Regiodivergent Approach to α- and β-(Arylthio)alkenylphosphane Oxides and Sulfides: Aminophosphanes as Synthetic Auxiliaries

Abstract

β-(Arylthio)ethenylphosphane oxides and sulfides are easily prepared by nucleophilic addition of thiophenols to the CºC bond of the respective P,P-diphenyl-P-phenylethynyl P(V) derivatives. The regioisomeric α-(arylthio) analogues can be also prepared, starting from the same activated alkynes, by sequential nucleophilic addition of aminophosphanes and thiophenols. In these latter cases, aminophosphanes, which are recovered at the end of the processes, act just as synthetic auxiliaries for modulating the regiochemical outcome of the global thiophenol addition.

alkynes - aminophosphanes - nucleophilic additions - phosphorus - regioselectivity

References and Notes

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10

Representative Experimental Procedure and Spectral Data for Compounds 3
A solution of P,P-diphenyl-P-phenylethynylphosphane oxide (1, 0.3 g, 1 mmol), 4-methoxythiophenol (0.21 g, 1.5 mmol), and KHMDS (0.5 M soln in toluene, 0.4 mL, 0.2 mmol) in toluene (20 mL) was refluxed for 12 h under a nitrogen atmosphere. Then the solvent was removed under reduced pressure, and the residue was purified by chromatography on deactivated silica gel (5% Et₃N in hexane) with EtOAc-hexane 1:1 (v/v) and then EtOAc to yield a mixture of Z- and E-isomers; R _f = 0.5 (EtOAc). The subsequent fractional crystallization allowed the separation of the two isomers.
( Z )- P , P -Diphenyl- P -[2-phenyl-2-(4-methoxyphenyl-thio)]ethenylphosphane Oxide ( Z -3b)
White needles (from CH₂Cl₂-Et₂O), mp 196-197 ˚C. IR (Nujol): 1589, 1544, 1491, 1439, 1246, 1181, 1119, 739, 719, 698 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 3.63 (s, 3 H, OCH₃), 6.51 (d, 2 H, ^³ J _HH = 8.9 Hz, H_Ar), 6.53 (d, 1 H, ^² J _HP = 20.0 Hz, CHP), 6.88 (d, 2 H, ^³ J _HH = 8.9 Hz, H_Ar), 7.16-7.19 (m, 3 H, Ph), 7.38-7.45 (m, 2 H, Ph), 7.46-7.51 (m, 6 H, Ph₂), 7.87-7.94 (m, 4 H, Ph₂). ^¹³C NMR (75 MHz, CDCl₃): δ = 55.08 (OCH₃), 114.08, 122.41 (d, ^¹ J _CP = 104.5 Hz, PCH=C), 123.18 (quaternary), 128.04, 128.48, 128.50 (d, ^³ J _CP = 12.2 Hz, C _m ), 129.26, 131.19 (d, ^² J _CP = 9.8 Hz, C _o ), 131.50 (d, ⁴ J _CP = 2.8 Hz, C _p ), 134.35 (d, ^¹ J _CP = 106.7 Hz, C _i ), 134.4, 139.03 (d, ^³ J _CP = 14.4 Hz, quaternary), 159.20 (d, ^² J _CP = 1.0 Hz, PCH=C), 161.28 (quaternary). ^³¹P NMR (121 MHz, CDCl₃): d = 19.90. MS (EI): m/z = 443 (10) [M + 1]⁺, 442 (10) [M]⁺, 201 (100). Anal. Calcd for C₂₇H₂₃O₂PS (442.51): C, 73.28; H, 5.24. Found: C, 73.41; H, 5.10.
( E )- P , P -Diphenyl- P -[2-phenyl-2-(4-methoxyphenyl-thio)]ethenylphosphane Oxide ( E -3b)
White needles (from CH₂Cl₂), mp 119-120 ˚C. IR (Nujol): 1588, 1554 1492, 1439, 1247, 1176, 1167, 1116, 703, 691 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 3.82 (s, 3 H, OCH₃), 5.78 (d, 1 H, ^² J _HP = 15.2 Hz, CHP), 6.95 (d, 2 H, ^³ J _HH = 9.0 Hz, H_Ar), 6.99-7.11 (m, 3 H), 7.17-7.30 (m, 7 H), 7.37-7.50 (m, 5 H), 7.55 (d, 2 H, ^³ J _HH = 9.0 Hz, H_Ar). ^¹³C NMR (75 MHz, CDCl₃): δ = 55.53 (OCH₃), 113.50 (d, ^¹ J _CP = 104.6 Hz, PCH=C), 115.51, 121.23 (quaternary), 128.10 (d, ^³ J _CP = 12.1 Hz, C _m ), 128.22, 129.23 (d, ⁴ J _CP = 1.2 Hz,), 129.39, 130.81 (d, ^² J _CP = 9.5 Hz, C _o ), 130.88 (d, ⁴ J _CP = 2.7 Hz, C _p ), 133.69 (d, ^¹ J _CP = 106.6 Hz, C _i ), 136.86 (d, ^³ J _CP = 6.5 Hz, quaternary), 137.41, 161.12 (quaternary), 164.79 (d, ^² J _CP = 4.7 Hz, PCH=C). ^³¹P NMR (121 MHz, CDCl₃): d = 17.90. MS (EI): m/z = 443 (11) [M + 1]⁺, 442 (28) [M]⁺, 201 (100). Anal. Calcd for C₂₇H₂₃O₂PS (442.51): C, 73.28; H, 5.24. Found: C, 73.39; H, 5.38.

