Lactonization/benzylic lactone reduction

The efficient stereocontrol observed in the benzylic lactone hydro-genolyses described in the section on Lactonization/Benzylic Lactone Reduction prompted an investigation into methods for preparing analogous fused bicyclic lactones from enamides 89, 92, 94, and 96. The possible intermediacy of benzylic carbocation 123 in the triethylsilane... 

The diversity of the products obtained by the three-component domino-Knoevenagel-hetero-Diels-Alder reaction can be further increased by a different work-up of the formed cycloadduct 141. Thus, hydrogenolytic removal of the Cbz-group in 141 led to 151 with a lactam and an aldehyde moiety by reaction of the formed secondary amine with the lactone moiety followed by elimination of benzyl alcohol. Reduction of 151 with lithium aluminum hydride gave benzoquinolizidine 152 (Scheme 5.30). Alkaloids of this type have so far not been found in nature, but it can be assumed that they might exist, since they could easily be formed from deacetylisopecoside 153, which is an intermediate in the biosynthesis of emetine 111. 

With the desired lactones 140, 134, 135, and 136 in hand, hydro-genolysis with a variety of heterogeneous catalysts was carried out following the general principles outlined in the section on Lactoniza-tion/Benzylic Lactone Reduction. The crude products containing acids 141 to 144 and their corresponding C-4 epimers 145 to 148 were... 

The reaction of lactones of benzyl alcohols with Et3SiH/TFA results in complete reduction of the alcohol part of the lactone to the methylene group while preserving the carboxylate function (Eq. 148).305... 

This compound, previously prepared174 in low yield from alginic acid, has been synthesized128 from 61 by oxidation at C-2, and stereospecific reduction of the intermediate methyl 5-0-benzyl-/3-D-nrab-ino-2-hexulofuranosidurono-6,3-lactone. Hydrogenolysis of the 5-0-benzyl group yielded the title compound in a superior yield. 

An unexpected result was obtained when DTBB-catalyzed lithiation was applied to the vinyl-oxetane 313 . After work-up, lactone 314 was isolated, the process being explained by an elimination reaction via a radical pathway more than by reduction of the benzyl radical into the anion. Thus, this hypothetical intennediate reacted with the lithium enolate of acetaldehyde, generated in situ by reductive decomposition of THF (Scheme 92). 

Miki and Hachiken reported a total synthesis of murrayaquinone A (107) using 4-benzyl-l-ferf-butyldimethylsiloxy-4fT-furo[3,4-f>]indole (854) as an indolo-2,3-quinodimethane equivalent for the Diels-Alder reaction with methyl acrylate (624). 4-Benzyl-3,4-dihydro-lfT-furo[3,4-f>]indol-l-one (853), the precursor for the 4H-furo[3,4-f>]indole (854), was prepared in five steps and 30% overall yield starting from dimethyl indole-2,3-dicarboxylate (851). Alkaline hydrolysis of 851 followed by N-benzylation of the dicarboxylic acid with benzyl bromide and sodium hydride in DMF, and treatment of the corresponding l-benzylindole-2,3-dicarboxylic acid with trifluoroacetic anhydride (TFAA) gave the anhydride 852. Reduction of 852 with sodium borohydride, followed by lactonization of the intermediate 2-hydroxy-methylindole-3-carboxylic acid with l-methyl-2-chloropyridinium iodide, led to the lactone 853. The lactone 853 was transformed to 4-benzyl-l-ferf-butyldimethylsiloxy-4H-furo[3,4- 7]indole 854 by a base-induced silylation. Without isolation, the... 

The at complex from DIB AH and butyllithium is a selective reducing agent.16 It is used tor the 1,2-reduction of acyclic and cyclic enones. Esters and lactones are reduced at room temperature to alcohols, and at -78 C to alcohols and aldehydes. Acid chlorides are rapidly reduced with excess reagent at -78 C to alcohols, but a mixture of alcohols, aldehydes, and acid chlorides results from use of an equimolar amount of reagent at -78 C. Acid anhydrides are reduced at -78 C to alcohols and carboxylic acids. Carboxylic acids and both primary and secondary amides are inert at room temperature, whereas tertiary amides (as in the present case) are reduced between 0 C and room temperature to aldehydes. The at complex rapidly reduces primary alkyl, benzylic, and allylic bromides, while tertiary alkyl and aryl halides are inert. Epoxides are reduced exclusively to the more highly substituted alcohols. Disulfides lead to thiols, but both sulfoxides and sulfones are inert. Moreover, this at complex from DIBAH and butyllithium is able to reduce ketones selectively in the presence of esters. 

Obayashi and Schlosser [43] have briefly described syntheses of erythro-sphingo-sine and threo-sphingosine from D-mannose and D-ribono-1,4-lactone, respectively. For the synthesis of ery/Aro-sphingosine (35) D-mannose was converted into benzyl 2,3 5,6-di-O-isopropylidene-manno-furanosides and hydrolysis of the 5,6-0-iso-propylidene group followed by periodate oxidation and borohydride reduction and protection gave the methoxymethyl ether (28). This was converted into the chloride... 

Analogues of 70 have been prepared by various methods including nucleophilic displacement of triflate esters attached directly to the oxetane ring (see Section 2.05.7.2) <2001TL4247>, from xylose, 145, via the benzyl-idene-protected oxetane, 146 (Scheme 24) <2004TA2667>, or from L-rhamnose, 147, via a l,4-lactone-2-O-triflate, 148 (and key oxetane 149 (Scheme 25)) <2004TA2681>. The /3-azidoester monomers formed by these methods were converted to the /3-amino acids and subsequently to /3-peptides by reduction of the azide and ester hydrolysis. 

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