| Research Abstract |
The Claisen ester condensation and aldol addition are well recognized as fundamental and useful C-C bond-forming reactions. Traditional Claisen condensations are conducted by alkali-metal basic reagents such as NaOR, NaH, LDA and LiHMDS. We have explored the Ti- or Zr- Claisen condensations and the related aldol additions from the recent standpoint of the green chemistry.
These characteristic features are as follows :
(1) Higher reaction velocity and yields compared with basic methods.
(2) Applicable to the substrates bearing basically unstable groups.
(3) Use of inexpensive and very low toxic metal reagents (TiCl_4 or ZrCl_4).
(4) Use of practical amines (Et_3N or Bu_3N) and solvents (toluene or CH_2Cl_2).
(5) Powerful Claisen condensation of α, α-disubstituted esters utilizing ZrCl_4.
(6) Application to the effective synthesis of a natural macrocyclic musk, civetone.
(7) Related powerful aldol-type reactions also applicable. (Recently, one of the present methods was applied to the multi-kg scale synthesis of the anti-MRSA carbapenem intermediate as the key step.)
To demonstrate the utility of these reactions, We performed the practical syntheses of the valuable perfumes such as macrocyclic musks (civetone and muscone), mints (mint lactone and menthofuran), jasmines (furanone analogs of jasmone and dehydrojasmone), and 1β-methylcarbapenem.
In conclusion, a variety of valuable fine chemicals and unique natural products could be synthesized using these original Ti-reactions.
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