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Org. Synth. 2019, 96, 400-417

DOI: 10.15227/orgsyn.096.0400

Preparation of a Diisopropylselenophosphoramide Catalyst and its Use in Enantioselective Sulfenoetherification

Submitted by Scott E. Denmark,* Pavel Ryabchuk, Hyung Min Chi, and Anastassia Matviitsuk¹

Checked by Michael Rombola and Sarah E. Reisman

1. Procedure (Note 1)

A. Dichloro(diisopropylamino)phosphine (1) A flame-dried, 250-mL, two-necked, round-bottomed flask (24/40 joints) (Note 2) containing a 16 x 37 mm Teflon-coated, ellipsoid-shaped magnetic stirring bar is fitted with a nitrogen inlet adaptor on the central neck and a rubber septa on the side neck, and a thermocouple probe is inserted through the septa. The flask is evacuated and back-filled with nitrogen three times. Phosphorus trichloride (2.0 mL, 22.9 mmol) is added via syringe through a rubber septum, followed by the addition of hexanes (50 mL) via syringe (Note 3) (Figure 1). The resulting solution is cooled to +2 °C (internal temperature) with an ice-bath, and diisopropylamine (6.0 mL, 42.8 mmol, 1.87 equiv) (Note 4) is added dropwise via syringe over 10 min, whereupon the solution immediately turns into a white suspension. The flask is removed from the bath and the mixture is stirred for 1 h at 23 °C (Figure 2).

Figure 1. Reaction set-up Figure 2. Reaction appearance

The gas inlet adaptor is replaced with an oven-dried Schlenk filter (160 mm long, Ø - 40 mm, medium porosity) and the white suspension is filtered to a flame-dried, 500-mL round-bottomed-flask under high vacuum (0.1 mmHg) (Note 5) (Figure 3). The resulting white cake is washed with hexanes (30 mL x 3) to give a turbid solution, and the filtrate is concentrated by rotary evaporation (23 °C, 10 mmHg). The crude material is transferred to a 50-mL, round-bottomed flask with 20 mL of hexanes, concentrated by rotary evaporation (23 °C, 10 mmHg) to afford 3.22 g (69%) of crude product as a cloudy oil. This oil is further purified by short-path distillation (bp = 49-50 °C, 0.7 mmHg) (Note 6) to yield 2.75 g (59%) of dichloro(diisopropylamino)phosphine 1 as a colorless solid which melts upon gentle warming (Notes 7 and 8).

Figure 3. Filtration process, with the cold bath removed for clarity of the photo

B. (R)-4-(Diisopropylamino)-3,5-dimethyl-4,5-dihydro-3H-dinaphtho[2,1-d:1',2'-f][1,3,2]diazaphosphepine-4-selenide) (R-cat). An oven-dried, 100-mL Schlenk flask, fitted with a rubber septum through which is inserted a thermocouple probe, is charged with a 1.7 cm, Teflon-coated, magnetic oval stir bar. The flask is evacuated under vacuum and back-filled with nitrogen three times. Under increased nitrogen flow the flask is charged with (R)-N,Nʹ-dimethyl-1,1'-binaphthyl-2,2'-diamine 2 (1.56 g, 5.0 mmol) followed by the addition of anhydrous THF (33 mL) via syringe and then is placed in a dry ice/i-PrOH bath (Notes 9 and 10). After stirring the solution for 30 min at −74 °C (internal temperature), a solution of n-BuLi in hexanes (4.29 mL, 2.33 M, 10.0 mmol, 2.0 equiv) is added dropwise over 10 min via syringe whereupon the solution turned deep-orange (Note 11). The flask is then removed from the cooling bath and the solution is stirred for 20 min such that the internal temperature reaches 8 °C and the orange color intensifies. Then the flask is immersed back into the dry ice/i-PrOH bath and the solution is stirred for another 30 min. When the solution reaches an internal temperature of −74 °C, a solution of dichloro(diisopropylamino)phosphine 1 (0.91 mL, 5.0 mmol, 1.0 equiv) in THF (8 mL) is added dropwise via syringe over 10 min (Note 12). The flask is then removed from the cooling bath and the solution is stirred for 45 min as the internal temperature reaches +18 °C and the solution turns from bright orange to yellow. The rubber septum is removed and under increased nitrogen flow selenium powder (1.18 g, 15.0 mmol, 3.0 equiv) is then added in one portion with a spatula whereupon the color turns brown-black immediately. The mixture is stirred at room temperature for 1 h (Note 13) and the resulting heterogeneous mixture is vacuum-filtered through a pad of Celite (25 g) in a sintered glass funnel (35 mm Ø, porosity 3) into a 250-mL, round-bottomed flask (Figure 4). The reaction flask and Celite are washed with EtOAc (5 × 50 mL) and the filtrate is combined before being concentrated by rotary evaporation (25 °C, ca. 20 mmHg) to afford a yellow foam (Figure 5).

