Development of Palladium-Catalyzed Decarboxylative Allylation of

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Development of Palladium-Catalyzed Decarboxylative Allylation of Electron-Deficient Sulfones and Identification of Unusual Side Products Monica A. Gill, and Jeffrey M. Manthorpe J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00068 • Publication Date (Web): 09 Apr 2019 Downloaded from http://pubs.acs.org on April 10, 2019

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The Journal of Organic Chemistry

Development of Palladium-Catalyzed Decarboxylative Allylation of Electron-Deficient Sulfones and Identification of Unusual Side Products Monica A. Gill* and Jeffrey M. Manthorpe* Carleton University Department of Chemistry 1121 Colonel By Drive 203 Steacie Building Ottawa, Ontario K1B 3Z8 Canada [email protected] [email protected] Typical Products O O S Ar O O O S

F3C

PdCp(1-cinnamyl) PPh3

O

53%

H

16% O O S Ar

O O S Ar

O O S Ar

THF, 65 °C 5h

CF3

O O S Ar

7%

24% Atypical Products

Abstract: The use of sulfones as electron-withdrawing groups in substrates for palladiumcatalyzed

decarboxylative

allylation

was

explored.

A

previously

published

trifluoromethanesulfonyl-based substrate was highly reactive and selective under mild conditions,

but

the

substrate

scope

was

not

readily

expanded.

Instead,

3,5-

bis(trifluoromethyl)phenyl (BTMP) sulfones were employed, thereby simultaneously retaining

ACS Paragon Plus Environment

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Page 2 of 41

most of the electron deficiency and providing facile synthetic access. Optimization of the catalytic conditions to maximize the product distribution to a synthetically useful level of allylation product over the protonation side product proved extremely challenging, with inconsistent and irreproducible results afforded with Pd2(dba)3 as the palladium source. A variety of substrates were subjected to the optimized catalytic conditions of PdCp(1-cinnamyl) and XANTPHOS in THF at 50 °C for 30 minutes. These conditions were applicable to all substrates with the exception of the α,α-dimethyl allyl ester, which required more forcing conditions and afforded four products: the allylation and protonation products, as expected, along with a cyclopropylation product and an unprecedented pseudodimeric product. The mechanism for the formation of these unusual side products is considered.

Introduction The Tsuji-Trost allylic alkylation is a well-established method of metal-catalyzed C-C bond construction.1–3 The intramolecular decarboxylative variant is a powerful subset of these reactions.4 While palladium is the most commonly used metal, others, including iridium,5,6 rhodium, molybdenum and nickel,7 and ruthenium,8–11 have been used. The substrates for these reactions are generally allylic β-keto esters; however, the use of other electron-withdrawing O EWG ester, ketone, EWG = nitro, nitrile, Existing etc. Work Pd(0)

O

R R

EWG =

SO2R

Pd(0) O O S R R R

EWG R R

R = Ph (work by Tunge et al.) R = CF3, 3,5-bis(trifluoromethyl)phenyl (this work)

Scheme 1. Pd-Catalyzed Decarboxylative Allylation ACS Paragon Plus Environment

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groups (EWGs) has been reported (Scheme 1).12,13 We became interested in the possibility of using allylic α-sulfonyl esters as substrates for a palladium-catalyzed decarboxylative allylation; the use of a sulfur-based EWG would permit further manipulation of the homoallylic products either by C-S bond cleavage or by use of the sulfone function. Initial efforts were directed towards using triflyl (-SO2CF3) as the EWG. Substrate 1 was prepared via a one-pot triflation of sec-butyllithium with N-phenyltriflimide, followed by acylation of the α-triflyl carbanion with allyl chloroacetate. We were pleased to observe that treatment of 1 with 5 mol% Pd2(dba)3 and 20 mol% PPh3 in THF gave homoallylic sulfone 2 in high yield (92%) with short reaction times at room temperature (Figure 1).14,15 During the course of these studies, Tunge and Weaver published a report describing Pd-catalyzed decarboxylative allylation on similar phenyl sulfone systems such as 3;16 however, these substrates required noticeably more forcing conditions. Notably, a 1:1 ratio of allylation 4 to protonation 5 products was produced when PPh3 was employed as ligand; optimized conditions used BINAP and afforded products 4 and 5 in a ratio of 11.3:1. The analogous protonation side product was not observed with the triflone substrate. Due to the high selectivity for the allylation product and the mild reaction conditions, the allylation chemistry of strongly electron-withdrawing sulfones was further explored. O O S F3C

O O 1

O O O S Ph O Ph Ph 3

5 mol% Pd2(dba)3 20 mol% PPh3 THF, rt, 20 min

5 mol% Pd2(dba)3 10 mol% BINAP toluene, 95 °C, 12-15 h

O O S F3C

O O S F3C

2 92% yield O O S Ph

H

not observed

+

Ph Ph 4 84% yield

O O S Ph

H

Ph Ph 5

Lead results for this work Allylation product exclusively

Optimized results from Tunge et al. Allylation to protonation side product ratio 11.3:1

Figure 1. Pd-catalyzed decarboxylative allylation of triflones (top) & phenyl sulfones (bottom)



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Results and Discussion As we have described previously,15 exhaustive efforts were made to expand the substrate scope of allylic α,α-dialkylated triflylacetates. The acylation of triflone anions, other than that generated from sec-butyllithium and N-phenyltriflimide, was found to be quite challenging; extensive efforts to elaborate the substrate scope using other secondary alkyllithiums were fruitless. It was anticipated that 3,5-bis(trifluoromethyl)phenyl (BTMP) sulfones would provide a reasonable compromise between the level of electron deficiency imparted by the triflones and the requisite nucleophilicity of their corresponding anion to alkylate smoothly, thus allowing much greater synthetic versatility and permitting preparation of a wide variety of substrates. The utility of BTMP sulfones as an alternative to triflones had been demonstrated by Nájera and coworkers.17–20 It was envisioned that the desired substrates could be prepared from an esterification of 6,21 followed by a sulfide to sulfone oxidation, and alkylation (Figure 2). The esterification was more challenging than anticipated, with most standard methods failing. Even in the presence of large excess of allyl alcohol, the transesterification of the ethyl ester to the allyl ester failed to reach (a)

1. PivCl, pyridine DCM, MW, 80 °C O

Ar

S

HO OH

6

R2-X, K2CO3

O R1

2. (NH4)6Mo7O24•4H2O H2O2, t-BuOH

Ar

X

O

R1

DMF, rt

7X=S 8 X = SO2

O O O S Ar O R2 R2 9

R1

F3C = Ar CF3 (b) O O O S Ar O 8

NaH, R2-X R1 DMF, 0 °C - rt

O O O S Ar O R2 10

R3-X or NCS, K2CO3 R1

DMF, rt

O O O S Ar O R2 R3

R1

11

Figure 2. (a) Synthesis of α,α-dialkylated substrates; (b) Synthesis of differentially substituted substrates


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completion – a peculiar behavior of allylic esters that was discussed briefly in the original report of Ti(OiPr)4 promoted transesterifiation.22 Conversion of 6 to the corresponding acyl chloride and addition of allyl alcohol gave low yields of 7a, possibly resulting from undesired ketene formation. Several mixed anhydride methods were attempted (ethyl chloroacetate, phenyl chloroacetate and Boc2O) but were plagued by displacement of allyl alcohol by the corresponding alcohol generated from the mixed anhydride (ethanol, phenol and tert-butanol, respectively). Armed with the understanding of the strong tendency for the allylic ester products to undergo transesterification, a new mixed anhydride esterification method was developed specifically for this work.21 Use of a pivaloyl mixed anhydride suppressed transesterification and provided synthetically useful amounts of the desired allylic esters; beneficially, this method required only 1 equivalent of the allylic alcohol, which was quite useful when using more precious allylic alcohols. Sulfides 7a-f were prepared in good to excellent yield (Table 1). Conditions for sulfide oxidation were then explored. The use of Oxone resulted in decomposition, while use of FeCl3/H5IO623 or MnSO4/H2O224 resulted largely in sulfoxide formation. However, chemoselective formation of sulfone was observed using catalytic ammonium molybdate and aqueous H2O2 as reoxidant.25 Use of tert-butanol as solvent was critical to suppress transesterification of the product, which was observed when i-PrOH and MeOH were used. Sulfones 8a-f were prepared in generally excellent yield. Table 1. Summary of results from preparation of α,α-dialkylated substrates Entry 1

HO

R1

Sulfide 7 (Yield) 7a (89%)

Sulfone 8 (Yield) 8a (86%)

R2-X

Prod (Yield)

BnBr

9a (98%) 2

MeI



Page 6 of 41

9b (95%) 3

EtI

4

PrI

5

n-hexylBr

9c (92%)

9d (90%)

9e (48%) 6

9f (27%) 7

9g (53%) 8

9h (89%) 9

7b (80%)

8b (99%)

BnBr

10

7c (75%)

8c (85%)

BnBr

11

7d (65%)

8d (94%)

BnBr

12

7e (76%)

8e (80%)

BnBr

9i (90%)

9j (94%)

9k (89%)

9l (75%)


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Similar to the findings of Tunge and Weaver16 in their studies of α,α-dialkylated phenyl sulfones, optimal results for dialkylation of BTMP sulfones 8 were achieved using K2CO3 and dry DMF. The crude reaction mixtures were typically quite clean and required column chromatography only to remove any residual alkyl halide and DMF. The yields of 9a-l were good to excellent, especially when activated electrophiles (such as benzyl bromide, methyl iodide, and allyl bromide) were employed. For less activated electrophiles (such as 1-bromohexane 9e and 1,6-dibromohexane 9f), the yields were substantially reduced despite longer reaction times and the addition of tetrabutylammonium iodide. To access substrates that were differentially substituted (Figure 2b), monoalkylated compounds were prepared by changing the base to NaH, lowering the temperature and carefully controlling the stoichiometry of the alkyl halide. Monoalkylated compounds 10a and 10b were prepared in moderate yield. The compounds were then easily alkylated or chlorinated using K2CO3 in dry DMF to give differentially substituted 11a-d (Table 2). Table 2. Summary of results from preparation of differentially substituted substrates Entry

R2–X

1

BnBr

Monoalkylated 10 (Yield)

Electrophile MeI

10a (40%) 2

Product 11 (Yield)

11a (69%) AllylBr

11b (79%) 3

NCS



Page 8 of 41

11c (78%) 4

EtI

MeI

10b (60%)

11d (94%)

