Synthesis of Vicinal Dichlorides via Activation of Aliphatic Terminal Epoxides with Triphosgene and Pyridine

Article abstract of DOI:10.1021/acs.joc.7b03197

Herein we report a novel synthetic reaction to convert unactivated terminal aliphatic epoxide to alkyl vicinal dichloride based on triphosgene-pyridine activation. Our methodology is operationally simple and readily tolerated by a broad of scope of substrates as well as protecting groups. Furthermore, these mild conditions generally yield clean reaction mixtures that are free of byproducts upon aqueous workup.

Full text of DOI:10.1021/acs.joc.7b03197

Subscriber access provided by Universitaetsbibliothek | Johann Christian Senckenberg
Note
Synthesis of Vicinal Dichlorides via Activation of Aliphatic
Terminal Epoxides with Triphosgene and Pyridine
Alexander H Cleveland, Frank R Fronczek, and Rendy Kartika
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b03197 • Publication Date (Web): 21 Feb 2018
Downloaded from http://pubs.acs.org on February 23, 2018
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 45
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
Synthesis of Vicinal Dichlorides via Activation of Aliphatic Terminal Epoxides with
Triphosgene and Pyridine
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Alexander H. Cleveland, Frank R. Fronczek, and Rendy Kartika*
Department of Chemistry
232 Choppin Hall
Louisiana State University
Baton Rouge, LA 70803
rkartika@lsu.edu
Abstract
Herein we report a novel synthetic reaction to convert unactivated terminal aliphatic epoxide to
alkyl vicinal dichloride based on triphosgeneꢀpyridine activation. Our methodology is
operationally simple and readily tolerated by a broad of scope of substrates as well as protecting
groups. Furthermore, these mild conditions generally yield clean reaction mixtures that are free
of byproducts upon aqueous workup.
1
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 45
1
2
3
4
5
6
7
8
9
The development of reactions to install carbonꢀchlorine bonds remains an important task
in organic synthesis due to the ubiquity of chlorine atoms in various organic molecules,
including natural products, pharmaceutical drugs, and agricultural agents.1 A particular
organochlorine structural motif that has been recently subjected to extensive synthetic studies is
the alkyl 1,2ꢀdichloride. The growing interests concerning this molecular structure are
essentially driven by the strong prevalence of repetitive vicinal dichloride subunits found in a
class of natural products, known as the chlorosulfolipids.2 While both classical and
contemporary methods to generate alkyl 1,2ꢀdichlorides are commonly approached via addition
of Cl2 (or their equivalents) across double bonds,3 synthetic applications of this strategy to
complex substrates bearing multiple π systems, viz. 1a, could be problematic due to the
substantial challenge in controlling regioselectivity of the chlorination toward a specific double
bond.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
A viable solution to this problem could be envisioned through the use of an epoxide as an
orthogonal precursor to alkyl 1,2ꢀdichlorides, viz. 1b. As a result of the two adjoining
electrophilic carbons, epoxides could theoretically be subjected to double nucleophilic
displacement by two chloride ions. There are a few reports demonstrating that treatment of
epoxide with Appelꢀtype activation conditions, i.e. triphenylphosphine and a source of
electrophilic chlorine,4 readily furnished the corresponding vicinal dichloride. Nonetheless,
similar to any synthetic transformations that rely on nucleophilic activation of reactive
intermediates using a stoichiometric amount of triphenylphosphine,5 these established
chlorination conditions suffered from disadvantages from both atom economical and operational
perspectives, as it is necessary and often difficult to purify the corresponding alkyl chloride from
2
ACS Paragon Plus Environment

Page 3 of 45
The Journal of Organic Chemistry
1
2
3
4
5
6
the leftover reagents and byproducts, especially given the potential instability of organochlorines
under column chromatographic separation.
7
8
Scheme 1. Chlorination Reactions via TriphosgeneꢀPyridine Activation
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Recognizing both the significant potentials and challenges of this useful synthetic
transformation, herein we report our investigation on the conversion of unactivated aliphatic
epoxides to alkyl vicinal dichlorides using our triphosgeneꢀpyridine activation technology.
Recently, our group has developed new chlorination reactions of through the use of triphosgene
as a source of chloride ions that can be effectively liberated upon treatment with pyridine.6 We
demonstrated that treatment of unactivated aliphatic secondary alcohols with triphosgene and
pyridine in dichloromethane at reflux successfully produced the corresponding secondary alkyl
chloride. This reaction was believed to have involved an intermediacy of pyridinium carbamate
ions which proceeded to decarboxylative nucleophilic substitution by chloride ions at the
carboxyl position in a stereospecific manner via an inversion of stereochemistry. Based on these
mechanistic considerations, we proposed that activation of an epoxide with triphosgene and
pyridine could potentially produce an analogous cationic intermediate in 2b (Scheme 1). Such a
reactive species should then undergo rapid decarboxylative fragmentation induced by chloride
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 45
1
2
3
4
5
6
ions to furnish the soughtꢀafter 1,2ꢀdichloride structural motif, thus producing CO2 gas as the
only byproduct of the reaction.
7
8
9
The results of our pilot and optimization studies are summarized in Table 1, in which 2ꢀ
benzyloxirane 3 was employed as a model substrate. Stemmed from our established protocols on
the conversion of ketones to vinyl chlorides,6b we utilized 1.0 equiv of triphosgene and 4.0 equiv
of pyridine in dichloromethane for the pilot experiments. While the reaction at room
temperature only produced complex mixtures, the target 1,2ꢀdichloride 4 was successfully
produced in 62% yield simply by warming the reaction to reflux (entries 1ꢀ2). The ensuing
screening of reaction concentrations and the molar amount of pyridine revealed that the use of
2.0 equiv of the base at 0.5 M concentration produced the highest yield (entries 3ꢀ5). As
indicated in entry 6, pyridine was found to play a crucial role. Without it, the starting material
was not largely affected as the reaction only produced a trace amount of chlorohydrin. Finally,
an attempt to further optimize the amounts of triphosgene and pyridine led us to a conclusion that
the use of 0.5 equiv of the chlorination reagent and 2.0 equiv of the base afforded the
corresponding vicinal dichloride 4 in satisfactory 88% yield (entry 7).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 1. Reaction Optimization
4
ACS Paragon Plus Environment

Page 5 of 45
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
[a] Progress of reaction was monitored by GC. [b] Isolated yield after column chromatography.
[c] The reaction mixture was stirred for 24 h. [d] The reaction never reached completion after 6
days.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
With the optimized reaction conditions in hand, we then examined the scope of epoxides
(Table 2). Our method proved to be compatible with various common protecting groups, such as
MOM 5a, acetyl 5b, PMB 5c, TBDPS 5d, and TBS 5e which furnished the corresponding alkyl
1,2ꢀdichlorides 6aꢀ6e in excellent yields (entries 1ꢀ5). Our ability to chlorinate epoxides using
triphosgene and pyridine is highly advantageous, considering that this methodology enables the
production of vicinal dichlorides orthogonally in the presence of πꢀsystems, which are typically
employed as precursors for the formation of 1,2ꢀdichlorides. For instance, the use of substrates
5f and 5g afforded products 6f and 6g in high yields, and both the allyl and propargyl groups
remained intact during the course of the reaction. When desired, access to bisꢀvicinal dichlorides
6h could be realized simply by using the corresponding bisꢀepoxide 5h and exposing it to a
double amount of the optimized molar equivalents of triphosgene and pyridine.
As shown in entries 9ꢀ11, the utility of industrially important glycidol as starting
materials in this chlorination reaction was examined. Indeed, treatment of benzyl, benzoyl, and
allyl protected glycidol 5iꢀ5k with triphosgene and pyridine under the optimized conditions
produced the corresponding dichlorinated glycerols 6iꢀ6k in moderate to high yields.
Interestingly, as opposed to the aliphatic substrates 5aꢀ5h, these glycerol systems required a
longer reaction time, suggesting that the adjacent oxygen atom perhaps readily deactivated the
epoxide moiety. Finally, we also attempted to simultaneously chlorinate the epoxide
functionality and secondary alcohol in 5l. Gratifyingly, activation of this substrate with excess
5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 45
1
2
3
4
triphosgene and pyridine successfully produced alkyl trichloride 6l in 71% yield in just 1 hour of
5
6
reaction time.
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 2. Scope of Substrates
6
ACS Paragon Plus Environment

