Hydroformylation/Wittig olefination

For domino hydroformylation/Wittig olefinations see a) B. Beeit, S. K. Zahn, Angew. Chem. 1999, 111, 1022-1024 Angew. Chem. Int. Ed. Engl. 

Scheme 13 Hydroformylation-Wittig olefination or Knoevenagel reaotion-hydrogenation.

A reaction in agreement with these efficiency criteria would be a domino stereoselective-hydroformylation-Wittig olefination process. This would require that the hydroformylation reaction be compatible with the presence of a Wittig ylid throughout the course of the reaction. 

Scheme IS. Domino hydroformylation-Wittig olefination. Reagents and conditions 1.1 Equiv.

The same catalytic system proved to be advantageous for the tandem hydroformylation (Wittig olefination) reaction of a more sophisticated vinyl acetate as substrate at about 10bar (Scheme 4.68) [41]. (-p)-Patulohde C, a compound exhibiting both antifungal and antibacterial activity, was obtained with 93% de (for more details and examples of stereoselective tandem reactions, see Section 5.5). 

The first hydroformylation-(Wittig olefination)-hydrogenation was reported by Breit and Zahn in 1999 (Scheme 5.135) [24]. The ortAo-diphenylphosphino-benzene group served as the stereodirecting group (see also Section 4.4) and... 

In 2013, Wong and Landis [26] investigated an asymmetric hydroformylation-(Wittig olefination) reaction of vinyl acetate by using a chiral catalyst based on (S,S,S)-BDP at 10bar (Scheme 5.136). After optimization, several other functionalized and nonfunctionalized olefins or 1,3-dienes could be converted under these conditions. 

Scheme 5.136 Asymmetric hydroformylation-(Wittig olefination) reaction.

A multiple one-pot iterative asymmetric hydroformylation-Wittig olefination was realized with a single catalyst loading (Scheme 5.137) [26]. Noteworthy, after each run, depressurization and injection of the allyl-substituted Wittig reagent was necessary in order to avoid the undesired hydroformylation of the Wittig ylide. In this manner, the dimer and the trimer of 4-hydroxyvalerate were prepared. 

Scheme 5.137 Synthesis of dimer and trimer of 4-hydroxyvalerate by iterative hydroformylation-(Wittig olefination) reaction using a single catalyst.

Farwick and Helmchen [28] prolonged the alkyl chain of chiral allylamines by a hydroformylation-(Wittig olefination) sequence (Scheme 5.139). Particular attention was paid to the choice of the JV-protective group. As expected in the Wittig olefination step, mainly the Z-configured olefins were formed. After selective removal of only one Af-protective group, the obtained Af-Boc protected methyl esters were converted via a diastereoselective aza-Michael reaction into the corresponding fi-proline derivatives. 

For the total synthesis of other macrocyles, such as (-)-pyrenophorol and (+)-decaestrictine via similar asymmetric hydroformylation-Wittig olefination cascade reactions, see Ref. (30). 

Rhodium-catalyzed hydroformylation of terminal alkenes in the presence of stabilized phosphorus yhdes was found to initiate a domino hydroformylation-Wittig olefination process. When monosuhstituted acceptor-stabilized phosphorus ylides were employed, a hydrogenation step follows the Wittig olefination to give a domino hydroformylation-Wittig olefination hydrogenation process (Equation 7.19) [166]. 

After successful hydroformylation one may decide to remove the catalyst-directing o-DPPB group, which may be achieved by simple alkaline hydrolysis (syn-6a—>syn-3) [10] or via hydride reduction after transferring the aldehyde e.g. to an alkene via Wittig olefination (syn-6b syn-23) [14]. 

Under hydroformylation conditions and in the presence of Ph3P=CHCOR, compound 189 leads to the oxo derivative 190. The process involves a sequence of reactions that includes initial hydroformylation to give the aldehyde 191 in a stereoselective way (see also Figme 26), Wittig olefination to give the trans conjugated alkene 192 and hydrogenation. 

Risi and Burke [29, 30] synthesized (+)-patulolide C, which is a macrocyhc compound isolated from a Penicillium urticae mutant via an asymmetric sequential hydroformylation-(intramolecular Wittig olefination) reaction applying... 

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