Figure 4. Filtration through Celite Figure 5. Crude as a yellow foam

The crude product is purified by flash chromatography on silica gel to afford (R)-cat (2.08 g, 80%) as a pale yellow solid (Note 14 and 15) (Figure 6).

Figure 6. Left: TLC of the crude reaction mixture. Middle: fractions 60-69 of the flash chromatography. Right: isolated product.

For further purification, the product is placed in a 100 mL round-bottomed flask equipped with a condenser, a 1.3 cm Teflon-coated magnetic stirbar, and 20 mL pentane. The mixture is refluxed for 2 min. The mixture is then cooled to room temperature, and the solids are filtered using a sintered glass funnel and a small amount of pentane (10 mL), leaving the purified product on the filter as a white solid. The solid is transferred into a 50-mL round-bottomed flask with dichloromethane (8 mL) and concentrated by rotary evaporation (25 °C, ca. 20 mmHg). The solid is then placed under vacuum for 18 h (0.1 mmHg, 70 °C) to give the (R)-cat (1.69 g, 65%) as a white powder (Note 16) (Figure 7).

Figure 7. (R)-cat upon trituration

C. [(1S,2R)-2-Methoxy-1-propylpentyl]thiobenzene (4). An oven-dried, 100-mL Schlenk flask, fitted with a rubber septum, is charged with a 2.1 cm Teflon-coated magnetic oval stir bar, phenylthiophthalimide (2.553 g, 10.0 mmol, 1.0 equiv), (R)-cat (260 mg, 0.5 mmol, 0.05 equiv), trans-4-octene 3 (1.122 g, 1.57 mL, 10.0 mmol), and methanol (641 mg, 810 µL, 20.0 mmol, 2.0 equiv). The flask is flushed with nitrogen via a nitrogen line and charged with anhydrous dichloromethane (50 mL) with a 50-mL syringe (Note 17) (Figure 8).

Figure 8. Reaction set-up

The stirred homogeneous solution is cooled to -20 °C using a cryocool unit (Note 18). After 10 min, the internal temperature is stabilized to -20 °C and MsOH (650 µL, 10.0 mmol, 1.0 equiv) is added dropwise to the cooled solution via syringe over 1 h (Note 19). The resulting yellow solution is stirred at -20 °C for 48 h (Note 20) (Figure 9).

The reaction is quenched by the addition of sat. aq. NaHCO₃ solution (50 mL) with stirring. The resulting biphasic mixture is transferred to a 250-mL separatory funnel and the reaction flask is rinsed with additional dichloromethane (20 mL). After vigorous extraction, the organic layer is separated and the remaining aqueous layer is further extracted with CH₂Cl₂ (2 x 50 mL). The combined organic extracts are dried over Na₂SO₄ (10 g), filtered through a 30-mL, coarse porosity sintered glass funnel, and then are concentrated on a rotary evaporator (23 °C, 10 mmHg) to afford yellow solid (4.06 g). The crude product is purified by flash chromatography on silica gel to afford 4 (1.66 g, 66%) as a pale-yellow oil (Notes 21 and 22).

Figure 9. Reaction temperature control

2. Notes

1. Prior to performing each reaction, a thorough hazard analysis and risk assessment should be carried out with regard to each chemical substance and experimental operation on the scale planned and in the context of the laboratory where the procedures will be carried out. Guidelines for carrying out risk assessments and for analyzing the hazards associated with chemicals can be found in references such as Chapter 4 of "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011; the full text can be accessed free of charge at https://www.nap.edu/catalog/12654/prudent-practices-in-the-laboratory-handling-and-management-of-chemical. See also "Identifying and Evaluating Hazards in Research Laboratories" (American Chemical Society, 2015) which is available via the associated website "Hazard Assessment in Research Laboratories" at https://www.acs.org/content/acs/en/about/governance/committees/chemicalsafety/hazard-assessment.html. In the case of this procedure, the risk assessment should include (but not necessarily be limited to) an evaluation of the potential hazards associated with Phosphorus trichloride, hexanes, diisopropylamine, (R)-N,Nʹ-dimethyl-1,1'-binaphthyl-2,2'-diamine, tetrahydrofuran, dry ice, isopropyl alcohol, n-butyllithium, selenium powder, Celite, ethyl acetate, silica gel, pentane, dichloromethane, phenylthiophthalimide, trans-4-octene, methane-sulfonic acid, sodium bicarbonate, sodium sulfate, 1,3,5-trimethoxybenzene, acetone, and CDCl₃.

