Tandem Reactions Combining Diels-Alder Reactions with Sigmatropic Rearrangement Processes and their Use in Synthesis

Abstract

Diels-Alder reactions and sigmatropic rearrangements are of paramount importance in synthesis. The tandem Diels-Alder/ sigmatropic rearrangement processes combining these two powerful methods is presented in this review. Both possible sequences of this tandem process are discussed and several successful examples of the synthesis of natural products using the combination of these two reactions as key step demonstrate the utility of these processes.

Synthesis of Substituted 1‐Thiocyanatobutadienes and Their Application in a Diels—Alder/[3,3] Sigmatropic Rearrangement Tandem Reaction.

“…The resulting mixture was magnetically stirred at 0 C for 30 min and then diluted in CH 2 Cl 2. The organic phase was washed with saturated aqueous NH 4 Cl, H 2 O, dried (MgSO 4 ), and concentrated in vacuo to get the product that was purified by chromatography on a silica gel column.…”

“…Procedure D: A solution of 1.1 eq of Li bis(trimethyldisilyl)amide (1 M in THF) was diluted 3 times in a THF=DMPU mixture to get a 0.33 M solution, which was cooled to À90 C. A 1.0 M solution of 1.0 eq of 11 in freshly distilled THF was then added dropwise while maintaining the temperature of the solution below À80 C. The orange solution was then magnetically stirred at À85 C for 45 min and 1.1 eq of the corresponding electrophile were added dropwise maintaining the temperature of the solution below À80 C. The temperature was then allowed to warm slowly to 0 C and the mixture was stirred for additional 1 h at 0 C. After diluting three times the reactions mixture with n-hexane, the solution was poured onto saturated aqueous NH 4 Cl. The organic phase was washed with H 2 O and brine, dried (MgSO 4 ), and concentrated in vacuo to get the product that was purified by chromatography on a silica gel column.…”

“…An attractive way to reduce the length of a synthetic pathway is to combine several transformations into one-pot reactions so called tandem, domino, or cascade reaction [1][2][3]. The tandem process Diels-Alder reaction= [3,3] sigmatropic rearrangement combines two well-known pericyclic reactions in one single synthetic step, which allows to obtain interesting synthetic building blocks efficiently [4]. Starting from (E)-1-thiocyanatobuta-1,3-diene (1) and acryloyl chloride led to a cis=trans 85:15 mixture of diastereoisomers of 1,4-substituted cyclohexene 3 in 84% yield [5] (Scheme 1).…”

Short synthesis of a tetrasubstituted tetrahydropyran with five stereogenic centres—stereoselective double tandem rearrangements and cyclisation

“…[1][2][3] This inevitably leads to a reduction in the number of steps required with associated savings in time and purification costs.…”

The Novel Sequence Diels-Alder Reaction/Ireland-Claisen Rearrangement Applied to Acyclic Dienophiles: New Insights into the Selectivity of the Ireland-Claisen Rearrangement

“…5 There are different reasons for the attractiveness of such processes. The sequence belongs to the class of heterogenerative coupled transformations, 1a as the first bond-forming reaction sets the stage for the next event generating new functionalities which were not present in the starting materials.…”