Gold-Catalysed Cycloisomerisation of Ynamides To Access 2,2-Disubstituted Tetrahydrothiophene Motifs

Abstract

Ynamides bearing a tethered allyl sulfoxide undergo a gold-catalysed cycloisomerisation to afford tetrahydrothiophene-2-carboxamides and their benzo-fused analogues. The reactions are initiated by a formal 7-endo-dig cyclisation and accommodate a range of different substituents. The use of N-allyl ynamides provided a route into novel spirocyclic ε-lactam structures.

Key words

gold - ynamides - isomerization - ylides - regioselectivity - thiophenecarboxamides

Publikationsverlauf

Eingereicht: 28. Januar 2021

Angenommen nach Revision: 13. März 2021

Accepted Manuscript online:
13. März 2021

Artikel online veröffentlicht:
07. April 2021

• References and Notes

• 1a Lee Y.-C, Kumar K. Isr. J. Chem. 2018; 58: 531
• 1b Quirós MT, Muñoz MP. Top. Heterocycl. Chem. 2016; 46: 117
• 2a Gorin DJ, Toste FD. Nature 2007; 446: 395
• 2b Fürstner A, Davies PW. Angew. Chem. Int. Ed. 2007; 46: 3410
• 2c Adcock HV, Davies PW. Synthesis 2012; 44: 3401
• 2d Zhang L. Acc. Chem. Res. 2014; 47: 877
• 2e Yeom H.-S, Shin S. Acc. Chem. Res. 2014; 47: 966
• 2f Wang Y, Muratore ME, Echavarren AM. Chem. Eur. J. 2015; 21: 7332
• 2g Harris RJ, Widenhoefer RA. Chem. Soc. Rev. 2016; 45: 4533
• 2h Ye L.-W, Zhu X.-Q, Sahani RL, Xu Y, Qian P.-C, Liu R.-S. Chem. Rev. 2021; in press
• 2i Wang T, Hashmi AS. K. Chem. Rev. 2021; in press
• 3a Pathania S, Narang RK, Rawal RK. Eur. J. Med. Chem. 2019; 180: 486
• 3b Feng M, Tang B, Liang SH, Jiang X. Curr. Top. Med. Chem. 2016; 16: 1200

For early examples, see:
• 4a Morita N, Krause N. Angew. Chem. Int. Ed. 2006; 45: 1897
• 4b Nakamura I, Sato T, Yamamoto Y. Angew. Chem. Int. Ed. 2006; 45: 4473

For a review, see:
• 4c Debrouwer W, Heugebaert TS. A, Roman BI, Stevens CV. Adv. Synth. Catal. 2015; 357: 2975
• 5 Davies PW, Albrecht SJ.-C. Angew. Chem. Int. Ed. 2009; 48: 8372
• 6a Lu B, Li Y, Wang Y, Aue DH, Luo Y, Zhang L. J. Am. Chem. Soc. 2013; 135: 8512
• 6b Shapiro ND, Toste FD. J. Am. Chem. Soc. 2007; 129: 4160
• 6c Li G, Zhang L. Angew. Chem. Int. Ed. 2007; 46: 5156
• 7a Hong F.-L, Ye L.-W. Acc. Chem. Res. 2020; 53: 2003
• 7b Campeau D, León Rayo DF, Mansour A, Muratov K, Gagosz F. Chem. Rev. 2021; in press
• 7c Evano G, Lecomte M, Thilmany P, Theunissen C. Synthesis 2017; 49: 3183
• 7d Wang X.-N, Yeom H.-S, Fang L.-C, He S, Ma Z.-X, Kedrowski BL, Hsung RP. Acc. Chem. Res. 2014; 47: 560
• 7e DeKorver KA, Li H, Lohse AG, Hayashi R, Lu Z, Zhang Y, Hsung RP. Chem. Rev. 2010; 110: 5064