The α,α-dibenzyl allyl ester 9a was chosen for optimization studies. Initial experiments employed Pd2(dba)3 and PPh3 in THF, as was used with the triflone substrate 1. Difficulties were encountered, however, with the reproducibility of results. The ratio of allylation to protonation products was highly variable under apparently identical reaction conditions. Additionally, there were experiments in which there was zero consumption of starting material, whereas the previous iteration of the experiment had yielded promising results. The issue was eventually traced to the quality of Pd2(dba)3; in particular, the presence or absence of palladium nanoparticles. While studying the complex nature of Pd2(dba)3 in solution, Zalesskiy and Ananikov26 found that commercial samples of the catalyst often contained up to 40% Pd nanoparticles in a wide range of sizes (10-200 nm). They reported a simple 1H NMR assay to determine the purity of Pd2(dba)3 (determined by the relative amount of free versus bound dba), as well as a purification method. The assay of the commercial samples that had been used by us revealed that even larger amounts of Pd nanoparticles than had been reported were present (see SI for full details). Purification of Pd2(dba)3 according to that procedure was performed and while the assay results were improved, the samples still contained substantial quantities of free dba. (See Supporting Information for assays and photos.) It was decided to use an alternate palladium precatalyst. We were pleased to observe that the use of PdCp(1-cinnamyl), developed by Baird and coworkers,27 gave highly reproducible results. Consistent reactivity was observed in side-by-side reactions as well as reactions run on different days. Treatment of 9a with PdCp(1-cinnamyl) and PPh3 gave 12a in reasonable yield; protonation product 13 was also observed. A solvent screen (Table 3, entries


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1-10) showed that ethereal solvents such as THF and diethyl ether promoted the formation of allylation product 12a (entries 1 and 2), while also minimizing the formation of protonation product 13. Ligand screening (Table 3, entries 11-24) was performed in THF at room temperature to improve the allylation to protonation ratio. A range of mono- and bidentate ligands was evaluated. The use of XANTPHOS (entry 24) yielded the most promising results, but the ratio of allylation to protonation products was not yet synthetically useful. Finally, increasing the reaction temperature to 50 °C using XANTPHOS as ligand resulted in 92:8 ratio of allylation (12a) to protonation (13) products. Table 3: Optimization of solvent and ligand

O O S Ar

PdCp(1-cinnamyl) (10 mol%) Monodentate Ligand (20 mol%) or Bidentate Ligand (10 mol%)

O O

O O S Ar

solvent, rt 0.03 M, 18 h

Ph Ph

+

Ph Ph

9a

H

Ph Ph

12a

13

Entry

Solvent

Liganda

%9ab

%12ab

%13b

1

THF

PPh3

0

81

19

2

Et2O

PPh3

0

81

19

3

PhMe

PPh3

100

0

0

4

DCM

PPh3

0

33

67

5

1,4-Dioxane

PPh3

100

0

0

6

DCE

PPh3

100

0

0

7

MeCN

PPh3

100

0

0

8

DMF

PPh3

100

0

0

9

DME

PPh3

100

0

0

10

MTBE

PPh3

0

0

100


O O S Ar


Page 10 of 41

11

THF

BINAP

0

41

59

12

THF

MeO-BIPHEP

0

16

84

13

THF

dppf

100

0

0

14

THF

DPEphos

100

0

0

15

THF

SEGPHOS

0

16

84

16

THF

CyJohnPhos

100

0

0

17

THF

P(2-furyl)3

100

0

0

18

THF

dppb

100

0

0

19

THF

0

0

100

PPh2 PPh2

20

THF

PBu3∙HBF4

100

0

0

21

THF

MeO

100

0

0

P

3

MeO

a

22

THF

DACH-phenyl

100

0

0

23

THF

iPr-PHOX

100

0

0

24

THF

XANTPHOS

0

84

16

25

THFc

XANTPHOS

0

92

8

Ligand structures shown in SI. bRatios determined by relative integration of 1H NMR

signals. cReaction was conducted at 50 °C. Using these optimized conditions, the substrate scope was evaluated (Table 4). It was found that α,α-dialkylated allylic esters (entries 1-8) were converted to the desired allylation products in good yields. Substitution in the 2-position of the allyl group resulted in a reduced yield (entry 9) but was well tolerated in the 3-position (entry 10) in the crotyl-based substrate. Likewise, the cinnamyl-based substrate (entry 12) resulted in a good yield. Substitution in the 1-


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position (entry 11) yielded the linear product. However, the yield was appreciably lower than for the crotyl analogue (51% vs 77%). Protonation product 13 was also isolated (16%). The corresponding branched product was not observed in any reactions. The differentially substituted substrates (entries 13-16) gave excellent yields with one exception. Entry 16, substituted with a methyl and an ethyl group, gave a substantially reduced yield in comparison with the other substrates. It is interesting to compare this yield (57%) to that of the diethyl substrate 9c (entry 2) (76%). This small structural change in the substrate resulted in a dramatic drop in yield. In addition, the cycloheptyl substrate 9f (entry 7) can be viewed as similar to 9c, though less sterically demanding because of the lack of rotational freedom of the a-substituents. In light of this, the attenuated yield of 9f (65%) further establishes a relationship between steric demand of the a-substituents and yield. Table 4. Substrate Scope PdCp(1-cinnamyl) (10 mol%) XANTPHOS (10 mol%)

O O O S Ar O R2 R3

R1

THF, 50 °C, 30 min

O O S Ar R2 R3

9a-l; 11a-d

Entry

12a-l; 14a-d

Substrate

1-8 Ar

O O S

O

R2

R3

O

9a-h

Product O O S Ar R2 R3

12a-h

% Yielda a R2,R3 = CH2Ph, 79% b R2,R3 = Me, 0% c R2,R3 = Et, 76% d R2,R3 = n-Pr, 82% e R2,R3 = hexyl, 86% f R2,R3 = -(CH2)6-, 65% g R2,R3 = allyl, 85%


R1


h R2,R3 = CH2CO2Et, 88% 9 Ar

O O S

O

Bn

Bn

Ar

O

Bn

Ar

O O S

O

Bn

Bn

Ar

O

Ar

O O S

O

Bn

Bn

Bn

Bn

12j

Ar

O

Ar

O O S

O

Bn

Bn

51% (+16% 13)

O O S Bn

Bn

12j

9k 12

77%

O O S

9j 11

Bn

12i

9i 10

69%

O O S

Ph

O

Ar

76%

O O S

9l

Ph

12l 13 Ar

O O S

90%

O O Ph

14a

11a 14 Ar

O O S

O O

Ar

Ph

Ph

14b

11b 15 Ar

O O S

O O

Cl

84%

O O S

Ph

11c

Ar

90%

O O S Cl Ph

14c


Page 12 of 41

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16 Ar

O O S

O O

11d a

Ar

57%

O O S

14d

% Yield refers to purified, isolated material.

This difference in product distribution based on small structural changes was further amplified by the α,α-dimethyl substrate 9b. Even after prolonged reaction times, the optimized conditions only resulted in recovered starting material. It was noted, however, that the recovery was never quantitative. We theorized that a catalytically inactive intermediate might be formed with this substrate, thereby consuming the palladium early in the reaction. Analysis of the crude mixtures by 1H NMR suggested that there was a small amount of allyl-containing material that was neither starting material, nor expected products. All attempts at isolation of this material were unsuccessful. The complete consumption of dimethyl substrate 9b was achieved in 5 h by raising the temperature to reflux; however, an interesting product distribution was obtained (Figure 3). In addition to allylation 12b (53%) and protonation 15 (16%) products, two additional products were observed. A cyclopropylation product 16 (7%), as well as a pseudodimeric product 17 (24%) were isolated and characterized. Dramatic changes in reactivity based on small structural changes suggest a narrow kinetic window for different pathways leading to these products. Lupton and coworkers invoked a similar argument to explain the unexpected side products O O S Ar F3C

O O O S

O

PdCp(1-cinnamyl) (10 mol%) PPh3 (20 mol%) THF, 65 °C 5h

CF3

12b O O S Ar

9b

16

Figure 3. Product distribution from anomalous substrate 9b ACS Paragon Plus Environment

O O S Ar

H

15 O O S Ar

O O S Ar 17


Page 14 of 41

obtained from the decarboxylative allylation of propargyl carbazole allyl carbonates when subtle protecting group changes were made.28 There are a few examples of cyclopropyl products from allylation-type processes. Hegedus reported in 1980 that ester enolates attacked the central carbon of a (π-allyl)palladium complexes in THF/HMPA/Et3N to give excellent yields of cyclopropane products29 and Hoffmann reported on the formation of cyclopropanes via attack on the central carbon of (π-allyl)palladium complexes by a variety of stabilized nucleophiles in the mid-1990s.30–33 Satake

34

reported the

cyclopropylation of silyl ketene acetals by allyl acetate using an allylpalladium-pyridinylpyrazole complex. The allylation product was competitive. Finally, Hou reported on amide enolates attacking allylic carbonates in an enantioselective fashion using a Pd catalyst bearing a specialized ferrocenyl-based phosphine ligand.35 We believe the work described in this Article to be the first report of an intramolecular decarboxylative cyclopropylation. The pseudodimeric product 17 appears to be unprecedented. Stoltz and coworkers have shown that a Pd(II), 16-electron species with a σ-bound, η1-allyl ligand is the resting state in the decarboxylative allylation of β-ketoesters.36 By invoking a similar intermediate (18), which would originate from oxidation insertion of Pd(0) to 9b, one could envision a carboxylate-assisted C-H

O O S Ar

O

O O S Ar

Pd O

O O S Ar

H

H H Pd

O O O H S Ar O

12b

18

C

O O O Pd S Ar O

H

O O S Ar

19 –CO2

O O S Ar

O O S Ar

+

Pd(0)

17

Figure 4. Possible mechanism for formation of side product 17 ACS Paragon Plus Environment

O O S Ar

Pd 20

O O S Ar

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activation of the allylation product 12b via a concerted metalation deprotonation (CMD)-type mechanism (Figure 4).37 While this CMD step is theoretically reversible, it is also possible to form a second carboxylate-bound intermediate 19; this step would be irreversible since protonation of the allyl ligand would yield propene. Subsequent decarboxylation of 19 and reductive elimination from intermediate 20 would result in the pseudodimer 17 and regenerate Pd(0). It is currently unclear if the formation of these products offer insight into the mechanism of decarboxylative allylation, or if this is unique to substrate 9b. The differences in reactivity and product distributions for substrates with very small structural changes (9b vs 11d vs 9c) suggests that the atypical products are accessible via narrow kinetic window controlled by the steric and/or electronic nature of the substrate.

