Aldehydes, allenic reduction

The full paper has appeared on a synthesis of steviol. The route was based on the stereocontrolled photoaddition of allene to the cyclopentene-1-aldehyde (178), reduction of the aldehyde, and then solvolysis of the methanesulphonate (179). Papers on the synthesis of the aromatic ether (180) and on the construction of the c/d ring system of the alkaloid chasmanine " have been published. 

The mechanism of [3 + 2] reductive cycloadditions clearly is more complex than other aldehyde/alkyne couplings since additional bonds are formed in the process. The catalytic reductive [3 + 2] cycloaddition process likely proceeds via the intermediacy of metallacycle 29, followed by enolate protonation to afford vinyl nickel species 30, alkenyl addition to the aldehyde to afford nickel alkoxide 31, and reduction of the Ni(II) alkoxide 31 back to the catalytically active Ni(0) species by Et3B (Scheme 23). In an intramolecular case, metallacycle 29 was isolated, fully characterized, and illustrated to undergo [3 + 2] reductive cycloaddition upon exposure to methanol [45]. Related pathways have recently been described involving cobalt-catalyzed reductive cyclo additions of enones and allenes [46], suggesting that this novel mechanism may be general for a variety of metals and substrate combinations. 

Lauryl alcohol has been prepared by the reduction of the aldehyde with zinc dust and acetic acid 1 by the reduction of esters of lauric acid with sodium and absolute alcohol 2 or with sodium, liquid ammonia, and absolute alcohol 3 by the reduction of lauramide with sodium and amyl alcohol.4 The method in the above procedure is essentially that described by Levene and Allen.5... 

Clavepictines A and B (210 and 211, respectively) were obtained from the allenic ester 227. The reduction of its ester group to aldehyde, followed of addition to the latter of hexylmagnesium bromide, OH protection, and N-deprotection gave compound 228. A silver(i)-mediated cyclization of this compound afforded quinolizidine 229 and its C-6 epimer in a 7 1 ratio (Scheme 44). The former compound was readily converted into the target alkaloids <1997JOC4550>. 

Carbon dioxide instead of aldehydes can be involved in Ni(0)-promoted reductive coupling reactions (Equations (76) and (77) Scheme 90).434,434a 434c A stoichiometric amount of Ni(COD)2/DBU reacts with C02 and dienes, alkynes, or allenes to afford a metallacycle intermediate. This metallacycle reacts with organozinc compounds or aldehydes in one-pot to give carboxylic acid derivatives. As shown in Scheme 90, double carboxylation occurs in the presence of dimethylzinc, where the stereochemical outcome is opposite to that of the reaction with diphenylzinc. 

Although detailed mechanistic studies are not reported, the postulated mechanism for the reductive cyclization of allenic carbonyl compounds involves entry into the catalytic cycle via silane oxidative addition. Allene silylrhodation then provides the cr-allylrhodium hydride A-18, which upon carbometallation of the appendant aldehyde gives rise to rhodium alkoxide B-14. Oxygen-hydrogen reductive elimination furnishes the hydrosilylation-cyclization product... 

A proposed mechanism of the bis(allene) cyclization involves the formation of the allyl(stannyl)palladium species 6, which undergoes carbocyclization to give vinyl(stannyl)palladium intermediate 7 (Scheme 36). Reductive elimination and cr-bond metathesis may lead to the formation of the m-pentane derivative and the bicyclic product, respectively. The cyclization of allenic aldehydes catalyzed by a palladium complex was also reported.163... 

The stereospecific reduction of a 2-butyne-l, 4-diol derivative and silver( I)-mediated cyclization of the resulting allene were successively applied to a short total synthesis of (+)-furanomycin 165 (Scheme 4.42) [68], Stereoselective addition of lithium acetylide 161 to Garner s aldehyde in the presence of zinc bromide afforded 162 in 77% yield. The hydroxyl group-directed reduction of 162 with LiAlH4 in Et20 produced the allene 163 stereospecifically. Cyclization followed by subsequent functional group manipulations afforded (+)-furanomycin 165. 

Phosphorylated allenes 195 (R1 = H or Me) are a source of secondary ( )-allylamines. The allenes are treated with an amine R2NH2 (R2 = t-Bu or 4-MeCgH4 and the products, which exist as equilibrium mixtures of enamines 196 and imines 197, are olefinated by successive reaction with methyllithium and an aldehyde R3CHO (R = i-Bu, 4-MeCgH4, PhCH2CH2 etc). Reduction with sodium borohydride finally yields the... 

