1What other alternatives to the aldol reaction do you know?ID. Allylations & CrotylationsI. Basic Principles- halolactonization of enones (erythronolide)- α-deoxigenation of α,β-epoxy ketones (erythronolide)- hetero-Diels-Alder synthesis of pyranones (epothilone)P. WipfChem 23201/20/20072Reviews:Merino, P.; Tejero, T.; Delso, J. I.; Mannucci, V. "Stereoselective allylation reactions of iminesand related compounds." Curr. Org. Synth. 2005, 2, 479-498.Kennedy, J. W. J.; Hall, D. G. "Recent advances in the activation of boron and siliconreagents for stereocontrolled allylation reactions." Angew. Chem., Int. Ed. 2003, 42, 4732-4739.Denmark, S. E.; Fu, J. P. "Catalytic enantioslelective addition of allylic organometallicreagents to aldehydes and ketones." Chem. Rev. 2003, 103, 2763-2793.Roush, W. R. Comprehensive Organic Synthesis 1991, vol. 2, p. 1.P. WipfChem 23201/20/20073M = B, Al, Si, Ti, Cr, Zr, Zn, Sn, In, Ba,.....Retrosynthetic SchemeEarly WorkPioneering papers on the stereocontrolled use of allylicorganometallics were reported by• Buse and Heathcock, THL 1978, 1865.• Hoffmann and Zeiss, Angew. Chem. Int. Ed. Engl. 1982, 18, 306.• Yamamoto et al., JACS 1980, 102, 306.P. WipfChem 23201/20/20074Regioselectivity of AllylationYanagisawa, A.; Habaue, S.; Yasue, K.; Yamamoto, H., "Allylbarium reagents:Unprecedented regio- and stereoselective allylation reactions of carbonylcompounds." J. Am. Chem. Soc. 1994, 116, 6130-6141.The stereochemical outcome of allyl-metal additions can be classified intothree groups:- I. the syn/anti ratio of the products reflects the Z/E geometry of thecrotyl moiety (B, Al, Sn, Si (Δ-reactions)).- II. syn-selective irrespective of olefin geometry (Sn, Si, Ti).- III. anti-selective irrespective of olefin geometry (Ti, Cr, Zr, In, Zn).P. WipfChem 23201/20/20075Caveat:→ transmetalation, and allyl-Ti is type I reagent! (THL 1984, 25, 3927):configurational stability: important for synthesis of type IorganometallicsP. WipfChem 23201/20/20076I. the syn/anti ratio of the products reflects the Z/E geometryof the crotyl moiety (B, Al, Sn, Si (Δ-reactions)).chair TS‡The dialkylcrotylboranes are the most reactive but also the leastconfigurationally stable of the allylborane reagents (borderline type III).anti synP. WipfChem 23201/20/20077Brown’s Allylboranes:Prolonged incubation at 0 °C affords enantiomerically enriched Ipc2BH,due to the equilibration of Ipc4B2H2 with α-pinene and Ipc3B2H3; thesymmetrical dimer crystallizes preferentially.P. WipfChem 23201/20/20078The crotylboranes are used immediately after methoxide decomplexationfrom the ate complex by boron trifluoride at -78 °C to avoid crotylisomerization.P. WipfChem 23201/20/20079Hoffmann, 1979: Boronates are more configurationally stablechair TS‡P. WipfChem 23201/20/200710Roush: Tartrate-derived allyl boronates:P. WipfChem 23201/20/200711Hayward, M. M.; Roth, R. M.; Duffy, K. J.; Dalko, P. I.; Stevens, K. L.;Guo, J.; Kishi, Y. Angew. Chem. Int. Ed. 1998, 37, 192.P. WipfChem 23201/20/200712Silacyclobutanes - Effect of strain-release on reactivityZhang, X.; Houk, K. N.; Leighton, J. L. "Origins of stereoselectivity in strain-release allylations." Angew. Chem., Int. Ed. 2005, 44, 938-941.Myers, Denmark, Utimoto:SilacyclobutanesDenmark