Synthesis of New (3-Aminopyrrolidin-3-yl)phosphonic Acid - A Cucurbitine Analogue - and (3-Aminotetrahydrothiophen-3-yl)phosphonic Acid via Phosphite Addition to Heterocyclic Hydrazones

Abstract

Hydrazones were prepared by condensation of carbo­cyclic and heterocyclic ketones with benzoyl- and tosylhydrazines. These hydrazones underwent nucleophilic addition with phosphite to provide efficiently (3-hydrazinopyrrolidin-3-yl)-, (3-hydrazino­tetrahydrothiophen-3-yl)-, (3-hydrazinotetrahydrofuran-3-yl)-, and (1-hydrazinocyclopentyl)phosphonates. Cleavage of the hydrazine N-N bonds followed by acidic hydrolysis of the phosphonate functions of the (3-aminoheterocyclopentyl)phosphonates gave the new (3-aminopyrrolidin-3-yl)- and (3-aminotetrahydrothiophen-3-yl)phosphonic acids. This synthesis was achieved in a four-step sequence from the appropriate ketones.

Key words

phosphonic acids - heterocycles - amines - cucurbitine analogue - nucleophilic additions

References

• 1a Kafarski P. Lejczak B. Phosphorus, Sulfur Silicon Relat. Elem.  1991,  63:  193 
• 1b Maier L. Phosphorus Sulfur Relat. Elem.  1983,  14:  295 
• 1c Baylis EK. Campbell CD. Dingwall J.-G. J. Chem. Soc., Perkin Trans. 1  1984,  2845 
• 1d Maier L. Phosphorus, Sulfur Silicon Relat. Elem.  1990,  53:  43 
• 1e Hudson HR. Pianka M. Phosphorus, Sulfur Silicon Relat. Elem.  1996,  109-110:  345 
• 2 Peyman A. Budt KH. Spanig J. Ruppert D. Angew. Chem., Int. Ed. Engl.  1993,  32:  1720 
• 3 Cheng L. Goodwin CA. Scully MF. Kakkar VV. Claeson G. Tetrahedron Lett.  1991,  32:  7333 
• 4 Kukhar VP. Hudson HR. Aminophosphonic and Aminophosphinic Acids   Wiley; New York: 2000. 
• For recent enantioselective synthesis of α-aminophosphonic acids, see:
• 5a Bennani YL. Hanessian S. Chem. Rev.  1997,  97:  3161 
• 5b Kolodiazhnyi OI. Tetrahedron: Asymmetry  1998,  9:  1279 ; and references cited therein
• 6a Vercruysse K. Dejugnat C. Munoz A. Etemad-Moghadam G. Eur. J. Org. Chem.  2000,  281 ; and references cited therein
• 6b Joly GD. Jacobsen EN. J. Am. Chem. Soc.  2004,  126:  4102 ; and references cited therein
• 7 For recent synthesis of cyclopropyl aminophosphonic acids, see: Yamazaki S. Takada T. Imanishi T. Moriguchi Y. Yamabe S. J. Org. Chem.  1998,  63:  5919 ; and references cited therein
• For synthesis of chiral nonracemic cyclopropyl amino­-phosphonic acids, see:
• 8a Fadel A. J. Org. Chem.  1999,  64:  4953 
• 8b Fadel A. Tesson N. Eur. J. Org. Chem.  2000,  2153 
• 8c Fadel A. Tesson N. Tetrahedron: Asymmetry  2000,  11:  2023 
• 8d Tesson N. Dorigneux B. Fadel A. Tetrahedron: Asymmetry  2002,  13:  2267 
• 9a Hercouet A. Le Corre M. Carboni B. Tetrahedron Lett.  2000,  41:  197 
• 9b For cyclobutyl and cyclopentyl derivatives, see: Guéguen C. About-Jaudet E. Collignon N. Savignac P. Synth. Commun.  1996,  26:  4131 
• For cyclopentyl derivatives, see:
• 10a Ranu BC. Hajra A. Green Chem.  2002,  4:  551 
• 10b Wieczorek JC. Gancarz R. Bielecki K. Grzys E. Sarapuk J. Phosphorus, Sulfur Silicon Relat. Elem.  2001,  174:  119 
• 10c Stoikov II. Repejkov SA. Antipin IS. Konovalov AI. Heteroat. Chem.  2000,  11:  518 
• 11a Wieczorek JS. Gancarz R. Bielecki L. Grzys E. Sarapuk J. Phosphorus, Sulfur Silicon Relat. Elem.  2000,  166:  111 
• 11b Matveera ED. Podrugina TA. Tishkovskaya EV. Tomilova LG. Zefirov NS. Synlett  2003,  2321 
• 11c Firouzabadi H. Iranpoor N. Sobhani S. Synthesis  2004,  2692 
• 12 For microwave assistance, see: Kabachnick MM. Zobnina EV. Belatskaya IP. Synlett  2005,  1393 ; and references cited therein
• 13 GABA-related drugs have shown promising properties as antiepileptic, antispastic, and antidepressive agents: Fonnum F. In Psychopharmacology   Vol. 18:  Meltzer H. Raven; New York NY: 1987.  p.173-182  
• 14a Tukanova SK. Dzhiembaev BZ. Butin BM. Zh. Obshch. Khim.  1991,  61:  1118 ; Chem. Abstr. 1992, 116, 6637
• 14b Gancarz R. Latajka R. Halama A. Kafarski P. Magn. Reson. Chem.  2000,  38:  867 
• 14c For aminophos-phonic acid derivatives of substituted piperidines and tetrathiophenes, see: Bosyakov YG. Maishinova GT. Logunov AP. Revenko GP. Izv. Nats. Akad. Nauk. Resp. Kaz., Ser. Khim.  1993,  6:  72 ; Chem. Abstr. 1995, 123, 112161
• For aminophosphonates of substituted tetrahydropyrans, see:
• 15a Kabatschnick MI. Izv. Akad. Nauk SSSR, Ser. Khim.  1967,  1362 
• 15b Kabatschnick MI. Bull. Acad. Sci. USSR, Div. Chem. Sci. (Engl. Transl.)  1967,  1379 
• 15c

  For unsubstituted tetrahydropyran derivatives, see ref. 16a.

