Synthesis of trimethylsilyl carboxylates by HMDS under solvent-free conditions

Article abstract of DOI:10.1016/j.tet.2016.08.003

A broad set of structurally different carboxylic acids were transformed into their trimethylsilyl esters with HMDS in a practically completely solvent-free process, while a catalytic amount of iodine was required in some cases. The process has several advantages over the known methods: untreated reactants, air atmosphere, mild and neutral conditions, no evolution of hydrogen halide, no need of an additional base, low amount of waste, completely without chromatography, low consumption of energy, and operational simplicity.

Full text of DOI:10.1016/j.tet.2016.08.003

Accepted Manuscript
Synthesis of trimethylsilyl carboxylates by HMDS under solvent-free conditions
Marjan Jereb, Janja Lakner
PII:
S0040-4020(16)30761-X
10.1016/j.tet.2016.08.003
TET 27984
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 15 April 2016
Revised Date: 21 July 2016
Accepted Date: 1 August 2016
Please cite this article as: Jereb M, Lakner J, Synthesis of trimethylsilyl carboxylates by HMDS under
solvent-free conditions, Tetrahedron (2016), doi: 10.1016/j.tet.2016.08.003.
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ACCEPTED MANUSCRIPT
Graphical abstract
1

ACCEPTED MANUSCRIPT
Synthesis of trimethylsilyl carboxylates by HMDS under solvent-free conditions
Marjan Jereb*, Janja Lakner
Department of Organic Chemistry, Faculty of Chemistry and Chemical Technology, Večna pot 113, 1001
Ljubljana, Slovenia. E-mail: marjan.jereb@fkkt.uni-lj.si; Fax: +386 1 241 9144; Tel: +386 1 479 8577
Dedicated to Professor Emeritus Miha Tišler on the ocassion of his 90th birthday.
A broad set of structurally different carboxylic acids were transformed into their trimethylsilyl esters
with HMDS in a practically completely solvent-free process, while a catalytic amount of iodine was
required in some cases. The process has several advantages over the known methods: untreated
reactants, air atmosphere, mild and neutral conditions, no evolution of hydrogen halide, no need of an
additional base, low amount of waste, completely without chromatography, low consumption of
energy and operational simplicity.
Keywords: Carboxylic acids, HMDS, trimethylsilyl carboxylates, solvent-free.
1. Introduction
Green and sustainable synthesis has become a necessity, in particular on an industrial scale.1 Organic
solvents represent one of the key factors contributing to the pollution, transformations under solvent-
2
free conditions bring several advantages in terms of cost-efficiency, waste-reduction, operational
simplicity and health hazard. Atom economy is another important parameter of reaction effectiveness.3
Trimethylsilyl carboxylates (TMSC) are important derivatives in protection group chemistry,4 and
they are valuable as reactants in other transformations.5 The introduction of the TMS group
considerably enhances the volatility of the product, thus making them suitable for GC-MS analysis.6
One of the key features of TMSC is the ease of the removal of TMS group, thus making this functional
group particularly valuable in the presence of other labile functionalities.7 A temporary TMS-
protection of amino and carboxylic group in amino acids, followed by N-acylation brings considerable
advantages in comparison with the Schotten-Baumann reaction, since the formation of oligomers is
prevented.8 TMS is an important protecting group in the transformation of antibiotics.9 TMS is a
protection of choice in the reduction of amino acids into amino alcohols.10 Poly(trimethylsilyl esters)
are an interesting family of the hydrolytically-degradable polymers with the tunable stabilities.11
The introduction of the TMS group into carboxylic acids could be accomplished by various TMS
sources i.e. TMSCl,12 allyltrimethylsilane in the presence of various catalysts,13
hexamethyldisilathiane,14 N,N’-bis[trimethylsilyl)urea,15 trimethylsilyl trichloroacetate,16 ketene
methyl trialkylsilyl acetals,17 trimethylsilyl enolate of pentane-2,4-dione/Et3B,18 N-trimethylsilyl-2-
oxazolidinone,19 hexamethyldisiloxane,20 trimethylsilyl trimethylsilylamidosulfonate,21 N,O-
bis(trimethylsilyl)acetamide,22
TMSOTf,23
TMSN3,24
TMSCN,25
trimethylsilyl
N,N-
dimethylcarbamate,26 N,O-bis(trimethylsilyl)trifluoroacetamide27 and others.
TMSC could be prepared also by other methods, i.e. transesterification of carboxylic esters with
TMSI,28 trimethyl(phenyl)silane/I2,29 TMSI/I2,30 TMSOTf,31 by thermal rearrangement of
(acyloxymethyl)diorganylsilanes32 and ozonolysis of silyl diazo compounds.33 Aldehydes and ketones
could be transformed into β-lactones which spontaneously rearrange to α,β-unsaturated esters.34
TMSC could be obtained by protodesilylation of aryltrimethylsilanes,35 by thermal decomposition of
2-trimethylsilyl alcohols,36 and by a reaction of TMSCl with monocarboxylates37 in the presence of
PEG400. An interesting synthesis of TMSC took place as a side reaction in the system cellulose/1-
alkyl-3-methyl-imidazolium ionic liquids. The attempted trimethylsilylation of cellulose in the
mentioned ionic liquids bearing acetate anion resulted in a formation of trimethylsilyl acetate instead
of silylated cellulose.38
2

ACCEPTED MANUSCRIPT
Hexamethyldisilazane (HMDS) was used for introduction of trimethylsilyl group in molecules with at
least one weakly bonded proton, in which both TMS groups could be delivered and ammonia is the
only waste product. Functionalization takes place under mild conditions, no halogen is released during
the reaction, and no additional base is needed. The main drawback of HMDS is its relatively weak
silylating power and, therefore, different catalysts and activators are needed. Several catalysts are
metal-based, air and moisture-sensitive, expensive and hazardous. However, there are examples in
which HMDS was found to be more reactive under solvent-free conditions (SFC), and reactions of the
same substrate took place without a catalyst,39 whereas a catalyst was required in a solution.40
HMDS was utilized in the synthesis of TMSC in solution,41 and there are isolated examples of its
reactivity under SFC.42 A lack of a systematic study of the reactivity of carboxylic acids with HMDS
prompted us to thoroughly examine the reactivity of an extensive set of structurally different
carboxylic acids with HMDS under SFC.
2. Results and discussion
Initially, the reactivity of aliphatic carboxylic acids was examined; the results are summarized in Table
1. Octanoic acid 1a was converted into its TMS ester 2a with 0.75 equiv. of HMDS in an uncatalyzed
reaction. The excess of HMDS was removed, and the product 2a was distilled under reduced pressure.
A catalytic amount (6–9%) of iodine was required in most of the cases, the amount of HMDS also
varied from acid to acid depending on the reactivity. Iodine was carefully removed after the reaction
by dilution with a small amount of TBME and sodium thiosulfate, and after removal of the insoluble
material by filtration; pure products were obtained following vacuum distillation. The selected acyclic,
cyclic, tricyclic, dicarboxylic and halogenated aliphatic acids 1b–1h were also converted into their
TMSC 2b–2h. Functionalization took place well regardless of the aggregate state of the acid; however,
reaction time was dependent on the solubility of acid in HMDS and on the amount of starting acid.
Table 1
Functionalization of aliphatic carboxylic acids 1a–1h into TMSC 2a–2h.a
Entry
RCOOH
1
HMDS
I2 (mol. %)
t (h)
RCOOTMS
Yield (%)b
(equiv.)
1
2
3
4
5
6
7
8
C7H15-
C9H19-
1a
1b
1c
1d
1e
1f
0.75
1
1
1
2
2
3.5
1
/
6
/
22
2
2a
2b
2c
2d
2e
2f
91
48
95
94
62
56
71
58
c-C6H11-
1-adamantyl-
-(CH2)-
-(CH2)2-
-(CH2)4-
Cl2CH-
96
72
64
63
18
96
/
9
9
9
/
1g
1h
2g
2h
a Reaction conditions: 1 (5–30 mmol) and HMDS (5–35 mmol), rt.
b Isolated yield.
Most of the tested acids were poorly soluble in HMDS, but one has to bear in mind that no solvent was
added to solubilize the acids, and reaction conditions were heterogeneous, and therefore significantly
more demanding than homogenous conditions. In several examples, complete homogenization of the
reaction mixture was achieved after a certain time of stirring, and this was a good indication of
1
complete conversion, and in such cases, H NMR analyses confirmed this. In addition, most of the
starting acids were noticeably polar and sparingly soluble in CDCl3, whereas all TMSC were freely
soluble in CDCl3, and solubility was another suggestion of full conversion.
We examined the reactivity of aryl-substituted carboxylic acids; the results are summarized in Table 2.
3

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Table 2
Synthesis of aryl-substituted trimethylsilyl esters 4.a
Entry
ArCOOH
3
HMDS
I2 (mol. %)
t (h)
ArCOOTMS
Yield (%)b
(equiv.)
4
4a
4b
4c
4d
4e
4f
4g
4h
4i
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
C6H5-
4-Cl-C6H4-
3-Cl-C6H4-
3-OMe-C6H4-
3-Me-C6H4-
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
1
2
2
1
1
1
1
1.5
2
1
1
1
0.75
1
2
0.75
2
1
1
2
3
6
3
3
3
3
6
3
3
3
/
6
3
/
3
3
9
/
18
6
60
1
91
71
75
69
70
54
62
68
56
92
97
50
89
94
61
74
38
90
92
85
46
0.83
72
96
68
44
24
46
96
23
40
25
23
91
72
24
64
52
4-F-C6H4-
2-Cl-4,5-diF-C6H2-
4-NO2-C6H4-
2-Br-5-CF3-C6H3-
2-I-C6H4-
2-Me-C6H4-
4-CH2Cl-C6H4-
4-Me-C6H4-
3,4-di-MeO-C6H3-
2-MeO-C6H4-
4-MeO-C6H4-
2,4-di-MeO-C6H3-
2,4,6-tri-Me-C6H2-
1-Naphthyl-
4j
4k
4l
4m
4n
4o
4p
4q
4r
4s
4t
/
10
9
2-Naphthyl-
2-COOH-C6H4-
3t
3u
3
4u
a Reaction conditions: 3 (4.65–30 mmol) and HMDS (4.65–30 mmol), rt.
b Isolated yield.
All tested acids 3 were poorly soluble solids in HMDS and therefore challenging substrates. We were
pleased that acids with both electron-releasing and electron-withdrawing substituents reacted well
furnishing TMSC 4a–4r. Moreover, the functionalization was successful in the case of strong
electron-donating groups (entries 15–17), and strong electron-withdrawing groups (entries 7–9). We
prepared several halogenated products that may be significant in various coupling reactions, in
medicinal or pesticide chemistry and useful substrates in nucleophilic substitutions (entries 2, 3, 6, 7,
9, 10 and 12). Sterically hindered 2,4,6-trimethylbenzoic acid 3r reacted unexpectedly smoothly
giving its derivative 4r in an uncatalyzed reaction (entry 18). Naphthalene derivatives 3s and 3t
efficiently produced the related 4s and 4t analogs in high yields (entries 19 and 20). The neighboring
carboxylic groups in phthalic acid 3u could be protected yielding 4u despite sterical hindrance (entry
21). In most cases 3–9 mol% of iodine was required; however, some uncatalyzed reactions took place
as well (entries 11, 14, 18 and 19). 0.5 equiv. of HMDS per COOH group would be theoretically a
sufficient amount of reagent; however, poor solubility of acids led to very long reaction times and
reactions were not complete. The lowest excess was 0.75 equiv. per COOH (entries 13 and 16); the
less reactive substrates required up to 2 equiv. per COOH (entries 2, 3, 9, 15, 17 and 20).
In continuation, we focused on hydroxy-substituted acids due to the possible additional
functionalization of hydroxy groups; the results are presented in Table 3.
Table 3
4