Conclusions A palladium-catalyzed decarboxylative allylation of electron-deficient sulfones has been developed. The presence of nanoparticles in commercial Pd2(dba)3 was found to be detrimental to this chemistry. Use of an alternate palladium precatalyst, PdCp(1-cinnamyl), was critical for reactivity and reproducibility. Solvent and ligand optimization were used to minimize the formation of the undesired protonation side product. The reaction gives homoallylic products in good to excellent yield at 50 °C with short reaction times. The major exception to this trend occurs when both α-positions contain methyl groups. At room temperature, it is proposed that a catalytically inactive species is formed, thus shutting down the catalytic cycle. The use of a higher temperature and a longer reaction time permitted the consumption of the starting material but gave a previously unobserved product distribution. Allylation, protonation, cyclopropylation and pseudodimeric products were isolated and characterized. This work highlights that the mechanism of palladium-catalyzed decarboxylative allylation is likely more complex than



previously accepted and suggests that multiple competing pathways may be occurring simultaneously.


Page 16 of 41

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Experimental Section General Methods: All reagents were purchased from commercial sources and were used as received, without further purification, unless otherwise noted. DCM, toluene and Et2O were distilled from CaH2 immediately prior to use. DME, MTBE, MeCN and DMF were distilled from CaH2 and stored over activated 4 Å molecular sieves under a nitrogen atmosphere. THF was distilled from lithium aluminum hydride or sodium/benzophenone prior to use. All alkyl halides were purified immediately prior to use by passage through a short column of activated basic alumina in a Pasteur pipet fitted with a cotton plug. Reactions were monitored by thin-layer chromatography (TLC) using glass-backed extra hard layer (60 Å) TLC plates from Silicycle and visualized by fluorescence quenching under ultraviolet (UV) light and/or staining using potassium permanganate or ceric ammonium nitrate. Microwave heating was performed in glass vials (crimp-sealed with a septum liner and a metal fastener) in a Biotage Initiator 2.5 instrument with temperature monitored by an external surface sensor; the absorption level set to normal. Flash column chromatographic (FCC) purification of products was performed either on Silia-P Flash silica gel from Silicycle using a forced flow of eluent by the method of Still et al.38 or by automated chromatography on a Biotage Isolera One equipped with a UV detector. Concentration in vacuo refers to rotary evaporation with a 40 °C water bath at the appropriate pressure for the given solvent. Yields refer to purified and spectroscopically pure compounds unless indicated as crude. NMR spectra were recorded on a Bruker Avance 300 MHz or Bruker Avance III 400 MHz or JEOL ECZS 400 MHz spectrometer. Chemical shifts are reported in parts per million (ppm). Spectra are referenced to the internal standard tetramethylsilane (TMS) (0.00 ppm). 19F NMR spectra are referenced to trifluorotoluene (–63.7 ppm). Infrared (IR) spectra were recorded on a Varian 1000 Scimitar Series or an ABB Bomem MB series



spectrometer and absorptions are given in wavenumbers (cm-1). High resolution mass spectrometry (HRMS) was performed on a Kratos Concept-11A mass spectrometer with an electron beam of 70 eV at the Ottawa-Carleton Mass Spectrometry Center at University of Ottawa, on a Bruker Maxis Impact Quadrupole-Time of Flight Mass Spectrometer in positive ESI mode at the McGill Chemistry Mass Spectrometry Center, or a SciEx Qstar XL hybrid quadrupole time-of-flight mass spectrometer in positive ESI mode at the Carleton Mass Spectrometry Center. Compounds 1-2,15 3-5,16 6, 7a-c, and 7e21 were prepared and characterized as previously reported. General Procedure for Esterification: A Biotage microwave vial was charged with a Tefloncoated stirbar and carboxylic acid 6 (1.0 equiv). DCM (0.5 M relative to carboxylic acid) was added to dissolve and the vial was sealed with a crimp top lid equipped with a septum. In sequence, pivaloyl chloride (1.0 equiv), base (2.0 equiv) and alcohol (1.0 equiv) were added by syringe through the septum. In the case of solid bases or alcohols, the final sealing of the tube was delayed until addition was complete. The vial was heated for the indicated time at the indicated temperature in the microwave reactor. The reaction mixture was then diluted with Et2O (3× the volume of DCM), causing a white precipitate to form. This was washed with ice cold 0.1 M H2SO4 (equal to volume of DCM). The layers were separated and the aqueous phase was extracted again with Et2O. The combined organic extracts were washed once with brine, then dried over anhydrous MgSO4, filtered and concentrated in vacuo. The crude product was purified via FCC using 5% EtOAc/hexanes. But-3-en-2-yl-2-((3,5-bis(trifluoromethyl)phenyl)thio)acetate (7d): Reaction Time & Temperature: 120 min, 80 °C. Base: Pyridine. Scale: 2.5 mmol. Yield: 579.0 mg, 65% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 7.80 (s, 2H), 7.69 (s, 1H), 5.77 (ddd, J = 16.8, 10.4, 6.0 Hz, 1H), 5.37 (quintet, J = 6.4 Hz, 1H), 5.23 (d, J = 16.8 Hz, 1H, unresolved additional fine coupling), 5.15 (d, J = 10.8 Hz, 1H, unresolved additional fine coupling), 3.73 (s, 2H), 1.30 (d, J


Page 18 of 41

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= 6.4 Hz, 3H). 13C{1H} NMR (CDCl3, 100 MHz): 167.9, 139.0, 136.6, 132.2 (q, J = 34 Hz), 128.5 (d, J = 3 Hz), 122.9 (q, J = 271 Hz), 120.1 (quintet, J = 4 Hz), 116.9, 73.1, 35.7, 19.6. 19F NMR (376 MHz): δ -64.0. IR (film): 3091, 2988, 2937, 1735, 1648, 1618, 1457, 1414, 1355, 1287, 1187, 1044. HRMS (ESI-TOF): m/z [M+Na]+ Calcd for C14H12F6NaO2S: 381.0360; Found: 381.0367. General Procedure for Sulfide Oxidation: Volumes are based on 1 mmol scale. The sulfide (1 equiv.) was dissolved in tert-butanol (0.4 M relative to sulfide), then ammonium molybdate tetrahydrate (0.1 equiv.) was added. Hydrogen peroxide (35% in water, 4 equiv.) was added via syringe, at which point the reaction mixture turned bright yellow. The reaction was stirred at room temperature until completion, as shown by TLC. The solvent was evaporated in vacuo, then the residue was partitioned in an equal volume of sat. NaHCO3(aq) (10 mL) and EtOAc (10 mL). The layers were separated, then the aqueous phase was extracted twice with EtOAc (10 mL each). The combined organic extracts were washed once with brine (15 mL), then dried over anhydrous MgSO4, filtered and concentrated in vacuo to yield a colorless or light yellow oil. Most substrates solidified to a waxy, off-white solid upon standing. Typically, the purity after this step was excellent and the compounds were used without further purification. Allyl 2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)acetate (8a): Scale: 9.0 mmol. Yield: 2.93 g, 86% (white solid). 1H NMR (CDCl3, 400 MHz): δ 8.42 (s, 2H), 8.19 (s, 1H), 5.83 (ddt, J = 17.2, 10.4, 6.0 Hz, 1H), 5.31 (2 overlapping dd, 2H), 4.61 (d, J = 6.0 Hz, 2H – some unresolved fine splitting observed), 4.24 (s, 2H).

13

C{1H} NMR (CDCl3, 100 MHz): 161.5, 141.3, 133.1 (q, J = 34

Hz), 130.3, 129.4 (unresolved fine splitting), 128.0 (quintet, J = 3 Hz), 122.3 (q, J = 272 Hz), 120.4, 67.3, 60.6. 19F NMR (376.5 MHz): δ -63.9. IR (film): 3086, 2950, 1740, 1361, 1283, 1151. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C13H10F6NaO4S 399.0102; Found 399.0091. 2-Methylallyl 2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)acetate (8b): Scale: 1.4 mmol. Yield: 539 mg, 99% (white solid). 1H NMR (CDCl3, 400 MHz): δ 8.42 (s, 2H), 8.18 (s, 1H), 4.96



(m, 1H), 4.95 (m, 1H), 4.53 (s, 2H), 4.25 (s, 2H), 1.71 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 161.5, 141.3, 138.3, 133.2 (q, J = 35 Hz), 129.4 (d, J = 4 Hz), 128.0 (unresolved fine splitting), 122.3 (q, J = 272 Hz), 114.9, 70.0, 60.6, 19.3. 19F NMR (376.5 MHz): δ -63.9. IR (film): 3088, 2949, 1731, 1362, 1189, 1152, 1129, 1101. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C14H12F6NaO4S 413.0258; Found 413.0238. But-2-en-1-yl-2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)acetate (8c): Scale: 1.1 mmol. Yield: 364.3 mg, 85% (white solid). 1H NMR (CDCl3, 400 MHz): δ 8.42 (s, 2H), 8.19 (s, 1H), 5.81 (m, 1H), 5.49 (dtq, J = 15.2, 6.8, 1.6 Hz, 1H), 4.68 (d, J = 7.2 Hz, 2H, cis isomer, 6%), 4.56 (d, J = 6.8 Hz, 2H trans isomer, 94%), 4.21 (s, 2H), 1.72 (dm, J = 6.4 Hz, unresolved fine coupling, 3H, trans isomer), 1.68 (m, 3H, cis isomer). 13C{1H} NMR (CDCl3, 100 MHz): δ 161.5, 141.3, 133.1 (q, J = 34 Hz), 129.4 (d, J = 3 Hz), 127.8 (unresolved fine splitting), 122.3 (q, J = 272 Hz), 123.2, 67.5, 60.6, 17.7. 19F NMR (376.5 MHz): δ -63.9. IR (film): 3088, 3012, 2951, 1731, 1396, 1363, 1285, 1285, 1153, 1127, 1101. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C14H12F6NaO4S 413.0258; Found 413.0246. But-3-en-2-yl 2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)acetate (8d): Scale: 1.3 mmol. Yield: 477.0 mg, 94% (white solid). 1H NMR (CDCl3, 400 MHz): δ 8.41 (s, 2H), 8.18 (s, 1H), 5.73 (ddq, J = 17.2, 10.4, 6.4 Hz, 1H), 5.33 (dt, J = 6.4, 6.4 Hz, 1H), 5.24 (d, J = 17.2 Hz, 1H), 5.18 (d, J = 10.4 Hz, 1H), 4.21 (s, 2H), 1.29 (d, J = 6.4 Hz, 3H). 13C{1H} NMR (CDCl3, 100 MHz): 161.0, 141.3, 135.9, 133.1 (q, J = 34 Hz), 129.4 (d, J = 4 Hz), 127.9 (quintet, J = 4 Hz), 122.3 (q, J = 272 Hz), 117.7, 74.3, 60.9, 19.5. 19F NMR (376 MHz): δ -63.9. IR (film): 3083, 3012, 2952, 1729, 1363, 1283, 1151, 1135, 1100. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C14H12F6NaO4S 413.0258; Found 413.0248. Cinnamyl 2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)acetate (8e): Scale: 1.5 mmol. Yield: 546.4 mg, 80% (white solid). 1H NMR (CDCl3, 400 MHz): δ 8.43 (s, 2H), 8.15 (s, 1H), 7.29-7.38 (mult, 5H), 6.64 (d, J = 16.0 Hz, some broadening of peaks, 1H), 6.16 (dt, J = 16.0, 6.8 Hz, 1H),


