Hexamethylphosphoric acid HMPA

Enolization of the /wtf-quinoncs 28 in the presence of hexamethylphosphoric acid (HMPA) forms the corresponding ortho-quinone methide intermediates, which undergo electrocyclic ring closure to afford 2-acyl-2//-chrornenes (Scheme 7) <20010L3875>. 

This important synthetic problem has been satisfactorily solved with the introduction of lithium dialkylamide bases. Lithium diisopropylamide (LDA, Creger s base ) has already been mentioned for the a-alkylation of acids by means of their dianions1. This method has been further improved through the use of hexamethylphosphoric triamide (HMPA)2 and then extended to the a-alkylation of esters3. Generally, LDA became the most widely used base for the preparation of lactone enolates. In some cases lithium amides of other secondary amines like cyclo-hexylisopropylamine, diethylamine or hexamethyldisilazane have been used. The sodium or potassium salts of the latter have also been used but only as exceptions (vide infra). Other methods for the preparation of y-Iactone enolates. e.g., in a tetrahydrofuran solution of potassium, containing K anions and K+ cations complexed by 18-crown-6, and their alkylation have been successfully demonstrated (yields 80 95 %)4 but they probably cannot compete with the simplicity and proven reliability of the lithium amide method. 

Hexahydro-3-(hydroxymethyl)-8a-methyl-2-phenyl[2S,3S,8aR]-5-oxo-5H-oxazolo-[3,2-a]pyridine 5H-Oxazolo[3,2-a]pyridin-5-one, hexahydro-3-(hydroxymethyl)-8a-methyl-2-phenyl-, (2S-(2a,3p,8ap)]- (116950-01-7), 69, 55 3,3A,3B,4,6A,7A-HEXAHYDRO-3,4,7-METHENO-7H-CYCLOPENTA[A]PENTALENE-DICARBOXYLIC ACID 3,4,7-Metheno-7H-cyclopenta[a]pentalene-7,8-dicarboxylic acid, 3,3a,3b,4,6a,7a-hexahydro- (61206-25-5), 68,198 HEXAHYDRO-4,4,7-TRIMETHYL-4H-1,3-BENZOXATHIIN 4H-1,3-BENZOXATHIIN, HEXAHYDRO-4,4,7-TRIMETHYL- (59324-06-0), 65, 215 Hexamethylphosphoric triamide (HMPA) (680-31-9), 66, 44, 45, 51, 88, 94 69, 48, 49 Hexanal (66-25-1), 69, 107... 

A solution of chromium trioxide in dilute sulfuric acid used in aqueous acetone is called Jones reagent [572]. Other solvents of chromium trioxide are ether [535] and hexamethylphosphoric triamide (HMPA) [543. Oxidations are also carried out with chromium trioxide adsorbed on Celite (diatomaceous earth) [53S], silica gel [537], or an ion exchanger such as Amberlyst A26 (a macroreticular quaternary ammonium salt anion exchanger) [571, 617]. Such oxidations often take place at room temperature and can be used not only for saturated alcohols but also for unsaturated and aromatic alcohols (equations 208 and 209). 

Oxidations with chromium trioxide (chromic oxide or chromic anhydride) and with chromic acid are carried out in different solvents, usually by adding solutions of chromic oxide or chromic acid to the solutions of the alcohols. When chromium trioxide dissolved in 80% acetic acid is added to a stirred solution of cis-2-phenylcyclohexanol in acetic acid at 50 °C and the mixture is allowed to stand at room temperature for 1 day, an 80% yield of 2-phenylcyclohexanone is obtained [576], Other solvents used are dimethylformamide [542], hexamethylphosphoric triamide (HMPA) [543], acetone [578, 5 i], ether [55 ], dichloromethane [555, 617], and benzene [571] (equation 249). 

Ring-opening reactions to yield aldehydes or ketones were reviewed [7-10]. Isomerization may be thermally induced [7] or may occur in the presence of basic or acidic agents [11]. Lithium bromide associated with tributylphosphine oxide or hexamethylphosphoric triamide (HMPA) has been used [12,13], but transition metal complexes may be more attractive [14-21]. In this work the performances of catalytic systems, e.g. "LiBr/HMPA/toluene", "Co2(CO) /MeOH", "NiBr2(PPh3)2/ Zn/PPh3/THF", etc. are compared for the isomerization of 3a and of analogues. Supported catalysts have also been studied. 

In considering the solvation of charged species by a polar solvent, the polar solvents we considered were hydrogen bond donors (protic polar solvents) such as water and alcohols. Some polar solvents—for example, Ai,77-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and hexamethylphosphoric acid triamide (HMPA)—are not hydrogen bond donors (they are aprotic polar solvents) (Table 10.7). 

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]. 

Hexamethylphosphoric acid triamide (HMPA) (2.0 equiv) was added. 

DMA, N.N -dimethylacetamide HMPA, hexamethylphosphoric acid triamide PTS, polyoxyethanylKX-... 

More recent work has shown that direct hydroxylation of enolate anions can be achieved with a molybdenum peroxide reagent, which consists of M0O5 as a complex with pyridine (C5H5N) and hexamethylphosphoric acid triamide (hexameth-ylphosphoramidate [HMPA], 0=P[N(CH3)2]3). As shown in Scheme 8.12, phenylcy-clohexanone is first converted to the corresponding anion (e.g., with n-butyUithium, BuLi, CH3CH2CH2CH2Li) and the latter is treated with the molybdenum complex... 

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