2. The use of 24/40 joints was critical to prevent solidifying of the methanesulfonic acid in the syringe. The use of smaller joints (14/20) resulted in significantly slower filtration of the amine salts.

3. Phosphorus trichloride (ReagentPlus, 99%) was purchased from Sigma-Aldrich Co. and was freshly distilled from CaH₂. Hexanes (Fisher, HPLC grade) was dried by percolation through two columns packed with neutral alumina under a positive pressure of argon.

4. Diisopropylamine (Alfa Aesar, 99+%) was freshly distilled from CaH₂.

5. To facilitate the transfer of the white precipitate to the porous filter, the original flask is washed with hexanes (3 x 30 mL), which is added via syringe through the rubber septum. A magnet is used to fix the stirbar to the bottom of the flask to prevent clogging. The filtrate is cooled in a dry ice/acetone bath during filtration.

6. Room temperature water was only intermittently run through the condenser during distillation to prevent clogging.

7. Characterization data for product 1: ¹H NMR pdf (300 MHz, CDCl₃) δ: 1.27 (d, J = 6.9 Hz, 12H), 3.92 (tt, J = 13.2, 6.8 Hz, 2H); ¹³C NMR pdf(75 MHz, CDCl₃) δ: 23.5 (d, J = 8.9 Hz), 48.3 (d, J = 13.9 Hz); ³¹P NMR pdf (121 MHz, CDCl₃) δ: 169.5 (s); mp = 26-27 °C (upon standing); bp = 49-50 °C (0.7 mmHg). The purity of 1 was determined to be 97% as measured by Quantitative - NMR pdf analysis using biphenyl as an internal standard.

8. A second reaction on identical scale provided 2.84 g (62%) of the compound 1 with identical purity.

9. THF (Fisher, HPLC grade) was dried by percolation through two columns packed with neutral alumina under a positive pressure of argon.

10. (R)-N,N'-Dimethyl-1,1'-binaphthyl-2,2'-diamine 2 can be synthesized following a previously published procedure (Org. Synth. 2019, 96, 382-399).

11. The internal temperature was monitored using digital thermometer, the temperature probe was placed through the rubber septum. The temperature was monitored during the addition and did not exceed −69 °C.

12. The temperature was monitored during the addition and did not exceed −65 °C.

13. Selenium (≥99.5%, powder, - 100 mesh) was purchased from Sigma-Aldrich Co. and used as received.

14. (R)-Cat was purified by flash column chromatography (silica gel, 90 g, diameter: 45 mm, height: 140 mm, ca. 25 mL fractions, column packed using hexanes, sample loaded as a suspension on Celite (5.0 g), eluent: hexanes, 0.2 L followed by 0.5 L of 99:1 hexanes/EtOAc, then 0.5 L of 98:2 hexanes/EtOAc, then 0.5 L of 97:3 hexanes/EtOAc, then 0.5 L of 96:4 hexanes/EtOAc and then 0.2 L of 95:5 hexanes/EtOAc). The product is obtained in fractions 51-83 (R_f 0.42 (hexanes/EtOAc, 9:1), which were concentrated by rotary evaporation (25°C, 10 mmHg). The observed impurity was collected in fractions 44-47 (41 mg, R_f0.50 (hexanes/EtOAc, 9:1). Unreacted 2 (34 mg, 2%, R_f0.28 (hexanes/EtOAc, 9:1) was recovered from fractions 84-94. The (R)-cat was triturated as described above to give a white powder. The purity was determined to be 96% as measured by Quantitative - NMR pdf analysis versus 1,3,5-trimethoxybenzene as an internal standard.