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Functionalization of hydroxy-substituted aryl acids with HMDS.a
Entry
ArCOOH
5
HMDS
I2 (mol. %)
t (h)
ArCOOTMS
Yield (%)b
(equiv.)
6
1
2
3
4
5
6
7
2-OH-C6H4-
2-OH-5-Cl-C6H3-
2-OH-5-t-Bu-C6H3-
3-OH-2-naphthyl-
4-OH-C6H4-
5a
5b
5c
5d
5e
5f
1.5
2
1
2
2
/
3
/
3
3
9
9
24
27
27
23
0.67
39
6a
6b
6c
6d
6e
6f
89
80
92
63
94
44
76
2,4-di-OH-C6H3-
2,6-di-OH-C6H3-
2
3
5g
16
6g
a Reaction conditions: 5 (5–10 mmol) and HMDS (7.5–30 mmol), rt.
b Isolated yield.
Initially, the reactivity of salicylic acid 5a was tested. The functionalization of carboxy and hydroxy
groups took place completely in 24 hours at room temperature thus yielding the corresponding product
6a in 89% yield (entry 1). In the literature, 6a was obtained in 96.5% yield after 24 hours of refluxing
of 5a and HMDS.31a Transformation can obviously be accomplished at room temperature at the same
time. 5-chlorosalicylic acid 5b and 5-tert-butylsalicylic acid 5c were effectively converted into the
related TMS-substituted products 6b and 6c (entries 2 and 3). 3-hydroxy-2-naphthoic acid 5d
smoothly yielded 6d in a reasonable yield (entry 4). The adjacent position of hydroxy and carboxy
groups is obviously not that sterically demanding to prevent functionalization. 4-hydroxybenzoic acid
5e was surprisingly reactive and gave 6e in 94% yield (entry 5). Dihydroxybenzoic acids 5f and 5g
furnished tri-TMS-substituted products 6f and 6g in good yields (entries 6 and 7). We were pleased
that two adjacent hydroxyl groups in 5g did not block the functionalization of the carboxy group, and
all three sites were functionalized (entry 7).
Next, we focused on variously aryl-alkyl substituted carboxylic acids; the results are presented in
Table 4. Neat phenylacetic acid 7a and its 4-methoxy derivative 7c yielded the corresponding TMS
esters 8a and 8c in excellent yields without catalyst (entries 1 and 3). Variously substituted acids 7b
and 7d also furnished the expected products (entries 2 and 4).
5

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Table 4
Functionalization of various phenyl-substituted acids into TMS derivatives 8.a
Entry
ArCOOH
7
HMDS
I2 (mol. %)
t (h)
ArCOOTMS
Yield (%)b
(equiv.)
8
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
8m
8n
8o
8p
8q
8r
8s
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
PhCH2-
4-Cl-C6H4-CH2-
4-OMe-C6H4-CH2-
3,4-di-OMe-C6H3-CH2-
2-OH-C6H4-CH2-
4-OH-C6H4-CH2-
Ph(OH)CH-
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
7m
7n
7o
7p
7q
7r
7s
1
1
1
1
2
3
3
3
2
1
2
1
1.5
2
1
1
1
1
/
6
/
72
24
68
0.17
8
98
54
91
55
84
61
59
20
82
50
92
46
60
59
34
82
36
91
50
3
3
9
9
9
9
3
3
3
10
10
3
3
3
/
1
3
PhOCH2-
PhSCH2-
PhCH2CH2-
48
55
6
20
21
48
25
1
40
68
22
92
4-OH-C6H4-CH2CH2-
C6H5-CH2(Br)CH-
Ph2CH-
Ph2(Me)C-
PhCOCH2CH2-
PhCH=CH-
4-OMe-C6H4-CH=CH-
3,4-di-OMe-C6H3-CH=CH-
3,4,5-tri-OMe-C6H2-CH=CH-
5
9
a Reaction conditions: 7 (5–10 mmol) and HMDS (5–30 mmol), rt.
b Isolated yield.
Hydroxy-substituted phenylacetic acids 7e and 7f yielded the related di-TMS-substituted products 8e
and 8f (entries 5 and 6) as well as (±)-mandelic acid 7g (entry 7). The functionalization of 2-
phenoxyacetic acid 7h gave product 8h in low yield (entry 8) while its sulfur analogue 7i produced 8i
in good yield (entry 9). 3-phenylpropanoic acid 7j and its derivatives 7k and 7l were transformed into
the related TMS-substituted derivatives (entries 10–12). Sterically demanding diphenyl-substituted
acids 7m and 7n were converted in 8m and 8n in reasonable yields (entries 13 and 14). 4-oxo-4-
phenylbutanoic acid 7o yielded 8o in modest yield (entry 15). The excess of HMDS varied from
substrate to substrate; in particular, in cases of poorly soluble acids, excess HMDS partly played a role
of solvent. Cinnamic acid 7p and it derivatives 7q–7s were efficiently transformed into the related
derivatives 8p–8s (entries 16–19); the best yields were obtained in the cases of 7p and 7r. It was
demonstrated that various substituents are compatible with the reaction conditions i.e. alkyl, thioalkyl,
halogen atoms as well as unsaturated functionalities.
We examined the effect of the structure of some heterocyclic carboxylic acids on the reaction with
HMDS; the results are summarized in Table 5. In particular, 5-membered aromatics are acid-sensitive,
and neutral reaction conditions with HMDS/I2 may be favorable for their functionalization.
Table 5
Transformation of heteroaryl carboxylic acids 9 into TMS derivatives 10.a
6

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Entry
ArCOOH
9
HMDS
I2 (mol. %)
t (h)
ArCOOTMS
Yield (%)b
(equiv.)
10
1
2
3
4
5
6
2-thienyl
2-thienylmethyl
3-thienylmethyl
2-furyl
9a
9b
9c
9d
9e
9f
1.5
1
1
2
1
9
3
/
9
3
9
0.25
0.5
3
96
42
19
10a
10b
10c
10d
10e
10f
67
53
88
31
38
61
3-furyl
3-pyridyl
2
a Reaction conditions: 9 (10 mmol) and HMDS (10–20 mmol), rt.
b Isolated yield.
Thiophene-2-carboxylic acid 9a was transformed into its TMS ester 10a in a short reaction time (entry
1). Thiopheneacetic acids 9b and 9c reacted well and both trimethylsilyl acetates 10b and 10c were
isolated in 53% and 88% yield, respectively (entries 2 and 3). Furyl-substituted acids 9d and 9e
reacted slowly; conversion was not complete, and both required products 10d and 10e were isolated in
moderate yield (entries 4 and 5). Nicotinic acid 9f was converted into its TMS ester 10f in 61% yield
(entry 6). 3-Thiopheneacetic acid 9c yielded product 10c in high yield in an uncatalyzed reaction.
Functionalization of the other substrates in Table 5 required a catalytic amount of iodine, and products
were isolated in moderate yields. The reason for lower yields could be potentially ascribed to the
additional complexation of iodine with the heteroatoms.
Finally, a reactivity of some Boc-protected amino acids was investigated; the results are presented in
Table 6.
7

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Table 6.
Conversion of N-Boc protected amino acids 11 into TMS esters 12.a
Entry
1
ArCOOH
11
HMDS
(equiv.)
I2 (mol. %)
/
t (h)
45
ArCOOTMS
Yield (%)b
93
12
11a
1
1
1
12a
12b
12c
2
3
11b
11c
/
/
24
3
94
88
4
5
11d
11e
1
1
/
/
17
24
12d
12e
96
96
6
11f
2
3
0.16
12f
50
a Reaction conditions: 11 (5 mmol) and HMDS (5–10 mmol), rt.
b Isolated yield.
With a protected amino group, the starting amino acids 11 are considerably polar and poorly soluble in
HMDS and were expected to be challenging substrates, but pleasingly neat Boc-glycine 11a and Boc-
β-alanine 11b yielded the related TMS derivatives 12a and 12b in excellent yields (entries 1 and 2).
Optically active Boc-L-valine 11c reacted smoothly in 3 hours, giving the corresponding 12c in very
good yield (entry 3). Functionalization of Boc-L-proline 11d led to the TMS-protected derivative 12d
13
in an excellent yield (entry 4). C NMR spectrum of 12d showed two sets of signals; thus indicating
the coexistence of two isomeric forms due to the restricted rotation, since the adjacent Boc and
COOTMS groups are sterically very demanding. To our surprise, the selected amino acids 11a–11e
reacted without a catalyst despite poor solubility. The initial heterogeneous reaction mixtures became
completely homogeneous after a certain period of stirring. Boc-L-phenylalanine 11e gave the related
TMS derivative 12e in an excellent yield (entry 5). A hydroxy analogue, Boc-L-tyrosine 11f yielded
its di-OTMS product 12f in the presence of iodine in 50% yield (entry 6).
The mechanism in the case of the iodine-catalyzed reaction is probably similar to the one described by
Karimi,43 whereas the mechanism of the uncatalyzed reaction must be different (Scheme 1). A
8

