Olefin protection strategy

Palladium-catalyzed, Wacker-type oxidative cycHzation of alkenes represents an attractive strategy for the synthesis of heterocycles [139]. Early examples of these reactions typically employed stoichiometric Pd and, later, cocat-alytic palladium/copper [140-142]. In the late 1970s, Hegedus and coworkers demonstrated that Pd-catalyzed methods could be used to prepare nitrogen heterocyles from unprotected 2-allylanilines and tosyl-protected amino olefins with BQ as the terminal oxidant (Eqs. 23-24) [143,144]. Concurrently, Hosokawa and Murahashi reported that the cyclization of allylphenol substrates can be accomplished by using a palladium catalyst with dioxygen as the sole stoichiometric reoxidant (Eq. 25) [145]. 

In the final synthesis a silicon tethered olefin was used as a protecting group that facilitates a RCM-ROM-RCM sequence. An alternative strategy was to carry out ROM-RCM with TBS protected alcohol (Scheme 20) and subsequent CM, but this strategy was low yielding. 

Compound 25, if not used in the RCM strategy, can be converted to aldehydes 26 by protection of the alcohol group and oxidative double bond cleavage (Scheme 7) [11, 13]. It is interesting to note that Schinzer et al. go the opposite way and synthesize alkene 25 from this aldehyde 26a obtained via a different route [olefination of protected (2S)-2-hydroxybutyrolactone with ArCH2P(0)(0Et)2 (3b) [21, 22] or ArCHjPBu +Cf (3c) [23]]. Nicolaou then transformed aldehyde 26b to the phosphonium salt 27 in three steps. 

Takahashi et al. also reported a route to muconin. Their synthesis adopted Keinan et al. s strategy to construct the stereochemistries by Sharpless AD and AE upon multiple olefin containing fatty acid (Scheme 10-35). The di-olefin 214 was subject to Sharpless AD conditions and then treated with acid, yielding a THP-containing diol. This diol was further protected as acetonide 215. The reversion of stereochemistry of alcohol 215 was achieved by Dess-Marlin oxidation and Zn(BH4)2 reduction. Williamson etherification of tosylate 216 and epoxide formation afforded tri-ring intermediate 217. Opening with acetylene, 217 was converted into the terminal alkyne 218, which was coupled with vinyl iodide to finally give muconin. 

Dithiolanes, also named five-membered 1,3-dithioacetals or A,3 -acetals, find wide applications in organic synthesis, particularly in protection of carbonyl functions and their reductive conversion to hydrocarbons or olefins. Due to the stability of 1,3-dithiolanes toward various reagents and reaction conditions, they have attained an important position in this area despite the fact that dedithioacetalization to the corresponding carbonyl compounds is sometimes not an easy process. There are three general strategies that can be used for deprotection of 1,3-dithiolanes involving... 

The strategy eluded to in Scheme 7.3.6 is elaborated upon in Scheme 8.10.3 and involves the allyl sugar derivative shown. Conversion of the allyl group to the phosphonium salt is accomplished in eight steps. Wittig olefination with the illustrated protected aldehyde provides the cis olefin which is dihydroxylated under asymmetric conditions and selectively protected as the PMB ether. 

Alkenes can be considered as a class of protected carbonyl compounds since they can be converted into carbonyls by ozonolysis. Hall [69] demonstrated a practical strategy for solid phase synthesis of peptide aldehydes using an olefinic linker, which was constructed using Wittig chemistry. After normal peptide synthesis using the alkene linker, ozonolysis of the linker and subsequent workup with... 

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