Neighboring Hydroxyl Group-Assisted Allylboration and Lewis Acid

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Neighboring Hydroxyl Group-Assisted Allylboration and Lewis Acid-Mediated Carbonyl-Ene Reaction for Access to Hapalindole Cyclohexane Core with Multiple Contiguous Stereogenic Centers Lu Li, Zhao Yang, Jiao Yang, Quanzheng Zhang, Qiuyuan Tan, Changhui Zhang, and Min Zhang J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02712 • Publication Date (Web): 09 Jan 2019 Downloaded from http://pubs.acs.org on January 9, 2019

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The Journal of Organic Chemistry

Neighboring Hydroxyl Group-Assisted Allylboration and Lewis Acid-Mediated Carbonyl-Ene Reaction for Access to Hapalindole Cyclohexane Core with Multiple Contiguous Stereogenic Centers Lu Li, Zhao Yang, Jiao Yang, Quanzheng Zhang, Qiuyuan Tan, Changhui Zhang and Min Zhang* Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Centre, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China O

OH

HO

OH

B

HFIP

+ RE

N Ts

RZ Ar RE

RZ

RE RZ

1) IBX

OH

B O

OH OH

2) LA

N Ts

N Ts Me

O

OH

Me

Me

OH

H

Ar HO M

Me O H

ABSTRACT：A neighboring hydroxyl group-assisted allylboration of 3-indolyl ketones with γ, γ-disubstituted allylboronic acids is reported, affording various 3-indolyl substituted homoallylic alcohols in good yields with excellent diastereoselectivies (up to >20:1 dr). The hydroxyl group not only played a vital role in the challenging allylboration but was elaborated for the subsequent construction of hapalindole cyclohexane core by a highly diastereoselective Lewis acid-catalyzed carbonyl-ene reaction. In the overall process, four contiguous stereogenic centers including two quaternary stereogenic centers were installed. Allylboration of carbonyl compounds represents one of the most efficient methods to build adjacent stereogenic centers, as it proceeds via a tight and highly organized Zimmerman-Traxler transition state.1 Due to the low reactivity of the commonly used allyl-BPin and allyl-BF3K, the stereoselective allylboration of ketones and ketimines with γ, γ-disubstituted allylboron reagents, which could provide direct access to chiral homoallylic alcohols with adjacent quaternary stereogenic centers, has met limited success.1 To improve the reactivity, Szabó and co-workers developed a practical method for the preparation of configurationally stable but more active γ, γ-disubstituted allylboronic acids from allyl alcohols,2a and the Aggarwal group realized the activation of γ, γ-disubstituted allylboronates by a treatment of n-BuLi/TFAA.3 Based on these methodology advancements, many ketones have been proved to be capable substrates.2,3 For the ketones substituted with the ubitigous indolyl group, however, only the activated 3-indolyl trifluoromethyl ketone was conducted with the γmonosubstituted allylboronate by Hoveyda and co-workers,4 allylboration of unactivated 3-indolyl ketones has not been explored. Recently, our group documented the first highly diastereoselective allylboration of ketimines with non-chiral γ,γdisubstituted allylboronic acids using the inexpensive chiral amino alcohol as the temporary auxiliary (Scheme 1a).5 The high reactivity and diastereoselectivity were attributed to the directing and rate-accelerating effect of the hydroxyl group of the chiral amino alcohol unit after a ligand exchange between the allylboronic acid and the hydroxyl group.5,6 Construction

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of adjacent quaternary stereogenic centers, especially by incorporating reaction partners in an intermolecular manner, remains a daunting challenge in modern organic synthesis.7 As our continuous interest in the construction of such structural motif particularly in complex molecular settings,8 we envisioned that the neighboring hydroxyl group-assisted strategy could be adapted for the allylboration of 3-indolyl hydroxylmethyl ketones. The hydroxyl group not only could functionalize as a directing group for the challenging allylboration, but also could be further utilized for the synthesis of cyclohexane core scaffold with multiple continuous stereogenic centers (Scheme 1b). As shown in Scheme 1c, such a core scaffold is widely distributed in a number of biologically active natural products, as exemplified by the indole alkaloids hapalindoles (9, 10) and welwitindolinones (11, 12).9 Due to the architectural complexity and notable biological profiles, numerous synthetic efforts have been devoted to the synthesis of these natural products.10 Since the core scaffolds of natural products have been referred as privileged structures for the development of novel drugs, development of efficient methods that enable rapid assembly of natural product core scaffolds, from the perspective of drug discovery, is of high value.11 Scheme 1. Neighboring Hydroxyl Group-Assisted Allylboration and Representative Indole Terpenoids a) Allylboration of ketimines assisted by the hydroxyl group (our previous work) HO

O

OH Ph

B

O + N H

RZ

1

OH

Ph

OH NH2 3

RE OH B

RE

RZ

2

O

H

NH

NH

N O Ph

4

N H

RZ RE O

b) Allylboration of ketones assisted by the neighboring hydroxyl group and Leiws acid-mediated carbonyl-ene rection to construct hapalindole core with adjacent quaternary stereogenic centers (this work) RE

OH

O +

2

RZ

HFIP

N 5a Ts

1) IBX

OH

OH OH

2) LA

N 6, 7 Ts

RZ Ar RE

N Ts Me

O B

H

Ar

OH

Me

Me

OH

HO M

O

8a

Me O H

c) Representative indole terpenoids containing polysubstituted cyclohexane motif Me

Me

Me H Me

SCN

H

H

Me

CN

H

H Me Me O

CN

O N H hapalindole Q (9)

N H

Cl Me

Cl

SCN

N H

O N

Me Me H O

N-methyl- Me hapalindolinone B welwitindolinone A welwitindolinone C (10) (11) isothiocyanate (12)

The initial attempts to validate the proposed allylboration were examined by the reaction of N-Ts-protected hydroxylmethyl 3-indolyl ketone 5a using the geranylboronic acid 2a as the allylboration reagent. To our delight, the desired allylboration product 6a was obtained in moderate yield with good diastereoselectivity in 24 h in the absence of any catalyst or additive (Table 1, entry 1). Encouraged by these results, and taking into account the fact that reaction additive might accelerate the reaction rate of the labile allylboronic acids thus improving the reaction yield,2f a variety of additives


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were then screened. The addition of t-BuOH did not improve the reaction efficiency, while the addition of acid AcOH resulted in slightly improved reaction rate, however, the strong acid TsOH produced reduced yield (entries 2–4). We were pleased to find that the fluorinated alcohols afforded much more improved results. When the reaction was carried out using 5 equivalents of HFIP as the additive, excellent yield and diastereoselectivity were obtained within a much shortened reaction time (1.5 h, entry 6).12 Changing the solvent from CH2Cl2 to other solvents did not improve the reaction efficiency (entries 7–9). Table 1. Reaction Optimizationa O

+ N 5a Ts

OH

OH B(OH)2 conditions

Me Me

Me 2a

entry additive solvent 1 none CH2Cl2 2 t-BuOH CH2Cl2 3 AcOH CH2Cl2 4 p-TsOH CH2Cl2 5 TFE CH2Cl2 6 HFIP CH2Cl2 7 HFIP toluene 8 HFIP THF 9 HFIP DMSO aConditions unless otherwise stated: 5a (0.1 mmol), 2a (0.15 mmol), mL). bIsolated yield of the major isomer 6a. cDetermined by 1H trifluoroethanol; HFIP = hexafluoroisopropyl alcohol.

Me

HO

Me N Ts

Me 6a

t (h) yieldb (%) d.r.c 24 75 >20:1 24 68 >20:1 12 82 >20:1 24 65 >20:1 24 90 >20:1 1.5 95 >20:1 4 95 >20:1 12 94 15:1 4 70 >20:1 additive (0.5 mmol), 4 Å molecular sieve (100 mg), solvent (3 NMR analysis of the crude reaction mixture. TFE = 2,2,2-

Having secured the optimal conditions, we then investigated the substitution scope of the hydroxylmethyl 3-indolyl ketones using the geranylboronic acid 2a and its configurational isomer nerylboronic acid 2b as the allylboration reagents (Table 2). Substrates with electron-donating or electron-withdrawing groups at the 5-position of the indolyl ring all underwent the allylboration efficiently, delivering the corresponding pairs of diastereomers in good yields and diastereoselectivities (entries 1–6). The substitution patterns had a negligible effect on the reactivity and diastereoselectivity, and substrates with the bromo atom on 4-, 5-, 6-, and 7-positions of indolyl ring were all tolerated in this cycloaddition (entries 5, 7, 8, 9), thus providing handles for the further derivation of these products. During this study, we observed that substrates without a N-Ts activating group led to much lower yield (entry 9).



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Table 2. Substrate Scopea OH Me

B(OH)2 Me

5

Me

2a HFIP

or

+ Me Me

X

Me 2b B(OH)2

4 Å MS CH2Cl2 0 °C

HO Me

Me

N 6 OH Ts or X 4 HO Me

Me

5

3

6

1

7

N Ts

Me 2

7

Me

with 2a with 2b yield (%) d.r. yield (%) d.r. 1 5a: X=H 95 (6a) >20:1 95 (7a) >20:1 2 5b: X=5-Me 90 (6b) >20:1 95 (7b) >20:1 3 5c: X=5-OMe 95 (6c) >20:1 95 (7c) >20:1 4 5d: X=5-Cl 81 (6d) >20:1 76 (7d) 19:1 5 5e: X=5-Br 95 (6e) 19:1 95 (7e) >20:1 6 5f: X=5-F 91 (6f) 16:1 91 (7f) >20:1 7 5g: X=4-Br 90 (6g) 16:1 90 (7g) 9:1 8 5h: X=6-Br 90 (6h) 16:1 90 (7h) >20:1 9b 5i: X=7-Br 62 (6i) 10:1 56 (7i) >20:1 10 5j: X=4-F 95 (6j) 13:1 95 (7j) >20:1 11 5k: X=6-F 92 (6k) 13:1 90 (7k) 10:1 aReaction conditions: 5 (0.1 mmol), 2a or 2b (0.15 mmol), HFIP (0.5 mmol), 4 Å molecular sieve (100 mg), CH Cl (3 mL), 0 °C, 2 2 1.5–12 h; yield is the isolated yield of the major isomer; d.r. was determined by 1H NMR or HPLC analysis of the crude reaction mixture. bNo N-Ts protecting group for 5i. entry

5

With a series of homoallylic alcohols 6 and 7 in hand, we envisioned that an intramolecular carbonyl-ene reaction of the corresponding aldehyde would result in a six-membered ring formation, thus providing hapalindole core scaffold with four continuous stereocenters. There are a number of precedents of Lewis acid-mediated intramolecular carbonyl-ene reaction of carbonyl compounds,13 to the best of our knowledge, however, aldehyde with an adjacent acid-labile, tertiary benzylic hydroxyl group has never been reported to be a substrate thus far. To validate the proposed challenging carbonylene reaction, a series of acids were screened using the in situ IBX-oxidized aldehyde 13a as the model substrate. Brønsted acids CSA and p-TsOH produced the expected product 8a in promising yields along with varied amount of the [1,2]-shift product 14 (Table 3, entries 1, 2). Among the Lewis acids screened, EtAlCl2 gave the best result presumably through the proposed fused chair transition state depicted in Table 3, producing 8a as the only observed diastereomer in 65% yield, while the commonly used Me2AlCl produced much lower yield of the expected product 8a despite with deduced amount of 14 (entries 4, 5). Under the optimal carbonyl-ene reaction conditions, 7a, 6c, 6e, 7c, and 7e were next investigated to briefly examine the application scope. All the substrates delivered the expected products with excellent diastereoselectivities (other diastereomers not observed) (Figure 1). The structure of the monoterpene core and the stereochemistry for the four contiguous stereogenic centers including two quaternary stereogenic centers were ascertained by the X-ray analysis of diastereomers 8c and 15c, and the same configuration was assigned to other products by analogy.


