Iron-Catalyzed Synthesis of Tetrahydronaphthalenes via 3,4-Dihydro-2H-pyran Intermediates

Abstract

The development of an iron(III)-catalyzed synthetic strategy toward functionalized tetrahydronaphthalenes is described. This approach is characterized by its operational simplicity and is distinct from currently available procedures that rely on [4 + 2]-cycloadditions. Our strategy takes advantage of the divergent reactivity observed for simple aryl ketone precursors to gain exclusive access to tetrahydronaphthalene products (23 examples). Detailed mechanistic investigations identified pyrans as reactive intermediates that afford the desired tetrahydronaphthalenes in high yields upon iron(III)-catalyzed Friedel-Crafts alkylation.

Carbonyl–Olefin Metathesis Catalyzed by Molecular Iodine

“…When the distance between the carbonyl and the olefin moieties was varied with different carbon chain linkers ( 1′ , Scheme a), the reaction outcomes changed vastly. γ,δ-Olefin ketone ( n = 1) gave the 3,4-dihydro-2 H -pyran 4 , presumably via a 6- endo - trig cyclization process similar to what was reported by Schindler and co-workers, while δ,ε-olefin ketone ( n = 2) gave the normal COM products ( 2a and 2a′ ). ε,ζ-Olefin ketone ( n = 3), on the other hand, did not convert to any cyclized products (see page S19 in the SI for more unproductive ε,ζ-olefin ketone substrates)…”

Hydrogen Bonding Networks Enable Brønsted Acid-Catalyzed Carbonyl-Olefin Metathesis

“…Friedel-Crafts alkylation fashion to form tetrahydronaphthalene product 6e', which became the single major product at elevated temperature. This reaction pathway 26 is directly relevant to the formation of products 4 in Scheme 3a, where presumably the carbocation intermediate from a COM process also underwent Friedel-Crafts alkylation reaction onto the adjacent aromatic ring to form the tricyclic system. Thus, we decided to carry out a comparative study where we performed two of each type of the 6endo-trig cyclization, the COM reactions and the interrupted COM reactions in different sets of conditions with pTSA/HFIP and TfOH/DCE (Table 2, for further details on these studies and also the reaction performances on the 5-exo-trig, 5-exo-dig cyclizations, see page S69 in the experimental SI).…”

Hydrogen Bonding Networks Enable Brønsted Acid‐Catalyzed Carbonyl‐Olefin Metathesis**

“…The substrate could also cyclize in a Friedel–Crafts alkylation fashion to form tetrahydronaphthalene product 6 e′ , which became the single major product at elevated temperature. This reaction pathway [31] is directly relevant to the formation of products 4 in Scheme 3a, where presumably the carbocation intermediate from a COM process also underwent Friedel–Crafts alkylation reaction onto the adjacent aromatic ring to form the tricyclic system [26a] . Such interrupted COM reaction is possible for this type of substrate but not the typical COM substrate (Scheme 3b), which can be attributed to the conformational arrangement of the initially formed six‐membered ring.…”