A novel tandem reaction by combination of Diels-Alder [4+2] cycloaddition and [3+2] IMCC (intramolecular cross-cycloaddition) of dienylcyclopropane 1,1-diesters has been successfully developed. In this reaction, three new rings and four new stereocenters were generated in one-pot. This supplies a strategy for rapid construction of 6,6-and 6,7-fused carbocyclic skeletons which are common cores in many biologically important natural products.Cycloaddition represents one of the most effective methods for rapid construction of cyclic skeletons. 1 Combination of two cycloadditions in one pot will supply an efficient strategy for construction of polycyclic skeletons in natural products, which is highly important but remains challenging in organic synthesis. Both 6,6-and 6,7-fused carbocyclic skeletons, including the ones with an embedded oxa-bridged ring, are common cores in many biologically important natural products ( Figure 1). 2 Recently we have developed a novel Lewis acids catalyzed intramolecular cross-cycloaddition (IMCC) of cyclopropanes, which provides a general and efficient strategy for the construction of bridged skeletons. 3 One of our ongoing research projects is to develop IMCC-based tandem reactions toward efficient construction of polycyclic skeletons in natural products. In this paper, we report a novel tandem reaction for construction of the 6,6-and 6,7-fused carbocyclic skeletons by the combination of the [3+2] IMCC 3e,f,4c of dienylcyclopropane 1,1-diester 4,5 and Diels-Alder [4+2] cycloaddition in one pot. Our test of this concept was initiated from the reaction of dienylcyclopropane 1,1-diester 1a (as a mixture of Z/E isomers, 1 equiv) and acrolein (2a; 20 equiv; Scheme 1 and Table 1, entry 1). When a mixture of 1a, 2a and hydroquinone (0.2 equiv) was refluxed in toluene in a sealed tube for 40 hours, besides the Diels-Alder [4+2] cycloadduct 3a, another 6,7-fused tricyclic product 4a was obtained via a domino Diels-Alder [4+2]/[3+2] IMCC process. The cycloadduct 3a was separated in a yield of 46% and as a mixture of diastereoisomers. To the best of our knowledge, this is the first example of cycloaddition of cyclopropane being promoted by phenol. A prolonged reaction time could promote the conversion of 3a to 4a but with a decreased yield. When toluene was evaporated and the solvent was switched to DCE, under catalysis of Sc(OTf) 3 (0.2 equiv) 6 4a was obtained exclusively as a mixture of two diastereoisomers with a ratio of 5:1 and a combined yield of 26%. Structure of the major isomer was determined by NMR and X-ray crystal structure analysis 7

A Lewis acid catalyzed domino aldol/homo‐Michael reaction of formylcyclopropane 1,1‐diesters with dicarbonyls has been successfully developed. This method provides efficient and direct construction of highly functionalized furans from easily available starting materials.

A modified total synthesis of cystothiazole A is described. In this synthetic strategy, a one-step transformation of acylated oxazolidinone to β-ketoester has been successfully applied, thus making the synthetic route more efficient. This method may also be potentially applied in synthesis of other related β-substituted-β-methoxyl acrylates (bb-MOAs).

Tandem Diels-Alder [4 + 2] Cycloadditions and Intramolecular [3 + 2] Cross-Cycloadditions of Dienylcyclopropane 1,1-Diesters. -While the first reaction step provides a mixture of four diastereomers, the second step completes the access to 6,6-and 6,7-fused carbocyclic skeletons with three new rings and four new stereocenters with moderate to excellent diastereoselectivities. -(REN, J.; BAO, J.; MA, W.; WANG*, Z.; Synlett 25 (2014) 16, 2260-2264, http://dx.

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