Probing the Effect of Allylic Substitution on Cyclic Ammonium Ylid Rearrangements

Abstract

The [2,3]-sigmatropic rearrangement of tetrahydropyridine-derived ammonium ylids is a valuable method for the preparation of substituted pyrrolidine carboxylates. The presence of an allylic substituent does not intrinsically reduce the yield of rearrangements, and the diastereoselectivity of rearrangement is related to the structure of the diazo reactant. The method represents a very rapid means of accessing complex pyrrolidines, as shown by preparation of a precursor to the core of lactacystin.

Key words

catalytic - asymmetric - rearrangement - lactacystin - ring-closing metathesis

References and Notes

• 1a Monaghan DT. Bridges RJ. Cotman CW. Annu. Rev. Pharmacol. Toxicol.  1989,  29:  365 
• 1b Moloney MG. Nat. Prod. Rep.  1998,  206 
• 1c Chamberlin R. Bridges R. In Drug Design for Neuroscience   Kozikowski AP. Raven Press; New York: 1993.  p.231-259  
• 1d McGeer EG. Olney JW. McGeer PL. Kainic Acid as a Tool in Neurobiology   Raven Press; New York: 1978. 
• Isolation of acromelic acids A and B:
• 2a Konno K. Shirahama H. Matsumoto T. Tetrahedron Lett.  1983,  24:  939 
• 2b Konno K. Hashimoto K. Ohfune Y. Shirahama H. Matsumoto T. J. Am. Chem. Soc.  1988,  110:  4807 
• Reviews:
• 3a Parsons AF. Tetrahedron  1996,  52:  4149 
• 3b Moloney MG. Nat. Prod. Rep.  1999,  16:  485 
• 3c Moloney MG. Nat. Prod. Rep.  2002,  19:  597 
• 3d Clayden J. Read B. Hebditch KR. Tetrahedron  2005,  61:  5713 
• See, for instance:
• 4a Meldrum B. Garthwaite J. Trends Pharmacol. Sci.  1990,  11:  379 
• 4b Watase H. Tomiie Y. Nitta I. Nature (London)  1958,  181:  761 
• 4c Daigo K.
  J. Pharm. Soc. Jpn.  1959,  79:  350 
• Recent synthetic efforts:
• 5a Baldwin JE. Fryer AM. Pritchard GJ. J. Org. Chem.  2001,  66:  2588 
• 5b Xia Q. Ganem B. Org. Lett.  2001,  3:  485 
• 5c Ni Y. Amarasinghe KKD. Ksebati B. Montgomery J. Org. Lett.  2003,  5:  3771 
• 5d Clayden J. Knowles FE. Baldwin IR. J. Am. Chem. Soc.  2005,  127:  2412 
• 5e Sakaguchi H. Tokuyama H. Fukuyama T. Org. Lett.  2008,  10:  1711 
• 5f Ni Y. Denmark SE. Liu JHC. Muhuhi JM. J. Am. Chem. Soc.  2009,  131:  14188 
• 5g Ni Y. Kassab RM. Chevliakov MV. Montgomery J. J. Am. Chem. Soc.  2009,  131:  17714 
• Isolation:
• 6a Omura S. Fujimoto T. Otoguro K. Matsuzaki K. Moriguchi R. Tanaka H. Sasaki Y.
  J. Antibiot.  1991,  44:  113 
• 6b Omura S. Matsuzaki K. Fujimoto T. Kosuge K. Furuya T. Fujita S. Nakagawa A. J. Antibiot.  1991,  44:  117 
• See, for instance:
• 7a Rock KL. Gramm C. Rothstein L. Clark K. Stein R. Dick L. Hwang D. Goldberg AL. Cell  1994,  78:  761 
• 7b King RW. Deshaies RJ. Peters JM. Kirschner MW. Science  1996,  274:  1652 
• 8a Corey EJ. Reichard GA. J. Am. Chem. Soc.  1992,  114:  10677 
• 8b Corey EJ. Reichard GA. Kania R. Tetrahedron Lett.  1993,  34:  6977 
• 8c Sunazuka T. Nagamitsu T. Matsuzaki K. Tanaka H. Omura S. Smith AB. J. Am. Chem. Soc.  1993,  115:  5302 
• 8d Uno H. Baldwin JE. Russell AT. J. Am. Chem. Soc.  1994,  116:  2139 
• 8e Chida N. Takeoka J. Tsutsumi N. Ogawa S. J. Chem. Soc., Chem. Commun.  1995,  793 
• 8f Nagamitsu T. Sunazuka T. Tanaka H. Omura S. Sprengeler PA. Smith AB. J. Am. Chem. Soc.  1996,  118:  3584 
• 8g Chida N. Takeoka J. Ando K. Tsutsumi N. Ogawa S. Tetrahedron  1997,  53:  16287 
• 8h Corey EJ. Li WD. Nagamitsu T. Angew. Chem. Int. Ed.  1998,  37:  1676 
• 8i Corey EJ. Li WD. Reichard GA. J. Am. Chem. Soc.  1998,  120:  2330 
• 8j Kang SH. Jun HS. Youn JH. Synlett  1998,  1045 
• 8k Kang SH. Jun HS. Chem. Commun.  1998,  1929 
• 8l Panek JS. Masse CE. Angew. Chem. Int. Ed.  1999,  38:  1093 
• 8m Iwama S. Gao WG. Shinada T. Ohfune Y. Synlett  2000,  1631 
• 8n Green MP. Prodger JC. Hayes CJ. Tetrahedron Lett.  2002,  43:  6609 
• 8o Brennan CJ. Pattenden G. Rescourio G. Tetrahedron Lett.  2003,  44:  8757 
• 8p Ooi H. Ishibashi N. Iwabuchi Y. Ishihara J. Hatekeyama S. J. Org. Chem.  2004,  69:  7765 
• 8q Wardrop DJ. Bowen EG. Chem. Commun.  2005,  5106 
• 8r Donohoe TJ. Sintim HO. Sisangia L. Ace KW. Guyo PM. Cowley A. Harling JD. Chem. Eur. J.  2005,  11:  4227 
• 8s Hayes CJ. Sherlock AE. Selby MD. Org. Biol. Chem.  2006,  4:  193 
• 8t Fukuda N. Sasaki K. Sastry TVRS. Kanai M. Shibasaki M. J. Org. Chem.  2006,  71:  1220 
• 8u Balskus EP. Jacobsen EN. J. Am. Chem. Soc.  2006,  128:  6810 
• 8v Gilley CB. Buller MJ. Kobayashi Y. Org. Lett.  2007,  9:  3631 
• 8w Yoon CH. Flanigan DL. Yoo KS. Jung KW. Eur. J. Org. Chem.  2007,  37 
• 8x Legeay J.-C. Langlois N. J. Org. Chem.  2007,  72:  10108 
• 8y Hayes CJ. Sherlock AE. Green MP. Wilson C. Blake AJ. Selby MD. Prodger JC. J. Org. Chem.  2008,  73:  2041 
• 9 Heath P. Roberts E. Wessel HP. Workman JA. Sweeney JB. J. Org. Chem.  2003,  68:  4083 
• 10 Fürstner A. Langemann K. J. Am. Chem. Soc.  1997,  119:  9130 
• 11 Kirkland TA. Lynn DM. Grubbs RH. J. Org. Chem.  1998,  63:  9904 
• 12 Merz A. Markl G. Angew. Chem., Int. Ed. Engl.  1973,  12:  845 
• See:
• 14a Mageswaran S. Ollis WD. Sutherland IO.
  J. Chem. Soc., Perkin. Trans. 1  1981,  1953 
• 14b Mageswaran S. Ollis WD. Sutherland IO. J. Chem. Soc., Chem. Commun.  1973,  656 
• 14c Sweeney JB. Tavassoli A. Carter NB. Hayes JF. Tetrahedron  2002,  58:  10113 ; and references therein
• Nitrogen asymmetry is a key controller in [2,3]-ammonium ylid rearrangements. See, for instance:
• 15a Hill RK. Chan TN. J. Am. Chem. Soc.  1966,  88:  866 
• 15b Sweeney JB. Tavassoli A. Workman JA. Tetrahedron  2006,  62:  11506 

