Diastereoselective Friedel–Crafts Alkylation of Hydronaphthalenes

Abstract

An efficient and versatile synthesis of chiral tetralins has been developed using both inter- and intramolecular Friedel-Crafts alkylation as a key step. The readily available hydronaphthalene substrates were prepared via a highly enantioselective metal-catalyzed ring opening of meso-oxabicyclic alkenes followed by hydrogenation. A wide variety of complex tetracyclic compounds have been isolated with high levels of regio-, diastereo-, and enantioselectivity.

cis-Diastereoselective synthesis of chroman-fused tetralins as B-ring-modified analogues of brazilin

“…The obsereved cis -diastereoselectivity in this work is consistent with the reported synthesis of related-tetracyclic molecules via Friedel–Crafts cyclization (Scheme 2, lower panel) promoted by metal-based Lewis acids [27–28]. Noteably, none of the synthesized molecules described in these two reports contains an angular –OH group.…”

“…Thus, we were concerned about the possibility of getting a mixture of 5 and 9 under the planned IFCEA cyclization of 6 . However, a literature survey indicated that cis -diastereoselective synthesis of related tetracyclic molecules via intramolecular Friedel–Crafts cyclization of tetralins (Scheme 2, lower panel) has been described by Lautens and co-workers [27–28]. …”

Access to Polycyclic Derivatives by Triflate‐Catalyzed Intramolecular Hydroarylation

“…Among the various catalysts investigated at 5 mol-% (Table 1, Entries 1-6), Sn(OTf) 2 , Al(OTf) 3 and Fe(OTf) 3 catalysed the intramolecular reaction of 1a in moderate yields (Table 1, entries 1-3). Sc(OTf) 3 , In(OTf) 3 and Bi(OTf) 3 were the most efficient catalysts (Table 1, Entries 4-6) and led to the expected bicyclic structure 2a in yields of 92-96 %.…”

“…Some selected examples are presented in Scheme 1, including celestolide, a commercial perfume component with an outstanding musk odour, [1] lasofoxifene for the treatment of osteoporosis, the anticancer agent podophyllotoxin [2] and the antifertility agent trans-1- (2-{4-[6,7,8,9-1 variety of polycyclic compounds have been isolated in high yields. Lactonisation could be observed for esters with 2,2-disubstituted terminal olefins through a Lewis acid catalysed reaction between the olefin and one of the ester groups.…”

“…Some selected examples are presented in Scheme 1, including celestolide, a commercial perfume component with an outstanding musk odour, [1] lasofoxifene for the treatment of osteoporosis, the anticancer agent podophyllotoxin [2] and the antifertility agent trans-1-(2-{4- [6,7,8,9-tetrahydro-2-methoxy-6-(phenylmethyl)-5H-benzocyclohepten-5-yl]phenoxy}ethyl)pyrrolidine. [3] Their challenging structures have led to a permanent interest in the development of efficient and selective syntheses.…”