Alcohol bicyclic primary

The total synthesis of the antimicrobial drimane-type sesquiterpene (-)-pereniporin A was achieved by the research team of K. Mori. The advanced intermediate bicyclic primary alcohol was first oxidized to the corresponding aldehyde using the Moffatt oxidation. Interestingly, the sensitive a-hydroxy aldehyde moiety in the product remained unchanged. The final step was a global deprotection followed by a spontaneous lactol formation. 

There was also obtained from the oil a second alcohol, which contains two double bonds, and is bicyclic. It is also a primary alcohol, but its characters have not been ascertained with accuracy. A mixture of bicyclic and tricyclic vetivenol isolated by means of phthalic acid had the following characters, from which those of bicyclic vetivenol may, to some extent, be deduced —... 

Blocking the C-l OH of D-fructose and L-sorbose (Scheme 25) was effected in excellent yields through regioselective isopropylidene acetalation of the free ketoses, followed by etherification (benzylation or allylation) of the remaining primary alcohol. Acid-catalyzed hydrolysis of the isopropylidene groups and condensation with HSCN efficiently produced a sole fused bicyclic OZT. 

Reduction of the bicyclic ketotosylate 332 which gave the exo-methylene primary alcohol product 335 via the intermediates 333 and 334 was observed by Kraus (93). 

Each diol was selectively tosylated on the primary alcohol to give syn and anti tosylates 55 which were each treated with base [the anion of DMSO MeS(0)CH2 ]—syn-55 cyclised to give the bicyclic ether 56 in good yield while anti-55 fragmented to give volatile hexenal 57. 

Palladium-catalyzed cycloisomerization of lactone 276 produced the tricyclic lactone 277 (Scheme 31). The lactone was saponified and the generated acid was decarboxylated to the bicyclic sulfone 278. Oxidation of the primary alcohol to the acid with Jones reagent was followed by esterification yielding 279. Now, the... 

In addition to this, there are several reports of asymmetric esterification of racemic alcohols with anhydrides as acyl donors. Examples include various primary and secondary alcohols, bicyclic secondary alcohols of the norbomane type, amino alcohols, and ferrocenes. This is exemplified in eq 9 for 1 -phenylethanol. ... 

Attention may be drawn to a new reagent, chromium trioxide in pyridine, that is said to oxidize primary alcohols to aldehydes. The potential importance of its application to bicyclic diacetals with free terminal groups is clear, both as a preparative method for aldoses and as a means of assigning conformations. 

Fragmentation of appropriate bicyclic sulfonyloxy alcohols or ketones is a general route towards cy-cloalkene ketones or carboxylic acids. Thus, the hydroazulene alcohol (59 Scheme 22), precursor for the synthesis of daucene (60), jaeschkeana diol and others, has been synthesized by a one-pot reaction (fragmentation and isopropylation) of the hydroxy tosylate (57) with Pr Li. The fragmentation of (57) to give the ketone (58) as the primary product can be achieved by treatment with pyridine. 

The first total synthesis of the clerodane alkaloid solidago alcohol was achieved in the laboratory of H.-S. Liu, using a highly diastereoselective DIels-Alder cycloaddition as the key step. The installation of the 3-furyl side chain required the conversion of the bicyclic primary alkyl bromide to the corresponding aldehyde. This was accomplished by the modified Kornblum oxidation, which employed silver tetrafluoroborate to activate the substrate. 

Whitesell and Minton have synthesized (- )-xylomollin (408), the only trans-fiised iridoid, from the racemic bicyclic diene 409. Control of the stereochemistry was effected in the first step by addition of the glyoxylate 410. The two products were separated and the major one, 411, was reduced with lithium aluminum hydride. Conversion of the primary alcohol to a methyl group, with concomitant inversion of stereochemistry at the secondary alcohol carbon atom was carried out by protection of the primary alcohol function (fert-butyldimethylsilyl), tosylation of the secondary hydroxyl, then removal of the silyl group with formation of an epoxide with inversion, and reduction (LiEtaBH) of the epoxide. The remaining steps are shown in Scheme 36. It remains to point out that isoxylomoUin (412) was produced preferentially, and is indeed formed from xylomollin (408) slowly in methanolic solution. ... 

Use of polymer-bound chlorite 11 was shown to be more efficient for the oxidation of secondary alcohols to the corresponding ketone [23c]. The method was applied to a series of complex synthetic intermediates and gave excellent results. Immobilized chlorite was shown to be also a very efficient co-oxidant in the conversion of primary alcohols into the corresponding carboxylic acid [24]. This method is particularly attractive due to the ease of purification, the excellent yields and purity obtained also on more complex structures. What makes these techniques particularly interesting is that they have found applications in the synthesis of complex molecules. It was the method of choice for the synthesis of intermediate 13, the core of azadirachtin, in studies towards the synthesis of this natural product by the Nicolaou group [25]. This bicyclic aldehyde was obtained very cleanly using this method (Scheme 4.2). 

Phenyl-l,2,4-triazoline-3,5-dione (589) reacts with primary alcohols ROH to yield the ester-amides (590) and nitrogen, while tertiary amines or pyridine afford the bicyclic compound (591). " With heptalene, a mixture of stereoisomeric cyclo-adducts (592) is obtained.Thermolysis of the amino-azimine (593) yields mainly phenyl isocyanate and dimethylcarbamoyl azide, Me2NCON3." ... 

Chloro-l,3-dimethylimidazolium chloride (DMC) [26] (R =R = Me, L = H in 11, Scheme 4.8a) not only acts as a powerful dehydration agent but also has unique and versatile abilities to chlorinate primary alcohols, to oxidize primary and secondary alcohols and to reduce sulfoxides and so on. In addition, DMC easily reacts with amines to yield the corresponding guanidines. Thus, methods of preparing monocyclic and bicyclic systems by application of DMC chemistry in the key steps have been developed [27] the reaction of DMC-type chloroamidine compounds with amines for trisubstituted mono-cyclic guanidines [27a] (Scheme 4.8a), the intramolecular cyclization of thiourea derivatives after activation with DMC for monosubstituted or disubstituted monocyclic and bicyclic guanidines [27b] (Scheme 4.8b), and the DMC mediated cyclization of... 

Scheme 10.15, which is appreciably shorter than 10.14, uses the same general methods to establish the stereochemical relationships. In step C, the cyclopropane ring is opened by protonation. The incipient carbonium ion is captured intramolecularly, and the cis relationship between the C-2 and C-5 substituent is thereby established. The geometry of the bicyclic ring system and the retention of stereochemistry in the Baeyer-Villiger reaction are used to ensure the cis stereochemistry of the substituents at C-1 and C-3, as in Scheme 10.14. Step A is an electrophilic substitution that is initiated by protonated formaldehyde. The resulting cation is captured by formic acid, and the primary alcohol is also formylated under the reaction conditions.

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