15. Characterization data for (R)-cat:¹H NMR pdf (500 MHz, CDCl₃) δ: 1.35 (br. s, 6H, HC(14) and HC(14')), 1.45 (br. s, 6H, HC(13) and HC(13')), 3.09 (d, J = 13.8 Hz, 3H, HC(11')), 3.33 (d, J = 12.5 Hz, 3H, HC(11)), 3.64 (br. s, 2H, HC(12) and HC(12')), 6.97 (d, J = 8.6 Hz, 1H, HC(9')), 7.10 (ddd, J = 8.2, 6.7, 1.4 Hz, 1H, HC(8')), 7.23 (ddd, J = 8.4, 6.6, 1.3 Hz, 1H, HC(8)), 7.28 (d, J = 7.4 Hz, 1H, HC(9)), 7.35 (t, J = 7.4 Hz, 1H, HC(7')), 7.43 (ddd, J = 8.1, 6.6, 1.4 Hz, 1H, HC(7)), 7.66 (d, J = 8.9 Hz, 1H, HC(3')), 7.70 (dd, J = 8.9, 1.4 Hz, 1H, HC(3)), 7.86 (d, J = 7.6 Hz, 1H, H(C(6')), 7.91 (t, J = 9.3 Hz, 2H, HC(4) and HC(4')), 7.98 (d, J = 8.9 Hz, 1H, HC(6)); ¹³C NMR pdf (126 MHz, CDCl₃) δ: 22.7 (C(14) and C(14')), 24.9 (C(13) and C(13')), 36.8 (d, J = 6.2 Hz, C(11')), 37.6 (d, J = 12.6 Hz, C(11)), 48.3 (C(12) and C(12')), 122.8 (C3), 123.0 (d, J = 2.6 Hz, C(3')), 124.8 (C(7'), 125.1 (C(7)), 125.7 (C(8')), 126.0 (C(8)), 127.4 (C(9')), 127.7-127.8 ((C(4), C(4'), C(1'), and C(9)), 128.2 (C(1)), 128.3 (C(6')), 129.0 (d, J = 1.9 Hz, C(6)), 130.7 (C(5)), 131.4 (d, J = 2.2 Hz, C(5')), 132.3 (d, J = 1.8 Hz, C(10')), 132.7 (C(10)), 142.2 (d, J = 1.8 Hz, C(2')), 143.4 (d, J = 6.1 Hz, C(2)); ³¹P NMR pdf (121 MHz, CDCl₃) δ: 79.7 (br s). IR (KBr): 3062, 2962, 1618, 1594, 1506, 1466, 1367, 1330, 1270, 1260, 1178, 1146, 1087, 982, 931, 848, 813, 750, 698, 634, 604 cm^-1. [α]²²_D = -418.99 (c = 0.935, CHCl₃) [non-linear ORD]; HRMS (ES): m/z calcd. for C₂₈H₃₃N₃PSe [M+H]: 522.1577, found: 522.1560; mp 148-149 °C.

16. A second reaction on the same scale provided 1.63 g (63%) of the compound (R)-cat with identical purity.

17. Although the reaction has not been shown to be specifically sensitive to oxygen or air, the reaction was run using anhydrous dichloromethane under N₂. Anhydrous dichloromethane in all sections was obtained by passing through activated alumina under atmosphere of argon (H₂O content <10 ppm, Karl Fisher titration).

18. The internal temperature of the solution was monitored via a thermocouple digital temperature probe. The temperature of the bath temperature fluctuated between -18 to -22 °C while the internal temperature stayed in a smaller window of fluctuation between -19 to -20 °C.

19. Methanesulfonic acid (≥99.5%) was purchased from Sigma-Aldrich Co and was distilled from P₂O₅. Methanesulfonic acid was added neat to the reaction mixture. However, because the melting point of the methanesulfonic acid is 19 °C, it was carefully added dropwise positioning the needle away from the solution to prevent solidifying. The use of a long-neck Synthware Modified Schlenk Tube Flask (purchased from Kemtech America) with a 24/40 joint was found to be necessary to prevent solidifying. Addition of methanesulfonic acid to flasks bearing 14/20 joints resulted in solidifying. Methanesulfonic acid could not be added as a solution in dichloromethane due to the partial phase separation from the dichloromethane over time.

