Enoates, addition reactions

This study also gives a good account of the stereoselectivity of the 2-diazobut-3-enoate addition reaction with styrene. There is a preference for the ester group... 

Conjugate addition reactions of acyclic Midiael acceptors possessing betetoatom-SLibstituted stereogenic centers in tlieir )>-positions may provide usefiil levels of diastereoselectivity. A typical example is given witli tlie y-alkoxy-substituted enoate 49 in Sdieme 6.8 [17]. High levels of diastereoselectivity in favor of tlie anii addition product SO were found in tlie course of dlmediylcuprate addition. 

Allylic silanes react with aldehydes, in the presence of Lewis acids, to give an allyl-substituted alcohol. In the case of benzylic silanes, this addition reaction has been induced with Mg(C104)2 under photochemical conditions. The addition of chiral additives leads to the alcohol with good asymmetric induction. In a related reaction, allylic silanes react with acyl halides to produce the corresponding carbonyl derivative. The reaction of phenyl chloroformate, trimethylallylsilane, and AICI3, for example, gave phenyl but-3-enoate. ... 

Obviously, the nature of the organocopper reagent is an important factor with respect to the stereochemical outcome of the cuprate addition. This is nicely illustrated for the cuprate addition reaction of enoate 75 (Scheme 6.15). Here, lithium di-n-butylcuprate reacted as expected by way of the modified Felkin-Anh transition state 77 (compare also 52), which minimizes allylic A strain, to give the anti adduct 76 with excellent diastereoselectivity [30]. Conversely, the bulkier lithium bis-(methylallyl)cuprate preferentially yielded the syn diastereomer 78 [30, 31]. It can be argued that the bulkier cuprate reagent experiences pronounced repulsive interactions when approaching the enoate system past the alkyl side chain, as shown in transition state 77. Instead, preference is given to transition state 79, in which repulsive interactions to the nucleophile trajectory are minimized. 

The addition to a, -unsaturated esters is usually difficult. However, under appropriate conditions, the 1,4-addition of diorganozincs to enoates is possiblc As mentioned above, Michael-addition reactions can also be catalyzed by Ni(II) salts . The 1,4-addition of functionalized organozinc iodides to enones in the presence of Ni(acac)2, a diamine as ligand and TMSCl provides, after hydrolysis, the Michael adducts in satisfactory yields . 

Although lower-order cuprate reagents will often engage in displacement reactions with alkyl halides, such reactions are usually slow. They are generally much less facile than 1,4-addition reactions to a,P-unsaturated enones or enoates. The latter processes are particularly facile when trimethylsilyl chloride is employed as an additive. It was Corey and Boaz10 who first recognised the accelerating effect of trimethylsilyl chloride on cuprate addition reactions to a,p-unsaturated carbonyls. Buszek therefore capitalised on Corey s earlier observations in his reaction of 10 with lithium dimethylcuprate to obtain 15. 

Due to their high conformational flexibility, chiral acyclic Michael acceptors often display low diastereofacial selectivities in copper-mediated conjugate addition reactions.80 Nevertheless, acceptable levels of diastereoselection can be obtained, in particular with heteroatom-substituted Michael acceptors. For example, treatment of the y-benzyloxymethyl-substituted enoate 100 with lithium dimethylcuprate in the presence of chlorotrimethylsilane gives the anti-adduct 101 with excellent diastereoselectivity (Scheme 26). a Products of this type can be easily... 

In a similar fashion, diastereoselective addition of the vinylcuprate 103 to the glyceraldehyde-derived enone 102 was used for the construction of the precursor 104 of iso[7]-levuglandin D2.92 Besides enones and enoates, heteroatom-substituted nitroolefins and a,/3-unsaturated phosphine oxides also participate in diastereoselective copper-mediated 1,4-addition reactions.93,93 1,938... 

As already mentioned, the steric course of acid- or base-catalyzed conjugate additions is usually subject to thermodynamic control. An interesting example of how hydrogen bonding in the product(s) may affect the stereochemical outcome of the addition reaction is provided by ajmalicine (25). When the enoate 25 was treated with 5% aqueous sulfuric acid, the 17-hydroxy-derivative 26 was obtained as a single diastereomer in 40% yield20. The configuration of the... 

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