Boron reagents, conjugate addition

This decision was in part motivated by the perceived difficulties of other methods. For example, benzylation of a chiral enolate would require the construction of a highly substituted, electron-rich benzylic halide, while the conjugate addition approach would require the use of an orf/io-disubstituted aryl-boron reagent. In addition to the appeal of using a Suzuki coupling partner with preexistent chirality, the synthesis of virgatolide B provided an excellent opportunity to validate the methodology of Molander within the context of total synthesis. 

Tandem processes mediated by triethylborane involving conjugate addition to enones followed by aldol reaction are reported (Scheme 52, Eq. 52a). More recently, a tandem process involving addition of an isopropyl radical to an o ,/3-unsaturated oxime ether afforded an azaenolate intermediate that reacts with benzaldehyde in the presence of trimethylaluminum. The aldol product cyclizes to afford an isopropyl substituted y-bulyroloaclonc in 61% overall yield (Scheme 52) [116]. In these reactions, triethylborane is acting as a chain transfer reagent that delivers a boron enolate or azaenolate necessary for the aldolization process. 

When the metallic additive to the intermediate 374 was zinc dihalide (or another Lewis acid, such as aluminum trichloride, iron trichloride or boron trifluoride), a conjugate addition to electrophilic olefins affords 381 . In the case of the lithium-zinc transmetallation, a palladium-catalyzed Negishi cross-coupling reaction with aryl bromides or iodides allowed the preparation of arylated componnds 384 ° in 26-77% yield. In addition, a Sn2 allylation of the mentioned zinc intermediates with reagents of type R CH=CHCH(R )X (X = chlorine, bromine) gave the corresponding compounds 385 in 52-68% yield. ... 

Boron reagents add to conjugated carbonyl compounds. Alkynyl borate esters (p. 815) give conjugate addition in the presence of boron trifluoride ethe-... 

The a,(3-unsaturated ester (8), aldehyde (9), and nitro (10) compounds participate as electrophiles in a number of useful conjugate addition reactions. Copper-catalyzed addition of Grignard reagents provides access to aryl butanoic acid derivatives substituted with an oxetane (equation 1 in scheme 13.7). The ester, aldehyde, and nitro electrophiles also undergo mild Rh-catalyzed additions of aryl and vinyl boronic acids (equation 2 through equation 4 in scheme 13.7). Interestingly, the unsaturated aldehyde participates readily in an amine conjugate addition to afford oxetane substituted 3-amino-acetaldehyde derivatives. 

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