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Table 3. Reaction Optimization of the Carbonyl-Ene Reactiona Me

Me H Me O LA

HO

6a IBX

N Ts 13a

H

Me OH OH

Ar

O H HO M proposed TS O

N Ts 8a Me

acid

Me

Me OH

1,2-shift

Me

Me Me

N 14 Ts

entry 1 2 3

acid CSA p-TsOH ZnBr2

yield/% of 8ab 10 5 36

yield/% of 14b 20 5 trace

4

Me2AlCl

33

trace

5 aReaction

EtAlCl2 65 trace conditions: 13a (0.2 mmol), IBX (0.4 mmol), DMSO (2 mL), rt; then acid (0.2 mmol), CH2Cl2 (3 mL), rt. bIsolated yield.

Figure 1. Carbonyl-Ene Reaction Products

MeO

OH OH N Ts 8a (65% yield, >20:1 d.r.)

Me

Me

Me

Me

N Ts 8b (62% yield, >20:1 d.r.)

OH OH N Ts 15a (65% yield, >20:1 d.r.)

OH OH N Ts 8c (60% yield, >20:1 d.r.)

Me

Me Me

Br

OH OH

Me

Me

MeO

Me OH OH

N Ts 15b (63% yield, >20:1 d.r.)

X-ray of 8c CCDC 1862412

Me Br

Me OH OH N Ts 15c (60% yield, >20:1 d.r.)

X-ray of 15c CCDC 1862411

To gain further insight into the mechanism of the allylboration, we conducted preliminary mechanistic investigations (Scheme 2). Compound 16 with the methyl-masked hydroxyl group produced none of the allylboration product under the typical conditions at 0 °C or at elevated temperatures using 2a or 2b as the allylation reagents, indicating that the hydroxyl group plays a vital role in the allylboration. On the basis of this study and our previous results,5 we propose a reaction model (Scheme 2). The reaction proceeded intramolecularly through a fused six-membered Zimmerman-Traxler transition state after a boronate is formed by a ligand change between the allylboronic acid and the hydroxyl group of the substrate. Under the chelation control, exquisite facial selectivity and rate acceleration were achieved, thus providing the allylboration products in high yields and with excellent diastereoselectivities. With reference to the studies by Hall and co-workers, 14 in which the allylboration is believed to be accelerated by coordination of the acid with the oxygen atom of allylboronate in the transition state, the rate-accelerating effect of HFIP (pka = 9.3) may be explained by its ability to form a hydrogen-bond with the allylboronic acid.12 Alternatively, HFIP could presumably increase the electrophilicity of the allylboronic acid after forming a more acidic boronate, thus accelerating the allylboration.2



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Scheme 2. Control Experiments and the Proposed Reaction Model for the Allylboration a) Control experiments O

OMe Me +

16

N Ts

B(OH)2 Me Me

Me Me

or

Me

2b

OH + 2

HFIP

HFIP 4 Å MS, CH2Cl2 0 °C

no allylboration product detected

B(OH)2

b) Plausible reaction model O

2a

RZ Ar R

E

N 5a Ts

RE RZ

O

OH B O proposed TS

6, 7

OH OH N Ts

In summary, we have developed a highly diastereoselective allylboration of 3-indolyl hydroxylmethyl ketones with γ, γdisubstituted allylboronic acids for the preparation of 3-indolyl substituted homoallylic alcohols that possess adjacent quanternary stereogenic centers. With the assistance of the neighboring hydroxyl group, high diastereoselectivities and yields for the allylboration have been achieved. Using geranylboronic acid 2a and its configurational isomer nerylboronic acid 2b, pairs of diastereomers with various substitutions on the indolyl groups have been prepared respectively. Taking advantage of the hydroxyl directing group, a subsequent highly diastereoselective Lewis acid-mediated carbonyl-ene reaction provided rapid access to the hapalindole core scaffold with two adjacent quaternary stereogenic centers out of four contiguous stereogenic centers, thus facilitating the preparation of natural product analogues and the further biological studies.

EXPERIMENTAL SECTION General Information. All commercially available reagents were used without further purification unless otherwise noted. All reactions were carried out under a positive pressure of dry nitrogen in oven–dried glassware with magnetic stirring. All solvents employed in the reactions were distilled from appropriate drying agents prior to use. 1H and 13C NMR spectra were obtained on an Agilent 400MR or 600MR DD2 spectrometer at ambient temperature. IR spectra were recorded on a Bruker 100 FT–IR spectrometer. The HRMS spectra were acquired on a 7 Tesla SolariX FT-ICR MS (Bruker Daltonics, Bremen, Germany) with an ESI source. X–ray crystallography analysis of single crystals was performed on an Agilent SuperNova–CCD X–Ray diffractometer. Melting points were recorded on a SGW X–4A apparatus. General Procedure for Preparation of hydroxylmethyl 3-indolyl ketones. α-Ketoaldehyde15 (1 mmol) was dissolved in a 1:10 mixture of MeOH and THF (5 mL) and added with NaBH4 (0.5 mmol) at 0 °C. After being stirred at 0 °C for an additional 30 min, the reaction was quenched with H2O (5 mL) and stirred for another 10 min. The resulting mixture was extracted with ethyl acetate (3 × 10 mL). The combined organic phase was washed with brine (3 × 10 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude hydroxylketone was purified by column chromatography on silica gel to afford the corresponding hydroxylketones in 70‒90% yield. To a stirred mixture of the hydroxylketone (1 mmol) in MeCN (10 mL) was added K2CO3 (1 mmol) and TsCl (1.1 mmol) at 0 °C under an atmosphere of N2. After being stirred at room temperature for ~12 h, the reaction was quenched with a


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saturated solution of NH4Cl (10 mL) and then stirred for an additional 10 min. The resulting mixture was extracted with ethyl acetate (3 × 15 mL). The oil layer was washed with brine (3 × 15 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by column chromatography on silica gel to afford the pure 3-indolyl ketone 5. General Procedure for the Allylboration. To a solution of compound 5 (0.1 mmol), HFIP (0.5 mmol), and 4 Å molecular sieve (100 mg) in CH2Cl2 (3 mL) added dropwise freshly prepared 2a or 2b2a, 5 (0.2 M in CHCl3, 0.15 mmol) at 0 °C. After being stirred at the same temperature until all the 5 was consumed (1.5‒12 h), the reaction mixture was added with an aqueous solution of formaldehyde (37%, 0.1 mL) and stirred for an additional 30 min. The resulting mixture was filtered, and the filtrate was diluted with brine (10 mL) and extracted with CH2Cl2 (3 × 10 mL). The combined organic phase was washed with brine (3 × 10 mL), dried over Na2SO4, filtered, and concentrated in vacuo. An appreciate amount of the crude residue sample was checked for the diastereomeric ratio by 1H NMR or HPLC. After the 1H NMR or HPLC analysis, all the crude residue was combined and purified by column chromatography on silica gel (Petroleum ether : EtOAc = 5 : 1) to afford allylboration product 6 or 7. General procedure for the carbonyl-ene reaction. To a solution of compound 6 or 7 (0.2 mmol) in DMSO (2 mL) was added IBX (0.4 mmol), the resulting reaction mixture was stirred for 10 h at room temperature. The mixture was then quenched with a saturated solution of Na2S2O3 (2 mL) and extracted with EtOAc (3 × 5 mL). The combined organic layer was washed with brine (3 × 5 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was used for the next carbonyl-ene reaction without further purification. To a solution of the above crude product in CH2Cl2 (5 mL) was added dropwise EtAlCl2 (0.4 mmol) at 78 °C. After being stirred for 30 min at the same temperature, the reaction was quenched with NaHCO3 (2 mL), then added with a saturated solution of potassium sodium tartrate and stirred until the reaction mixture became homogeneous. The resulting mixture was extracted with CH2Cl2 (3 × 5 mL), and the combined organic phase was washed with brine (3 × 5 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The resulting crude residue was purified by column chromatography on silica gel (Petroleum ether : EtOAc = 10 : 1) to afford the pure product 8 or 15. Procedure for the preparation of 16. Silver(I) oxide (75 mg, 0.61 mmol, 2 eq) was added to a solution of 5a (100 mg, 0.30 mmol, 1 eq) in methyl iodide (2 mL). The resulting mixture was then stirred at r.t. for 24 h. The mixture was filtered, and the filtrate was washed with CH2Cl2, dried over Na2SO4, filtered, and concentrated in vacuo. Purification of the crude residue by column chromatography on silica gel afforded 16 (73 mg, 70%) as a white solid. Mp = 123.5-126.5 °C. 1H NMR (400 MHz, CDCl3) δ 8.49 (s, 1 H), 8.33 (dd, J = 7.0, 2.1 Hz, 2 H), 7.94 (dd, J = 7.0, 1.6 Hz, 1 H), 7.84 (d, J = 8.4 Hz, 2 H), 7.40‒7.32 (m, 2 H), 7.29 (s, 1 H), 4.49 (s, 2 H), 3.52 (s, 3 H), 2.36 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 193.3, 146.1, 134.6, 134.5, 132.8, 130.4, 127.9, 127.3, 125.9, 125.0, 123.1, 118.4, 113.2, 77.05, 59.6, 21.8 ppm. IR (KBr): ʋmax = 3477, 3416, 1619, 1376, 1175, 750, 573, 475 cm-1. HRMS (ESI): Calcd for C18H18NO4S, [M+H]+: 344.0951, found: 344.0953. 2-Hydroxy-1-(1-tosyl-1H-indol-3-yl)ethan-1-one (5a). Yellow solid, 246.8 mg, 75% yield, mp = 180.7‒183.9 °C. 1H NMR (400 MHz, CDCl3) δ 8.26‒8.24 (m, 2 H), 7.95 (d, J = 7.5 Hz, 1 H), 7.84 (d, J = 8.4 Hz, 2 H), 7.43‒7.35 (m, 2 H), 7.29 (d, J = 8.2 Hz, 2 H), 4.78 (d, J = 4.4 Hz, 2 H), 3.48 (t, J = 4.7 Hz, 1 H), 2.37 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 194.0, 146.4, 134.9, 134.4,