ACCEPTED MANUSCRIPT
plausible explanation could be that RCOOH attacks the silicon atom in HMDS, and TMSNH fragment
traps the proton yielding RCOOTMS and TMSNH2. The latter acts as a silylating reagent to some
extent, because ammonia is formed as well. Reactions of salicylic acid 5a and mandelic acid 7g with
HMDS were examined with the Nessler’s reagent. In both cases, ammonia was clearly detected over
the reaction mixture, and it can be concluded that both TMS groups from HMDS participate in
functionalization of carboxylic acid in both catalyzed and uncatalyzed reactions.
Scheme 1. Plausible reaction pathways
The heterogeneous reaction conditions prevent establishing the structure–reactivity relationships that
are common in the homogeneous solutions. There is hardly to find any correlation between the
structure and reactivity in a series of the benzoic acids. The acidity and nucleophilicity parameters are
not likely to be the key factors determining the reactivity of the carboxylic acids in this case. In
general, the tested acids are sparingly soluble in HMDS; however, the hydrogen bonding between the
carboxylic acids and HMDS might influence the solubility and reactivity of the acids. It appears that
solubility of the acids in HMDS is one the main factor governing the reactivity, and consequently
there is no obvious correlation between the structure and reactivity.
3. Conclusions
A structurally broad set of carboxylic acids were functionalized with neat HMDS under SFC, many
acids reacted without a catalyst, and some of them required a catalytic amount of iodine. Aliphatic
mono- and dicarboxylic-, cyclic- and halo-substituted acids were converted into their TMS esters.
Numerous aromatic mono- and bicyclic- and several hydroxy-substituted aromatic acids were
efficiently converted into their TMS derivatives; functionalization of hydroxy groups took place as
well. Different phenyl-alkyl substituted- and heterocyclic carboxylic acids were converted into their
TMS analogues. N-Boc protected amino acids were effectively transformed into the related TMS
esters in uncatalyzed reactions. Despite the generally low solubility of the acids and heterogeneous
reaction conditions, the reactions proceeded successfully, and a reasonable excess of HMDS was used.
This functionalization is environmentally friendly for several reasons. Reactions were performed
practically without any solvents, cost-effectively, completely without chromatography; products were
isolated by distillation only. Neutral reaction conditions have several advantages over the alternative
conditions where hydrogen halide release requires the use of an additional base. The process is
remarkably operationally simpler than the majority of the reported examples, because
functionalization is realizable in non-extra-dried glassware and in the presence of air without dry inert
gas. Scale-up is feasible; we showed examples with up to 30 mmol of the starting acid. The
9

ACCEPTED MANUSCRIPT
transformation is a good example of waste minimization; the excess of HMDS could be reused, and
ammonia was practically the only discarded material.
4. Materials and methods
4.1. General information
Reactions were carried out in closed round-bottom flasks with stirring at room temperature without the
exclusion of air. Glassware was not extra-dried, although isolated products start to hydrolyze rapidly
in air. Most of the carboxylic acids and HMDS were obtained from commercial sources and used as
1
received. All products were characterized by their H NMR, 13C NMR, 19F NMR and IR spectra,
13
whereas novel products were characterized with CHN/HRMS analyses as well. The 1H and C NMR
spectra were recorded on Bruker Avance 300 DPX, Bruker Avance III 400 and Bruker Avance III 500
instruments. The 19F NMR spectra were only recorded on Bruker Avance III 500 instrument. Chemical
shifts are reported in δ (ppm) values relative to the TMS (δ = 0.00 ppm) and to the residual CHCl3 (δ =
1
7.26 ppm) for H NMR, and to the central line of CDCl3 (δ = 77.00 ppm) for 13C NMR. 19F NMR
spectra are referred to CFCl3 (δ = 0.00 ppm). IR spectra were obtained with a Perkin-Elmer Spectrum
100 instrument. GC-MS spectra were obtained on Hewlett Packard HP 6890 Series (GC System and
Mass Selective Detector). Optical rotations were measured with Perkin Elmer 241 MC polarimeter.
The melting points were determined in open-capillaries on Büchi 535 apparatus and are uncorrected.
(±)-2-Bromo-3-phenylpropanoic acid 7l was prepared according to the published procedure.44
Cinnamic acids 7q–7s were prepared as previously reported.45
4.2. Representative procedure of the non-catalyzed functionalization of carboxylic acids with HMDS
under SFC
To octanoic acid 1a (4.32 g, 30 mmol) HMDS (3.63 g, 22.5 mmol) was added, and the mixture was
stirred at room temperature until the complete consumption 1a. The initial heterogeneous reaction
mixture became homogeneous, and 1H NMR analysis confirmed full conversion. The excess of HMDS
was distilled off under reduced pressure, and distillation of the crude product furnished trimethylsilyl
octanoate 2a (5.91 g, 91%) as a transparent oil. The distilled excess of HMDS could be reused.
4.3. Representative procedure of I2-catalyzed functionalization of carboxylic acids with HMDS
To a mixture of decanoic acid 1b (1.72 g, 10 mmol) and HMDS (1.61 g, 10 mmol), iodine (0.15 g, 0.6
mmol) was added, and the mixture was stirred at room temperature until the complete conversion of
1
1b. The initial heterogeneous reaction mixture became homogeneous, and H NMR analysis
confirmed full conversion. A brown reaction mixture was diluted with a few drops of TBME, and
anhydrous sodium thiosulfate was added in small portions during stirring at room temperature. After
some time of stirring, the reaction mixture decolorized (the color of iodine disappeared). In some
cases, the color of iodine persisted for hours, and then small portions of sodium thiosulfate
pentahydrate were added. Further stirring reduced iodine, and the brown color disappeared. In a few
cases, iodine disappeared during the reaction, and its removal was not needed. The reaction mixture
was diluted with a small volume of TBME and filtered. The filtrate was concentrated under reduced
pressure, and the thus-obtained reaction mixture was subjected to a vacuum distillation. After removal
of excess of HMDS, the distillation of crude product gave trimethylsilyl decanoate 2b (1.18 g, 48%) as
a slightly yellow oil. The distilled excess of HMDS could be reused.
Trimethylsilyl octanoate 2a
1a (4.32 g, 30 mmol), HMDS (3.63 g, 22.5 mmol); transparent oil, (5.91 g, 91%); IR (neat) 2927,
2857, 1708, 1413, 1252, 1053, 935, 843, 756 cm ˗1; δH (500 MHz, CDCl3) 2.28 (t, J = 7.4 Hz, 2H),
1.62–1.51 (m, 2H), 1.35–1.19 (m, 8H), 0.87 (t, J = 6.9 Hz, 3H), 0.26 (s, 9H); δC (125 MHz, CDCl3)
10

ACCEPTED MANUSCRIPT
174.5, 35.9, 31.7, 29.0, 29.0, 25.0, 22.6, 14.0, −0.3; m/z (EI) 216 (<1 M+), 201 (22), 117 (40), 99 (<1),
75 (100), 73 (89%); HRMS (EI): [M−Me]+, found 201.1310. [C10H21O2Si]+ requires 201.1306.
Trimethylsilyl decanoate5g 2b
1b (1.72 g, 10 mmol), HMDS (1.61 g, 10 mmol), I2 (0.15 g, 0.6 mmol); slightly yellow oil, (1.18 g,
48%); IR (neat) 2924, 2855, 1718, 1367, 1252, 1180, 847, 762, 729 cm ˗1; δH (300 MHz, CDCl3) 2.27
(t, J = 7.5 Hz, 2H), 1.65–1.50 (m, 2H), 1.33–1.21 (m, 12H), 0.90–0.83 (m, 3H), 0.26 (s, 9H); δC (75
MHz, CDCl3) 174.4, 35.9, 31.8, 29.4, 29.3, 29.2, 29.1, 25.0, 22.6, 14.0, −0.3.
Trimethylsilyl cyclohexanecarboxylate46 2c
1c (0.64 g, 5 mmol), HMDS (0.81 g, 5 mmol); transparent oil, (0.95 g, 95%); IR (neat) 2931, 2856,
1713, 1450, 1312, 1249, 1195, 1176, 1135, 939, 847, 763, 732 cm ˗1; δH (300 MHz, CDCl3) 2.30–2.18
(m, 1H), 1.95–1.84 (m, 2H), 1.79–1.57 (m, 3H), 1.48–1.20 (m, 5H), 0.27 (s, 9H); δC (75 MHz, CDCl3)
176.8, 44.4, 29.0, 25.8, 25.4, −0.2.
Trimethylsilyl adamantane-1-carboxylate47 2d
1d (0.90 g, 5 mmol), HMDS (0.81 g, 5 mmol); white crystalline product, (1.18 g, 94%), m.p. 31.1–
31.6 ºC; IR (neat) 2906, 2851, 1703, 1327, 1272, 1246, 1076, 909, 844, 765, 730 cm ˗1; δH (500 MHz,
CDCl3) 2.03–1.98 (m, 3H), 1.87–1.84 (m, 6H), 1.75–1.65 (m, 6H), 0.26 (s, 9H); δC (125 MHz, CDCl3)
178.6, 41.4, 38.8, 36.5, 28.0, −0.3.
Bis(trimethylsilyl)malonate48 2e
1e (1.04 g, 10 mmol), HMDS (3.23 g, 20 mmol), I2 (0.23 g, 0.9 mmol); yellow oil, (1.54 g, 62%); IR
˗1
(neat) 2962, 1715, 1411, 1335, 1282, 1252, 1195, 1156, 951, 838, 761, 714 cm ; δH (500 MHz,
CDCl3) 3.31 (s, 2H), 0.27 (s, 18 H); δC (125 MHz, CDCl3) 166.9, 44.8, −0.5.
Bis(trimethylsilyl)succinate49 2f
1f (1.18 g, 10 mmol), HMDS (3.23 g, 20 mmol), I2 (0.23 g, 0.9 mmol); slightly yellow crystalline
solid, (1.47 g, 56%), m.p. 50.4–50.7 ºC; IR (neat) 2964, 1701, 1421, 1329, 1248, 1175, 1160, 936,
836, 800, 762, 734, 702 cm˗1; δH (500 MHz, CDCl3) 2.58 (s, 4H), 0.27 (s, 18H); δC (125 MHz, CDCl3)
172.9, 30.9, −0.3.
Bis(trimethylsilyl)adipate50 2g
1g (1.46 g, 10 mmol), HMDS (5.65 g, 35 mmol), I2 (0.23 g, 0.9 mmol); yellow oil, (2.07 g, 71%); IR
(neat) 2958, 1714, 1368, 1252, 1181, 1147, 919, 846, 763, 730 cm ˗1; δH (300 MHz, CDCl3) 2.35–2.25
(m, 4H), 1.65–1.55 (m, 4H), 0.25 (s, 18H); δC (75 MHz, CDCl3) 173.9, 35.5, 24.4, −0.3.
Trimethylsilyl 2,2-dichloroacetate51 2h
1h (1.29 g, 10 mmol), HMDS (1.61 g, 10 mmol); transparent oil, (1.16 g, 58%); IR (neat) 2960, 1747,
1728, 1300, 1255, 1180, 1053, 952, 843, 821, 762, 725, 680 cm ˗1; δH (300 MHz, CDCl3) 5.88 (s, 1H),
0.36 (s, 9H); δC (75 MHz, CDCl3) 163.8, 65.5, −0.7.
Trimethylsilyl benzoate51 4a
3a (3.66 g, 30 mmol), HMDS (4.84 g, 30 mmol), I2 (0.23 g, 0.9 mmol); yellow oil, (5.32 g, 91%); IR
(neat) 2961, 1698, 1452, 1314, 1284, 1252, 1175, 1115, 1069, 1026, 844, 760, 734, 707, 619 cm ˗1; δH
(500 MHz, CDCl3) 8.00–7.95 (m, 2H), 7.50–7.45 (m, 1H), 7.39–7.32 (m, 2H), 0.33 (s, 9H); δC (125
MHz, CDCl3) 166.7, 132.9, 131.3, 130.1, 128.2, −0.2.
Trimethylsilyl 4-chlorobenzoate 4b
11