Page 7 of 45
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
[a] Progress of reaction was monitored by GC. [b] Isolated yield after column chromatography.
[c] A mixture of inseparable diastereomers. [d] 1.0 equiv of triphosgene and 4.0 equiv of
pyridine was employed.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
It is important to note that every epoxide listed in Table 2 led to a clean and quantitative
conversion of the epoxide moiety to its corresponding vicinal dichloride as monitored by GCꢀ
analyses of the crude reaction mixtures. The reduced isolation yields are most likely originated
from the loss of products due to their volatility or decomposition during silica gel column
chromatographic purification. In fact, chromatographic purification became essentially optional,
considering the high purity of the crude products upon reaction workup.
Scheme 2. Identification of Reaction Intermediates
O
Reaction
Conditions
O
Cl
Cl
OH
Cl
O
Ph
Ph
Ph
Cl
Ph
Cl
+
+
3
7
8
4
Reaction
Reaction Conditions:
triphosgene (0.5 equiv), pyridine(2.0 equiv)
CH2Cl2 (0.5 M), reflux
Conditions
86%
Progress of Reaction by GC-MS Analyses [aꢀc]
3
‡
time = 0 min
7
8
7a
time = 30 min
time = 60 min
time = 120 min
8a
4
time = 210 min
9.0
10.0
11.0
12.0
13.0
Retention time (min)
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 45
1
2
3
4
5
6
7
8
9
[a] All compounds are assumed to elicit identical GC responses. [b] Based on MS analyses,
compounds 7a and 8a are presumably regioisomers of compounds 7 and 8, respectively. [c]
Naphthalene (‡) was added into the reaction mixture as a reference.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
To probe the plausible reaction mechanism for this methodology, we designed and
executed several experiments as depicted in Schemes 2 and Table 3. First, we monitored the
progress of our chlorination reaction by periodically subjecting aliquots of the crude reaction
mixture to GCꢀMS analyses (see Supporting Information). Using 2ꢀbenzyloxirane 3 as the
starting material, this study revealed the presence of two transient reaction intermediates, βꢀ
chloro chloroformate 7 and chlorohydrin 8. Attempts to isolate these compounds by prematurely
quenching the reaction only led to the isolation of chlorohydrin 8 by column chromatography. In
fact, βꢀchloro chloroformate 7 was not detected upon aqueous workup, suggesting that
chlorohydrin 8 might be generated conceivably as a byproduct from the hydrolysis of
chloroformate 7. Nonetheless, the role of chlorohydrin 8 as an actual reaction intermediate could
not be ruled out, considering that treatment of this compound with triphosgene and pyridine
under the optimized conditions also furnished vicinal dichloride 4 in 86% yield. Monitoring the
progress of this reaction by GCꢀMS analyses of the reaction mixture again revealed the presence
of βꢀchloro chloroformate intermediate 7.
The fate of the stereochemical information in this chlorination reaction was then
examined (Table 3). We found that the use of diastereomerically pure Mosher esterꢀderived (R)ꢀ
glycidol 9a and (2R)ꢀoxiranebutanol 9b produced chiral vicinal dichlorides 10a and 10b,
respectively, as a single diastereomer. These findings, therefore, suggested that our triphosgeneꢀ
8
ACS Paragon Plus Environment

Page 9 of 45
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
pyridine activation did not compromise the enantiomeric purity of the starting epoxides.
Furthermore, our studies confirmed that this chlorination methodology resulted in an inversion of
stereochemistry based on the Xꢀray structures of 3,5ꢀdinitrobenzoate esterꢀderived (R)ꢀglycidol
(+)-9c and the corresponding vicinal dichloride product (-)-10c.7
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 3. Stereochemical Analyses
[a] Progress of reaction was monitored by GC. [b] Isolated yield after column chromatography.
[c] Diastereomeric purity of 9a and 10a was determined by GC and NMR (1H, 13C, and 19F). [d]
Diastereomeric purity of 9b and 10b was determined by 13C NMR. See Supporting Information
for [c]ꢀ[e].
We also repeated this experiment with TBDPSꢀprotected glycidol (-)-9d to rule out
possible anchimeric assistance inherent to substrates 9aꢀ9c in regulating stereospecificity
(Scheme 3). Chlorination of this substrate with triphosgeneꢀpyridine, followed by removal of the
silyl ether and acylation of the unmasked hydroxy group with 3,5ꢀdinitrobenzoyl chloride
produced vicinal dichloride (-)-10c. An optical rotation measurement of this compound ([α]23
=
D
9
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 45
1
2
3
4
5
6
7
8
9
ꢀ20.0) revealed a value that was within an agreement with (-)-10c ([α]23D = ꢀ21.0) obtained from
(+)-9c, implying that chlorination of substrate (-)-9d also proceeded via an inversion of
stereochemistry.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 3. Exclusion of Anchimeric Assistance
Our experimental data collectively led us to propose a reaction mechanism as depicted in
Scheme 4. Reaction of epoxides 12 with triphosgene and pyridine is believed to produce
transient βꢀchloro chloroformate 14 via a sequence of nucleophilic ring opening at the less
congested βꢀcarbon by excess chlorides ions, liberated upon decomposition of triphosgene by
pyridine, followed by chloroformylation of the emerging chlorohydrin anion 13 by the in situ
generated phosgene.8 Analogous to our previous studies,6c βꢀchloro chloroformate 14 was
further activated by pyridine to putative pyridinium carbamate ion 15, allowing for the
penultimate decarboxylative nucleophilic substitution by chloride ions at the αꢀcarbon to
produce the observed vicinal dichloride 17, while regenerating pyridine and releasing CO2 as the
byproduct. This step would naturally invert the stereochemistry of the starting epoxide 12.
Nonetheless, given the close proximity of the electrophilic αꢀcarbon from an adjacent chlorine
10
ACS Paragon Plus Environment

Page 11 of 45
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
substituent, we could not exclude the possibility for pyridinium carbamate ion 15 to undergo
decarboxylative selfꢀdecomposition to generate chloronium ion 16 through the release of
pyridine and CO2. The ensuing nucleophilic ring opening to this intermediate by chloride ions,
again at the sterically more accessible βꢀcarbon, would result in the production of vicinal
dichloride 17 also with an inversion of stereochemistry. Either pathways would readily retain
enantiomeric purity.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 4. Proposed Reaction Mechanism.
Conclusion
In summary, we have developed a new method to chlorinate terminal epoxides to the
corresponding vicinal dichlorides in a stereospecific manner using triphosgeneꢀpyridine
activation. There are several advantageous associated with our technology. First, triphosgene
exists as crystalline materials, and it can be conveniently handled under normal laboratory safety
practices.9 Second, our conditions were found to be very mild and readily tolerated by a broad
range of substrates and protecting groups.10 Lastly, this triphosgeneꢀpyridine activation often
leads to very clean crude mixtures as carbon dioxide and base are the byproducts. Furthermore,
the absence of chromatographically nuisance byproducts rendered this novel methodology a
11
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 45
1
2
3
4
5
6
substantial improvement from the classical Appel chlorination reactions that are always
hampered by the challenging removal of the excess reagents and their resulting byproducts.
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Experimental Section
All materials, unless otherwise stated, were purchased from commercial sources and
utilized without further purification. Anhydrous reactions were conducted in ovenꢀdried
glassware, which was then cooled under vacuum and purged with nitrogen gas. Anhydrous
solvents (dichloromethane, toluene, acetonitrile, diethyl ether, and tetrahydrofuran) were filtered
through activated 3Å molecular sieves under nitrogen in a solvent purification system. Reactions
were either monitored by analytical thin layer chromatography (TLC Silica Gel 60 F254, Glass
Plates) and analyzed using 254 nm UV light and anisaldehyde – sulfuric acid or potassium
permanganate stains, or via Gas Chromatography – Mass Spectrometry (GCꢀMS). The column
for the GCꢀMS system was TGꢀSQC (15m x 0.25mm x 0.25µm). Low and high mass readings
were set to 60 to 400 amu, respectively. Oven, inlet, and detector temperatures were set to
250ºC, and helium was used as the inert carrier gas. Column chromatography was completed
1
13
using silica gel or neutral alumina. Unless otherwise noted, all H and C NMR spectra were
recorded in CDCl3 using spectrometers operating at either 400 MHz for 1H and 100 MHz for 13C
1
13
or 500 MHz for H and 125 MHz for C. Chemical shifts (δ) are reported in ppm relative to
residual CHCl3 as an internal reference (1H: 7.26 ppm, 13C: 77.00 ppm). Coupling constants (J)
are reported in Hertz (Hz). Peak multiplicity is indicate as follows: s (singlet), d (doublet), t
(triplet), q (quartet), p (pentet), x (septet), h (heptet), b (broad), and m (multiplet). FTꢀIR spectra
were recorded using thin film, and absorption frequencies were reported in reciprocal
centimeters (cmꢀ1). High Resolution Mass Spectrometry (HRMS) analyses were performed
12
ACS Paragon Plus Environment