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131.5, 130.5, 127.4, 127.2, 126.2, 125.2, 122. 8, 117.5, 113.4, 65.9, 21.8 ppm. IR (KBr): ʋmax = 3418, 1673, 1538, 1446, 1378, 1294, 1177, 1142, 1110, 1084, 986, 912, 814, 750, 705, 661, 571, 538 cm-1. HRMS (ESI): Calcd for C17H15NNaO4S, [M+Na]+: 352.0614, found: 352.0610. 2-Hydroxy-1-(5-methyl-1-tosyl-1H-indol-3-yl)ethan-1-one (5b). White solid, 205.8 mg, 60% yield, mp = 194.6‒197.7 °C. 1H NMR (400 MHz, CDCl3) δ 8.21 (s, 1 H), 8.03 (s, 1 H), 7.82 (d, J = 8.7 Hz, 3 H), 7.26 (d, J = 8.7 Hz, 2 H), 7.20 (d, J = 8.5 Hz, 1 H), 4.77 (d, J = 4.1 Hz, 2 H), 3.53 (t, J = 4.6 Hz, 1 H), 2.43 (s, 3 H), 2.35 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 194.1, 146.2, 135.1, 134.4, 133.0, 131.6, 130.4, 127.6, 127.4, 127.3, 122.5, 117.3, 113.0, 65.8, 21.7, 21.5 ppm. IR (KBr): ʋmax = 3461, 1671, 1539, 1450, 1377, 1266, 1176, 1138, 1111, 1081, 989, 936, 810, 740, 703, 679, 586, 545 cm-1. HRMS (ESI): Calcd for C18H17NNaO4S, [M+Na]+: 366.0771, found: 366.0776. 2-Hydroxy-1-(5-methoxy-1-tosyl-1H-indol-3-yl)ethan-1-one (5c). White solid, 251.3 mg, 70% yield, mp = 167.5‒168.7 °C. 1H NMR (400MHz, CDCl3) δ 8.18 (s, 1 H), 7.84‒7.80 (m, 3 H), 7.73 (t, J = 1.8 Hz, 1 H), 7.28 (d, J = 8.2 Hz, 2 H), 7.00 (dt, J = 9.1, 1.6 Hz, 1 H), 4.76 (d, J = 4.6 Hz, 2 H), 3.85 (s, 3 H), 3.47 (t, J = 4.8 Hz, 1 H), 2.37 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 194.1, 157.9, 146.3, 134.4, 131.8, 130.4, 129.4, 128.4, 127.3, 117.3, 116.0, 114.2, 104.3, 65.7, 55.9, 22.8 ppm. IR (KBr): ʋmax = 3414, 1671, 1535, 1479, 1377, 1263, 1218, 1174, 1080, 987, 812, 679, 591, 550 cm-1. HRMS (ESI): Calcd for C18H17NNaO5S, [M+Na]+: 382.0720, found: 382.0726. 1-(5-Chloro-1-tosyl-1H-indol-3-yl)-2-hydroxyethanone (5d). White solid, 273 mg, 75% yield, mp = 228.1‒229.9 °C. 1H NMR (400MHz, CDCl3) δ 8.27 (d, J = 2.0 Hz, 1 H), 8.23 (s, 1 H), 7.87 (d, J = 8.9 Hz, 1 H), 7.82 (d, J = 8.2 Hz, 2 H), 7.36 (dd, J = 9.0, 2.1 Hz, 1 H), 7.31 (d, J = 8.1 Hz, 2 H), 4.76 (d, J = 4.6 Hz, 2 H), 3.47 (t, J = 4.8 Hz, 1 H), 2.39 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 193.7, 146.6, 134.1, 133.1, 132.4, 131.3, 130.6, 128.4, 127.3, 126.6, 122.5, 116.9, 114.4, 65.8, 21.8 ppm. IR (KBr): ʋmax = 3419, 1619, 1440, 1383, 1119, 1087, 985, 735, 671, 582 cm-1. HRMS (ESI): Calcd for C17H14ClNNaO4S, [M+Na]+: 386.0224, found: 386.0228. 1-(5-Bromo-1-tosyl-1H-indol-3-yl)-2-hydroxyethanone (5e). Yellow solid, 257 mg, 63% yield, mp = 211.2‒213.3 °C. 1H NMR (400 MHz, CDCl3) δ 8.44 (d, J = 1.9 Hz, 1 H), 8.21 (s, 1 H), 7.83‒7.80 (m, 3 H), 7.50 (dd, J = 8.8, 2.0 Hz, 1 H), 7.31 (d, J = 8.1 Hz, 2 H), 4.75 (d, J = 4.3 Hz, 2 H), 3.39 (t, J = 4.7 Hz, 1 H) , 2.39 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 193.7, 146.7, 134.1, 133.5, 132.2, 130.6, 129.2, 128.8, 127.3, 125.5, 119.0, 116.7, 114.7, 65.8, 21.8 ppm. IR (KBr): ʋmax = 3417, 1673, 1536, 1440, 1382, 1296, 1179, 1159, 1119, 1085, 984, 917, 812, 723, 667, 581, 542 cm-1. HRMS (ESI): Calcd for C17H14BrNNaO4S, [M+Na]+: 429.9719, found: 429.9718. 1-(5-fluoro-1-tosyl-1H-indol-3-yl)-2-hydroxyethanone (5f). White solid, 243 mg, 70% yield, mp = 199.0‒200.6 °C. 1H NMR (400 MHz, CDCl3) δ 8.25 (s, 1 H), 7.95 (dd, J = 8.9, 2.6 Hz, 1 H), 7.70 (dd, J = 9.1, 4.3 Hz, 1 H), 7.82 (d, J = 8.1 Hz, 2 H), 7.31 (d, J = 8.1 Hz, 2 H), 7.13 (td, J = 9.0, 2.6 Hz, 1 H), 4.76 (d, J = 4.2 Hz, 2 H), 3.41 (t, J = 4.7 Hz, 1 H), 2.39 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 193.7, 160.7 (d, J = 241 Hz), 146.6, 132.6, 131.1, 130.6, 128.4 (d, J = 11 Hz), 127.3, 114.6 (d, J = 7 Hz), 114.4 (d, J


Page 9 of 20 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


= 9 Hz), 108.7 (d, J = 25 Hz), 65.8, 21.8 ppm. IR (KBr): ʋmax = 3415, 1618, 1540, 1447, 1381, 1173, 990, 681, 585 cm-1. HRMS (ESI): Calcd for C17H14FNNaO4S, [M+Na]+: 370.0520, found: 370.0525. 1-(4-bromo-1-tosyl-1H-indol-3-yl)-2-hydroxyethanone (5g). Yellow solid, 253 mg, 62% yield, mp = 102.3‒105.5 °C. 1H NMR (400 MHz, CDCl3) δ 8.08 (s, 1 H), 7.97 (d, J = 8.4 Hz, 1 H), 7.81 (d, J = 8.2 Hz, 2 H), 7.53 (d, J = 7.8 Hz, 1 H), 7.30‒7.23 (m, 3 H), 4.73 (d, J = 3.7 Hz, 2 H), 3.44 (t, J = 4.8 Hz, 1 H), 2.38 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 195.3, 146.6, 136.1, 134.0, 130.5, 130.4, 129.8, 127.3, 126.9, 126.9, 119.4, 114.9, 112.6, 68.4, 21.8 ppm. IR (KBr): ʋmax = 3416, 1619, 1380, 1333, 1163, 1086, 1002, 814, 743, 704, 661, 612, 574, 540 cm-1. HRMS (ESI): Calcd for C17H14BrNNaO4S, [M+Na]+: 429.9719, found: 429.9721. 1-(6-Bromo-1-tosyl-1H-indol-3-yl)-2-hydroxyethanone (5h). Yellow solid, 285.6 mg, 70% yield, mp = 157.8‒160.2 °C. 1H NMR (400 MHz, CDCl3) δ 8.20 (s, 1 H), 8.10 (d, J = 8.7 Hz, 2 H), 7.83 (d, J = 8.1 Hz, 2 H), 7.45 (dd, J = 8.5, 1.8 Hz, 1 H), 7.32 (d, J = 8.1 Hz, 2 H), 4.76 (d, J = 4.5 Hz, 2 H), 3.44 (t, J = 4.8 Hz, 1 H), 2.39 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 193.8, 146.7, 135.4, 134.1, 131.7, 130.6, 128.6, 127.3, 126.1, 124.0, 120.0, 117.3, 116.4, 65.8, 21.8 ppm. IR (KBr): ʋmax = 3417, 3262, 1619, 1535, 1381, 1303, 1162, 1097, 988, 913, 815, 666, 577, 536 cm-1. HRMS (ESI): Calcd for C17H14BrNNaO4S, [M+Na]+: 429.9719, found: 429.9720. 1-(7-Bromo-1H-indol-3-yl)-2-hydroxyethanone (5i). Yellow solid, 177.8 mg, 70% yield, mp = 183.9‒186.7 °C. 1H NMR (400 MHz, DMSO-d6) δ 12.19 (s, 1 H), 8.40 (s, 1 H), 8.19 (d, J = 8.0 Hz, 1 H), 7.45 (d, J = 7.6 Hz, 1 H), 7.15 (t, J = 7.8 Hz ,1 H), 5.03 (t, J = 5.9 Hz, 1 H) , 4.60 (d, J = 5.0 Hz, 2 H) ppm. 13C NMR {1H} (100 MHz, DMSO-d6) δ 194.8, 134.7, 134.2, 127.2, 125.5, 123.3, 120.6, 114.2, 104.7, 65.6 ppm. IR (KBr): ʋmax = 3409, 1617, 1433, 1066, 784 cm-1. HRMS (ESI): Calcd for C10H8BrNNaO2, [M+Na]+: 275.9631, found: 275.9638. 1-(4-Fluoro-1-tosyl-1H-indol-3-yl)-2-hydroxyethanone (5j). Yellow solid, 246.4 mg, 71% yield, mp = 189.2‒190.9 °C. 1H NMR (400 MHz, CDCl3) δ 8.32 (s, 1 H), 7.84 (d, J = 8.5 Hz, 2 H), 7.79 (d, J = 8.3 Hz, 1 H), 7.38‒7.30 (m, 3 H), 7.06 (dd, J = 11.1, 8.5 Hz, 1 H), 4.82 (d, J = 4.1 Hz, 2 H), 3.50 (t, J = 4.8 Hz, 1 H), 2.39 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 193.3, 155.8 (d, J = 251 Hz), 146.6, 137.2 (d, J = 10.0 Hz), 134.0, 132.4, 130.5, 127.4, 127.0 (d, J = 8.0 Hz), 117.0 (d, J = 4.0 Hz), 115.0 (d, J = 22.0 Hz), 111.0 (d, J = 22.0 Hz), 109.7 (d, J = 11.0 Hz), 67.0 (d, J = 11.0 Hz), 21.8 ppm. IR (KBr): ʋmax = 3479, 1639, 1619, 1536, 1493, 1379, 1179, 1073, 941, 740, 705, 615, 577, 476 cm-1. HRMS (ESI): Calcd for C17H14FNNaO4S, [M+Na]+: 370.0520, found: 370.0524. 1-(6-Fluoro-1-tosyl-1H-indol-3-yl)-2-hydroxyethanone (5k). White solid, 263.7 mg, 76% yield, mp = 194.2‒195.0 °C. 1H NMR (400 MHz, CDCl3) δ 8.24‒8.20 (m, 2 H), 7.84 (d, J = 8.4 Hz, 2 H), 7.67 (dd, J = 9.3, 2.3 Hz, 1 H), 7.32 (d, J = 8.1 Hz, 2 H), 7.12 (td, J = 9.0, 2.4 Hz, 1 H), 4.76 (d, J = 4.4 Hz, 2 H), 3.41 (t, J = 4.7 Hz, 1 H), 2.39 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 193.9, 161.4 (d, J = 243 Hz), 146.6, 134.9 (d, J = 12.0 Hz), 134.0, 131.6 (d, J = 4.0 Hz), 130.6, 127.3, 123.9 (d, J = 10.0 Hz), 123.5, 117.2, 113.7 (d, J = 28.0 Hz), 65.7, 21.8 ppm. IR (KBr): ʋmax = 3415, 1618, 1540, 1380, 1179, 1103, 996, 940, 681, 580 cm-1. HRMS (ESI): Calcd for C17H14FNNaO4S, [M+Na]+: 370.0520, found: 370.0525. (2S,3S)-3,7-Dimethyl-2-(1-tosyl-1H-indol-3-yl)-3-vinyloct-6-ene-1,2-diol (±6a). Colorless liquid, 44.5 mg, 95% yield, 24 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 8.2 Hz, 1 H), 7.86 (d, J = 8.0 Hz, 1 H), 7.72 (d, J = 8.4 Hz, 2 H), 7.48 (s, 1 H), 7.27‒7.25 (m,



