Abstract
A range of α-amino esters can be turned into sulfonylhydantoins 2 in a single, atom-economic step using sulfamide and DBU. This procedure obviates
the need for a three- or four-step sequence utilised by traditional procedures. Two
new six-membered analogues 3 and 4 have also been prepared utilising novel synthetic protocols.
Key words
amino acids - sulfonamides - heterocycles - medicinal chemistry - phosphates
References
<A NAME="RD32104ST-1">1 </A>
Vorreither HK.
Ziegler E.
Monatsh. Chem.
1965,
96:
216
2a </A>
Kuang R.
Epp JS.
Ruan S.
Chong LS.
Venkataraman R.
Tu J.
He S.
Truong TM.
Groutas WC.
Bioorg. Med. Chem.
2000,
8:
1005
2b </A>
Kuang R.
Epp JS.
Ruan S.
Yu H.
Huang P.
He S.
Tu J.
Schechter NM.
Turbov J.
Froelich CJ.
Groutas WC.
J. Am. Chem. Soc.
1999,
121:
8128
3a </A>
Albericio F.
Garcia J.
Michelotti EL.
Nicolás E.
Tice CM.
Tetrahedron Lett.
2000,
41:
3161
3b </A>
Albericio F.
Bryman LM.
Garcia J.
Michelotti EL.
Nicolás E.
Tice CM.
J. Comb. Chem.
2001,
3:
290
<A NAME="RD32104ST-4">4 </A>
Mantegani S.
Brambilla E.
Caccia C.
Chiodini L.
Ruggieri D.
Lamberti E.
Di Salle E.
Salvati P.
Farmaco
1998,
53:
293
<A NAME="RD32104ST-5">5 </A>
Muller GW.
DuBois GE.
J. Org. Chem.
1989,
54:
4471
6a </A>
Crenshaw RR, and
Algieri AA. inventors; U.S. Patent 4,394,508.
6b </A>
Duery L.
Reinelt S.
Seiler P.
Diederich F.
Helv. Chim. Acta
1999,
82:
2432
6c </A>
Dewynter G.
Aouf N.
Regainia Z.
Montero J.-L.
Tetrahedron
1996,
52:
993
7a </A>
Coppola GM,
Davies JW,
Jewell CF,
Li C.-Y,
Wareing JR,
Sperbeck DM,
Stams TM,
Topiol SW, and
Vlattas I. inventors; WO 2003/082841.
; Chem. Abstr.
2003 , 139: 307766
7b </A>
Saunders JO,
Miknis GF, and
Blake JF. inventors; WO 2004/062664.
; Chem. Abstr.
2004 , 141 , 157120
<A NAME="RD32104ST-8">8 </A>
Lee C.-H.
Korp JD.
Kohn HJ.
J. Org. Chem.
1989,
54:
3077
<A NAME="RD32104ST-9">9 </A>
Graf R.
Chem. Ber.
1959,
92:
509
<A NAME="RD32104ST-10">10 </A>
Lee H.-C.
Kohn HJ.
J. Org. Chem.
1990,
55:
6098
<A NAME="RD32104ST-11">11 </A>
Sulfamide (159 mg, 1.65 mmol) was added to methyl N -(2-methoxybenzyl)glycinate (345 mg, 1.65 mmol) followed by addition of DBU (0.25
mL, 1.65 mmol) in a 10 mL pyrex tube under an argon stream. The reaction was then
heated to 160 °C at which point the reaction became homogeneous and bubbling was observed.
After 15 min, the reaction was cooled to r.t. and diluted with 1 M NaOH (40 mL) and
Et2 O (20 mL) and shaken until all the gum dissolved. The aqueous layer was separated,
acidified with 6 M HCl until pH 1 and then extracted with EtOAc (2 × 20 mL). The combined
EtOAc layers were dried (MgSO4 ), filtered and evaporated to form a beige solid. Trituration with Et2 O-hexanes (1:5, 5 mL) followed by filtration afforded the sulfonylhydantoin product
(Table
[1 1 H NMR (300 MHz, DMSO): δ = 3.80 (s, 3 H), 4.00 (s, 2 H), 4.24 (s, 2 H), 6.93 (t, J = 7.5 Hz, 1 H), 7.01 (d, J = 8.0 Hz, 1 H), 7.29-7.37 (m, 2 H), 8.60 (br s, 1 H). 13 C NMR (75 MHz, DMSO): δ = 45.1, 55.3, 55.8, 111.3, 120.7, 123.7, 129.7, 129.9, 157.5,
168.6. HRMS (TOF MS EI+ ): m /z calcd for C10 H12 N2 O4 S: 256.0518; found: 256.0521.
<A NAME="RD32104ST-12">12 </A>
Tan CYK.
Weaver DF.
Tetrahedron
2002,
58:
7449 ; and references cited therein
<A NAME="RD32104ST-13">13 </A>
Morris J.
Wishka DG.
J. Org. Chem.
1991,
56:
3549
<A NAME="RD32104ST-14">14 </A>
Dolongo S.
Bodina RI.
Lipina S.
Berkova GA.
Perekalin VV.
J. Org. Chem. USSR
1991,
27:
1951
<A NAME="RD32104ST-15">15 </A>
Hawkins JM.
Lewis TA.
Raw AS.
Tetrahedron Lett.
1990,
31:
981
<A NAME="RD32104ST-16">16 </A>
Chatterjee AK.
Choi T.-L.
Grubbs RH.
Synlett
2001,
1034