Page 20 of 41

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4.77 (dd, J = 6.4, 0.8 Hz, 2H), 4.25 (s, 2H). 13C{1H} NMR (CDCl3, 100 MHz): δ 161.6, 141.3, 136.2, 135.5, 133.6 (q, J = 34 Hz), 129.4 (d, J = 4 Hz), 128.7, 128.6, 127.9 (unresolved fine splitting), 126.7, 122.3 (q, J = 272 Hz), 120.8, 67.3, 60.5. 19F NMR (376 MHz): δ -63.9. IR (film): 3088, 3029, 2996, 2940, 1738, 1364, 1337, 1315, 1279, 1156, 1137, 1102. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C19H14F6NaO4S 475.0415; Found 475.0406. General Procedure for α,α-Dialkylation of Sulfones: Volumes are based on 1 mmol scale. An oven-dried round-bottom flask was charged with the appropriate sulfone (1 equiv). Under an inert atmosphere, dry DMF (10 mL) (0.1 M relative to sulfone) was added via syringe. Finely powdered anhydrous K2CO3 (5 equiv) was added to the reaction mixture in a single portion. The reaction mixture was allowed to stir for 15 minutes at room temperature. Typically, the reaction mixture turned yellow in color during this time. Purified alkyl halide (5 equiv, if volatile; 2.3 equiv, if not) was added via syringe to flask. The reaction mixture stirred at room temperature until deemed complete by TLC. The reaction mixture was diluted with water (50 mL) (5x volume of DMF), then extracted five times with EtOAc (10 mL each). The combined organic extracts were washed once with water, once with brine, then dried over anhydrous MgSO4, filtered and concentrated in vacuo. The material was purified by FCC (typically 5% EtOAc/hexane) to give the desired product. Allyl 2-benzyl-2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)-3-phenylpropanoate (9a): Scale: 6.64 mmol. Yield: 3.66 g, 98% (colorless oil, may solidify upon standing). 1H NMR (CDCl3, 400 MHz): δ 8.16 (s, 2H), 8.02 (s, 1H), 7.21 – 7.22 (m, 10H), 5.81 (ddt, J = 17.2, 10.8, 6.0 Hz, 1H), 5.34 (br s, 1H), 5.28 – 5.30 (m, 1H), 4.62 (d, J = 6.0 Hz, 2H), 3.52 (d, J = 14.0 Hz, 2H), 3.44 (d, J = 14.0 Hz, 2H). 13C{1H} NMR (CDCl3, 100 MHz): 167.1, 141.4, 133.7, 132.1 (q, J = 34 Hz), 131.04 (d, J = 4 Hz), 130.95, 130.0, 122.4 (q, J = 271 Hz), 120.7, 79.4, 67.2, 39.6. 19F NMR (376.5 MHz): δ –63.6. IR (film): 3091, 3070, 3035, 2936, 1738, 1650, 1625, 1603, 1497, 1456,



1427, 1357, 1334, 1280, 1186, 1145, 1098, 1032. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C27H22F6NaO4S 579.1041; Found 579.1054. Allyl 2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)-2-methylpropanoate (9b): Scale: 0.66 mmol. Yield: 252.9 mg, 95% (colorless oil, may solidify). 1H NMR (CDCl3, 400 MHz): δ 8.32 (s, 2H), 8.18 (s, 1H), 5.86 (ddt, J = 16.3, 10.5, 5.9 Hz, 1H), 5.39 – 5.26 (m, 2H), 4.62 (dt, J = 5.9, 1.3 Hz, 2H), 1.69 (s, 6H). 13C{1H} NMR (CDCl3, 100 MHz): 168.0, 138.7, 132.5 (q, J = 35 Hz), 130.9 (d, J = 3 Hz), 130.4, 127.7 (quintet, J = 3 Hz), 122.4 (q, J = 272 Hz), 119.9, 69.9, 67.1, 20.0. 19F NMR (376.5 MHz): δ –63.8. IR (film): 3090, 2995, 2950, 1745, 1651, 1626, 1606, 1470, 1393, 1360, 1334, 1316, 1281, 1181, 1137, 1097. HRMS (ESI/Q-TOF) m/z: [M+Na]+ Calcd for C15H14F6NaO4S 427.0415; Found 427.0418. Allyl 2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)-2-ethylbutanoate (9c): Scale: 0.66 mmol. Yield: 261.8 mg, 92% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.29 (s, 2H), 8.15 (s, 1H), 5.83 (ddt, J = 17.2, 10.8, 6.0 Hz, 1H), 5.31 (d, J = 17.2 Hz, 1H), 5.28 (d, J = 10.4 Hz, 1H), 4.58 (d, J = 6.0 Hz), 2.27 (dq, J = 14.8, 7.6 Hz, 2H), 2.01 (dq, J = 14.8, 7.2 Hz, 2H), 1.09 (t, J = 7.2 Hz). 13C{1H} NMR (CDCl3, 100 MHz): 167.2, 139.9, 132.4 (q, J = 34 Hz), 130.8 (d, J = 3 Hz), 130.4, 127.4 (quintet, J = 3 Hz), 122.4 (q, J = 272 Hz), 119.9, 77.8, 66.9, 23.5, 8.7. 19F NMR (376.5 MHz): δ -63.8. IR (film): 3089, 2983, 2950, 2892, 1743, 1729, 1453, 1359, 1332, 1315, 1281, 1228, 1186, 1145, 1096. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C17H18F6NaO4S 455.0728; Found 455.0726. Allyl 2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)-2-propylpentanoate (9d): Scale: 1.3 mmol. Yield: 538.2 mg, 90% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 5.83 (ddt, J = 16.4, 10.4, 6.0 Hz, 1H), 5.27 – 5.33 (m, 2H), 4.56 (d, J = 6.0 Hz, 2H), 2.11 (m, 2H), 1.90 (m,, 2H), 1.67 – 1.56 (m, 2H), 1.40 – 1.29 (m, 2H), 0.95 (t, J = 7.3 Hz, 6H). 13C{1H} NMR (CDCl3, 100 MHz): 167.4, 139.7, 132.3 (q, J = 35 Hz), 130.8 (d, J = 3 Hz), 130.5, 127.4 (quintet, J = 3 Hz), 122.4 (q, J = 272 Hz), 119.8, 66.8, 32.7, 17.5, 14.3. 19F NMR (376.5 MHz): δ –63.8. IR (film): 3089, 2970,


Page 22 of 41

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2939, 2879, 1745, 1731, 1651, 1626, 1605, 1467, 1359, 1334, 1315, 1281, 1187, 1149, 1098. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C19H22F6NaO4S 483.1041; Found 483.1032. Allyl 2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)-2-hexyloctanoate (9e): Scale: 0.53 mmol. Yield: 139.5 mg, 48% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.27 (s, 2H), 8.14 (s, 1H), 5.83 (ddt, J = 17.2, 10.4, 6.0 Hz, 1H), 5.27 – 5.33 (m, 2H), 4.56 (d, J = 6.0 Hz, 2H), 2.08 – 2.15 (m, 2H), 1.89 - 1.95 (m, 2H), 1.20 – 1.37 (m, 16H), 0.86 – 0.88 (m, 6H). 13C{1H} NMR (CDCl3, 100 MHz): 167.5, 139.7, 132.4 (q, J = 43 Hz), 130.8 (unresolved fine splitting), 130.5, 127.5, 122.4 (q, J = 280 Hz), 120.0, 76.7, 66.9, 31.3, 30.6, 29.6, 23.9, 22.5, 14.0. 19F NMR (376.5 MHz): δ –63.8. IR (film): 2959, 2926, 1732,1359, 1280, 1186, 1146, 1101. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C25H34F6NaO4S 567.1980; Found 567.1992. Allyl 1-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)cycloheptanecarboxylate (9f): Scale: 0.40 mmol. Yield: 50.0 mg, 27% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.25 (s, 2H), 8.14 (s, 1H), 5.85 (ddt, J = 17.2, 10.4, 6.0 Hz, 1H), 5.32 (d, J = 17.6 Hz + additional unresolved fine coupling, 1H), 5.29 (d, J = 10.0 Hz + additional unresolved fine coupling, 1H), 4.61 (d, J = 6.0 Hz, 2H), 2.25 – 2.40 (m, 4H), 1.81 – 1.87 (m, 2H), 1.43 – 1.64 (m, 6H). 13C{1H} NMR (CDCl3, 100 MHz): 167.9, 139.1, 132.4 (q, J = 35 Hz), 130.8 (unresolved fine coupling), 130.5, 127.5 (app t, J = 4 Hz), 122.4 (q, J = 272 Hz), 119.9, 77.6, 67.1, 30.9, 29.2, 23.4. 19F NMR (376.5 MHz): δ –63.8. IR (film): 3086, 2934, 2863, 1743, 1732, 1464, 1359, 1334, 1315, 1280, 1181, 1142, 1102. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C19H20F6NaO4S 481.0884; Found 481.0883. 2-allyl 1,3-diethyl 2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)propane-1,2,3-tricarboxylate (9g): Scale: 0.80 mmol. Yield: 233.0 mg, 53% (white solid). 1H NMR (CDCl3, 400 MHz): δ 8.33 (s, 2H), 8.20 (s, 1H), 5.83 (ddt, J = 17.2, 10.8, 6.0 Hz, 1H), 5.31 (overlapping doublets, 2H), 4.61 (d, J = 6.0 Hz, 2H), 4.22 – 4.17 (m, 4H), 3.44 (AB, J = 16.8 Hz, 2H), 3.36 (AB, J = 16.8 Hz, 2H), 1.31 (t, J = 7.2 Hz, 6H).

13

C{1H} NMR (CDCl3, 100 MHz): 168.9, 165.7, 137.3, 132.8 (q, J =



35 Hz), 131.1 (unresolved fine coupling), 130.2, 128.3, 122.3 (q, J = 272 Hz), 120.0, 72.6, 67.7, 61.5, 33.3, 13.9. 19F NMR (376.5 MHz): δ –63.9. IR (film): 3088, 2987, 2945, 2910, 1741, 1650, 1626, 1606, 1449, 1416, 1397, 1359, 1344, 1282, 1186, 1149, 1106, 1062, 1029. HRMS (ESITOF) m/z: [M+Na]+ Calcd for C21H22F6NaO8S 571.0837; Found 571.0845. Allyl 2-allyl-2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)pent-4-enoate (9h): Scale: 1.3 mmol. Yield: 527.3 mg, 89% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.30 (s, 2H), 8.16 (s, 1H), 5.89 – 5.78 (m, 3H), 5.35 – 5.18 (m, 6H), 4.59 (d, J = 6.0 Hz, 2H), 2.93 (dd AB, J = 14.4, 6.8 Hz, 2H), 2.80 (dd AB, J = 14.4, 6.8 Hz, 2H).

