Highly Diastereoselective Synthesis of N-tert-Butylsulfinylpropargylamines through Direct Addition of Alkynes to N-tert-Butanesulfinimines

Abstract

Direct addition of a variety of alkynes to N-tert-butanesulfinyl aldimines in the presence of a suitable base provided the corresponding N-tert-butylsulfinylpropargylamines in high yields and high diastereoselectivity.

Key words

imine - alkynylation - N-tert-butylsulfinylpropargyl­amine - diastereoselectivity

References and Notes

• 1a Porco JA. Schoenen FJ. Stout TJ. Clardy J. Schreiber SL. J. Am. Chem. Soc.  1990,  112:  7410 
• 1b Kauffman GS. Harris GD. Dorow RL. Stone BPR. Parsons RL. Pesti J. Magnus NA. Fortunak JM. Confalone PN. Nugent WA. Org. Lett.  2000,  2:  3119 
• Some examples of preparation of propargylic amines:
• 2a Fujisawa T. Nagai M. Koike Y. Shimizu M. J. Org. Chem.  1994,  59:  5865 
• 2b Enders D. Schankat J. Helv. Chim. Acta  1995,  78:  970 
• 2c Harwood LM. Vines KJ. Drew MGB. Synlett  1996,  1051 
• 2d Brasseur D. Marek I. Normant J.-F. Tetrahedron  1996,  52:  7235 
• 2e Sato Y. Nishimata T. Mori M. Heterocycles  1997,  44:  443 
• 2f Cossy J. Poitevin C. Pardo DG. Peglion J.-L. Dessinges A. Synlett  1998,  251 
• 2g Courtois G. Desre V. Miginiac L. J. Organomet. Chem.  1998,  570:  279 
• 2h Florio S. Troisi L. Capriati V. Suppa G. Eur. J. Org. Chem.  2000,  65:  3793 
• For examples, see:
• 3a Huffman MA. Yasuda N. DeCamp AE. Grabowski EJJ. J. Org. Chem.  1995,  60:  1590 
• 3b Fischer C. Carreira EM. Org. Lett.  2001,  3:  4319 
• 3c Li C.-J. Wei C. Chem. Commun.  2002,  268 
• 3d Wei C. Li C.-J. J. Am. Chem. Soc.  2002,  124:  563 
• 3e Jiang B. Si Y.-G. Tetrahedron Lett.  2003,  44:  6767 
• 3f Benaglia M. Negri D. DellAnna G. Tetrahedron Lett.  2004,  45:  8705 
• 3g Fischer C. Carreira EM. Org. Lett.  2004,  6:  1497 
• 3h Jiang B. Si YG. Angew. Chem. Int. Ed.  2004,  43:  216 
• 3i Wei CM. Li CJ. J. Am. Chem. Soc.  2002,  124:  5638 
• 3j Lee KY. Lee CG. Na JE. Kim JN. Tetrahedron Lett.  2005,  46:  69 
• 3k Ji JX. Wu J. Chan ASC. Proc. Nat. Acad. Sci. U.S.A.  2005,  102:  11196 
• 3l For a review, see: Si YG. Huang H. Jiang B. Chin. J. Org. Chem.  2004,  24:  1389 
• 4a Babler JH. Liptak VP. Phan N. J. Org. Chem.  1996,  61:  416 
• 4b Tzalis D. Knochel P. Angew. Chem. Int. Ed.  1999,  38:  1463 
• 4c Anand NK. Carreira EM. J. Am. Chem. Soc.  2001,  123:  9687 
• 4d Moor D. Pu L. Org. Lett.  2002,  4:  1855 
• 4e Li X. Lu G. Kwok WH. Chan ASC. J. Am. Chem. Soc.  2002,  124:  12636 
• 4f Ishikawa T. Mizuta T. Hagiwara K. Aikawa T. Kudo T. Saito S. J. Org. Chem.  2003,  68:  3702 
• For a review on reaction of tert-butanesulfinyl imines, see:
• 5a Ellman JA. Owens TD. Tang TP. Acc. Chem. Res.  2002,  35:  984 
• 5b For a review on reaction of p-toluene-sulfinyl imines, see: Zhou P. Chen B.-C. Davis FA. Tetrahedron  2004,  60:  8003 
• 6a Tang TP. Volkman SK. Ellman JA. J. Org. Chem.  2001,  66:  8772 
• 6b Barrow JC. Ngo PL. Pellicore JM. Selnick HG. Nantermet PG. Tetrahedron Lett.  2001,  42:  2051 
• 6c Lettan RB. Scheidt KA. Org. Lett.  2005,  7:  3227 
• 7a Li AH. Dai LX. Hou XL. Chem. Commun.  1996,  491 
• 7b Wang DK. Dai LX. Hou XL. Chem. Commun.  1997,  1231 
• 7c Hou XL. Zheng XL. Dai LX. Tetrahedron Lett.  1998,  39:  6949 
• 7d Wang DK. Zhou YG. Tang Y. Hou XL. Dai LX. J. Org. Chem.  1999,  64:  4233 
• 7e Yang XF. Zhang MJ. Hou XL. Dai LX. J. Org. Chem.  2002,  67:  8097 
• 7f Hou XL. Fan RH. Dai LX. J. Org. Chem.  2002,  67:  5295 
• 7g Li BF. Yuan K. Zhang MJ. Wu H. Dai LX. Wang QR. Hou XL. J. Org. Chem.  2003,  68:  6264 
• 7h Fan RH. Zhou YG. Zhang WX. Hou XL. Dai LX. J. Org. Chem.  2004,  69:  335 
• 7i Fan RH. Hou XL. Dai LX. J. Org. Chem.  2004,  69:  689 
• 7j Ding CH. Dai LX. Hou XL. Synlett  2004,  2218 
• 8a Ding CH. Dai LX. Hou XL. Tetrahedron  2005,  61:  9586 
• 8b Ding CH. Dai LX. Hou XL. Synlett  2004,  1691 
• 11a Castro CE. Stephens RD. J. Org. Chem.  1963,  28:  2163 
• 11b Simandi LI. In The Chemistry of Functional Groups   Patai S. Rappoport Z. Wiley; New York: 1983.  Suppl. C, Part 1:  p.529-534  
• 11c Chodkiewicz W. Ann. Chim. (Paris)  1957,  2:  819 
• 11d Sevin A. Chodkiewicz W. Cadiot P. Bull. Soc. Chim. Fr.  1974,  913 
• 11e Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett.  1975,  4467 
• 12a Liu GC. Cogan DA. Owens TD. Tang TP. Ellman JA. J. Org. Chem.  1999,  64:  1278 
• 12b Weix DJ. Ellman JA. Org. Lett.  2003,  5:  1317 

