A short and convenient way to produce the Taxol™ A-ring utilizing the Shapiro reaction

Abstract

Shapiro reaction was utilized in an ef®cient route to a Taxole A-ring building block. Commercially available 2-methyl-1,3cyclohexanedione was converted in three simple steps to various arenesulfonylhydrazones and then to the target molecule with the Shapiro reaction. Remarkable differences were observed in the reactivity and stability of different hydrazones and their dianions in the Shapiro reaction. This pathway is the shortest one reported to give the target molecule in good overall yield. The use of different electrophiles in the ®nal Shapiro reaction step allows alternative ways to prepare the target alcohol.

The organocatalytic three-step total synthesis of (+)-frondosin B

“…Much to our delight, addition of vinyl lithium reagent 8 —readily accessible by the Shapiro reaction of known hydrazone 9—to aldehyde ( R )- 7a proceeded smoothly to give allylic alcohol 10 as an inconsequential mixture of diastereomers. 39,40 Hydrazone 9 can be prepared in one step from commercially available starting materials, namely by condensation of 2,2-dimethylcyclohexanone ( 3 ) and trisylhydrazide (trisyl = 2,4,6-triisopropylbenzenesulfonyl). 40,41 With the allylic alcohol 10 in hand, we next turned our attention to closure of the final seven-membered ring of frondosin B.…”

“…39,40 Hydrazone 9 can be prepared in one step from commercially available starting materials, namely by condensation of 2,2-dimethylcyclohexanone ( 3 ) and trisylhydrazide (trisyl = 2,4,6-triisopropylbenzenesulfonyl). 40,41 With the allylic alcohol 10 in hand, we next turned our attention to closure of the final seven-membered ring of frondosin B. We envisioned that a π-allyl Friedel–Crafts cyclization might serve this purpose, 42–44 with the assumption that the allylic alcohol 10 might form a π-allyl cation in the presence of a suitable transition metal catalyst.…”

Synthesis of a Novel Taxa‐Oxa‐Sugar Hybrid Core Structure by Tandem Cross‐Enyne Metathesis/IMDA

“…The ketone 19, obtained as the major product, was further converted into its tosylhydrazone derivative 21 in good yield. [35] The ketone 19 was also treated with trisyl hydrazide (TrisNHNH 2 ) in THF in the presence of catalytic amounts of p-toluenesulfonic acid (pTsA) to provide the trisylhydrazone 22 in 62 % yield. [36] Scheme 3.…”

“…The tosylhydrazone 21 was treated with nBuLi (3.3 equiv.) in THF to generate the vinyllithium species, [35] which was quenched with the aldehyde 14 to give a mixture of the separable epimeric alcohols 30 and 31 in almost 1:1 ratio (32 % combined yield). The yield of the Shapiro reaction was improved substantially (60 %) by using the trisylhydrazone 22 instead of 21 (Scheme 6).…”

Taxol: Synthesis, Bioactive Conformations, and Structure-Activity Relationships in Its Analogs

“…For example, new procedures were proposed for building up ring A [80][81][82], ring B [83][84][85], and BC fragment [86] as intermediates in the Mukaiyama synthesis. Shing et al [87] obtained the CD fragment in 21 steps starting from (S)-(+)-carvone, while Toyota et al [88] synthesized the AB fragment from bicyclo-[3.2.1]octane derivative.…”