1,n-Rearrangement of Allylic Alcohols Promoted by Hot Water: Application to the Synthesis of Navenone B, a Polyene Natural Product

Abstract

It was reported for the first time that hot water as a mildly acidic catalyst efficiently promoted 1,n-rearrangement (n = 3, 5, 7, 9) of allylic alcohols. In some cases, the rearrangement reactions joined isolated C-C double or triple bonds to generate conjugated polyene or enyne structure motifs. We used the 1,3-rearrangement reaction of an allylic alcohol in hot water as part of an attractive new strategy for construction of the polyene natural product navenone B by iterative use of a Grignard reaction, a 1,3-rearrangement of the resulting allylic alcohol, and subsequent oxidation of the rearranged product.

Solvent-Free Mizoroki-Heck Reaction Applied to the Synthesis of Abscisic Acid and Some Derivatives

“…A small amount of the expected product 3a was isolated along with the side product 4 (entry 2). The formation of 4 can be explained by a 1,3-rearrangement of the allylic alcohol, a transformation previously described by Qu and co-workers under a thermal activation in water [48]. The use of acetonitrile moreover of an additional ligand induced no positive change (entries 3 and 4) [49].…”

“…Surprisingly, only degradation was observed. Since conjugated products are prompted to make versatile rearrangement [47,48], the reaction was next performed in a flask protected from natural light. A small amount of the expected product 3a was isolated along with the side product 4 (entry 2).…”

Alcohol Dehydrogenases and N‐Heterocyclic Carbene Gold(I) Catalysts: Design of a Chemoenzymatic Cascade towards Optically Active β,β‐Disubstituted Allylic Alcohols

“…Both sequential and cascade approaches provided the desired alcohols in very high to excellent optical purities (93‐>99 % ee ), compounds that were recovered in moderate to high isolated yields (up to 86 % for the ( R )‐alcohols and up to 80 % for the ( S )‐alcohols), obtaining lower yields for alcohol 5 r due to the high volatility of this aliphatic substrate. The reaction resulted unsuccessful for the synthesis of alcohol 5 x due to the spontaneous 1,3‐rearrangement of the final product in aqueous medium [67] forming the achiral ( E )‐2‐methyl‐4‐phenylbut‐3‐en‐2‐ol and therefore hampering the development of a stereoselective process. In fact, when the chemically synthesized racemic 5 x was incubated in the bioreduction medium without enzyme, the isomerization reaction occurred.…”

Unprecedented Mechanism of an Organocatalytic Route to Conjugated Enynes with a Junction to Cyclic Nitronates

“…While, with strong bases DBU 7 and 1-(2-aminoethyl)-piperazine 10 nitronate 6a was clearly the major product with all other bases enyne emerged as major product (except for 11 where no enyne 5a was generated). [18] Hence, we mainly focused on examining the scope of conjugated enynes 5. For the conjugated enyne 5 no clear correlation was observed between basicity, yield and rate most probably due to the complex mechanism.…”

“…Dynemicin A, [1] Terbinafine [2,3] (Lamisil®), callipeltosides [4] or Neocarzinostatin [5] ], nitronates, especially cyclic nitronates, find application in the synthesis of biologically active compounds, [6,7] drug candidates [8][9][10] and natural products. [18] On the other hand, numerous metal-free procedures for the synthesis of cyclic nitronates already exist among which intramolecular cyclization via substitution and cycloadditions are commonly employed. The most established methods for the formation of conjugated enynes are metal catalyzed cross-couplings exploiting the presence of double and triple bonds in the starting materials.…”