A straightforward route to spiroketals

A straightforward route to 1,7-dioxa-, 1,4,7-trioxa- and 1,4,7,10-tetraoxaspiro[5.5]undecanes, starting from commercially available 3-chloro-2(chloromethyl)prop-1-ene, is described.     

A convenient access to thermodynamically nonstabilised spiroketal isomers: the first synthesis of (Z)-7-methyl-1,6-dioxaspiro[4.5]decane

Functionalised hydroxy α-alkynones were transformed to the corresponding spiroketals by a one-pot cascade consisting of palladium-catalysed hydrogenation of the triple bond, hydroxyl group deprotection and spirocyclisation under mild nonacidic conditions. The reaction does not rely upon thermodynamic control to set the configuration of the ketal stereocentre so that both the anomerically stabilised and nonstabilised isomers are similarly accessible.     

A novel and highly stereoselective route for the synthesis of non-racemic 3-substituted isoindolin-1-one targets

A new, versatile and highly stereoselective approach for the synthesis of non-racemic 3-substituted isoindolin-1-ones is described from a readily available chiral template. The potential of this new protocol is demonstrated through the synthesis of an enantiomerically enriched 3-alkyl N-H isoindolin-1-one target with an e.e. of 98%.     

A short,versatile route towards benzothiadiazinyl radicals

A family of substituted 1,2,4-benzothiadiazine 1-chlorides have been prepared by treatment of N-arylamidines in neat thionyl chloride at reflux. The S(iv) 1-chlorides are readily reduced under mild conditions to persistent 1,2,4-benzothiadiazinyl radicals which have been characterised by EPR spectroscopy and cyclic voltammetry. Crystallographic studies on isolated radicals indicate that the radicals dimerise via pancake bonding in the solid-state, resulting in spin-pairing and net diamagnetism.

A family of 1,2,4-benzothiadiazinyl radicals are accessible from 1,2,4-benzothiadiazine 1-chlorides which can be prepared in a single step by treatment of N-arylamidines in neat thionyl chloride at reflux.     

A new route to optically pure highly functionalized tetrahydro-isoquinolines with a quaternary carbon stereocenter

A facile synthesis of highly substituted, optically pure tetrahydro-isoquinolines with a quaternary carbon stereocenter is described. Glycolic cleavage of 1,2-dihydroxy-hexahydro-pyrrolo-isoquinolines 1 affords a mixture of cyclic hemiacetals, which can be converted via intramolecular chemoselective Cannizzaro reaction into respective β-amino alcohols, whereas the IBX oxidation gives N-formyl aldehydes. We have demonstrated the utility of such synthons by the synthesis of (+)-6,7-dimethoxy-salsoline-1-carboxylic acid and its new 1-phenyl analogue.     

A stereoselective route to 6-substituted pyrrolo-1,5-benzoxazepinones and their analogues

We developed a novel and convenient stereoselective path for the preparation of pyrrolo-1,5-benzoxazepinones (PBOs). This innovative route envisaged the employment of (−)-menthol as convenient chiral auxiliary and a key S_NAr for the stereoselective preparation of a tertiary aryl–alkyl ether. As a further advancement, we exploited this newly conceived synthetic route for the preparation of 2-substituted PBO analogues to either undergo biological evaluation themselves or give access to a variety of further functionalization options.     

A versatile route to benzocanthinones

Benzocanthinone (1) and five analogs (10, 12-15) were prepared by radical-induced cyclizations of halo N-aroyl derivatives of β-carboline and carbazole.     

A short route toward chiral, polyhydroxylated indolizidines and quinolizidines

In this paper, a rapid route toward functionalized bicyclic alkaloids is presented. In only three steps, an easily accessible carbohydrate derivative was converted into iodomethyl indolizidine 13, which can equilibrate to the corresponding iodoquinolizidine 15. We provide strong evidence that this equilibration proceeds via an aziridinium ion intermediate. Furthermore, nucleophilic substitution of the iodomethyl indolizidine as well as the aziridinium intermediate gives access to highly functionalized indolizidine and quinolizidine alkaloids.     