13

C{1H} NMR (CDCl3, 100 MHz): 166.5, 139.4, 132.5

(q, J = 34 Hz), 130.9 (d, J = 3 Hz), 130.3, 127.7 (quintet, J = 3 Hz), 122.4 (q, J = 271 Hz), 120.9, 76.0, 67.2, 35.0. 19F NMR (376.5 MHz): δ –63.8. IR (film): 3087, 3026, 2987, 2954, 1859, 1733, 1641, 1626, 1605, 1439, 1359, 1339, 1316, 1281, 1214, 1188, 1147, 1100. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C19H18F6NaO4S 479.0728; Found 479.0730. 2-Methylallyl 2-benzyl-2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)-3-phenylpropanoate (9i): Scale: 0.51 mmol. Yield: 261.6 mg, 90% (white solid). 1H NMR (CDCl3, 400 MHz): δ 8.14 (s, 2H), 8.01 (s, 1H), 4.97 (s, 2H), 4.54 (s, 2H), 3.54 (d, J = 14.0 Hz, 2H), 3.46 (d, J = 14.0 Hz, 2H), 1.62 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz): 167.2, 141.4, 138.0, 133.7, 132.2 (q, J = 35 Hz), 130.9, 128.3, 127.7, 127.2 (app t, J = 3 Hz), 122.4 (q, J = 272 Hz), 115.3, 79.4, 69.9, 39.5, 19.5. 19F NMR (376.5 MHz): δ –63.6. IR (film): 3090, 3035, 2935, 1736, 1660, 1625, 1603, 1497, 1455, 1357, 1335, 1315, 1280, 1187, 1147, 1098, 1033. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C28H24F6NaO4S 593.1197; Found 593.1184. But-2-en-1-yl 2-benzyl-2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)-3-phenylpropanoate (9j): Scale: 0.31 mmol. Yield: 166.3 mg, 94% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.16 (s, 2H), 8.02 (s, 1H), 7.21 (br s, 10H), 5.77 – 5.85 (m, 1H – mixture of cis/trans), 5.44 – 5.52 (m, 1H – mixture of cis/trans), 4.70 (d, J = 6.8 Hz, 2H, minor cis isomer – 5 %), 4.56 (d, J = 6.8 Hz, 2H, major trans isomer – 95%), 3.51 (d, J = 14.0 Hz, 2H), 3.42 (d, J = 14.0 Hz, 2H), 1.72 (d, J =


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6.4 Hz, 3H, major trans isomer), 1.68 (d, J = 7.6 Hz, 3H, minor cis isomer) . 13C{1H} NMR (CDCl3, 100 MHz): 167.1, 141.5, 133.8, 133.7, 132.0 (q, J = 34 Hz), 130.9 (broadened shoulder; overlapping peak likely), 128.2, 127.6, 127.1 (app t, J = 4 Hz), 122.3 (q, J = 272 Hz), 123.1, 79.2, 67.3 (major isomer), 61.9 (minor isomer), 39.5, 17.6 (major isomer), 13.0 (minor isomer). 19

F NMR (376.5 MHz): δ -63.6. IR (film): 3091, 3066, 3034, 2943, 1733, 1497, 1456, 1357,

1335, 1315, 1280, 1186, 1145, 1098. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C28H24F6NaO4S 593.1197; Found 593.1195. But-3-en-2-yl 2-benzyl-2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)-3-phenylpropanoate (9k): Scale: 0.49 mmol. Yield: 249.6 mg, 89% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.19 (s, 2H), 8.03 (s, 1H), 5.71 (ddd, J = 17.2, 10.4, 6.4 Hz, 1H), 5.39 (dq, J = 6.4, 6.4 Hz, 1H), 5.23 (d, J = 17.6 Hz, 1H), 5.18 (d, J = 10.8 Hz, 1H), 3.42 – 3.55 (m, 4H), 1.27 (d, J = 6.4 Hz, 3H). 13

C{1H} NMR (CDCl3, 100 MHz): 166.9, 141.3, 135.7, 133.74, 133.69, 132.0 (q, J = 5 Hz), 131.0

(d, J = 3 Hz), 130.9, 128.1, 127.59, 127.55, 127.1 (app t, J = 3 Hz), 122.4 (q, J = 271 Hz), 117.9, 79.1, 74.7, 39.5, 39.3, 19.3. 19F NMR (376 MHz): δ - 63.6. IR (film): 3091, 3067, 3035, 2987, 2936, 1726, 1625, 1603, 1497, 1456, 1358, 1336, 1315, 1280, 1187, 1145, 1099, 1034. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C28H24F6NaO4S 593.1197; Found 593.1201. Cinnamyl 2-benzyl-2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)-3-phenylpropanoate (9l): Scale: 0.19 mmol. Yield: 89.6 mg, 75% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.18 (s, 2H), 8.00 (s, 1H), 7.34 – 7.35 (m, 5H), 7.19 – 7.22 (m, 10H), 6.62 (d, J = 16.0 Hz, 1H), 6.13 (dt, J = 16.0, 6.8 Hz, 1H), 4.78 (d, J = 6.4 Hz, 2H), 3.53 (d, J = 14.0 Hz, 2H), 3.45 (d, J = 14.0 Hz, 2H).

13

C{1H} NMR (75 MHz): 167.3, 141.4, 136.5, 135.6, 133.7, 132.1 (q, J = 35 Hz), 131.1 (d, J

= 3 Hz), 131.0, 128.7, 128.6, 128.3, 127.8, 127.2 (quintet, J = 4 Hz), 126.8, 122.4 (q, J = 273 Hz), 120.6, 79.3, 67.2, 39.7.19F NMR (376.5 MHz): δ –63.6. IR (film): 3089, 3030, 2957, 1731, 1357, 1279, 1185, 1144, 1096, 1096. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C33H26F6NaO4S 655.1354; Found 655.1363.



General Procedure for Monoalkylation of Sulfones: Volumes are based on 1 mmol scale. A dry round-bottom flask was charged with the appropriate sulfone (1.0 mmol, 1 equiv). Under an inert atmosphere, dry DMF (10 mL) (0.1 M relative to sulfone) was added via syringe. Sodium hydride (dry) was added (1.1 equiv) to this solution in 2-3 portions. The reaction mixture was allowed to stir for 30 minutes at room temperature. Typically, the reaction mixture turned yellow in color during this time. All alkyl halides were purified immediately prior to use by passage over a short column of activated basic alumina in a Pasteur pipet fitted with a cotton plug. Purified alkyl halide (1.2 equiv. for BnBr; 1.3 equiv. for EtI) was added via syringe to the reaction flask. The reaction mixture was stirred at room temperature until deemed complete by TLC. The reaction mixture was quenched with saturated NH4Cl(aq) (2 mL), then diluted with water (50 mL) (5x volume of DMF), then extracted five times with EtOAc (10 mL each). The combined organic extracts were washed once with water, once with brine, then dried over anhydrous MgSO4, filtered and concentrated in vacuo. The material was purified by FCC (typically 5% EtOAc/hexane) to afford the desired product. Allyl 2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)-3-phenylpropanoate (10a): Scale: 0.53 mmol. Yield: 99.7 mg, 40% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.33 (s, 2H), 8.18 (s, 1H), 7.22 – 7.29 (m, 3H), 7.13 – 7.15 (m, 2H), 5.61 (ddt, J = 17.2, 10.8, 6.0 Hz, 1H), 5.15 (d, J = 10.8 Hz, 1H), 5.11 (dd, J = 17.2, 1.2 Hz, 1H), 4.45 (d, J = 6.0 Hz, 2H), 4.31 (dd, J = 11.2, 3.6 Hz, 1H), 3.50 (dd, J = 13.6, 3.6 Hz, 1H), 3.18 (dd, J = 11.6, 13.2 Hz, 1H). 13C{1H} NMR (CDCl3, 100 MHz): δ 164.5, 139.8, 134.5, 133.0 (q, J = 34 Hz), 130.9, 129.9 (d, J = 4 Hz), 129.0, 128.9, 128.0 (app t, J = 3 Hz), 127.7, 122.3 (q, J = 272 Hz), 119.8, 72.2, 67.0, 32.6. 19F NMR (376 MHz): δ –63.8. IR (film): 3092, 3038, 2949, 1742, 1360, 1342, 1318, 1281, 1189, 1145, 1104. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C20H16F6NaO4S 489.0571; Found 489.0570. Allyl 2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)butanoate (10b): Scale: 0.53 mmol. Yield: 128.4 mg, 60% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.32 (s, 2H), 8.17 (s, 1H), 5.80 (ddt,


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J = 17.2, 10.4, 6.4 Hz, 1H), 5.31 (d, J = 17.2 Hz, 1H), 5.27 (d, J = 10.8 Hz, 1H), 4.60 (d, J = 6.0 Hz, 2H), 3.98 (dd, J = 11.2, 3.6 Hz, 1H), 2.13 – 2.23 (m, 1H), 1.86 – 1.98 (m, 1H), 1.04 (t, J =7.2 Hz). 13C{1H} NMR (CDCl3, 100 MHz): δ 165.0, 139.8, 132.9 (q, J = 35 Hz), 130.4, 130.0 (unresolved fine coupling), 127.8 (unresolved fine coupling), 122.3 (q, J = 272 Hz), 120.2, 72.3, 67.1, 20.7, 11.4. 19F NMR (376 MHz): δ –63.9. IR (film): 3092, 2981, 2941, 2886, 1744, 1462, 1361, 1339, 1281, 1184, 1144, 1104. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C15H14F6NaO4S 427.0415; Found 427.0405. General Procedure for Differentially Substituted α,α-Dialkylated Sulfones: Volumes are based on 1 mmol scale. A dry round-bottom flask was charged with the appropriate monoalkylated sulfone 10a or 10b (1.0 mmol, 1 equiv). Under an inert atmosphere, dry DMF (10 mL) (0.1 M relative to sulfone) was added via syringe. Finely powdered anhydrous K2CO3 (5 equiv) was added to the reaction mixture in a single portion. The reaction mixture was allowed to stir for 15 minutes at room temperature. Typically, the reaction mixture turned yellow in color during this time. All alkyl halides were purified immediately prior to use by passage over a short column of activated basic alumina in a Pasteur pipet fitted with a cotton plug. Purified alkyl halide (5 equiv. for MeI and allyl bromide; 2.3 equiv. for BnBr) was added via syringe to flask. The reaction mixture stirred at room temperature until deemed complete by TLC. The reaction mixture was diluted with water (50 mL) (5x volume of DMF), then extracted five times with EtOAc (10 mL each). The combined organic extracts were washed once with water, once with brine, then dried over anhydrous MgSO4, filtered and concentrated in vacuo. The material was purified by FCC (typically 5% EtOAc/hexane) to yield the product. Allyl 2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)-2-methyl-3-phenylpropanoate (11a): Scale: 0.21 mmol. Yield: 69.7 mg, 69% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.34 (s, 2H), 8.19 (s, 1H), 7.21 – 7.27 (m, 3H), 7.05 – 7.08 (m, 2H), 5.80 (ddt, J = 17.6, 10.0, 6.0 Hz, 1H), 5.26 – 5.30 (m, 2H), 4.57 – 4.59 (m, 2H), 3.46 (d, J = 12.8 Hz, 1H), 3.12 (d, J = 12.8 Hz,



