3
[C(CH3)3], 8.6 (CH3). MS (EI, 70 eV): m/z (%) = 212 (100) [(M-C4H7)+].
N-tert-Butoxycarbonyl-7-methyl-3-aza-9-oxatricyclo[5.3.0.01,5]decan-8-one (19a) The compound was
prepared from photoprecursor 18a (50.0 mg, 0.19 mmol) in 38 mL of MeCN by irradiation for 2 h (5
mM). Purification of the crude by column chromatography (heptane:EtOAc 1:1) afforded the
photoproduct 19a as an white solid (46.1 mg, 92%). mp 101 °C. Rf = 0.33 (heptane:EtOAc 1:1). IR
t
1
(ATR): υ (cm-1) = 2976 (s, C-H), 1755 (s, C=O), 1685 (s, O-C=O), 1363 (m, Bu). H NMR (600 MHz,
CDCl3): δ (ppm) 4.34 (d, 2J = 9.9 Hz, 1 H10), 4.03 (d, 2J = 9.9 Hz, 1 H10), 3.91 (br. s, 1 H2), 3.58 (br. s, 1
H4), 3.24 (dd, 2J = 11.7 Hz, 3J = 6.5 Hz, 1 H4), 2.96 (d, 2J = 12.5 Hz, 1 H2), 2.77 (virt. dd, 3J = 14.7 Hz, 3J
3
2
2
3
= J = 6.7 Hz, 1 H5), 2.53 (dd, J = 12.7 Hz, 1 H6), 1.73 (dd, J = 12.7 Hz, J = 6.7 Hz, 1 H6), 1.49 [s,
C(CH3)3], 1.24 (s, CH3). 13C NMR (151 MHz, CDCl3): δ (ppm) 180.8 (C8), 154.8 (COOtBu), 80.2
[C(CH3)3], 71.1 (C10), 53.3 (C4), 51.7 (C2), 46.9 (C7), 42.5 (C1), 39.3 (C6), 35.5 (C5), 28.5 [C(CH3)3], 16.2
(CH3). MS (EI, 70 eV): m/z (%) = 212 (100) [(M-C4H7)+]. HRMS (ESI): Calculated for C14H21NO4
[(M)+] = 267.1471. Found = 267.1474
tert-Butyl N-(2-methylallyl)-N-[(4-methyl-5-oxo-2H-furan-3-yl)methyl]carbamate (18b) To a
solution of bromide 17a (2.60 g, 13.6 mmol, 1.0 eq) in THF (14 mL) at 0 °C was dropwise added a
solution of Et3N (5.70 mL, 40.8 mmol, 3 eq) and 2-methylprop-2-en-1-amine (1.24 mL, 13.6 mmol, 1.0
eq) in THF (14 mL). The resulting solution was stirred at room temperature for 12 h. The precipitate was
filtered off, washed with THF, and the solvent was removed in vacuum. The crude material was purified
by column chromatography (heptane:EtOAc 1:3) and the amine was used for protection reactions without
further purification. To a solution of the amine (2.25 g, 12.4 mmol, 1.0 eq) in dry THF (25 mL) was
added Boc2O (2.98 g, 13.7 mmol, 1.1 eq). The resulting solution was stirred at 40 °C for 75 min. After
that time, the solvent was removed under reduced pressure and the residue purified by column
chromatography (heptane:EtOAc 1:1) to afford the Boc-protected product 18b as a light yellow oil (3.30
g, 87%). Rf = 0.52 (heptane:EtOAc 1:1). IR (ATR): υ (cm-1) = 3079 (w, C=C), 2971 (s, C-H), 1755 (s,
C=O), 1690 (s, O-C=O), 1365 (m, tBu), 883 (m, C=C). 1H NMR (600 MHz, CDCl3): δ (ppm) 4.93 (br. s,
1 H3’), 4.79 (br. s, 1 H3’), 4.68 (br. s, 2 H2), 4.16 (br. s, CH2), 3.72 (br. s, 2 H1’), 1.85 (s, CH3), 1.69 (s,
CH3), 1.47 [(s, C(CH3)3)]. 13C NMR (151 MHz, DMSO-d6): δ (ppm) 179.7 (C5), 162.9 (C4), 159.6

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HETEROCYCLES, Vol. 88, No. 2, 2014
(COOtBu), 146.2 (C3), 127.9 (C2’), 117.3 (C3’), 84.8 [C(CH3)3], 75.9 (C2), 58.1 (C1’), 47.8 (CH2), 33.1
[C(CH3)3], 24.8 (CH3), 13.5 (CH3). MS (EI, 70 eV): m/z (%) = 226 (100) [(M-C4H7)+]. HRMS (ESI):
+
Calculated for C15H23NO4 [(M)]+ = 281.1609. Found = 281.1603.
