Basicity unsaturated, conjugate addition

P carbon atom of an a 3 unsatu rated carbonyl compound is elec trophilic nucleophiles especially weakly basic ones yield the prod ucts of conjugate addition to a 3 unsaturated aldehydes and ketones... 

After successful installation of the first two stereocenters, our attention was focused on elaboration of the terminal alkene in 64 (Scheme 6.9). Treatment with disiamylborane followed by oxidative workup afforded primary alcohol 65 in good yield (70-85 %). A side product containing a mixture of two diastereomers (66) was also observed and resulted from conjugate addition of the alkoxide formed during basic workup onto the unsaturated ester. Maintaining the temperature at 0 °C by a slow, dropwise quench during the oxidative workup was necessary to minimize the amount of the undesired cyclization product (66). Subsequent oxidation of the primary alcohol 65 using Dess-Martin periodinane [28] and a Pinnick oxidation afforded carboxylic acid 67 [29]. 

In basic aqueous solutions with a [Rh(COD)2]BF4 catalyst, phenyltin trichloride was found to react with aromatic aldehydes or unsaturated ketones. In the presence of a strong aqueous alkali (KOH) PhSnCU is readily hydrolysed and the products of this reaction, such as e.g. PhSn(OH)3 add to the carbonyl function of aldehydes or undergo conjugate addition to unsaturated ketones (Scheme 6.35). In the absence of KOH no reaction takes place at all. Yields are generally high [73]. 

The conjugate addition of a thiol, methanethiol, to the a,(5-unsaturated aldehyde acrolein may be used in the synthesis of the amino acid methionine. Under basic conditions, the nucleophile will be the thiolate anion, and 1,4-addition leads to the thia-aldehyde. Methionine may then be obtained via... 

Preliminary mechanistic studies show no polymerization of the unsaturated aldehydes under Cinchona alkaloid catalysis, thereby indicating that the chiral tertiary amine catalyst does not act as a nucleophilic promoter, similar to Baylis-Hilhnan type reactions (Scheme 1). Rather, the quinuclidine nitrogen acts in a Brpnsted basic deprotonation-activation of various cychc and acyclic 1,3-dicarbonyl donors. The conjugate addition of the 1,3-dicarbonyl donors to a,(3-unsaturated aldehydes generated substrates with aU-carbon quaternary centers in excellent yields and stereoselectivities (Scheme 2) Utility of these aU-carbon quaternary adducts was demonstrated in the seven-step synthesis of (H-)-tanikolide 14, an antifungal metabolite. 

According to the Lewis theory, alkaline earth metal hydroxides are weaker bases than their oxides, the order of the strength of the basic sites being Ba(OH)2> SrO(OH)2 > Ca(OH)2 > Mg(OH)2. The hydroxides have been used recently as solid catalysts for organic transformations, such as the conjugate addition of methanol to a, S-unsaturated carbonyl compounds (12), cyanoethylation of alcohols (163,164), and transesterification reactions (166,167,171,172) which are described above. The extensive work of Sinisterra et al. (282) on the number and nature of sites and on the catalytic activity of the most basic alkali metal hydroxide, Ba(OH)2, is emphasized. It was found that commercial barium hydroxide octahydrate can be converted into... 

The conjugate addition of organometallic reagents to a./i-unsaturated compounds is one of the basic methods in our repertoire for the construction of carbon-carbon bonds. These addition reactions have been used as key steps in the synthesis of numerous biologically active compounds, and show a broad scope due to the large variety of donor and acceptor compounds that can be employed. It is evident that a tremendous effort has been devoted over the last three decades to develop asymmetric variants of this reaction. ... 

Weakly basic nucleophiles react with a,/3-unsaturated carbonyl compounds by conjugate addition. 

While THF or CH2CI2 are the most commonly used solvents, the solubility of the reagents or the catalyst may dictate the use of other solvents. Reactions are usually slow in DMF and in CH3CN when DABCO, DBU or DMAP were used as catalysts. An often-observed byproduct of the aza-MBH reaction is a bridged compound of type 97. This product is the result of a stepwise addition of 95 to 75 via the Mannich reaction, followed by an intramolecular conjugated addition (Michael addition) of the formed anion to the a,/ -unsaturated ketone, and thus due to the elevated basicity of the catalyst (Scheme 5.21) [92]. 

When a nucleophile reacts with an a,/3-unsaturated carbonyl compound, it may bond to either of the two electrophilic carbons. If it bonds to the carbonyl carbon, the reaction is termed a normal addition or a 1,2-addition (because the nucleophile and electrophile have added to adjacent positions). If, instead, it bonds to the /3-carbon, the reaction is termed a conjugate addition or a 1,4-addition. The following mechanism operates under basic conditions ... 

A useful application of these reagents is in conjugate addition to unsaturated carbonyl compounds. Few d1 reagents will do this as most arc very basic and prefer to add direcdy to the carbonyl... 

Ballini, R., Marotta, E., Petrini, M., and Rosini, G. 1986. Conjugate addition of nitro derivatives to aP-unsaturated carbonyl compounds on basic alumina. Synthesis, 3 237-8. 

Sammes and cowoikers devised a promising solution to the synthesis of substituted P-silyl sulfones, which has been exploited in a new approach to the antibiotic bicyclomycin (Scheme 44). In their approach the P-silyl sulfone (125) was prepared by conjugate addition of the lithium enolate of the mono-imino ether derivative (123) of a dioxopiperazine to the unsaturated P-silyl sulfone (124). After oxidative cyclization to the bicyclic system (126), the latent alkene functionality was unleashed in 89% yield on treatment with TBAF in THF at room temperature to give the basic skeleton of bicyclomycin. 

Conjugate addition of nitroalkanes to a,6-unsaturated carbonyl compounds has been achieved using basic alumina, in the absence of a solvent.36 3-Nitropropanal has been prepared by conjugate addition of nitrite anion to acrolein reduction to 3-nitropropanol was effected with borane-dimethyl sulphide.36 -Nitro-acids and u-nitro-esters have been prepared by ring cleavage of 2-nitrocycloalkanones (Scheme 163).362... 

In basic media, peroxides are deprotonated and the product is a peroxy anion, which reacts with conjugated carbonyl derivatives at the C-terminus (1,4-addition, conjugate addition). Hydrogen peroxide, for example, reacts with base to give the hydroperoxide anion (HOO ), which adds to a, 3-unsaturated ketones, aldehydes... 

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