Stereocontrolled construction of tetrasubstituted tetrahydrofurans: synthesis of 2,5-anhydro d-glucitol

A highly stereoselective construction of 2,3,4,5-tetrasubstituted tetrahydrofurans has been accomplished by an unusual intramolecular 5-endo-tet cyclization of 2,3-epoxy alcohols involving hydroxyl nucleophile. The method has been utilized for the synthesis of 2,5-anhydro d-glucitol through two different approaches starting from the chiral molecule, l(+)-diethyl tartarate or from the non-chiral compound, allyl bromide or cis-but-2-ene-1,4-diol. This synthetic method is a useful example of 5-endo-tet cyclization of 2,3-epoxy alcohols.     

Stereocontrolled concise synthesis of (±)-halosaline through intramolecular C-H amination

Total synthesis of 2-(2-hydroxyalkyl)-piperidine alkaloid (±)-halosaline is described from 7-octen-4-ol using a Rh-catalyzed chemo- and diastereo-selective intramolecular CH amination of sulfamate ester, ring-closing metathesis, and S_N2 displacement reaction of the six-membered ring sulfamidate as the key steps.     

Stereocontrolled construction of tetrahydrofurans and gamma-butyrolactones using organomolybdenum chemistry

[reaction: see text]. Diastereoselective conversion of pi-allylmolybdenum complex aldehyde 1 to organometallic triol 4 and diols 5, 10, and 13 is described. Stereocontrolled demetalation of 4, 5, and 13 was accomplished, leading to hydroxylated tetrahydrofurans and gamma-butyrolactones, as single diastereoisomers.     

Sequential assembly strategy for tetrasubstituted olefin synthesis using vinyl 2-pyrimidyl sulfide as a platform

We have developed a programmable and diversity-oriented synthetic scheme for tetrasubstituted olefins through a site-selective and sequential assembly of pi-components onto a C=C core of vinyl 2-pyrimidyl sulfide. Noteworthy features are that (i) all components assembled stem from readily available organic halides or their Grignard reagents, (ii) the installation at the desired position can be achieved by the addition of the components in the appropriate order, and (iii) simple alteration of addition order in the sequence results in the production of all possible regio- and stereoisomers of multisubstituted olefins.     

A practical route to enantiopure, highly functionalized seven-membered carbocycles and tetrahydrofurans: concise synthesis of (+)-nemorensic Acid

Highly diastereoselective thermal [5C+2C] intramolecular pyrone-alkene cycloadditions can be achieved by introducing a homochiral p-tolylsulfinyl group at a suitable position of the alkene. The resulting adducts can be readily desulfinylated to give optically active 8-oxabicyclo[3.2.1]octane derivatives. Interestingly, switching from a sulfinyl to a sulfonimidoyl group allows one to reverse the direction of the diastereofacial selectivity and thereby produces oxa-bridged carbocyclic systems enantiomeric to those obtained from the sulfinyl precursors. Cleavage of the oxa-bridge on the desulfurated adducts yields highly functionalized seven-membered carbocyclic derivatives in enantiopure form. Alternative cleavage of the seven-membered carbocycle provides enantiomerically enriched tetrahydrofurans. We have exploited this reaction pathway for the synthesis of the naturally occurring enantiomer of nemorensic acid.     

A diastereoselective ring contraction of 1,3-dioxepins to 2,3,4-trisubstituted and tetrasubstituted tetrahydrofurans

A modular and diastereoselective approach to 2,3,4-trisubstituted and tetrasubstituted tetrahydrofurans is reported. The use of dioxepins containing an embedded vinyl acetal functionality leads to a Lewis acid-mediated [1,3] ring contraction to afford tetrahydrofurans in good yield and excellent diastereoselectivity. The use of TMSOTf in MeCN leads to the 2,3-cis/3,4-trans diastereomer while SnCl4 in CH2Cl2 provides the 2,3-trans/3,4-cis diastereomer. A variety of substituents are tolerated at each position. The presence of Lewis basic functionality under the SnCl4 conditions alters the reaction favoring the diastereomer formed under the TMSOTf conditions. We present conclusive evidence that the products of each of these reactions are formed under kinetic control. We further provide stereochemical models consistent with each of these rearrangement reactions that account for the formation of the major diastereomer in each case.     

Synthesis of substituted tetrahydrofurans and tetrahydropyrans. 2. Stereocontrolled acid-catalyzed cyclizations

A new acid-catalyzed synthesis of thermodynamically stable 2,5-substituted tetrahydrofurans and 2,6-substituted tetrahydropyrans was developed in order to apply to the synthesis of complex polyether antibiotics.     

