Lactones partial reduction

With the co side chain at C-12 in place, we are now in a position to address the elaboration of the side chain appended to C-8 and the completion of the syntheses. Treatment of lactone 19 with di-isobutylaluminum hydride (Dibal-H) accomplishes partial reduction of the C-6 lactone carbonyl and provides lactol 4. Wittig condensation8 of 4 with nonstabilized phosphorous ylide 5 proceeds smoothly and stereoselectively to give intermediate 20, the bistetra-hydropyranyl ether of ( )-1, in a yield of -80% from 18. The convergent coupling of compounds 4 and 5 is attended by the completely selective formation of the desired cis C5-C6 olefin. 

The most widely used reagent for partial reduction of esters and lactones at the present time is diisobutylaluminum hydride (DiBAlH).83 By use of a controlled amount of the reagent at low temperature, partial reduction can be reliably achieved. The selectivity results from the relative stability of the hemiacetal intermediate that is formed. The aldehyde is not liberated until the hydrolytic workup and is therefore not... 

MISCELLANEOUS BENZOHETEROCYCLES Partial reduction of lactone 166 (using for example diisobutylaluminum hydride in the cold) affords lactol 167. Condensation with nitromethane leads to the corresponding alkylated tetrahydrobenzopyran 170. The sequence probably starts by aldol reaction of the hydroxylactone form of the lactol (168) with nitrome thane to give the vinyl nitro intermediate 169 ... 

The dianion derived from but-2-ynoic acid reacts with aldehydes to give 5-hydroxyalk-2-ynoates (539). Partial reduction over a Lindlar catalyst and acid-catalyzed cyclization of the resulting enoate gives the dihydropyran-2-one (78LA337). The route is exemplified by the synthesis of the naturally occurring massoia lactone (Scheme 200). In previous work (46JCS954) the hydroxyalkynoic acids themselves, obtained from epoxides and acetylene, were used. 

The combination of polymethylhydrosiloxane (PMHS) and catalytic amounts of TBAF (1 mol%) and Cp2Ti(OC6H4Cl-4)2 (2 mol%) provides an efficient and convenient method for the partial reduction of lactones 187 to lactols 189 via hydrosilylation and subsequent hydrolysis of the resulting O-silyllactols 188 (equation 76)184. 

Although Sml2 has been used for the partial reduction of a-heteroatom-sub-stituted esters, lactones and amides (see Section 4.5), the reduction of simple, unfunctionalised substrates is not usually possible. It is now clear that in certain cases reduction using Sml2 is possible provided that an activating additive is... 

A special case is lactone formation after the partial reduction of a dicarbonic acid... 

Whitesell s synthesis of ( )-sarracenin [( )-495] (Vol. 4, p. 501, Ref. 314) has been published in full." It is worthwhile noting certain difficulties reported at the end of the synthesis involving the apparently simple steps shown in Scheme 48. Partial reduction of the lactone function in 496 with diisobutylaluminum hydride requires two equivalents, the first of which is taken up by complexation with the carbomethoxy group. Even with this problem solved, the yield of sarracenin [( )-495] from 496 was only 15%, and it is impossible to see where the loss was because of the instability of the intermediate compounds.Because both epimers of 497 were available in an earlier step toward 496, Whitesell also synthesized the as yet unnatural episarracenin with an epimeric 8-methyl group. 

The structure of ophiobolin A (5.137) was established by chemical degradation and by X-ray crystallography of a bromo derivative. The spectroscopic characteristics of ophiobolin A led to the identification of the oxygen functions and the double bonds. The relationship between the aldehyde and the cyclo-pentanone was revealed by the formation of a y-lactone on reduction and partial re-oxidation. A cyclic pyridazine was formed with hydrazine. Tetra-hydro-ophiobolin A formed an unusual cyclic peroxide involving these two groups. Vigorous oxidation of tetrahydro-ophiobolin A afforded a heptanoic acid lactone, which revealed the structure of the side-chain. 

Other syntheses of the tetracyclic intermediates 434 and 436 that merit mention, and thus constitute additional formal syntheses of (-1-)-quebrachamine, have been contributed by Fuji et aL and by Asaoka and Takei. Fuji s approach (279) starts with the chiral lactone 446, which is readily available from 2-ethyl-5-valerolactone. Partial reduction to the aldehyde stage, followed by acetal formation, gave 447, which on condensation and reduction (lithium aluminum hydride) gave a mixture of C-3 epimers 434, the late intermediate in the (+)-quebrachamine synthesis (Scheme 41). 

No doubt joining the alkyne to the alkene could also have been done by a coupling reaction in the coordination sphere of a metal but an alternative is to imagine the alkene as coming from the dehydration of an alcohol 251. This allows disconnection to the known lactone 250. The synthesis of the alkyne uses DIBAL for partial reduction and the differential protection of the two OH groups by more or less hindered silyl groups. 

Many natural products and natural aroma components contain 2-furanone units and considerable synthetic work has thereby been engendered.In the context of these natural products, the name buteno-lide is generally employed and compounds are therefore numbered as derivatives of 4-hydroxybutenoic acid and not as a furan, for example a tetronic acid is a 3-hydroxybut-2-enolide. Butenolides can be converted into furans by partial reduction of the lactone, then dehydration.""... 

Irradiation of the aldehyde (253) in the presence of KOH-02-Rose Bengal gave the ketone (297) which was readily converted into progesterone/ A series of 18-substituted progesterones has been synthesized from the 18-nitrile (298) which could only be satisfactorily hydrolysed, to give the lactone (300), by partial reduction to the alcohol (299) followed by treatment with KOH-Bu OH/ Two syntheses of 17a-hydroxymethylprogesterone (302) have been reported. The first involved the intermediacy of the previously described lactone... 

Acid derivatives are also reduced by L1A1H4. Reduction of the highly reactive acid chlorides 2 and acid anhydrides27 is rapid. Partial reduction of aromatic anhydrides to lactones has been reported by controlling the stoichiometry of L1A1H4 and the anhydride.28 In most cases, however, complete reduction to the diol... 

Butenolides can be converted into furans by partial reduction of the lactone, then dehydration. ... 

Lactone 260 can be transformed into the aggregation pheromone ( S)-( + )-sulcatol (617) in three steps by catalytic hydrogenation of the olefin, partial reduction of the lactone to a lactol, and Wittig olefination with isopropylidenetriphenylphosphorane (Scheme 86). 

The avermectins, which possess potent anthelmintic and insecticidal activities, have structural features similar to the milbemycins. The C-15 to C-28 spiroketal-containing unit (690) of avermectin Bia aglycone (691) is s)mthesized in optically pure form by coupling L-malic acid-derived lactone 687 with D-glucose-derived acetylene 688. Partial reduction of the... 

Some basic reactions of f 5-parasorbic acid were investigated, such as the partial reduction of the lactone grouping to form 2-hydroxy-6-methyl-5,6-dihy-dro-2H-pyran (128), glycosidation of 128, and addition reaction of some nucleophiles to he double bond to yield 4-substituted lactones (129). 

Coupling the amine 92 and the acid 91 gave amide 93. Partial reduction of the lactone produced the hemiacetal (94) which, on acid treatment. 

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