Conjugate addition reactivity sequence

Care must also be taken when choosing the reaction partners within reactions. Nucleophiles that have been reported to be effective in conjugate addition processes can also undergo 1,2-addition reactions and these possibilities must be addressed in reaction design. For example, aldehydes and ketones have been shown to undergo a bis-indole alkylation sequence in the presence of achiral amine 139 (42-84% yield 1-10 mol% catalyst) [189]. This additional reactivity was exploited in the... 

In both of these cases, the site of nucleophilic attack is determined simply by reactivity the more reactive the carbonyl group, the more direct addition to C=0 will result. The most reactive carbonyl groups, as you saw in Chapter 10, are those that are not conjugated with O or N (as they are in esters and amides), and particularly reactive are acyl chlorides and aldehydes. In general, the proportion of direct addition to the carbonyl group follows the reactivity sequence in the margin. 

The conjugate addition of a nucleophile to a, 3-unsaturated carbonyl compounds results in formation of the corresponding enolate subsequent to the initial addition step. This reactive intermediate can be trapped by a variety of electrophiles, and thus opens up opportunities for tandem reaction sequences [108]. 

The lower-order silyl cuprates are apparently less reactive than the higher-order cuprates in conjugate addition reactions. Reagent (1) has been added in an addition-elimination sequence to an alkylidenemalonate system as a route to vinylsilanes (eq 4). ... 

Methyl vinyl ketone (entry 3) and the tert-butyl cation (entry 4) are also reactive toward complex 3. The naphthalenium complexes resulting from the addition of these electrophiles will add the conjugate base of dimethyl malonate (generated in situ from a combination of dimethyl malonate (DMM) and diisopropylethylamine (DIEA)) to complete the tandem additions. Oxidation of the resulting complexes yields cis-l,4-dihydronaphthalenes. The entire sequence of complexation, tandem addition, and demetalation employed for all entries in Table 4 can be performed using bench-top conditions (i.e., a non-inert atmosphere). 

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