Thermal Isomerization of Isoborneols and Dehydroisoborneols to New Chiral Building Blocks in Terpenoid Synthesis

Abstract

The substituted isoborneols 1a ± 1g and 5,6-dehydroisoborneols 6a ± 6c, readily prepared in excellent yields from ()-camphor and ()-5,6-dehydrocamphor (2) by aryl, vinyl, or alkyl Grignard addition in the presence of stoichiometric amounts of CeCl 3 , were thermally isomerized in a flow reactor system under DGPTI (dynamic gas-phase thermo-isomerization) conditions at temperatures between 480 and 6308 to give the enantiomerically pure monocyclic carbonyl compounds 7a ± 7d, 19a, b, 23, and 24. In all cases, product formation proceeded highly regio-as well as stereoselectively. The absolute configurations of the new stereogenic centers were determined by 1 H-NOE measurements. DGPTI of the aryl substrates 1a ± 1d is proposed to effect initial cleavage of the weakest single bond in the molecule under formation of a diradical intermediate state followed by intramolecular H-abstraction to afford the acetophenone derivatives 7a ± 7d. This reaction path was further supported by a 2 H-labeling study showing the OH group to be the exclusive H-source. In contrast, DGPTI of the vinyl substrates 1e and 6b allowed concerted retro-ene and oxy-Cope rearrangements. In the case of 5,6-dehydro-2-phenylisoborneol (6a), concomitant diradical and retro-DielsÀAlder reaction pathways could be observed. In addition, a new route to ()-trans-a-campholanic acid (9) and ()-trans-a-dihydrocampholytic acid (14) is presented by regioselective BaeyerÀVilliger oxidation and subsequent hydrolysis of 7c and 7d, respectively.

Development of a Scalable Lanthanide Halide/Quaternary Ammonium Salt System for the Nucleophilic Addition of Grignard Reagents to Carbonyl Groups and Application to the Synthesis of a Remdesivir Intermediate

“…Table reports the average of the two experimental runs. The analytical data of the product in both experiments were found to be in good agreement with previously reported literature data …”

“…1-Isopropyl-cyclohexanol was obtained as a colorless oil (1.28 g, 88% yield, 77% yield after correction for solvent content). The analytical data were found to be in good agreement with previously reported literature data …”

Synthesis of β-acetoxy alcohols by PhI(OAc)2-mediated metal-free diastereoselective β-acetoxylation of alcohols

“…All derivatives of alcohol 1 has been reported before and their spectroscopic data matched the literature values: 1a-c, 22 1d, 23 1e-f, 24 1g, 25 1h, 24 1i, 26 1j-l, 27 1m, 28 1o, 29 1p, 22 1q, 30 1r-s, 31 1t, 32 1u, 33 1v-w, 34 1x, 35 1y. 36…”

Nickel-Catalyzed Reductive Deoxygenation of Diverse CO Bond-Bearing Functional Groups

“…was prepared from flavanone (47) according to a modified General Procedure A, using 2.4 equivalents of TMDSO and quenching with 1.0 M HCl post-reaction. Column chromatography was performed using a gradient of 1→15% ethyl acetate in hexanes to afford (48) as an off-white solid (28 mg, 68% yield).…”

“…Characterization data matched those previously reported. 47 80a) and 1.81 ppm (for 80b) were used to assess diastereoselectivity. In both cases, a 1:1 ratio of 80a:80b was observed.…”