ACCEPTED MANUSCRIPT
3b (1.56 g, 10 mmol), HMDS (3.23 g, 20 mmol), I2 (0.15 g, 0.6 mmol); yellow oil, (1.63 g, 71%); IR
(neat) 2961, 1698, 1592, 1487, 1401, 1290, 1280, 1253, 1170, 1116, 1103, 1090, 1015, 846, 830, 768,
733, 682 cm ˗1; δH (500 MHz, CDCl3) 7.98–7.94 (m, 2H), 7.41–7.37 (m, 2H), 0.39 (s, 9H); δC (125
MHz, CDCl3) 165.8, 139.3, 131.5, 129.8, 128.5, −0.2; m/z (EI) 228 (4 M+), 213 (66), 169 (63), 139
(100), 111 (67), 75 (50%); HRMS (EI): [M−Me]+, found 213.0129. [C9H10ClO2Si]+ requires 213.0134.
Trimethylsilyl 3-chlorobenzoate 4c
3c (1.56 g, 10 mmol), HMDS (3.23 g, 20 mmol), I2 (0.075 g, 0.3 mmol); yellow crystalline solid, (1.72
g, 75%), m.p. 29.0–29.2 ºC; IR (neat) 2961, 1697, 1573, 1476, 1415, 1296, 1253, 1134, 1071, 883,
843, 764, 745, 717, 666 cm ˗1; δH (500 MHz, CDCl3) 8.01–7.98 (m, 1H), 7.94–7.90 (m, 1H), 7.53–7.49
(m, 1H), 7.39–7.34 (m, 1H), 0.40 (s, 9H); δC (125 MHz, CDCl3) 165.4, 134.3, 133.1, 132.9, 130.1,
129.5, 128.2, −0.2; m/z (EI) 228 (8 M+), 213 (97), 169 (67), 139 (100), 111 (75), 75 (50%); HRMS
(EI): M+, found 228.0363. [C10H13ClO2Si]+ requires 228.0368.
Trimethylsilyl 3-methoxybenzoate 4d
3d (1.52 g, 10 mmol), HMDS (1.61 g, 10 mmol), I2 (0.075 g, 0.3 mmol); yellow oil, (1.55 g, 69%); IR
(neat) 2959, 1697, 1586, 1487, 1454, 1431, 1291, 1253, 1224, 1182, 1100, 1080, 1042, 919, 906, 845,
790, 765, 734, 682 cm ˗1; δH (500 MHz, CDCl3) 7.66–7.61 (m, 1H), 7.58–7.54 (m, 1H), 7.36–7.31 (m,
1H), 7.12–7.07 (m, 1H), 3.85 (s, 3H), 0.40 (s, 9H); δC (125 MHz, CDCl3) 166.6, 159.5, 132.7, 129.2,
122.5, 119.4, 114.5, 55.4, −0.2; m/z (EI) 224 (18 M+), 209 (68), 165 (63), 135 (100), 107 (31%);
HRMS (EI): M+, found 224.0873. [C11H16O3Si]+ requires 224.0864.
Trimethylsilyl 3-methylbenzoate 4e
3e (1.36 g, 10 mmol), HMDS (1.61 g, 10 mmol), I2 (0.075 g, 0.3 mmol); yellow oil, (1.45 g, 70%); IR
(neat) 2960, 1697, 1590, 1426, 1296, 1284, 1253, 1204, 1108, 1082, 910, 847, 791, 763, 744, 682, 667
cm ˗1; δH (500 MHz, CDCl3) 7.88–7.82 (m, 2H), 7.39–7.34 (m, 1H), 7.34–7.29 (m, 1H), 2.40 (s, 3H),
0.40 (s, 9H); δC (125 MHz, CDCl3) 166.9, 138.0, 133.7, 131.2, 130.6, 128.1, 127.3, 21.2, −0.2; m/z
(EI) 208 (13 M+), 193 (84), 149 (65), 119 (100), 91 (68%); HRMS (EI): M+, found 208.0919.
[C11H16O2Si]+ requires 208.0914.
Trimethylsilyl 4-fluorobenzoate 4f
3f (1.40 g, 10 mmol), HMDS (1.61 g, 10 mmol), I2 (0.075 g, 0.3 mmol); yellow oil, (1.14 g, 54%); IR
(neat) 2962, 1698, 1601, 1507, 1287, 1253, 1152, 1117, 1089, 872, 841, 774, 733, 685 cm ˗1; δH (500
MHz, CDCl3) 8.04–7.94 (m, 2H), 7.06–6.98 (m, 2H), 0.36 (s, 9H); δC (125 MHz, CDCl3) 165.6 (d, J =
253.6 Hz), 165.5, 132.5 (d, J = 9.3 Hz), 127.5 (d, J = 2.6 Hz), 115.2 (d, J = 22.0 Hz), −0.4; δF (470
MHz, CDCl3) −106.4–(−106.3) (m, 1F); m/z (EI) 212 (3 M+), 197 (68), 153 (70), 123 (100), 95 (73%);
HRMS (EI): M+, found 212.0670. [C10H13FO2Si]+ requires 212.0664.
Trimethylsilyl 2-chloro-4,5-difluorobenzoate 4g
3g (1.93 g, 10 mmol), HMDS (1.61 g, 10 mmol), I2 (0.15 g, 0.6 mmol); red oil, (1.65 g, 62%); IR
(neat) 2963, 1719, 1698, 1595, 1503, 1399, 1307, 1252, 1220, 1178, 1108, 847, 785, 734 cm ˗1; δH
(500 MHz, CDCl3) 7.73 (dd, J = 10.5 Hz, J = 8.5 Hz, 1H), 7.22 (dd, J = 9.8 Hz, J = 6.9 Hz, 1H), 0.35
(s, 9H); δC (125 MHz, CDCl3) 163.1, 151.9 (dd, J = 258.6 Hz, J = 13.6 Hz), 148.4 (dd, J = 250.5 Hz, J
= 12.6 Hz), 130.4 (dd, J = 8.4 Hz, J = 3.6 Hz), 127.0 (t, J = 4.2 Hz,), 121.1 (dd, J = 19.8 Hz, J = 1.3
Hz), 120.3 (d, J = 20.3 Hz), −0.3; δF (470 MHz, CDCl3) −138.7–(−138.6) (m, 1F), −129.6–(−129.5)
(m, 1F); m/z (EI) 264 (3 M+), 249 (57), 175 (100), 147 (63), 73 (18%); HRMS (EI): [M−Me]+, found
248.9952. [C9H8ClF2O2Si]+ requires 248.9945.
Trimethylsilyl 4-nitrobenzoate 4h
12

ACCEPTED MANUSCRIPT
3h (1.67 g, 10 mmol), HMDS (2.42 g, 15 mmol), I2 (0.075 g, 0.3 mmol); yellow solid, (1.63 g, 68%),
m.p. 105.9–106.6 ºC; [Found: C, 50.06; H 5.27; N 5.99. C10H13NO4Si requires C, 50.19; H 5.48; N
5.85]; IR (neat) 2962, 1689, 1605, 1521, 1425, 1347, 1310, 1278, 1248, 1101, 1011, 930, 876, 850,
821, 801, 789, 714 cm ˗1; δH (500 MHz, CDCl3) 8.30–8.24 (m, 2H), 8.22–8.16 (m, 2H), 0.42 (s, 9H);
δC (125 MHz, CDCl3) 164.7, 150.5, 136.8, 131.2, 123.4, −0.3.
Trimethylsilyl 2-bromo-5-(trifluoromethyl)benzoate 4i
3i (1.34 g, 5 mmol), HMDS (1.61 g, 10 mmol), I2 (0.04 g, 0.15 mmol); orange oil, (0.96 g, 56%). IR
(neat) 2960, 1717, 1608, 1337, 1291, 1251, 1172, 1128, 1081, 1030, 844, 787, 735, 699 cm ˗1: δH (500
MHz, CDCl3) 8.10 (d, J = 1.6 Hz,1H), 7.78 (d, J = 8.3 Hz, 1H), 7.53 (dd, J = 8.3 Hz, J = 1.6 Hz, 1H),
0.43 (s, 9H); δC (125 MHz, CDCl3) 164.6, 135.2, 133.8, 129.8 (q, J = 33.6 Hz), 128.7 (m), 126.0 (m),
123.3 (q, J = 274.4 Hz), −0.3; δF (470 MHz, CDCl3) −63.4 (s); m/z (EI) 340 (<1 M+), 325 (36), 281
(14), 251 (57), 223 (33), 144 (100), 75 (70), 73 (57%); HRMS (EI): M+, found 339.9747.
[C11H12BrF3O2Si]+ requires 339.9737.
Trimethylsilyl 2-iodobenzoate52 4j
3j (2.48 g, 10 mmol), HMDS (1.61 g, 10 mmol), I2 (0.075 g, 0.3 mmol); yellow oil, (2.93 g, 92%); IR
(neat) 2958, 1705, 1583, 1428, 1298, 1253, 1136, 1105, 1043, 1015, 850, 762, 741 cm ˗1; δH (300
MHz, CDCl3) 7.97 (dd, J = 7.7 Hz, J = 1.1 Hz, 1H), 7.86 (dd, J = 7.7 Hz, J = 1.7 Hz, 1H), 7.36 (ddd, J
= 7.7 Hz, J = 7.7 Hz, J = 1.1 Hz, 1H), 7.10 (ddd, J = 7.7 Hz, J = 7.7 Hz, J = 1.7 Hz, 1H), 0.41 (s, 9H);
δC (75 MHz, CDCl3) 166.0, 141.3, 135.7, 132.5, 131.5, 127.7, 94.3, −0.2.
Trimethylsilyl 2-methylbenzoate53 4k
3k (1.36 g, 10 mmol), HMDS (1.61 g, 10 mmol); transparent oil, (2.01 g, 97%); IR (neat) 2962, 1697,
1301, 1252, 1145, 1134, 1079, 873, 836, 760, 734, 692, 661 cm ˗1; δH (300 MHz, CDCl3) 8.05–7.97
(m, 1H), 7.46 –7.37 (m, 1H), 7.32–7.21 (m, 2H), 2.66 (s, 3H), 0.44 (s, 9H); δC (75 MHz, CDCl3)
167.5, 140.7, 132.0, 131.7, 131.3, 130.5, 125.6, 22.0, −0.2.
Trimethylsilyl 4-(chloromethyl)benzoate 4l
3l (1.71 g, 10 mmol), HMDS (1.61 g, 10 mmol), I2 (0.15 g, 0.6 mmol); slightly yellow oil, (1.22 g,
50%); IR (neat) 2961, 1696, 1414, 1310, 1287, 1252, 1177, 1118, 1105, 1019, 839, 798, 709 cm˗1; δH
(300 MHz, CDCl3) 8.06–7.99 (m, 2H), 7.48–7.41 (m, 2H), 4.61 (s, 2H), 0.40 (s, 9H); δC (75 MHz,
CDCl3) 166.2, 142.2, 131.4, 130.5, 128.4, 45.4, −0.2; m/z (EI) 242 (6 M+), 227 (100), 183 (55), 153
(98), 125 (35), 89 (60), 73 (20%); HRMS (EI): M+, found 242.0527. [C11H15ClO2Si]+ requires
242.0525.
Trimethylsilyl 4-methylbenzoate 4m
3m (4.08 g, 30 mmol), HMDS (3.63 g, 22.5 mmol), I2 (0.23 g, 0.9 mmol); yellow oil, (5.56 g, 89%);
IR (neat) 2959, 1696, 1611, 1408, 1284, 1252, 1176, 1109, 1052, 1020, 835, 764, 733, 688 cm ˗1; δH
(500 MHz, CDCl3) 7.96–7.91 (m, 2H), 7.25–7.19 (m, 2H), 2.41 (s, 3H), 0.40 (s, 9H); δC (125 MHz,
CDCl3) 166.8, 143.5, 130.1, 128.9, 128.6, 21.6, −0.2; m/z (EI) 208 (10 M+), 193 (51), 149 (61), 119
(100), 91 (64%); HRMS (EI): M+, found 208.0912. [C11H16O2Si]+ requires 208.0914.
Trimethylsilyl 3,4-dimethoxybenzoate54 4n
3n (1.82 g, 10 mmol), HMDS (1.61 g, 10 mmol); transparent, viscous oil, (2.39 g, 94%); IR (neat)
2958, 1687, 1598, 1512, 1463, 1416, 1344, 1296, 1267, 1252, 1223, 1176, 1132, 1107, 1024, 930,
846, 795, 770, 735 cm ˗1; δH (500 MHz, CDCl3) 7.66 (dd, J = 8.4 Hz, J = 1.5 Hz, 1H), 7.53 (d, J = 1.5
Hz, 1H), 6.86 (d, J = 8.4 Hz, 1H), 3.92 (s, 3H), 3.91 (s, 3H), 0.38 (s, 9H); δC (125 MHz, CDCl3) 166.6,
152.9, 148.5, 124.2, 123.8, 112.3, 110.0, 55.9, 55.8, −0.2.
13

