Site isolation thimbles

Other Cascade Reactions with Incompatible Catalysts - Polydimethylsiloxane (PDMS) Thimbles for Generic Site Isolation... 

The same approach has also been used in a reaction cascade involving 4-dimethy-laminopyridine (DMAP) and an acid catalyst [35], These two catalysts are mutually incompatible as the add quenches the DMAP, but site isolation using a PDMS thimble enables the cascade to proceed successfully (Figure 5.3). 

Site Isolation of Water from L1A1H4. Water was successfully added to the interior of a PDMS thimble and site isolated from LiAlHa that was added to the exterior to complete a two-step, one-pot reaction as shown in eq 3. In this reaction, 74 equiv of water was added for every 1.25 equiv of L1A1H4, so control reactions where water and L1A1H4 were not site isolated by the walls of a PDMS thimble failed to yield the product. 

Site Isolation of the Grubbs Catalyst from the Sharpless Dihydroxylation Catalyst. The Grubbs catalyst was site isolated from AD-mix to complete cascade reactions as shown in eqs 13-15. The Grubbs catalyst was added to the interior of a thimble with CH2Cl2 [BMIM][PF6] and the metathesis reaction was run to completion. Next, the AD-mix was added to the exterior of a thimble with 1 1 (v/v) f-Bu0H H20 or 1 2 3 (v/v/v) [BMIM][PF6] H20 acetone. The product of the metathesis reaction fluxed to the exterior and reacted to yield the diol. 

The Gmbbs catalyst was site isolated using the thimbles and solvents described here. Less than 1% fluxed to the exterior even after 24 h. In contrast, Os(VIII) fluxed to the interior of the thimble but this had no apparent impact on the yields and enantiomeric excesses. An achiral product was also isolated to demonstrate that the two-step process was successful for a cyclic substrate. The yields for the reactions ranged from 61 to 95% and the enantiomeric excesses were 84—98%. The enantiomeric excesses matched those reported by others for identical substrates in reactions completed in glass vessels. 

Site Isolation of Polymeric Catalysts. A common method to site isolate catalysts from the products of a reaction is to attach the catalyst to a polymer that can be precipitated at the end of a reaction. " Catalysts attached to a polymer are generally not site isolated from other catalysts attached to a different polymer such that only one catalyst can be added to a reaction mixture. The use of PDMS thimbles solves this problem. ... 

Striking differences in yields were observed in reactions mn with or without PDMS thimbles. The acid catalyst was either PTSA or commercially available beads with PTSA bonded to the backbone (eq 21). The basic catalyst was either DMAP, commercially available beads with DMAP bonded to the backbone (eq 22), or a linear polymer (eq 18). Six reactions were completed with either PTSA or the beads with PTSA and each of the three different bases. In reactions with PDMS thimbles to site isolate the acid from the base, the isolated yields of the final product were 71-93%. The lowest yields were when DMAP was the basic catalyst. This result was probably due to the flux of DMAP through the thimhles that quenched some of the acid on the interior of the thimhle. 

In five of the six reactions without thimbles to site isolate the acid and base catalysts, the isolated yields of the product ranged from 0 to 15%. Only in the reaction with polymeric beads with PTSA and beads with DMAP did the isolated yield reach 50%. In summary, the PDMS thimbles successfully site isolated polymeric catalysts from one another and this approach should work for other polymeric catalysts. 

In each of these reactions, the Pd was site isolated on the interior of the thimbles. To characterize the concentration of Pd in the products, the reactions were run to completion and the product was extracted to the exterior. The solvent on the exterior of the thimble was isolated and removed. The concentration of Pd in the product was found by ICP-MS. Between 0.225 and < 0.002% of the Pd that was added to the interior of the thimble was found in the products on the exterior of the thimbles. In other words, >99.998% and no less than 99.775% of the Pd remained on the interior of the thimbles even after the product was extracted to the exterior. 

The reason for the low flux of PdCl2 was that it was soluble only in polar protic solvents. Its solubility in PDMS was negligible, so it did not flux through the walls of the thimbles. When phosphines were added to the reaction mixture to coordinate to PdC and render it less polar, the phosphines and Pd readily fluxed through the walls of the PDMS thimbles. This method demonstrates that catalysts that do not partition into PDMS will remain site isolated by it. 

Final Notes. Small molecules, organometallic catalysts, inorganic catalysts, and polymeric catalysts were all successfully site isolated at levels up to >99.998% using PDMS thimbles. When site isolating catalysts or reagents, the most important parameters to consider are the solubilities and rates of diffusion within the swollen PDMS matrix and the solubilities in the organic solvents on the interior and exterior of thimbles. 

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