Tetrahydrofurans, formation

The attempted allylation of the aldehyde shown in the following equation resulted in unanticipated tetrahydrofuran formation ... 

Scheme 18 Tetrahydrofuran formation with the Barton decarboxylation reaction as radical source...

Scheme 15 Radical tandem sequence for tetrahydrofuran formation...

Scheme 16 Reaction energies of tetrahydrofuran formation via Sh2 mechanism...

These findings imply that, in the case of secondary radicals, the trapping with a second equivalent of Cp2TiCl can compete with tetrahydrofuran formation, and that -hydride elimination can kinetically compete with protonation of Ti - C bonds under our protic conditions [65,66,73,74], It remains to be seen how the reaction can be completely driven toward the tricyclic system 60 by ligand variation of the catalyst. 

The same basic strategy was applied to the synthesis of the smaller fragment benzyl ester 28 as well (Scheme 4). In this case, aldehyde 22 prepared from (S)-2-hydroxypentanoic acid [9] was allylated with ent-10 and tin(IV) chloride, and the resulting alcohol 23 was converted to epimer 24 via Mitsunobu inversion prior to phenylselenenyl-induced tetrahydrofuran formation. Reductive cleavage of the phenylselanyl group, hydrogenolysis of the benzyl ether, oxidation, carboxylate benzylation, and desilylation then furnished ester 28. 

Examples of cyclization of y,<5-unsaturated alcohols in the prostaglandin syntheses abound among the more recent is the tetrahydrofuran formation by cyclization of an intermediate iodonium ion (Scheme 51) (81JCS(P1)1312). 

Tandem carbonyl ylide generation from the reaction of metallo carbenoids with carbonyl continues to be of great interest both mechanistically and synthetically. Effective carbonyl ylide formation in transition metal catalyzed reactions of diazo compounds depends on the catalyst, the diazo species, the nature of the interacting carbonyl group and competition with other processes. The many structurally diverse and highly successful examples of tetrahydrofuran formation cited in this mini-review clearly indicate that the tandem cyclization/cycloaddition cascade of metallo carbenoids has evolved as an important strategy in both carbo- and heterocyclic synthesis. 

Bromolactonization of 450 enabled stereoselective attack of peracid at the endocyclic double bond of 451 (Scheme 54). Assistence of the benzyl ether led to tetrahydrofuran formation, debenzylation, and the secondary alcohol at C(3). Subsequently, the pentacyclic bromolactone 452 was reductively cleaved with zinc and the resulting acid was protected as methylester 453. Since lactonization by... 

Recently [13, 16] we have shown the possibility of efficient promotion of VPO precursor with bismuth compounds. The present paper reports new results on promotion of VPBiO precursor with lanthanum compounds (previously a similar catalyst was shown to be active in tetrahydrofuran formation [17]). Table 5 compares the properties of traditionally prepared VPBiLaO sample (by simultaneous introduction of bismuth and lanthanum additives in the course of the synthesis of VPO precursor) with that (VPBiO-La-M) produced by the mechanochemical treatment of VPBiO precursor and lanthanum oxide powders. The treatment in the latter case was carried out for 10 min. in ethanol medium. 

This reaction type can also be applied to tetrahydrofuran formation and its stereoselectivity is markedly influenced by substituents on the chain and at the double bond49,3 -56. Starting from 5-hydroxy-l-heplenes 3, palladium-catalyzed alkoxycarbonylation leads to 2.5-disubstituted tetrahydrofurans 4 in good yield. Tetrahydrofuran formation is sterically unselective when the substituent R1 at the double bond is hydrogen or methyl however, when R1 is a methoxy group, formation of an isomer of type 4A is highly favored (d.r. >95 5)49,55. 

Oxidation of Alcohols, Phenols, and Ethers. A primary alcohol can be retained when a secondary alcohol is oxidized to a ketone. Tetrahydrofuran formation (eq 3) predominates in molecules with rigid Irameworks, which are favorable to 5-hydrogen abstraction by an alkoxyl radical. 

---