Page 13 of 45
The Journal of Organic Chemistry
1
2
3
4
5
6
using Electron Spray Ionization – Time of Flight (ESIꢀTOF) method. See Supporting
Information for the chemical structures of compounds S1 ꢀ S10.
7
8
9
2-Benzyloxirane (3). Allylbenzene S1 (1.17 mL, 8.46 mmol) was added to a 100ꢀmL
roundꢀbottom flask and dissolved in CH2Cl2 (17 mL). The solution was then cooled to 0 °C and
mCPBA (2.80 g, 12.7 mmol, 77 wt %) was added in one portion. The solution was allowed to
warm to room temperature overnight. After completion of reaction as determined by TLC, the
reaction was cooled to 0 °C and quenched with 1 M NaOH (10 mL). Upon separation of the two
layers, the aqueous layer was extracted with CH2Cl2 (3 x 15 mL). The combined organic layers
were then dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting
crude oil was then purified by column chromatography using a 10% ꢀ 20% EtOAc in hexanes
gradient to afford epoxide 3 as a clear oil in 91% yield (340 mg, 1.45 mmol). 1H NMR (400
MHz, CDCl3) δ 7.38 – 7.32 (m, 2H), 7.31 – 7.24 (m, 3H), 4.31 – 4.24 (m, 1H), 3.74 (dd, J =
11.3, 4.5 Hz, 1H), 3.67 (dd, J = 14.1, 5.6 Hz, 1H), 3.32 (dd, J = 14.6, 7.3 Hz, 1H), 3.08 (dd, J =
14.2, 7.3 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 136.3, 129.5, 128.6, 127.2, 61.0, 47.5, 41.0.
Compound 3 is known.5d
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(2,3-Dichloropropyl)benzene (4). Epoxide 3 (111 mg, 0.827 mmol) was added to a 15ꢀ
mL pressure vessel. This compound was dissolved in CH2Cl2 (1.6 mL), followed by the addition
of triphosgene (123 mg, 0.414 mmol). After complete dissolution of triphosgene, pyridine (134
µL, 1.65 mmol) was added. The vessel was sealed and heated to gentle reflux in a warm sand
bath. After 3 hours, the starting material was fully consumed as determined by GC analysis.
The reaction was cooled to room temperature and quenched with 2 M HCl (1 mL). Upon
separation of the two layers, the aqueous layer was extracted with CH2Cl2 (3 x 10 mL). The
combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced
13
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 45
1
2
3
4
pressure. The resulting crude oil was then purified by column chromatography using 10% EtOAc
5
6
1
in hexanes to afford product 4 as a clear oil in 88% yield (137 mg, 0.724 mmol). H NMR (400
7
8
9
MHz, CDCl3) δ 7.37 – 7.32 (m, 2H), 7.31 – 7.26 (m, 3H), 4.30 – 4.24 (m, 1H), 3.74 (dd, J =
11.2, 4.4 Hz, 1H), 3.67 (dd, J = 11.3, 6.8 Hz, 1H), 3.32 (dd, J = 14.2, 5.2 Hz, 1H), 3.08 (dd, J =
14.2, 7.6 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 136.3, 129.5, 128.6, 127.2, 61.0, 47.4, 41.0.
Compound 4 is known.5d
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(2,3-Dichloropropyl)benzene (4). Chlorohydrin 8 (53 mg, 0.311 mmol) was added to a
15ꢀmL pressure vessel. This compound was dissolved in CH2Cl2 (0.6 mL), followed by the
addition of triphosgene (46 mg, 0.155 mmol). After complete dissolution of triphosgene,
pyridine (50 µL, 0.621 mmol) was added. The vessel was sealed and heated to gentle reflux in a
warm sand bath. After 1 hour, the starting material was fully consumed as determined by GC
analysis. The reaction was cooled to room temperature and quenched with 2 M HCl (1 mL).
Upon separation of the two layers, the aqueous layer was extracted with CH2Cl2 (3 x 10 mL).
The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced
pressure. The resulting crude oil was then purified by column chromatography using 10% EtOAc
in hexanes to afford product 4 as a clear oil in 86% yield (50 mg, 0.265 mmol). NMR spectra
are identical to those of dichloride 4 prepared from epoxide 3.
2-(4-(Methoxymethoxy)butyl)oxirane (5a). 5ꢀhexenꢀ1ꢀol S2 (1.5 mL, 12.5 mmol) was
added to a 50ꢀmL roundꢀbottom flask and dissolved in CH2Cl2 (12 mL). The solution was
subsequently cooled to 0 °C, m-CPBA (4.20 g, 18.7 mmol, 77 wt %) was added in one portion.
The reaction mixture was allowed to warm to room temperature. Upon complete consumption of
starting material as determined by TLC, the solution was cooled to 0 °C and quenched with 1 M
NaOH (5 mL). Upon separation of the two layers, the aqueous layer was extracted with CH2Cl2
14
ACS Paragon Plus Environment

