Phosphonium azides, reactions

The synthesis of phosphazenes starting from aminophosphonium salts appears to be conveniently accomplished by the reaction of the phosphonium azide with sodamide in liquid ammonia solution 49... 

Abolishing the need for heavy metal oxidants, Shechter and coworkers introduced a novel method for hydrazone dehydrogenation by reacting lithium hydrazraiides with phosphonium azide 55 (Scheme 21) [53]. The inherently basic reaction... 

Conversion of aromatic amines to azides was studied by Scechter et al. <2002TL8421> and these studies lead to the recognition of a new approach to tetrazolo[l,5- ]pyridine. Thus, reaction of 2-aminopyridine 142 with butyl-lithium followed by treatment with azidotris(diethylamino)phosphonium bromide gave rise to tetrazolo[l,5- ]pyr-idine 1 in 80% yield. The first intermediate is obviously the azide 7. 

Historically, the methods used for ring closure of linear precursor peptides via amide bond formation evolved in parallel to the methods applied in segment condensations from the azide and active ester procedures to the use of coupling reagents such as DCC in the presence of additives, or of the more recently developed phosphonium and uronium/gua-nidinium reagents. In all cases the choice of method is mainly dictated by the epimerization problem when chiral amino acids act as the carboxy component in the cyclization reaction, and by other side reactions. 

A stereospecific synthesis of aziridine 266 has been reported by Ittah et al. from arene oxide 1 by treatment with sodium azide, followed by tri-phenylphosphine reaction. The reaction proceeds via a phosphonium hydroxide intermediate (267).157... 

Reaction of vinyl phosphonium salts with sodium azide also yields triazoles via triazoline intermediates by elimination of triphenylphosphine (Scheme 130).418... 

In 1991, Duncia et al. reported on the synthesis of 1,5-disubstituted tetrazoles from secondary amides and azidotrimethylsilane under the conditions of the Mitsunobu reaction <1996CHEC-II(4)621>. The Mitsunobu protocol was successfully applied to the conversion of AT(cyanoethyl)amide into tetrazole 510. The tetrazole ring in this event forms by the cyclization of an imidoyl azide (not shown in the scheme) whose precursor is the phosphonium imidate 509 (Scheme 67) <2000JME488>. 

Schroedel and Schmidpeter reported the preparation of triphenylphosphonio-substituted 1,2,3,4-triazaphospholes 95 by cycloaddition reactions of phosphonium salts 94 (generated in situ from dichlorophosphane 93) with phenyl azide (Scheme 6). A novel phosphoniotriazaphospholide 96 was prepared by the reaction of dichlorophosphane 93 with trimethylsilyl azide and isolated in 28% yield as a relatively stable colorless powder with decomposition point above 105 °C <1997CB89>. 

Two reaction intermediates were generated neither of which were isolated. The first, azi-dotris(diethylamino)phosphonium bromide, (Et2N)3P+N3Br , was formed by the reaction of hexaethyl phosphorous triamide, bromine and sodium azide. It has also been prepared starting with phosphorous trichloride (1). The second reaction intermediate, dimethyl /3-keto-o -diazo phosphate (I), is the base catalysis product of azidotris(diethylamino)-phosphonium bromide and dimethyl-2-oxopropyl phosphate. 

Aziridino-steroids (e.g. 486) are available by reduction of suitable iodo-azides with lithium aluminium hydride, but fewer side-reactions occur if the iodo-azide (484) is first treated with triphenylphosphine, or with a phosphite ester. Loss of nitrogen leads to the iV-phosphonium aziridine derivative (485), which is smoothly reduced by lithium aluminium hydride to give the aziridine. The exact mechanism of nitrogen loss in the first step is uncertain. 

Cinnolines may be formed by the cyclization of 2-hydrazone or 2-hydrazonophosphorane derivatives of 3-(2-fluoro- or chlorophenyl)-3-oxopropionates (Scheme 87), which are prepared from the oxopropionates via reaction with /i-toluenesulfonyl azide and treatment of the diazo derivatives with phosphines. Simple hydrazones undergo cyclization by displacement of fluoride under thermal or basic conditions, and reaction of chloro compounds is successful under basic conditions, though Wolff-Kishner reduction may compete in the absence of a methyl group on the terminal nitrogen. The diazo compounds cyclize, via tri- -butylphosphazines, more readily than do the hydrazones and base catalysis is not required it may be that cyclization proceeds via a phosphonium salt, with subsequent hydration and elimination of tri- -butylphosphine oxide. The triphenylphosphazines do not cyclize, but are labile intermediates to the hydrazones <88Cpbi321>. 

The Huisgen 1,3-dipolar cycloaddition of azides to alkynes or nitriles as dipolaro-philes, resulting in 1,2,3-triazoles or tetrazoles, is one of the most powerful click reactions . A limitation of this approach, however, is the absence of regiospecificity normally found in thermal 1,3-cycloaddition of nonsymmetrical alkynes this leads to mixtures of the different possible regioisomers. In other reports, classical 1,3-dipolar cycloadditions of azides to metal acetylides, alkynic Grignard reagents, phosphonium salts and acetylenic amides have been described. Extended reaction times and high temperatures are required in most of the reactions, but they can also be performed more effectively with the aid of microwave irradiation. The main results reported are reviewed in this section. 

Fluorophosphoranes can be obtained from phosphonous and phosphinous halides by reactions with arsenic or antimony obtained with KHF2 (6.518). Some phosphinous halides react with sulphur compounds to give phosphinothioites (9.420), with phenyl azide to give monophosphazenes (7.447), and with ylids fluorides (6.504, 6.505). Hydrofluorophosphoranes produces phosphonium salts (6.377). Phosphonous and phosphinous halides can be condensed to form polyphosphines or cyclic derivatives (6.660, 6.666,6.680,6.684), or reacted to give P-P linkages (6.737). 

The Mitsunobu reaction has also been employed for the synthesis of substituted tetrazoles. The reaction proceeds via a cyano compound in the presence of trimethylsilyl azide and the DEAD/TTP couple. The activated phosphonium intermediate 238 is thought to react with the azide to give the desired tetrazole derivative. The ethylcyano sidechain on the tetrazole can be removed with 2 N NaOH in THF. ° This reaction has found application in the preparation of tetrazole based growth hormone sccretagogues. ... 

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