B Ring Synthesis
The coupling of ring A and ring C created the 8 membered B ring. One connection was made via a nucleophilic addition of a vinyllithium compound to an aldehyde and the other connection through a pinacol coupling reaction of two aldehydes (Scheme 4).
A Shapiro reaction of the vinyllithium compound derived from hydrazone 4.1 with aldehyde 4.2 makes the first connection that will become the B ring. The control of stereochemistry in 4.3 is thought to be derived from the relative hindrance of the Si face in the orientation shown on the right, due to the proximity of the axial methyl group. Epoxidation with vanadyl(acetylacetate) converted alkene 4.5 to epoxide 4.4, which, upon reduction with lithium aluminium hydride, gave diol 4.5. This diol was then protected as carbonate ester 4.6. The carbonate group also served to create rigidity in the ring structure for the imminent pinacol coupling reaction. The two silyl ether groups were removed, and diol 4.7 was then oxidized to give dialdehyde 4.8 using N-methylmorpholine N-oxide in the presence of a catalytic amount of tetrapropylammonium perruthenate. In the final step of the formation of Ring B, a pinacol coupling using conditions developed by McMurry (titanium(III) chloride and a zinc/copper alloy) gave diol 4.9.
| Scheme 4 |
|---|
Read more about this topic: Nicolaou Taxol Total Synthesis
Famous quotes containing the words ring and/or synthesis:
“Full fathom five thy father lies,
Of his bones are coral made;
Those are pearls that were his eyes;
Nothing of him that doth fade,
But doth suffer a sea-change
Into something rich and strange.
Sea-nymphs hourly ring his knell:
Ding-dong.
Hark! Now I hear them—ding-dong bell.”
—William Shakespeare (1564–1616)
“It is not easy to construct by mere scientific synthesis a foolproof system which will lead our children in a desired direction and avoid an undesirable one. Obviously, good can come only from a continuing interplay between that which we, as students, are gradually learning and that which we believe in, as people.”
—Erik H. Erikson (20th century)