Page 15 of 45
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
(3 x 15 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated
under reduced pressure. The resulting crude oil was then purified by column chromatography
using a 10% ꢀ 35% EtOAc in hexanes gradient to afford 4ꢀ(oxiranꢀ2ꢀyl)butanꢀ1ꢀol S3 as a clear
9
1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
oil in 86% yield, (1.25 g, 10.8 mmol). H NMR (400 MHz, CDCl3) δ 3.66 – 3.60 (m, 2H), 2.93
– 2.88 (m, 1H), 2.76 – 2.71 (m, 1H), 2.48 – 2.44 (m, 1H), 1.65 – 1.49 (m, 6H). 13C NMR (101
MHz, CDCl3) δ 62.5, 52.2, 47.0, 32.3, 32.1, 22.2. Compound S3 is known.11a
4ꢀ(Oxiranꢀ2ꢀyl)butanꢀ1ꢀol S3 (207 mg, 1.78 mmol) was added to a 50ꢀmL round bottom
flask. The epoxide was subsequently dissolved in CH2Cl2 (7 mL) and DIPEA (477 µL, 2.67
mmol) was added. MOMCl (203 µL, 2.67 mmol) was then added dropwise and off gassing was
observed. After 4 hours, the reaction was determined to be complete by TLC analysis and 2 M
HCl (2 mL) was added to quench. Upon separation of the two layers, the aqueous layer was
extracted with CH2Cl2 (3 x 15 mL). The combined organic layers were dried over Na2SO4 and
concentrated under reduced pressure. The resulting crude oil was then purified by column
chromatography using 10% EtOAc in hexanes to afford 5a as a clear oil in 73% yield (209 mg,
1.30 mmol). 1H NMR (400 MHz, CDCl3) δ 4.61 (s, 2H), 3.53 (t, J = 6.5 Hz, 2H), 3.35 (s, 3H),
2.93 – 2.88 (m, 1H), 2.74 (dd, J = 5.0, 3.9 Hz, 1H), 2.46 (dd, J = 5.1, 2.9 Hz, 1H), 1.70 – 1.61
(m, 2H), 1.59 – 1.50 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 96.4, 67.5, 55.1, 52.2, 47.0, 32.2,
29.5, 22.7. Compound 5a is known.11b
4-(Oxiran-2-yl)butyl acetate (5b). 4ꢀ(Oxiranꢀ2ꢀyl)butanꢀ1ꢀol S3 (200 mg, 1.72 mmol)
was added to a 50ꢀmL round bottom flask followed by DMAP (212 mg, 1.89 mmol). CH2Cl2
(4.7 mL) was added and the solution was cooled to – 78 ºC. Acetic anhydride (179 µL, 1.89
mmol) was added dropwise and the temperature was maintained at – 78 ºC. After 1 hour, the
reaction was determined to be complete by TLC analysis. The crude solution was allowed to
15
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 45
1
2
3
4
5
6
7
8
9
warm to room temperature and quenched with 15% NaOH (2 mL). Upon separation of the two
layers, the aqueous layer was extracted with CH2Cl2 (3 x 10 mL). The combined organic layers
were dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting crude
oil was then purified by column chromatography using 15% EtOAc in hexanes to afford 5b as a
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
clear oil in 80% yield (200 mg, 1.26 mmol). H NMR (400 MHz, CDCl3) δ 4.05 (t, J = 5.7 Hz,
2H), 2.92 – 2.86 (m, 1H), 2.75 – 2.71 (m, 1H), 2.48 – 2.43 (m, 1H), 2.03 (s, 3H), 1.72 – 1.63 (m,
2H), 1.63 – 1.46 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 171.2, 64.2, 52.0, 46.9, 32.0, 28.4,
22.5, 20.9. Compound 5b is known.11c
2-(4-((4-Methoxybenzyl)oxy)butyl)oxirane (5c). 4ꢀ(Oxiranꢀ2ꢀyl)butanꢀ1ꢀol S3 (193
mg, 1.66 mmol) was added to a vacuum purged 50ꢀmL round bottom flask followed by PMBꢀ
TCA (690 µL, 3.32 mmol). CH2Cl2 (8.3 mL) was subsequently added to dissolve the reaction
components and the solution was cooled to 0 ºC. CSA (38 mg, 0.166) was added in one portion
and the reaction was allowed to gradually warm to room temperature. After 43 hours, the
reaction was determined to be complete by TLC analysis and NaHCO3 (2 mL) was added to
quench the reaction. Upon the separation of the two layers, the aqueous layer was extracted with
CH2Cl2 (3 x 10 mL). The combined organic layers were dried over Na2SO4 and concentrated
under reduced pressure. The crude oil was then purified by column chromatography using 10%
1
EtOAc in hexanes to afford 5c as a clear oil in 71% (277 mg, 1.17 mmol). H NMR (400 MHz,
CDCl3) δ 7.27 (d, J = 7.9 Hz, 2H), 6.89 (d, J = 10.0 2H), 4.44 (s, 2H), 3.81 (s, 3H), 3.46 (t, J =
8.6 Hz, 2H), 2.93 – 2.88 (m, 1H), 2.74 (t, J = 4.2, Hz, 1H), 2.46 (dd, J = 5.1, 2.5 Hz, 1H), 1.71 –
1.62 (m, 2H), 1.58 – 1.50 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 159.1, 130.7, 129.2, 113.7,
72.5, 69.8, 55.24, 52.2, 47.0, 32.3, 29.51, 22.7. Compound 5c is known.11d
16
ACS Paragon Plus Environment

Page 17 of 45
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Tert-butyl(4-(oxiran-2-yl)butoxy)diphenylsilane (5d). 4ꢀ(Oxiranꢀ2ꢀyl)butanꢀ1ꢀol S3
(177 mg, 1.52 mmol) was combined with imidazole (114 mg, 1.67 mmol) in a 50ꢀmL roundꢀ
bottom flask. CH2Cl2 (3.0 mL) added and the solution was cooled to 0 ºC. TBDPSCl (430 µL,
1.67 mmol) was added dropwise. After stirring overnight, the reaction was quenched with 2 M
HCl (2 mL). Upon separation of the two layers, the aqueous layer was extracted with CH2Cl2 (3
x 10 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated
under reduced pressure. The crude oil was then purified by column chromatography using 1%
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
EtOAc in hexanes to afford 5d as a clear oil in 71% (380 mg, 1.07 mmol). H NMR (400 MHz,
CDCl3) δ 7.69 – 7.64 (m, 4H), 7.45 – 7.35 (m, 5H), 3.68 (t, J = 5.6 Hz, 2H), 2.93 – 2.86 (m, 1H),
2.74 (t, J = 4.7 Hz, 1H), 2.45 (dd, J = 5.1, 2.8 Hz, 1H), 1.66 – 1.49 (m, 2H), 1.05 (s, 9H). 13C
NMR (126 MHz, CDCl3) δ 135.5, 134.8, 134.0, 129.5, 127.7 127.6, 63.6, 52.3, 47.1, 32.3, 32.2,
26.9, 22.3, 19.2. Compound 5d is known.11e
Tert-butyldimethyl(4-(oxiran-2-yl)butoxy)silane (5e). 4ꢀ(Oxiranꢀ2ꢀyl)butanꢀ1ꢀol S3
(284 mg, 2.44 mmol) was added to a 50ꢀmL roundꢀbottom flask and dissolved in CH2Cl2 (12
mL). TBSCl (387 mg, 2.57 mmol) was subsequently added and the solution was cooled to 0 °C.
Imidazole (250 mg, 3.67 mmol) followed by DMAP (10 mg) were then added and the reaction as
allowed to warm to room temperature. After stirring for 3 hours, the reaction was cooled and
quenched with 2 M HCl (3 mL). Upon separation of the two layers, the aqueous layer was
extracted with CH2Cl2 (3 x 10 mL). The combined organic layers were dried over Na2SO4,
filtered, and concentrated under reduced pressure. The crude oil was then purified by column
chromatography using 5% EtOAc in hexanes to afford 5e as a clear oil in 89% yield (501 mg,
1
2.17 mmol). H NMR (400 MHz, CDCl3) δ 3.64 – 3.59 (m, 2H), 2.94 – 2.88 (m, 1H), 2.74 (dd, J
= 5.0, 3.9 Hz, 1H), 2.46 (dd, J = 5.0, 2.7 Hz, 1H), 1.62 – 1.48 (m, 6H), 0.89 (s, 9H), 0.04 (s, 6H).
17
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 45
1
2
3
4
5
13C NMR (101 MHz, CDCl3) δ 62.9, 52.3, 47.1, 32.6, 32.3, 26.0, 22.3, 18.3, ꢀ5.30. Compound
5e is known.11f
6
7
8
9
2-(4-(Prop-2-yn-1-yloxy)butyl)oxirane (5f). 4ꢀ(Oxiranꢀ2ꢀyl)butanꢀ1ꢀol S3 (324 mg,
2.79 mmol) was added to a 50ꢀmL roundꢀbottom flask and dissolved in THF (2.8 mL). The
resulting solution was cooled to 0 °C. Neat NaH (134 mg, 5.58 mmol) was quickly added in one
portion and after the cessation gas evolution, propargyl bromide (311 µL, 2.79 mmol) was added
slowly, dropwise. After 6 hours, the reaction was determined to be complete by TLC analysis
and cooled to 0 °C. The reaction was then quenched with saturated NH4Cl (1 mL). Upon
separation of the two layers, the aqueous layer was extracted with CH2Cl2 (3 x 10 mL). The
combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced
pressure. The crude oil was then purified by column chromatography using a 5% ꢀ 15% EtOAc
in hexanes gradient to afford 5f as a yellow oil in 55% yield (237 mg, 1.54 mmol). 1H NMR
(400 MHz, CDCl3) δ 4.12 (t, J = 2.1 Hz, 2H), 3.52 (dd, J = 7.7, 5.6 Hz, 2H), 2.92 – 2.87 (m, 1H),
2.76 – 2.71 (m, 1H), 2.48 – 2.43 (m, 1H), 2.41 (t, J = 2.6 Hz, 1H), 1.68 – 1.60 (m, 2H), 1.58 –
1.49 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 79.9, 77.3, 77.0, 76.7, 74.1, 69.8, 58.0, 52.1, 47.0,
32.2, 29.2, 22.6. IR (cmꢀ1): f = 3262, 3047, 2861, 1480, 1442, 1094, 944, 916, 783, 753. HRMSꢀ
ESI: (M + H)+ = 155.1067 calcd for C9H15O2, found = 155.1070.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2-(4-(Allyloxy)butyl)oxirane (5g). 4ꢀ(Oxiranꢀ2ꢀyl)butanꢀ1ꢀol S3 (183 mg, 1.57 mmol)
was added to a 50ꢀmL roundꢀbottom flask and dissolved in THF (2.0 mL). The resulting
solution was cooled to 0 °C. Neat NaH (77 mg, 3.15 mmol) was added in one portion and after
the cessation of gas evolution, allyl bromide (136 µL, 1.57 mmol) was added slowly, dropwise.
After stirring overnight, the reaction was determined to be complete by TLC analysis and cooled
to 0 °C. The reaction was then quenched with saturated NH4Cl (1.0 mL). Upon separation of
18
ACS Paragon Plus Environment