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1 H), 7.21‒7.17 (m, 3 H), 5.80 (dd, J = 17.6, 10.8 Hz, 1 H), 5.20 (d, J = 10.8 Hz, 1 H), 5.01 (d, J = 17.6 Hz, 1 H), 4.97‒4.93 (m, 1 H), 4.15‒4.08 (m, 1 H), 3.81 (dd, J = 11.5, 6.3 Hz, 1 H), 2.98 (s, 1 H), 2.32 (s, 3 H), 2.03‒1.55 (m, 6 H), 1.50 (s, 3 H), 1.35‒1.23 (m, 2 H), 1.04 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 145.1, 142.8, 135.5, 135.1, 131.3, 130.7, 130.0, 126.9, 125.7, 124.8, 124.5, 123.9, 123.5, 123.4, 116.3, 113.8, 80.6, 66.2, 47.4, 35.2, 25.8, 22.9, 21.7, 17.8, 17.2 ppm. IR (KBr): ʋmax = 3415, 1620, 1445, 1371, 1123, 747, 667, 574, 539 cm-1. HRMS (ESI): Calcd for C27H33NNaO4S, [M+Na]+: 490.2022, found: 490.2016. (2S,3S)-3,7-Dimethyl-2-(5-methyl-1-tosyl-1H-indol-3-yl)-3-vinyloct-6-ene-1,2-diol (±6b). Colorless liquid, 43.4 mg, 90% yield, 32 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.5 Hz, 1 H), 7.71 (d, J = 8.0 Hz, 2 H), 7.66 (s, 1 H), 7.44 (s, 1 H), 7.18 (d, J = 8.0 Hz, 2 H), 7.10 (d, J = 8.5 Hz, 1 H), 5.81(dd, J = 17.6, 10.8 Hz, 1 H), 5.17 (d, J = 10.9 Hz, 1 H), 5.03 (d, J = 9.3 Hz, 1 H), 4.97 (t, J = 6.8 Hz, 1 H), 4.14 (dd, J =11.6, 3.1 Hz, 1 H), 3.81 (dd, J = 11.5, 6.8 Hz, 1 H), 2.95 (s, 1 H), 2.39 (s, 3 H), 2.32 (s, 3 H), 1.80‒1.55 (m, 6 H), 1.51 (s, 3 H), 1.40‒1.24 (m, 2 H), 1.04 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 145.0, 142.9, 135.1, 133.8, 133.0, 131.3, 131.0, 129.9, 126.8, 126.0, 125.9, 124.9, 123.7, 123.3, 116.3, 113.4, 80.7, 66.3, 47.4, 35.2, 25.8, 23.0, 21.7, 21.6, 17.8, 17.2 ppm. IR (KBr): ʋmax = 3478, 3415, 1639, 1619, 1266, 741, 705, 593, 542, 477 cm-1. HRMS (ESI): Calcd for C28H35NNaO4S, [M+Na]+: 504.2179, found: 504.2181. (2S,3S)-2-(5-Methoxy-1-tosyl-1H-indol-3-yl)-3,7-dimethyl-3-vinyloct-6-ene-1,2-diol (±6c). Colorless liquid, 47.3 mg, 95% yield, 24 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 9.0 Hz, 1 H), 7.68 (d, J = 8.0 Hz, 2 H), 7.40 (s, 1 H), 7.37 (s, 1 H), 7.17 (d, J = 7.9 Hz, 2 H), 6.89 (d, J = 9.1 Hz, 1 H), 5.79 (dd, J = 17.5, 10.8 Hz , 1 H), 5.20 (d, J = 10.8 Hz, 1 H), 5.02 (d, J = 17.6 Hz, 1 H), 4.94 (t, J = 6.5 Hz, 1 H), 4.09 (d, J = 11.4 Hz, 1 H), 3.85‒3.74 (m, 4 H), 2.99 (s, 1 H), 2.31 (s, 3 H), 1.77‒1.55 (m, 5 H), 1.50 (s, 3 H), 1.37‒1.26 (m, 2 H), 1.04 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 156.3, 145.0, 142.8, 135.0, 131.9, 131.3, 130.3, 129.9, 126.8, 126.2, 124.8, 123.9, 116.3, 114.5, 113.6, 106.3, 80.7, 66.3, 55.8, 47.5, 35.2, 25.8, 22.9, 21.7, 17.8, 17.1 ppm. IR (KBr): ʋmax = 3415, 3055, 2927, 1618, 1470, 1371, 1266, 1173, 1086, 746, 705, 596, 542 cm-1. HRMS (ESI): Calcd for C28H35NNaO5S, [M+Na]+: 520.2128, found: 520.2133. (2S,3S)-2-(5-Chloro-1-tosyl-1H-indol-3-yl)-3,7-dimethyl-3-vinyloct-6-ene-1,2-diol (±6d). Colorless liquid, 40.7 mg, 81% yield, 49 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 7.93 (s, 1 H), 7.88 (d, J = 8.9 Hz, 1 H), 7.69 (d , J = 8.1 Hz, 2 H), 7.45 (s, 1 H), 7.24‒7.19 (m, 3 H), 5.82 (dd, J = 17.6, 10.9 Hz, 1 H), 5.24 (d, J = 10.8 Hz, 1 H), 5.04 (d, J = 17.6 Hz, 1 H), 4.97 (t, J = 7.1 Hz, 1 H), 4.06 (dd, J = 11.6, 4.8 Hz, 1 H), 3.83 (dd, J = 11.4, 6.6 Hz, 1 H), 2.91 (s, 1 H), 2.34 (s, 3 H), 1.80‒1.69 (m, 2 H), 1.66 (s, 3 H), 1.54 (s, 1 H), 1.51 (s, 3 H), 1.35‒1.26 (m, 2 H), 1.01 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 145.5, 142.5, 134.8, 133.8, 132.4, 131.6, 130.1, 129.4, 126.9, 126.4, 124.9, 124.7, 123.4, 123.3, 116.9, 114.7, 80.7, 66.4, 47.6, 35.2, 25.9, 23.0, 21.7, 17.8, 17.4 ppm. IR (KBr): ʋmax = 3480, 3416, 1619, 1442, 1373, 1174, 672, 590, 478 cm-1. HRMS (ESI): Calcd for C27H32ClNNaO4S, [M+Na] +: 524.1633, found: 524.1632. (2S,3S)-2-(5-Bromo-1-tosyl-1H-indol-3-yl)-3,7-dimethyl-3-vinyloct-6-ene-1,2-diol (±6e). Colorless liquid, 51.9 mg, 95% yield, 19 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 8.09 (s, 1 H), 7.83 (d, J = 8.7 Hz, 1 H), 7.69 (d, J = 8.0 Hz, 2 H), 7.43 (s, 1 H), 7.37 (d, J = 5.2 Hz,


