Synthesis laurenyne

Eight- and nine-membered cyclic ethers are also generated via type-III reactions by treating the 5-hexen-l-ol acetals with Lewis acids. 8-endo Cyclization of 5-hexenyl methoxyethoxymethyl ether in the presence of two equivalents of tin(IV) chloride forms a 2 1 mixture of chlorinated and unsaturated 1 -oxycyclooctanes 11 and 1232. Vinylsilane undergoes an 8-endo Prins cyclization. After O-desilylation, oxocene 13, which is used as a precursor in a laurenyne synthesis, is obtained in 37% yield33. 

Boeckman Jr. RK, Zhang J, Reeder MR (2002) Synthetic and Mechanistic Studies of the Retro-Claisen Rearrangement 4. An Application to the Total Synthesis of (+)-Laurenyne. Org Lett 4 3891... 

Laurenyne (1) was first isolated by Thomson and coworkers in 1980, and the absolute configuration was first incorrectly assigned via X-ray crystallography to be 2S,7S,SS. The absolute configuration was revised to be all-(7 ) in 1988 by Overman and Thompson after the first total synthesis of (-)-laurenyne. ... 

In this chapter, the total synthesis of (+)-laurenyne (1) published by Boeckman et al. in 2002 will be described. Starting from a readily available chiral diol, two of the stereogenic centers are constructed via selective CBS-reduction of ketones. 

Boeckman et al. describe the enantioselective total synthesis of (H-)-laurenyne (1) in nearly 5 % overall yield over 22 linear steps, which translates to an average yield of 87 %. Starting from a readily available chiral substrate, two stereogenic centers are build up catalytically via diastereoselective CBS reduction. Though the... 

Through the efforts of the Overman research group, the acetal-vinylsilane cyclization reaction has been shown to be a useful strategy for the stereoselective preparation of a variety of medium-sized oxygen heterocycles. This cyclization strategy has been used successfully in the asymmetric synthesis of the marine natural product (-)-laurenyne (40a), an eight-membered cyclic ether. These molecules are members of an unusual class of C-15 nonisoprenoid metabolites. 

Overman has also shown that eight- and nine-membered cyclic ethers can be prepared by type 111 cy-clizations.136 Treatment of (257) with 2 equiv. of SnCL for 13 h at -20 C gives (258), which cyclizes to give a 2 1 mixture of (259) and (260) in 83% yield.137 Cleaner reaction mixtures have been obtained using vinylsilanes, as in the synthesis of laurenyne.138 SnCU-mediated cyclization of acetal (261) in CH2CI2 at 0 C, followed by 0-desilylation produces oxocene (262) in 37% yield as the sole cyclic ether (Scheme 38). 

Reactions with Other Electrophiles.4 a(-(Trimethylsilyl)-vinyllithium reacts with ethylene oxide to give an intermediate which has been used to set up an impressive eight-memberedring cyclization for the synthesis of (—)-laurenyne (eq 10). Here, vinyltrimethylsilane was preferred over the simple vinyl moiety because of its greater reactivity. 

Boeckman RK, Zhang J, Reeder MR. Synthetic and mechanistic studies of the retro-Claisen rearrangement 4. An application to the total synthesis of (+)-laurenyne. Org. Lett. 2002 4(22) 3891-3894. 

Overman, L.E. and Thompson, A.S. (1988) Total synthesis of (—)-laurenyne. Use of acetyl-initiated cyclizations to prepare functionalized eight-membered cyclic ethers./. Am. Chem. Soc., 110, 2248-2256. 

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