20. The solution is stirred at 600 rpm throughout the reaction. The reaction becomes heterogeneous as it proceeds due to the formation of phthalimide crystals. A reaction previously monitored by TLC and ¹H NMR on a smaller scale was found to have reached >95% conversion by 48 h. For this reaction, it was checked at 48 h by TLC on Merck silica gel 60 F254 TLC glass plates and visualized with UV light and ceric ammonium nitrate staining solution. R_f (product): 0.55 (40:1 hexanes/acetone).

21. The crude product was loaded onto a column (silica gel, 300 g, diameter: 60 mm, height: 150 mm) that was dry packed with 1.5 L of 40:1 hexanes:acetone, ca. 50 mL fractions, sample loaded as a suspension on Celite (5.0 g), eluent: 1.5 L of 40:1 hexanes:acetone. The desired product was obtained in fractions 13-26, which was concentrated by rotary evaporation (23 °C, 10 mmHg). The product has been characterized as follows: ¹H NMR pdf (500 MHz, CDCl₃) δ: 0.91 (t, J = 7.0 Hz, 3H), 0.93 (t, J = 7.0 Hz, 3H), 1.28 - 1.37 (m, 1H), 1.39 - 1.59 (m, 4H), 1.62 - 1.73 (m, 3H), 3.20 (dt, J = 9.3, 4.0 Hz, 1H), 3.30 (dt, J = 8.2, 4.2 Hz, 1H), 3.38 (s, 3H), 7.20 (m, 1H), 7.27 (m, 2H), 7.42 (m, 2H); ¹³C NMR pdf (126 MHz, CDCl₃) δ: 14.0, 14.1, 19.2, 20.9, 33.0, 33.8, 53.1, 58.4, 83.5, 126.6, 128.9, 131.8, 136.8; IR (neat): 3075, 2957, 2934, 2872, 2826, 1584, 1478, 1465, 1439, 1376, 1300, 1259, 1225, 1191, 1142, 1095, 1025, 1025, 962, 932, 888, 826, 746, 691 cm^-1; HRMS (ESI): m/z calcd for C₁₅H₂₄OS [M+NH₄] 270.1886, found 270.1878; [α]²²_D = -14.8° (c = 1.12, CHCl₃). SFC analysis was performed using a Mettler SFC supercritical CO₂ analytical chromatography system (CO₂ = 1450 psi, column temperature = 40 °C, with a Chiralcel IC column (2% iPrOH/CO₂, 2.5 mL/min, 210 nm): 98.2:1.8 e.r. (t_R (major) = 3.8 min, t_R (minor) = 6.9 min). The purity was determined to be 96% as measured by Quantitative - NMR pdf analysis versus 1,3,5-trimethoxybenzene.

22. A second reaction on the same scale provided 1.52 g (60%) of the compound with identical purity.

Working with Hazardous Chemicals

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3. Discussion

Sulfur-containing groups are frequently found in many pharmaceutical and agricultural agents, as well as in natural products.² In addition thioethers have a rich functional group chemistry making them useful sites of manipulation. Introduction of thioethers via alkene sulfenofunctionalization is a very powerful transformation, which results in a simultaneous formation of vicinal stereocenters.³ Despite the attractiveness of this approach the stereocontrolled transfer of sulfur groups to alkenes remains underdeveloped and, for a long time, only two examples of direct enantioselective sulfenofunctionalization were known, both employing chiral reagents in stoichiometric quantities.⁴

The diastereo- and enantioselective intermolecular sulfenoetherification described herein employs a BINAM-based selenophosphoramide catalyst developed in our laboratories.⁵ The reaction proceeds through formation of an enantioenriched thiiranium ion,⁶ which is subsequently captured by a nucleophile to afford the product. The stereodetermining step is the formation of the thiiranium ion, which is configurationally stable below 0 °C.⁷ Because of the intermediacy of the thiiranium ion, this method exclusively affords anti products with exceptional diastereoselectivity.

The catalytic cycle begins with a transfer of a phenylsulfenyl moiety from A to the Lewis basic selenium atom and generation of the catalytically active species B (Scheme 1). Evidence for theses species is provided by X-ray crystallography and ³¹P NMR spectroscopy.^5a,g Transfer of the sulfenium ion from B to an alkene forms intermediate thiiranium ion C, which is then captured with a nucleophile to afford the corresponding enantioenriched sulfenofunctionalized product D.

