Conjugate reduction of polyfunctional α,β-unsaturated carbonyl compounds using [(Ph3P)CuH]6. Compatibility with halogen, sulfonate, and γ-oxygen and sulfur substituents
✍ Scribed by Thomas M. Koenig; John F. Daeuble; Donna M. Brestensky; Jeffrey M. Stryker
- Publisher
- Elsevier Science
- Year
- 1990
- Tongue
- French
- Weight
- 301 KB
- Volume
- 31
- Category
- Article
- ISSN
- 0040-4039
No coin nor oath required. For personal study only.
✦ Synopsis
In contrast to organocuprate conjugate addition and standard methods for conjugate reduction, use of the stable copper0 hydride cluster, [(ph3p)cuH)6, allows chemoselective conjugate reduction of o&msaturated carbonyl compounds substituted at the ~position with leaving groups. In addition, the compatibility of the conjugate mduction with organic halides and sulfonate groups is demonstrated.
Chemoselective conjugate reduction of Cz&msatumted carbonyl functionality in polyfunctional molecules is complicated by the pmsence of heteroatom substituents at the 7-carbon and aliphatic carbon-halide bondr anywhem in the substrate. Catalyst poisoning or hydrogenolysis may complicate double bond reduction under candition~ of catalytic hydmgenation,l and such functionality generally does not survive dissolving metal reductions or any methodology in which electmn transfer to the unsaturated carbonyl is mechanistically relevant Most of the hydride methodology developed for conjugate reduction, including both main group and transition metal reagents, suffers from similar problems in chemoselectivity.3
Conjugate reduction or reductive silylation of a$-unsaturatea carbonyl compounds using the stabk copper@ hydride complex [@%3P)oghas the advantages of performance and ccnvenience; the reagent is commercially available~ and readily manipulated, reduces a large range of substrates both mgioselectively and stereoselcctively under mild conditions, will not reduce isolated double bonds or carbonyl groups, and tolerates water and unprotected hydroxy functionality.~ Furthumore, this conjugate hydride reduction can be performed either stoichiometrically (up to six hydride equivalents per cluster) or catalytically, using hydrogen as the source of active hydride.7 Mechanistic work suggested that conjugate reduction is prece&d by coordination of the copper to the electrondeficient double bond and that an electron-transfer at any stage of the reaction is not required.7~s
This in tum suggests that, in contrast to organocuprate reactivity,9 conjugate reduction using [(ph3p)cwe may not be accompanied by a buildup of negative charge at the F, potentially allowing conjugate reduction of substrates incorporating heteroatom functionality at the 7+&ion.lo In addition, based on the low basicity/mtcleophilicity of this reagent compamd to the various hydridocuprate reagents,rl compatibility with organic halides was anticipated.
The initial substrate investigated was quinone monoketal 1, 12 with the conjugate reduction conducted using excess 0.5 N pH 7 phosphate buffer (10 equiv) instead of water to minimize potential base-catalyzed aromati-