Page 19 of 45
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
the two layers, the aqueous layer was extracted with CH2Cl2 (3 x 10 mL). The combined organic
layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude oil
was then purified by column chromatography using a 5% ꢀ 10% EtOAc in hexanes gradient to
9
1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
afford 5g as a clear oil in 87% yield (214 mg, 1.37 mmol). H NMR (400 MHz, CDCl3) δ 5.89
(ddt, J = 16.0, 10.7, 5.7 Hz 1H), 5.21 (dd, J = 13.8, 6.6 Hz, 2H), 3.94 (dd, J = 5.6, 1.7 Hz, 2H),
3.42 (t, J = 6.2 Hz, 2H), 3.03 – 2.82 (m, 1H), 2.72 (dd, J = 10.9, 1.8 Hz, 1H), 2.45 (dd, J = 9.4,
1.9 Hz, 1H), 1.63 (t, J = 7.7 Hz, 2H), 1.56 – 1.45 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 134.9,
116.7, 71.7, 70.0, 52.2, 47.0, 32.2, 29.5, 22.7. Compound 5g is known.11g
2-((4-(Oxiran-2-yl)butoxy)methyl)oxirane (5h). 5ꢀHexenꢀ1ꢀol S2 (480 µL, 3.99 mmol)
was added to a 50ꢀmL roundꢀbottom flask and dissolved in THF (8.0 mL). The resulting solution
was cooled to 0 °C. Neat NaH (240 mg, 9.98 mmol) was added in one portion and after the
cessation of gas evolution, allyl bromide (520 µL, 5.99 mmol) was added slowly, dropwise.
After stirring overnight, the reaction was determined to be complete by TLC analysis and cooled
to 0 ºC. The reaction was then quenched with saturated NH4Cl (5 mL). Upon separation of the
two layers, the aqueous layer was extracted with CH2Cl2 (3 x 15 mL). The combined organic
layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting
crude oil was then purified by column chromatography using a 5% ꢀ 10% EtOAc in hexanes
1
gradient to afford 6ꢀ(allyloxy)hexꢀ1ꢀene S4 as a clear oil in 85% yield (475 mg, 3.38 mmol). H
NMR (400 MHz, CDCl3) δ 5.91ꢀ5.86 (m, 1H), 5.80 (ddt, J = 17.0, 10.3, 6.7 Hz, 1H), 5.23 (d, J =
16.3 Hz, 1H), 5.16 (d, J = 10.5, 1H), 5.00 (d, J = 17.1 Hz, 1H), 4.96 (d, J = 9.9 Hz, 1H), 3.96 (d,
J = 5.6 Hz, 2H), 3.43 (t, J = 6.7 Hz, 2H), 2.07 (q, J = 7.2 Hz, 2H), 1.66 – 1.55 (m, 2H), 1.52 –
1.39 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 138.7, 135.1, 116.6, 114.5, 71.7, 70.2, 33.5, 29.2,
25.5. Compound S4 is known.11h
19
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 45
1
2
3
4
5
6
7
8
9
6ꢀ(Allyloxy)hexꢀ1ꢀene S4 (458 mg, 3.27 mmol) was added to a 50ꢀmL roundꢀbottom
flask, followed by CH2Cl2 (7.0 mL). The solution was subsequently cooled to 0 °C. mCPBA
(2.20 g, 9.80 mmol, 77 wt %) was added in one portion and the solution was allowed to warm to
room temperature overnight. Upon complete consumption of starting material as determined by
TLC, the solution was cooled to 0 °C and quenched with 1 M NaOH (3 mL). Upon separation of
the two layers the aqueous layer was extracted with CH2Cl2 (3 x 10 mL). The combined organic
layers were dried over Na2SO4, filtered. and concentrated under reduced pressure. The crude oil
was then purified by column chromatography using a 10% ꢀ 20% EtOAc in hexanes gradient to
afford 5h as an inseparable mixture of diastereomers as a clear oil in 65% yield, (364 mg, 2.11
mmol). 1H NMR (400 MHz, CDCl3) δ 3.70 (dd, J = 11.8, 2.8 Hz, 1H), 3.49 (qt, J = 8.9, 6.1 Hz,
2H), 3.35 (dd, J = 11.2, 6.2 Hz, 1H), 3.15 – 3.10 (m, 1H), 2.92 – 2.87 (m, 1H), 2.75 (dt, J = 19.8,
4.3 Hz, 2H), 2.59 (dd, J = 5.0, 2.5 Hz, 1H), 2.45 (dd, J = 5.1, 3.1 Hz, 1H), 1.63 (p, J = 7.2, 6.4
Hz, 2H), 1.58 – 1.48 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 71.4, 71.2, 52.1, 50.8, 47.0, 44.2,
32.2 29.4, 22.6. IR (cmꢀ1): f = 3050, 2992, 2932, 2862, 1481, 1434, 1337, 1256, 1159, 1104,
835, 758. HRMSꢀESI: (M + H)+ = 173.1172 calcd for C9H16O3, found = 173.1175.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2-((Benzyloxy)methyl)oxirane (5i). Glycidol S5 (447 µL, 6.75 mmol) was added to a
100ꢀmL roundꢀbottom flask and dissolved in THF (23 mL). The resulting solution was then
cooled to 0 °C. Neat NaH (200 mg, 8.20 mmol) was then added in one portion. After the
cessation of the evolution of gas, benzyl bromide (1.20 mL, 10.1 mmol) was added slowly,
dropwise. After 7 hours, the reaction was determined to be complete by TLC analysis and the
reaction mixture was cooled to 0 °C. The cooled solution was then quenched with saturated
NH4Cl (5 mL). Upon separation of the two layers, the aqueous layer was extracted with CH2Cl2
(3 x 15 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated
20
ACS Paragon Plus Environment