ACCEPTED MANUSCRIPT
Trimethylsilyl 2-methoxybenzoate55 4o
3o (1.52 g, 10 mmol), HMDS (3.23 g, 20 mmol), I2 (0.075 g, 0.3 mmol); yellow oil, (1.37 g, 61%); IR
(neat) 2960, 1704, 1600, 1489, 1464, 1437, 1313, 1245, 1134, 1078, 1048, 1024, 872, 831, 752, 698,
655 cm ˗1; δH (300 MHz, CDCl3) 7.87–7.81 (m, 1H), 7.44–7.36 (m, 1H), 6.94–6.86 (m, 2H), 3.84 (s,
3H), 0.35 (s, 9H); δC (75 MHz, CDCl3) 165.4, 159.9, 133.6, 132.4, 120.3, 119.7, 111.9, 55.7, −0.3.
Trimethylsilyl 4-methoxybenzoate56 4p
3p (4.56 g, 30 mmol), HMDS (3.63 g, 22.5 mmol), I2 (0.23 g, 0.9 mmol); yellow oil, (4.95 g, 74%); IR
(neat) 2959, 1690, 1605, 1510, 1287, 1250, 1165, 1118, 1101, 1030, 840, 776, 756, 734, 692 cm ˗1; δH
(500 MHz, CDCl3) 8.00–7.93 (m, 2H), 6.90–6.83 (m, 2H), 3.79 (s, 3H), 0.37 (s, 9H); δC (125 MHz,
CDCl3) 166.3, 163.2, 132.0, 123.6, 113.3, 55.1, −0.3.
Trimethylsilyl 2,4-dimethoxybenzoate 4q
3q (1.82 g, 10 mmol), HMDS (3.23 g, 20 mmol), I2 (0.23 g, 0.9 mmol); yellow oil, (0.96 g, 38%); IR
(neat): 2959, 1698, 1674, 1605, 1574, 1504, 1461, 1439, 1416, 1248, 1210, 1162, 1136, 1082, 1029,
845, 740, 694 cm ˗1; δH (500 MHz, CDCl3) 7.92–7.87 (m, 1H), 6.46–6.41 (m, 2H), 3.86 (s, 3H), 3.80
(s, 3H), 0.34 (s, 9H); δC (125 MHz, CDCl3) 164.9, 164.4, 162.2, 134.8, 112.5, 104.2, 98.7, 55.7, 55.3,
−0.2; m/z (EI) 254 (7 M+), 239 (12), 165 (100), 73 (9%); HRMS (EI): M+, found 254.0976.
[C12H18O4Si]+ requires 254.0969.
Trimethylsilyl 2,4,6-trimethylbenzoate 4r
3r (0.76 g, 4.65 mmol), HMDS (0.75 g, 4.65 mmol); transparent oil, (0.99 g, 90%); IR (neat) 2959,
1703, 1612, 1428, 1275, 1253, 1171, 1086, 845, 743, 699 cm ˗1; δH (500 MHz, CDCl3) 6.86 (s, 2H),
2.35 (s, 6H), 2.29 (s, 3H), 0.42 (s, 9H); δC (125 MHz, CDCl3) 170.1, 138.9, 134.8, 132.2, 128.4, 21.1,
19.9, −0.2; m/z (EI) 236 (11 M+), 221 (24), 147 (100), 119 (18), 91 (20), 73 (14%); HRMS (EI): M+,
found 236.1227. [C13H20O2Si]+ requires 236.1227.
Trimethylsilyl 1-naphthoate 4s
3s (1.72 g, 10 mmol), HMDS (1.61 g, 10 mmol); slightly yellow oil, (2.26 g, 92%); IR (neat) 2959,
1689, 1509, 1282, 1243, 1197, 1137, 1001, 882, 840, 778, 727, 653, 624 cm ˗1; δH (300 MHz, CDCl3)
9.23–9.16 (m, 1H), 8.37–8.32 (m, 1H), 8.06–8.00 (m, 1H), 7.93–7.86 (m, 1H), 7.71–7.63 (m, 1H),
7.59–7.48 (m, 2H), 0.54 (s, 9H); δC (75 MHz, CDCl3) 167.4, 133.8, 133.6, 131.7, 131.2, 128.4, 127.7,
127.6, 126.0, 124.3, −0.1; m/z (EI) 244 (12 M+), 229 (32), 185 (39), 155 (87), 127 (100%); HRMS
(EI): M+, found 244.0908. [C14H16O2Si]+ requires 236.0914.
Trimethylsilyl 2-naphthoate 4t
3t (1.72 g, 10 mmol), HMDS (3.23 g, 20 mmol), I2 (0.25 g, 1.0 mmol); bright yellow solid, (2.08 g,
85%), m.p. 71.1–72.6 °C; [Found: C, 68.45; H 6.72. C14H16O2Si requires C, 68.81; H 6.60]; IR (neat)
3059, 1688, 1353, 1302, 1248, 1235, 1197, 1152, 1131, 1093, 974, 895, 836, 783, 766, 734 cm ˗1; δH
(300 MHz, CDCl3) 8.64–8.60 (m, 1H), 8.12–8.05 (m, 1H), 8.00–7.93 (m, 1H), 7.92–7.84 (m, 2H),
7.63–7.50 (m, 2H), 0.47 (s, 9H); δC (75 MHz, CDCl3) 166.9, 135.5, 132.5, 131.6, 129.3, 128.6, 128.1,
128.0, 127.7, 126.5, 125.7, −0.1.
Bis(trimethylsilyl)phthalate57 4u
4u (0.83 g, 5 mmol), HMDS (2.42 g, 15 mmol), I2 (0.11 g, 0.45 mmol); yellow oil, (0.71 g, 46%); IR
(neat) 2962, 1703, 1286, 1251, 1128, 1072, 843, 760, 722, 697 cm ˗1, δH (300 MHz, CDCl3) 7.74–7.66
(m, 2H), 7.52–7.45 (m, 2H), 0.39 (s, 18H); δC (75 MHz, CDCl3) 167.6, 133.6, 130.6, 128.9, −0.3.
Trimethylsilyl 2-((trimethylsilyl)oxy)benzoate58 6a
14

