Allylic derivatives tetrahydrofuran synthesis

Schmitt A, Reissig H-U (2000) On the stereoselectivity of y-lactol substitutions with allyl-and propargylsilanes - synthesis of disubstituted tetrahydrofuran derivatives. Eur J Org Chem 3893-3901... 

While the notion that the alkoxides derived from aliphatic alcohols are poor nucleophiles toward 7r-allylmetal complexes has prevailed over the years, much progress made in the recent past has rendered the transition metal-catalyzed allylic alkylation a powerful method for the O-allylation of aliphatic alcohols. In particular, owing to the facility of five- and six-membered ring formation, this process has found extensive utility in the synthesis of tetrahydrofurans (THFs) (Equation (29))150-156 and tetrahydropyrans (THPs).157-159 Of note was the simultaneous formation of two THP rings with high diastereoselectivity via a Pd-catalyzed double allylic etherification using 35 in a bidirectional synthetic approach to halichondrin B (Equation (30)).157 The related ligand 36 was used in the enantioselective cyclization of a Baylis-Hillman adduct with a primary alcohol (Equation (31)).159... 

The selective intramolecular nucleophilic addition of a hydroxy group at Cyof a ruthenium allenylidene generated by activation of propargylic alcohol by RuCl(Cp)(PPh3)2/NH4PF6 provides a ruthenium vinylidene species, which reacts with allylic alcohols as previously described in the section Formation of Unsaturated Ketones (Eq. 11, Scheme 18) [79]. This unprecedented tandem reaction makes possible the construction of tetrahydrofuran derivatives in good yields and has been used as a key step in the synthesis of (-)calyculin A [80]. 

Allyl propargyl ethers are easily cyclized to tetrahydrofuran derivatives by titanocene- and zirconocene-mediated reactions. Thus, these compounds are convenient starting materials for the stereoselective synthesis of highly substituted 3-alkylidenetetrahydrofurans (Scheme 72) <1996TL9059>. It is noteworthy that the titanocene- and zirconocene-mediated reactions show opposite (Z)/( )-selectivities. 

An interesting application of the asymmetric alkoxyselenenylation of alkenes to natural product synthesis was reported recently by Wirth, who described a short procedure to obtain some furofuran lignans 147]. The total synthesis of (+)-Samin 53 [47 a] is shown in Scheme 7. The protected allylic alcohol 50 was treated with the selenyl triflate derived from diselenide 29 in the presence of 2,3-butadien-l-ol, and afforded the addition product 51 in 55% yield and with a diastereomeric ratio of 15 1. The favored 5-exo-trig radical cyclization of the major isomer afforded the tetrahydrofuran derivative 52 from which the final product was obtained through few classical steps. 

Application of this reaction to a,ct)-bisallylic halides makes the synthesis of medium and large rings possible. Treatment of l,l-bis(chloromethyl)-ethylene (CVII) with nickel carbonyl in tetrahydrofuran gives the dimer CVIII and trimer CIX in 11 and 54% yield, respectively (Corey and Sem-melhack, 1966). These products are derived by intermolecular coupling, followed by intramolecular coupling of allylic chlorides. The nine-membered carbocycle (CIX) was produced by the coupling of CVn and the dichloride... 

The highly nucleophilic double bond of allyltrimethylsilanes (46) renders them most useful synthetic intermediates. They will substitute acetals under acid conditions and selectively allylate ketones to provide a new synthesis of homo-allyl alcohols and a route to derivatives of tetrahydrofuran (47) (Scheme 14). The synthesis of a mixture of isomers from the allyl transfer to aldehyde (48) supports a non-concerted process [equation (56)] while methyl substituted allyl-silanes will isomerize if catalysed by Bu 4NF [equation (57)]. ... 

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