Reduction/oxidation sequence

When morphine is subjected to a similar reduction-oxidation sequence (1- 10), there is obtained hydromorphone (10). ... 

Reduction is used for carbonyl functionalities [71, 230] such as thioesters [231], amides [232], and carbamates [233], as well as for sulfur [234] and selenium [122] compounds. Recently, the synthesis of a potential carbohydrate vaccine is described via an reduction-oxidation sequence [235]. An efficient solid-phase synthesis of pyrimidine derivatives that involved reduction of the corresponding nitro derivatives was developed by Makara et al. in 2001 (Scheme 3.9) [236]. 

With the fully functionalized heterocyclic core completed, synthetic attention next focused on introduction of the 3,5-dihydroxyheptanoic acid side-chain. This required initial conversion of the ethyl ester of 35 to the corresponding aldehyde through a two-step reduction/oxidation sequence. In that event, a low-temperature DIBAL reduction of 35 provided primary alcohol 36, which was then oxidized to aldehyde 37 with TRAP. Subsequent installation of the carbon backbone of the side-chain was accomplished using a Wittig olefination reaction with stabilized phosphonium ylide 38 resulting in exclusive formation of the desired -olefin 39. The synthesis of phosphonium ylide 38 will be examined in Scheme 12.5 (Konoike and Araki, 1994). 

Cyclopentadiene reacts slowly with DISN giving 123, which, although resistant to oxidation to the diazaindene 124, can be converted to the pyrazine 125 by a reduction/oxidation sequence. Attempts to oxidize 125 to 124 were also unsuccessful (84JOC813) (Scheme 42). 

You may have noticed that only one of the three alkyl groups of a trialkyl-borane is converted to an aldehyde by the carbonylation-reduction-oxidation sequence. To ensure that carbonylation takes the desired course without wasting the starting alkene, hydroboration is achieved conveniently with a hindered borane, such as 9-BBN, 12. With 12, only the least-hindered alkyl group rearranges in the carbonylation step ... 

The total synthesis of (+)-Macbecin I 78 [39] began with aldehyde 73, prepared via the addition of optically pure crotylsilane onto a benzylic acetal, which underwent an SMS reaction to give ester 75 in a 12 1 syn/anti ratio. Oxidative cleavage of the double bond, Wittig olefination of the resulting aldehyde and a reduction-oxidation sequence yielded a,/ -unsaturated aldehyde 76. A second SMS reaction was then performed leading to polyether 77 (dr > 20 1) that contains all the chiral centers of (+)-Macbecin I 78, Scheme 13.31. 

Another electrophilic cyclization strategy is reported in which polyphosphoric acid cyclization of thienyl 2-hydrazones (89) affords l-(p-nitrophenyl)thieno[3,2-c]pyrazoles (90) (Equation (23)) <67CJC697>. On initial analysis, the process appears limited to p-nitrophenylhydrazones but the p-nitrophenyl unit is easily removed in a tandem reduction-oxidation sequence to afford the 1H-thieno[3,2-c]pyrazoles (3). 

A simultaneous reduction-oxidation sequence of hydroxy carbonyl substrates in the Meerwein-Ponndorf-Verley reduction can be accomplished by use of a catalytic amount of (2,7-dimethyl-l,8-biphenylenedioxy)bis(dimethylaluminum) (8) [33], This is an efficient hydride transfer from the sec-alcohol moiety to the remote carbonyl group and, because of its insensitivity to other functionalities, should find vast potential in the synthesis of complex polyfunctional molecules, including natural and unnatural products. Thus, treatment of hydroxy aldehyde 18 with 8 (5 mol%) in CH2CI2 at 21 °C for 12 h resulted in formation of hydroxy ketone 19 in 78 % yield. As expected, the use of 25 mol% 8 enhanced the rate and the chemical yield was increased to 92 %. A similar tendency was observed with the cyclohexanone derivative. It should be noted that the present reduction-oxidation sequence is highly chemoselective, and can be utilized in the presence of other functionalities such as esters, amides, rert-alco-hols, nitriles and nitro compounds, as depicted in Sch. 10. 