9

X-ray analysis of products 3aa showed that main product has anti-configuration.

10

Typical Procedure for 1,2-Addition of Alkynes to Imine in the Presence of LiHMDS. Phenylacetylene 2a (60 mg, 0.6 mmol) was added to the mixture of LiHMDS (0.6 mmol, 1 M solution in THF) and n-hexane (3.0 mL) at -78 °C. 2-Methyl-N-(pentylidene)-propan-2-sulfinamide 1c (57 mg, 0.3 mmol) was added subsequently and the resulting mixture was stirred for 30 min at the same temperature. Then the reaction mixture was warmed to r.t. and stirred till complete consumption of substrate (monitored by TLC). The reaction mixture was quenched with 5 mL of sat. NH₄Cl aq solution. The aqueous layer extracted with CH₂Cl₂ (3 × 10 mL). The combined organic layer was dried over anhyd Na₂SO₄, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography on silical gel and gave propargylamine 3ca; 66 mg, 76% yield. ¹H NMR (CDCl₃/TMS): δ = 0.93 (t, J = 7.2 Hz, 3 H), 1.24 (s, 9 H), 1.34-1.53 (m, 4 H), 1.76-1.85 (m, 2 H), 3.43 (d, J = 6.0 Hz, 1 H), 4.25 (dd, J = 6.0, 13.5 Hz, 1 H), 7.27-7.32 (m, 3 H), 7.42-7.46 (m, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 13.98, 22.23, 22.50, 27.72, 36.57, 48.07, 56.06, 84.68, 89.05, 122.59, 128.16, 128.26, 131.70; IR (film): ν = 3249, 1491, 1045 cm^-1; MS (EI): m/z (%) = 234 (1.07) [M - 57]⁺, 189 (28), 171 (12), 57 (100). Anal. Calcd for C₁₇H₂₅NOS: C, 70.06; H, 8.65; N, 4.81. Found: C, 69.94; H, 8.66; N: 4.54.

13

A product with 96% de was obtained when optically active 1a and 2a were used as substrates.