Synthetic Studies On A New Type Of 1,3-Diol And It's Synthetic Application

Chiral 1,3-diol motif exists extensively in many natural compounds and pharmaceutical moleculars.It has been widely roported that chiral 1,3-diol plays a very important role in the organic synthesis:?1?working as an important synthon to construct complex compounds,?2?acting as chiral ligand or catalyst in asymmetric synthesis,?3?using as a chiral resolving agent to seperate racemic compounds.Therefore,the construction of chiral 1,3-diol scaffold represents a significant task for organic chemists.In this thesis,we mainly focused on the synthesis of a new type of1,3-diol and it's synthetic application.The main results could be summarized and shown as follows:In the first part,we presented a novel approach for the preparation of chiral1-?hydroxymethyl?-1-vinyl-1,2,3,4-tetrahydronaphthalen-2-ol?1,3-diol?.The racemic1,3-diol was easily accessible in four steps from commercially available1,4-diol-2-butyne.Firstly,1,4-dibromo-2-butyne was obtained through bromination with PBr₃.Then the Zn-mediated addition reaction of phenylpropyl aldehyde provided 4-methylene-1-phenylhex-5-en-3-ol?butadienol?.Subsequent selective monoepoxidationbyusingVO?OiPr?3andTBHPreadilygave3-phenyl-1-?2-vinyloxiran-2-yl?propan-1-ol?epoxide?.Finally,an intramolecular Friedel-Crafts reaction catalyzed by Zn?NTf₂?₂ was carried out to generate the desired racemic 1,3-diol in gram scales and 21%of total yield.Then we obtained two enantiomers by using D-camphor as chiral resolving agent.After a single resolution,ee?enantiomeric excess?value of both enantiomers could reach to 95%.the chemical structure of these compounds were determined by NMR and ee value was determined by chiral HPLC.In the second part,we investigated the synthtic application of the 1,3-diol.With1,3-diol on hand:1)primary hydroxyl group of 1,3-diol was selectively toslated with TsCl to generate the product with a good leaving group.Under basic condition,oxetane containing a tetrahydronaphthalene structure was obtianed in 61%yield;2)The synthesis of monophosphite compounds was tried through the following two-step procedure.1,3-Diol was firstly transformed into the phosphochloridite with PCl₃ in the presence of base,then L-?-?-menthol was added.Another approach involving the pretreatment of L-?-?-menthol with PCl₃ with a base gave the desired dichlorophosphite,followed by mixing with 1,3-diol.Thus far,no desired monophosphite compounds were successfully obtained.Further studies with the1,3-diol are still on going in our lab.