Chiral a-substituted allylboronates in a one-pot three-component asymmetric allylic alkylation/carbonyl allylation reaction sequence -Applications to the syntheses of (+)-(3R,5R)-3-hydroxy-5-decanolide and (-)-massoialactone

Article abstract of DOI:10.1139/V09-036

The use of different organomagnesium reagents in the copper-catalyzed allylic alkylation of 3-chloropropenyl with chiral phosphoramidite ligands produces the desired a-substituted allylic boronate reagents in high and with modest to high enantioselectivities (up to 96% ee). The size of the incoming alkyl substituent the organomagnesium reagent was found to impact the yield and selectivity of the allylic alkylation. A one-pot for the preparation of these chiral allylic boronates followed by a Lewis acid (BF3) catalyzed addition to aldehydes the desired allylboration products, homoallylic secondary alcohols, in good yields and very high diastereoselectivity.three-component reaction methodology was applied to the syntheses of two lactone-containing natural , (-)-massoialactone and (+)-(3R,5R)-3-hydroxy-5-decanolide. The key step of these syntheses involved the pot enantioselective copper-catalyzed allylic alkylation/allylboration reaction with a benzylic aldehyde, and the desired product in 87% yield, 92% e,and high E/Z selectivity in a ratio of 22:1. Remarkably, the alkylation step of this sequential reaction was performed with a low catalyst loading of 2 mol% on a scale >15 mmol that can provide multiple grams of the three-component product.