Selective Mono‐allylation of 1,3‐Diketones and Their Use in the Synthesis of 3‐Allyl Chromones and Benzannulated 6,5‐Bicyclic Ketals

Abstract

The selective mono‐allylation of 1,3‐diketone containing compounds is described. The reaction proceeds under mild reaction conditions and in moderate to high yield (66–99 %). Using this procedure to access the key mono‐allylated intermediate, the hitherto difficult to access 3‐allyl chromones were synthesized in excellent yield (87–98 %). Finally, the utility of this newly developed procedure was showcased through the rapid synthesis of the scaffold of the xyloketal family of natural products.

The Synthesis of (±)‐Oxyisocyclointegrin

“…[1] One of the most studied subsets of these natural products are the morusins [morusin (1), cyclomorusin (2), neocyclomorusin (3), Figure 1]. [4] In a forward synthetic sense, the synthesis began with the known ketone 12, which was prepared from the commercially available 2,4,6-trihydroxyacetophenone following literature procedures (Scheme 2). [2] Among the first reported compounds from this family of structurally related molecules are integrin (4) and oxyisocyclointegrin (5).…”

“…To the best of our knowledge no biological activity data for either 4 or 5 has been reported in the literature. [4] Subsequent treatment of 15 with 10 % H 2 SO 4 in AcOH provided the 3-allylflavone 16 in an excellent yield. Herein we report the first total synthesis of the natural products integrin (4) and oxyisocyclointegrin (5) as well as preliminary biological data indicating both compounds possess moderate to weak antibacterial and anticancer properties.…”

“…After extensive screening, [8] it was found that irradiation of integrin (4) in the presence of oxygen, with a high pressure mercury lamp for 7 hours, provided a mixture of oxyisocyclointegrin and its hydroperoxide (1:4 ratio, respectively determined by 1 H NMR). Construction of the flavone core.…”

Synthetic Strategies towards the Synthesis of Oxyisocyclointegrin

“…Synthesis of this intermediate flavone required the formation of a mono‐α‐allyl‐1,3‐diketone, which could be difficult to access through classical nucleophilic substitution methods due to the potential for over allylation of the α‐carbon. Recent work conducted in our laboratory led to the discovery of an intramolecular Tsuji–Trost‐type allyl migration, which exclusively provides mono‐α‐allyl‐1,3‐diketones in good yields . To test the validity of this approach a model system was constructed (Scheme ).…”

“…The 1,3‐diketone 28 was synthesized in high yield from 2‐allyloxyacetophenone and methyl‐2‐methoxybenzoate. The Tsuji–Trost allyl migration, and subsequent acid promoted cyclization provided the flavone 29 in 18 % yield over 2 steps (Scheme ). Treatment of 29 with BBr 3 produced the desired phenol 30 in 79 % yield.…”