Hexamethylphosphoric triamide, reduction

Isoquinoline can be reduced quantitatively over platinum in acidic media to a mixture of i j -decahydroisoquinoline [2744-08-3] and /n j -decahydroisoquinoline [2744-09-4] (32). Hydrogenation with platinum oxide in strong acid, but under mild conditions, selectively reduces the benzene ring and leads to a 90% yield of 5,6,7,8-tetrahydroisoquinoline [36556-06-6] (32,33). Sodium hydride, in dipolar aprotic solvents like hexamethylphosphoric triamide, reduces isoquinoline in quantitative yield to the sodium adduct [81045-34-3] (25) (152). The adduct reacts with acid chlorides or anhydrides to give N-acyl derivatives which are converted to 4-substituted 1,2-dihydroisoquinolines. Sodium borohydride and carboxylic acids combine to provide a one-step reduction—alkylation (35). Sodium cyanoborohydride reduces isoquinoline under similar conditions without N-alkylation to give... 

Hexamethylphosphoric triamide (HMPT) is a high-boiling solvent particularly satisfactory for dissolving metals or organometallic compounds. It has been found to be an ideal solvent in which to conduct the reduction of a,jS-unsaturated ketones by alkali metals. 

Reduction of alkynes with sodium in ammonia,147 lithium in low-molecular-weight amines,148 or sodium in hexamethylphosphoric triamide containing /-butanol as a proton source149 leads to the corresponding is-alkene. The reaction is assumed to involve successive electron-transfer and proton-transfer steps. 

A very rare example of preferential photochemical reduction of an a-C-F bond rather than a //-chlorine occurs with chlorofluoropropanoates, in which this unusual selection in radical reactions is achieved by photochemical reduction.107 In oc.oc-difluoro esters 6 both C-F bonds can be reduced stepwise using hexamethylphosphoric triamide as the solvent and hydrogen donor.108 100... 

On the pages which follow, general methods are illustrated for the synthesis of a wide variety of classes of organic compounds including acyl isocyanates (from amides and oxalyl chloride p. 16), epoxides (from reductive coupling of aromatic aldehydes by hexamethylphosphorous triamide p. 31), a-fluoro acids (from 1-alkenes p. 37), 0-lactams (from olefins and chlorosulfonyl isocyanate p. 51), 1 y3,5-triketones (from dianions of 1,3-diketones and esters p. 57), sulfinate esters (from disulfides, alcohols, and lead tetraacetate p. 62), carboxylic acids (from carbonylation of alcohols or olefins via carbonium-ion intermediates p. 72), sulfoxides (from sulfides and sodium periodate p. 78), carbazoles... 

The radical anions have been likewise characterized by methods ranging from the various electrochemical techniques supplemented by EPR/ENDOR measurements to electron transmission spectroscopy. Radical anions can be conveniently generated in a matrix by Co y irradiation, e.g. in CD3OD, or in the liquid phase by potassium metal reduction in solvents such as hexamethylphosphoric triamide or dimethoxyethane. These ions have the n structure expected from calculations [14, 15, 25, 26]. 

The solvent employed in the reduction can be critical in determining the course of the reaction. Donor solvents, e.g., ethers, often are used. The donor solvents stabilize the Li" " cation, making the reaction energetically feasible e.g., C6H5CH=CHCgH5 with Li metal to give a dianion proceeds to at least 50 % completion within a few hours in ether or dimethoxyethane (DME), but not in benzene even after extended reaction. The popular ethereal solvents are DME and tetrahydrofuran (THF) often ether is not an adequate solvent. Hexamethylphosphoric triamide (HMPA) complexes Li strongly and may be used as a solvent. Hexamethylphosphoric triamide causes tumors and should be handled in a hood with appropriate protective measures. ... 

Solvent effects Birch reduction. 1,2-Dimethoxyethane (Glyme) and Dimethyl ether (see Naphthalene-Sodium), Dimethylformamide. Dimethyl sulfone. Dimethyl sulfoxide. Diphenyl sulfoxide. Ethylene glycol. N-EthylmorphoUne. Hexamethylphosphoric triamide. Methylal. Methylene chloride. Methyl ethyl ketone. N-Methyl-2-pyrrolidone. Nitrometbane. Nitrosyl chloride. Phenetole. Tetrahydrofurane. Tetramethylene sulfone. Tetramethylene sulfoxide. Triethanolamine. Triethyl phosphate. Trifluoroacetic acid,... 

Similarly, treatment of (-)-(R)-1 -fluoro-1 -iodo-2,2-diphenylcyclopropane with samarium diiodide in tetrahydrofuran containing hexamethylphosphoric triamide gave (-)-(5)-l-fluoro-2,2-diphenylcyclopropane (25), 1,1-diphenylallene (26), and 2-fluoro-l,l-diphenylpropene (27) in 55,18 and 1 % yield, respectively. However, synthetically useful reductions involving cyclo-... 

Reduction, a.ji-Unsaturated ketones are reduced to the corresponding saturated ketones by lithium (or potassium) in hexamethylphosphoric triamide. Use of ether as a cosolvent improves the yield, for in its absence some of the unsaturated ketone escapes reduction.9 Yields are comparable to those obtained in liquid ammonia. 

Solutions of sodium in hexamethylphosphoric triamide containing r-butanol are effective for reduction of aikenes. 

BIRCH REDUCTION, which see. Hexamethylphosphoric triamide. Sodium-Ammonia. 

On the pages which follow, general methods are illustrated for the synthesis of a wide variety of classes of organic compounds including acyl isocyanates (from amides and oxalyl chloride p. 16), epoxides (from reductive coupling of aromatic aldehydes by hexamethylphosphorous triamide p. 31), a-fluoro acids (from... 

Enantioselective reduction of acetylenic ketones is a route frequently used to prepare the starting materials. The synthesis of a dihydrocompactin precursor 10 involves such a reaction sequence via Ireland rearrangement of 8477. Problems arising with considerable C-silylation of the ester enolate in the rearrangement of 8 can be overcome by adding hexamethylphosphoric triamide to the enolate (1.2 mL/mmol), followed by four equivalents of /ert-butylchlorodimethyl-silane in tetrahydrofuran. The product ester 9 is obtained as a 12 1 mixture of diastereomers in 81 % yield ... 

Alkali metals arc usually dissolved or suspended in liquid ammonia or low molecular weight aliphatic amines, hexamethylphosphoric triamide or alcohols. Often these reductions are carried out in the presence of a cosolvent, such as diethyl ether, tetrahydrofuran or 1,2-dimethoxyethane, in order to increase the solubility of the ketone in the reaction mixture. Ethanol (pKa 15.9), 2-propanol (pKa 16.5), 2-methyl-2-propanol (p a 18), water (pK 15.7) and ammonium chloride (pKa 9.2) arc the usual proton donors. Thus, ammonium chloride is the strongest acid that can be incorporated into liquid ammonia. Proton donors are present in the reaction medium from the beginning, added concurrently with the ketone, or are added during product isolation (" aprotic reduction ). 

---