Diastereoselective Addition of γ-Substituted Allylic Nucleophiles to Ketones: Highly Stereoselective Synthesis of Tertiary Homoallylic Alcohols Using an Allylic Tributylstannane/Stannous Chloride System

The diastereoselective addition of γ-substituted allylic nucleophiles to ketones has been
accomplished to give tertiary homoallylic alcohols. The reaction of tributylcinnamyltin 1a with simple ketones
2 in the presence of stannous chloride (SnCl2) gave the tertiary homoallylic alcohols 3, which include the
anti form (based on Ph and OH), with high diastereoselectivity. In the reaction course, transmetalation of
tributylcinnamyltin 1a with SnCl2 proceeds to form an active nucleophile which is tentatively considered to
be a cinnamyltin(II) species. A cyclic transition state A is favorable because the chlorinated tin(II) center is
highly capable of accepting ligands. The other diastereomers (syn form) 4 were obtained in the reaction of
tributylcinnamyltin 1a with ketones 2 by the use of BF3·OEt2 instead of SnCl2. This reaction proceeds through
an acyclic transition state in which BF3 acts as a Lewis acid for activation of ketones. When 3-tributylstannylcyclohexene 1b or 3-tributylstannylcyclopentene 1c was used with SnCl2, high diastereoselective
formation of the corresponding homoallylic alcohols 6 which have the syn form (based on ring chain and
OH) was observed. The selectivity was also explained by the cyclic transition state B. When tributylcrotyltin
1d or 1e was used, the stereochemistry of the products depends on the additives (SnCl2 or BF3·OEt2),
substituents of ketones, and reaction temperature. It is interesting that those additives compensate for
each other in terms of diastereoselective alkylation. The alkylation of α-alkoxy, aryloxy, or hydroxyketones
16 was achieved in extremely high selectivity using an allylic tributyltin 1a−c/SnCl2 system. The chelation
by carbonyl and β-oxygens provides a rigid transition state (E or F) for selective reactions. It is noted that
the hydroxyketone can be used without protection in this reaction system. The relative stereochemistry of
the produced tertiary homoallylic alcohols was determined on the basis of X-ray analyses.