This review highlights the advances in the literature up to May 2009 in the synthesis of spirocyclic indoline natural products. The focus is on formation of the spirocyclic chiral center, including both enantioselective and diastereoselective methods. This review is split into two main sections, the first consisting of the formation of spirooxindoles and their application towards oxindole alkaloids, and the second covering asymmetric synthesis of spiroindoline natural products. Conclusion

The asymmetric synthesis of the oxindole alkaloid horsfiline is described. A palladium-catalyzed asymmetric allylic alkylation (AAA) is used to set the spiro(pyrrolidine-oxindole) stereogenic center.(-)-Horsfiline was first isolated in 1991 from the leaves of the Horsfieldia superba plant by Bodo and co-workers. 1 Biologically active alkaloids such as spirotryptostatin A and B, vincristine, and vinblastine have resulted in increased interest for oxindole natural products such as horsfiline. The unique spiro stereogenic center of horsfiline has challenged synthetic chemists to develop imaginative approaches towards its construction. As a result, there has been much synthetic effort towards horsfiline, resulting in several syntheses, three of which were asymmetric. 2 In 1994, Borschberg confirmed the absolute configuration of horsfiline through the synthesis of both enantiomers via a diastereoselective oxidative rearrangement of a (L)-tryptophan derivative. 2i In 1999, Fuji et al. used a chiral auxiliary for nitro-olefination of a substituted oxindole to set the stereochemistry at the quaternary chiral center. 2h Palmisano and co-workers used an azomethine ylide cycloaddition reaction to form the pyrrolidine, and subsequently formed the oxindole by intramolecular cleavage of the chiral auxiliary. 2fWe envisioned constructing the stereogenic quaternary carbon via a palladium-catalyzed asymmetric allylic alkylation (AAA) employing oxindole as the nucleophile. The use of 3-aryl oxindoles in palladium AAA has been previously reported, 3 however oxindole nucleophiles with substituents other than aryl groups have not been employed in this chemistry. In our proposed synthesis of horsfiline, an ester or aldehyde substituent in the 3 position would provide a stabilized, compatible nucleophile for palladium allylic alkylation (Scheme 1). The carbonyl group also provides a handle for further manipulation. Oxidative cleavage of the allyl group followed by reductive amination would introduce the nitrogen of the pyrrolidine. Cyclization via reductive amination or S N 2 substitution would complete the tricyclic system. bmtrost@stanford.edu. Initially, an aldehyde was installed in the 3 position of the oxindole following a known procedure using sodium methoxide and ethyl formate. 4 However, the product from the AAA reaction with allyl acetate was unstable to purification ( Figure 1), resulting in deformylation. NIH Public AccessTo avoid this decomposition, the aldehyde functionality was changed to an ester. A rhodiumcatalyzed C-H insertion method developed by Padwa and co-workers was used to build the desired oxindole. 5 Refluxing p-anisidine with 2,4-dimethoxybenzaldehyde in toluene followed by reduction of the imine with sodium borohydride in methanol resulted in quantitative yield of the desired amine 3 (Scheme 2). Acylation with the acid chloride derivative of ethyl diazoacetate in the presence of triethylamine, led to formation of amide 4 in 90% yield. Padwa discovered that Rh 2 (acac) 4 led to β-lactam formation wit...

In this laboratory experiment, students work in pairs to synthesize a simple aliphatic polycarbonate via ring-opening polymerization of trimethylene carbonate using 1,8-diazabicyclo[5.4.0]undec-7-ene and thiourea as organocatalysts. Following polymer isolation, students cool the material in a dry ice/acetone bath to observe its glasstransition behavior. This experiment is convenient to perform under teaching laboratory conditions and reinforces key concepts learned in second-year undergraduate organic chemistry, for example, nucleophilic acyl substitution, transesterification reactions, and Lewis acidity−basicity. Additionally, the experiment introduces students to polymer chemistry, heterocycles, materials science, and green chemistry. It also covers interesting concepts that are less frequently encountered at the undergraduate level such as biomimetic chemistry, bifunctional catalysis, and polymer−glass transitions.

Morita-Baylis-Hillman diene adducts are used as substrates in the palladium-catalyzed asymmetric allylic alkylation reaction with oxygen and carbon nucleophiles in good regio- and enantioselectivity.

The oxa-Pictet-Spengler reaction of 1-(3-furyl)alkan-2ols with aldehydes catalyzed by p-toluenesulfonic acid gives good yields of the corresponding cis-5,7-disubstituted 4,5-dihydro-7Hfurano[2,3-c]pyrans.