Page 21 of 45
The Journal of Organic Chemistry
1
2
3
4
under reduced pressure. The crude oil was then purified by column chromatography 5% ꢀ 10%
5
6
1
EtOAc in hexanes gradient to afford 5i as a clear oil in quantitative yield. H NMR (400 MHz,
7
8
9
CDCl3) δ 7.39 – 7.27 (m, 5H), 4.62 (d, J = 11.9 Hz, 1H), 4.56 (d, J = 11.9 Hz, 1H), 3.77 (dd, J =
11.6, 3.1 Hz, 1H), 3.45 (dd, J = 11.3, 5.9 Hz, 1H), 3.22 – 3.16 (m, 1H), 2.83 – 2.78 (m, 1H), 2.62
(dd, J = 5.4, 2.5 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 137.9, 128.4, 127.7, 73.3, 70.8, 50.8,
44.3. Compound 5i is known.11i
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Oxiran-2-ylmethyl benzoate (5j). DMAP (82 mg, 0.675 mmol) was added to a 100ꢀmL
roundꢀbottom flask. Glycidol S5 (895 µL, 13.5 mmol) and pyridine (1.15 mL, 14.2 mmol) were
added stepwise and the contents were subsequently dissolved in CH2Cl2 (13 mL). The solution
was then cooled to 0 °C before the dropwise addition of benzoyl chloride (1.65 mL, 14.2 mmol).
After stirring for 6 hours, the reaction was determined to be complete by TLC analysis and
subsequently cooled to 0 °C. The cooled reaction mixture was then quenched with 2 M HCl (3
mL). Upon separation of the two layers, the aqueous layer was extracted with CH2Cl2 (3 x 10
mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated under
reduced pressure. The crude oil was then purified by column chromatography using a 5% ꢀ 10%
1
EtOAc in hexanes gradient to afford 5j as clear oil in 21% yield (498 mg, 2.79 mmol). H NMR
(400 MHz, CDCl3) δ 8.07 (d, J = 8.2 Hz, 2H), 7.56 (t, J = 8.0 1H), 7.45 (t, J = 7.9 Hz, 2H), 4.65
(dd, J = 12.2, 3.1 Hz, 1H), 4.17 (dd, J = 12.9, 6.1 Hz, 1H), 3.34 (m, 1H), 2.89 (t, J = 4.4 Hz, 1H),
2.73 (dd, J = 4.9, 2.6 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 166.2, 133.2, 129.7, 129.6, 128.4,
49.5, 44.7. Compound 5j is known.11f
2-((Allyloxy)methyl)oxirane (5k). Glycidol S5 (448 µL, 6.75 mmol) was added to a 50ꢀ
mL roundꢀbottom flask and dissolved in THF (13 mL). The resulting solution was then cooled
to 0 °C. Neat NaH (324 mg, 8.20 mmol) was added in one portion and after the cessation of the
21
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 45
1
2
3
4
5
6
7
8
9
evolution of gas, allyl bromide (1.20 mL, 10.1 mmol) was added slowly, dropwise. After 7
hours, the reaction was determined to be complete by TLC analysis and the reaction was cooled
to 0 °C. The cooled solution was then quenched with saturated NH4C (5 mL). Upon separation
of the two layers, the aqueous layer was extracted with EtOAc (3 x 15 mL). The combined
organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The
crude oil was then purified by column chromatography using a 10% ꢀ 20% EtOAc in hexanes
gradient to afford 5k as a clear oil in 43% yield (334 mg, 2.93 mmol). 1H NMR (400 MHz,
CDCl3) δ 5.89 (ddt, J = 16.2, 11.0, 5.9 1H), 5.28 (d, J = 17.8 Hz 1H), 5.19 (d, J = 10.4 Hz 1H),
4.03 (dq, J = 13.0, 5.9 Hz 2H), 3.71 (dd, J = 11.6, 3.1 Hz, 1H), 3.39 (dd, J = 11.2, 5.2 Hz, 1H),
3.18 – 3.12 (m, 1H), 2.79 (t, J = 4.4 Hz, 1H), 2.60 (dd, J = 5.2, 2.6 Hz, 1H). 13C NMR (101
MHz, CDCl3) δ 134.4, 117.3, 72.2, 70.7, 50.7, 44.3. Compound 5k is known.11j
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
6-(Oxiran-2-ylmethoxy)-1-phenylhexan-2-ol (5l). CuI (30 mg, 0.160 mmol) was added
50ꢀmL roundꢀbottom flask while the flask was still hot. The flask was then vacuum purged with
N2 and gradually cooled to room temperature. Phenylmagnesium bromide (1.1 mL, 3.20 mmol,
3 M in THF) was added to the flask and the solution was cooled to ꢀ78 °C. After cooling for 5
minutes, epoxide 5g (250 mg, 1.60 mmol) was added via cannula in a solution of THF (5.3 mL),
dropwise. After 5 minutes, the reaction was then warmed to 0 °C. After 1 hour, the reaction was
determined to be complete by TLC analysis and quenched with saturated NH4Cl (1 mL), while
still at 0 °C. Upon separation of the two layers, the aqueous layer was back extracted with Et2O
(3 x 10 mL). The combined organic layers were, dried over Na2SO4, filtered, and concentrated
under reduced pressure. The resulting crude oil was then purified by column chromatography
using a 10% ꢀ 20% EtOAc in hexanes gradient to afford 6ꢀ(allyloxy)ꢀ1ꢀphenylhexanꢀ2ꢀol S6 as a
1
clear oil in 91% yield (340 mg, 1.45 mmol). H NMR (500 MHz, CDCl3) δ 7.31 (t, J = 7.2 Hz,
22
ACS Paragon Plus Environment

Page 23 of 45
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
2H), 7.26 – 7.20 (m, 3H), 5.91 (ddt, J = 17.2, 10.8, 5.6 Hz, 1H), 5.27 (dd, J = 17.2, 1.3 Hz, 1H),
5.17 (dd, J = 10.3, 1.5 Hz, 1H), 3.96 (d, J = 5.7, 1.5 Hz, 2H), 3.88 – 3.79 (m, 1H), 3.44 (t, J =
6.3, 1.3 Hz, 2H), 2.83 (dd, J = 13.9, 4.4 Hz, 1H), 2.66 (dd, J = 13.6, 8.1 Hz, 1H), 1.68 – 1.42 (m,
6H). 13C NMR (126 MHz, CDCl3) δ 138.5, 135.0, 129.4, 128.5, 126.4, 116.7, 72.5, 71.8, 70.2,
44.0, 36.5, 29.6, 22.4. IR (cmꢀ1): f = 3415, 3062, 2935, 1602, 1495, 1347, 1269, 1100, 997, 853,
746. HRMSꢀESI: (M + H)+ = 235.1693 calcd for C15H23O2, found = 235.1695.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
6ꢀ(Allyloxy)ꢀ1ꢀphenylhexanꢀ2ꢀol S6 (340 mg, 1.45 mmol) was added to 50ꢀmL roundꢀ
bottom flask, and dissolved in CH2Cl2 (3 mL). The solution was then cooled to 0 °C and
mCPBA (535 mg, 2.17 mmol, 70 wt %) was added in one portion. The solution was allowed to
warm to room temperature gradually. After 28 hours, the reaction was determined to be
complete by TLC analysis. The reaction was then cooled to 0 °C and quenched with 1 M NaOH
(3 mL). After separation of the two layers, the aqueous layer was extracted with CH2Cl2 (3 x 10
mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated under
reduced pressure. The crude oil was then purified by column chromatography using a 10% ꢀ
50% EtOAc in hexanes gradient to afford 5m as a 1:1 mixture of inseparable diastereomers as a
1
clear oil in 83% yield, (303 mg, 1.21 mmol). H NMR (400 MHz, CDCl3) δ 7.34 – 7.28 (m, 4H),
7.26 – 7.19 (m, 6H), 3.87 – 3.79 (m, 2H), 3.71 (dd, J = 11.7, 3.3 Hz, 2H), 3.59 – 3.45 (m, 4H),
3.37 (dd, J = 11.7, 5.8 Hz, 2H), 3.17 – 3.11 (m, 2H), 2.87 – 2.77 (m, 4H), 2.66 (dd, J = 13.5, 8.4
Hz, 2H), 2.60 (dd, J = 5.2, 2.9 Hz, 2H), 1.67 – 1.42 (m, 12H). 13C NMR (126 MHz, CDCl3) δ
138.6, 129.4, 128.6, 126.5, 72.5, 71.5, 71.5, 50.9, 44.3, 44.1, 36.5, 29.6, 22.3. IR (cmꢀ1): f =
3446, 3059, 3000, 2935, 2862, 1601, 1495, 1394, 1030, 852, 701. HRMSꢀESI: (M + H)+ =
251.1642 calcd for C15H23O3, found = 251.1649.
23
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 45
1
2
3
4
5
6
7
8
9
1,2-Dichloro-6-(methoxymethoxy)hexane (6a). Epoxide 5a (113 mg, 0.705 mmol) was
added to a 15ꢀmL pressure vessel. This compound was dissolved in CH2Cl2 (1.4 mL), followed
by the addition of triphosgene (105 mg, 0.353 mmol). After complete dissolution of triphosgene,
pyridine (114 µL, 1.41 mmol) was added. The vessel was sealed and heated to gentle reflux in a
warm sand bath. After 1 hour, the starting material was fully consumed as determined by GC
analysis. The reaction was cooled to room temperature and quenched with 2 M HCl (1 mL).
Upon separation of the two layers, the aqueous layer was extracted with CH2Cl2 (3 x 10 mL).
The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced
pressure. The resulting crude oil was then purified by column chromatography using 10% EtOAc
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
in hexanes to afford product 6a as a clear oil in 70% yield (107 mg, 0.497 mmol). H NMR (400
MHz, CDCl3) δ 4.61 (s, 2H), 4.04 (dddd, J = 8.7, 7.5, 5.0, 3.6 Hz, 1H), 3.77 (dd, J = 11.3, 5.1
Hz, 1H), 3.65 (dd, J = 11.3, 7.6 Hz, 1H), 3.57 – 3.51 (m, 2H), 3.36 (s, 3H), 2.04 (m, 1H), 1.84 –
1.47 (m, 4H). 13C NMR (100 MHz, CDCl3) δ 96.5, 67.4, 61.0, 55.2, 48.1, 34.8, 29.1, 22.7. IR
(cmꢀ1): f = 2941, 2871, 2772, 1457, 1440, 1146, 1041, 918, 729. HRMSꢀESI: (M + Na)+ =
237.0420 calcd for C8H16Cl2NaO2, found = 237.0416.
5,6-Dichlorohexyl acetate (6b). Epoxide 5b (131 mg, 0.828 mmol) was added to a
vacuum cooled, nitrogen purged 15ꢀmL pressure vessel. This compound was dissolved in
CH2Cl2 (1.6 mL), followed by the addition of triphosgene (123 mg, 0.414 mmol). After
complete dissolution of triphosgene, pyridine (134 µL, 1.66 mmol) was added. The vessel was
sealed and heated to gentle reflux in a warm sand bath. After 1 hour, the starting material was
fully consumed as determined by GC analysis. The reaction was cooled to room temperature and
quenched with 2 M HCl (1 mL). Upon separation of the two layers, the aqueous layer was
extracted with CH2Cl2 (3 x 10 mL). The combined organic layers were dried over Na2SO4,
24
ACS Paragon Plus Environment

