Addition of Oxygen and Nitrogen Nucleophiles

Various bioactive synthetic targets contain aminoindanol backbones and, therefore, many different strategies to access them have been developed. Among them, the Friedel-Crafts reaction is a common strategy, although harsh reaction conditions and the requirement for electron-rich aromatic rings limit the scope of this reaction type. 

3 Domino Processes with the Aldol Reaction as Subsequent Step 285 Ph 

Recently, the group extended this methodology to a-substituted acroleins and applied their reaction nicely to the short synthesis of various enantio-enriched y-butyrolactone natural products [35aj. 

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Additions of oxygen and nitrogen nucleophiles to vinyloxiranes can be achieved with Pd(0) catalysis [103, 104]. Acetate, silanols, amines, sulfonamides, and azide have been used as nucleophiles, and the stereochemical outcome of these additions, where applicable, is normally the result of two consecutive SN2 reactions. This is demonstrated by the additions of NaNHTs to vinylepoxides 29 and 30, affording syn- and anti-amino alcohols 31 and 32, respectively, in good yields and with high diastereoselectivities (Scheme 9.22) [105]. 

Conjugated dienes coordinated to palladium(Il) undergo nucleophilic addition of oxygen and nitrogen nucleophiles from the opposite side of the palladium center to give Ti-allylpalladium complexes. Subsequent reaction of the 7C-allyl complexes with another molecule of nucleophile results in the 1.4-addition of two kinds of nucleophiles to dienes. The direction of the second nucleophilic attack is dependent on the nature of the nucleophiles as well as the reaction conditions. Representative examples... 

Addition of oxygen and nitrogen nucleophiles to the dioxide 128 yielding 129 and 130, respectively, is reversible [199], while amine adducts of the dioxide 131 undergo ring opening to give sulfinic acid derivatives 132 (Scheme 72) [200]. 

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