Novel Preparation Of Chiral Diols And Their Application To Organic Synthesis

Chiral diols are one of the most important classes of chiral ligands, and they are the starting materials for preparing chiral diamines, diphosphines, etc. Therefore they play an inportant role in organic synthesis. Natural tartaric acid is one of the most availiable multifunctional chiral diols. It can be prepared into a variety of chiral 1, 4-diols or 1,2-diols useful for asymmetric synthesis via appropriate chemical transformation. For instance, (2R,3R)-1,4-dimethoxy-1,1,4,4-tetraphenylbutane-2,3-diol, which was prepared from natural tartaric acid, a sterically hindered chiral diol, not only has been used as an effective protecting group of alkylboronic acid, but also the generated chiral boronate ester exhibited excellent chiral induction in asymmetric epoxidation, asymmetric [4+2] cycloaddition, asymmetric addition, Johnson rearrangement, and [3,3]σrearrangement. (1S,2S)-2-amino-l-(4-nitrophenyl) propane-1,3-diol ((1S,2S)-ANP), a by-product of chloramphenicol production, is a multifunctional chiral 1,3-diol. Its price is very cheap, and it was widely used in organic synthesis. In addition, chiral pinanediol is also an important chiral diol. In the present thesis, novel preparation for some spiroborated chiral 1,4-diols and hindered 2, 3-diols, and catalytic activity of (1S,2S)-ANP toward multicomponent Hantzsch reaction as well as an improved preparation of chiral pinanediol were described.The thesis is devided into 5 chapters.In chapter 1, the progress in the latest years in the preparation of chiral diols and their application to organic synthesis are reviewed, and the content of the thesis was outlined.In chapter 2,12 kinds of chiral boron compounds having 1,4-dihydroxy structural unit and an O4B skeleton were synthesized, and their functional group transformation was investigated and a new convenient preparative procedure for sterically hindered chiral 2,3-diol was established.Natural tartaric acid dialkyl ester is allowed to directly phenylated with PhMgBr to prepare (R,R)-1,1,4,4-tetraphenylbutanetetraol, and then reacted with borane, boric acid, trialkyl borate, or sodium borohydride, furnished high-yieldingly selective 2,3-cycloborating product——chiral spiroboric acid or spiroborate salts with an O4B framework, where the two hydroxy groups at 1,4-position were not reacted. The chiral spiroboric acid or spiroborate salts were transformed into other metal salts, ammonium salts or phosphonium salt through simple acid-base reaction or metathetical reaction. It was observed that a decarboxylation reaction took place when the chiral spiroboric acid was refluxed with L-proline in toluene, and a tetrahydro-pyrrole salt of the chiral spiroboric acid was obtained in high yield, of which the O4B framework structure has been proved by the single crystal X ray differaction analysis. The spiroborate salts were methylated with methyl iodide and sequentially deborated, (2R,3R)-1,4-dimethoxy-1,1,4,4-tetraphenylbutane-2,3-diol was obtained in more than 90% overall yield. Therfore a simple, convenient properation for the sterically hindered C2 chiral diol was established.In addition, asymmetric catalytic activity of a chiral spiroborate salt toward cyclopropanation of an olefin was preliminarily examined.In chapter 3, one-pot synthesis of 1,4-dihydropyridnes via Hantzsch four-component reaction catalyzed by (1S,2S)-ANP and its derivatives, (1S,2S)-2-(dimethylamino)-l-(4-nitrophenyl)propane-1,3-diol ((1S,2S)-DMANP) and (1 S,2S)-2-amino-1-(4-nitrophenyl)-3-(trityloxy)propan-1-ol ((1S,2S)-TPANP), were examined. The results showed that (1S,2S)-ANP was the most effective catalyst. When (1S,2S)-ANP loading was 10%,1,4-dihydropyridine compounds were gained in up to 95% yield by stirring dimedone, alkyl acetoacetate, aldehyde and ammonium acetate at room temperature for 4-5 hours. However, these chiral 2-amino-1,3-propanediol derivatives all do not show asymmetric catalytic activity. A possible reaction mechanism was suggested.Three chiral compounds derived from L-proline were also tested, observed that they could catalyze the Hantzsch reaction, but as the above, also do not show asymmetric catalysis activity. In chaper 4, one-pot, three-component synthesis of tetrahydrochromene derivatives catalyzed by (1S,2S)-ANP was investigated. Optimizing the reaction conditions,19 kinds of 2-amino-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydrochromene-3-carbonitrile derivatives were synthesized. When the catalyst loading was 10 mol%, target products of up to 99% yield were gained by stirring a mixture of dimedone, aldehydes and malononitrile at room temperature for 5-20 min. A possible reaction mechanism was suggested. Cheap catalyst, mild reaction conditions, short reaction time and high yield are the major advantages of this method.In chapter 5, chiral pinanediol was prepared by an improved oxidation of a-pinene using potassium permanganate. Under the condition of phase transfer catalyst, change of adding sequence for the reactants and 10 mol% of the catalyst loading led to the yield of the desired product increase about one third compared with that in the literature. It operationally is convenient for using centrifugal separation to remove by-product MnO2.Attempt to improve the enantiomeric excess of pinanediol by using of boron chemical method met without success.