Dihydropyran ring-closing metathesis

A similar strategy has been employed in the synthesis of a dihydropyran required to achieve the synthesis of (—)-lanlimalide (Scheme 23). Thns, ally-lation of the secondary alcohol resnlting from a methallylation of 3-tri-n-butylstannylacrolein provided unsymmetrical ether 182, which is closed to a pyran with a ring-closing metathesis using Schrock s molybdennm catalyst. 

Schmidt B, Westhus M (2000) Diastereoselectivity in a ring closing metathesis reaction with a remote stereogenic centre leading to quaternary dihydropyrans. Tetrahedron 56 2421-2426... 

Schmidt B, Nave S. Synthesis of Dihydrofurans and Dihydropyrans with Unsaturated Side Chains Based on Ring Size-Selective Ring-Closing Metathesis. Adv Syndi Catal. 2007 349(l-2) 215-230. 

The transition-metal-catalyzed olefin metathesis is a still recent, but already well-established, development, which has evolved toward a highly useful synthetic tool [27]. The ring-closing variant of this reaction ]ring-closing metathesis (RCM)] has proved to be very suitable for the preparation of carbo- and heterocycles of any ring size, except for those that are strained ]28, 29]. In the case of 5,6-dihydropyran-2-ones, RCM of homoaUyl acrylates has very often been used for the direct creation of this heterocyclic system, most particularly in the past decade (Figure 2.4). Allyl esters of fi,y-unsaturated acids may also be subjected to RCM with the formation of P,y-unsaturated 8-lactones, which can be easily isomerized by acid or base catalysis to their a,fi-unsaturated counterparts ]6, 30-39]. 

Figure 2.4 Formation of 5,6-dihydropyran-2-ones via ring-closing metathesis of unsaturated esters.

Mulzer, J. and Hanbauer, M. (2000) Synthesis of the C1-C12-dihydropyran segment of the antitumor agent laulimalide by ring closing metathesis. Tetrahedron Lett., 41, 33-36. 

In recent years, ring-closing olefin metathesis (RCM) has attracted organic chemists as a versatile cyclization method via carbon-carbon bond formation, and had a great impact on the synthesis of natural products [29,30]. In the syntheses of dihydropyrans of marine macrolides, allyl homoallyl ethers 28 have been cyclized to dihydropyrans 29 via RCM. This methodology has been seen in the syntheses of laulimalide by Mulzer [31,32], Crim-mins [33], and Nelson [34] (Scheme 9). 

---