ACCEPTED MANUSCRIPT
5a (0.69 g, 5 mmol), HMDS (1.21 g, 7.5 mmol); yellow oil, (1.26 g, 89%); IR (neat) 2958, 1706,
1600, 1484, 1449, 1310, 1290, 1245, 1158, 1130, 1077, 1041, 920, 840, 762, 699 cm ˗1; δH (300 MHz,
CDCl3) 7.85–7.80 (m, 1H), 7.39–7.33 (m, 1H), 7.01–6.96 (m, 1H), 6.88–6.84 (m, 1H), 0.39 (s, 9H),
0.27 (s, 9H); δC (75 MHz, CDCl3) 166.2, 155.5, 133.2, 132.2, 123.8, 121.7, 121.1, 0.3, −0.1.
Trimethylsilyl 5-chloro-2-((trimethylsilyl)oxy)benzoate 6b
5b (1.73 g, 10 mmol), HMDS (3.23 g, 20 mmol), I2 (0.075 g, 0.3 mmol); yellow-orange oil, (2.54 g,
80%); IR (neat) 2959, 1710, 1474, 1406, 1285, 1250, 1229, 1144, 1104, 1074, 922, 880, 840, 760,
740, 713 cm ˗1; δH (500 MHz, CDCl3) 7.78 (d, J = 2.8 Hz, 1H), 7.30 (dd, J = 8.7 Hz, J = 2.8 Hz, 1H),
6.79 (d, J = 8.7 Hz, 1H), 0.38 (s, 9H), 0.26 (s, 9H); δC (125 MHz, CDCl3) 164.8, 154.2, 133.0, 131.7,
126.0, 124.9, 123.1, 0.2, −0.1; m/z (EI) 316 (<1 M+), 301 (7), 243 (<1), 227 (<1), 73 (100%); HRMS
(EI): M+, found 338.1739. [C12H18ClO3Si2]+ requires 338.1728.
Trimethylsilyl 5-(t-butyl)-2-((trimethylsilyl)oxy)benzoate 6c
5c (1.94 g, 10 mmol), HMDS (1.61 g, 10 mmol); transparent oil, (3.1 g, 92%); IR (neat) 2959, 1704,
1493, 1309, 1249, 1154, 1119, 1074, 933, 894, 836, 758 cm ˗1; δH (300 MHz, CDCl3) 7.84 (d, J = 2.7
Hz, 1H), 7.38 (dd, J = 8.6 Hz, J = 2.7 Hz, 1H), 6.79 (d, J = 8.6 Hz, 1H), 1.31 (s, 9H), 0.40 (s, 9H),
0.27 (s, 9H); δC (75 MHz, CDCl3) 166.9, 153.0, 143.6, 130.3, 128.7, 122.9, 121.0, 34.0, 31.3, 0.3, 0.0;
m/z (EI) 338 (<1 M+), 323 (30), 265 (2), 249 (4), 73 (100%); HRMS (EI): [M−Me]+, found 301.0487.
[C17H30O3Si2]+ requires 301.0478.
Trimethylsilyl 3-((trimethylsilyl)oxy)-2-naphthoate 6d
5d (1.88 g, 10 mmol), HMDS (3.23 g, 20 mmol), I2 (0.075 g, 0.3 mmol); yellow, viscous oil, (2.09 g,
63%); IR (neat) 3057, 2959, 2902, 1705, 1630, 1594, 1497, 1460, 1446, 1337, 1283, 1250, 1207,
1176, 1146, 1135, 1063, 929, 892, 835, 742 cm ˗1; δH (500 MHz, CDCl3) 8.33 (s, 1H), 7.80–7.75 (m,
1H), 7.65–7.60 (m, 1H), 7.45–7.39 (m, 1H), 7.33–7.28 (m 1H), 7.18 (s, 1H), 0.40 (s, 9H), 0.29 (s, 9H);
δC (125 MHz, CDCl3) 166.2, 151.6, 136.1, 133.2, 128.6, 128.2, 128.0, 126.2, 125.1, 124.4, 116.6, 0.2,
−0.1; m/z (EI) 332 (<1 M+), 317 (18), 259 (1), 73 (100%); HRMS (EI): M+, found 332.1259.
[C17H24O3Si2]+ requires 332.1259.
Trimethylsilyl 4-((trimethylsilyl)oxy)benzoate58 6e
5e (1.38 g, 10 mmol), HMDS (3.23 g, 20 mmol), I2 (0.075 g, 0.3 mmol); yellow oil, (2.66 g, 94%); IR
(neat) 2960, 1694, 1601, 1508, 1415, 1307, 1252, 1161, 1116, 1096, 909, 843, 781, 758, 737, 717 cm
˗1; δH (500 MHz, CDCl3) 7.98–7.93 (m, 2H), 6.88–6.83 (m, 2H), 0.38 (s, 9H), 0.28 (s, 9H); δC (125
MHz, CDCl3) 166.4, 159.6, 132.1, 124.5, 119.6, 0.1, −0.2.
Trimethylsilyl 2,4-bis((trimethylsilyl)oxy)benzoate 6f
5f (1.54 g, 10 mmol), HMDS (3.23 g, 20 mmol), I2 (0.23 g, 0.9 mmol); yellow oil, (1.63 g, 44%); IR
(neat) 2959, 1702, 1598, 1562, 1490, 1420, 1247, 1183, 1133, 1082, 1002, 903, 836, 749 cm ˗1; δH
(500 MHz, CDCl3) 7.78 (d, J = 8.7 Hz, 1H), 6.48 (dd, J = 8.7 Hz, J = 2.3 Hz, 1H), 6.32 (d, J = 2.3 Hz,
1H), 0.36 (s, 9H), 0.27 (s, 9H), 0.27 (s, 9H); δC (125 MHz, CDCl3) 165.7, 159.8, 157.4, 133.9, 116.9,
113.4, 113.1, 0.2, 0.2, 0.0; m/z (EI) 370 (<1 M+), 355 (25), 297 (<1), 281 (5), 73 (100%); HRMS (EI):
[M−Me]+, found 355.1217. [C15H27O4Si3]+ requires 355.1212.
Trimethylsilyl 2,6-bis((trimethylsilyl)oxy)benzoate 6g
5g (1.54 g, 10 mmol), HMDS (4.84 g, 30 mmol), I2 (0.23 g, 0.9 mmol); yellow oil, (2.80 g, 76%); IR
(neat) 2959, 1712, 1593, 1576, 1462, 1317, 1249, 1112, 1063, 837, 750 cm ˗1; δH (300 MHz, CDCl3)
7.05 (t, J = 8.2 Hz, 1H), 6.46 (d, J = 8.2 Hz, 2H), 0.26 (s, 18H), 0.38 (s, 9H); δC (75 MHz, CDCl3)
166.7, 153.0, 129.5, 121.7, 112.5, 0.3, −0.1; m/z (EI) 370 (<1 M+), 355 (16), 297 (<1), 281 (1), 73
(100%); HRMS (EI): [M−Me]+, found 355.1215. [C15H27O4Si3]+ requires 355.1212.
15

ACCEPTED MANUSCRIPT
Trimethylsilyl 2-phenylacetate5g 8a
7a (1.36 g, 10 mmol), HMDS (1.61 g, 10 mmol); transparent oil, (2.05 g, 98%); IR (neat) 2959, 1714,
1251, 1221, 1171, 943, 841, 751, 724, 694 cm ˗1; δH (500 MHz, CDCl3) 7.27–7.21 (m, 2H), 7.21–7.15
(m, 3H), 3.53 (s, 2H), 0.19 (s, 9H); δC (125 MHz, CDCl3) 172.0, 134.3, 129.2, 128.4, 126.8, 42.8,
−0.4.
Trimethylsilyl 2-(4-chlorophenyl)acetate5g 8b
7b (1.71 g, 10 mmol), HMDS (1.61 g, 10 mmol), I2 (0.15 g, 0.6 mmol); yellow oil, (1.31 g, 54%); IR
(neat) 2961, 1714, 1492, 1411, 1343, 1252, 1223, 1171, 1091, 1017, 935, 842, 805, 762, 714 cm ˗1; δH
(300 MHz, CDCl3) 7.25–7.18 (m, 2H), 7.16–7.09 (m, 2H), 3.52 (s, 2H), 0.21 (s, 9H); δC (75 MHz,
CDCl3) 171.5, 132.8, 132.8, 130.6, 128.5, 42.1, −0.4.
Trimethylsilyl 2-(4-methoxyphenyl)acetate5g 8c
7c (1.66 g, 10 mmol), HMDS (1.61 g, 10 mmol); transparent oil, (2.16 g, 91%); IR (neat) 2958, 1711,
1613, 1512, 1247, 1169, 1035, 946, 846, 791, 763, 724, 708 cm ˗1; δH (500 MHz, CDCl3) 7.22–7.17
(m, 2H), 6.90–6.85 (m 2H), 3.79 (s, 3H), 3.57 (s, 2H), 0.28 (s, 9H); δC (125 MHz, CDCl3) 172.4,
158.5, 130.2, 126.4, 113.8, 55.1, 41.9, −0.4.
Trimethylsilyl 2-(3,4-dimethoxyphenyl)acetate5g 8d
7d (1.96 g, 10 mmol), HMDS (1.61 g, 10 mmol), I2 (0.075 g, 0.3 mmol); yellow oil, (1.49 g, 55%); IR
(neat) 2957, 1711, 1514, 1464, 1420, 1253, 1235, 1173, 1141, 1028, 845, 845, 791, 759, 717 cm ˗1; δH
(500 MHz, CDCl3) 6.81–6.78 (m, 3H), 3.85 (s, 3H), 3.84 (s, 3H), 3.53 (s, 2H), 0.25 (s, 9H); δC (125
MHz, CDCl3) 172.2, 148.7, 147.9, 126.8, 121.3, 112.3, 111.0, 55.7, 55.7, 42.3, −0.4.
Trimethylsilyl 2-((2-trimethylsilyl)oxy)phenyl)acetate59 8e
7e (1.52 g, 10 mmol), HMDS (3.23 g, 20 mmol), I2 (0.075 g, 0.3 mmol); transparent oil, (2.48 g,
84%); IR (neat) 2960, 1717, 1493, 1454, 1343, 1250, 1211, 1167, 933, 916, 837, 752, 723, 693 cm ˗1;
δH (500 MHz, CDCl3) 7.21–7.13 (m, 2H), 6.95–6.91 (m, 1H), 6.84–6.80 (m, 1H), 3.59 (s, 2H), 0.30 (s,
9H), 0.29 (s, 9H); δC (125 MHz, CDCl3) 172.1, 153.6, 131.0, 128.1, 125.8, 121.2, 118.4, 37.7, 0.4,
−0.3.
Trimethylsilyl 2-((4-trimethylsilyl)oxy)phenyl)acetate59 8f
7f (1.52 g, 10 mmol), HMDS (4.84 g, 30 mmol), I2 (0.23 g, 0.9 mmol); yellow oil, (1.82 g, 61%); IR
(neat) 2960, 1715, 1610, 1509, 1249, 1166, 912, 840, 759, 718 cm ˗1; δH (300 MHz, CDCl3) 7.17–7.10
(m, 2H), 6.84–6.76 (m, 2H), 3.55 (s, 2H), 0.27 (s, 9H), 0.27 (s, 9H); δC (75 MHz, CDCl3) 172.2, 154.0,
130.2, 127.3, 119.9, 42.0, 0.1, −0.4.
Trimethylsilyl 2-phenyl-((2-trimethylsilyl)oxy)acetate60 8g
7g (1.52 g, 10 mmol), HMDS (4.84 g, 30 mmol), I2 (0.23 g, 0.9 mmol); yellow oil, (1.75 g, 59%); IR
(neat); 2957, 1736, 1714, 1288, 1252, 1213, 1181, 1127, 1071, 949, 887, 843, 758, 726, 696 cm ˗1; δH
(500 MHz, CDCl3) 7.47–7.42 (m, 2H), 7.36–7.26 (m, 3H), 5.14 (s, 1H), 0.20 (s, 9H), 0.13 (s, 9H); δC
(75 MHz, CDCl3) 172.2, 139.3, 128.2, 128.0, 126.6, 74.8, −0.1, −0.5.
Trimethylsilyl 2-phenoxyacetate61 8h
7h (1.52 g, 10 mmol), HMDS (4.84 g, 30 mmol), I2 (0.23 g, 0.9 mmol); yellow, viscous oil, (0.46 g,
20%); IR (neat) 2960, 1743, 1717, 1599, 1494, 1304, 1253, 1199, 1174, 1086, 922, 847, 753, 690 cm
˗1; δH (500 MHz, CDCl3) 7.32–7.26 (m, 2H), 7.01–6.96 (m, 1H), 6.93–6.88 (m, 2H), 4.58 (s, 2H), 0.33
(s, 9H); δC (125 MHz, CDCl3) 169.0, 157.6, 129.4, 121.4, 114.5, 65.6, −0.5.
16

