Stereocontrolled functionalization

Stereocontrolled functionalization of steroidal side chains in nature is closely related to the function of steroids in living organisms. The regio- and stereochemistry of functional groups exert strong influence on the biological activities of steroids. Due to their multi-functional nature, the homoenolates provide an effective tool for synthetic efforts in this field. 

The C32-C37 segment [83] Butenolide 113 [89] was treated with lithium dimethyl cuprate [89] and further transformed into epoxide 115. A two-carbon extension followed by a stereocontrolled functionalization of the butenolide as described for the construction of the C14-C20 segment readily gave lactone 116. Necessary adjustments of the oxidation level at C s and C39 with concomitant configurational inversion at C37 executed in a seven-step route as exposed in Scheme 14 provided the required C32-C37 segment 117. 

Woodward s synthesis of erythronolide A (13) takes advantage of a rigid dithiodecalin ring 11 as a template that is relied upon in the sequential stereocontrolled functionalization of the ring carbons (Scheme 1.2) [14, 15], These ultimately constitute the C9-C13 subunit found in erythronolide A. After having fulfilled their role as conformation locks, the sulfides are re-ductively excised from 11 to reveal the requisite, stereochemically rich fragment 12. 

Apply stereoselective transforms to reduce the number of reactive functional groups, especially those of sufficient reactivity to cause interference with stereocontrolled C-C disconnective transforms. 

A drawback of tlie Z enoates is usually lower reactivity, rehected in prolonged reaction times and bigliet reaction temperatures. Tliis may be overcome by switdi-ing to more reactive enone systems. Tlius, addition of tlie functionalized cyano-G dnian cuprate s7stem 67 to Z enone 66 proceeded smootlily at low temperatures, witli excellent acydic steteocontrol at tlie /J-steteocenter [26, 27]. Stereocontrol upon... 

The intramolecular cycloaddition of a nitrile oxide (a 1,3-dipole) to an alkene is ideally suited for the regio- and stereocontrolled synthesis of fused polycyclic isoxazolines.16 The simultaneous creation of two new rings and the synthetic versatility of the isoxa-zoline substructure contribute significantly to the popularity of this cycloaddition process in organic synthesis. In spite of its high degree of functionalization, aldoxime 32 was regarded as a viable substrate for an intramolecular 1,3-dipolar cycloaddition reaction. Indeed, treatment of 32 (see Scheme 17) with sodium hypochlorite... 

More functionalized 5,6-dihydro-2H-pyran-derivatives 71 and 72 have been prepared [26] by cycloaddition of 1 -methoxy-3-trialkylsilyloxy-1,3-butadienes 69 with t-butylglyoxylate (70) (Scheme 5.6). Whereas thermal reactions did not occur in good yields because of the decomposition of the cycloadducts, application of pressure (10 kbar) allowed milder conditions to be used, which markedly improved the reaction yields. The use of high pressure also gives preferentially en Jo-adduct allowing a stereocontrolled synthesis of a variety of substituted 5,6-dihydro-2H-pyran-derivatives, which are difficult to prepare by other procedures. 

Posner G. H. Stereocontrolled Synthesis of Functionalized Cyclohexenes Via Diels-Alder Cycloadditions of 2-Pyrones and 2-Pyridones-Applications to Synthesis of Physiologically Active Compounds in Stereocontrolled Org. Synth. 1994 177, Ed. Trost B. M., Pb. Blackwell Oxford... 

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