Bates reagent

Such condensation reactions are also promoted by certain trTvalent phosphorus compounds, e.g. triphenyl phosphite (2) or diphenyl ethylphosphonite (3), or to a lesser extent by pFosphonate esters, e.g. diphenyl n-butylphosphonate (3). "Bates reagent," p-oxobi s[tri s(cTi methyl ami no)phosphoni urn] bi s-tetra-f1uoroborate (2) may also be used to activate the carboxyl function towards amide bond formation during peptide synthesis (4) and to bring about the Beckmann rearrangement of ketoximes (F). 

DPPA, the Bates reagent and BOP are toxic, the latter due to the formation of HMPA. A substitute for the widely used BOP is TBTU which releases tetramethylurea as a harmless side product. 

Independent work of Kenner [57], Castro [58], Hmby [59], and Yamada [60] has shown the potential of applying derivatives of trisdimethylaminophos-phonium salts for the activation of carboxylic acids and subsequent preparation of amides and peptides (Fig. 7). The first phosphonium salt-based reagents commercially available were pi-oxo-bis-[tris(dimethylamino)-phos-phonium]-bis-tetrafluoroborate (22) ( Bates reagent ) [61] and benzotria-zol-1 -yl-iV-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (23) (BOB) [62]. Later, Coste et al. [63] described the pyrrolidino derivative of BOP, benzotriazol-1 -yl-7V-oxy-tris(pyrrolidino)phosphonium hexafluorophosphate (24) (PyBOP), which does not form carcinogenic hexamethylphosphoric triamide (HMPA) as a by-product [64]. Furthermore, phosphonium salts derived from HOAt, such as (7-azabenzotriazol-l-yloxy)-tris(dimethylamino)-phosphonium hexafluorophosphate (25) (AOP) and (7-azabenzotriazol-l-yloxy)-tris(pyrrolidino)phosphonium hexafluorophosphate (26) (PyAOP), have also been prepared and are generally more efficient than BOP and PyBOP [31,65,66]. 

Baeyei-Villigei oxidation, 110, 286-287 Basketene, 41 Bates Reagent, 425 9-BBN, 62-64... 

The phosphonium method was originally developed from derivatives of tris-dimethylaminophosphonium salts for the activation of carboxylic acids [10-13]. The first developed phosphonium salt-type reagents were //-oxo-bis-[tris(dimethyl-amino)phosphonium]-bis-tetrafiuoroborate (Bates Reagent) and benzotriazol-l-yl-N-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP). Although... 

Sbcondaby and Tertiary Alkyl Ketones from Carboxylic Acid Chlobides and Lithium Phenylthio alkyl)odi>bate Reagents ... 

The biomimetic phosphoric acid mixed anhydride concept stimulated further search for activating reagents that produce derivatives of acylamino acids (and peptides) in more simple ways than the ones mentioned earlier in the Chapter (on p. 78) An interesting attempt in this direction is the so called Bates reagent [47] which on reaction with carboxylic acids yields acyloxyphosphonium salts. 

In more recent years phosphonium derivatives such as Bates reagent (Bates et ai. 1975)... 

A rather different approach to peptide bond formation and amide synthesis in general is to treat a mixture of a carboxylic acid and an amine with an isocyanide 2-Morpholinoethyl Isocyanide is especially suitable), which effectively acts as a dehydrating agent (eq 3). The procedure can result in extensive racemization of both reactants and products which may be supressed by the addition of HOSu presumably an HOSu ester is the penultimate intermediate. The addition of HOSu also decreases racemization in polypeptide synthesis when Bates reagent [(Me2N)sP+]20 (BF4 )2 is used as the coupling agent. ... 

The possible instability of reagents in the reductive step was recognized by Sternberg (1) and has been discussed by other workers (8, 11, 14). Nevertheless, much concern has focused on the tetrahydrofuran-derived C HgO fragment (1, 13), which, although implicated in the lithium naphthalenide studies by Fujita (33), does not seem to be important in the Sternberg procedure. Our model studies on the naphthalene-sodium-tetrahydrofuran system indicate instead that the decomposition pathway suggested by Bates (34) for the tetrahydrofuran-butyllithium interaction is operative ... 

