Bicyclic alcohols synthesis

Laqua, H. Frohlich, R. Wibbeling, B. Hoppe, D. Synthesis of enantioenriched indene-de-rived bicyclic alcohols and tricyclic cyclopropanes via (-)-sparteine-mediated lithiation of a racemic precursor and kinetic resolution during the cyclocarbolithiation. J. Organomet. Chem. 2001, 624, 96-104. 

There exists also a synthesis of cyclopentadecanone (VII/81) and ( )-mus-cone, based on a three-carbon annulation of cyclic ketones followed by the regioselective radical cleavage of the zero bridge of the so formed bicyclic system [44], The synthesis of cyclopentadecanone is summarized in Scheme VII/16. The cyclization of VII/78 to the bicyclic alcohol VII/79 proceeds best (94 % yield) with samarium diiodide in the presence of hexamethylphosphoric acid triamide and tetrahydrofuran [45], The oxidative cleavage of VII/79 to the ring expanded product VII/80, was performed by treatment with mercury(II)-oxide and iodine in benzene, followed by irradiation with a 100 Watt high pressure mercury arc. Tributyltinhydride made the de-iodination possible. 

Bicyclic alcohol 97 was utilized in a total synthesis of the natural product (—)-xialenon A (Scheme 43) <2002CC2436, 2003T9719>. 

Molander, G. A., Etter, J. B. Lanthanides in organic synthesis. Synthesis of bicyclic alcohols. Tetrahedron Lett. 1984, 25, 3281-3284. 

Formation of a bicyclic alcohol by radical cyclization involving a methylene-cyclopropane unit and a propargyl ether makes the method most valuable for a synthesis of paeonilactone-B... 

Different concept of 2-deoxy-KDO synthesis was presented by Craig [151]. The synthetic route started from epoxide 281 and 3,3-dimethoxy-l-(phenylsulfonyl)-propane which were transformed, after several manipulation, to bicyclic alcohol 284 (Scheme 60). 

Note added in proof. ktotA synthesis of (-)-xialenon A using bicyclic alcohol 77 [Eq. (26)] represents the first application of enantioselective a-hthiation transannular C-H insertion of epoxides in natural product synthesis [78]. The first enantioselective generation - intermo-lecular nucleophile trapping of a lithium carbenoid has been described, via enantioselective a-deprotonation of the epoxides of oxa- and aza-bicyclic alkenes [e.g. 93 Eq. (30)] using alkyl-lithiums in the presence of (-)-sparteine or bisoxazoline 5 [Eq. (3)] [79]. Insertion of a second... 

Chapelo, C. B., P. Hallett, B. Lythgoe, I. Waterhouse, and P. W. Wright Calciferol and its Relatives. Part 19. Synthetic Applications of Cyclic Orthoesters Stereospecific Synthesis of a Bicyclic Alcohol Related to the Vitamins D. J. Chem. Soc. Perkin 11977,1211. 

Mao B, Fananas-Mastral M, Lutz M, Feringa BL (2013) Diversity-oriented enantioselective synthesis of highly functionalized cyclic and bicyclic alcohols. Chem Eur J 19 761-770... 

We also achieved the synthesis of methyl tuberonate (MTA, 13) (Scheme 4). Bicyclic alcohol 14 was converted to diol 15. The key of the synthesis was... 

Molander and Etter (1986a) reported the reductive coupling of 2-(ca-iodoalkyl) cycloalka-nones by Sml2 in THF in the presence of catalytic amounts of iron tris-(dibenzoylmethane), [Fe(DBM)3], These reactions gave excellent yields of bicyclic alcohols This methodology is especially useful in the synthesis of 6-membered rings (eq. (48), table 7). 

Epoxide 163, proceeding from the enantioselective cis-dihydroxylation of farnesyl acetate and a dehydratation step, upon treatment with catalytic Ti(III), afforded the bicyclic alcohol 164, which was used in the synthesis of the potent anti-inflammatory myrrhanol (Scheme 25.75)." ... 

The General Synthesis of Medium and MacrocycUc Ketones Based on Ring Expansion by the Photolysis of the Hypoiodites of Bicyclic Alcohols... 

A 6-endo cyclization by a y-epoxy alcohol can be accomplished through the presence of an appropriately disposed electron-withdrawing group, as found in the total synthesis of (+)-phonomactin. Treatment of the hydroxy-epoxy ketone 30 (R = H) with HC1 afforded the bicyclic compound 31, containing a pyran-4-one ring, in which nucleophilic attack of the y-OH group occurred at the oxirane carbon distal from the unfavorable electronic effect of the carbonyl group (Scheme 8.7) [20a]. 

Intramolecular versions of the Diels-Alder reaction are well known, and this is a powerful method for the synthesis of mono- and polycyclic compounds.There are many examples and variations. One interesting internal Diels-Alder reaction links the diene and dienophile by a C—O—SiR2—or a C—O—SiR2—O—C linkage. Internal cyclization to give a bicyclic product is followed by cleavage of the O-Si unit to give a monocyclic alcohol. 

Scheme 13.17 depicts a synthesis based on enantioselective reduction of bicyclo[2.2.2]octane-2,6-dione by Baker s yeast.21 This is an example of desym-metrization (see Part A, Topic 2.2). The unreduced carbonyl group was converted to an alkene by the Shapiro reaction. The alcohol was then reoxidized to a ketone. The enantiomerically pure intermediate was converted to the lactone by Baeyer-Villiger oxidation and an allylic rearrangement. The methyl group was introduced stereoselec-tively from the exo face of the bicyclic lactone by an enolate alkylation in Step C-l. 

The grem-dibromocyclopropanes 152 bearing a hydroxyalkyl group, prepared by the addition of dibromocarbene to allylic or homoallylic alcohols, undergo an intramolecular reductive carbonylation to the bicyclic lactones 153. bicyclic lactone derived from prenyl alcohol is an important precursor for the synthesis of ris-chrysanthemic acid. (Scheme 54)... 

Azido derivatives of furazans have proved to be particularly useful for the synthesis of heterocyclic systems. Thus, by 1,3-dipolar addition of l-azido(4-amino-l,2,5-oxadiazol-3-yl)aldoxime 186 to propargyl alcohol and phenylacetyl-ene, bicyclic 4-amino-l,2,5-oxadiazol-3-yl(4-R-l,2,3-triazol-l-yl)ketoximes 187 were obtained (Equation 34) which in reaction with acetic anhydride afforded the corresponding 0-acyl derivatives <2003RJ0574>. 

Homochiral hydroxyproline 139 served as the starting material for the synthesis of various bicyclic[5.5]hydantoins 140 (Scheme 19). The corresponding amino derivatives 142 were also available by oxidation of the alcohol 141 and reductive amination of the ketone followed by separation of diastereomers by silica gel column chromatography (Equation 19) <2005BML1161>. 

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