Cycloaddition, tetrahydrofuran diastereoselective

As for oxygen heterocycles, several reports involving the diastereoselective synthesis of highly substituted tetrahydrofuran derivatives have appeared. SnCLj-mediated [3 + 2] cycloaddition of allylsilane with optically active a-ketoesters affords 211 with excellent diastereoselectivity (equation 173)314-317. 

The Lewis acid-catalysed 3 + 2-cycloaddition of cyclopropanes with aldehydes yields tetrahydrofurans with high diastereoselectivity.22 The enantiospecific Sn(II)-and Sn(IV)-catalysed formal 3 + 2-cycloadditions of aldehydes with donor-acceptor (g) cyclopropanes produce optically active tetrahydrofurans23 The bulky phosphites and phosphoramidites are excellent ligands which promote the Pd-catalysed 3 + 2-intramolecular cycloaddition between alkylidenecyclopropanes and alkynes24 The... 

The influence of Lewis acids on the diastereoselectivity of the cycloaddition of /f-alkoxyalde-hydes has also been studied35. Magnesium bromide, highly effective for a-alkoxyaldehydes, fails in the case of the cycloaddition of aldehyde 10 to diene 2 and the reaction does not exhibit any selectivity, probably due to a change of mechanism to Mukaiyama s aldol type. One reason may be the change of solvent from tetrahydrofuran to a mixture of benzene and diethyl ether. The additions of aldehyde 10 to other dienes are more selective but diastereoselectivity is still much lower than for the a-alkoxy aldehydes. Boron trifluoride-diethyl etherate complex also leads to a mixture of four possible products. Excellent selectivity is achieved for the titanium(IV) chloride catalyzed addition of aldehyde 10a to diene 2b, 11c is obtained as the only product. 

Isoxazolidines 92 were converted into 3-nitro-4-hydroxymethyl tetrahydrofurans 94 by treatment with TBAF. The process is believed to occur through the formation of nitroso intermediates 93, that undergo a spontaneous aerobic oxidation. The two-step sequence of intramolecular silylnitronate olefin cycloaddition (ISOC) followed by oxidative ring cleavage was diastereoselective and allowed complete control of the relative configuration of the newly created stereocenters <040L2027>. 

The tin(IV) chloride-promoted [3 + 2] cycloaddition of allysilanes and a-ketoesters provides a versatile diastereoselective route to silyl-substituted tetrahydrofurans via 1,2-silyl migration (Equation (106)) <94CL627, 94TL8401>. 

In 2006 Chen et al. [128] reported the first organocatalyzed stereoselective [3 + 2] dipolar cycloaddition of azomethine imines with aliphatic a,p-unsaturated aldehydes using chiral secondary amine catalyst 59. The desired cycloaddition products were obtained with good yields, good diastereoselectivities and good enantioselectivities for both electron-rich and electron-poor aromatic azomethine imines. In contrast, aliphatic azomethine imines (R = -Pr) led to poorer results (40% yield and 77% ee). Investigation of a variety of solvents and additives revealed that tetrahydrofurane/HaO mixture and 10 mol% of trifluoroacetic acid were preferred. No reaction was observed when aromatic a,p-unsaturated aldehydes were used. The authors proposed an iminium ion mechanism that could proceed via the transition states shown in Scheme 11.47. 

The use of the cyclitol, L-quebrachitol, as chiral auxiliary for ketone alkylation has been extended to additions of silyl enol ethers and silyl enol esters, providing a-hydroxyacid precursors, 269 with d.e. > 98% in most cases (Scheme 56). [Grignard, alkylithium and allylsilane additions to this substrate, Vol. 26, p. 319, ref. 93]. The same a-keto esters bearing this L-quebrachitol auxiliary undergo diastereoselective [3+2] cycloadditions with allylsilanes, providing a route to chiral functionalized tetrahydrofurans 270. ... 

Allylation adducts of ( )-Y-(dimethylphenylsilyl)allylboronate 47 selectively undergo addition reactions with aldehydes. Lewis acid catalyzed [3 + 2] cycloaddition reaction of these allylsilanes with various aldehydes, e.g., 55, provides tetrahydrofuran adducts with high diastereoselectivity. ... 

Cycloaddition Reaction. A one-step diastereoselective synthesis of cis-2,5-disubstituted tetrahydrofurans via Hf(OTf)4-catalyzed [3 + 2] cycloadditions of donor-acceptor (D-A) cyclopropanes and aldehydes has been reported (eq 13). ... 

Waser and coworkers have reported the first use of amino cyclopropanes in [3+2]-cycloadditions with aldehydes to give amino tetrahydrofurans with high levels of diastereoselectivity (Scheme 22) [22]. A wide range of activators could be used in these reactions including normally inert Lewis acids like FeCL on AI2O3. In contrast to the Johnson et al. work mentioned above, racemic tetrahydrofurans resulted from the use of enantiomerically eiuiched aminocyclopropanes implying that the reaction proceeds through a zwitterionic intermediate. 

Addition of an T -allyl-Fp complex to this compound affords an T -aIlyl-Fp-substituted cycloheptatriene system. Two double bonds are involved in an (T -diene)iron complex. The remaining free double bond of the silyl enol ether attacks as a nucleophile at the cationic r -alkene-Fp moiety to form an (Tj -diene)iron complexed cyclopentane annulated cycloheptadienone. Treatment with CAN in methanol under carbon monoxide atmosphere releases the methoxycarbonyl-substituted free ligand (Scheme 4-25). Reaction of the Ti -dienyliumiron intermediate of Scheme 4-25 with an ( , Z)-isomeric mixture of ri -crotyl-Fp proceeds with high diastereoselectivity. Four new stereogenic centers are formed in the course of this formal [3+2] cycloaddition. A hetero [3+2] cycloaddition is also feasible between T -ailyl-Fp complexes and aromatic aldehydes in the presence of zinc chloride or titanium(IV) chloride to provide tetrahydrofuran derivatives (Scheme 4-26). A 1,2-shift of the iron complex fragment occurs in the course of this reaction. Employment of imines affords the corresponding pyrrolidines. ... 

The cobalt complexed cyclopropane diester 4 was then reacted with a variety of aldehydes in the presence of boron trifluoride etherate in dichloromethane to afford the desired tetrahydrofurans 5 in high yields with poor diastereoselective control (Scheme 10.6). The cycloaddition reaction was limited to electron deflcient aromatic, aliphatic, and functionalized aldehydes, where no reaction was observed with electron rich aromatic aldehydes. The tetrahydrofurans were obtained as a 1 1 mixture of cis- and fran -isomers, where the best diastereomeric ratio obtained was 2 1 (5d) in favor of the fran -isomer. Modifying the temperature of the reaction had little effect on the diastereoselectivity. Confirmation of the stereochemistry was achieved by X-ray and NMR analysis of the separated diastereoisomers, including... 

---