• 16a Tukanova SK. Dzhiembaev BZ. Khalilova SF. Butin BM. Zh. Obshch. Khim.  1993,  63:  938 ; Chem. Abstr. 1993, 119, 250038
• 16b Kiyashev DK. Turisbekova LK. Sadykov TS. Erzhanov KB. Nurakhov DB. Izv. Akad. Nauk Kaz. SSR, Ser. Khim.  1990,  6:  82 ; Chem. Abstr. 1991, 114: 122537
• 16c

  See ref. 14c.

• 17a Fang SD. Li LG. Niu G. Tseng KF. Sci Sin.  1961,  10:  845 
• 17b Shiao SH. Shao BJ. Ho YH. Yang YC. Mao CP. Sci Sin.  1962,  11:  1527 
• 18a Sun TT. Loh SH. Chow SW. Kyi ZY. Sci Sin.  1961,  10:  852 
• 18b Monteiro HJ. J. Chem. Soc., Chem. Commun.  1973,  2 
• 18c Morimoto Y. Achiwa K. Chem. Pharm. Bull.  1987,  35:  3845 
• 18d Mamoun O. Benhaoua H. Danion-Bougot R. Danion D. Synth. Commun.  1995,  25:  1295 
• 18e Williams RM. Fegley GJ. Tetrahedron Lett.  1992,  33:  6755 
• 18f Paik S. Kwak HS. Park TH. Bull. Korean Chem. Soc.  2000,  21:  131 
• 19 For the synthesis of cucurbitine derivatives, see: Tanaka K.-I. Suzuki H. Sawanishi H. Heterocycles  1996,  43:  205 
• 20a Rabasso N. Louaisil N. Fadel A. Tetrahedron  2006,  62:  7445 
• 20b Louaisil N. Rabasso N. Fadel A. Synthesis  2007,  289 
• 21 For a review, see: Zhou P. Chen B.-C. Davis FA. Tetrahedron  2004,  60:  8003 ; and references cited therein
• 22 Kaboudin B. Rahmani A. Synthesis  2003,  2705 
• 23 Chandrasekhar S. Narsihmulu C. Sultana SS. Saritha B. Prakash SJ. Synlett  2003,  505 
• Additions of phosphites to hydrazones have been reported rarely, see:
• 24a Inokawa S. Nakatsukasa Y. Horisaki M. Yamashita M. Yosida H. Ogata T. Synthesis  1977,  179 
• 24b Yamashita M. Takeuchi J. Nakatani K. Oshikawa T. Inokawa S. Bull. Chem. Soc. Jpn.  1985,  58:  377 
• 24c Yamamoto H. Hanaya T. Kawamoto H. Inokawa S. Chem. Lett.  1989,  121 
• 25a Wu Y.-H. Gould WA. Lobeck WG. Roth HR. Feldkamp RF. J. Med. Chem.  1962,  5:  752 
• 25b Yadav JS. Sarkar S. Chandrasekhar S. Tetrahedron  1999,  55:  5449 
• 27a Lipton MF. Shapiro RH. J. Org. Chem.  1978,  43:  1409 
• 27b Okimoto M. Chiba T. J. Org. Chem.  1990,  55:  1070 
• 28 Krzyzanowska B. Stec WJ. Synthesis  1982,  270 
• 29 Kim S. Yoon J.-Y. J. Am. Chem. Soc.  1997,  119:  5982 
• 30a Ogawa C. Sugiura M. Kobayashi S. J. Org. Chem.  2002,  67:  5359 
• 30b Burk MJ. Feaster JE. J. Am. Chem. Soc.  1992,  114:  6266 
• 31 Molander GA. McKie JA. J. Org. Chem.  1992,  57:  3132 
• 32a Denmark SE. Nicaise O. Edwards JP. J. Org. Chem.  1990,  55:  6219 
• 32b Job A. Janeck CF. Bettray W. Peters R. Enders D. Tetrahedron  2002,  58:  2253 
• 32c Agami C. Couty F. Rabasso N. Tetrahedron  2001,  57:  5393 
• 33a Bournaud C. Bonin M. Micouin L. Org. Lett.  2006,  8:  3041 
• 33b Mellor JM. Smith NM. J. Chem. Soc., Perkin Trans. 1  1984,  2927 
• 33c Brown CA. Brown HC. J. Am. Chem. Soc.  1963,  85:  1003 
• 33d Bertelson RC. Glanz KD. J. Org. Chem.  1972,  37:  2207 
• 35a Girard P. Namy J.-L. Kagan HB. J. Am. Chem. Soc.  1980,  102:  2693 
• 35b Wipf P. Wenkatraman S. J. Org. Chem.  1993,  58:  3455 

26

Ketone 8 was prepared from its corresponding alcohol by use of the Dess-Martin oxidation reagent.

34

For hydrolysis with TMSI, see the experimental section

36

Unfortunately, HRMS could not be carried out despite use of various kinds of methods, including ESI, EI, or CI.