Development of a scalable synthetic route towards a 2,2,6-trisubstituted chiral morpholine via stereoselective hydroalkoxylation

A scalable synthetic route towards a chiral 2,2,6-trisubstituted chiral morpholine, which is a known opioid antagonist, was developed. The synthetic route involves incorporating an aryl group via Suzuki-Miyaura coupling and stereoselective hydroalkoxylation catalyzed by trifluoromethanesulfonic acid. Late stage incorporation of both the aryl and N-alkyl groups make this route suitable for further SAR studies on this molecule.     

A short route to chiral synthons for eicosanoids with a hydropyran fragment

Institute of Organic Chemistry, Ural Branch, Russian Academy of Sciences, 450054 Ufa. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 5, pp. 1233–1234, May, 1992.     

Asymmetric aldol reactions using chiral CF3-Oxazolidines (Fox) as chiral auxiliary

The aldol reactions of amide enolates derived from a trifluoromethylated oxazolidine (Fox) chiral auxiliary occur in good yields with a moderate anti diastereoselectivity (Li and Na enolates) to a high syn diastereoselectivity (boron enolate). After removal, the Fox chiral auxiliary is very conveniently and efficiently recovered in basic conditions.     

A concise synthesis of (+)-pancratistatin using pinitol as a chiral building block

A concise approach toward (+)-Pancratistatin has been achieved via 12 steps from pinitol. An ultrasound assisted arylcerium induced ring opening of cyclic sulfate was employed as a key step.     

Higher terpenes from lower terpenes: A short,simple and versatile route to bisabolane sesquiterpenoids

An efficient procedure for the elaboration of abundantly available monoterpenes to bisabolane sesquiterpenes utilising catalysed ene addition as the key reaction is described.     

Synthesis of vinylic iodides for incorporation into the C17-C27 fragment of bryostatins

Vinylic iodides were identified as useful intermediates for the synthesis of the C17-C27 fragment of the bryostatins with control of the geometry of the exocyclic methoxycarbonylmethylene group. Following literature precedent, the Piers (E)-stereoselective addition of tributyltin hydride to an alkynoate followed by ester reduction and tin-iodine exchange gave vinylic iodides that could be used to form the C20-C21 bond of the bryostatins. Chelation controlled addition of lithiated 3-silyloxypropynes to 2-alkoxyaldehydes followed by reductive iodination was used to prepare vinylic iodides that could be used in the complementary assembly of the C21-C22 bond of the bryostatins. Initial studies of the synthesis of intermediates for metathesis studies using metal catalysed reactions of a vinylic iodide for C21-C22 bond formation were complicated by cyclisation reactions.     

A highly stereoselective route to medium-ring-sized trans-alkenolides via oxidative fragmentation of bicyclic oxycyclopropane precursors: application to the synthesis of (+)-recifeiolide

A new approach to the synthesis of medium-ring-sized trans-alkenolides, based on the oxidative fragmentation of a three-carbon ring in hydroxyalkyl substituted bicyclo[n.1.0]alkan-1-ols readily available from 2-alkylidenecycloalkanones, is described. This methodology was applied to the six-step transformation of cyclooctanone to the natural 12-membered trans-alkenolide antibiotic (+)-recifeiolide.     

A novel approach to functionalized (E)-1,4-diaryl-1-butenes by Heck reaction and their applications for the construction of dibenzylbutyrolactone lignan skeletons by radical cyclization

A highly regio- and stereoselective [Pd(allyl)Cl]₂ catalyzed Heck reaction of aryl iodides and electronically neutral terminal olefins generated in situ by fluoride induced protiodesilylation of alkenylsilanol derivatives under mild conditions has been developed. The products, viz. terminally substituted styrenes and (E)-1,4-diaryl-1-butenes were obtained in very good yields. The dibenzylbutyrolactone lignan skeletons have been prepared employing two regio- and stereoselective Bu₃SnH-mediated radical cyclization routes.