3- Methylenetetrahydrofurans, from

Fallacious acetateItriphenylphosphineltri-n-butyltin acetate 3-Methylenetetrahydrofurans from 0x0 compds. 

Annulation to carbonyl functions has also been achieved with Trost s bifunctional reagents. Whereas the parent silyl acetate (97) yields only simple alkylation products with aldehydes under normal conditions, addition of only a few mole % of trimethyltin acetate to the reaction mixture results in facile formation of methylenetetrahydrofurans Furthermore, excellent diastereoselectivity is observed in the cycloaddition to a galactose-derived aldehyde (125) (equation 136). The tin acetate co-catalyst also promotes addition to relatively unreactive ketone carbonyls, such as in the case of benzofuran (126) and the acetylenic ketone (127) (equations 137, 138). It is remarkable that even the sterically hindered enone (128) reacts preferentially at the ketone function (equation 139). A tributyltin analog (129) of (97) has been used in the stepwise formation of a methylenetetrahydrofuran from aldehydes. Similarly, pyrrolidines can be prepared from the corresponding imines in two steps via a Lewis acid-catalyzed 1,2-addition of the tin reagent, which is then followed by a Pd-catalyzed cyclization (equation 140). Direct formation of pyrrolidine from the imine is possible if one uses a mesylate analog of (97) and a nickel(O) catalyst (equation 141). ... 

Pentyn-l-ol has been prepared from 4-penten-l-ol3 by bromi-nation followed by dehydrobromination with alkali,7 by the reaction of 3-bromodihydropyran with w-butylsodium or w-butyl-lithium,6 8 by the reaction of 2-methylenetetrahydrofuran with w-amylsodium or w-butyllithium,8 and by the method used in this preparation.9... 

Methylenetetrahydrofurans can also be realized by an intramolecular radical cyclization of bromoalkynes utilizing indium(I) iodide as a radical initiator <06TL2859>. 3-Diiodomethylenetetrahydrofurans were also prepared from l,to-diiodo-l-alkynes in the presence of l-hexynyllithium<06CC638>. 

The Cu(I)-catalyzed cyclization for the formation of ethyl ( )-tetrahydro-4-methylene-2-phenyl-3-(phenylsulfonyl)furan-3-carboxylate 82 has been accomplished starting from propargyl alcohol and ethyl 2-phenylsulfonyl cinnamate. Upon treatment with Pd(0) and phenylvinyl zinc chloride as shown in the following scheme, the methylenetetrahydrofuran 82 can be converted to a 2,3,4-trisubstituted 2,5-dihydrofuran. In this manner, a number of substituents (aryl, vinyl and alkyl) can be introduced to C4 <00EJO1711>. Moderate yields of 2-(a-substituted N-tosyIaminomethyl)-2,5-dihydrofurans can be realized when N-tosylimines are treated with a 4-hydroxy-cis-butenyl arsonium salt or a sulfonium salt in the presence of KOH in acetonitrile. The mechanism is believed to involve a new ylide cyclization process <00T2967>. 

Adenosine analogues where the furanose ring was replaced with alternative dihydro- and tetrahydrofurans were prepared from 6-chloro-9-(4-methylenetetrahydrofuran-3-yl)-9/7-purine <2002T4865>. Of particular interest was the transformation of the exocyclic alkene on the THF ring first by dihydroxylation, then elimination to yield (4-(6-aminopurin-9-yl)-2,5-dihydrofuran-3-yl)methanol after amination of the purine ring at C-6. This A-alkenylpurine was reduced (Pd/C, H2, 25 psi, 73% yield) to provide the tetrahydrofuran-3-yl derivative. 

Methylenetetrahydrofurans and 4-methylenepyrrolidines.1 The adducts formed by Lewis acid-catalyzed reaction of 1 with an aldehyde or ketone undergo cyclization to 4-methylenetetrahydrofurans in the presence of a Pd(0) catalyst prepared from Pd(OAc)2, P(C6H5)3, and BuLi, and a base, DBU or N(C2H5)3 (1.5 equiv.). 

Promoted by copper iodide, a large array of 3-methylenetetrahydrofurans were synthesized from propargylic alkoxides as nucleophiles and activated alkenes as Michael acceptors. One of these reactions is shown below <02TL2609>. 

The adduct obtained from the stereo- and regiospecific [5+2] cycloaddition of the 3-oxidopyrylium ylide 27 to 3-methylenetetrahydrofuran-2-one is readily converted into the polycycle 28 which is a late intermediate in the synthesis of the polygalolides <07OL873>. 

Furan and related cycles (methylenetetrahydrofuran, methylenedihydrofuran) are usually formed in preference to pyrans from alkynes (Table 15) - 347-349, Processes... 

Alternatively, 2-(chloromethyl)-3-iodo-l-propene reacted with aldehydes or ketones to give after basic treatment methylenetetrahydrofuran in excellent yields. The reaction is as expected chemo- and regioselective conjugated carbonyl compounds gave 1,2-addition, and aldehydes react more preferably than ketones [106]. Simharly, 3-chloro-homoallylic alcohols were prepared in high yields from the reaction of 2,3-dichloropropene with carbonyl compounds in a two-phase system containing a small amount of acetic acid. In this reaction, the presence of water in the reaction medium was shown to be essential as the reaction did not occur under non-aqueous conditions [107]. 

Dihydrofuran skeletons can also be realized from 3-methylenetetrahydrofurans via a series of reactions <05EJO4852 05TL4859>, from acid treatment of hexa-2,4-dienel,2-diols <05TL5369>, and from alkylidenecarbenes as illustrated below <05TL7483>. 

Cyclization. On treatment with La[N(SiMe3)2]3, a 4-alkynol forms the alkoxide which cyclizes to give 2-methylenetetrahydrofuran the isomer with endocyclic double bond is also formed from 3,4-pentadienol. A modified trisfhexamethyldisilazide) of lanthanum (and of several other rare earth metals) (1) catalyzes intramolecular hydroamina-tion of alkynylamines and the products also undergo hydrosilylation. ... 

Methylenetetrahydrofurans have been prepared starting from the allylstannane (25) via Lewis acid catalysed addition to ketones... 

---