A diversity-oriented approach for the synthesis of various structurally different molecular frameworks from readily accessible and common precursors is described A Claisen rearrangement followed by ring-closing metathesis or ethylene-promoted ring-closing enyne metathesis has been utilized as the key synthetic transformation to generate naphthoxepine derivatives The ring-closing metathesis approach has also been used to generate spirocyclic compounds and the pleiadene framework

Diversity‐Oriented Approach to Biologically Relevant Molecular Frameworks Starting with β‐Naphthol and Using the Claisen Rearrangement and Olefin Metathesis as Key Steps

The total synthesis of xanthohumol (1) was accomplished in 10% overall yield from phloracetophenone after six steps. Insertion of a prenyl group onto the aryl ring was achieved by a para-Claisen rearrangement after using a Mitsunobu reaction to establish the key prenyl ether precursor. A Claisen-Schmidt condensation was deployed to construct the chalcone scaffold followed by removal of MOM protecting groups under acidic conditions that were optimized to prevent concomitant cyclization to the flavone.

Total synthesis of xanthohumol.

A rapid entry to C-prenylcarbazoles: total synthesis of clausamine C-D, clausevatine D and clausine F.

Expeditious photochemical reaction toward the preparation of substituted chroman-4-ones

Depending on the nature of N- and C-substituents, nitrones exhibit diverse reactivity towards electron deficient acetylenes. Observed reactions include formal 1,3-dipolar cycloaddition and nucleophilic addition reactions. Possible involvement of zwitterionic intermediates and an unusual 1-aza-Cope rearrangement account for the generation of unexpected 1 : 1 adducts in the reaction of N-arylnitrones.

Diverse reactivity of nitrones towards electron deficient acetylenes

Claisen rearrangements of the 3-methylbut-2-enyl(prenyl) ethers 3 and 9 of 2-acetyl-1-hydroxyand 1-acetyl-2-hydroxynaphthalenes 1 and 2 and the bis(3-methylbut-2-enyl) ethers 12 and 18 of 2,4-and 4,6-diacetylresorcinols 11 and 17 have been studied under a variety of thermal and catalytic conditions. 2-Acetyl-4-(3- methylbut-2-enyl) naphthalene-1-ol 4 was the sole product on rearrangement of compound 3, in DMA or neat. Under catalytic conditions 3,4-dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran 7 was obtained in poor yield. An isomeric pyran, 1,2-dihydro-3,3-dimethyl-3H-naphtho[2,1-b]pyran 10(25–43%) was obtained under both thermal and catalytic conditions from 9. The rearrangement of 12 under thermal conditions (DMA and neat) furnished 3-acetyl-2,4-dihydroxy5-(3-methylbut-2-enyl)acetophenone 13 and 3,8-diisopropylbenzo[1,2-b: 3,4-b′]difuran 14. PdII mediated rearrangement of 12 gave only the partially deprenylated ether, 3-acetyl-4-hydroxy-2-(3-methylbut-2-enyloxy)acetophenone 15(29%). While the isomeric ether 18 gave the monoprenyl ether, 5-acetyl-4-hydroxy-2-(3-methylbut-2-enyloxy)acetophenone 19 in quantitative yield (95%). The rearrangement products were characterised and their formation rationalised in terms of allowed sigmatropic shifts ([3,3] prenyl and [1,5] H) followed by loss of prenyl or acetyl groups. The reactions of prenyl ethers are both comparable to those of the corresponding allyl ethers and consistent with the greater fixed double-bond character of the naphthalene system compared to that of benzene. Prenyl derivatives of benzene and naphthalene containing ortho-hydroxyacetophenone units were formed which have potential in synthesis.

Claisen rearrangement of prenyl ethers of isomeric acetylnaphthols and bisprenyl ethers of 4,6- and 2,4-diacetylresorcinols

Thermal Claisen rearrangement of the allyl ethers (3) and (12) of the isomeric 2-acetyl-1-hydroxy- and 1-acetyl-2-hydroxy-naphthalenes (1) and (2) has been studied by heating each in refluxing N,N-dimethylaniline (DMA) and neat at 185 °C under an N2 atmosphere. 2-Acetyl-4-allyl-1-hydroxynaphthalene (4), the sole product isolated from (3), was isolated in 56 and 88% yield respectively under the two sets of conditions. The rearrangement of the allyl ether (12) gave 3-acetyl-1-allyl-2-hydroxynaphthalene (13)(18%) and 2-acetoxy-1-allylnaphthalene (14)(23%) in N,N-DMA while in the neat rearrangement it gave (14) as the major product (70%) along with 1-allyl-2-hydroxynaphthalene (17)(20%). The rearrangement of the allyl ether (7), obtained on further allylation of (4), furnished 2,4-diallyl-1-hydroxynaphthalene (8), (15%) and (4)(15%) in DMA while it gave 1-acetoxy-2,4-diallylnaphthalene (9) as the sole product (67%) in the neat rearrangment. The rearrangement of the allyl ether (15), obtained by further allylation of (13), in DMA gave 3-acetyl-1,1-diallylnaphthalen-2(1H)-one (16)(20%) along with (13)(6%). The various rearrangement products have been characterised by their spectroscopic data (UV, IR, 1H NMR, and EI-MS) and the reactions rationalised by the allowed sigmatropic shifts such as [3,3] allyl, [1,5] acetyl followed by loss of allyl or acetyl groups. The significant differences noticed in the reactions of the isomeric series of allyl ethers are consistent with the greater fixed double-bond character of the naphthalene system compared to that of benzene as well as the positional isomerism that exists in the allyl ethers. The above Claisen rearrangement studies result in the isolation of some interesting naphthylallyl derivatives with orhto-hydroxyacetophenone units which form useful synthetic intermediates for preparing several naphthyl-α- and γ-pyrone derivatives of pharmacological activity.

B. M. Isaa

Papers

Claisen rearrangement of prenyl ethers of isomeric acetylnaphthols and bisprenyl ethers of 4,6- and 2,4-diacetylresorcinols

Thermal Claisen rearrangement of allyl ethers of isomeric acetylnaphthols

Claisen Rearrangement of Prenyl Ethers of Isomeric Acetylnaphthols and Bisprenyl Ethers of 4,6‐ and 2,4‐Diacetylresorcinols.

Thermal Claisen Rearrangement of Allyl Ethers of Isomeric Acetylnaphthols.

Claisen Rearrangement of Allyl Ethers of Isomeric Acetylnaphthols Under Catalytic Conditions.