For early examples see:
• 8a Davies PW, Cremonesi A, Martin N. Chem. Commun. 2011; 47: 379
• 8b Li C, Zhang L. Org. Lett. 2011; 13: 1738
• 8c Davies PW, Cremonesi A, Dumitrescu L. Angew. Chem. Int. Ed. 2011; 50: 8931
• 8d Kramer S, Odabachian Y, Overgaard J, Rottländer M, Gagosz F, Skrydstrup T. Angew. Chem. Int. Ed. 2011; 50: 5090
• 8e Mukherjee A, Dateer RB, Chaudhuri R, Bhunia S, Karad SN, Liu R.-S. J. Am. Chem. Soc. 2011; 133: 15372
• 8f Dateer RB, Shaibu BS, Liu R.-S. Angew. Chem. Int. Ed. 2012; 51: 113
• 8g Rettenmeier E, Schuster AM, Rudolph M, Rominger F, Gade CA, Hashmi AS. K. Angew. Chem. Int. Ed. 2013; 52: 5880
• 8h Li L, Shu C, Zhou B, Yu Y.-F, Xiao X.-Y, Ye L.-W. Chem. Sci. 2014; 5: 4057 ; For reviews, see ref. 7
• 9a Dos Santos M, Davies PW. Chem. Commun. 2014; 50: 6001
• 9b Baker T, Davies PW. Eur. J. Org. Chem. 2019; 2019: 5201
• 10 Adcock HV, Langer T, Davies PW. Chem. Eur. J. 2014; 20: 7262
• 11 Hamada T, Ye X, Stahl SS. J. Am. Chem. Soc. 2008; 130: 833
• 12 Cycloisomerisation of Ynamides: General Procedure AuPicCl₂ (5.0 mol%, 5 μmol) was added to a 0.2 M solution of the appropriate ynamide in DCE (0.1 mmol) in a flame-dried Schlenk tube under argon, and the mixture was heated at 70 °C. Upon completion of the reaction (TLC), the crude mixture was passed through a small plug of silica to remove gold residues. The solvent was then evaporated, and the residue was purified by column chromatography (hexanes–EtOAc). 1-Allyl-N-benzyl-N-(methylsulfonyl)-1,3-dihydro-2-benzothiophene-1-carboxamide (4b) Purified by column chromatography [silica gel, hexanes–EtOAc (7:3)] as a yellow viscous oil; yield: 31 mg (81%). IR (neat): 2925 (w), 1679 (s), 1351 (s), 1162 (s) cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 2.92 (s, 3 H) overlaps with 3.01–2.95 (m, 1 H), 3.10 (dd, J = 14.2, 7.4 Hz, 1 H), 4.19 (d, J = 14.2 Hz, 1 H), 4.33 (d, J = 16.0 Hz, 1 H), 4.41 (d, J = 14.2 Hz, 1 H), 4.83 (d, J = 16.0 Hz, 1 H), 4.92–5.05 (m, 2 H), 5.46–5.64 (m, 1 H), 7.14–7.31 (m, 9 H). ¹³C NMR (101 MHz, CDCl₃): δ = 238.0, 43.3, 47.2, 50.6, 69.0, 120.1, 125.2, 125.3, 127.8, 127.9, 128.4, 128.5, 128.6, 132.2, 135.6, 140.2, 141.0, 175.1. MS (TOF ES⁺): m/z = 410 (100%) [M + Na]⁺. HRMS (TOF ES⁺): m/z calcd for C₂₀H₂₁NNaO₃S₂: 410.0861; found: 410.0859. N,3-Diallyl-N-(methylsulfonyl)-2-thiaspiro[4.5]decane-3-carboxamide (9) Colourless viscous oil; yield: 21.3 mg (60%); IR (neat): 2924 (s), 2852 (m), 1681 (s), 1352 (s), 1165 (s) cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 1.21–1.63 (m, 10 H), overlaps with 1.53 (d, J = 13.6 Hz, 1 H), 2.55 (dd, J = 14.4, 7.2 Hz, 1 H), 2.70 (dd, J = 14.4, 5.8 Hz, 1 H), 2.69 (d, J = 10.7 Hz, 1 H), 2.77 (d, J = 10.7 Hz, 1 H), 2.96 (d, J = 13.6 Hz, 1 H), 3.28 (s, 3 H), 4.39–4.56 (m, 2 H), 5.05–5.20 (m, 2 H), 5.25–5.42 (m, 2 H), 5.63–5.81 (m, 1 H), 5.86–6.03 (m, 1 H). ¹³C NMR (101 MHz, CDCl₃): δ = 23.0, 24.0, 26.1, 34.6, 37.8, 43.3, 44.5, 45.8, 46.5, 47.7, 62.3, 119.5, 132.5, 132.8, 174.6. MS (TOF ES⁺): m/z = 380 (100%). HRMS (TOF ES⁺): m/z calcd for C₁₇H₂₇NNaO₃S₂: 380.1330; found: 380.1338.
• 13 To complement the 2-thiaspiro[4.5]decane motif 5 accessed from ynamides 2, their alkyne precursor was tested under the conditions previously developed for the reaction of terminal alkynes (see ref. 5), providing access to a 2-thiaspiro[5.5]undecan-4-one motif (see SI).
• 14a Zheng Y, Tice CM, Singh SB. Bioorg. Med. Chem. Lett. 2014; 24: 3673
• 14b Zheng Y.-J, Tice CM. Expert Opin. Drug Discovery 2016; 11: 831
• 15 Spagnol G, Heck M.-P, Nolan SP, Mioskowski C. Org. Lett. 2002; 4: 1767
• 16 Attempts to extrude sulfur dioxide from 13 were unsuccessful with no conversion even in diphenyl ether at 280 °C.