Synthesis and functional group transformations

Several reaction types and functional group transformations will be outlined in the following sections with a major emphasis on those biocatalytic processes of major impact on enantioselective synthesis and chiral product preparation. 

In organic synthesis, a variety of enzyme-catalyzed reactions have been examined recently with expectations of highly regio- and enantioselective reactions and functional group transformation under... 

In 1967, Corey defined synthons as structural units within a molecule which are related to possible synthetic operations1. In organic synthesis, synthetic operations denote structural transformations of the molecule. This chapter deals with a number of very important synthetic operations, namely carbon-carbon bond formation and functional group transformations utilizing sulfonic acids, esters and their derivatives as synthons2. 

Enantioselective synthesis of (—)trachelanthamidine (127) took place from allylic iodoacetamide (128) by atom-transfer annulation <88JA7536> and functional group transformation. 

The prime objective and major aim of this study was to combine the efficiency of biosynthetic redox pathways and the modularity of synthesis by functional group transformations applied to diverse substrates based on the promiscuity of enzymes. Designing and evaluating the feasibility of a multi-enzyme-catalyzed cascade process in Hving microbial cells enabled the creation of an artificial mini -metaboHc pathway connected to the primary metabolism via redox-cofactor... 

An analogous Johnson-Claisen rearrangement/RCM sequence was used by Ghosh et al. in the synthesis of the carbocychc core of the nucleoside (—)-BCA (16), a protential inhibitor of HIV reverse transcriptase (Scheme 1.4) [6]. The chiral cyclopentene 20 was obtained in excellent yield through a [Ru]-I-mediated RCM of 1,6-diene 19. Further epoxidation and functional group transformations led to (—)-BCA core structure 23. 

An ability to fonn caibon-caibon bonds is fundamental to organic synthesis. The addition of Grignaid reagents to aldehydes and ketones is one of the most frequently used reactions in synthetic organic chemistry. Not only does it pennit the extension of caibon chains, but because the product is an alcohol, a wide variety of subsequent functional group transformations is possible. 

Azaloxan (12) is an antidepressant agent. Its synthesis can be accomplished starting with the reaction of catechol (7) and 3,4-dibromobutyronitrile (obtained by addition of bromine to the olefin) to give l,4-benzodioxan-2-ylacetonitrile (8). A series of functional group transformations ensues [hydrolysis to the acid (9), reduction to the alcohol (10) and conversion to a tosylate (11)] culminating in an SN-2 displacement reaction on tosylate 11 with l-(4-piperidinyl)-2-imidazolidi-none to give azaloxan (12) [3]. 

The 6-substituted 1,4-dioxocins can be used to prepare other 6-substituted derivatives by simple functional group transformations.4,8,9 Especially interesting is the synthesis of the 4/7-4-oxo-2,3-dihydropyran-2-yl-substituted derivative 16 from l,4-dioxocin-6-carbaldehyde (15) by a cyclocondcnsation with Danishefsky s diene.9 Dehydrogenation of 16 yields 2 which can be isomerized to the corresponding isomeric. sr/i-benzene dioxide 3 (X = 4/f-4-oxopyran-2-yl), which is identical with and proved the structure of the naturally occurring antibiotic LL-Z 1220.10... 

Yokoyama, M., Kashiwagi, M., Iwasaki, M. et al. (2004) Realization of the synthesis of a,a-disubstituted carbamylacetates and cyanoacetates by either enzymatic or chemical functional group transformation, depending upon the substrate specificity of Rhodococcus amidase. Tetrahedron Asymmetry, 15, 2817-2820. 

The Coleman synthesis commenced with a [4+2] cyclization to achieve naphthalene 30 (Scheme 7.4). This convergent process required four steps to obtain diene 27 and five steps to attain dieneophile 28. Three further functional group transformations were required to complete aldehyde 31. This novel process realized the installation of all the carbon and oxygen substituents in a regioselective manner. 

As for heterogeneous olefin polymerization catalysis, the activity of rare-earth metal catalysts may be also enhanced in organic transformations by the use of silica supports or other carriers [7]. Indeed, several catalytic C-C and C-X (with X = H/D, Si, O) bond formation reactions as weU as functional group transformations witness to the potential of SOLn/AnC-based heterogeneous catalysts for fine chemical synthesis. 

The structural similarity between claenone (42) and stolonidiol (38) enabled Yamada to exploit an almost identical strategy for the total synthesis of (-)-stolonidiol (38) [40]. A short retrosynthetic analysis is depicted in Fig. 12. An intramolecular HWE reaction of 68 was successfully applied for the macrocyclization. The highly substituted cyclopentanone 69 was made available by a sequence that is highlighted by the sequential Michael-Mi-chael addition between the enolate 53 and the a, -unsaturated ester 70 followed by a retro-aldol addition. However, as is the case for the claenone (42) synthesis, the synthesis of stolonidiol (38) is characterized by numerous functional and protecting group transformations that are a consequence of Yamada s synthetic strategy. 

---