Access to the corresponding enantiopure hydroxy esters 133 and 134 of smaller fragments 2 with R =Me employed a highly stereoselective (ds>95%) Evans aldol reaction of allenic aldehydes 113 and rac-114 with boron enolate 124 followed by silylation to arrive at the y-trimethylsilyloxy allene substrates 125 and 126, respectively, for the crucial oxymercuration/methoxycarbonylation process (Scheme 19). Again, this operation provided the desired tetrahydrofurans 127 and 128 with excellent diastereoselectivity (dr=95 5). Chemoselective hydrolytic cleavage of the chiral auxiliary, chemoselective carboxylic acid reduction, and subsequent diastereoselective chelation-controlled enoate reduction (133 dr of crude product=80 20, 134 dr of crude product=84 16) eventually provided the pure stereoisomers 133 and 134 after preparative HPLC. 

Selective 1,4-reduction of unsaturated aldehydes and ketones by 6 occurs smoothly in THF between —25 °C and room temperature within a few hours (Eq. 5.7). Particularly noteworthy is the realization that phosphines are noticeably absent from the reaction medium. The analogous combination of CuCl/BusSnH in N-methyl-2-pyrrolidinone (NMP) or DMF does not behave identically [22], failing to react with the hindered substrate isophorone, whereas a 72% yield of the corresponding reduced ketone is formed with reagents XCu(H)Li/Bu3SnH. Nonetheless, a form of CuH is being generated in this more polar medium, effectively utilized by Tanaka to arrive at 3-norcephalosporin 8 upon reaction with allenic ester 7 (Scheme 5.3). 

Reductive coupling of 1,1-dimethylallene and 5-nitro-2-furancarboxaldehyde under a deuterium atmosphere provides the product of ferf-prenylation incorporating deuterium at the interior vinylic position (80% H). This result is consistent with a mechanism involving allene-aldehyde oxidative coupling. However, alternate pathways involving allene hydrometallation to furnish allyliridium species cannot be excluded on the basis of these data (Scheme 10). 

Certain structural indications of thromboxane A2 biosynthesis inhibition and hence potential therapeutic utility in arterial thrombosis prompted the synthesis of the pyridine prostanoid 544 (Scheme 165) (83TL3291). Brief metalation of 42 followed by DMF quench afforded aldehyde 541, which upon Homer-Emmons chain extension, reduction, and protection gave 542. Having served as a DMG, the bromo function was subjected to metal-halogen exchange, transmetalation (CuCN), and condensation with an iodo allene to furnish the 3,4-disubstituted pyridine 543. The latter was transformed into two derivatives 544 (with and without double bond), which were shown to be effective inhibitors of thromboxane A2. 

The use of chiral oxazaborolidines as catalysts for the enantioselective addition of alkynylboranes to aldehydes took place in a manner analogous to the asymmetric reduction of ketones with boranes mediated by proline-derived oxazaborolidines (Equation (127)).587 Addition of alkynylboranes to A-aziridinylimines provided a convenient method to prepare allenes from carbonyl compounds (Equation (128)).5... 

An interesting and useful variation on the electroreductive cyclization theme calls for the use of substrates wherein an allene or alkyne is tethered to an aldehyde or ketone [38]. As exemplified by the conversion of 139 or 143 to 141, the reductive cyclizations lead to an allylic alcohol. This functionality, of course, is exceptionally useful, offering the opportunity for a host of followup reactions to be employed. 

Reductive deoxygenation-rearrangement of 2-yne-l,4-diols to 1,3-dienes is a useful synthetic procedure since a large variety of ynediols are available in a few steps by sequential reaction at both ends of acetylene with aldehydes. Acetylenic 1,4-diols can be deoxygenated reductively by lithium aluminium hydride to form conjugated dienes of high stereoisomeric purity (equation 9). A modification to this procedure is the use of acetylenic 1,4-diol mono-THP derivative. Allenic tertiary alcohols which are intermediates in the reaction can be separated and subjected to reductive elimination rearrangement... 

Synthesis of the acyclic portion began, as in the previous synthesis, with enantiomerically pure citronellol (25). Protection of the alcohol as the benzyl ether and oxidative cleavage of the olefin to the aldehyde gave 26 (85%). Chain extension via the masked acyl anion equivalent 27, alcohol protection, and concomitant -elimination and isomerization of the allene to die alkyne with butyl lithium gave 28. The resulting protected ketone must now be converted to the P-alcohol required for the completion of the synthesis. Thus hydrolysis to die ketone followed by enantioselective reduction with (—)-N-methylephedrine-... 

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