and co-workers proposed that the silicon atom constrained in afour-membered ring (a silacyclobutane) should behave like acoordinatively unsaturated group III element (J. Am. Chem. Soc. 1994,116, 7026). Oshima et al. showed that 1-phenyl-3-buten-1-ol was obtainedin 85% yield by heating a mixture of a silacyclobutane and benzaldehydefor 12 h at 130 °C (J. Org. Chem. 1994, 59, 7152):P. WipfChem 23201/20/200713Due to the compression of the C-Si-C angle, silacyclobutanes are muchstronger Lewis acids than methyl-substituted silanes. The reaction ofallylsilanes takes place via pentacoordinate trigonal bipyramidal transitionstates. The strong ability of tetravalent silicon to expand its valency and thestrong ability of silicon constrained in a four-membered ring to attractelectrons are the most important factors that make silacyclobutanes veryreactive (Omoto, K.; Fujimoto, H. J. Am. Chem. Soc. 1997, 119, 5366-72).Preparation of silacyclobutane:P. WipfChem 23201/20/200714Transition state:Also:Transition state:II. syn-selective irrespective of olefin geometry (Sn, Si, Ti).Y. Yamamoto:P. WipfChem 23201/20/200715antiperiplanar vs. synclinal transition state: S. E. Denmark, Helv. Chim. Acta1983, 66, 1655; J. Am. Chem. Soc. 1987, 109, 2512; Tetrahedron 1989, 45,1053.→ the LA influences the properties of the reaction taking place from thesynclinal and antiperiplanar arrangements, with the former in general beingthe more important:P. WipfChem 23201/20/200716Related: Prins reactionLA = H+ is inappropriate. Why?P. WipfChem 23201/20/200717• Reactions of Allyl- and Crotylsilanes• Tetraorganosilanes• Electrophiles• Regiochemistry• Selected synthetic applications1970Chain Extension of Organosilanes1980Golden Age of Allylsilanes / Propargylsilanes / Vinylsilanes1990Asymmetric Applications2000Activation/Generalization of ScopeMechanismsβ effectAllylsilanesVinylsilanesβ effectP. WipfChem 23201/20/200718Stereochemistryanti-SE’ :Attack trajectory of electrophile is determined by - steric effects (vs Si) - electronic effects (antiperiplanar to C-Si bond)Ground state control; A1,3 strain is minimizedchiral allylsilanes react antarafacially (JACS 1982, 104, 4963):P. WipfChem 23201/20/200719He, F.; Bo, Y.; Altom, J. D.; Corey, E. J. "Enantioselective totalsynthesis of aspidophytine." J. Am. Chem. Soc. 1999, 121,6771-6772.P. WipfChem 23201/20/200720P. WipfChem 23201/20/200721Key Cyclization Mechanism:Reactions with sugar acetals and ketals (Kishi, JACS 1982, 104, 4976):Carba-Ferrier (Danishefsky, JACS 1987, 109, 8117)P. WipfChem 23201/20/200722Lowe, Jason T.; Wrona, Iwona E.; Panek, James S. Total Synthesis ofBistramide A. Organic Letters ACS ASAP.P. WipfChem 23201/20/200723Preparation of cis- and trans-Silyl Epoxy EstersPreparation of cis- and trans-Silyl Epoxy EstersP. WipfChem 23201/20/200724Comparison of (E)- and (Z)-Crotylsilanes in [4+2]-AnnulationComparison of (E)- and (Z)-Crotylsilanes in [4+2]-AnnulationP. WipfChem 23201/20/200725Synthesis of the C1-C13 Fragment of Bistramide AP. WipfChem 23201/20/200726P. WipfChem 23201/20/200727III. anti-selective irrespective of olefin geometry (Ti, Cr, Zr,In, Zn).Heathcock-Hiyama (1978):The principal
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