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1 H), 7.20 (d, J = 8.1 Hz, 2 H), 5.82 (dd, J = 17.6, 10.9 Hz, 1 H), 5.25 (d, J = 10.9 Hz, 1 H), 5.04 (d, J = 17.6 Hz, 1 H), 4.97 (t, J = 7.0 Hz, 1 H), 4.05 (d, J = 11.3 Hz, 1 H), 3.83 (d, J = 11.8 Hz, 1 H), 2.91 (s, 1 H), 2.34 (s, 3 H), 1.82‒1.69 (m, 2 H), 1.66 (s, 3 H), 1.52 (s, 3 H), 1.37‒1.28 (m, 2 H), 1.01 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 145.5, 142.4, 134.6, 134.1, 132.8, 131.6, 130.1, 127.4, 126.8, 126.4, 126.2, 124.6, 123.2, 117.1, 117.0, 115.0, 80.6, 66.3, 47.5, 35.1, 25.9, 22.9, 21.7, 17.8, 17.3 ppm. IR (KBr): ʋmax = 3415, 2926, 1637, 1618, 1438, 1374, 1175, 741, 671, 588, 540, 473 cm-1. HRMS (ESI): Calcd for C27H32BrNNaO4S, [M+Na]+: 568.1128, found: 568.1121. (2S,3S)-2-(5-Fluoro-1-tosyl-1H-indol-3-yl)-3,7-dimethyl-3-vinyloct-6-ene-1,2-diol (±6f). Colorless liquid, 44.1 mg, 91% yield, 16 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 7.90 (dd, J = 4.6, 9.2 Hz, 1 H), 7.69 (d, J = 8.0 Hz, 2 H), 7.60 (dd, J = 10.1, 2.6 Hz, 1 H), 7.46 (s, 1 H), 7.20 (d, J = 8.0 Hz, 2 H), 7.00 (td, J = 9.0, 2.6 Hz, 1 H), 5.80 (dd, J = 17.6, 10.9 Hz, 1 H), 5.23 (d, J = 10.8 Hz, 1 H), 5.02 (d, J = 17.6 Hz, 1 H), 4.95 (t, J = 7.2 Hz, 1 H), 4.05 (d, J = 11.5 Hz, 1 H), 3.82 (dd, J = 11.7, 5.5 Hz, 1 H), 2.92 (s, 1 H), 2.33 (s, 3 H) , 1.86‒1.54 (m, 6 H), 1.51 (s, 3 H), 1.34‒1.26 (m, 1 H), 1.01 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 159.5 (d, J = 238 Hz), 145.3, 142.5, 134.8, 132.2 (d, J = 10.0 Hz), 131.8, 131.5, 130.0, 126.8, 126.7, 124.7, 123.8 (d, J = 4.0 Hz), 116.8, 114.6 (d, J = 9.0 Hz), 112.7 (d, J = 26.0 Hz), 109.5 (d, J = 26.0 Hz), 80.6, 66.3, 47.6, 35.2, 25.8, 23.0, 21.7, 17.8, 17.2 ppm. IR (KBr): ʋmax = 3415, 2928, 1618, 1463, 1373, 1173, 1117, 811, 666, 592, 543 cm-1. HRMS (ESI): Calcd for C27H32FNNaO4S, [M+Na]+: 508.1928, found: 508.1926. (2S,3S)-2-(4-Bromo-1-tosyl-1H-indol-3-yl)-3,7-dimethyl-3-vinyloct-6-ene-1,2-diol (±6g). Colorless liquid, 49.2 mg, 90% yield, 16 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 8.06 (d, J = 8.3 Hz, 1 H), 7.72 (d, J = 8.0 Hz, 2 H), 7.54 (d, J = 7.8 Hz, 2 H), 7.21 (d, J = 8.1 Hz, 2 H), 7.09 (t, J = 6.4 Hz, 1 H), 5.87 (dd, J = 17.6, 10.9 Hz, 1 H), 5.16 (d, J = 10.8 Hz, 1 H), 5.00 (t, J = 6.6 Hz, 1 H), 4.92 (d, J = 17.6 Hz, 1 H), 3.97‒3.93 (m, 2 H), 2.34 (s, 3 H), 1.83‒1.62 (m, 6 H), 1.52-1.36 (m, 5 H), 1.09 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 145.6, 142.8, 137.3, 134.7, 131.4, 130.5, 130.1, 127.1, 124.9, 124.8, 116.1, 113.8, 113.4, 67.50, 48.0, 35.7, 25.8, 23.1, 21.7, 17.8, 17.7 ppm. IR (KBr): ʋmax = 3480, 3415, 1618, 1373, 1174, 743, 616, 574, 479 cm-1. HRMS (ESI): Calcd for C27H32BrNNaO4S, [M+Na]+: 568.1128, found: 568.1124. (2S,3S)-2-(6-Bromo-1-tosyl-1H-indol-3-yl)-3,7-dimethyl-3-vinyloct-6-ene-1,2-diol (±6h). Colorless liquid, 49.2 mg, 90% yield, 16 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 8.14 (s, 1 H), 7.77 (d, J = 8.6 Hz, 1 H), 7.72 (d, J = 8.3 Hz, 2 H), 7.41 (s, 1 H), 7.30 (dd, J = 8.7, 1.8 Hz, 1 H), 7.22 (d, J = 8.1 Hz, 2 H), 5.77 (dd, J = 17.6, 10.9 Hz, 1 H), 5.20 (d, J = 10.8 Hz, 1 H), 5.01 (d, J = 17.6 Hz, 1 H), 4.94 (t, J = 7.0 Hz, 1 H), 4.05 (d, J = 9.3 Hz, 1 H), 3.81 (dd, J = 11.6, 5.8 Hz, 1 H), 2.96 (s, 1 H), 2.35 (s, 3 H), 1.78‒1.65 (m, 6 H), 1.51 (s, 3 H), 1.33‒1.23 (m, 2 H), 1.01 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 145.5, 142.5, 136.1, 134.7, 131.5, 130.2, 129.8, 126.9, 126.8, 125.6, 124.9, 124.6, 123.6, 118.3, 116.7, 116.6, 80.6, 66.2, 47.4, 35.2, 25.9, 22.9, 21.7, 17.8, 17.2 ppm. IR (KBr): ʋmax = 3432, 2926, 1636, 1374, 1175, 1143, 812, 736, 670, 579, 541 cm-1. HRMS (ESI): Calcd for C27H32BrNNaO4S, [M+Na]+: 568.1128, found: 568.1124. (2S,3S)-2-(7-Bromo-1H-indol-3-yl)-3,7-dimethyl-3-vinyloct-6-ene-1,2-diol (±6i). Colorless liquid, 24.3 mg, 62% yield, 10 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 8.44 (s, 1 H), 7.85 (d, J = 8.1 Hz, 1 H), 7.34 (d, J = 7.7 Hz, 1 H), 7.21 (d, J = 2.5 Hz, 1 H), 6.99 (t, J = 7.9



Page 12 of 20

Hz, 1 H), 5.87 (dd, J = 17.6, 10.9 Hz, 1 H), 5.24 (d, J = 10.9 Hz, 1 H), 5.09 (d, J = 17.6 Hz, 1 H), 4.98 (t, J = 6.2 Hz, 1 H), 4.24 (d, J = 11.5 Hz, 1 H), 3.85 (dd, J = 11.3, 8.3 Hz, 1 H), 2.90 (s, 1 H), 1.80‒1.62 (m, 6 H), 1.50 (s, 3 H), 1.43‒1.26 (m, 2 H), 1.11 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 143.4, 135.2, 131.3, 128.2, 125.0, 124.9, 124.4, 121.7, 121.2, 118.3, 116.0, 105.0, 80.9, 66.4, 47.7, 35.3, 25.8, 23.0, 17.8, 17.1 ppm. IR (KBr): ʋmax = 3439, 2923, 1621, 1554, 1336, 1083, 739, 531 cm-1. HRMS (ESI): Calcd for C20H26BrNNaO2, [M+Na]+: 414.1039, found: 414.1043. (2S,3S)-2-(4-Fluoro-1-tosyl-1H-indol-3-yl)-3,7-dimethyl-3-vinyloct-6-ene-1,2-diol (±6j). Colorless liquid, 46.2 mg, 95% yield, 13 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.3 Hz, 1 H), 7.74 (d, J = 8.4 Hz, 2 H), 7.63 (s, 1 H), 7.23‒7.20 (m, 3 H), 6.93 (dd, J = 12.7, 8.0 Hz, 1 H), 5.82 (dd, J = 17.6, 10.9 Hz, 1 H), 5.14 (d, J = 10.8 Hz, 1 H), 4.98 (t, J = 6.8 Hz, 1 H), 4.90 (d, J = 17.6 Hz, 1 H), 4.33 (s, 1 H), 3.92 (dd, J = 11.7, 4.6 Hz, 1 H), 3.23 (s, 1 H), 2.34 (s, 3 H), 1.78‒1.65 (m, 5 H), 1.51 (s, 3 H), 1.50‒1.26 (m, 2 H), 1.02 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 155.1 (d, J = 245 Hz), 145.4, 142.4, 137.7 (d, J = 10.0 Hz), 134.8, 131.4, 130.1, 127.1, 125.2 (d, J = 9.0 Hz), 124.8, 121.7, 115.9, 110.3 (d, J = 3.0 Hz), 110.1, 109.9, 80.1, 66.0 (d, J = 11.0 Hz), 47.7, 35.0, 25.8, 23.1, 21.7, 17.8, 17.1 ppm. IR (KBr): ʋmax = 3469, 2925, 1486, 1427, 1374, 1178, 1071, 781, 719, 668, 577, 548 cm-1. HRMS (ESI): Calcd for C27H32FNNaO4S, [M+Na]+: 508.1928, found: 508.1927. (2S,3S)-2-(6-Fluoro-1-tosyl-1H-indol-3-yl)-3,7-dimethyl-3-vinyloct-6-ene-1,2-diol (±6k). Colorless liquid, 44.7 mg, 92% yield, 13 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 7.86 (dd, J = 9.1, 5.6 Hz, 1 H), 7.72 (d, J = 8.2 Hz, 2 H), 7.68 (dd, J = 9.9, 2.7 Hz, 1 H), 7.41 (s, 1 H), 7.22 (d, J = 8.0 Hz, 2 H), 6.95 (td, J = 9.0, 2.4 Hz, 1 H), 5.80 (dd, J = 17.6, 10.9 Hz, 1 H), 5.22 (d, J = 10.9 Hz, 1 H), 5.02 (d, J = 17.6 Hz, 1 H), 4.95 (t, J = 7.0 Hz, 1 H), 4.07 (dd, J = 11.9, 3.0 Hz, 1 H), 3.82 (dd, J = 11.8, 6.2 Hz, 1 H), 2.94 (s, 1 H), 2.34 (s, 3 H) , 1.79‒1.68 (m, 2 H), 1.65 (s, 3 H), 1.58‒1.53 (m, 1 H), 1.50 (s, 3 H), 1.37‒1.26 (m, 2 H), 1.02 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 160.7 (d, J = 241 Hz), 145.4, 142.6, 135.7 (d, J = 12.0 Hz), 134.9, 131.5, 130.1, 127.4, 126.9, 125.3, 124.8, 124.7, 123.7, 116.6, 111.9 (d, J = 23.0 Hz), 100.9 (d, J = 28.0 Hz), 80.7, 66.4, 47.5, 35.2, 25.8, 23.0, 21.7, 17.8, 17.2 ppm. IR (KBr): ʋmax = 3480, 3415, 1637, 1617, 1482, 1373, 1174, 600, 481 cm-1. HRMS (ESI): Calcd for C27H32FNNaO4S, [M+Na]+: 508.1928, found: 508.1927. (2S,3R)-3,7-Dimethyl-2-(1-tosyl-1H-indol-3-yl)-3-vinyloct-6-ene-1,2-diol (±7a). Colorless liquid, 44.5 mg, 95% yield, 24 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 8.3 Hz, 1 H), 7.87 (d, J = 8.1 Hz, 1 H), 7.71 (d, J = 8.1 Hz, 2 H), 7.42 (s, 1 H), 7.25 (t, J = 7.6 Hz, 1 H), 7.17 (t, J = 7.7 Hz, 3 H), 5.90 (dd, J = 17.7, 10.9 Hz, 1 H), 5.17 (d, J = 10.9 Hz, 1 H), 4.97‒4.89 (m, 2 H), 4.03 (d, J = 11.6 Hz, 1 H), 3.77 (dd, J = 11.5, 6.3 Hz, 1 H), 3.26 (s, 1 H), 2.29 (s, 3 H), 1.82‒1.67 (m, 2 H), 1.63 (s, 3 H), 1.49 (s, 3 H), 1.35‒1.20 (m, 2 H), 0.95 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 145.1, 142.8, 135.4, 131.0, 130.7, 122.9, 126.8, 125.4, 125.0, 124.4, 124.1, 123.5, 123.6, 123.3, 115.3, 113.6, 80.6, 66.2, 47.1, 34.7, 25.8, 22.8, 21.6, 17.7, 17.2 ppm. IR (KBr): ʋmax = 3479, 3415, 1638, 1618, 1445, 1371, 1175, 747, 667, 602, 538, 447 cm-1; HRMS (ESI): Calcd for C27H33NNaO4S, [M+Na]+: 490.2023, found: 490.2023.


