A novel lithium iodide-promoted vinylcyclopropane-cyclopentene rearrangement: Efficient synthesis of bicyclo[3.3.0]oct-6-en-2-one, versatile building block for polycyclopentanoid natural products

A Palladium‐Catalyzed Formal (4+1) Annulation: A New Approach to Cyclopentene Construction

“…As an example of the two-step sequence, treatment of e-dienyl b-keto ester 1 with a catalytic amount of palladium acetate, 2.5 equivalents of copper(II) isobutyrate, and 1.0 equivalent of magnesium perchlorate in DMSO at 65 8C for 12 h led to isolation of the 7-vinylbicyclo[4.1.0]-2-heptanone derivative 2 in 92% yield as a 10:1 mixture of diastereomers (Scheme 1). Treatment of 2 with 1.5 equivalents of magnesium iodide in acetonitrile at 40 8C led to isolation of the bicyclo[4.3.0]non-7ene-2-one derivative 3 in 86 % yield (Scheme 1).The oxidative cyclopropanation step (1!2) that is key to the Coscia-Lambert annulation protocol builds upon the work of Bäckvall and Andersson, [9] Ikegama et al, [10] Widenhoefer et al, [11] and Yang et al [12] Nevertheless, this transformation is unique with respect to palladium catalysis. Oxidative cyclopropanation of 1 presumably occurs through outer-sphere attack of the Mg II -stabilized enol moiety of I on the palladium h 2 -diene moiety coupled with loss of HO 2 CR and tautomerization to form palladium p-allyl intermediate II (Scheme 2).…”

“…Oxidative cyclopropanation of 1 presumably occurs through outer-sphere attack of the Mg II -stabilized enol moiety of I on the palladium h 2 -diene moiety coupled with loss of HO 2 CR and tautomerization to form palladium p-allyl intermediate II (Scheme 2). [11,12] Subsequent outer-sphere attack of the enol moiety at the proximal carbon atom of the p-allyl moiety of II [10] coupled with loss of a second molecule of HO 2 CR would form 2 with concomitant reduction of Pd II to Pd 0 . Palladium(0) is then oxidized by the copper(II) salt to regenerate the catalytically active Pd II species.…”

“…The oxidative cyclopropanation step (1!2) that is key to the Coscia-Lambert annulation protocol builds upon the work of Bäckvall and Andersson, [9] Ikegama et al, [10] Widenhoefer et al, [11] and Yang et al [12] Nevertheless, this transformation is unique with respect to palladium catalysis. Oxidative cyclopropanation of 1 presumably occurs through outer-sphere attack of the Mg II -stabilized enol moiety of I on the palladium h 2 -diene moiety coupled with loss of HO 2 CR and tautomerization to form palladium p-allyl intermediate II (Scheme 2).…”

“…Palladium(0) is then oxidized by the copper(II) salt to regenerate the catalytically active Pd II species. Interestingly, employment of copper(II) acetate rather than copper(II) isobutyrate as the Attack of the enol carbon at the internal carbon of the p-allyl moiety of II to form the vinyl cyclopropyl group of 2, as opposed to attack at the terminal p-allyl carbon atom [9,10] to directly form the desired cyclopentene necessitates a secondary VCP!CP rearrangement to complete the formal (4+1) annulation. Although this kind of rearrangement has been realized under a variety of conditions, [13] none of the common protocols proved effective for the conversion of 2 to 3.…”

“…As a solution to this problem, Coscia and Lambert developed a magnesium iodide mediated conversion (Scheme 1). The process takes advantage of the known propensity of iodide ions to undergo homoconjugate ring-opening addition to VCPs [10] coupled with the Mg II stabilization of the b-keto ester derived enolate III [Eq. (1)].…”