From Cyclic Precursors

One method to generate cyclic amino acids is to begin with a cyclic precursor. Refunctionalization of the existing groups lead to the amino acid. 

Diethyl malonate was converted to cyclobutane derivative 7.8 by classical condensation chemistry. 1 Saponification of the ester moieties was followed by thermal decarboxylation to give 7.9. Esterification, deprotection of the alcohol and conversion to a tosylate allowed its displacement by ammonia to give methyl 3-amino-cyclobutane carboxylate (7.10, as a 33 67 cis. trans mixture) but the yield was remarkably poor.l 

A better method used irons-cyclobutane dicarboxylate (7.11) and selective hydrolysis of one ester liberated an acid that could be reduced with borane to give 7.12.2 Conversion of that alcohol to a tosylate was followed by reaction with 

A different approach converted the ketone moiety in cis-pinononic acid [7.75, derived by permanganate oxidation of (-)-2-hydroxy pinocamphone] to an oxime (7.16). Raney nickel reduction and Beckmann rearrangement of the oxime gave 7.77. Subsequent treatment with hydrazine gave 3-amino-2,2-dimethyl-cyclobutane carboxylic acid (7.75). 

Another tefunctionalization reaction converted an allylic acetate to a 38 62 

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Scheme 9.19 Formation and trapping of monomeric (Tbt)B=E (E = S, Se) from cyclic precursors.

R Dreher, K Poralla, WA Konig. Synthesis of w-alicyclic fatty acids from cyclic precursors by Bacillus subtilis. J Bacteriol 127 1136-1140, 1976. 

Some ylides from cyclic precursors are thermally labile and isomerize to iodo-enol ethers for example, the ylide of dimedone afforded 2-iodo-3-phenoxy-5,5-dimethyl-2-cyclohexanone [41], A similar reaction involving cleavage of the I-Cphenyi bond occurred with triethylphosphite 2-iodo-3-ethoxy-5,5-dimethyl-2-cyclohexen-l-one was the main product (65%) [42],... 

One way around this difficulty is to generate the tetramethylenes from the cyclobutane adducts. The cyclobutane adduct of NVCz and tetracyanoethylene placed in a solution of excess /V-vinylcarbazole causes cationic homopolymerization of the latter [136]. However a cyclobutane whose substitution pattern will lead on cleavage to a tetramethylene diradical at reasonable temperatures has not yet been found. A possible explanation is that a tetramethylene diradical has one less bond than a tetramethylene zwitterion, and so is less stable [137]. Another explanation may be that tetramethylene zwitterions prefer to exist in the cis form for coulombic reasons, but tetramethylene diradicals appear to prefer a trans, extended conformation and are difficult to generate from cyclic precursors. 

Table 3 Major products formed from cyclic precursors on ZSMS and Mordenite ...

Fragmentation reactions may be used to prepare cyclic or acyclic alkenes from cyclic precursors. The stereochemistry of the alkene can be set up by controlling the relative stereochemistry of the cyclic substrate, a process that is normally relatively easy. The ketone 35, for example, an intermediate in a synthesis of juvenile hormone, was obtained stereospecifically from the bicyclic compound 33 using two successive... 

Scheme 3 depicts preparative routes to NHC I from cyclic precursors. The extrusion of heterocumulenes, such as carbon dioxide from suitable precursors II, the deprotonation of hetarenium salts HI, the a-ehmination... 

The preparation of acyclic molecules from cyclic precursors is a well-known strategy. The ability to control relative stereochemistry and regiochemistry in the reactions of cyclic molecules is important since cleavage of that ring transfers the resident stereochemistry and/or regiochemistry to the acyclic product Several methods will be described in this chapter that lead to the synthesis of amino acids, particularly substituted amino acids, from various cyclic precursors. 

Scheme 1.5 Preparation of NHCs from cyclic precursors.

Poly(Aryl Ether) From Cyclic Precursors... 

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