N-tert-Butoxycarbonyl-5-methyl-7-methyl-3-aza-9-oxatricyclo[5.3.0.01,5]decan-8-one
(19b) The
compound was prepared from photoprecursor 18b (3.30 g, 11.7 mmol) in 98 mL of MeCN by irradiation
for 1 h (120 mM). Purification of the crude by column chromatography (heptane:EtOAc 1:1) afforded the
photoproduct 19b as a white solid (2.73 g, 85%). mp 97 °C. Rf = 0.44 (heptane:EtOAc 1:1). IR (ATR): υ
(cm-1) = 2970 (s, C-H), 1768 (s, C=O), 1690 (s, O-C=O), 1365 (m, tBu). 1H NMR (400 MHz, DMSO-d6):
δ (ppm) 4.30 (d, 2J = 10.2 Hz, 1 H10), 4.01 (d, 2J = 10.2 Hz, 1 H10), 3.84 (d, 2J = 12.5 Hz, 1 H2), 3.56 (d,
2J = 11.4 Hz, 1 H4), 3.10 (d, 2J = 12.5 Hz, 1 H2), 2.80 (d, 2J = 11.4 Hz, 1 H4), 1.98 (d, 2J = 12.6 Hz, 1 H6),
2
1.79 (d, J = 12.6 Hz, 1 H6), 1.46 [s, C(CH3)3], 1.15 (s, CH3), 1.12 (s, CH3). 13C NMR (151 MHz,
DMSO-d6): δ (ppm) 182.5 (C8), 154.1 (COOtBu), 79.3 [C(CH3)3], 67.2 (C10), 58.7 (C4), 53.6 (C2), 47.6
(C7), 42.7 (C1), 42.5 (C6), 41.7 (C5), 28.5 [C(CH3)3], 18.8 (CH3), 16.1 (CH3). MS (EI, 70 eV): m/z (%) =
281 (5) [(M)+], 226 (20) [(M-C4H8)+], 208 (11), 57 (100) [(M-C11H14NO4)+]. HRMS (ESI): Calculated for
C15H23NO4 [(M)+] = 281.1609. Found = 281.1613.
tert-Butyl allyl[(4-fluoro-5-oxo-2,5-dihydrofuran-3-yl)methyl]carbamate (20) To a solution of the
bromide 17b (1.00 g, 5.13 mmol, 1.0 eq) in THF (15 mL) at 0 °C was dropwise added a solution of Et3N
(2.14 mL, 15.4 mmol, 3 eq) and prop-2-en-1-amine (0.39 mL, 5.13 mmol, 1.0 eq) in THF (15 mL). The
resulting solution was stirred at room temperature for 12 h. The precipitate was filtered off, washed with
THF, and the solvent was removed in vacuum. The crude material was purified by column
chromatography (heptane:EtOAc 1:3) and the product was used in the next step without further
purification. The amine was dissolved in dry THF (8 mL) and Boc2O was added (714 mg, 3.27 mmol, 1.1
eq). The resulting solution was stirred at 40 °C for 2 h. After that time, the solvent was removed under
reduced pressure and the residue purified by column chromatography (heptane:EtOAc 1:1) to afford the
Boc-protected product 20 as a colorless oil (797 mg, 59%). Rf = 0.49 (heptane:EtOAc 1:1). IR (ATR): υ
t
(cm-1) = 3083 (w, C=C), 2978 (s, C-H), 1778 (s, C=O), 1688 (s, O-C=O), 1366 (m, Bu), 1111 (s, C-F),
888 (m, C=C). 1H NMR (300 MHz, CDCl3): δ (ppm) 5.76 (ddt, 3J = 16.8 Hz, 3J = 10.6 Hz, 3J = 6.1 Hz, 1
4
H2’), 5.26-5.12 (m, 2 H3’), 4.75 (d, JF = 5.7 Hz, 2 H2), 4.18 (br. s, 2 H1’), 3.81 (br. s, CH2), 1.47 [s,
C(CH3)3]. 13C NMR (91 MHz, CDCl3): δ (ppm) 164.7 (d, 2JF = 31.1 Hz, C5), 155.6 (COOtBu), 143.9 (d,
2
1JF = 276.2 Hz, C4), 135.2 (d, JF = 5.5 Hz, C3), 132.8 (C3’), 117.9 (C2’), 81.1 [C(CH3)3], 67.6 (C2), 50.8
(CH2), 40.2 (C1’), 28.3 [C(CH3)3]. MS (EI, 70 eV): m/z (%) = 216 (100) [(M-C4H7)+].

