Synthesis of new fused isoquinolines via reissert compounds

Abstract

Reissert compounds 2 derived from isoquinoline, chloroformates and TMS-cyanide were alkylated in position 1. The resulting alkylation products 3 as well as the precursors 2 reacted with Grignard reagents affording imidazoisoquinolines 4, 5, 7 and 8 by addition to the cyano group and Grignard reduction or by twofold addition to the cyano group, respectively. In both cases the alcohol of the 2-alkoxycarbonyl moiety was eliminated by attack of the N-atom at the carbonyl carbon atom. Under acid conditions, 1-benzylated Reissert compound 3h cyclised by attack of the resulting N-acyliminium C-atom at the o-position of the benzyl ring to form tetracyclic 1,3-bridged tetrahydroisoquinolines 10 and 11. Bromocyclisation of 1-allyl-2-menthyloxycarbonyl-substituted Reissert compounds 3b, c led to tricyclic dibromo products 12, in which the menthol moiety was split off and addition to the enamine double bond occurred. A 2-menthyloxycarbonyl group in Reissert compounds 2a and 3 failed to exert an asymmetric induction in all cases.

Stereoselective 1-arylation of isoquinolines via chiral N-acylisoquinolinium salts

“…12,13 In this way, a variety of electron rich aryl and auxiliary in the Reissert reaction (addition of cyanide to position 1) with isoquinolines but in contrast to first assumptions, 16 the reaction was not stereoselective but gave 1:1 mixtures of epimers. 18,20 As an extension of our interest in the application of (R)-menthyl chlorocarbonate and α-amino acid fluorides as auxiliaries in stereoselective 1,2-additions to isoquinolines [16][17][18] we sought their application in the stereoselective introduction of aryl groups into position 1.…”

Isoquinoline- and piperazinedione-derived α-acylamino peroxide moieties in asymmetric oxidation of sulphides and epoxidation of naphthoquinones

“…[27][28][29][30] However, the original assumption of complete diastereoselective formation of the 1,2-adducts was erroneous, as found out by two independent groups. 28,29 Instead, 1:1 mixtures of epimers were formed. As an alternative to those nucleophiles used before, it would be interesting to investigate how hydrogen peroxide behaves when used in such additions to isoquinolines.…”

“…However, stereoselectivity could not be achieved, as it was also missing before in analogous reactions with cyanide as nucleophile. 27,29 Thus all these products 11 and 12 were not useful in asymmetric oxidations of sulphides 1. As a consequence and having in mind the in situ formation of α-aminohydroperoxide moieties from flavine-derived cyclophanes and hydrogen peroxide in the stereoselective sulphoxidations, 21 our strategy was turned to the combination of hydrogen peroxide, isoquinolines 7 and (R)-menthyl chloroformate 8 and metal compounds as additives (Scheme 3).…”