Page 25 of 45
The Journal of Organic Chemistry
1
2
3
4
filtered, and concentrated under reduced pressure. The resulting crude oil was then purified by
5
6
column chromatography using 10% EtOAc in hexanes to afford product 6b as a clear oil in 86%
7
8
1
yield (151 mg, 0.708 mmol). H NMR (400 MHz, CDCl3) δ 4.08 (t, J = 6.3 Hz, 2H), 4.05 – 3.98
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(m, 1H), 3.77 (dd, J = 10.8, 5.0 Hz, 1H), 3.64 (dd, J = 10.7, 6.9 Hz, 1H), 2.08 – 1.98 (m, 4H),
1.79 – 1.59 (m, 4H), 1.56 – 1.45 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 171.1, 64.0, 60.8,
48.0, 34.6, 28.0, 22.4, 20.9. IR (cmꢀ1): f = 2953, 1733, 1434, 1365, 1039, 807, 729. HRMSꢀESI:
(M + H)+ = 213.0444 calcd for C8H15Cl2O2, found = 213.0452.
1-(((5,6-Dichlorohexyl)oxy)methyl)-4-methoxybenzene (6c). Epoxide 5c (122 mg,
0.516 mmol) was added to a 15ꢀmL pressure vessel. This compound was dissolved in CH2Cl2
(1.0 mL), followed by the addition of triphosgene (76 mg, 0.258 mmol). After complete
dissolution of triphosgene, pyridine (83 µL, 1.03 mmol) was added. The vessel was sealed and
heated to gentle reflux in a warm sand bath. After 1 hour, the starting material was fully
consumed as determined by GC analysis. The reaction was cooled to room temperature and
quenched with 2 M HCl (1 mL). Upon separation of the two layers, the aqueous layer was
extracted with CH2Cl2 (3 x 10 mL). The combined organic layers were dried over Na2SO4,
filtered, and concentrated under reduced pressure. The resulting crude oil was then purified by
column chromatography using 10% EtOAc in hexanes to afford product 6c as a clear oil in 80%
1
yield (135 mg, 0.463 mmol). H NMR (400 MHz, CDCl3) δ 7.26 (d, J = 8.4 Hz 2H), 6.89 (d, J =
8.6 Hz 2H), 4.44 (s, 2H), 4.07 – 3.98 (m, 1H), 3.81 (s, 3H), 3.75 (dd, J = 11.2, 5.3 Hz, 1H), 3.64
(dd, J = 11.2, 7.2 Hz, 1H), 3.46 (t, J = 6.2 Hz, 2H), 2.04 – 1.95 (m, 1H), 1.78 – 1.45 (m, 5H).
13C NMR (101 MHz, CDCl3) δ 159.2, 130.6, 129.2, 113.8, 72.6, 69.6, 61.1, 55.3, 48.2, 34.9,
29.1, 22.7. IR (cmꢀ1): f = 3001, 2936, 1612, 1458, 1361, 1244, 1209, 1172, 1097, 730. HRMSꢀ
ESI: (M + Na)+ = 313.0733 calcd for C14H20Cl2NaO2, found = 313.0722.
25
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 45
1
2
3
4
5
6
7
8
9
Tert-butyl((5,6-dichlorohexyl)oxy)diphenylsilane (6d). Epoxide 5d (122 mg, 0.516
mmol) was added to a 15ꢀmL pressure vessel. This compound was dissolved in CH2Cl2 (1.0
mL), followed by the addition of triphosgene (76 mg, 0.258 mmol). After complete dissolution
of triphosgene, pyridine (83 µL, 1.03 mmol) was added. The vessel was sealed and heated to
gentle reflux in a warm sand bath. After 1 hour, the starting material was fully consumed as
determined by GC analysis. The reaction was cooled to room temperature and quenched with 2
M HCl (1 mL). Upon separation of the two layers, the aqueous layer was extracted with CH2Cl2
(3 x 10 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated
under reduced pressure. The resulting crude oil was then purified by column chromatography
using 10% EtOAc in hexanes to afford product 6d as a clear oil in 88% yield (135 mg, 0.463
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
mmol). H NMR (400 MHz, CDCl3) δ 7.26 (d, J = 8.4 Hz 2H), 6.89 (d, J = 8.6 Hz 2H), 4.44 (s,
2H), 4.07 – 3.98 (m, 1H), 3.81 (s, 3H), 3.75 (dd, J = 11.2, 5.3 Hz, 1H), 3.64 (dd, J = 11.2, 7.2
Hz, 1H), 3.46 (t, J = 6.2 Hz, 2H), 2.04 – 1.95 (m, 1H), 1.78 – 1.45 (m, 5H). 13C NMR (101
MHz, CDCl3) δ 159.2, 130.6, 129.2, 113.8, 72.6, 69.6, 61.1, 55.3, 48.2, 34.8, 29.1, 22.7. IR (cmꢀ
1): f = 3001, 2936, 1612, 1585, 1361, 1244, 1209, 1097, 820, 730. HRMSꢀESI: (M + Na)+ =
313.0733 calcd for C14H20Cl2NaO2, found = 313.0722.
Tert-butyl((5,6-dichlorohexyl)oxy)dimethylsilane (6e). Epoxide 5e (154 mg, 0.668
mmol) was added to a 15ꢀmL pressure vessel. This compound was dissolved in CH2Cl2 (1.3
mL), followed by the addition of triphosgene (99 mg, 0.334 mmol). After complete dissolution
of triphosgene, pyridine (108 µL, 1.34 mmol) was added. The vessel was sealed and heated to
gentle reflux in a warm sand bath. After 1 hour, the starting material was fully consumed as
determined by GC analysis. The reaction was cooled to room temperature and quenched with 2
M HCl (1 mL). Upon separation of the two layers, the aqueous layer was extracted with CH2Cl2
26
ACS Paragon Plus Environment

