Lithium benzyl oxide cleavage

Scheme 10.8 outlines the application of rhodium-catalyzed allyhc amination to the preparation of (il)-homophenylalanine (J )-38, a component of numerous biologically active agents [36]. The enantiospecific rhodium-catalyzed allylic amination of (l )-35 with the lithium anion of N-benzyl-2-nitrobenzenesulfonamide furmshed aUylamine (R)-36 in 87% yield (2° 1° = 55 1 >99% cee) [37]. The N-2-nitrobenzenesulfonamide was employed to facilitate its removal under mild reaction conditions. Hence, oxidative cleavage of the alkene (R)-36 followed by deprotection furnished the amino ester R)-37 [37, 38]. Hydrogenation of the hydrochloride salt of (l )-37 followed by acid-catalyzed hydrolysis of the ester afforded (i )-homophenylalanine (R)-3S in 97% overall yield. 

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-... 

The completion of the synthesis of key intermediate 2 requires only a straightforward sequence of functional group manipulations. In the presence of acetone, cupric sulfate, and camphorsulfonic acid (CSA), the lactol and secondary hydroxyl groups in 10 are simultaneously protected as an acetonide (see intermediate 9). The overall yield of 9 is 55 % from 13. Cleavage of the benzyl ether in 9 with lithium metal in liquid ammonia furnishes a diol (98% yield) which is subsequently converted to selenide 20 according to Grie-co s procedure22 (see Scheme 6a). Oxidation of the selenium atom... 

The perhydro-isoxazolo[2,3-fl]pyridine system offers a route to 2,6-disubstituted piperidines. For example, the reaction between styrene and the substituted 3,4,5,6-tetrahydropyridine-l-oxide (69) gives the isoxa-zolidine (70) which, on benzylation, gives 71. This was subjected to reductive cleavage of the N—O bond with lithium aluminum hydride, followed by mesylation of the aminodiol produced. Treatment of the mesylate with lithium triethylborohydride gave the trans-2,6-disubstituted piperidine... 

On the other hand, reductive cleavage of the dienone lactam 91 with chromium(II) chloride gave the dibenz[with lithium aluminum hydride. Deprotection of 76biosynthetic precursor of the Schelhammera alkaloids. Oxidation of the diphenol 76a by potassium ferricyanide in the two-phase system gave the expected 5,7-fused dienone 77 in 61% yield (50). 

Thus, the aldol shown, which is susceptible to Sharpless-type epoxidation, has been obtained from phytal and the protected hydroquinone (ref. 120). Formation of the epoxide presumably with a chiral peracid (or perhaps with a conventional peracid relying on the asymmetry of the substrate) and then cleavage reductively in t-butyl methyl ketone containing lithium aluminium hydride led to a diol. The benzylic hydroxyl group of this was hydrogenolysed to afford the hydroquinone dimethyl ether in 85% yield. Ceric ammonium nitrate (CAN) oxidation afforded the intermediate benzoquinone hydrogenation of which was reported to result in 2R,4 R,8 R-a-tocopherol by, presumably, avoidance of a racemisation step. 

The electrolytic oxidation of the sodium salt of (+ )-N-ethoxycarbonyl-Al-norarmepavine (46) led to the dimeric mixtures (47) and (48). The latter mixture was converted into a mixture of dauricine analogues (49) via O-benzylation, reduction with lithium aluminium hydride, and hydrogenolytic debenzylation. This transformation represents the first preparation of an analogue of a natural bis-benzylisoquinoline by oxidation of a phenolic monomeric benzylisoquinoline. Detailed studies on the mass-spectral cleavage patterns of bisbenzylisoquinolines have appeared. 

The myo-inositol acceptor l-0-allyl-2,3,4,5-tetra-0-benzyl-D-myo-inositol was synthesized from meso-2,5-di-0-benzoyl-myo-inositol for use in the total synthesis of a heptaose mimetic, a GPI anchor compound of T. brucei (see Vol. 32, p.71. ref. 156). The inositol was desymmetrized using the bis(spiroketal) protected intermediate 175 to enable the stepwise glycosylation at 0-6 and attachment of a phosphoglyceride moiety at 0-1. Cleavage of the dispoke was effected by oxidizing the thiophenyl substituents with mCPBA and then treating the product disulfone with lithium hexamethyldisilazide in THF. In a similar synthesis... 

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