1H), 1.58 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 167.1, 138.7, 133.1, 132.6 (q, J = 34 Hz), 131.1 (d, J = 3 Hz), 130.3, 130.2, 128.7, 127.8, 122.4 (q, J = 272 Hz), 120.0, 74.6, 67.2, 39.0, 15.4. 19F NMR (CDCl3, 282 MHz): –63.9. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C21H18F6NaO4S 503.0728; Found 503.0722 .

Allyl 2-benzyl-2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)pent-4-enoate (11b): Scale: 0.30 mmol. Yield: 120.0 mg, 79% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.35 (s, 2H), 8.15 (s, 1H), 5.93 – 6.03 (m, 1H), 5.82 (ddt, J = 16.8, 10.4, 6.4 Hz, 1H), 5.27 – 5.33 (m, 2H), 5.14 – 5.20 (m, 2H), 3.39 (d, J = 13.2 Hz, 2H), 3.34 (d, J = 13.2 Hz, 2H), 2.88 (dd, J = 16.0, 6.0 Hz, 1H), 2.77 (dd, J = 15.6, 7.6 Hz, 1H). 13C{1H} NMR (CDCl3, 100 MHz) 166.7, 140.0, 133.1, 132.4 (q, J = 35 Hz), 131.4, 131.3 (d, J = 4 Hz), 130.9, 130.2, 128.6, 127.9, 127.6 (quintet, J = 4 Hz), 122.4 (q, J = 272 Hz), 120.3, 120.0, 77.6, 67.2, 38.4, 35.4. 19F NMR (376 MHz): δ –63.8. IR (film): 3086, 2945, 1731, 1359, 1280, 1187, 1147, 1099. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C23H20F6NaO4S 529.0884; Found 529.0859. Allyl 2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)-2-chloro-3-phenylpropanoate (11c) The monobenzylated sulfone 11a (138 mg, 0.30 mmol, 1 equiv) was dissolved in THF (3 mL, 0.1 M relative to sulfone). Finely powdered K2CO3 (207 mg, 1.50 mmol, 5 equiv) was added, and the flask contents were stirred for 15 min at room temperature. N-Chlorosuccinimide (40 mg, 0.30 mmol, 1 equiv) was then added in a single portion. The reaction mixture was stirred overnight, then the solvent was removed in vacuo. The crude product was purified via FCC (5% EtOAc/hexane) to give 116 mg (78%) chlorinated product 11c as a colorless oil. 1H NMR (CDCl3, 400 MHz): δ 8.39 (s, 2H), 8.20 (s, 1H), 5.77 (ddt, J = 17.6, 10.8, 6.0 Hz, 1H), 5.26 (overlapping dd, 2H), 4.63 (dd, J = 12.8, 6.0 Hz, 1H), 4.55 (dd, J = 12.8, 6.0 Hz, 1H), 4.13 (d, J = 13.6 Hz, 1H), 3.52 (d, J = 13.6 Hz, 1H). 13C{1H} NMR (CDCl3, 100 MHz) 162.6, 137.1, 132.8 (q, J = 35 Hz), 131.5 (d, J = 3 Hz), 131.4, 129.6, 128.5, 128.3, 122.3 (q, J = 272 Hz), 88.6, 68.6,


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39.2.

19

F NMR (376 MHz): δ –63.8. IR (film): 3094, 3040, 2949, 1748, 1358, 1358, 1281, 1189,

1155, 1104. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C20H15ClF6NaO4S 523.0181; Found 523.0181. Allyl 2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)-2-methylbutanoate (11d): Scale: 0.29 mmol. Yield: 128.6 mg, 94% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 5.85 (ddt, J = 17.2, 11.6, 5.6 Hz, 1H), 5.35 - 5.28 (m, 2H), 4.56 – 4.66 (m, 2H), 2.10 (dq, J = 13.2, 7.6 Hz, 1H), 1.94 (dq, J = 13.2, 7.2 Hz, 1H), 1.67 (s, 3H), 0.94 (t, J = 7.2 Hz). 13C{1H} NMR (CDCl3, 100 MHz): δ 167.3, 138.8, 132.5 (q, J = 35 Hz), 130.9 (unresolved), 130.5, 127.6 (septet, J = 4 Hz), 122.4 (q, J = 271 Hz), 120.0, 74.4, 67.1, 26.7, 15.2, 8.6. 19F NMR (376 MHz): δ –63.8. IR (film): 3092, 2992, 2949, 2886, 1748, 1735, 1360, 1334, 1314, 1281, 1179, 1148, 1093. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C16H16F6NaO4S 441.0571; Found 441.0570. General Procedure for Pd-Catalyzed Decarboxylative Allylation: Volumes are based on 0.14 mmol scale. A flame-dried Schlenk flask was charged with η5-cyclopentadienyl-η3-1phenylallylpalladium (10 mol %) and XANTPHOS (10 mol%), then the flask was purged and backfilled three times with argon. Freshly distilled THF (5 mL) (0.028 M relative to substrate) was added via syringe. The flask was immersed in a preheated 50 °C oil bath for 60 minutes to form the active catalyst. The substrate (1 equiv) was dissolved in 1 mL of dry THF and added dropwise to the catalyst solution via syringe. The reaction was stirred at 50 ˚C and was monitored by TLC until starting material was completely consumed (approx. 30 mins). The reaction was then quenched with brine (5 mL), then extracted three times with EtOAc (10 mL each). The combined organic extracts were washed once with brine (10 mL), then dried over anhydrous MgSO4, filtered and concentrated in vacuo. The crude residue was purified by FCC (2.5% - 10% EtOAc/hexanes). (2-allyl-2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)propane-1,3-diyl)dibenzene (12a): Scale: 0.14 mmol. Yield: 58.0 mg, 79% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.04 (s,



2H), 7.95 (s, 1H), 7.20 – 7.24 (m, 10H), 6.06 (ddt, J = 16.8, 10.4, 6.4 Hz, 1H), 5.29 (dd, J = 10.4, 1.6 Hz, 1H), 5.23 (dd, J = 16.8 Hz, 1.6 Hz, 1H), 3.34 (d, J = 14.0 Hz, 2H), 3.15 (d, J = 14.0 Hz, 2H), 2.63 (d, J = 6.8 Hz, some unresolved fine coupling, 2H). 13C{1H} NMR (CDCl3, 100 MHz): δ 141.1, 134.3, 131.9 (q, J = 34 Hz), 131.7, 131.3, 130.8 (d, J = 3 Hz), 128.4, 127.7, 126.9 (unresolved mult), 122.3 (q, J = 271 Hz), 120.6, 72.3, 39.1, 37.2. 19F NMR (376 MHz): δ –63.6. IR (film): 3089, 3032, 2930, 1357, 1328, 1309, 1280, 1186, 1141, 1098. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C26H22F6NaO2S 535.1142; Found 535.1162. 1-((3-ethylhex-5-en-3-yl)sulfonyl)-3,5-bis(trifluoromethyl)benzene (12c): Scale: 0.27 mmol. Yield: 79.6 mg, 76% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.32 (s, 2H), 8.14 (s, 1H), 5.82 (ddt, J = 17.2, 10.4, 6.8 Hz, 1H), 5.10 – 5.16 (overlapping dd, 2H), 2.46 (d, J = 6.8 Hz, 2H), 1.85 (dq, J = 15.2, 7.6 Hz, 2H), 1.76 (dq, J = 15.2, 7.2 Hz, 2H), 1.07 (t, J = 7.6 Hz, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 140.3, 132.6 (q, J = 34 Hz), 131.3, 130.5 (d, J = 3 Hz), 127.1 (septet, J = 3 Hz), 122.4 (q, J = 272 Hz), 119.5, 70.0, 37.0, 25.1, 8.21. 19F NMR (376 MHz): δ –63.9. IR (film): 3086, 2981, 2948, 2890, 1640, 1626, 1605, 1456, 1360, 1326, 1308, 1281, 1185, 1146, 1099. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C16H18F6NaO2S 411.0829; Found 411.0817. 1-((4-propylhept-1-en-4-yl)sulfonyl)-3,5-bis(trifluoromethyl)benzene (12d): Scale: 0.14 mmol. Yield: 47.5 mg, 82% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.31 (s, 2H). 8.15 (s, 1H), 5.81 (ddt, J = 17.2, 10.4, 6.8 Hz, 1H), 5.09 – 5.16 (overlapping dd, 2H), 2.46 (d, J = 6.8 Hz, 2H), 1.63 – 1.70 (m, 4H), 1.45 – 1.58 (m, 4H), 0.91 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 140.1, 132.6 (q, J = 34 Hz), 131.5, 130.5 (d, J = 3 Hz), 127.1 (septet, J = 3 Hz), 122.4 (q, J = 272 Hz), 119.5, 70.1, 37.7, 34.9, 16.9, 14.5. 19F NMR (376 MHz): δ –63.9. IR (film): 3089, 2968, 2878, 1359, 1280, 1186, 1143, 1098. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C18H22F6NaO2S 439.1142; Found 439.1135. 1-((7-allyltridecan-7-yl)sulfonyl)-3,5-bis(trifluoromethyl)benzene (12e): Scale: 0.53 mmol. Yield: 139.5 mg, 86% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.31 (s, 2H), 8.14 (s, 1H),


