Allylboration/lactonization reaction

A neat hydroformylation - allylboration - hydroformylation reaction sequence reported by Hoffmann el al. afforded the pyrano-fused oxepanes 135 and 136 (48% total yield ca 1 1 ratio) from the precursor 134 the compound 134 required a number of steps for synthesis from the alcohol 130, the ethynyl ether 131, and the boronate 133 (by addition of 132) in moderate overall yield. Dess-Martin oxidation of 135 and 136 then afforded the final lactones 137 and 138 [01NJC102],... 

Kennedy and Hall have reported a one-pot allylboration/lactonization using the tetra-substituted 2-alkoxycarbonyl aUylboronates 17 (Section 6.2.1.2) [39]. These allyl-boronates react with aldehydes, thermally and under Lewis acid catalysis, to first provide the hydroxy-ester intermediate 119 (Equation 58). This initial product cyclizes under the reaction conditions by lactonization to afford a-exomethylene y-lactones 120. This facile cyclization is probably a manifestation of the gem-dialkyl effect. In-... 

As already mentioned, we had a number of options for reaction conditimis at our disposal when we began looking at the key allylboration/lactonization step. Thermal conditions were the traditimial way, either under standard or microwave-promoted heating. Furthermore, we could also make use of the... 

As demonstrated by Hoffmann and coworkers, hydroformylation can also be combined with an allylboration and a second hydroformylation, which allows the formation of carbocycles and also heterocycles [213]. A good regioselectivity in favor of the linear aldehyde was obtained by use of the biphephos ligand [214]. Reaction of the allylboronate 6/2-76 having an B-configuration with CO/H2 in the presence of catalytic amounts of Rh(CO)2(acac) and biphephos led to the lactol 6/2-80 via 6/2-77-79 (Scheme 6/2.17). In a separate operation, 6/2-80 was oxidized to give the lactone 6/2-81 using tetrabutyl ammonium perruthenate/N-methylmorpholine N-oxide. 

Other annellated tetrahydropyranes have been prepared by a hydroformylation-allylboration-hydroformylation sequence (Scheme 5.84) [76]. By treatment of an allyl amine derivative with syngas, a cascade reaction was initiated consisting of hydroformylation and hemiacetal formation, followed by a second hydroformylation-hemiacetal formation step. The product was converted via Ley-Griffith oxidation into the corresponding lactone. 

Recently we undertook the preparation of chiral lactones of different ring sizes utilizing chiral homoallylic alchols derived from the asymmetric allylboration of appropriate aldehydes as the starting materials (6-S). Our procedures are reviewed here. The application of our allylboration-esterification-ring closing metathesis reaction sequence for the synthesis of biologically active natural products (S-/i) are also summarized. 

Aggarwal performed the stereoselective total synthesis of solandelactones E and F by a stereocontrolled allylboration reaction of the eight-membered lactone 83, which was prepared by cyclization of 81 (Scheme 5.28) [76]. Treatment of the seco-acid 81 under Yamaguchi conditions according to the protocol previously established by Martin et al. [73] and Pietruszka [75] for a similar reaction resulted in the formation of the target lactone 82 in good yield. 

One approach that was influential in our research on the synthesis and applications of allylboronates to access a-methylene y-lactones, which was reported by Sidduri and Knochel, utilize a mixed zinc copper reagent that allowed for the one-pot preparation of a-methylene y-lactones (Equation 10). The desired copper-based allylation reagents are formed with high selectivity through a cfs-carbocupration, and the diastereoselectivity of aldehyde addition is high, which suggests a Type I chair-Uke transition state similar to allylboration reactions (see Section 5.1). 

Before this total synthesis project began, we had just completed a diversity-oriented synthesis project that made use of the allylboration reaction to access simple substituted a-methylene y-lactones, which were further functionalized using a variety of transition metal-catalyzed reactions. We were now interested in applying this allylboration methodology to pursue a target-oriented synthetic problem that would demonstrate its suitability toward a complex natural product. Chinensiolide B presented this sort of challenge. 

Examination of the allylboration reaction with cyclic aldehydes 12 and 13 did provide us with useful additional information. Reaction of xmsubstituted allylboronate 10 with aldehyde 13 under acid-catalyzed conditions was successful in generating the ot-methylene y-lactone product (Scheme 4, Equation 1) but, unfortunately, there was no diastereoselectivity. Furthermore, when the more substituted allylboronate 11 was used, there was no reaction at all (Scheme 4, Equation 2). Attempts with other reaction conditions (thermal, Lewis acid-catalyzed) also proved unsuccessful. Although our planned... 

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