Tris(dimethylaniino)phosphonium anhydride bis(tetrafluoroborate) (Bate s reagent)... 

Posner and Canella used the directed metalation technology for phenol C-alkylation (equation 35) phenol was dimetalated at both the hydroxy group and the < -position with t-butyllithium, and treatment with methyl iodide gave o-cresol . Brandsma and coworkers employed a complex reagent of butyllithium, Af,Af,A, A -tetramethylethylenediamine, and potassium t-butoxide for the metalation . Bates and Siahaan metalated cresols with butyl-lithium and potassium f-butoxide, and the o- and m-isomers gave the organometallic intermediate in good yield, while the yield was fair for the p-isomer . The Simmons-Smith... 

A variety of olefinic hydrocarbons have been dimetallated [1]. Most of the papers on this subject have been published by the groups of Klein and Bates. The usual base-solvent systems for the dimetallations are BuLi TMEDA-hexane and BuLi t-BuOK in hexane or homologues. In practice, clean dimetallations are not easily realizable. The result is very often a mixture of the mono- and dimetallated hydrocarbon and after reaction with some electrophilic reagent a corresponding mixture of mono- and disubstituted product is obtained. Examples of dimetallation reactions with preparative significance are the formations of the following species ... 

Prolonged interaction at room temperature between BuLi TMEDA and an excess of isobutene affords isobutenyllithium, as appeared from the results of subsequent reactions with electrophilic reagents [1]. When the metallation is carried out with a 1 2 molar ratio of isobutene and BuLi-TMEDA in hexane, mainly dilithiated isobutene is formed [2], Bates et al. [3] reacted isobutene with two mol equivalents of the Lochmann-Schlosser reagent in hexane and observed a much faster dimetallation. It should be pointed out that this dimetallation takes place under heterogeneous conditions and in the apolar, inert solvent hexane. Our attempts to achieve a more complete dimetallation by carrying out the reaction in the presence... 

The precipitate dissolves in excess reagent, when tetrahydroxoplum-bate(ll) ions are formed ... 

A.J. Bates, I.J. Galpin, A. Hallett, D. Hudson, G.W. Kenner, G.W. Ramage, R.C. Sheppard, A new reagent for peptide synthesis /z-oxo-bis-[tris-(dimethylamino)phosphonium]-bis-tetrafluoroborate. Helv. Chim. Acta. 58 688-696 (1975)... 

Lead tetramethyl results In fifty per cent yield. After separation of lead from mineral samples. Bate, Miller and Kulp (b8) then treat the dlchloride with excess methyl grignard reagent to accomplish the conversion. The excess grignard reagent is then... 

Hexahydroxydiphenic acid in a bound form (3) is readily detected in a plant extract by an old but very distinctive color test - the Procter-Paessler reaction. Esters of type 3 react with nitrous acid to give a carmine or rose red, changing to brown-green, then purple, and finally indigo blue. The chemical basis of this reaction has not been discussed but it has been employed by Bate-Smith (6, 7) for the quantitative determination of 3 in plant extracts, and it forms the basis of a very useful spray reagent for the detection of 3 by paper chromatography (6, 7, 43). 

Chabt 2. Experimental reactivity diagrams for charged reagents. Bates relative to a given position (= 1). Data deduced from refs. 20, 29, and 99. 

Scheme 58 Formal synthesis of ( )-swainsonine (roc-378) by Bates and coworkers. " Reagents and conditions (a) Zn, AcOH (b) o-NsCI, Na2C03 (c) Grubbs II catalyst (6) (5 mol%), (Z)-AcOCH=CHOAc, CH2CI2, reflux (d) (PPh3)4Pd (5 mol%), tetramethylguani-dine, THF, rt (e) 2-BnO-1-Me-pyridinium triflate, MgO, CICH2CH2CI, then chromatography (f) EtSH, K2CO3, DMF (g) H2C=CHCH2Br, NaOH (h) Grubbs I catalyst (5) (5 mol%), p-TsOH (1 equiv.).

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