Four homoallyl ortho-vinylaryl ketones (10a-d) -1,8dienes of sorts -were prepared by several approaches. In the presence of 1-2 mol-% Grubbs-II catalyst, they ring-closed to give 6,7-dihydrobenzocyclohepten-5-ones (11a-d) in 90-96 % yield. With SeO 2 the parent compound (11a) delivered benzocyclohepten-5-one (13a) and/or selenium-containing compounds (18)(19)(20)(21)(22) but no more than traces of 6,7-benzotropolone (5a). However, 5a was accessible from compound 11a via the sodium enolate and allowing it to react with a stream of oxygen [a] Scheme 1. Top: our previously established ring-closing olefin metathesis ("RCM")/ketal hydrolysis route to type-5 6,7-benzotropolones. [9] Underneath: regiocomplementary processings of a type-4 RCM product via the dibromide 7 and the bromoolefins 7 or iso-7 by cross-couplings and hydrolyses giving type-8 or type-iso-8 6,7-benzotropolones, respectively. [10] The Arican routes of Scheme 1 have a major drawback, though, namely the harsh conditions required for hydrolyzing a type-4 ketal in the last step: Liberating the enol required refluxing with 10 equiv. of tosic acid and 100 equiv. of water in acetonitrile for 1 h -2 d. [9,10] These conditions were applicable to certain type-9 or type-iso-9-ketals, as well ( Figure 2). When their substituent R was Et, Ph, CO 2 Me or CO 2 Et, such hydrolyses also proceeded well. [9] However, when their substituent R was CH=CH-CO 2 iPr (in 9a or iso-9a), HC=CH 2 (in 9c or iso-9c) or C≡C-SiMe 3 (in iso-9c) the substrate vanished under hydrolysis conditions without delivering any benzotropolone. [9,10] The C≡C-SiMe 3 -containing ketal 9b was an in-between-case: Its hydrolysis released a benzotropolone as expected but the sidechain R had been converted into C(=O)-CH 3 . [10] Eur.2930 Scheme 2. Can 6,7-benzotropolones 5 be reached via an RCM/oxidation route rather than via the RCM/hydrolysis route of Scheme 1? A 4-e 2 oxidation 11 → 5 would be required overall, but two 2-e 2 oxidations 11 → 12 and 12 → 5 might be used as an alternative.
5.We wondered whether step 2 might be disadvantaged vs. a dehydration delivering the benzotropone 13. While 13 looks like a dead-end at first, it might be re-routable towards 5. This is because unsubstituted benzotropone (13, all R = H) gave unsubstituted benzotropolone (5, all R = H) by endoperoxide formation and an ensuing reduction with thiourea. [11] Consequently, benzotropones 13 appeared as conceivable intermediates of our Scheme-2 strategy towards benzotropolones.
A Modified Synthesis of 6,7-BenzotropoloneOur proof-of-principle benzotropolone synthesis by the approach of Scheme 1 delivered the parent compound 5a and is shown in Scheme 3 and Scheme 5. Scheme 3 advances to the RCM product and Scheme 5 supplements its oxidation. Scheme 3. Reaching the RCM product 11a, our synthetic precursor of unsubstituted benzotropolone (5a).Our synthesis began by a salt-free Wittig methylidenation of ortho-bromobenzaldehyde (14, Scheme 3). [12] The resulting ortho-bromostyrene (15) was treated sucessively with nBuLi and the...
