Reductions pivalic acid

A potential liability associated with such reductive hydroacylations resides in the fact that only one acyl residue of the symmetric anhydride is incorporated into the coupling product. For more precious carboxylic acids, selective acyl transfer from mixed anhydrides is possible. Mixed anhydrides derived from pivalic acid are especially convenient, as they may be isolated chromato-graphically in most cases. In practice, mixed anhydrides of this type enable completely branch-selective hydroacylation with selective delivery of the aromatic and a,()-unsalurated acyl donors (Scheme 19). 

Scheme 19 Selective acyl transfer in reductive hydroacylations involving mixed carboxylic anhydrides derived from pivalic acid...

M Fe over the rate in the absence of Fe" ". The reaction was hindered by complexation of Fe " by CN , and produced pivalic acid as a by-product. Reduction was promoted more effectively by Cu than by Fe, and N-aryl-hydroxylamines added to the reaction mixture were oxidized to nitroso... 

Immediate sodium borohydride (NaBfLt) reduction gave lactam 44. Bischler-Napieralski cyclization of 44 followed by NaBfLt reduction yielded ( )-methyl-0-acetyl-isoreserpate (45). The correct stereochemistry at C-3 was obtained by first lactonizing compound 45 epimerization with pivalic acid then resulted in ( )-reserpic acid lactone (47). Treatment with base followed by acylation with TMBCI yielded racemic reserpine. The stereochemical considerations involved in the epimerization reaction will be discussed later. 

Abrahamsson K, Melander M, Eriksson BO, Holme E, Jodal U, Jonasson A. Transient reduction of human left ventricular mass in carnitine depletion induced by antibiotics containing pivalic acid. Br Heart J 1995 74 656-9. 

This method involves the reduction of compound 1 in the presence of Raney nickel, aqueous ammonia, and methanol resulting in 2, followed by condensation of 2 with 3 in the presence of pivalic acid, cyclohexane, and isopropyl... 

For hydrogenation of unfunctionalized ketones the only efficient solid catalyst is Ni [13]. Catalyst pretreatment conditions are similar to those used for catalysts in the hydrogenation of /6-ketoesters. A major difference is the application of pivalic acid in greater than stoichiometric amounts during the hydrogenation reaction. This additive, with sufficient Na" ions, enhanced the ee from 2 to 80-85% in the reduction of a variety of 2-alkanones. 

When the mixed anhydride between 4-ethyl-4-pentenoic acid and pivalic acid (prepared using pivaloyl chloride on the pentenoic acid) was treated with the lithium salt of (i )-4-benzyl-2-oxazolidinone an imide was formed where one (the bottom as drawn) face is encumbered by the bulky benzyl group. Thus, cyanoeth-ylation occurred with diastereoselectivity, and a single isomer was isolated. Reduction of the imide with sodium borohydride (NaBU,) then resulted in the formation of the primary alcohol, and the latter was protected as the f-butyldiphenylsilyl (TBDPS)... 

Heating a DMA/pivalic acid solution of 6-(phenylamino)hex-2-ynoates in the presence of Pd(OAc)2 under an oxygen atmosphere gives pyrrolo[l,2-fl]indoles by a domino sequence involving intramolecular aminopalladation followed by C-H activation and reductive elimination (Scheme 141). ... 

The projected free radical cyclization proceeded as planned to give 172. Ozonolysis of the vinyl group, oxidation of the resulting aldehyde to an acid, and alkylation with diazomethane provided projected intermediate 162. Reduction of the lactone provided 173. Treatment of 173 with 6-methoxytryptamine and pivalic acid then provided a nearly equal mixture of lactams 174 (isoreserpine stereochemistry at Cg) and 175 (reserpine stereochemistry at C3). The correct C3 stereoisomer was moved forward to 176 (protection of the tertiary alcohol followed by reduction of the lactam). The silyl ethers were removed, the secondary ether was re-protected, and reaction with samarium iodide accomplished reduction of the a-hydroxy ester to provide 177. Removal of the TBS group and esterification of the alcohol completed the synthesis of reserpine. 

Activity is also retained when oxygen at the 21 position is replaced by sulfur. Preparation of one of these compounds follows a route quite analogous to the foregoing thus, displacement of the mesylate group in the cortisone (56) derivative 57 with the anion from thiopivalic acid affords thioester 58. Reduction of the 11-ketone by means of borohydride affords tixocortol pivalate (59)[13j. 

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