ACCEPTED MANUSCRIPT
Trimethylsilyl 2-(phenythio)acetate5g 8i
7i (1.68 g, 10 mmol), HMDS (3.23 g, 20 mmol), I2 (0.23 g, 0.9 mmol); brown oil, (1.96 g, 82%); IR
(neat) 2960, 1711, 1584, 1482, 1439, 1408, 1284, 1252, 1175, 1132, 942, 843, 761, 738, 689 cm ˗1; δH
(500 MHz, CDCl3) 7.42–7.37 (m, 2H), 7.32–7.26 (m, 2H), 7.24–7.18 (m, 1H), 3.64 (s, 2H), 0.24 (s,
9H); δC (125 MHz, CDCl3): δ 169.7, 135.1, 129.8, 128.9, 126.7, 38.1, −0.5.
Trimethylsilyl 3-phenylpropanoate59 8j
7j (1.50 g, 10 mmol), HMDS (1.61 g, 10 mmol), I2 (0.075 g, 0.3 mmol); yellow oil, (1.13 g, 50%); IR
(neat) 2959, 1714, 1497, 1454, 1417, 1368, 1295, 1252, 1184, 1078, 946, 846, 763, 727, 698 cm ˗1; δH
(500 MHz, CDCl3) 7.23–7.17 (m, 2H), 7.14–7.09 (m, 3H), 2.85 (t, J = 7.6 Hz, 2H), 2.55 (t, J = 7.6 Hz,
2H), 0.19 (s, 9H); δC (125 MHz, CDCl3) 173.4, 140.6, 128.4, 128.2, 126.1, 37.3, 31.0, −0.3.
Trimethylsilyl 3-(4-((trimethylsilyl)oxy)phenyl)propanoate59 8k
7k (1.66 g, 10 mmol), HMDS (3.23 g, 20 mmol), I2 (0.075 g, 0.3 mmol); yellow oil, (2.87 g, 92%); IR
(neat) 2960, 1715, 1610, 1510, 1248, 1184, 1101, 913, 839, 759, 733 cm ˗1; δH (500 MHz, CDCl3)
7.09–7.04 (m, 2H), 6.79–6.74 (m, 2H), 2.86 (t, J = 7.5 Hz, 2H), 2.60 (t, J = 7.5 Hz, 2H), 0.26 (s, 9H),
0.25 (s, 9H); δC (125 MHz, CDCl3) 173.5, 153.4, 133.5, 129.2, 119.9, 37.6, 30.2, 0.1, −0.3.
Trimethylsilyl 2-bromo-3-phenylpropanoate 8l
7l (2.30 g, 10 mmol), HMDS (1.61 g, 10 mmol), I2 (0.075 g, 0.3 mmol); slightly yellow oil, (1.39 g,
46%); [Found: C, 47.81; H 5.61. C12H17BrO2Si requires C, 47.84; H 5.69]; IR (neat) 2961, 1710, 1492,
1312, 1272, 1253, 1180, 1045, 977, 884, 832, 754, 727, 706, 653, 630 cm ˗1; δH (500 MHz, CDCl3)
7.32–7.19 (m, 5H), 4.37 (dd, J = 8.4 Hz, J = 7.0 Hz, 1H), 3.42 (dd, J = 14.1Hz, J = 8.4 Hz, 1H), 3.22
(dd, J = 14.1 Hz, J = 7.0 Hz, 1H), 0.26 (s, 9H); δC (125 MHz, CDCl3) 169.2, 136.9, 129.1, 128.5,
127.2, 47.2, 41.2, −0.6.
Trimethylsilyl 2,2-diphenylacetate62 8m
7m (1.59 g, 7.5 mmol), HMDS (1.82 g, 11.25 mmol), I2 (0.19 g, 0.75 mmol); yellow solid, (1.27 g,
60%), m.p. 76.1–76.3 ºC; IR (neat) 3025, 1701, 1497, 1449, 1411, 1308, 1282, 1250, 1222, 1198,
1168, 1079, 1033, 960, 913, 840, 747, 733, 695, 671, 637 cm ˗1; δH (500 MHz, CDCl3) 7.20–7.07 (m,
10H), 4.85 (s, 1H), 0.12 (s, 9H); δC (125 MHz, CDCl3) 172.7, 139.0, 128.6, 128.5, 127.1, 58.7, −0.4.
Trimethylsilyl 2,2-diphenylpropanoate 8n
7n (1.70 g, 7.5 mmol), HMDS (2.42 g, 15 mmol), I2 (0.19 g, 0.75 mmol); transparent oil, (1.32 g,
59%); [Found: C, 72.18; H 7.59. C18H22O2Si requires C, 72.44; H 7.43]; IR (neat) 2959, 1708, 1600,
1494, 1445, 1375, 1249, 1219, 1190, 1120, 1104, 1076, 1055, 1029, 901, 847, 789, 732, 698, 660 cm
˗1; δH (500 MHz, CDCl3) 7.24–7.11 (m, 10H), 1.82 (s, 3H), 0.14 (s, 9H); δC (125 MHz, CDCl3) 175.1,
144.5, 128.0, 127.9, 126.6, 57.4, 27.0, −0.5.
Trimethylsilyl 4-oxo-4-phenylbutanoate 8o
7o (1.78 g, 10 mmol), HMDS (1.61 g, 10 mmol), I2 (0.075 g, 0.3 mmol); yellow-orange oil, (0.85 g,
34%); [Found: C, 62.04; H 7.18. C13H18O3Si requires C, 62.37; H 7.25]; IR (neat) 2961, 1714, 1686,
1596, 1448, 1401, 1357, 1252, 1218, 1171, 887, 842, 761, 731, 688 cm-1; δH (400 MHz, CDCl3) 7.99–
7.93 (m, 2H), 7.57–7.51 (m, 1H), 7.47–7.40 (m, 2H), 3.25 (t, J = 6.6 Hz, 2H), 2.76 (t, J = 6.6 Hz, 2H),
0.27 (s, 9H); δC (100 MHz, CDCl3) 198.1, 173.3, 136.5, 133.0, 128.5, 127.9, 33.4, 29.7, −0.4.
(E)-Trimethylsilyl 3-phenylacrylate59 8p
7p (1.48 g, 10 mmol), HMDS (1.61 g, 10 mmol), I2 (0.075 g, 0.3 mmol); yellow oil, (1.81 g, 82%); IR
(neat) 2959, 1687, 1633, 1449, 1315, 1298, 1279, 1252, 1202, 1184, 974, 843, 770, 736, 710, 683 cm
17

ACCEPTED MANUSCRIPT
˗1; δH (500 MHz, CDCl3) 7.65 (d, J = 15.9 Hz, 1H), 7.54–7.49 (m, 2H), 7.41–7.34 (m, 3H), 6.42 (d, J =
15.9 Hz, 1H), 0.37 (s, 9H); δC (125 MHz, CDCl3) 167.0, 145.2, 134.4, 130.1, 128.8, 128.0, 119.8,
−0.2.
(E)-Trimethylsilyl 3-(4-methoxyphenyl)acrylate59 8q
7q (1.07 g, 6 mmol), HMDS (0.97 g, 6 mmol), I2 (0.05 g, 0.20 mmol); brown oil, (0.54 g, 36%); IR
(neat) 2959, 1682, 1630, 1602, 1575, 1511, 1463, 1442, 1422, 1321, 1301, 1286, 1247, 1204, 1169,
1030, 977, 825, 784, 762, 724 cm ˗1; δH (500 MHz, CDCl3) 7.59 (d, J = 15.8 Hz, 1H), 7.49–7.43 (m,
2H), 6.92–6.87 (m, 2H), 6.28 (d, J = 15.8 Hz, 1H), 3.83 (s, 3H), 0.35 (s, 9H); δC (125 MHz, CDCl3)
167.4, 161.3, 144.9, 129.7, 127.1, 117.3, 114.3, 55.3, −0.1.
(E)-Trimethylsilyl 3-(3,4-dimethoxyphenyl)acrylate54 8r
7r (1.04 g, 5 mmol), HMDS (0.81 g, 5 mmol); yellow, viscous oil, (1.28 g, 91%); IR (neat) 2958,
1682, 1627, 1598, 1510, 1464, 1420, 1294, 1250, 1179, 1158, 1137, 1024, 976, 841, 806, 760, 723 cm
˗1; δH (500 MHz, CDCl3): δ 7.48 (d, J = 15.8 Hz, 1H), 7.00–6.91 (m, 2H), 6.77–6.71 (m, 1H), 6.19 (d,
J = 15.8 Hz, 1H), 3.79 (s, 3H), 3.78 (s, 3H), 0.27 (s, 9H); δC (125 MHz, CDCl3) 166.9, 150.7, 148.8,
144.9, 127.1, 122.3, 117.2, 110.7, 109.3, 55.5, 55.4, −0.4.
(E)-Trimethylsilyl 3-(3,4,5-trimethoxyphenyl)acrylate59 8s
7s (1.19 g, 5 mmol), HMDS (4.04 g, 25 mmol), I2 (0.11 g, 0.45 mmol); yellow solid, (0.77 g, 50%),
m.p. 75.9–78.5 ºC; IR (neat) 2968, 2942, 1674, 1580, 1505, 1464, 1420, 1277, 1246, 1127, 979, 840,
703 cm ˗1; δH (300 MHz, CDCl3) 7.54 (d, J = 15.8 Hz, 1H), 6.74 (s, 2H), 6.31 (d, J = 15.8 Hz, 1H),
3.88 (s, 6H), 3.88 (s, 3H), 0.35 (s, 9H); δC (75 MHz, CDCl3) 166.9, 153.4, 145.1, 140.1, 130.0, 119.2,
105.3, 60.9, 56.1, −0.2.
Trimethylsilyl thiophene-2-carboxylate24 10a
9a (1.28 g, 10 mmol), HMDS (2.42 g, 15 mmol), I2 (0.23 g, 0.9 mmol); brown oil, (1.34 g, 67%); IR
(neat) 2961, 1685, 1524, 1416, 1360, 1296, 1272, 1252, 1229, 1096, 1076, 1035, 841, 767, 714, 654
cm ˗1; δH (400 MHz, CDCl3) 7.76 (dd, J = 3.8 Hz, J = 1.2 Hz, 1H), 7.54 (dd, J = 4.9 Hz, J = 1.2 Hz,
1H), 7.08 (dd, J = 4.9 Hz, J = 3.8 Hz, 1H), 0.39 (s, 9H); δC (100 MHz, CDCl3) 162.0, 135.7, 133.8,
132.6, 127.8, −0.2.
Trimethylsilyl 2-(thien-2-yl)acetate5g 10b
9b (1.42 g, 10 mmol), HMDS (1.61 g, 10 mmol), I2 (0.075 g, 0.3 mmol); brown oil, (1.13 g, 53%); IR
(neat) 2960, 1716, 1252, 1211, 1177, 940, 842, 761, 692 cm ˗1; δH (400 MHz, CDCl3) 7.22 (dd, J = 5.1
Hz, J = 1.3 Hz, 1H), 6.96 (dd, J = 5.1 Hz, J = 3.5 Hz, 1H), 6.91–6.94 (m, 1H), 3.84 (d, J = 0.7 Hz,
2H), 0.30 (s, 9H); δC (100 MHz, CDCl3) 170.8, 135.5, 126.6, 126.6, 124.9, 37.0, −0.3.
Trimethylsilyl 2-(thien-3-yl)acetate 10c
9c (1.42 g, 10 mmol), HMDS (1.61 g, 10 mmol); transparent oil, (1.89 g, 88%); IR (neat) 2960, 1713,
1409, 1252, 1195, 938, 841, 754, 710, 691, 611 cm ˗1; δH (400 MHz, CDCl3) 7.28 (dd, J = 5.0 Hz, J =
3.0 Hz, 1H), 7.16–7.12 (m, 1H), 7.04 (dd, J = 5.0 Hz, J = 0.9 Hz, 1H), 3.66 (s, 2H), 0.29 (s, 9H); δC
(100 MHz, CDCl3) 171.6, 134.0, 128.5, 125.5, 122.6, 37.3, −0.3; m/z (EI) 214 (6 M+), 199 (7), 97 (11),
75 (29), 73 (100%); HRMS (EI): M+, found 214.0485. [C9H14O2SSi]+ requires 214.0479.
Trimethylsilyl furan-2-carboxylate 10d
9d (1.12 g, 10 mmol), HMDS (3.23 g, 20 mmol), I2 (0.23 g, 0.9 mmol); yellow oil, (0.57 g, 31%); IR
(neat) 2960, 1697, 1578, 1473, 1394, 1309, 1254, 1230, 1182, 1124, 1077, 1013, 934, 842, 754, 726
cm ˗1; δH (400 MHz, CDCl3) 7.58–7.54 (m, 1H), 7.16–7.12 (m, 1H), 6.50–6.46 (m, 1H), 0.38 (s, 9H);
18

