Trans-Olefin benzylation

INTRA- AND INTERMOLECULAR KULINKOVICH CYCLOPROPANATION REACTIONS OF CARBOXYLIC ESTERS WITH OLEFINS BICYCLO[3.1.0]HEXAN-1-OL AND trans-2-BENZYL-l-METHYLCYCLOPROPAN-l-OL... 

Because the olefin geometry in compound 9 will most certainly have a bearing on the stereochemical outcome of the hydroboration step, a reliable process for the construction of the trans trisubsti-tuted olefin in 9 must be identified. A priori, the powerful and predictable Wittig reaction28 could be used to construct E u, [3-unsaturated ester 10 from aldehyde 11. Reduction of the ethoxycarbonyl grouping in 10, followed by benzylation of the resulting primary alcohol, would then complete the synthesis of 9. Aldehyde 11 is a known substance that can be prepared from 2-furylacetonitrile (12). 

A cursory inspection of key intermediate 8 (see Scheme 1) reveals that it possesses both vicinal and remote stereochemical relationships. To cope with the stereochemical challenge posed by this intermediate and to enhance overall efficiency, a convergent approach featuring the union of optically active intermediates 18 and 19 was adopted. Scheme 5a illustrates the synthesis of intermediate 18. Thus, oxidative cleavage of the trisubstituted olefin of (/ )-citronellic acid benzyl ester (28) with ozone, followed by oxidative workup with Jones reagent, affords a carboxylic acid which can be oxidatively decarboxylated to 29 with lead tetraacetate and copper(n) acetate. Saponification of the benzyl ester in 29 with potassium hydroxide provides an unsaturated carboxylic acid which undergoes smooth conversion to trans iodolactone 30 on treatment with iodine in acetonitrile at -15 °C (89% yield from 29).24 The diastereoselectivity of the thermodynamically controlled iodolacto-nization reaction is approximately 20 1 in favor of the more stable trans iodolactone 30. 

Following Uskokovic s seminal quinine synthesis [40], Jacobsen has very recently reported the first catalytic asymmetric synthesis of quinine and quinidine. The stereospecific construction of the bicyclic framework, introducing the relative and absolute stereochemistry at the Cg- and expositions, was achieved by way of the enantiomerically enriched trans epoxide 87, prepared from olefin 86 by SAD (AD-mix (3) and subsequent one-pot cyclization of the corresponding diol [2b], The key intramolecular SN2 reaction between the Ni- and the Cg-positions was accomplished by removal of the benzyl carbamate with Et2AlCl/thioanisole and subsequent thermal cyclization to give the desired quinudidine skeleton (Scheme 8.22) [41],... 

Hori and co-workers accomplished the first synthesis of azathianaphthalene and azathiaphenanthrene in 1979 <79TL3969>. Their approach began with the formation of an olefin from o rt/20 -ni t ro b e n za 1 dehyde 43, via a Wittig reaction with an ylide and a subsequent reduction with zinc to afford cis and trans ortho-aminostyryl methyl sulfide 45. The cis-olefin was then treated with NCS, AgCKAi and KOH to yield 2-methyl- l-aza-2-thianaphthalene 47 in 41% yield. 9-Methyl- 10-aza-9-thiaphenanthrene 48a and 9-ethyl-10-aza-9-thiaphenanthrene 48b were obtained in a similar fashion in almost quantitative yields, whereas 6-benzyl-67/-d i b e n zo [ c, e] [ 1,2 J t h i azi n cs 50 were isolated in moderate yields via a 1,2-rearrangement (Scheme 13) <90TL7021>. 

The is-olefin was prepared as a trans-amide bond replacement. A number of compounds incorporating substituents to mimic both natural and unnatural amino acid sidechains were prepared by adapting chemistry developed by Ibuka for the synthesis of Zs-olefin peptide isosteres (see Scheme l).40,41 The key step involved anti-SN2 displacement of vinyl mesylate 8 by boron trifluoride-activated cuprate addition. Compounds containing butyl, propyl, and benzyl substituents at the allylic positions to mimic the aj and sidechains produced potent FTase inhibitors (Table 4). 

Eliminations from the benzyl derivatives of Figure 4.3 take place preferentially to form the trans- and only to a lesser extent the civ-olefin. This is independent of whether the elimination mechanism is vyw-selective or awfi-selective or neither. 

Mixed esters of oxalate containing one benzylic substituent are reduced in good yield using in situ trans-esterification to the corresponding hydrocarbon and oxalate half-ester [72]. Esters of vicinal diols (including cyclic carbonate esters) [73] and -halo esters [74] are often reduced to the corresponding olefin [72,75]. 

An interesting olefination of electron-deficient ketones by alkanesulfonyl halides using KF probably involves sulfene formation. The removal of the fluorenylmethoxy-carbonyl (Fmoc) group from amino acids and peptides with KF/18-crown-6 does not affect methyl, ethyl, f-butyl, benzyl, and p-methoxybenzyl groups. Actually tran-scarbamoylation (into Boc and Cbz groups) can be accomplished in one flask, by presenting the proper electrophiles in the reaction mixture. ... 

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