Asymmetric synthesis of chiral synthons bearing alkynyl group organoaluminum-promoted pinacol-type rearrangement

Lessons from total synthesis of hybrid natural products

“…Although the latter unit could be derived from the 1,2‐shift of an epoxy alcohol, the issue was the poor migratory aptitude of an alkynyl group, sp hybridization 29a. We found that complexation with cobalt carbonyl endows the alkynyl group with an excellent migrating ability 29b…”

“…Given the two‐carbons between the aromatic and isoprenoid portions can be derived from an ethynyl group, final disconnection suggested a benzene and a 1,3‐diol with a quaternary chiral center as two early intermediates 28. Although the latter unit could be derived from the 1,2‐shift of an epoxy alcohol, the issue was the poor migratory aptitude of an alkynyl group, sp hybridization 29a. We found that complexation with cobalt carbonyl endows the alkynyl group with an excellent migrating ability 29b…”

Molecular orbital studies on the Wagner-Meerwein migration in some acyclic pinacol—pinacolone rearrangements

“…Known since 1860, 5 the pinacol-pinacolone rearrangement has been subjected to much experimental research 6 pertaining to its stereochemistry [7][8][9][10] and the relative migratory [11][12][13][14] aptitudes of various groups. Pinacols themselves are made by the reduction of ketones with bivalent metals, usually magnesium, under anhydrous conditions.…”

Chapter 5. Aliphatic compounds. Part (ii) Other aliphatic compounds

“…The synthesis of hydroxyketones has again been the focus of intense activity reflecting their importance in natural product synthesis. In this context, ketones (38) are derived from !-lactic acid uia an acylation-reduction sequence employing lithium bis-p-tolylthiomethanide; ketones (38) can then be enantioselectively reduced and deprotected to yield chiral aldehydes (39).33 On the other hand, chiral epoxy silyl ethers (40) rearrange to chiral phydroxyketones (41) stereo~pecifically.~~ In this case, titanium tetrachloride proves to be the most effective Lewis acid catalyst for the rearrangement and migratory aptitudes prove to be fairly typical of pinacolonetype rearrangements.…”

“…In contrast, the synthesis of chiral acetylenic ketones such as (44) depends on the facile aluminiumcatalysed pinacol rearrangement of alcohols (45). 39 The rearrangement occurs with very high selectivity with the acetylenic group acting as the non-migrating one. The same paper also describes the stereospecific reduction of the acetylenic ketones (44) to chiral alcohols with high threo selectivity.…”