11 Dickstein JI. Millar SI. In The Chemistry of the Carbon-Carbon Triple Bond   Part 2:  Patai S. Wiley; Chichester: 1978.  p.813 

12

Representative Experimental Procedure and Spectral Data for Compounds 6
A solution of P,P-diphenyl-P-phenylethynylphosphane oxide (1, 0.3 g, 1 mmol), P,P-diphenyl-P-(4-tolylamino)-phosphane (0.44 g, 1.5 mmol), and KHMDS (0.5 M soln in toluene, 0.4 mL, 0.2 mmol) in anhyd toluene (20 mL) was refluxed for 24 h under a nitrogen atmosphere. Then, the solvent was removed under reduced pressure, and the residue was purified by chromatography on deactivated silica gel (5% Et₃N in hexane) with EtOAc-hexane 1:1 (v/v) and then EtOAc to yield 6a as orange prisms (from CH₂Cl₂-Et₂O), mp 153-155 ˚C. IR (Nujol): 1505, 1439, 1331, 1181, 1119, 722, 706, 695 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 2.29 (s, 3 H, CH₃), 6.82-6.86 (m, 6 H, H_Ar and Ph), 6.93-6.99 (m, 3 H, H_Ar and Ph), 7.17-7.26 (m, 4 H, Ph₂), 7.29-7.45 (m, 12 H, Ph₂), 7.63 (t, 1 H, ^² J _HP = ^³ J _HP = 21.2 Hz, CH), 7.64-7.69 (m, 4 H, Ph₂). ^¹³C NMR (100 MHz, CDCl₃): δ = 20.74 (CH₃), 124.06 (d, ^³ J _CP = 18.5 Hz, C₂-Ar), 127.35, 128.06 (d, ⁵ J _CP = 1.2 Hz, C₄-Ph), 128.26 (d, ^³ J _CP = 12.1 Hz, C _m ), 128.47 (d, ^³ J _CP = 12.1 Hz, C _m ), 128.87 (d, ^¹ J _CP = 102.5 Hz, C _i ), 129.55, 129.60, 130.77 (d, ^² J _CP = 9.7 Hz, C _o ), 131.30 (d, ⁴ J _CP = 2.7 Hz, C _p ), 131.92 (d, ⁴ J _CP = 2.4 Hz, C _p ), 132.80 (d, ^² J _CP = 9.2 Hz, C _o ), 133.12 (d, ^¹ J _CP = 105.4 Hz, C _i ), 134.00 (t, ^² J _CP = ^³ J _CP = 8.9 Hz, quaternary, C₁-Ph), 137.90 [dd, ^¹ J _CP = 87.6 Hz, ^² J _CP = 5.4 Hz, PCH = CP], 147.97 (d, ^² J _CP = 2.0 Hz, quaternary, C₁-Ar), 152.62 [d, ^¹ J _CP = 65.6 Hz, PCH=CP], C₄-Ar not observed. ^³¹P NMR (121 MHz, CDCl₃): δ = 4.39 (d, ^³ J _PP = 45.4 Hz, P=N), 18.03 (d, ^³ J _PP = 45.4 Hz, P=O). MS (EI): m/z = 594 (13) [M + 1]⁺, 593 (28) [M]⁺, 291 (100). Anal. Calcd for C₃₉H₃₃NOP₂ (593.20): C, 78.91; H, 5.60; N, 2.36. Found: C, 79.04; H, 5.46; N, 2.26.

