Urethans aldehydes, synthesis

A total synthesis of O-methylarnottianamide (223) was performed by Falck et al. (177) (Scheme 34). The regio- and stereospecific cycloaddition of the 2,4-dinitrophenyl (DNP) salt of 6,7-methylenedioxyisoquinoline (218) with a-methoxystyrene 219 resulted in 220. Compound 220 was hydrolyzed, then aromatized, and the resultant aldehyde was oxidized to carboxylic acid 221. Curtius rearrangement of the appropriate azide yielded urethane 222, which... 

At low temperatures, the Zn enolate derived from dimethyl 3-methylpent-2-endioate 39 reacts with aldehydes in a one-pot aldolisation and cyclisation to yield the syn-dihydropyran-2-one 40. At the higher temperatures necessary to achieve reaction with a-aminoaldehydes, the anri-products predominate indicating thermodynamic control (Scheme 22) <99T7847>. An aldol condensation features in the asymmetric synthesis of phomalactone. The key step is the reaction of the enolate of the vinylogous urethane 41 with crotonaldehyde which occurs with 99% syn-diastereoselectivity and in 99% ee (Scheme 23) <99TL1257>. 

Another chiral vinylogous urethane, 677, played a central role in the synthesis of (- )-652 by Lhommet and co-workers (Scheme 90) 494). This compound, prepared from (/ )-a-methylbenzylamine (678) (495), was diastereoselectively hydrogenated over platinum oxide to give the amino-ester 679 (de >95%). More significantly, methylation of the anion of 679 under conditions of kinetic control afforded 680 (de ca 98%) in 33% overall yield from the chiral amine 496). Wittig reaction of the aldehyde derivative 681 with the stabilized ylide l-(triphenylphosphoranylidene)-2-heptanone yielded 682 (90%) as a 4 1 mixture of E and Z isomers. When this product... 

Numerous procedures have been reported for the synthesis of iV-protected-a-amino aldehydes [78]. The A-protected a-amino aldehydes can be prepared either by oxidation of the corresponding A-protected j8-amino alcohols with oxidants such as pyridinium dichromate [79,80] or SOs-pyridine-di-methyl sulfoxide (DMSO) [81] or under Swem conditions [DMSO-oxalyl chloride-A,A-diisopropylethylamine (DIEA)] [81-83], by reduction of esters with diisobutyl aluminum hydride (DIBAL) [84], by reduction of A,A-disubstituted amides [85-87], by reduction of urethane-protected A-carboxy-... 

The Ag- or Pd-mediated intramolecular cyclization of urethanes onto allylic substituents is used in the synthesis of piperidine alkaloids <97JOC776, 97CL221>. Similarly, the tungsten-mediated cyclization of urethanes on alkynes via the metal vinylidene carbene has been reported <97TL7687>. Ni-catalyzed intramolecular cyclization of a 1,3-diene side chain of 5 8 onto an aldehyde affords a precursor to the indolizidine alkaloid (-)-elaeokanine C <97TL3931>. 

Elsewhere, two methods for the preparation of 2-( -alkylamino)-1,3-diols from 2,3-epoxy-alcohols were described. The first involved sequential transformation of the epoxy-alcohol into an epoxy-urethane and thence to a 2-oxazolidinone, the second consisting of treating the epoxide derivative directly with benzyl isocyanate and sodium hydride in THE (Scheme 20). This methodology was utilised in the synthesis of (+)-erythro-dihydrosphlngoslne from palmitic aldehyde. 

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