methodology & mechanism
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Organosilanes have long been considered an environmentally superior alternative to their corresponding tin analogues. We have been especially interested in Pd-mediated reductions employing polymethylhydrosiloxane (PMHS). PMHS is an easily handled, inexpensive, non-toxic, and mild reducing agent. Although relatively inert towards organic functionality, PMHS can transfer its hydride to a variety of metal catalysts (including Sn, Ti, Zn, Cu, and Pd), which can then participate in a wide range of reductions. The combination of catalytic Pd(OAc)2 and PMHS was recognized by Chauhan to lead to formation of palladium nanoparticles, We have shown this combination is particularly effective in the room temperature reduction of aromatic nitro groups to amines. These reactions can be accomplished in high yield, with wide functional group tolerance, and short reaction times (30 minutes) using a combination of palladium(II) acetate, aqueous potassium fluoride, and polymethylhydrosiloxane (PMHS). Replacing PMHS/KF with triethylsilane allows aliphatic nitro groups to be reduced to their hydroxylamines.
Related reaction sequences have also been worked out for the reductions of acid chlorides to aldehydes and the dehalogenations of aromatic halides, including chlorides.
Organosilanes have also proven to be excellent substrates in Wittig rearrangements. Wittig rearrangements of alpha-lithiated ethers have proven to be a valuable tool for organic chemists. We have studied the Wittig rearrangements of alpha-alkoxysilanes, promoted by the action of methyllithium. Depending on both the substrate and reaction conditions employed, [2,3], [1,2], or [1,4]-Wittig rearrangements can be realized. Furthermore the sigmatropic shifts can often be followed by other synthetically useful in situ chemical events.
Most interestingly, we have established that, upon deprotonation with s-BuLi, alpha-benzyloxyallylsilanes undergoes [1,4]-Wittig rearrangement with unprecedented selectivity. By concluding the reaction with the addition of an electrophile, alpha-benzyloxyallylsilane serves as a unique source of a variety of alpha-substituted acylsilanes. This is significant in that relative to its [1,2]- and [2,3]-counterparts, the [1,4]-Wittig remains a reaction of many questions. For example, whether the [1,4]-mechanism is concerted or involves a radical-radical anion dissociation-recombination is still debated. The substrate scope of the [1,4]-Wittig is also not well documented and thus its potential in synthetic organic chemistry is unclear. Moreover, for substrates capable of both pathways, strong preference for [1,4] over [1,2] bond reorganizations are rarely realized.
We continue to explore the chemistry of alpha-silyl ethers and their derivatives. Much of this recent work is centered around the stereochemical aspects of these reagents/reactions.
Selected organosilane related publications:
“C–O Hydrogenolysis Catalyzed by Pd-PMHS Nanoparticles
in the Company of Chloroarenes” Rahaim, R. J., Jr.; Maleczka, R. E.,
Jr. Org. Lett. 2011, 13, 584–587.
“Enzymatic Kinetic Resolution of alpha-Hydroxysilanes”
An, I.; Onyeozili, E. N.; Maleczka, R. E., Jr. Tetrahedron: Asymmetry 2010, 21, 527–534.
“Pd-Catalyzed Silane/Siloxane Reductions in the One-Pot Conversion of Nitro Compounds to Their Amines, Hydroxylamines, Amides, Sulfonamides, and Carbamates” Rahaim, R. J., Jr.; Maleczka, R. E., Jr. Synthesis 2006, 3316–3340.
“Studies on the Deprotonation and Subsequent [1,4]-Wittig Rearrangement of alpha-Benzyloxy-allylsilanes” Onyeozili, E. N.; Maleczka, R. E., Jr. Tetrahedron Lett. 2006, 47, 6565–6568.
“alpha-Substituted Acylsilanes via a Highly Selective [1,4]-Wittig Rearrangement of alpha-Benzyloxyallylsilane” Onyeozili, E. N.; Maleczka, R. E., Jr. Chem. Commun. 2006, 2466–2468.
“Pd(0)-Catalyzed PMHS Reductions of Aromatic Acid Chlorides to Aldehydes” Lee, K.; Maleczka, R. E., Jr. Org. Lett. 2006, 8, 1887–1888.
“Pd-Catalyzed Silicon Hydride Reductions of Aromatic and Aliphatic Nitro Groups” Rahaim, R. J., Jr.; Maleczka, R. E., Jr. Org. Lett. 2005, 7, 5087–5090.