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5.81 (ddt, J = 17.2, 10.4, 6.8 Hz, 1H), 5.09 – 5.16 (overlapping doublets, 2H), 2.46 (d, J = 7.2 Hz, 2H), 1.65 – 1.69 (m, 4H), 1.46 – 1.47 (m, 4H), 1.20 – 1.35 (br s, w/ shoulder, 12H), 0.88 (t, J = 6.8 Hz, 6H). 13C{1H} NMR (CDCl3, 100 MHz): δ 140.1, 132.6 (q, J = 34 Hz), 131.5, 130.5 (unresolved fine coupling), 127.1 (unresolved fine coupling), 122.4 (q, J = 272 Hz), 119.5, 70.1, 37.6, 32.7, 31.5, 29.8, 23.4, 22.6, 13.9. 19F NMR (376 MHz): δ –63.9. IR (film): 3085, 2959, 2859, 1640, 1625, 1605, 1464, 1359, 1327, 1308, 1266, 1185, 1103, 1022. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C24H34F6NaO2S 523.2081; Found 523.2080. 1-allyl-1-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)cycloheptane (12f): Scale: 0.14 mmol. Yield: 37.7 mg, 65% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.33 (s, 2H), 8.15 (s, 1H), 5.93 (ddt, J = 17.2, 10.4, 7.6 Hz, 1H), 5.17 (d, J = 9.6 Hz, 1H), 5.10 (dd, J = 17.2, 1.2 Hz, 1H), 2.40 (d, J = 7.2 Hz, 2H), 2.25 (dd, J = 15.2, 10.0 Hz, 2H), 1.64 – 1.79 (m, 4H), 1.40 – 1.60 (m, 6H). 13

C{1H} NMR (CDCl3, 100 MHz): δ 139.7, 132.6 (q, J = 35 Hz), 132.0, 130.8 (unresolved fine

coupling), 127.1 (septet, J = 3 Hz), 122.4 (q, J = 272 Hz), 119.5, 70.4, 41.3, 32.9, 30.9, 23.4. 19F NMR (376 MHz): δ –63.8. IR (film): 3089, 2931, 2865, 1464, 1359, 1326, 1308, 1280, 1185, 1139, 1102. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C18H20F6NaO2S 437.0986; Found 437.0966. 1-((4-allylhepta-1,6-dien-4-yl)sulfonyl)-3,5-bis(trifluoromethyl)benzene (12g): Scale: 0.14 mmol. Yield: 54.3 mg, 85% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.35 (s, 2H), 8.15 (s, 1H), 5.89 (ddt, J = 17.2, 10.0, 7.2 Hz, 3H), 5.17 (d, J = 10.8 Hz, 3H), 5.16 (d, J = 17.2 Hz, 3H), 2.53 (d, J = 6.8 Hz, 6H). 13C{1H} NMR (CDCl3, 100 MHz): δ 139.7, 132.5 (q, J = 34 Hz), 131.1 (broadened; appears to be overlapping peaks), 127.5 (septet, J = 3 Hz), 122.4 (q, J = 272 Hz), 120.2, 69.0, 37.3. 19F NMR (376 MHz): δ –63.9. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C18H18F6NaO2S 435.0829; Found 435.0823. Diethyl 3-allyl-3-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)pentanedioate (12h): Scale: 0.14 mmol. Yield: 65.2 mg, 88% (white solid). 1H NMR (CDCl3, 400 MHz): δ 8.46 (s, 2H), 8.18 (s,



1H), 5.96 (ddt, J = 17.2, 10.0, 7.2 Hz, 1H), 5.22 (d, J = 10.0 Hz, 1H), 5.17 (d, J = 18.0 Hz, 1H), 4.11 (q, J = 7.2 Hz, 4H), 3.06 (d, J = 16.4 Hz, 2H), 2.99 (d, J = 16.8 Hz, 2H), 2.75 (d, J = 7.2 Hz, 2H), 1.28 (t, J = 7.2 Hz, 6H). 13C{1H} NMR (CDCl3, 100 MHz): δ 168.9, 138.5, 132.8 (q, J = 34 Hz), 131.1 (d, J = 4 Hz), 130.7, 127.8 (septet, J = 3 Hz), 122.4 (q, J = 272 Hz), 120.9, 67.3, 61.2, 37.8, 35.1, 13.9. 19F NMR (376 MHz): δ –63.8. IR (film): 3087, 2986, 1739, 1359, 1333, 1315, 1281, 1186, 1147, 1099. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C20H22F6NaO6S 527.0939; Found 527.0919. (2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)-2-(2-methylallyl)propane-1,3-diyl)dibenzene (12i): Scale: 0.16 mmol. Yield: 58.3 mg, 69% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 7.87 (s, 1H), 7.82 (s, 2H), 7.31 – 7.32 (m, 4H), 7.25 – 7.27 (m, 6H), 5.17 (s, 1H), 5.14 (s, 1H), 3.34 (s, 4H), 2.62 (s, 2H), 1.89 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 141.8, 139.7, 134.7, 131.7 (q, J = 34 Hz), 131.5, 130.3, 128.4, 127.7, 126.6 (unresolved fine coupling), 122.3 (q, J = 272 Hz), 118.2, 73.6, 40.5, 39.2, 26.0. 19F NMR (376 MHz): δ –65.5. IR (film): 3089, 3032, 2930, 1497, 1456, 1357, 1308, 1280, 1185, 1140, 1097. HRMS (ESI-TOF) m/z: [M+K]+ Calcd for C27H24F6KO2S 565.1038; Found 565.1048. (2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)-2-(but-2-en-1-yl)propane-1,3-diyl)dibenzene (12j): Scale: 0.14 mmol, Yield: 56.9 mg, 77% (colorless oil). 1H NMR (CDCl3, 300 MHz): δ 8.02 (s, 2H), 8.00 (s, minor isomer), 7.95 (s, 1H), 7.92 (s, minor isomer), 7.21-7.27 (m, 10H), 5.72 – 5.84 (m, minor isomer), 5.59 – 5.64 (m, 2H), 3.41 (d, J = 14.4 Hz, minor isomer), 3.34 (d, J = 14.1 Hz, 2H), 3.124 (d, J = 14.1 Hz, 2H), 3.116 (d, J = 14.1 Hz, 2H), 2.56 (m, 2H), 1.72 (d, J = 3.6 Hz, 3H), 1.54 – 1.57 (m, minor isomer). 13C{1H} NMR (CDCl3, 75 MHz): 141.6, 141.1 (minor isomer), 134.5, 134.4 (minor), 131.9 (q, J = 35 Hz), 131.3, 130.7 (d, J = 3 Hz), 130.5 (unresolved shoulder, minor isomer), 129.0 (minor isomer), 128.3, 127.8 (minor isomer), 127.6, 126.8 (quintet, J = 4 Hz), 123.8, 123.2 (minor isomer), 122.4 (q, J = 273 Hz), 72.6, 72.2 (minor isomer), 39.2, 36.0 (minor isomer), 30.4, 29.7 (minor isomer), 18.1, 13.2 (minor isomer). 19F


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NMR (CDCl3, 282.39 MHz): δ –63.6 (major isomer), - 63.7 (minor isomer), 3.8 : 1 ratio, based on integration. IR (film): 3089, 3066, 3033, 2922, 2858, 1625, 1603, 1497, 1455, 1437, 1357, 1326, 1307, 1279, 1185, 1140, 1098. HRMS (ESI/Q-TOF) m/z: [M+K]+ Calcd for C27H24F6KO2S 565.1038; Found 565.1019. (4-benzyl-4-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)pent-1-ene-1,5-diyl)dibenzene (12l): Scale: 0.14 mmol. Yield: 62.8 mg, 76% (colorless oil). 1H NMR (CDCl3, 300 MHz): δ 8.06 (s, 2H), 7.94 (s, 1H), 7.28 – 7.34 (m, 15H), 6.51 (d, J =15.9 Hz, broadened peaks, unresolved fine coupling, 1H), 6.14 (dt, J = 15.6, 6.6 Hz, 1H), 3.43 (d, J = 14.4 Hz, 2H), 3.26 (d, J = 14.1 Hz, 2H), 2.80 (dd, J = 6.6, 1.2 Hz, 2H). 13C{1H} NMR (CDCl3, 75 MHz): δ 141.3, 136.3, 135.2, 134.4, 132.1 (q, J = 35 Hz), 131.4, 130.6 (d, J = 3.4 Hz), 128.9 (minor isomer), 128.8 (minor isomer), 128.7 (quintet, J = 3.4 Hz), 128.5, 128.4 (minor isomer), 128.0, 127.7, 127.1 (minor isomer) 127.0, 126.3, 122.5, 122.3 (q, J = 274 Hz), 72.6, 39.2, 36.6. 19F NMR (CDCl3, 282.39 MHz) – 63.7 (major isomer), –64.0 (minor isomer) (19 : 1 ratio, based on integration). IR (film): 3065, 3032, 2932, 1953, 1884, 1830, 1734, 1623, 1602, 1496, 1455, 1350, 1307, 1279. HRMS (ESI/Q-TOF) m/z: [M+Na]+ Calcd for C32H26F6KO2S 627.1195; Found 627.1192. (2-((3,5-bis(trifluoromethyl)phenyl)sulfonyl)propane-1,3-diyl)dibenzene (13): White solid, 1

H NMR (CDCl3, 400 MHz): δ 8.04 (s, 2H), 7.85 (s, 1H), 7.08 – 7.15 (m, 6H), 6.40 – 6.96 (m,

4H), 3.80 (quintet, J = 6.8 Hz, 1H), 3.36 (dd, J = 14.4, 6.4 Hz, 2H), 2.98 (dd, J = 14.8, 6.8 Hz, 2H). 13C{1H} NMR (CDCl3, 100 MHz): δ 142.2, 136.3, 132.6 (q, J = 34 Hz), 128.83, 128.75, 128.6 (unresolved fine coupling), 127.1, 126.9 (quintet, J = 4 Hz), 122.2 (q, J = 272 Hz), 67.5, 33.7. 19F NMR (376 MHz): δ –63.9. IR (film): 3066, 3031, 2932, 1626, 1603, 1498, 1456, 1359, 1328, 1311, 1280, 1184, 1144, 1104, 1030. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C23H18F6NaO2S 495.0829; Found 495.0827.



