Nucleophilic Addition of H and R—A Review

We begin our study of nucleophilic additions to aldehydes and ketones by briefly reviewing nucleophilic addition of hydride and carbanions, two reactions examined in Sections 20.4 and 20.10, respectively. 

Treatment of an aldehyde or ketone with either NaBIii or LiAlIii foDowed by protonation forms a 1° or 2° alcohol. NaBHj and LiAlHj serve as a source of hydride, H —the nucleophile—and the reaction results in addition of the elements of H2 across the C-O 71 bond. Addition of H2 reduces the carbonyl group to an alcohol. 

Hydride reduction of aldehydes and ketones occurs via the two-step mechanism of nucleophilic addition— that is, nucleophilic attack of H followed by protonation—shown previously in Section 20.4B. 

The stereochemistry of hydride reduction and Grignard addition was discussed previously in Sections 20.5 and 20.1 OB, respectively. 

Treatment of an aldehyde or ketone with either NaBH4 or LiAlH4 followed by protonation 

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Reviews on stoichiometric asymmetric syntheses M. M. Midland, Reductions with Chiral Boron Reagents, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 2, Academic Press, New York, 1983 E. R. Grandbois, S. I. Howard, and J. D. Morrison, Reductions with Chiral Modifications of Lithium Aluminum Hydride, in J. D. Morrison, ed.. Asymmetric Synthesis, Vol. 2, Chap. 3, Academic Press, New York, 1983 Y. Inouye, J. Oda, and N. Baba, Reductions with Chiral Dihydropyridine Reagents, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 4, Academic Press, New York, 1983 T. Oishi and T. Nakata, Acc. Chem. Res., 17, 338 (1984) G. Solladie, Addition of Chiral Nucleophiles to Aldehydes and Ketones, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 6, Academic Press, New York, 1983 D. A. Evans, Stereoselective Alkylation Reactions of Chiral Metal Enolates, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 1, Academic Press, New York, 1984. C. H. Heathcock, The Aldol Addition Reaction, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 2, Academic Press, New York, 1984 K. A. Lutomski and A. I. Meyers, Asymmetric Synthesis via Chiral Oxazolines, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 

In this reaction, the nucleophile attacks the carbonyl group, giving a tetrahedral intermediate, which is then treated with a proton source in a separate step. In this process, two groups (R and H) have added across the C O Tt bond in a 1,2-addition (for a review of the difiFerence between 1,2-additions and 1,4-additions, see Section 17.4). 

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