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(2S,3R)-3,7-Dimethyl-2-(5-methyl-1-tosyl-1H-indol-3-yl)-3-vinyloct-6-ene-1,2-diol (±7b). Colorless liquid, 45.8 mg, 95% yield, 31 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 8.4 Hz, 1 H), 7.71 (d , J = 8.5 Hz, 2 H), 7.67 (s, 1 H), 7.39 (s, 1 H), 7.19 (d, J = 8.0 Hz, 2 H), 7.10 (d, J = 8.6 Hz, 1 H), 5.93 (dd, J = 17.8, 10.9 Hz, 1 H), 5.20 (d, J = 10.8 Hz, 1 H), 4.98‒4.92 (m, 2 H), 4.11 (d, J = 11.4 Hz, 1 H), 3.84 (dd, J = 12.0, 6.9 Hz, 1 H) , 3.16 (s, 1 H), 2.39 (s, 3 H), 2.32 (s, 3 H), 1.71‒1.69 (m, 2 H), 1.65 (s, 3 H), 1.50 (s, 3 H), 1.34‒1.25 (m, 2 H), 0.98 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 145.0, 142.9, 135.1, 133.7, 133.0, 131.1, 129.9, 126.9, 126.0, 125.6, 125.1, 123.9, 123.3, 115.4, 113.4, 80.8, 66.4, 47.2, 34.8, 25.8, 22.8, 21.7, 17.8, 17.4 ppm. IR (KBr): ʋmax = 3416, 3055, 1618, 1317, 1265, 1173, 747, 705, 592, 542 cm-1. HRMS (ESI): Calcd for C28H35NNaO4S, [M+Na]+: 504.2179, found: 504.2180. (2S,3R)-2-(5-Methoxy-1-tosyl-1H-indol-3-yl)-3,7-dimethyl-3-vinyloct-6-ene-1,2-diol (±7c). Colorless liquid, 47.3 mg, 95% yield, 45 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 9.0 Hz, 1 H), 7.69 (d, J = 8.0 Hz, 2 H), 7.40 (s, 1 H), 7.34 (s, 1 H), 7.19 (d, J = 8.0 Hz, 2 H), 6.90 (d, J = 9.1 Hz, 1 H), 5.81 (dd, J = 17.7, 10.9 Hz, 1 H), 5.20 (d, J = 10.9 Hz, 1 H), 4.96‒4.92 (m, 2 H), 4.06 (d, J = 11.4 Hz, 1 H), 3.84 (d, J = 11.7 Hz, 1 H), 3.78 (s, 3 H), 3.19 (s, 1 H), 2.32 (s, 3 H), 1.70‒1.68 (m, 2 H), 1.64 (s, 3 H), 1.50 (s, 3 H), 1.34‒1.24 (m, 2 H), 0.98 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 156.3, 145.1, 142.8, 135.0, 132.2, 131.2, 130.2, 129.9, 126.8, 125.7, 125.0, 124.0, 115.5, 114.4, 113.8, 106.3, 80.8, 66.5, 55.8, 47.3, 34.9, 25.8, 22.8, 21.7, 17.8, 17.2 ppm. IR (KBr): ʋmax = 3416, 2926, 1618, 1471, 1370, 1222, 1173, 1086, 812, 740, 667, 597, 542 cm-1. HRMS (ESI): Calcd for C28H35NNaO5S, [M+Na]+: 520.2128, found: 520.2128. (2S,3R)-2-(5-Chloro-1-tosyl-1H-indol-3-yl)-3,7-dimethyl-3-vinyloct-6-ene-1,2-diol (±7d). Colorless liquid, 38.2 mg, 76% yield, 19 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 7.94 (s, 1 H), 7.89 (d, J = 8.8 Hz, 1 H), 7.70 (d , J = 8.1 Hz, 2 H), 7.40 (s, 1 H), 7.25‒7.20 (m, 3 H), 5.90 (dd, J = 17.7, 10.9 Hz, 1 H), 5.22 (d, J = 10.9 Hz, 1 H), 4.98‒4.91 (m, 2 H), 4.04 (dd, J = 11.4, 3.7 Hz, 1 H), 3.88 (dd, J = 11.4, 3.4 Hz, 1 H), 3.16 (s, 1 H), 2.35 (s, 3 H), 1.72‒1.66 (m, 2 H), 1.65 (s, 3 H), 1.50 (s, 3 H), 1.33‒1.24 (m, 2 H), 0.97 (s, 3 H) ppm. 13C

NMR {1H} (100 MHz, CDCl3) δ 145.5, 142.4, 134.6, 133.6, 132.5, 131.3, 130.1, 129.2, 126.8, 126.0, 124.8, 124.7, 123.6, 123.4,

115.8, 114.5, 80.6, 66.4, 47.2, 34.7, 25.8, 22.8, 21.7, 17.8, 17.2 ppm. IR (KBr): ʋmax = 3477, 3415, 1619, 1441, 1174, 672, 590, 477 cm-1. HRMS (ESI): Calcd for C27H32ClNNaO4S, [M+Na]+ 524.1633, found: 524.1632. (2S,3R)-2-(5-Bromo-1-tosyl-1H-indol-3-yl)-3,7-dimethyl-3-vinyloct-6-ene-1,2-diol (±7e). Colorless liquid, 51.9 mg, 95% yield, 32 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 8.10 (s, 1 H), 7.83 (d, J = 8.9 Hz, 1 H), 7.70 (d, J = 8.1 Hz, 2 H), 7.38‒7.36 (m, 2 H), 7.21 (d, J = 8.0 Hz, 2 H), 5.89 (dd, J = 17.6, 10.9 Hz, 1 H), 5.21 (d, J = 10.9 Hz, 1 H), 4.98‒4.91 (m, 2 H), 4.03 (d, J = 11.2 Hz, 1 H), 3.88 (dd, J = 11.6, 6.7 Hz, 1 H), 3.17 (s, 1 H), 2.34 (s, 3 H), 1.77‒1.65 (m, 2 H), 1.65 (s, 3 H), 1.50 (s, 3 H), 1.37‒1.24 (m, 2 H), 0.97 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 145.5, 142.6, 134.8, 134.1, 133.0, 131.3, 130.1, 127.5, 126.9, 126.5, 125.9, 124.9, 123.6, 117.1, 115.9, 115.0, 80.7, 66.5, 47.3, 34.8, 25.8, 22.9, 21.7, 17.8, 17.3 ppm. IR (KBr): ʋmax = 3422, 2924, 1636, 1507, 1438, 1374, 1176, 741, 672, 586, 539 cm-1. HRMS (ESI): Calcd for C27H32BrNNaO4S, [M+Na]+: 568.1128, found: 568.1120. (2S,3R)-2-(5-Fluoro-1-tosyl-1H-indol-3-yl)-3,7-dimethyl-3-vinyloct-6-ene-1,2-diol (±7f). Colorless liquid, 44.2 mg, 91% yield, 45 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 7.90 (dd, J = 9.1, 4.6 Hz, 1 H), 7.70 (d, J = 8.1 Hz, 2 H), 7.62 (dd, J = 10.0, 2.6 Hz, 1 H), 7.41 (s, 1 H), 7.21 (d, J = 8.1 Hz, 2 H), 7.01 (td , J = 8.9, 2.5 Hz, 1 H), 5.90 (dd, J = 17.7, 10.9 Hz, 1 H), 5.21 (d, J = 10.9 Hz, 1 H), 4.96‒4.91