1-((2-methyl-1-phenylpent-4-en-2-yl)sulfonyl)-3,5-bis(trifluoromethyl)benzene (14a): Scale: 0.15 mmol. Yield: 58.8 mg, 90% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.35 (s, 2H), 8.16 (s, 1H), 7.26 – 7.30 (m, 3H), 7.14 – 7.16 (m, 2H), 5.90 (ddt, J = 17.2, 10.4, 6.8 Hz, 1H), 5.16 (dd, J = 10.0, 1.2 Hz, 1H), 5.07 (dd, J = 16.8, 1.6 Hz, 1H), 3.16 (d, J = 13.6 Hz, 1H), 3.08 (d, J = 13.2 Hz, 1H), 2.46 (dd, J = 15.6, 7.2 Hz, 1H), 2.36 (dd, J = 15.6, 6.8 Hz, 1H), 1.29 (s, 3H). 13

C{1H} NMR (CDCl3, 100 MHz): δ 139.3, 134.0, 132.7 (q, J = 34 Hz), 131.7, 131.0, 130.9 (d, J

= 3 Hz), 128.4, 127.5, 127.3 (septet, J = 3 Hz), 122.4 (q, J = 272 Hz), 119.5, 67.4, 39.0, 38.3, 19.5. 19F NMR (376 MHz): δ –63.8. IR (film): 3086, 3032, 2983, 238, 1359, 1280, 1186, 1144. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C20H18F6NaO2S 459.0829; Found 459.0814. 1-((4-benzylhepta-1,6-dien-4-yl)sulfonyl)-3,5-bis(trifluoromethyl)benzene (14b): Scale: 0.18 mmol. Yield: 70.3 mg, 84% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.27 (s, 2H), 8.10 (s, 1H), 7.20 – 7.29 (m, 5H), 5.90 (ddt, J = 17.2, 10.4, 6.8 Hz, 2H), 5.20 (dd, J = 10.0, 1.2 Hz, 2H), 5.15 (dd, J = 17.2, 1.6 Hz, 2H), 3.22 (s, 2H), 2.51 (d, J = 6.8 Hz, 4H). 13C{1H} NMR (CDCl3, 75 MHz): δ 140.2, 134.2, 132.3 (q, J = 34 Hz), 131.6, 131.1, 128.5, 127.6, 127.3 (quintet, J = 4 Hz), 122.4 (q, J = 272 Hz), 120.1, 70.6, 38.0, 37.6. 19F NMR (CDCl3, 282 MHz): δ –63.9. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C22H20F6NaO2S 485.0986; Found 485.0967. 1-((2-chloro-1-phenylpent-4-en-2-yl)sulfonyl)-3,5-bis(trifluoromethyl)benzene (14c): Scale: 0.19 mmol. Yield: 89.7 mg, 90% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.41 (s, 2H), 8.16 (s, 1H), 7.31 (s, 5H), 5.83 (ddt, J = 16.8, 10.0, 6.8 Hz, 1H), 5.16 – 5.23 (overlapping dd, 2H), 3.64 (d, J = 14.0 Hz, 1H), 3.39 (d, J = 14.4 Hz, 1H), 2.91 (dd, J = 15.6, 6.8 Hz, 1H), 2.78 (dd, J = 15.6, 6.4 Hz, 1H). 13C{1H} NMR (CDCl3, 100 MHz): δ 137.9, 132.5 (q, J = 34 Hz), 132.2, 131.9, 131.8, 131.4, 130.2, 128.4, 128.1, 127.9 (septet, J = 3 Hz), 122.3 (q, J = 271 Hz), 120.7, 87.9, 40.9, 40.8. 19F NMR (376 MHz): δ –63.8. IR (film): 3089, 3035, 2932, 1359, 1342, 1316, 1281. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C19H15ClF6NaO2S 479.0283; Found 479.0285.


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1-((3-methylhex-5-en-3-yl)sulfonyl)-3,5-bis(trifluoromethyl)benzene (14d): Scale: 0.20 mmol. Yield: 41.9 mg, 57% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.32 (s, 2H), 8.16 (s, 1H), 5.82 (ddt, J = 17.6, 10.0, 7.6 Hz, 1H), 5.18 (d, J = 10.8 Hz, 1H), 5.15 (dd, J = 17.2, 1.2 Hz, 1H), 2.60 (dd, J = 14.8, 7.2 Hz, 1H), 2.37 (dd, J = 14.4, 7.2 Hz, 1H), 1.87 (dq, J = 14.4, 7.6 Hz, 1H), 1.71 (dq, J = 14.8, 7.6 Hz, 1H), 1.06 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 139.3, 132.7 (q, J = 35 Hz), 131.3, 130.6 (unresolved fine splitting), 127.2 (septet, J = 3 Hz), 122.4 (q, J = 272 Hz), 119.9, 66.7, 37.5, 26.4, 19.5, 8.3. 19F NMR (376 MHz): δ –63.8. IR (film): 3087, 2981, 2946, 1463, 1360, 1327, 1309, 1281, 1185, 1143, 1098. HRMS (ESI-TOF): m/z calcd for C15H16F6NaO2S: 397.0673; Found: 397.0649. Modified Procedure for Pd-Catalyzed Decarboxylative Allylation of 9b: A flame-dried Schlenk flask was charged with η5-cyclopentadienyl-η3-1-phenylallylpalladium (21.4 mg, 0.074 mmol, 0.1 equiv) and PPh3 (39.3 mg, 0.150 mmol, 0.2 equiv), then the flask was purged and backfilled three times with argon. Freshly distilled THF (26 mL) was added via syringe. The flask was immersed in a preheated 65 °C oil bath for 30 minutes to form the active catalyst. The substrate 10b (300 mg, 0.74 mmol, 1.0 equiv) was dissolved in 3 mL of dry THF and added dropwise to the catalyst solution via syringe. The reaction was stirred at 65 °C and was monitored by TLC until starting material was completely consumed (approx. 5 h). The reaction was then quenched with 20 mL brine and extracted three times with 30 mL EtOAc. The combined organic extracts were washed once with 50 mL brine, then dried over anhydrous MgSO4, filtered and concentrated in vacuo. The crude residue was purified by FCC (2.5% - 10% EtOAc/hexanes). 1-((2-methylpent-4-en-2-yl)sulfonyl)-3,5-bis(trifluoromethyl) benzene (12b): Yield: 140.8 mg, 53% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.33 (s, 2H), 8.17 (s, 1H), 7.29 (ddt, J = 16.8, 10.0, 7.2 Hz, 1H), 5.22 (d, J = 10.0 Hz, 1H), 5.15 (d, J = 16.8 Hz, 1H), 2.47 (d, J = 7.2 Hz), 1.32 (s, 6H). 13C{1H} NMR (CDCl3, 100 MHz): δ 138.6, 132.8 (q, J = 33 Hz), 130.7 (d, J = 3 Hz),



130.6, 127.3 (septet, J = 3 Hz), 122.4 (q, J = 272 Hz), 63.5, 39.2, 20.5. 19F NMR (376 MHz): δ – 63.8. IR (film): 3087, 2983, 2941, 1642, 1626, 1606, 1471, 1390, 1360, 1327, 1309, 1281, 1267, 1183, 1140, 1096. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C14H14F6NaO2S 383.0516; Found 383.0505. 1-(Isopropylsulfonyl)-3,5-bis(trifluoromethyl)benzene (15): Yield: 38.0 mg, 16% (white solid). 1H NMR (CDCl3, 400 MHz): δ 8.35 (s, 2H), 8.17 (s, 1H), 3.29 (septet, J = 6.8 Hz, 1H), 1.35 (d, J = 6.8 Hz, 6H). 13C{1H} NMR (CDCl3, 100 MHz): δ 140.1, 133.1 (q, J = 34 Hz), 129.4 (d, J = 4 Hz), 130.6, 127.4 (septet, J = 3 Hz), 122.4 (q, J = 272 Hz), 55.9, 15.5. 19F NMR (376 MHz): δ –63.9. IR (film): 3089, 2984, 2943, 1362, 1330, 1313, 1281, 1184, 1143, 1106, 1055. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C11H10F6NaO2S 343.0203; Found 343.0203. 1-((2-cyclopropylpropan-2-yl)sulfonyl)-3,5-bis(trifluoromethyl)benzene (16): Yield: 17.5 mg, 7% (colorless oil). 1H NMR (CDCl3, 300 MHz): δ 8.38 (s, 2H), 8.15 (s, 1H), 1.23 (s, 6H), 1.17 (tt, J = 8.4, 5.7 Hz, 1H), 0.44 – 0.50 (m, 2H), 0.14 – 0.19 (m, 2H). 13C{1H} NMR (CDCl3, 100 MHz): δ 140.1, 133.1 (q, J = 34 Hz), 129.4 (d, J = 4 Hz), 130.6, 127.4 (septet, J = 3 Hz), 122.4 (q, J = 272 Hz), 55.9, 15.5. 19F NMR (376 MHz): δ –63.7. IR (film): 3089, 3016, 2986, 2940, 2882, 1742, 1626, 1606, 1472, 1394, 1360, 1325, 1308, 1281, 1185, 1133, 1096. HRMS: (ESI-TOF) m/z: [M+Na]+ Calcd for C14H14F6NaO2S 383.0516; Found 383.0520. 5,5'-(2,4-dimethylhept-6-ene-2,4-diyldisulfonyl)bis(1,3-bis(trifluoromethyl) benzene) (17): Yield: 61.0 mg, 24% (colorless oil). 1H NMR (CDCl3, 400 MHz): δ 8.32 (s, 2H), 8.28 (s, 2H), 8.20 (unresolved s, 1H), 8.19 (unresolved s, 1H), 5.65 – 5.76 (m, 1H), 5.18 (d, J = 10.4 Hz, unresolved additional fine coupling, 1H), 5.07 (d, J = 16.8 Hz, unresolved additional fine coupling, 1H), 2.62 (dd, J = 7.6, 14.8 Hz, 1H), 2.49 (AB, J = 15.2 Hz, 1H), 2.38 (AB, J = 15.2 Hz, 1H), 2.14 (dd, J = 14.8, 6.8 Hz, 1H), 1.65 (s, 3H), 1.63 (s, 3H), 1.44 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 138.8, 137.9, 133.1 (q, J = 35 Hz), 133.0 (q, J = 35 Hz), 131.0 (unresolved fine coupling), 130.8 (unresolved fine coupling), 130.1, 127.8 (unresolved fine coupling), 127.6


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(unresolved fine coupling), 122.3 (q, J = 271 Hz), 122.2 (q, J = 271 Hz), 121.5, 67.4, 65.9, 41.8, 36.9, 22.3, 22.1, 21.3. 19F NMR (376 MHz): δ –63.8, –63.9. IR (film): 3089, 2984, 1359, 1326, 1309, 1281, 1268, 1185, 1143, 1095. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C25H22F12NaO4S2 701.0666; Found 701.0664. Supporting Information Structures of abbreviated ligands listed in Table 3. 1H and 13C{1H} NMR spectra for all new compounds. Acknowledgements This work was supported by NSERC (Discovery and RTI programs), Canada Foundation for Innovation (Leaders Opportunity Fund), Ontario Research Fund, Carleton University and the Government of Ontario (Ontario Graduate Scholarship for M.G.). References (1)

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Development of Palladium-Catalyzed Decarboxylative Allylation of

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