The origin for the improved selectivity of above described diisopropylamine substituted catalyst over the other previously developed selenophosphoramide catalysts could be attributed to the increased steric interactions.^5a,g Enhanced steric interactions with the diisopropylamino group leads to better differentiated transition states of alkene and catalytically active species during the formation of thiiranium ion. Previously reported intermolecular sulfenylation of 4-octene employing a less sterically demanding azepane substituted selenophosphoramide catalyst afforded phenylthio methyl ether with a lower er (Table 1, entry 2). Introducing even greater steric interaction by substitution on the 2,6-position of the phenyl on the sulfenylating reagent with bulkier isopropyl groups showed further enhanced enantioselectivity (entry 4). Thiofunctionalization of the same substrate with a new sulfenylating agent was exceptionally selective even at elevated temperatures.^5g The suitability of a terminal double bond was also showcased in an intermolecular functionalization with 1-octene and MeOH as the nucleophile (entries 5 and 6). Other oxygen-based nucleophiles were tested in the described transformation; for example, acetic acid was an effective nucleophile for the intermolecular thiofunctionalization giving corresponding 4-(5-phenylthio)octyl acetate in good yield and er (entry 3).

Scheme 1.Proposed catalytic cycle of Lewis-base catalyzed sulfenofunctionalization.

Table 1. Intermolecular sulfenofunctionalization.

The scope of the sulfenofunctionalization has been further extended to intramolecular sulfenofunctionalization by employing oxygen-,^5a,g nitrogen-,^5d and carbon-based^5b,c,e nucleophiles tethered to the unactivated alkenes. Various enantiomerically enriched tetrahydropyrans, − furans and lactones can be constructed from corresponding acids and alcohols (eq 1-3). Nitrogen-containing heterocycles, such as piperidines, pyrrolidines and azepanes can be accessed via sulfenoamination of corresponding tosyl-protected amines (eq 4-5). Finally, sulfenofunctionalization can also incorporate aromatic nucleophiles in intramolecular carbosulfenylation yielding enantioenriched decalins (eq 6).

Finally, the selenophosphoramide catalyst has also been used in enantioselective sulfenylation of silyl enol ethers to afford α-sulfenylated ketones (eq 7)^.5f For this transformation a new sulfenylating agent that did not require additional Brønsted acid activation is employed. N-Phenylthiosaccharin successfully transfers the S-phenyl moiety to the substrate under acid-free conditions, avoiding acidic hydrolysis of the silyl enol ether.

References and Notes

Department of Chemistry, Roger Adams Laboratory, University of Illinois at Urbana-Champaign. Urbana, IL, 61801, email: sdenmark@illinois.edu, ORCID: 0000-0002-1099-9765.
(a) Metzner, P. & Thuillier, A. Sulfur Reagents in Organic Synthesis (Academic Press, 1994). (b) Page, P. (ed.) Organosulfur Chemistry: Synthetic Aspects (Academic Press, 1995). (c) Prinsep, M. R. Sulfur-containing natural products from marine invertebrates. Stud. Nat. Prod. Chem. 2003, 28, 617-751.
de la Mare, P. B. D. & Bolton, R. (eds) in Electrophilic Additions to Unsaturated Systems 2^nd edn, Vol. 9, 198-246 (Elsevier, 1982).
(a) Archer, N. J., Rayner, C. M., Bell, D.; Miller, D. Synlett., 1994, 617-619. (b) Lucchini, V., Modena, G. & Pasquato, L. J. Chem. Soc. Chem. Commun. 1994, 1565-1566.
(a) Denmark, S. E.; Kornfilt, D. J.-P.; Vogler, T. J. Am. Chem. Soc. 2011, 133, 15308-15311. (b) Denmark, S. E.; Jaunet, A. J. Am. Chem. Soc. 2013, 135, 6419-6422. (c) Denmark, S. E.; Jaunet, A. J. Org. Chem. 2014, 79, 140-171. (d) Denmark, S. E.; Chi, H. M. J. Am. Chem. Soc. 2014, 136, 3655-3663. (e) Denmark, S. E.; Chi, H. M. J. Am. Chem. Soc. 2014, 136, 8915-8918. (f) Denmark, S. E.; Rossi, S.; Webster, M. P.; Wang, H. J. Am. Chem. Soc. 2014, 136, 13016-13028. (g) Denmark, S. E.; Hartmann, E.; Kornfilt, D. J. P.; Wang, H. Nat. Chem., 2014, 6, 1056-1064
(a) Smit, W. A., Zeﬁrov, N. S., Bodrikov, I. V.; Krimer, M. Z. Acc. Chem. Res. 1979, 12, 282-288. (b) Rayner, C. M. in Organosulfur Chemistry: Synthetic Aspects (ed. Page, P.) Ch. 3 (Academic Press, 1995).
Denmark, S. E.; Vogler, T. Chem. Eur. J. 2009, 15, 11737-11745.