HETEROCYCLES, Vol. 88, No. 2, 2014
1097
N-tert-Butoxycarbonyl-7-fluor-3-aza-9-oxatricyclo[5.3.0.01,5]decan-8-one (21) The compound was
prepared from photoprecursor 20 (474 mg, 1.75 mmol) in 350 mL of MeCN by irradiation for 2 h (5 mM).
Purification of the crude by column chromatography (heptane:EtOAc 1:1) afforded the photoproduct 21
as a white solid (374 mg, 79%). mp 156 °C. Rf = 0.28 (heptane:EtOAc 1:1). IR (ATR): υ (cm-1) = 2979 (s,
t
1
C-H), 17768 (s, C=O), 1683 (s, O-C=O), 1362 (m, Bu), 1100 (s, C-F). H NMR (300 MHz, CDCl3): δ
(ppm) 4.38 (dd, 2J = 9.9 Hz, 4JF = 2.8 Hz, 1 H10), 4.24 (d, 2J = 9.9 Hz, 1 H10), 4.18 (d, 2J = 12.5 Hz, 1 H2),
3.73 (br. s, 1 H4), 3.35 (dd, 2J = 11.7 Hz, 3J = 6.1 Hz, 1 H4), 3.10 (dd, 2J = 12.5 Hz, 4JF = 0.9 Hz, 1 H2),
2
3
3
3
3
3
2.73 (ddd, J = 11.9 Hz, J = 7.1 Hz, JF = 4.6 Hz, 1 H6), 2.40 (virt. qd, J = J = 7.1 Hz, J = 3.8 Hz, 1
13
2
H5), 2.26-2.23 (m, 1 H6), 1.47 [s, C(CH3)3]. C NMR (151 MHz, CDCl3): δ (ppm) 173.0 (d, JF = 25.6
Hz, C8), 154.7 (COOtBu), 144.1 (d, 1JF = 156.8 Hz, C7), 80.5 [C(CH3)3], 71.3 (C10), 51.3 (m, C4), 45.1 (m,
2
C2), 45.0 (m, C1), 33.5 (m, C5), 32.8 (d, JF = 23.7 Hz, C6), 28.4 [C(CH3)3]. MS (EI, 70 eV): m/z (%) =
271 (5) [(M+H)]+, 216 (20) [(M-C4H8)+], 198 (19), 171 (7), 57 (100) [(M-C9H9FNO2)+]. HRMS (ESI):
+
Calculated for C13H18FNO4 [(M)]+ = 271.1220. Found = 271.1223.
Diethyl 2-allyl-2-[(5-oxo-2,5-dihydrofuran-3-yl)methyl]malonate To a solution of potassium
tert-butoxide (370 mg, 3.3 mmol, 1.1 eq) in DMSO (6.0 mL) at 23 °C was added diethyl 2-allylmalonate
(654 µL, 3.3 mmol, 1.1 eq) and the resulting yellow solution was stirred for 10 min, then
4-(bromomethyl)-2(5H)-furanone (4) (531 mg, 3.0 mmol, 1.0 eq) was added (exothermic, immediately a
deep blue color developed) and the mixture was stirred at 23 °C for 40 min. Poured into NH4Cl (sat.),
extracted with EtOAc, the organic layer washed with brine and dried over Na2SO4. Removal of the
solvent in vacuum left a dark brown oil which was purified by flash chromatography (silica gel, 20 g, 0%
to 25% EtOAc in heptane) to give diethyl 2-allyl-2-((5-oxo-2,5-dihydrofuran-3-yl)methyl)malonate (197
1
mg, 22%) as a colorless oil. Rf = 0.45 (heptane:EtOAc 1:1). H NMR (600 MHz, CDCl3):  (ppm)
5.97-5.79 (m, 1 H4), 5.62 (ddt, 3J = 17.1 Hz, 3J = 10.0 Hz, 3J = 7.4 Hz, 1 H2’), 5.22-5.05 (m, 2 H3’), 4.74 (d,
4J = 1.8 Hz, 2 H2), 4.29-4.14 (m, 2 x OCH2CH3), 2.97 (d, 4J = 1.1 Hz, CH2), 2.72 (dt, 3J = 7.4 Hz, 4J = 1.2
Hz, 2 H1’), 1.31-1.16 (m, 2 x OCH2CH3). MS (EI, 70 eV): m/z (%) = 297 (100) [(M+H)]+. HRMS (ESI):
Calculated for C15H20O6 [(M+)] = 296.1260. Found = 296.1263.