Stereoselective synthesis of hydroxy-substituted tetrahydrofurans

Iodocyclizations of 4-alkene-1,3-diol derivatives proceed with high stereocontrol to provide cis 2-iodomethyl-3-hydroxy(alkoxy)tetrahydrofurans. The effect of alkoxy substituents on the diastereoselectivity has also been assessed.     

Stereocontrolled synthesis of onchidins

[structure: see text] The first total synthesis of a molecule possessing the stereochemistry proposed for onchidin is described. The structure synthesized appears to be different from that of the marine natural product.     

Diastereoselective synthesis of 2,5-disubstituted tetrahydrofurans

This review focuses on synthetic methods allowing the preparation of 2,5-disubstituted tetrahydrofurans reported in the literature between 1993 and 2008.     

Stereocontrolled synthesis of dihydropseudoclovene-B

Aryl participated intramolecular cyclisation of the bromophenol 16 yielded the dienone 17 which was converted into dihydropseudoclovene-B (7) via a stereocontrolled route.     

Reagent-controlled stereoselective synthesis of lignan-related tetrahydrofurans

The reaction of ring-closing metathesis-derived cyclic allylsiloxanes 3 with aldehydes in the presence of a Lewis acid gives 2,3,4-trisubstituted tetrahydrofurans related to the furanolignan family of natural products. The reactions proceed with complete 3,4-trans stereoselectivity, whereas the C-2 stereochemistry depends on both the aldehyde and Lewis acid used. When boron trifluoride etherate is used with aliphatic or electronically neutral aryl aldehydes, the reactions favor the production of the 2,3-cis isomer 8, whereas electron-rich aryl aldehydes lead to the 2,3-trans isomer 9 by Lewis acid-mediated isomerization of the kinetically favored cis isomer. The isomerization can be avoided by use of TMSOTf as a promoter, and hence, the stereochemistry can be tuned by appropriate choice of reagent. Cleavage of the pendant 3-ethenyl group installs the 3-hydroxymethyl group common to the furanolignans.     

Stereocontrolled total synthesis of pancratistatin

A new total synthesis of the antitumor alkaloids, pancratistatin (1), has been accomplished from readily available staring materials. The Claisen rearrangement of dihydropyranethylene 5 was employed to construct the A and C rings. Stereo- and regiocontrolled functional group interchange, such as iodolactonization, dihydroxylations, and a cyclic sulfate elimination reaction, allows for the production of the target natural product. [reaction: see text]     

An iodocyclization approach toward diastereoselective synthesis of highly functionalized tetrasubstituted tetrahydrofurans with 2,5-trans and 2,5-cis relationships from pyranoside derived acyclic oximes

An efficient method to obtain novel tetrasubstituted tetrahydrofurans with C2 and C5 substitution in trans- and cis-relative configurations has been reported.     

Stereocontrolled synthesis of (+)-boronolide

Boronolide was synthesized stereoselectively from hydroxyacetylfuran 5 and valeraldehyde 6 using a novel dizinc aldol catalyst. Ring closing metathesis provides the lactone ring. The synthesis requires 12 steps and proceeds in 26% overall yield. [reaction: see text]     

Stereocontrolled synthesis of lepadiformine A

In this paper we present results of a study into whether the tricyclic core of the lepadiformines A-C can be accessed via intramolecular hetero-Diels-Alder cycloaddition. We are able to demonstrate that such a process is possible and that the reaction proceeds in an endo-selective fashion, providing the correct relative stereochemistry for this family of natural products. By employing this approach we have been able to develop a short (7 step) synthesis of (+/-)-lepadiformine A, starting from commercially-available trans-2-nonenal.     

Stereocontrolled synthesis of beta-difluoromethylated materials

Investigation of synthetic routes for regio- and stereocontrolled fluorinated materials with a difluoromethyl group, using ethyl bromodifluoroacetate as a starting material, is described. In particular, (E)-difluoromethylated trisubstituted olefins were prepared via the proton migration reaction catalyzed by using fluoride anion. Further, optically active beta-difluoromethyl esters were obtained by the enzymatic resolution.     

Enantiospecific synthesis of tetrasubstituted δ-lactones

For investigations concerning the selectivity of polyketide synthases (PKSs) which have been rationally engineered through genetic techniques the synthesis of substituted δ-lactones is of great importance. An enantiospecific route towards eight of the possible sixteen stereoisomers was developed which is also readily adaptable for the introduction of alkyl modifications and isotopic labels.