Try to draw the transition state of the rearrangement after the reduction-oxidation sequence of both ester functionalities. 

The reduction-oxidation sequence is needed to obtain the dialdehyde, which may even be isolated when handled carefully. 

A simultaneous reduction/oxidation sequence of hydroxy carbonyl substrates in the Meerwein-Ponndorf-Verley reduction can be accomplished by use of a catalytic amount of (2,7-dimethyl-l,8-biphenylenedioxy)bis(dimethylaluminum) (49). This represents an efficient hydride transfer from the sec-alcohol moiety to the remote carbonyl group and, due to its insensitivity to other functionalities, should find vast potential in the synthesis of complex polyfunctional molecules including both natural... 

The reversibility of this phenomenon indicates that during high temperature reduction a reduced sulfur species is formed which migrates to the Pt surface and poisons the Pt surface. Subsequent oxygen treatment oxidizes this sulfur species and the oxidized species migrates back to the support. The oxidized species do not leave the catalyst since the reduction - oxidation sequence produces the same effects over several cycles (see Runs 6 to 9, Table III). 

An aldol condensation (selectivity 100 1) between e reagent 106a (produced from optically active mandelic acid), known to induce (f ) chirality, and propionaldehyde, followed by desilylation and oxidative cleavage of the resulting a-hydroxy ketone gave the p-hydroxy acid 107 in 85% yield. Esterification, silylation, and a reduction-oxidation sequence then afforded a 75% overall yield... 

Masamune has also completed a synthesis of tylonide hemiacetal (291) based on the creative use of enantioselective aldol condensations, as shown in Scheme 2.26. The aldol condensation of 328, derived from (/f)-hexahydromandelic acid and prop anal, was found to be >100 1 diastereoselective, affording the 2,3 syn compound 329 in 97% yield. Transformation to the p,7-unsaturated ester 330 occurred via selenoxide elimination and periodate cleavage followed by esterification. Formation of the silyl ether, reduction, and protection of the ester followed by ozonolysis of the terminal olefin gave the diol-protected aldehyde 331. The C-11 to C-15 segment 332 was then completed via chain elongation and a subsequent reduction-oxidation sequence in 34% overall yield from 330. 

White undertook a rather different approach to the construction of 56, as shown in Scheme 4.15. Hagemann s ester (62) was converted to the related dienol acetate and reduced to give a 68% yield of the hydroxy ester 63, contaminated with a small amount of the isomeric allylic alcohol. A reduction-oxidation sequence produced the intermediate aldehyde, which was subjected to chain extension by Wadsworth-Emmmons reaction to produce the diene ester 64 in 56% yield. 

The total synthesis of dihydrolycorine (38), the sole hydrogenation product of lycorine (6 R1 + R2 = CH2, R3 = R4 = H) and an alkaloid in its own right, has been reported.27 Scheme 3 shows how treatment of the Diels-Alder adduct (33) with methanol gave a mixture of two half-esters which were directly subjected to Friedel-Crafts cyclization to give the indanone ester (34) and a rearrangement product. Attempted Schmidt ring expansion on (34) failed, but a prior reduction-oxidation sequence followed by treatment with sodium azide and hydrolysis produced the desired lactam (35) and an isomeric compound whose structure remains undetermined. Lactam (35) was readily converted into a chain-extended... 

The synthesis of the other monooxazole, 1584 also began with Gamer s acid 1572. Chattopadhyay and Pattenden described the conversion of 1572 to 49 (Scheme 1.14). A straightforward reduction-oxidation sequence afforded 1581... 

A further application of the enamide photocyclization in yohimbine synthesis is demonstrated by Ninomiya s preparation of naucleficine (378) (Scheme 3.64) (68) Enamide 376, prepared from 336 and aroyl chloride 375, was irradiated under non-reducing conditions to form oxygambirtannine (127). Finally, a reduction-oxidation sequence afforded the target. 

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