Enantioselective synthesis polyene cyclization

Enantioselective Polyene Cyclization Catalyzed SnCU-BINOL Derivatives. Non-enzymatic enantioselective polyene cyclizations are very attractive alternatives to the multistep synthesis from naturally occurring chiral synthons. The authors have succeeded in the first enantioselective biomimetic cyclization of polyprenoids catalyzed by LBA. (—)-Ambrox is the most important commercial substitute for ambergris, due to its unique olfactory and fixative properties. The successful preparation of (—)-ambrox has been achieved by the enantioselective cyclization of homofamesol promoted by (/ )-BINOL-Me-SnCl4, although the enantioselectivity and diastereoselectivity is moderate (eq 10). 

Non-enzymatic enantioselective polyene cyclizations are very attractive alternatives to multistep synthesis from naturally occurring chiral synthons. 

For nongroup-selective examples, one of the first reports of an enantioselective intramolecular Mizoroki-Heck reaction was a polyene cyclization (Scheme 12.22) [23b], The trienyl triflate 5 underwent two intramolecular cyclization reactions to give the tricycle 6 in high yield and 45% ee. A cascade intramolecular Mizoroki-Heck-hydride capture sequence was used in the synthesis of retinoid derivatives from aryl iodide 100 to give benzofuran 101 in 80-81% ee [49]. Poor enantioselectivity was observed when neutral reaction conditions were employed. 

Conventional multistep synthesis of natural products reduces the overall yield of the target molecules. In contrast, biomimetic enantioselective domino reactions, promoted by small-molecule artificial enzymes, are more useful for the practical synthesis of natural products and related compounds. The stereoselective formation of polycyclic isoprenoids by the cyclase-induced cyclization of polypren-oids is one of the most remarkable steps in biosynthesis because this reaction results in the formation of several new quaternary and tertiary stereocenters and new rings in a single step. The use of biomimetic polycyclization with artificial cyclase is the most ideal chemical method for the synthesis of these polycyclic terpenoids. In this chapter, biosynthesis of polycyclic terpenoids, biomimetic stereoselective polyene cyclization induced by artificial cyclases, and total synthesis of bioactive natural products using stereoselective polyene cyclization as a key step will be discussed. 

In 2010, Toste s group reported the first example of a highly enantioselective polyene cyclization reaction in which transition metal-promoted alkyne activation serves as the cyclization initiating event [34], The (MeO-DTBM-BIPHEP)gold(I)-catalyzed reaction offers an efficient method for the stereoselective synthesis of polycyclic compounds... 

Rapid and economical synthesis of steroids or terpenes skeletons is possible through the organo-SOMO-catalyzed polyene asymmetric cyclization at room temperature [54]. This methodology allows the formation in a one-pot procedure of up to 6 new C-C bonds, 11 stereogenic centers, and 5 quaternary stereocenters with high yields and enantioselectivities (Scheme 7.36). 

The chemical simulation of this biosynthetic process has been developed as an important methodology in organic synthesis. Van Tamelen reported the add-catalyzed cyclization of chiral terminal epoxides of polyprenoids [11]. In contrast, Johnson adopted the acid-catalyzed cyclization of poly-prenic acetals derived from chiral diols [12]. In addition to these pioneering studies, the biomimetic polyene cycliza-tions of polyprenoids, which are induced by a variety of electrophiles such as proton, oxonium ion, halonium ion [13], or metal ion [14], have also been developed. Despite extensive studies on these diastereoselective olefin cyclizations, enantioselective processes using synthetic chiral catalysts had not been developed for a long time. In 1999, Yamamoto s... 

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