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(m, 2 H), 4.03 (dd, J = 11.6, 3.8 Hz, 1 H), 3.87 (dd, J = 11.1, 7.9 Hz, 1 H), 3.15 (s, 1 H), 2.34 (s, 3 H) , 1.76‒1.64 (m, 6 H), 1.50 (s, 3 H), 1.30‒1.23 (m, 2 H), 0.97 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 159.5 (d, J = 238 Hz), 145.4, 142.6, 134.9, 132.3 (d, J = 10.0 Hz), 131.8, 131.3, 130.1, 126.9, 126.4, 124.9, 124.0 (d, J = 4.0 Hz), 115.8, 114.6 (d, J = 9.0 Hz), 112.7 (d, J = 25.0 Hz), 109.5 (d, J = 25.0 Hz), 80.6, 66.5, 47.3, 34.8, 25.8, 22.8, 21.7, 17.8, 17.2 ppm. IR (KBr): ʋmax = 3416, 2968, 1619, 1462, 1372, 1173, 1118, 897, 811, 688, 666, 593, 543 cm-1. HRMS (ESI): Calcd for C27H32FNNaO4S, [M+Na]+: 508.1928, found: 508.1927. (2S,3R)-2-(4-Bromo-1-tosyl-1H-indol-3-yl)-3,7-dimethyl-3-vinyloct-6-ene-1,2-diol (±7g). Colorless liquid, 49.2 mg, 90% yield, 9 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 8.06 (d, J = 8.3 Hz, 1 H), 7.73 (d, J = 7.9 Hz, 2 H), 7.52 (d, J = 7.4 Hz, 1 H), 7.22 (d, J = 8.0 Hz, 2 H), 7.10 (t, J = 8.1 Hz, 1 H), 5.75 (dd, J = 17.8, 11.3 Hz, 1 H), 5.22 (d, J = 11.1 Hz, 1 H), 5.03‒4.92 (m, 2 H), 4.16 (s, 1 H), 3.98 (s, 1 H), 2.34 (s, 3 H), 2.04‒2.00 (m, 1 H), 1.75‒1.59 (m, 7 H), 1.52 (s, 3 H), 1.06 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 145.3, 142.1, 136.7, 134.0, 131.2, 130.0, 129.8, 127.6, 126.8, 124.7, 124.4, 120.1, 116.4, 113.0, 80.9, 67.1, 47.9, 35.3, 25.6, 22.8, 21.4, 17.5, 17.2 ppm. IR (KBr): ʋmax = 3479, 3415, 3055, 1618, 1373, 1265, 1174, 743, 668, 574, 541, 474 cm-1. HRMS (ESI): Calcd for C27H32BrNNaO4S, [M+Na]+: 568.1128, found: 568.1120. (2S,3R)-2-(6-Bromo-1-tosyl-1H-indol-3-yl)-3,7-dimethyl-3-vinyloct-6-ene-1,2-diol (±7h). Colorless liquid, 49.2 mg, 90% yield, 37 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 8.14 (s, 1 H), 7.80 (d, J = 8.6 Hz, 1 H), 7.72 (d, J = 8.4 Hz, 2 H), 7.35 (s, 1 H), 7.31 (dd, J = 8.9, 1.7 Hz, 1 H), 7.23 (d, J = 8.0 Hz, 2 H), 5.89 (dd, J = 17.7, 10.9 Hz, 1 H), 5.19 (d, J = 10.6 Hz, 1 H), 4.95‒4.90 (m, 2 H), 4.03 (d, J = 11.4 Hz, 1 H), 3.85 (dd, J = 11.8, 5.6 Hz, 1 H), 3.19 (s, 1 H), 2.35 (s, 3 H), 1.75‒1.57 (m, 6 H), 1.49 (s, 3 H), 1.34‒1.18 (m, 2 H), 0.95 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 145.5, 142.6, 136.0, 134.8, 131.3, 130.2, 126.9, 126.8, 125.2, 125.0, 124.9, 124.0, 118.4, 116.6, 115.7, 80.7, 66.4, 47.2, 34.8, 25.8, 22.8, 21.7, 17.8, 17.2 ppm. IR (KBr): ʋmax = 3520, 2925, 1597, 1420, 1374, 1175, 1145, 1088, 958, 813, 736, 671, 595, 579, 542 cm-1. HRMS (ESI): Calcd for C27H32BrNNaO4S, [M+Na]+: 568.1128, found: 568.1125. (2S,3R)-2-(7-Bromo-1H-indol-3-yl)-3,7-dimethyl-3-vinyloct-6-ene-1,2-diol (±7i). Colorless liquid, 22 mg, 56% yield, 30 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 8.45 (s, 1 H), 7.85 (d, J = 8.1 Hz, 1 H), 7.34 (d, J = 7.6 Hz, 2 H), 7.18 (d, J = 2.4 Hz, 1 H), 6.99 (t, J = 7.9 Hz, 1 H), 6.02 (dd, J = 17.8, 10.9 Hz, 1 H), 5.22 (d, J = 10.9 Hz, 1 H), 5.04‒4.97 (m, 2 H), 4.22 (d, J = 11.4 Hz, 1 H), 3.86 (dd, J = 11.4, 7.6 Hz, 1 H), 3.10 (s, 1 H), 1.82‒1.72 (m, 3 H), 1.62 (m, 3 H), 1.51 (s, 3 H), 1.43‒1.26 (m, 2 H), 1.05 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 143.4, 135.2, 131.1, 128.3, 125.2, 124.8, 124.4, 121.7, 121.2, 118.7, 115.0, 105.0, 80.9, 66.6, 47.3, 34.7, 25.8, 22.8, 17.8, 17.4 ppm. IR (KBr): ʋmax = 3439, 2923, 1621, 1554, 1336, 1083, 739, 531 cm-1. HRMS (ESI): Calcd for C20H26BrNNaO2, [M+Na]+: 414.1039, found: 414.10420. (2S,3R)-2-(4-Fluoro-1-tosyl-1H-indol-3-yl)-3,7-dimethyl-3-vinyloct-6-ene-1,2-diol (±7j). Colorless liquid, 46.2 mg, 95% yield, 32 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.4 Hz, 1 H), 7.75 (d, J = 8.0 Hz, 2 H), 7.64 (s, 1 H), 7.26‒7.20 (m, 3 H), 6.91 (dd, J = 12.8, 8.2 Hz, 1 H), 5.87‒5.78 (m, 1 H), 5.17 (d, J = 10.8 Hz, 1 H), 5.00‒4.90 (m, 2 H), 4.35 (s , 1 H), 3.92 (d, J = 11.4 Hz, 1 H), 3.50 (s, 1 H), 2.33 (s, 3 H) , 1.78‒1.62 (m, 6 H), 1.51 (s, 3 H), 1.36‒1.21 (m, 2 H), 0.99 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 155.0 (d, J = 245 Hz), 145.4, 142.7, 137.7 (d, J = 9.0 Hz), 134.7, 131.2, 130.1, 127.1, 125.2 (d, J = 9.0 Hz), 125.0, 115.7, 110.3,


Page 15 of 20 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


110.2, 110.0, 109.8, 79.7, 66.0 (d, J = 10.3 Hz), 47.4, 34.8, 25.9, 22.8, 21.7, 17.8, 16.8 (d, J = 3.0 Hz) ppm. IR (KBr): ʋmax = 3517, 2924, 1633, 1487, 1427, 1179, 1092, 1071, 781, 741, 673, 576, 548 cm-1. HRMS (ESI): Calcd for C27H32FNNaO4S, [M+Na]+: 508.1928, found: 508.1928. (2S,3R)-2-(6-Fluoro-1-tosyl-1H-indol-3-yl)-3,7-dimethyl-3-vinyloct-6-ene-1,2-diol (±7k). Colorless liquid, 43.7 mg, 90% yield, 10 : 1 d.r.. 1H NMR (400 MHz, CDCl3) δ 7.88 (dd, J = 8.8, 5.4 Hz, 1 H), 7.72 (d, J = 8.1 Hz, 2 H), 7.68 (dd, J = 9.9, 2.4 Hz, 1 H), 7.36 (s, 1 H), 7.23 (d, J = 8.0 Hz, 2 H), 6.95 (td , J = 9.1, 2.3 Hz, 1 H), 5.91 (dd, J = 17.7, 10.8 Hz, 1 H), 5.20 (d, J = 10.9 Hz, 1 H), 4.96‒4.92 (m, 2 H), 4.04 (d, J = 11.4 Hz, 1 H), 3.86 (dd, J = 11.5, 6.2 Hz, 1 H), 3.17 (s, 1 H), 2.35 (s, 3 H) , 1.76‒1.67 (m, 2H), 1.63 (s, 3 H), 1.49 (s, 3 H), 1.29‒1.22 (m, 2 H), 0.97 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 160.6 (d, J = 241 Hz), 145.5, 142.6, 135.5 (d, J = 12.0 Hz), 134.6, 131.2, 130.1, 127.5, 126.9, 124.9, 123.9, 115.6, 111.9 (d, J = 24.0 Hz), 100.7 (d, J = 28.0 Hz), 80.6, 66.4, 47.1, 34.8, 25.8, 22.7, 21.4, 17.4, 17.1 ppm. IR (KBr): ʋmax = 3416, 1637, 1373, 1175, 1110, 683, 583, 544 cm-1. HRMS (ESI): Calcd for C27H32FNNaO4S, [M+Na]+: 508.1928, found: 508.1927. (1S,2S,3S,6S)-6-Methyl-3-(prop-1-en-2-yl)-1-(1-tosyl-1H-indol-3-yl)-6-vinylcyclohexane-1,2-diol (±8a). Colorless liquid, 60.4 mg, 65% yield. 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.3 Hz, 1 H), 7.83 (d, J = 8.0 Hz, 1 H), 7.70 (d, J = 8.5 Hz, 2 H), 7.49 (s, 1 H), 7.3 (t, J = 7.3 Hz, 1 H), 7.17 (d, J = 7.8 Hz, 3 H), 6.08 (dd, J = 17.6, 10.8 Hz, 1 H), 4.94 (s, 2 H), 4.88 (d, J = 10.9 Hz, 1 H), 4.70 (d, J = 17.7 Hz, 1 H), 4.35 (d, J = 10.3 Hz, 1 H), 3.70 (t, J = 6.5 Hz, 1 H), 2.94 (s, 1 H), 2.61 (td, J = 11.7, 4.6 Hz, 1 H), 2.30 (s, 3 H), 2.21 (td, J = 13.3, 4.5 Hz, 1 H), 1.85 (s, 3 H), 1.82‒1.68 (m, 2 H), 1.37‒1.26 (m, 1 H), 0.98 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 146.5, 144.9, 144.8, 135.3, 135.2, 129.9, 126.9, 124.9, 124.2, 123.5, 123.1, 113.6, 113.4, 112.7, 79.5, 71.4, 68.0, 47.7, 44.8, 32.3, 25.7, 25.4, 21.6, 20.8, 19.5 ppm. IR (KBr): ʋmax = 3416, 2927, 1619, 1370, 1175, 1125, 908, 746, 585, 539 cm-1. HRMS (ESI): Calcd for C27H31NNaO4S, [M+Na] +: 488.1866, found: 488.1865. (1S,2S,3S,6R)-6-Methyl-3-(prop-1-en-2-yl)-1-(1-tosyl-1H-indol-3-yl)-6-vinylcyclohexane-1,2-diol (±15a). Colorless liquid, 60.5 mg, 65% yield. 1H NMR (400 MHz, CDCl3) δ 7.97 (s, 1 H), 7.92 (d, J = 8.2 Hz, 1 H), 7.70 (d, J = 8.3 Hz, 2 H), 7.43 (s, 1 H), 7.27‒7.21 (m, 1 H), 7.19‒7.16 (m, 3 H), 6.05 (dd, J = 17.5, 10.9 Hz, 1 H), 4.97 (d, J = 11.2 Hz, 1 H), 4.93‒4.92 (m, 2 H), 4.79 (d, J = 17.5 Hz, 1 H), 4.18 (s, 1 H), 2.64 (td, J = 4.3, 11.5 Hz, 1 H), 2.30 (s, 3 H), 2.09 (td, J = 14.0, 4.5 Hz, 1 H), 1.85 (td, J = 13.4, 3.7 Hz, 1 H), 1.82 (s, 3 H), 1.64‒1.55 (m, 2 H), 1.35‒1.23 (m, 1 H), 1.01 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 146.4, 144.8, 141.7, 135.1, 129.7, 126.7, 124.1, 123.0, 114.3, 113.4, 113.3, 79.6, 72.1, 47.4, 45.6, 32.4, 25.2, 23.3, 21.5, 19.2 ppm. IR (KBr): ʋmax = 3475, 3415, 2928, 1619, 1446, 1370, 1175, 1126, 748, 584, 539, 474 cm-1. HRMS (ESI): Calcd for C27H31NNaO4S, [M+Na]+: 488.1866, found: 488.1865. (1S,2S,3S,6S)-1-(5-methoxy-1-tosyl-1H-indol-3-yl)-6-methyl-3-(prop-1-en-2-yl)-6-vinylcyclohexane-1,2-diol (±8b). Colorless oil, 61.4 mg, 62% yield. 1H NMR (600 MHz, CDCl3) δ 7.82 (d, J = 9.1 Hz, 1 H), 7.68 (d, J = 8.1 Hz, 2 H), 7.41 (s, 1 H), 7.36 (s, 1 H), 7.17 (d, J = 8.1 Hz, 2 H), 6.86 (dd, J = 9.1, 2.4 Hz, 1 H), 6.04 (dd, J = 17.7, 10.8 Hz, 1 H), 4.95 (d, J = 10.2 Hz, 2 H), 4.89 (d, J = 11.0 Hz, 1 H), 4.74 (d, J = 17.7 Hz, 1 H), 4.28 (brs, 1 H), 3.78 (s, 3 H), 2.91 (s, 1 H), 2.60 (td, J = 12.6, 4.5 Hz, 1 H), 2.32 (s, 3 H), 2.21 (td, J = 13.5, 4.3 Hz, 1 H), 1.86 (s, 3 H), 1.78‒1.66 (m, 3 H), 1.36‒1.34 (m, 1 H), 0.97 (s, 3 H) ppm. 13C NMR {1H} (150 MHz, CDCl3) δ