ACCEPTED MANUSCRIPT
δC (100 MHz, CDCl3) 158.2, 146.3, 145.7, 118.3, 111.8, −0.2; m/z (EI) 184 (7 M+), 169 (44), 125
(100), 95 (44%); HRMS (EI): M+, found 184.0551. [C8H12O3Si]+ requires 184.0551.
Trimethylsilyl furan-3-carboxylate 10e
9e (1.12 g, 10 mmol), HMDS (1.61 g, 10 mmol), I2 (0.075 g, 0.3 mmol); yellow oil, (0.69 g, 38%); IR
(neat) 2961, 1700, 1574, 1507, 1399, 1316, 1254, 1164, 1076, 1006, 966, 845, 797, 772, 732 cm ˗1; δH
(300 MHz, CDCl3) 7.96 (dd, J = 1.4 Hz, J = 0.6 Hz, 1H), 7.41–7.38 (m, 1H), 6.71 (dd, J = 1.8 Hz, J =
0.6 Hz, 1H), 0.35 (s, 9H); δC (75 MHz, CDCl3) 163.0, 148.3, 143.7, 120.9, 110.2, −0.2; m/z (EI) 184 (8
M+), 169 (46), 125 (100), 95 (56), 73 (7), 67 (6%); HRMS (EI): M+, found 184.0555. [C8H12O3Si]+
requires 184.0551.
Trimethylsilyl nicotinate42b 10f
9f (1.23 g, 10 mmol), HMDS (3.23 g, 20 mmol), I2 (0.23 g, 0.9 mmol); yellow oil, (1.19 g, 61%); IR
(neat) 2960, 1701, 1590, 1419, 1292, 1253, 1127, 1024, 845, 828, 763, 728, 700 cm ˗1; δH (300 MHz,
CDCl3) 9.17–9.12 (m, 1H), 8.73–8.67 (m, 1H), 8.26–8.19 (m, 1H), 7.36–7.29 (m, 1H), 0.34 (s, 9H);
δC (75 MHz, CDCl3) 165.0, 153.0, 151.2, 137.5, 127.1, 123.1, −0.4.
Trimethylsilyl 2-((t-butoxycarbonyl)amino)acetate 12a
11a (0.87 g, 5 mmol), HMDS (0.81 g, 5 mmol); transparent oil, (1.15 g, 93%); IR (neat) 3367, 2977,
1703, 1509, 1367, 1252, 1209, 1161, 1055, 953, 843, 762 cm ˗1; δH (300 MHz, CDCl3) 5.14–5.00 (m,
1H), 3.87–3.77 (m, 2H), 1.40 (s, 9H), 0.25 (s, 9H); δC (75 MHz, CDCl3) 170.5, 155.6, 79.6, 43.4, 28.2,
−0.4; m/z (EI) 247 (<1 M+), 191 (4), 158 (5), 73 (100), 57 (88%); HRMS (EI): [M−C4H8]+, found
191.0611. [C6H13NO4Si]+ requires 191.0609.
Trimethylsilyl 3-((t-butoxycarbonyl)amino)propanoate 12b
11b (0.95 g, 5 mmol), HMDS (0.81 g, 5 mmol); transparent oil, (1.23 g, 94%); IR (neat) 3368, 2977,
1710, 1505, 1366, 1251, 1165, 842, 762, 725 cm ˗1; δH (300 MHz, CDCl3) 5.12–4.96 (m, 1H), 3.37–
3.25 (m, 2H), 2.48 (t, J = 6.1 Hz, 2H), 1.40 (s, 9H), 0.25 (s, 9H); δC (75 MHz, CDCl3) 172.9, 155.8,
79.2, 36.2, 36.1, 28.3, −0.3; m/z (EI) 261 (<1 M+), 188 (7), 172 (5), 116 (15), 75 (35), 73 (33), 57
(100%); HRMS (EI): [M−C4H8]+, found 205.0773. [C7H15NO4Si]+ requires 205.0765.
(S)-Trimethylsilyl 2-((t-butoxycarbonyl)amino)-3-methylbutanoate 12c
24
11c (1.09 g, 5 mmol), HMDS (0.81 g, 5 mmol); transparent oil, (1.28 g, 88%), [α]D +9.5 (c 1.03,
CH2Cl2); IR (neat) 3367, 2966, 1707, 1497, 1365, 1253, 1209, 1159, 845, 763, 726 cm ˗1; δH (300
MHz, CDCl3) 5.08–4.93 (m, 1H), 4.22–4.08 (m, 1H), 2.21–2.03 (m, 1H), 1.41 (s, 9H), 0.92 (d, J = 6.9
Hz, 3H), 0.84 (d, J = 6.9 Hz, 3H), 0.26 (s, 9H); δC (75 MHz, CDCl3) 172.5, 155.7, 79.4, 59.3, 31.1,
28.2, 18.9, 17.4, −0.4; m/z (EI) 289 (<1 M+), 200 (<1), 188 (5), 172 (12), 116 (60), 73 (50), 57 (100%).
(S)-1-t-butyl 2-(trimethylsilyl)pyrrolidine-1,2-dicarboxylate 12d
24
11d (1.08 g, 5 mmol), HMDS (0.81 g, 5 mmol); transparent oil, (1.38 g, 96%); [α]D -62.5 (c 1.04,
CH2Cl2); IR (neat) 2975, 2881, 1728, 1699, 1391, 1365, 1252, 1201, 1159, 1118, 845, 763 cm ˗1; δH
(500 MHz, CDCl3) two forms of product in a relative ratio 2:1; 4.21 (minor), (dd, J = 8.9 Hz, J = 3.5
Hz, 1H), 4.13 (dd, J = 8.9 Hz, J = 3.9 Hz), 3.52–3.29 (m, 2H), 2.24–2.08 (m, 1H), 1.96–1.75 (m, 3H),
1.41 (minor) (s, 9H), 1.38, 0.25 (s, 9H), 0.24 (minor); δC (125 MHz, CDCl3) 173.3, 173.2, 154.2,
153.8, 79.6, 79.4, 59.9, 59.8, 46.4, 46.2, 30.7, 29.7, 28.3, 28.2, 24.2, 23.4, −0.4, −0.4; m/z (EI) 287 (<1
M+), 186 (7), 170 (12), 114 (63), 73 (36), 70 (100), 57 (63%).
(S)-Trimethylsilyl 2-((t-butoxycarbonyl)amino)-3-phenylpropanoate 12e
11e (1.33 g, 5 mmol), HMDS (0.81 g, 5 mmol); transparent, viscous oil, (1.62 g, 96%); [α]D24 +42.8 (c
1.15, CH2Cl2); IR (neat) 3351, 2976, 1708, 1496, 1365, 1253, 1163, 1053, 846, 763, 731, 699 cm ˗1; δH
19

ACCEPTED MANUSCRIPT
(300 MHz, CDCl3) 7.35–7.13 (m, 5H), 5.12–4.96 (m, 1H), 4.62–4.46 (m, 1H), 3.17–3.07 (m, 2H),
1.44 (s, 9H), 0.28 (s, 9H); δC (75 MHz, CDCl3) 171.9, 155.0, 136.3, 129.4, 128.3, 126.8, 79.6, 55.3,
38.1, 28.3, −0.4; m/z (EI) 337 (<1 M+), 236 (1), 220 (14), 91 (17), 73 (31), 57 (100%).
(S)-Trimethylsilyl 2-((t-butoxycarbonyl)amino)-3-(4-((trimethylsilyl)oxy)phenyl)propanoate 12f
11f (1.41 g, 5 mmol), HMDS (1.61 g, 10 mmol), I2 (0.04 g, 0.15 mmol); Slightly yellowish viscous
oil, (1.06 g, 50%); [α]D24 +11.4 (c 1.08, CH2Cl2); IR (neat) 3441, 2962, 1711, 1609, 1509, 1364, 1250,
1166, 914, 839, 757 cm ˗1; δH (300 MHz, CDCl3) 7.03–6.94 (m, 2H), 6.76–6.66 (m, 2H), 5.12–4.96 (m,
1H), 4.51–4.37 (m, 1H), 3.06–2.92 (m, 2H), 1.39 (s, 9H), 0.22 (s, 9H), 0.21 (s, 9H); δC (75 MHz,
CDCl3) 171.8, 154.9, 154.0, 130.3, 129.0, 119.7, 79.3, 55.2, 37.2, 28.2, 0.0, −0.5; m/z (EI) 425 (<1
M+), 308 (23), 179 (100), 73 (50), 57 (42).
Acknowledgments
We would like to express our gratitude to Prof. A. Togni, E. Pietrasiak and Mass Spectrometry
Laboratory at ETH Zurich, Switzerland for their kind, swift and generous response with HRMS
analyses. Prof. J. Cerkovnik for GC-MS analyses, Prof. D. Dolenc for a sample of 2-hydroxy-5-t-
butylbenzoic acid, and the Ministry of Education, Science and Sport for the financial support (P1-
0134) are gratefully acknowledged.
Supplementary data
1
Copies of H, 13C and 19F NMR spectra of all products and mass spectra of novel compounds are
provided.
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