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16

Representative Experimental Procedure and Spectral Data for Compounds 8
A solution of 6a (0.78 g, 1.32 mmol) and 4-methoxythio-phenol (0.21 g, 1.5 mmol) in anhyd toluene (20 mL) was refluxed for 12 h under a nitrogen atmosphere. Then, the solvent was removed under reduced pressure, and the residue was purified by chromatography on deactivated silica gel (5% Et₃N in hexane) with EtOAc-hexane 1:1 (v/v) and then EtOAc.
( Z )- P , P -Diphenyl- P -[2-phenyl-1-(4-methylphenyl-thio)]ethenylphosphane Oxide ( Z -8b)
R _f = 0.7 (EtOAc); white prisms (from CH₂Cl₂-Et₂O), mp 126-127 ˚C. IR (Nujol): 1589, 1493, 1434, 1298, 1246, 1201, 723, 694 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 3.66 (s, 3 H, OCH₃), 6.45 (d, 2 H, ^³ J _HH = 8.9 Hz, H_Ar), 6.72 (d, 2 H, ^³ J _HH = 8.9 Hz, H_Ar), 7.31-7.38 (m, 7 H, Ph₂ and Ph), 7.44-7.47 (m, 2 H, Ph), 7.78-7.81 (m, 4 H, Ph₂), 7.88-7.90 (m, 2 H, Ph), 8.27 (d, 1 H, ^³ J _HP = 17.3 Hz, CHP). ^¹³C NMR (100 MHz, CDCl₃): δ = 55.26 (OCH₃), 114.34, 124.63 (d, ^³ J _CP = 1.5 Hz, quaternary, C₁-Ar), 125.37 (d, ^¹ J _CP = 97.1 Hz, PC=CH), 128.22 (d, ^³ J _CP = 2.1 Hz, C _m ), 128.38, 129.72, 130.25, 130.42 (d _right , C _i ), 130.77, 131.87 (d, ⁴ J _CP = 2.8 Hz, C _p ), 132.38 (d, ^² J _CP = 9.7 Hz, C _o ), 134.58 (d, ^³ J _CP = 15.7 Hz, quaternary, C₁-Ph), 152.14 (d, ^² J _CP = 13.7 Hz, PC=CH), 158.25 (quaternary). ^³¹P NMR (162 MHz, CDCl₃): d = 28.30. MS (EI): m/z = 443 (23) [M + 1]⁺, 442 (66) [M]⁺, 303 (100). Anal. Calcd for C₂₇H₂₃O₂PS (442.51): C, 73.28; H, 5.24. Found: C, 73.15; H, 5.32.
( E )- P , P -Diphenyl- P -[2-phenyl-2-(4-methoxyphenyl-thio)]ethenylphosphane Oxide ( E -8b)
R _f = 0.55 (EtOAc); colourless oil. IR (Nujol): 1593, 1491, 1291, 1246, 1176, 1115, 722, 694 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 3.79 (s, 3 H, OCH₃), 6.83 (d, 2 H, ^³ J _HH = 8.8 Hz, H_Ar), 7.01-7.03 (m, 3 H), 7.24 (d, 1 H, ^³ J _HP = 48.2 Hz, CHP), 7.29-7.33 (m, 6 H, Ph₂), 7.37-7.42 (m, 4 H, Ph), 7.72-7.77 (m, 4 H, Ph₂). ^¹³C NMR (75 MHz, CDCl₃): δ = 55.42 (OCH₃), 115.19, 124.11 (d, ^³ J _CP = 5.0 Hz, quaternary, C₁-Ar), 127.67, 128.07 (d, ^³ J _CP = 12.2 Hz, C _m ), 128.28, 129.73, 131.66 (d, ⁴ J _CP = 3.0 Hz, C _p ), 131.92 (d, ^² J _CP = 9.3 Hz, C _o ), 131.97 (d, ^¹ J _CP = 89.8 Hz, PC=CH), 132.23 (d, ^¹ J _CP = 106.2 Hz, C _i ), 135.12, 135.52 (d, ^³ J _CP = 5.0 Hz, quaternary, C₁-Ph), 146.26 (d, ^² J _CP = 7.4 Hz, PC=CH), 160.13 (quaternary). ^³¹P NMR (121 MHz, CDCl₃): δ = 25.39. MS (EI): m/z = 442 (10) [M]⁺, 105 (100). Anal. Calcd for C₂₇H₂₃O₂PS (442.51): C, 73.28; H, 5.24. Found: C, 73.16; H, 5.32.

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