Cycloalkenes reductive, selective

An obvious drawback in RCM-based synthesis of unsaturated macrocyclic natural compounds is the lack of control over the newly formed double bond. The products formed are usually obtained as mixture of ( /Z)-isomers with the (E)-isomer dominating in most cases. The best solution for this problem might be a sequence of RCAM followed by (E)- or (Z)-selective partial reduction. Until now, alkyne metathesis has remained in the shadow of alkene-based metathesis reactions. One of the reasons maybe the lack of commercially available catalysts for this type of reaction. When alkyne metathesis as a new synthetic tool was reviewed in early 1999 [184], there existed only a single report disclosed by Fiirstner s laboratory [185] on the RCAM-based conversion of functionalized diynes to triple-bonded 12- to 28-membered macrocycles with the concomitant expulsion of 2-butyne (cf Fig. 3a). These reactions were catalyzed by Schrock s tungsten-carbyne complex G. Since then, Furstner and coworkers have achieved a series of natural product syntheses, which seem to establish RCAM followed by partial reduction to (Z)- or (E)-cycloalkenes as a useful macrocyclization alternative to RCM. As work up to early 2000, including the development of alternative alkyne metathesis catalysts, is competently covered in Fiirstner s excellent review [2a], we will concentrate here only on the most recent natural product syntheses, which were all achieved by Fiirstner s team. 

In a process that is complementary to Lindlar reduction of cyclic alkynes, Fiirstner and Radkowski reported the chemo- and stereoselective reduction of cycloalkynes (formed by ringclosing alkyne metathesis) to (E)-cycloalkenes using ruthenium-catalyzed (nms-selective hydrosilylation followed by desilylation by AgF (dark, rt) (Scheme 1) <02CC2182>. Employing this process, the 21-membered macrocycle is formed in 85% yield with almost complete -stereoselectivity. 

Zeolite titanium beta has been tested in the liquid- and gas-phase Meerwein-Ponndorf-Verley reduction of cyclohexanones and the Oppenauer oxidation of cyclohexanols. A high selectivity towards the thermodynamically unfavourable cis-alcohol was observed, which has been ascribed to transition-state selectivity in the pores of the zeolite. Under gas-phase conditions the dehydration of alcohols to cycloalkenes is observed as a side reaction. The catalyst was found to be active even in the presence of water and ammonia. 

Hydroboration. Hydroborations with this reagent have been reviewed Brown concludes that the regio- and stereoselectivity of 9-BBN surpass those of other hydroboration reagents. An example of the marked stereospecificity of hydroboration with 9-BBN is the reduction of 1-substituted cycloalkenes to trc/i5-2-methylcycloalkanols (equation I). The same selectivity is shown in the hydroboration of 1,3-dimethylcycloalkenes (equation II). In fact this method is... 

The ruthenium-catalyzed hydrosilylation/protodesilylation protocol is a useful method for stereoselective internal alkyne (cycloalkyne) reduction to (E)-alkenes [(iJ)-cycloalkenes] and is a complement to the cis selectivity observed in the Lindlar reduction (eqs. (27) and (28)) (184,185). The utility of this reaction sequence is attributed to the fact that many of the knovra methods for transforming ahquies to ( )-alkenes either have poor selectivity or are incompatible with common functional groups. 

---