Appendix
Chemical Abstracts Nomenclature (Registry Number)

Phosphorus trichloride: Phosphorus trichloride; (7719-12-2)

Diisopropylamine: diisopropylamine; (108-18-9)

1,1-Dichloro-N,N-diisopropylphosphanamine: Dichloro-N,N-diisopropylamino-phosphane; (1) (921-26-6)

(R)-N,Nʹ′-dimethyl-1,1'-binaphthyl-2,2'-diamine: [1,1'-Binaphthalene]-2,2'-diamine, N2,N2'-dimethyl-, (1R)-; (2) (93713-30-5)

n-Butyllithium: Lithium, butyl-; (109-72-8)

Selenium: Selenium (7782-49-2)

(R)-4-(Diisopropylamino)-3,5-dimethyl-4,5-dihydro-3H-dinaphtho[2,1- d:1',2'-f][1,3,2]diazaphosphepine-4-selenide) (R-cat): 4H-Dinaphtho[2,1-d:1',2'-f] [1,3,2]diazaphosphepin-4-amine, 3,5-dihydro-3,5-dimethyl-N,N-bis(1-methylethyl)-, 4-selenide, (11bR)- ; (1627528-49-7)

Phenylthiophthalimide: 1H-Isoindole-1,3 (2H)-dione, 2-(phenylthio)-; (14204-27-4)

trans-4-Octene: 4-Octene, (4E)-; (3) (14850-23-8)

Methanol: Methanol; (67-56-1)

MsOH: Methanesulfonic acid; (75-75-2)

[(1S,2R)-2-Methoxy-1-propylpentyl]thiobenzene: [(1S,2R)-2-Methoxy-1-propylpentyl]thiobenzene; (4) (1202357-37-6)

	Scott E. Denmark was born in Lynbrook, New York on 17 June 1953. He obtained an S.B. degree from MIT in 1975 and his D.Sc.Tech. (with Albert Eschenmoser) from the ETH Zürich in 1980. That same year he began his career at the University of Illinois. He was promoted to associate professor in 1986, to full professor in 1987 and since 1991 he has been the Reynold C. Fuson Professor of Chemistry. His research interests include the invention of new synthetic reactions, organoelement chemistry and the origin of stereocontrol in fundamental carbon-carbon bond forming processes.
	Pavel Ryabchuk was born in Moscow, Russia in 1986. He received his diploma in chemistry from Moscow State University in 2008. He obtained his Ph.D. in chemistry in 2013 for research conducted under Professor Michael Rubin. He was a postdoctoral researcher with Professor Scott E. Denmark at University of Illinois at Urbana-Champaign from 2014-2016 and is currently a postdoctoral research associate with Professor Matthias Beller at the Leibniz Institute in Rostok.
	Hyung Min Chi was born in Champaign, IL in 1984. He received his Bachelor's degree in chemistry from Seoul National University in 2009 and his Ph.D. with Professor Scott E. Denmark's at University of Illinois at Urbana-Champaign in 2016 on the enantioselective, catalytic sulfenoamination and carbosulfenylation reactions of unactivated olefins with selenophosphoramide catalysts. He is currently a postdoctoral research associate with Prof. Scott Snyder at the University of Chicago.
	Anastassia Matviitsuk was born in Narva, Estonia in 1989. She received her BSc and MSc degrees in chemistry from Humboldt University of Berlin (with Professor Rainer Mahrwald). She obtained her Ph.D. in chemistry in 2018 from University of St Andrews for research conducted under the supervision of Professor Andrew D. Smith. She is currently a postdoctoral researcher in Professor Scott E. Denmark's research laboratory at University of Illinois at Urbana-Champaign.
	Michael Rombola was born in Rochester, NY in 1989. He received a B.S. in biology from Cornell University in 2011. He earned a Ph.D. in organic chemistry from the University of Chicago in 2018 working in the lab of Prof. Viresh H. Rawal. He is currently a postdoctoral researcher in the lab of Prof. Sarah E. Reisman at the California Institute of Technology.

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