3,3-Diethoxycarbonyl-9-oxatricyclo[5.3.0.01,5]decan-8-one (25) The compound was prepared from the
above-mentioned photoprecursor diethyl 2-allyl-2-[(5-oxo-2,5-dihydrofuran-3-yl)methyl]malonate (24.0
mg, 0.81 µmol) in 18 mL of MeCN by irradiation for 5 h (5 mM). Purification of the crude by column
chromatography (heptane:EtOAc 1:1) afforded the photoproduct 25 as a colorless oil (10.9 mg, 45%). Rf
= 0.41 (heptane:EtOAc 1:1). 1H NMR (600 MHz, CDCl3):  (ppm) 4.35 (d, 2J = 9.7 Hz, 1 H10), 4.28 (q, 3J
= 7.2 Hz, OCH2CH3), 4.22-4.17 (m, OCH2CH3), 4.16 (d, 2J = 9.7 Hz, 1 H10), 2.89 (ddd, 3J = 10.0 Hz, 3J =

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HETEROCYCLES, Vol. 88, No. 2, 2014
3.9 Hz, 3J = 1.0 Hz, 1 H5), 2.87-2.83 (m, 1 H7), 2.77 (d, 2J = 14.1 Hz, 1 H2), 2.50 (dd, 2J = 14.4, 3J = 10.0 Hz,
1 H4), 2.54-2.47 (m, 1 H4), 2.27 (dd, 2J = 13.3 Hz, 3J = 2.1 Hz, 1 H6), 2.04 (ddd, 2J = 13.3 Hz, 3J = 9.1 Hz,
2
3
3
3J = 3.9 Hz, 1 H6), 2.02 (d, J = 14.1 Hz, 1 H2), 1.31 (t, J = 7.2 Hz, OCH2CH3), 1.25 (t, J = 7.1 Hz,
OCH2CH3). 13C NMR (151 MHz, CDCl3): δ (ppm) 180.2 (C8), 171.5/171.4 (2 × COOEt), 75.2 (C10), 62.3
(C3), 62.0/61.9 (2 × OCH2CH3), 51.7 (C1), 42.2 (C7), 40.3/40.2 (C2, C4), 39.6 (C5), 27.8 (C6), 14.1/14.0 (2
× OCH2CH3). MS (EI, 70 eV): m/z (%) = 297 (100) [(M+H)]+. HRMS (ESI): Calculated for C15H20O6
[(M)]+ = 296.1260. Found =296.1260.
ACKNOWLEDGEMENTS
D.A.F. wishes to acknowledge funding by the Roche Postdoc Fellowship (RPF) Program.
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18. Colorless fragment, C13H19NO4, Mr = 253.29; monoclinic, space group P21/n (Nr. 14), a = 10.633(2),
b = 6.3900(13), c = 20.622(4) Å, = 90°, β = 102.39(3)°, = 90°, V = 1368.5(5) Å3, Z = 4,
(MoK) = 0.70000 Å,  = 0.091 mm-1, calcd = 1.229 gcm-3, T = 89(2) K, F(000) = 544, max: 26.38°,
R1 = 0.0455 (2786 observed data), wR2 = 0.1176 (all 2786 data), GOF = 1.072, 167 parameters,
max/min = 0.334/-0.287 eÅ3; CCDC-947434 (5a).
19. B. M. Trost, C. Jiang, and K. Hammer, Synthesis, 2005, 3335.
20. Colorless fragment, C16H19NO4S, Mr = 321.38; monoclinic, space group P21/c (Nr. 14), a = 39.216(8),
b = 5.9050(12), c = 13.085(3) Å, = 90°, β = 96.31(3)° = 90°, V = 3011.7(10) Å3, Z = 8, (MoK)
= 0.70000 Å,  = 0.233 mm-1, calcd = 1.418 gcm-3, T = 89(2) K, F(000) = 1360, max: 23.25°, R1 =
0.0736 (4314 observed data), wR2 = 0.2073 (all 4314 data), GOF = 1.227, 402 parameters, max/min
= 0.524/-0.399 eÅ3; CCDC-947433 (9b).
21. J. Hierold and D. W. Lupton, Org. Lett., 2012, 14, 3412.
22. (a) T. D. W. Claridge, S. G. Davies, J. A. Lee, R. L. Nicholson, P. M. Roberts, A. J. Russell, A. D.
Smith, and S. M. Toms, Org. Lett., 2008, 10, 5437; (b) J.-H. Park, Y. R. Lee, M. W. Chun, L. S.
Jeong, C.-K. Lee, and H.-D. Kim, Nucleosides & Nucleotides, 2003, 22, 659.
23. D. A. Fort, T. J. Woltering, M. Nettekoven, H. Knust, and T. Bach, Angew. Chem. Int. Ed., 2012, 51,
10169.