Esters, hydroxy from aldehydes

Good yields of aldehydes from esters as well as hydroxyaldehydes from lactones can be obtained by reduction with NaAlH4 at low temp.— E NaAlH4 in tetra-hydrofuran added gradually at —45 to —60° to a soln. of methyl hydro-cinnamate in the same solvent, and the product isolated after 3 hrs. stirring -> hydrocinnamaldehyde. Y 80%.—Similarly d-Valerolactone 8-hydroxy-valeraldehyde. Y 75%. F. e. s. L. I. Zakharkin et al., Tetrah. Let. 1963, 2087. 

AT-Boc group, was followed by reductive debenzylation of 30 and Yamaguchi lactonization of the resultant hydroxy acid to provide macrodiolide 31 in 25% yield accompanied by a dimer. Finally, removal of the N-Boc group and reductive N-methylation yielded pamamycin-607 (lb). In total, ca. 40 steps were required to access the target from ester 4, aldehyde 22, and allyl stannanes 10 and ent-lO. 

A stereochemical behavior similar to that of the 1-bromo-l-lithio aUcene 164 with regard to chiral aldehydes is shown by the hthiated methoxyallene 183. When added to iV,iV-dibenzylated a-aminoaldehydes 188, it reacts with non-chelate control so that awh -carbinols 189 are obtained predominantly. Diastereomeric ratios of 189 190 range from 80 20 to 95 5. As outlined above, the hydroxyalkylated allenes 189/190 can be converted into furanones 191/192 upon treatment with potassium f-butoxide and subsequent acid hydrolysis" . When, on the other hand, the adducts of 183 to the aldehydes 193 are submitted to an ozonolysis, A-protected a-hydroxy-/3-amino esters 194/195 result (Scheme 25)"" . 

The carbonyl ylide generated from metal carbene can also add to C=0 or C=N bonds. The [2 + 3]-cycloaddition of carbonyl ylide with G=0 bond has been used by Hodgson and co-workers in their study toward the synthesis of zaragozic acid as shown in Scheme n 27a,27d Recently, a three-component reaction approach to syn-a-hydroxy-f3-amino ester based on the trapping of the carbonyl ylide by imine has been reported.The reaction of carbonyl ylide with aldehyde or ketone generally gives l,3-dioxolanes. Hu and co-workers have reported a remarkable chemoselective Rh2(OAc)4-catalyzed reaction of phenyl diazoacetate with a mixture of electron-rich and electron-deficient aryl aldehydes. The Rh(ii) carbene intermediate reacts selectively with electron-rich aldehyde 95 to give a carbonyl ylide, which was chemospecifically trapped by the electron-deficient aldehyde 96 to afford 1,3-dioxolane in a one-pot reaction (Equation (12)). 

Transfer of hydrogen from C-4" of uridine 5 -(a-D-glucopyranosylur-onic acid pyrophosphate) to C-3 of the apiosyl group in the ester 117 has been demonstrated.4458 The conversion of 116a into 118 was hypothesized446 to involve aldol cleavage, isomerization of the resulting a-hydroxy aldehyde, and intramolecular, aldol reaction as shown. 

The derived hydroxy-aldehyde was selectively oxidised via its cyanohydrin derivative to the corresponding hydroxy-methyl ester 9. Thinyl radical, generated photolytically from thiophenol, attacked, due to steric reason, regioselectively the terminus of the arylacetylene unit... 

Recently, Corey and coworkers prepared the cinchonidine-derived bifluoride 20 from the corresponding bromide by passage of a methanolic solution through a column of Amberlyst A-26 OH- form, and subsequent neutralization with 2 equiv. of 1 N HF solution and evaporation (the modified method C in Scheme 9.5). The catalytic activity and chiral efficiency of 20 (dried over P205 under vacuum) have been demonstrated by the development of a Mukaiyama-type aldol reaction of ketene silyl acetal 21 with aldehydes under mild conditions, giving mostly syw-P-hydroxy-a-amino esters 22 as the major diastereomer with good to excellent enantiomeric excesses (Table 9.4) [23],... 

Tetramethylcyclohexanes.—Esters of ferulol (145) are present in Scaevola lobelia243 and Cenolophium fischeri244 (cf. Vol. 5, p. 28), and spectroscopic data are recorded for the ester (146) of the isomeric hydroxy-aldehyde isolated from the latter and from Bupleurum gilbraltaricum.244... 

The reaction of a-fluoro-/f-hydroxy-a-phenylsulfanyl esters 4, which can be readily synthesized from aldehydes and ethyl bromofluoroacetate, with diethylaminosulfur triduoride leads to the formation of a,o -difluoro-/I-phenylsulfanyl esters Instead of the expected substitution of the j8-hydroxy group by fluorine, a rearrangement via an episulfonium ion and addition of a fluoride ion % to the ester function gives the a,a-difluorinated product 5. The reaction proceeds under mild conditions with moderate to good yields. In the case of ethyl 2-fluoro-3-hydroxy-3-phenyl-2-(phcnylsulfanyl)propanoate only the nonrearranged product ethyl 2.3-di-fluoro-3-phenyl-2-(phenylsulfanyr)propanoate was isolated. 

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. 

Boc-L-Leucinal 1s a useful chiral synthon in the preparation of the natural amino acid statine [S-(R, R )]-4-am1no-3-hydroxy-6-methylheptanoic acid (3S.4S). The procedure reported here Is based on the method of Fehrentz and Castro for the preparation of optically active Boc amino aldehydes from a-amino acids. It Is satisfactory on a kilogram scale. Boc-L-Leucinal has also been prepared by the reduction of Boc-L-leucine methyl ester with d1Isobutyl aluminum hydride or by oxidation of Boc-L-leucinolThe reaction conditions described here differ from those In the literature. The N-... 

A series of innovative investigations by Kiyooka and co-workers have introduced the use of tandem reaction processes that commence with a stereoselective aldol addition reaction and are followed by C=0 reduction [13]. A chiral oxazaboroli-dine complex prepared from BH3-THF and A-/ -toluenesulfonyl (L)-valine controls the absolute stereochemical outcome of the aldol reaction. In a subsequent reaction, the /i-alkoxyboronate effects intramolecular reduction of the ester to furnish the corresponding /i-hydroxy aldehyde. 

A marked improvement of the enantioselectivity was achieved by Corey and coworkers by using a bifluoride catalyst 4 [5]. Bi fluoride derivatives such as 4 are usually less hygroscopic than monofluorides such as 1 and thus easier to handle. Using catalyst 4 (10 mol%), the silyl enol ethers S reacted with various aliphatic aldehydes smoothly at —70 °C via the aldol coupling reaction to afford the chiral 5-hydroxy-a-amino esters 6 with moderate to good enantioselectivily for the syn adduct (72-89% ee) (Scheme 8.2). However, the diastereoselectiviy varied from 1 1 to 13 1 (syn anti). 

---