Hexafluorophosphate coupling reagent

B Castro, JR Dormoy, G Evin, B Castro. Peptide coupling reagents IV (1) — benzotriazole V-oxytrisdimethylamino phosphonium hexafluorophosphate (B.O.P.) Tetrahedron Lett 1219, 1975. 

V Dourtoglou, J-C Ziegler, B Gross. L hexafluorophosphate de O-benzotriazolyl-AW-tetramethyluronium hexafluorophosphate a new and efficient peptide coupling reagent. Tetrahedron Lett 1269, 1978. 

S Chen, J Xu. A new coupling reagent for peptide synthesis. Benzotriazol-yl-bis(pyr-rolidino)-carbonium hexafluorophosphate (BCC). Tetrahedron Lett 33, 647, 1992. 

LA Carpino, A El-Faham. Tetramethylfluoroformidinium hexafluorophosphate a rapid-acting peptide coupling reagent for solution and solid phase peptide synthesis. J Am Chem Soc 117, 5401, 1995. 

NMR data were used to prove the structure of peptide-coupling reagents -[(6-nitrobenzotriazol-lyl)oxy]tris(dimethylamino)-, -(pyrrolidino)phosphonium hexafluorophosphates [829-831], l-(2-nitrobenzenesulfonyloxy)-6-nitrobenzotri-azole [832], and l-(2-naphthylsulfonyloxy)-6-nitrobenzotriazole [833], complexes of 5-nitrobenzotriazole with palladium(II) and platinum(II) [834], some explosive substances such as 1-picrylbenzotriazole mono- and polynitro derivatives [835] as well as that of the Mesenheimer a-complexes and 4,6-dinitrobenzotriazole-l-oxide [836, 847],... 

Peptide coupling reagent bromotris(pyrrolidino)phosphonium hexafluorophosphate (PyBrOP) was used in synthesis of 10-membered succinyl bis(amide) 27 in 57% yield (Equation 3) <2002TL2593>. Similarly, 1,6-diazacyclo-decane substituted on only one nitrogen atom was prepared by reaction of A -trityl-protected linear triamine with succinyl anhydride. The amides were further reduced to amines using LAH <2002TL2593>. 

Kiso s synthetic strategy follows the work of Heathcock [8]. He also uses titanium tetrachloride as the reagent for the multiple ring closure. His work focusses on an effective preparation of the peptide precursor for the multiple ring closure. For this purpo.se he introduces a new coupling reagent 2-chloro-l,3-dimethylimidazo-lidium hexafluorophosphate (CIP) 81 (Scheme 20). 

Coupling reagents A,A -dicyclohexylcarbodiimide (DCC), A,A -diisopropyl-carbodiimide (DIC), 1-hydroxybenzotriazol (HOBt), and (9-benzotriazolyl-A,A, A, A -tetramethyluronium hexafluorophosphate (HBTU)" (Fluka, or Applied Biosystems, SARF Paris, France). 

A novel (and cheaper) method for the preparation of the peptide-coupling reagent benzotriazolyloxytris(dimethylamino)phosphonium hexafluorophosphate (i.e. BOP reagent) has been described. ... 

Peptide coupling. The tetrafluoroborate and hexafluorophosphate salts are developed as peptide coupling reagents, illustrated by the preparation of dipeptides and tripeptides. 

Meutermans and Alewood [48] reported the solid-phase synthesis of tetrahydroisoquinolines 13 and dihydroisoquinolines 13a using the Bischler-Napieralski reaction (Fig. 5). The polystyrene resin-bound deprotected L-3,4-dimethoxyphenylalanine was acylated with acetic acid derivatives using N- [(IH-benzotriazol-1 -yl)(dimethylamino)methylene] -iV-methylmethana-minium hexafluorophosphate A-oxide (HBTU) as a coupling reagent. The product obtained was then treated with phosphorus oxychloride under optimized conditions to afford a Bischler-Napieralski cyclization. Hutchins and Chapman [49] reported the synthesis of tetrahydroisoquinolines 13b and 4,5,6,7-tetrahydro-3H-imidazol[4,5-c]pyridines 14 via cyclocondensation of the appropriate dipeptidomimetic with various aldehydes (Fig. 6). 

More recently, the use of phosphonium (e.g., benzotriazole-1-yl-oxy-tris-pyrrolidino phosphonium hexafluorophosphate (PyBOP)) and uronium (e.g., 2-(1H- benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU)) coupling reagents have gained wide use in effecting peptide bond formation, particularly in SPPS (Fig. 7.6). The structures of PyBOP and HBTU both incorporate an equivalent of HOBt, and the final reactive Boc or Fmoc amino acid species is the corresponding OBt active ester (13). 

HAPipU reagent, a HOAt-derived uronium-type coupling reagent (- uronium reagents) structurally similar to HATU and HAPyU, named O-(7-azabenzotriazol-1 -yl) -1, l,3,3-bis(penta-metllylene)uronium hexafluorophosphate. The correct lUPAC name corresponding to the solid-state stmcture is l-[bis-(piperidino) methyliumyl] -1H-1,2,3 -triazo-lo [4,5 -ii]pyridine-3 -oxide hexafluorophos -phate. 

TFFH reagent, tetramethyl fluoroformami-dinium hexafluorophosphate, [(Me2N)2 CF]+ PF(i , a non-hygroscopic, stable salt suitable for generating acyl fluoride in situ (- Fmoc amino acid fluorides), but also applicable as coupling reagent for solution-or solid-phase peptide synthesis [L. A. Carpino, A. El-Faham, J. Am. Chem. Soc. 1995, 117, 5401]. 

An easy and convenient one-pot procedure for the synthesis of Weinreb amides <1981TL3815> and hydro-xamates has been reported more recently <2001JOC2534>. The method avoids the use of expensive and toxic coupling reagents such as benzotriazol-l-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP), dicyclohexylcarbodiimide (DCC), and, in addition, the nonfacile removal of their excess from the reaction mixtures (Scheme 60). 

Several reports have dealt with the use of phosphinic pseudodipeptide building blocks in peptide couplings where both phosphinic and carboxylic acids are unprotected. Among the coupling reagents used successfully for such transformations are W,W -carbonyldiimidazole (CDl) [66-68], (benzotriazol-l-yloxy)tris (dimethylamino)phosphonium hexafluorophosphate (BOP) [69, 70],... 

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