13

Key Data
^¹H NMR (400 MHz, CDCl₃): δ = 2.28 (3 H, s), 2.28-2.35
(1 H, m), 2.35-2.41 (1 H, m), 2.60-2.70 (1 H, m), 2.75-2.85 (1 H, m), 2.90 (1 H, d), 2.90 (1 H, d), 3.50-3.57 (1 H, br m), 3.70 (3 H, s), 5.20-5.28 (1 H, m), 5.73-5.81 (1 H, m). ^¹³C NMR (100 MHz, CDCl₃): δ = 39.0, 41.3, 42.6, 52.4, 55.1, 65.2, 72.3, 128.8 , 135.5, 172.3. MS (CI⁺): m/z (%) = 182(100) [MH⁺], 122(75), 79, 49. HRMS: m/z calcd for C₁₀H₁₅NO₂: 182.1182; found: 182.1181.

16

Prepared from methyl 4-methyl-3-oxopentanote and trisyl azide (MeCN, Et₃N, r.t. 20 h).
Key Data R _f = 0.29 (PE-EtOAc, 9:1): Anal. Calcd (%) for C₇H₁₀N₂O₃: C, 49.41; H, 5.92; N, 16.46. Found: C, 49.39; H, 6.20; N, 16.33. IR (neat): ν_max = 2976, 2874, 2130, 1725, 1658, 1437, 1308 cm^-¹. ^¹H NMR (250 MHz, CDCl₃): δ = 1.15 [6 H, d,
J = 6.8 Hz, CH(CH ₃)₂], 3.59 [1 H, sept, J = 6.8 Hz, CH(CH₃)₂], 3.85 (2 H, s, OCH₃). ^¹³C NMR (62.5 MHz, CDCl₃): δ = 18.9 (2 × CH₃), 37.2 [CH(CH₃)₂], 52.5 (OCH₃), 53.8 (CN₂), 162.0 (CO₂), 197.3 (CO). MS (CI⁺): m/z (%) = 171.1 (80) [MH⁺], 145.1 (100). HRMS: m/z calcd for C₇H₁₀N₂O₃: 171.0770; found: 171.0771.

17

The relative stereochemistry of cis- and trans- 10 was deduced from NOE experiments (alkene methine-ring methyl interactions), which will be reported elsewhere in due course.

18

The necessary analytical experiments to rigorously confirm these structural deductions are currently in progress.