Tandem 4+2 cycloaddition/allylboration

Vaultier and co-workers were the first to demonstrate the utility of 1-borono-l,3-butadienes in [4+2] cycloadditions with electron-poor dienophiles such as maleic anhydride and maleimides (Equation 32) [78]. As exemplified with diene 56, the [4+2] cycloaddition unmasks an allylboronate, 57, which at that time was isolated prior to its use in aldehyde allylboration. Lallemand and Six later showed that this sequence can be performed easily as a one-pot, three-component process [79], and the same group used this chemistry as an approach to the synthesis of clerodin [80]. Since then, the one-pot tandem [4+2] cycloaddition/allylboration strategy has been extended to the construction of highly functionalized heterocycles (Section 6.4.1.1). 

Scheme9.33 Synthesis of hydroxylated cyclohexenes via tandem [4+2] cycloaddition/allylboration.

Intermolecular Allylboration. A tandem aza[4+2] cycloaddition/allyl-boration three-component reaction has been designed based on the prece-dented carbocyclic [4- -2] cycloaddition/allylboration and a snbsequent one-pot variant. Thns, the thermal reaction between hydrazonobutadienes 138, A-substitnted maleimides, and aldehydes provides polysnbstituted a-hydroxy-alkylpiperidines 141 via the cyclic allylboronate intermediate 139 and the proposed chairlike transition stmctnre 140 (Eq. 103). Monoactivated dienophiles like acrylates fail to react with heterodienes 138 bnt the scope of aldehydes is very broad both ahphatic and aromatic aldehydes are snitable, inclnding electron-rich ones. An inverse electron-demand variant to access the corresponding dihy-dropyran derivatives via the intermediacy of enantiomerically enriched pyranyl allylic boronate 76 has been snbsequently developed (see Eq. 64). ° ... 

Three-component Hetero-[4+2]-cycloaddition-Allylboration Tandem Reaction... 

Inspired by the pioneering work of Vaultier and co-workers on the two-step carbo-cyclic [4+2] cycloaddition/allylboration [78] and the one-pot variant by LaUemand [79], Tailor and HaU described the first tandem aza[4+2]cycloaddition/allylboration three-component reaction [129]. Thermal reaction between hydrazonobutadienes 91, N-substituted maleimides, and aldehydes provides polysubstituted a-hydroxyalkyl-piperidines 94 via the allylboronate intermediate 92 and the proposed allylboration transition structure 93 (Equation 48) [130], A variant of this process, an aza[4+2]cy-cloaddition/aUylboration/retro-sulfinyl-ene, has been applied to the total synthesis of palustrine alkaloids [131]. 

The one-pot cycloaddition/allylboration sequence has also been carried out to trap the apparently unstable intermediates and afford the corresponding alcohols directly after hydrolysis. The diastereoselectivity is similar to that observed using the previous two-step methodology [67], This tandem reaction was used towards the synthesis of complex natural products such as clerodin (Scheme 9.31) [68]. 

Scheme9.36 A tandem aza [4-h2] cycloaddition/allylboration for the synthesis of a-hydroxylated piperidine derivatives.

These dienes (15) can be engaged in a tandem sequence [4 + 2] cycloaddition followed by the allylboration of an aldehyde which leads to cyclohexenyl alcohols after hydrolysis. This is illustrated below by a sequence involving a D.A cyloaddition with maleic... 

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