Primary from hydride reduction

From intermediate 28, the construction of aldehyde 8 only requires a few straightforward steps. Thus, alkylation of the newly introduced C-3 secondary hydroxyl with methyl iodide, followed by hydrogenolysis of the C-5 benzyl ether, furnishes primary alcohol ( )-29. With a free primary hydroxyl group, compound ( )-29 provides a convenient opportunity for optical resolution at this stage. Indeed, separation of the equimolar mixture of diastereo-meric urethanes (carbamates) resulting from the action of (S)-(-)-a-methylbenzylisocyanate on ( )-29, followed by lithium aluminum hydride reduction of the separated urethanes, provides both enantiomers of 29 in optically active form. Oxidation of the levorotatory alcohol (-)-29 with PCC furnishes enantiomerically pure aldehyde 8 (88 % yield). 

The homology between 22 and 21 is obviously very close. After lithium aluminum hydride reduction of the ethoxycarbonyl function in 22, oxidation of the resultant primary alcohol with PCC furnishes aldehyde 34. Subjection of 34 to sequential carbonyl addition, oxidation, and deprotection reactions then provides ketone 21 (31% overall yield from (—)-33). By virtue of its symmetry, the dextrorotatory monobenzyl ether, (/ )-(+)-33, can also be converted to compound 21, with the same absolute configuration as that derived from (S)-(-)-33, by using a synthetic route that differs only slightly from the one already described. 

Cembranoids The first macrocyclic diterpene isolated from an Eremophila species was the triol (99) produced by E. clarkei (96). The resin obtained from this plant was a complex mixture of compounds from which the crystalline triol could be obtained with difficulty from the neutral fraction. Larger quantities of triol were available after methylation and lithium aluminium hydride reduction of the acidic fraction. The plane structure of 99 was established by conversion of the triol to a crystalline stereoisomer of cembrane (100) as shown in Scheme 25. The two dihydrotriols (101 and 102) obtained in this sequence also served to prove the location of the hydioxymethylene groups on the cembrane skeleton. Since both 101 and 102 are optically active, the symmetrical 4,12-cis arrangement of the primary alcohol groups can be excluded. Furthermore, the 4, 2-trans-disposition of these groups can also be excluded since elimination of the asymmetry at Cl leads to two different olefins (103 and 104). 

Alternatively, the diastereomeric mixture of aldol adducts undergoes lithium aluminum hydride reduction, primary alcohol silylation, and chromatographic separation to afford 291. Subsequent Mitsunobu inversion at C-3 to furnish the j -alcohol 292 followed by a depro-tective sequence and ring closure provides (+ )-castanospermine (293). This poly-hydroxylated indolizidine alkaloid isolated from Castanospermum australe and Alexa leipetala is a potent inhibitor of various a- and j8-glucosidases [98] (Scheme 68). 

Finally, the etiojervane analogue of corticosterone (236) has been synthesized from jervine (231), through the known intermediate (232). The unsaturated a-hydroxy-ester (233) was prepared from (232) by a Darzens reaction, followed by boron trifluororide rearrangement. Selective catalytic hydrogenation and lithium aluminium hydride reduction gave a tetraol, isolated as its acetonide (234), which by oxidation at C-3 gave the ajS-unsaturated ketone (235). The last steps of the sequence, which involved modifications of the side-chain, entailed acid hydrolysis, acetylation of the primary alcohol, and oxidation at C-20 to give (236)." ... 

A Pinner reaction between the primary amine (403) and the thioimidate (404) (from the thioamide and iodomethane) gave xylamidine (405) (Scheme 5.94.). Base catalysed reaction between 2-chloropropionitrile and 3-methoxyphenol followed by lithium aluminium hydride reduction provided the amine (403). Xylamidine is a powerful 5HT2 receptor antagonist, and has some value in pharmacological research [551],... 

N-Sitylimine 89 in ether at -78°C was asymmetrically alkylated with butyl-Uthium in the presence of the diUthium alkoxide of the chiral diol 93 (76%, 62% ee) (Scheme 27) [76]. Addition of the preformed (-)-sparteine (19)-BuLi complex to benzaldehyde N-diisobutylaluminoimine 90, prepared in situ from partial reduction of benzonitrile with diisobutylaluminum hydride, in pentane at -78°C gave the primary amine 92 in good ee (70% yield, 74% ee) [77]. The use of polymer-supported amino alcohol 94 in THF at -78°C allows the asymmetric alkylation of an M-borylimine 91 to give the primary amine 92 with 44% ee [77]. 

Valenta et al. confirmed the structure by synthesis of a lyconnotine derivative (98). They converted the alkaloid to ketone CVII which was synthesized in an unequivocal fashion. Ketone CVII was derived from lyconnotine according to the following scheme. Hydride reduction of lyconnotine followed by catalytic reduction and subsequent acetylation gave the saturated diacetate CVIII which deactivated preferentially at the primary hydroxyl group. The hydroxy acetate was then converted to the bromide which underwent hydrogenolysis on treatment with Zn in acetic acid. Hydrolysis of the monoacetate and oxidation of the result-... 

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