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155.9, 146.4, 145.1, 144.9, 135.1, 130.2, 129.9, 126.8, 114.3, 113.5, 112.7, 106.7, 79.5, 71.5, 55.7, 47.7, 44.8, 31.9, 25.3, 21.7, 21.0, 19.4 ppm. IR (KBr): ʋmax = 3541, 2941, 1598, 1470, 1369, 1219, 1173, 1124, 1090, 1036, 910, 811, 735, 679, 593, 542 cm-1. HRMS (ESI): Calcd for C28H33NNaO5S, [M+Na] +: 518.1972, found: 518.1961. (1S,2S,3S,6R)-1-(5-methoxy-1-tosyl-1H-indol-3-yl)-6-methyl-3-(prop-1-en-2-yl)-6-vinylcyclohexane-1,2-diol (±15b). Colorless oil, 62.3 mg, 63% yield. 1H NMR (600 MHz, CDCl3) δ 7.81 (d, J = 9.3 Hz, 1 H), 7.67 (d, J = 8.1 Hz, 2 H), 7.53 (s, 1 H), 7.34 (s, 1 H), 7.27‒7.21 (m, 1 H), 7.17 (d, J = 8.0 Hz, 2 H), 6.87 (dd, J = 9.0, 2.4 Hz, 1 H), 6.05 (brs, 1 H), 4.99 (d, J = 11.1 Hz, 1 H), 4.93 (d, J = 9.6 Hz, 2 H), 4.80 (d, J = 17.4Hz, 1 H), 4.12 (brs, 1 H), 3.78 (s, 3 H), 2.94 (brs, 1 H), 2.63 (td, J = 10.5, 3.0 Hz, 1 H), 2.32 (s, 3 H), 2.08 (td, J = 14.1, 4.2 Hz, 1 H), 1.86-1.79 (m, 5 H), 1.60‒1.56 (m, 2 H), 1.02(s, 3 H) ppm. 13C NMR {1H} (150 MHz, CDCl3) δ 156.1, 146.5, 144.9, 141.8, 135.1, 129.8, 126.8, 114.5, 114.2, 113.5, 106.5, 79.7, 72.4, 55.7, 47.6, 45.8, 32.7, 25.3, 23.5, 21.7, 19.3 ppm. IR (KBr): ʋmax = 3543, 2937, 1598, 1470, 1369, 1220, 1173, 1123, 1036, 911, 811, 735, 680, 594, 543 cm-1. HRMS (ESI): Calcd for C28H33NNaO5S, [M+Na] +: 518.1972, found: 518.1983. (1S,2S,3S,6S)-1-(5-Bromo-1-tosyl-1H-indol-3-yl)-6-methyl-3-(prop-1-en-2-yl)-6-vinylcyclohexane-1,2-diol (±8c). Colorless liquid, 65.4 mg, 60% yield. 1H NMR (400 MHz, CDCl3) δ 8.03 (s, 1 H), 7.79 (d, J = 8.9 Hz, 1 H), 7.68 (d, J = 8.2 Hz, 2 H), 7.43 (s, 1 H), 7.32 (dd, J = 8.0, 4.0 Hz, 1 H), 7.20 (d, J = 8.0 Hz, 2 H), 6.07 (dd, J = 17.5, 11.0 Hz, 1 H), 4.97 (d, J = 10.0 Hz, 2 H), 4.89 (d, J = 10.9 Hz, 1 H), 4.69 (d, J = 17.7 Hz, 1 H), 4.22 (d, J = 10.2 Hz, 1 H), 2.92 (s, 1 H), 2.62‒2.56 (m, 1 H), 2.33 (s, 3 H), 2.24‒2.16 (m, 1 H), 1.86 (s, 3 H), 1.80‒1.64 (m, 2 H), 1.37‒1.32 (m, 1 H), 0.96 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 146.2, 145.3, 144.6, 134.9, 134.0, 132.8, 130.0, 127.1, 126.8, 126.6, 126.2, 124.4, 116.8, 114.9, 113.9, 113.1, 79.3, 71.4, 47.9, 44.6, 32.2, 25.1, 21.6, 20.6, 19.3 ppm. IR (KBr): ʋmax = 3475, 3415, 1637, 1618, 1439, 1373, 1176, 668, 588, 540, 473 cm-1. HRMS (ESI): Calcd for C27H30BrNNaO4S, [M+Na]+: 566.0971, found: 566.0966; m. p.: 192.5‒195.4 oC. (1S,2S,3S,6R)-1-(5-Bromo-1-tosyl-1H-indol-3-yl)-6-methyl-3-(prop-1-en-2-yl)-6-vinylcyclohexane-1,2-diol (±15c). Colorless liquid, 65.4 mg, 60% yield. 1H NMR (400 MHz, CDCl3) δ 8.17 (s, 1 H), 7.78 (d, J = 8.8 Hz, 1 H), 7.68 (d, J = 8.0 Hz, 2 H), 7.37 (s, 1 H), 7.32 (dd, J = 8.9, 1.9 Hz, 1 H), 7.18 (d, J = 8.1 Hz, 2 H), 6.07 (dd, J = 17.6, 10.9 Hz, 1H), 5.00 (d, J = 10.0 Hz, 1 H), 4.93 (d, J = 10.9 Hz, 2 H), 4.76 (d, J = 17.7 Hz, 1 H), 4.08 (d, J = 10.4 Hz, 1 H), 3.01 (s, 1H), 2.61 (t, J = 9.2 Hz, 1 H), 2.32 (s, 3 H), 2.09 (t, J = 13.6 Hz, 1 H), 1.81 (s, 3 H), 1.59-1.51 (m, 3 H), 1.00 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 146.3, 145.2, 144.5, 134.9, 133.7, 129.9, 127.1, 126.8, 116.8, 114.8, 114.7, 113.8, 79.5, 72.2, 47.7, 45.7, 32.2, 25.1, 23.1, 21.6, 19.3 ppm. IR (KBr): ʋmax = 3480, 3415, 2927, 1619, 1440, 1373, 1175, 911, 804, 706, 668, 588, 540, 475 cm-1. HRMS (ESI): Calcd for C27H30BrNNaO4S, [M+Na]+: 566.0971, found: 566.0968. (3S)-2-Hydroxy-3,7-dimethyl-1-(1-tosyl-1H-indol-3-yl)-3-vinyloct-6-en-1-one (±14). Using CSA as the acid, 20% yield of 14 was isolated. Colorless liquid. 1H NMR (400 MHz, CDCl3) δ 8.31‒8.27 (m, 2 H), 7.95 (d, J = 8.0 Hz, 1 H), 7.82 (d, J = 8.0 Hz, 2 H), 7.40‒7.32 (m, 2 H), 7.26 (d, J = 8.0 Hz, 2 H), 5.70 (dd, J = 10.8, 17.5 Hz, 1H), 5.13 (d, J = 10.9 Hz, 1 H), 5.08‒5.02 (m, 2 H), 4.56 (d, J = 7.7 Hz, 1 H), 3.34 (d, J = 7.8 Hz, 1 H), 2.35 (s, 3 H), 1.94‒1.84 (m, 2 H), 1.66 (s, 3 H), 1.62‒1.54 (m, 4 H), 1.49‒1.41 (m, 1


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H), 1.10 (s, 3 H) ppm. 13C NMR {1H} (100 MHz, CDCl3) δ 197.0, 146.2, 142.8, 137.4, 134.5, 133.9, 131.6, 130.4, 127.6, 127.3, 126.1, 125.1, 124.5, 123.1, 120.3, 115.3, 113.2, 80.8, 45.5, 36.3, 25.8, 21.7, 19.7, 17.8 ppm. IR (KBr): ʋmax = 3416, 2925, 1619, 1536, 1378, 1140, 1089, 988, 750, 662, 574, 537 cm-1. HRMS (ESI): Calcd for C27H31NNaO4S, [M+Na]+: 488.1866, found: 488.1865. ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website at DOI: 1H

NMR, 13C NMR spectra of new compounds, and Crystallographic Data of 8c and 15c (PDF)

AUTHOR INFORMATION Corresponding Author *E-mail: [email protected] ORCID Min Zhang: 0000-0002-3851-7836 Notes The authors declare no competing financial interest. ACKNOWLWDGMENTS We are grateful for the financial support from National Natural Science Foundation of China (21672029, 21871033), Chongqing Science and Technology Commission (cstc2018jcyjAX0421), and Sharing Fund of Large-scale Equipment (201712150118) of Chongqing University. We thank Mr Xiangnan Gong (CQU) for X-ray crystallographic analysis.

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