Synthesis with tetrahydrofuran

The alkynyl reagent 9 was recently introduced for the dia stereoselective synthesis of tertiary propargylic alcohols144. 9 can be prepared as a solid 1 1 complex with tetrahydrofuran by treatment of 9-methoxy-9-borabicyclo[3.3.1]nonane with (trimethylsilylethynyl)lithium, followed by addition of boron trifluoride-diethyl ether complex. The nucleophilic addition of reagent 9 to (R)-2-methoxy-2-methylhexanal (10) afforded a mixture of the diastereomers 11 with a considerable preference to the nonchelation-controlled (3S,4R)-isomer144. 

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... 

Use of TMSCl in combination with HMPA, DMAP, or TMEDA all favored 1,2-addition over 1,4-addition. Sequential a-alkoxyalkylcuprate conjugate addition, enolate trapping with TMSCl, and silyl enol ether alkylation provides a one-pot synthesis of tetrahydrofurans (Scheme 3.35) [129]. Cyclic enones afford as-fused tetrahydrofurans, while acyclic systems give complex mixtures of diastereomers. a-Alkoxyalkylcopper reagents also participate in allylic substitution reactions with ammonium salts [127]. 

Silver(I) catalyzed cyclizations of allenic alcohols (202) lead to 2,5-dihydrofurans (203) (79S743), whilst another mild method for the synthesis of tetrahydrofurans is the intramolecular oxymercuration-demercuration process. Geraniol, when treated with mer-cury(II) acetate and subsequently with sodium borohydride, gave a tetrahydrofuran. 

An efficient synthesis of tetrahydrofuran-derived spiro-p-lactams has been reported to be performed by a Staudinger-type reaction of either 2- or 3-tetra-hydrofuroyl chloride with imines [66]. The reaction was carried out by adding Et3N... 

The most general method for the synthesis of tetrahydrofurans based upon the IMSC methodology was developed by Overman et al. [53, 54, 94—96] For example, condensation of alcohol 221 with an aldehyde or a ketone in the presence of a Lewis acid leads to the formation of the carbocations 222a,b. The tertiary carboca-tion 222a undergoes a pinacol rearrangement and forms the desired heterocycle 224 (Scheme 13.82). Overman et al. used this approach during the synthesis of the various cladiellin diterpenes, which possess the core skeleton 224 [53]. 

An efficient and operationally simple synthesis of tetrahydrofuran-derived spiro-P-lactams 15 and 16 using the Staudinger reaction of unsymmetrical cyclic ketones has been described <02JCS(P1)571 02SL69>. Similarly, spiro-P-lactams 17 were synthesized via Staudinger reaction of imines derived from 7-oxanorbomenone with alkoxyacetyl chlorides <02TL6405>. 

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 . 

Allylsilanes are commonly employed as nucleophiles in the synthesis of tetrahydrofurans, as exemplified by Scheme 64. Oxidative formation of an oxonium intermediate 49 is followed by a highly stereoselective spontaneous cyclization with the tethered allylsilane moiety <2000JOG3252>. 

The variation in solvents that are available for synthesis with the aid of organomagnesium compounds is rather limited most of the research in this field is done in ethereal solvents, such as diethyl ether, di-n-butyl ether, tetrahydrofuran, furan, anisole, and 1,2-dimethoxyethane. Some amines, such as triethylamine, dimethylaniline, and a few others of that type, have also been applied. 

Problem 31.8 An oider process for the synthesis of both the adipic acid and the hexamethylenediamine needed in the manufacture of Nylon 66 (Sec. 32.7) started with tetrahydrofuran. Using only familiar chemical reactions, suggest possible steps in their synthesis. 

Nakada, M., Iwata, Y., Takano, M. Reaction of dianions of acetoacetic esters with epibromohydrin derivatives a novel synthesis of tetrahydrofuran derivatives and tetrahydropyran derivatives. Tetrahedron Lett. 1999,40, 9077-9080. 

Finally, although 2-lithio-l,3-dithianes do not usually react with tetrahydrofurans, an intramolecular ring opening of such heterocycles has been once reported and has been applied to the synthesis of a di-thiane derived from a functionalized cyclohexanone (Scheme 67). 7,29S... 

The methods of synthesis (direct perfluoroalkylation or building block approach) of perfluoroalkyl carbohydrates 42-44 with tetrahydrofuran fragments were described in the detailed review of Ref. 54... 

Figure 14.7 TEM ofPANI hollow spheres produced by chemical polymerization of aniline on polystyrene particles and removal with tetrahydrofuran, and decorated with gold nanoparticles. (Reprinted with permission from Langmuir, Polyaniline / Au composite hollow spheres Synthesis, characterisation, and application to the detection of dopamine by X. M. Feng, C.J. Mao, C. Yang et al., 22, 9, 4384-4389. Copyright (2006) American Chemical Society)...

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