Cyclization enantioselective polyene

Jt-allyl complex can be generated after cyclization, as suggested by Takacs in a Fe(0)-catalyzed cyclization of polyenes. It also can be preformed if an active functional group is present in the allylic position. The palladium-catalyzed intramolecular cycloisomerization reaction of allylic acetates is an efficient method for constructing five- or six-membered rings [56, 57]. An asymmetric approach to this transformation has been studied and so far only poor enantioselectivity has been achieved (0-20% ee) [58]. Very recently, Zhang et al. also reported a Rh-catalyzed cycloisomerization involving a Jt-allylrhodium intermediate formed from an allylic halide [59]. 

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). 

Enantioselective Polyene Cyclization Catalyzed by SnCl4 BINOL Derivatives... 

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

Another example of an enantioselective polyene cyclization is the formation of tetracycle 103 (Scheme 12.23). Enantioselectivities of the 6-exo followed by 6-endo cyclization were moderate to good using BINAP. Of note is the substantial increase in enantioselectivity... 

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... 

SCHEME 9.13 Enantioselective polyene cyclization promoted by LBA 7-SnCl. ... 

In 2007, Gagne s group succeeded in a regio- and diastereoselective oxidative polycyclization of di- and trienols catalyzed achiral [(dppe)Pt] dications, wherein turnover was achieved by the trityl cation abstracting a hydride from a putative [(dppe)Pt-H] intermediate [32i]. One year later, Gagne s group developed the catalytic enantioselective polyene cyclization induced by [(S)-(xylyl-PHANEPHOS) Pt][(BF )j] catalyst, which was prepared from (S)-(xylyl-PHANEPHOS)PtIj and AgBF in situ (Scheme 9.21) [32j]. This asymmetric catalysis enables the oxidative cascade cyclization of polyalkene substrates [32k] (Scheme 9.15). 

In 2013, Gagne s group demonstrated catalytic enantioselective polyene cyclization and C3-fluorination for... 

SCHEME 9.19 Enantioselective polyene cyclizations promoted by dicationic Pt(II) complexes. 

SCHEME 9.21 Chiral Pt(ll)-induced enantioselective polyene cyclizations. 

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... 

In 2010, Loh s group reported a highly efficient catalytic enantioselective polyene cyclization [52]. An a-ketoester was demonstrated to initiate enantioselective cationic polyene cyclization catalyzed by a Sc(OTf)3-Pybox Lewis acid catalyst (Scheme 9.39). 

These catalytic enantioselective polyene cyclizations have been accomplished through the use of substrates with the appropriate functional groups on the reactive sites, such as aldehydes and hydroxylactams. Therefore, these methods cannot be applied to the enantioselective cyclization of simple isoprenoids with a terminal isoprenyl group. 

SCHEME 9.40 Enantioselective polyene cyclization via organo-SOMO catalysis. 

In 2014, Corey s group demonstrated the synthetic application of LBA (/ )-13 Sba5 in catalyzed enantioselective polyene cyclization [21b] by three different ways in which the LBA could be used to initiate enantioselective, cationic polycycUzations at a nonterminal jt-bond. 

The first way involves activation of an internal double bond by an electron-supplying jt-attachment [21b]. This type of process is quite useful, as is demonstrated by the especially simple, enantioselective syntheses of three well-known natural products. Thus, (-i-)-dysideapalaunic acid, dehydroabietic acid, and 4-epipodocarpic acid were synthesized through very short pathways including an enantioselective polyene cyclization under the influence of the LBA at -78°C for 15 min (Scheme 9.50). 

Chiral pyrogallol (14) derived LBA (15) was developed for enantioselective polyene cyclization reaction as an artificial cyclase by Yamamoto, Ishihara and coworkers in 2004 (Scheme 1.23) [26]. Various tricyclic skeletons have been synthesized with good enantioselectivities (79-85% ee) in the presence of chiral LBA (15). 

Scheme 1.23 SnCU-chiral pyrogallol complex (15) as a new LBA for enantioselective polyene cyclization.

Yamamoto and Ishihara et al. developed enantioselective polyene cyclization with predictable absolute configurations and excellent enantioselectivities using the chiral LBA (Scheme 10.23) [45]. They further succeeded in produdng new chiral LBA consisting of chiral pyrogallol derivatives and SnCU, which effedively promotes the cyclization of 2-geranylphenol derivatives (Scheme 10.24) [46]. 

Optically active aliphatic propargylic alcohols are converted to corticoids (90% ee) via biomimetic polyene cyclization, and to 5-octyl-2(5ii)-furanone. The ee s of propargylic alcohols obtained by this method are comparable with those of the enantioselective reduction of alkynyl ketones with metal hydrides, catalytic enantioselective alkylation of alkynyl aldehydes with dialkyIzincs using a chiral catalyst ((S)-Diphenyl(l-methylpyrrolidin-2-yl)methanol) (DPMPM), and the enantioselective alkynylation of aldehydes with alkynylzinc reagents using A(A-dialkylnorephedrines. °... 

Despite extensive studies on acid-catalyzed diastereoselective polyene-cyclizations, their enantioselective behavior have not yet been reported. The stereochemical implications of polyene-cyclizations can be explained by the Stork-Eschenmoser hypothesis [140], and the most important feature required for an artificial cyclase is asymmetric induction during the initial protonation. Very recently, the author and Yamamoto et al. succeeded in the first enantioselective biomimetic cyclization of polypre-noids catalyzed by LB A [141]. 

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. 

The most recent highlight in enantioselective radical domino processes can be attributed again to the MacMillan group, in their development of an efficient polyene domino cyclization via the organo-SOMO catalysis strategy [85] (Scheme 5.57). 

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). 

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. 

---