Tetrahydrofuran, synthesis

This group is cleaved,during an iodine-promoted tetrahydrofuran synthesis. 

In analogy with the strategy of carbocyclic construction, 1,6-enynes containing an oxygen heteroatom in the carbon atom sequence have been used for 3,4-disubstituted tetrahydrofuran synthesis. The simplest example is given by the hydrosilylation of enyne at room temperature (Reaction 7.38) [49]. Tetrahydrofurans with an exocyclic methylene functionality can also be prepared from the appropriate alkynes, such as 32, with (TMS)3SiH in refluxing benzene which afforded exclusive formation of the exomethylene in the Z conformation (Reaction 7.39) [50]. 

Table5.2 Impurityand optical purityofthe batch and microreactor processes in the (S)-2-acetyl tetrahydrofuran synthesis [29].

The synthesis of dihydrofuran derivatives such as 177 has been performed to explore scope and limitations of the Lewis acid promoted hydroxyalkylation of siloxycyclopropanes. Table 6 shows that aromatic as well as aliphatic ketones can efficiently be incorporated. Enolization of ketones does not occur and a 1-methyl group at the cyclopropane is no obstacle for the reaction, which now binds the carbonyl compound to a quartemary center with surprisingly high efficiency (entry 5). Albeit there are some restrictions with regard to the substitution pattern of the cyclopropanes, bicyclic siloxycyclopropanes also give good yields (e.g. entry 6 and Eq. 76). Further examples of the tetrahydrofuran synthesis from intermediate y-lactols with... 

OXAZOLIDINECARBOXYLATE has previously been described in Volume 70 of Organic Sytheses. An alternative procedure for the preparation of this compound is presented in this volume along with its use in a dia-stereoselective addition reaction with 2-TRIMETHYLSILYLTH1AZOLE to provide a compound bearing a 2-amino-1,3-diol substructure that appears in a variety of natural products. The conversion of abundantly available isosorbide into OSO ISOPROPYLIDENE-l ti-DIANHYDRO-d-GLUCITOL provides a potentially useful carbohydrate-deri ved material for the use in complex tetrahydrofuran synthesis. Finally, asymmetric reduction of an a,j9-unsaturated acylstannane with (R)-BINAL provides access to (S,E)-l-(METHOXYMETHOXY)-l-TRIBUTYLSTANNYL-2-BUTENE, an a-alkoxy allylstannane that has been used in enantioselective vicinal diol synthesis amongst other transformations. 

Dipolar cycloaddition of alkenes with carbonyl ylides generated in situ is a versatile method for tetrahydrofuran synthesis. The synthetic potential of such transformations has been reviewed <2005JOM(690)5533, 2003BMI6-253>. In addition, the stereoselective [3 + 2] annulation of allyl silanes has become a reliable protocol for the synthesis of tetrahydrofurans as demonstrated in several total syntheses . Such a [3 + 2] annulation, for example, affords the tetrahydrofuran product 11 as a single stereoisomer (Scheme 15) <2002OL2945>. Lanthanide salts serve as efficient Lewis acid catalysts in similar [3 + 2] cycloaddition reactions . 

Overman and Pennington have developed a versatile methodology for stereoselective tetrahydrofuran synthesis based on pinacol terminated Prins cyclizations. The general reaction is outlined in Scheme 63. A review on the strategic use of these cascade reactions in natural product synthesis has been published <2003JOC7143>. 

Similarly, intramolecular Pauson-Khand reactions can be utilized for tetrahydrofuran synthesis, when the tethers are oxa substituted. Ligand effects on stereoselectivity in Rh(i)-catalyzed asymmetric Pauson-Khand-type reactions have been investigated and ee s of up to 92% have been achieved with the 2,2-bis(diphenyl-phosphanyl)-l,l-binaphthyl (BINAP) ligand and a Rh(i) precatalyst (Equation 91). However, it has to be noted that the ee is highly substrate dependent, and considerably lower in most other cases <2006S4053>. 

Tsuji-Trost allylation reactions offer multiple pathways to tetrahydrofuran synthesis including C-C bond-formation steps. A palladium-catalyzed sequence of allylic alkylation and Hiyama cross-coupling provides a convenient synthesis of 4-(styryl)-lactones (Scheme 67) <2006SL2231>. 

Styrenes and styrene oxides can be combined in a highly chemo- and regioselective fashion to yield 2,4-bis-aryl-substituted tetrahydrofurans using an iron catalyst <2005CC1996>. This tetrahydrofuran synthesis developed by Hilt et al. opens an unprecedented way for the one-step synthesis of racemic calyxolane A and calyxolane B with moderate diastereoselectivities. The iron-catalyzed ring-expansion reaction of epoxyalkenes was considerably... 

J E G E R Tetrahydrofuran synthesis Free radical ring closure of alcohols with Pb[Pg.99]

Koert, U. Stereoselective synthesis of oligo-tetrahydrofurans. Synthesis 1995, 115-132. 

Other types of heterofunctionalized cyclopropane derivatives used as starting materials in transition metal mediated conversions are acylcyclopropanes and similar systems. These systems, being electrophilic cyclopropanes, are opened by carbanion nucleophiles (e.g. cuprates, see Section l.B.2.1.3.) or nucleophilic transition-metal centers. In combination with siloxy groups, push-pull (capto-dative) substituted cyclopropanes are available as homoenolate precursors via Lewis acid mediated ring opening (see Section 1. B.2.1.4.).. This latter procedure has been used in tetrahydrofuran synthesis. 

Tetrahydrofurans, synthesis via intramolecular cyclization of unsaturated hydroxy compounds 82KGS1443. 

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