Page 27 of 45
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
(3 x 10 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated
under reduced pressure. The resulting crude oil was then purified by column chromatography
using 10% EtOAc in hexanes to afford product 6e as a clear oil in 80% yield (135 mg, 0.463
9
1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
mmol). H NMR (400 MHz, CDCl3) δ 4.09 – 3.99 (m, 1H), 3.76 (dd, J = 11.3, 5.2 Hz, 1H), 3.68
– 3.61 (m, 3H), 2.07 – 1.96 (m, 1H), 1.79 – 1.67 (m, 1H), 1.67 – 1.44 (m, 4H), 0.90 (s, 9H), 0.05
(s, 6H). 13C NMR (101 MHz, CDCl3) δ 62.7, 61.2, 48.2, 34.9, 32.1, 26.0, 22.3, 18.3, ꢀ5.3. IR
(cmꢀ1): f = 2929, 1472, 1387, 1253, 1095, 833, 774. HRMSꢀESI: (M + H)+ = 285.1203 calcd for
C12H27Cl2OSi, found = 285.1204.
1,2-Dichloro-6-(prop-2-yn-1-yloxy)hexane (6f). Epoxide 5f (123 mg, 0.797 mmol) was
added to a 15ꢀmL pressure vessel. This compound was dissolved in CH2Cl2 (1.6 mL), followed
by the addition of triphosgene (118 mg, 0.399 mmol). After complete dissolution of triphosgene,
pyridine (130 µL, 1.60 mmol) was added. The vessel was sealed and heated to gentle reflux in a
warm sand bath. After 1 hour, the starting material was fully consumed as determined by GC
analysis. The reaction was cooled to room temperature and quenched with 2 M HCl (2 mL).
Upon separation of the two layers, the aqueous layer was extracted with CH2Cl2 (3 x 10 mL).
The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced
pressure. The resulting crude oil was then purified by column chromatography using 10% EtOAc
1
in hexanes to afford product 6f as a clear oil in 86% yield (144 mg, 0.689 mmol). H NMR (400
MHz, CDCl3) δ 4.13 (d, J = 2.6 Hz, 2H), 4.08 – 3.99 (m, 1H), 3.76 (dd, J = 11.2, 5.1 Hz, 1H),
3.65 (dd, J = 11.6, 7.3 Hz, 1H), 3.54 (t, J = 6.0 Hz, 2H), 2.42 (t, J = 2.3 Hz, 1H), 2.08 – 1.97 (m,
1H), 1.80 – 1.71 (m, 1H), 1.71 – 1.57 (m, 3H), 1.55 – 1.46 (m, 1H). 13C NMR (101 MHz,
CDCl3) δ 79.9, 74.2, 69.7, 61.0, 58.1, 48.2, 34.8, 28.9, 22.6. IR (cmꢀ1): f =3296, 2944, 1438,
27
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 45
1
2
3
4
5
1355, 1270, 1181, 1097, 919, 814. HRMSꢀESI: (M + H)+ = 209.0494 calcd for C9H15Cl2O,
found = 209.0494.
6
7
8
9
6-(Allyloxy)-1,2-dichlorohexane (6g). Epoxide 5g (119 mg, 0.762 mmol) was added to
a 15ꢀmL pressure vessel. This compound was dissolved in CH2Cl2 (1.5 mL), followed by the
addition of triphosgene (113 mg, 0.381 mmol). After complete dissolution of triphosgene,
pyridine (123 µL, 1.52 mmol) was added. The vessel was sealed and heated to gentle reflux in a
warm sand bath. After 1 hour, the starting material was fully consumed as determined by GC
analysis. The reaction was cooled to room temperature and quenched with 2 M HCl (1 mL).
Upon separation of the two layers, the aqueous layer was extracted with CH2Cl2 (3 x 10 mL).
The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced
pressure. The resulting crude oil was then purified by column chromatography using 10% EtOAc
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
in hexanes to afford product 6g as a clear oil in 90% yield (145 mg, 0.687 mmol). H NMR (400
MHz, CDCl3) δ 5.91 (ddt, J = 15.9, 10.3, 5.6 Hz, 1H), 5.42 – 4.93 (m, 2H), 4.04 (dddd, J = 8.9,
7.4, 5.1, 3.7 Hz, 1H), 3.97 (dt, J = 5.6, 1.5 Hz, 2H), 3.84 – 3.58 (m, 2H), 3.45 (t, J = 6.0 Hz, 2H),
2.38 – 1.90 (m, 1H), 1.83 – 1.37 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 134.9, 116.8, 71.9,
69.9, 61.1, 48.2, 34.9, 29.1, 22.7. IR (cmꢀ1): f = 3014, 2940, 2861, 1646, 1478, 1456, 1102, 923.
HRMSꢀESI: (M + H)+ = 211.0651 calcd for C9H17Cl2O, found = 211.0648.
1,2-Dichloro-6-(2,3-dichloropropoxy)hexane (6h). Epoxide 5h (152 mg, 0.883 mmol)
was added to a 15ꢀmL pressure vessel. This compound was dissolved in CH2Cl2 (1.8 mL),
followed by the addition of triphosgene (262 mg, 0.883 mmol). After complete dissolution of
triphosgene, pyridine (285 µL, 3.53 mmol) was added. The vessel was sealed and heated to
gentle reflux in a warm sand bath. After 2 hours, the starting material was fully consumed as
determined by GC analysis. The reaction was cooled to room temperature and quenched with 2
28
ACS Paragon Plus Environment

Page 29 of 45
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
M HCl (1 mL). Upon separation of the two layers, the aqueous layer was extracted with CH2Cl2
(3 x 10 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated
under reduced pressure. The resulting crude oil was then purified by column chromatography
using 10% EtOAc in hexanes to afford product 6h as a clear oil in 81% yield (201 mg, 0.713
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
mmol). H NMR (400 MHz, CDCl3) δ 4.16 (p, J = 11.2, 5.2 Hz, 1H), 4.08 – 4.00 (m, 1H), 3.85
(dd, J = 11.2, 6.2 Hz, 1H), 3.75 (dq, J = 11.2, 5.4 Hz, 4H), 3.65 (dd, J = 11.2, 7.6 Hz, 1H), 3.53
(t, J = 6.3 Hz, 2H), 2.08 – 1.99 (m, 1H), 1.80 – 1.44 (m, 6H). 13C NMR (101 MHz, CDCl3) δ
71.3, 71.0, 60.9, 58.2, 48.1, 45.3, 34.7, 28.8, 22.5. IR (cmꢀ1): f = 2944, 2866, 1667, 1457,1432,
1256, 1117, 818, 731. HRMSꢀESI: (M + H)+ = 281.0028 calcd for C9H17Cl4O, found =
281.0028.
((2,3-Dichloropropoxy)methyl)benzene (6i). Epoxide 5i (188 mg, 1.16 mmol) was
added to a 15ꢀmL pressure vessel. This compound was dissolved in CH2Cl2 (2.3 mL), followed
by the addition of triphosgene (172 mg, 0.579 mmol). After complete dissolution of triphosgene,
pyridine (187 µL, 2.32 mmol) was added. The vessel was sealed and heated to gentle reflux in a
warm sand bath. After 6 hours, the starting material was fully consumed as determined by GC
analysis. The reaction was cooled to room temperature and quenched with 2 M HCl (1 mL).
Upon separation of the two layers, the aqueous layer was extracted with CH2Cl2 (3 x 10 mL).
The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced
pressure. The resulting crude oil was then purified by column chromatography using 10% EtOAc
1
in hexanes to afford product 6i as a clear oil in 87% yield (222 mg, 1.01 mmol). H NMR (400
MHz, CDCl3) δ 7.40 – 7.31 (m, 5H), 4.65 – 4.57 (m, 2H), 4.19 (p, J = 5.3 Hz, 1H), 3.89 (dd, J =
11.6, 6.6 Hz, 1H), 3.83 – 3.75 (m, 3H). 13C NMR (101 MHz, CDCl3) δ 137.5, 128.5, 127.9,
127.7, 73.5, 70.4, 58.3, 45.3. Compound 6i is known.12a
29
ACS Paragon Plus Environment