Epoxy alcohol fragmentation

Previous work by Holton [15] on the synthesis of taxane ring systems, indicated that the preparation of the bicyclo[5.3.1]undecane skeleton lies basically on the work of Biichi on patchouli alcohol [16], which led him to the development of the so-called "epoxy alcohol fragmentation" [15a]. 

An easy, silica gel-promoted 6-endo cyclization of y-epoxy alcohol 32 to pyran 33, followed by acid-catalyzed spiroketalization of the keto diol 34, afforded the common tricyclic spiroketal fragment 35 of lituarines A, B, and C (Scheme 8.8) [20b],... 

Deoxygenation of a,f)-Epoxy Alcohols with Concomitant Fragmentations 415... 

Deoxygenation of a, fi-Epoxy Alcohols with Concomitant Fragmentations 417... 

In Holton s and Wender s work, the total synthesis was achieved by sequentially forming the AB ring through the fragmentation of epoxy alcohols derived from (—)-camphor and a-pinene. Nicolau s, Danishefsky s, and Kuwa-jima s total syntheses involved B ring closure connecting the A and C rings, whereas in Mukaiyama s synthesis, the aldol reaction was extensively applied to construct the polycyclic system. 

Red-Al first generates one equivalent of hydrogen gas from epoxy alcohols A (Figure 17.43). An O—A1 bond forms in the resulting trialkoxyaluminate D. The epoxy fragment in D then is reduced via an intramolecular reaction. The transfer of a hydride ion from aluminum leads selectively to the formation of a 1,3-diol, since the approach path that would lead to the 1,2-diol cannot be collinear to the C—O bond that would have to be broken (stereoelectronics , cf. Section 2.4.3). 

With 114 in hand, deprotection of the acetate unit, followed by acid-induced cyclization, furnished epoxy-alcohol 115 in good yields. The authors used another acid-catalyzed cyclization to form the C-ring of the desired fragment 116 in a regio- and stereoselective manner. Thus, functional group manipulation of 115 and cyclization upon exposure to Ti(0-iPr)4 [62] afforded compound 116 in 58% yield. This synthesis proceeded in 14 steps from famesyl acetate (108) with 1.5%... 

Oxidation of 19-hydroxycholesteryl acetate (614) with Pb(OAc)4 is known to proceed with fragmentation to give the 19-nor-A -product (615). The 5/3,6j -epoxy-derivative (616) is now reported to undergo a similar fragmentation on neutral alumina, giving the 5(10)-en-6 -ol (617) the 5a,6a-epoxide was stable on alumina. The 5jS,6j -epoxy-alcohol (616) reacted with Pb(OAc)4 with attack of the 19-alkoxy-radical upon C-11 to give the lljS,19-ether (618). ... 

Azamacrolide 32e was synthesized from epoxy alcohol 91 (Scheme 6.18). Base-mediated fragmentation of epoxy chloride 91a and alkylation followed by acetylene-zipper reaction gave terminal alkyne 93. Alkylation of 93 and hydrogenation furnished diene 94. Conversion of alcohol into aminoethanol derivative followed by oxidation afforded the acid 94, which on macrolactonization gave azamacrolide (—)-32e (Scheme 6.18). 

Reagent for characterisation of alcohols and sugars, dehydrations and epoxy ketone fragmentations. Mp 108-110°. 

A 2-cyclohexenone derivative can be transformed into the corresponding epoxy tosyl-hydrazone by sequential treatment with peracid and tosylhydrazine. The elimination of nitrogen and p-toluenesulfinate and fragmentation after rearrangement to the 3-tosylazo allylic alcohol may occur under mild conditions. Carbonyl compounds with 5,6-triple bonds are formed in high yields (J. Schreiber, 1967 M. Tanabe, 1967). If one applies this reaction to a 9,10-epoxy-1-decalone, a ten-membered 5-cyclodecyn-l-one ring is formed (D. Felix, 1971). This product is an important intermediate in the perfume industry and has been used on a large scale. For this purpose Eschenmoser developed a synthesis in which the readily removed styrene was split off instead of a sulfmic acid. Thus a l-amino-2-phenylaziridine hydrazone was used instead of a tosylhydrazone (D. Felix, 1968). ... 

Epoxides will fragment if carbanions are formed adjacent to the epoxide ring. Decomposition of the hydrazone of an epoxy ketone in the presence of base may lead to an allylic alcohol (Scheme 2.24). Since the epoxy ketone may be prepared from an unsaturated ketone, this can form part of a sequence for the 1- 3 transposition of an oxygen function. 

Several 21,22-seco-diacids (150) have been prepared in the 20/S,28-epoxy-18a,19/8H-ursane series by oxidation of the corresponding 22-hydroxymethylene-21-ketones (151). Reaction of the 21-ketone (152) with oxygen in an alkaline medium afforded the a-hydroxy-acid (153) and the seco-diacid (150). ° Several interesting reactions were observed during this work. ° While pyrolysis of the a-acetoxy-acid (154) yielded the ketone (155) pyrolysis of the seco-diacid anhydride resulted in loss of carbon monoxide and formation of the lactone (156). Lead tetra-acetate oxidation of the ketone (155) [or the hydroxy-acid (153)] followed a Baeyer-Villiger pathway to the lactone (156). The ketone (155) was very susceptible to reduction in the presence of alcoholic alkali. The mass spectral fragmentation of a series of compounds based on 20/8,28-epoxy-18a,19/8H-ursane has been examined. ... 

Preparation of the hydroxypentanoic acid fragment was initiated by addition of the protected propargyl alcohol anion 109 to ethylene oxide. After silylation of the resulting alcohol, the ethoxy ethyl group was removed and the alkyne partially reduced to afford the (2)-alcohol 110 in 52% overall yield. Enantiospecific epoxidation of 110 under Sharpless s conditions and subsequent oxidation provided a 69% yield of diastereomerically pure epoxy acid 111. Treatment with trimethylaluminum gave almost exclusively the p-methyl acid, which was acylated to afford 112 (78%). 

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