Topic 18: Nucleophilic Sigma Bonds

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1 Professor David L. Van Vranken Chemistry 201: rganic eaction Mechanisms I Topic 18: ucleophilic Sigma Bonds E E C E eferences: terature cited

2 ecall the Six Types of Canonical Frontier rbitals We ve already discussed the interactions of 3 types of filled orbitals and 3 types of unfilled orbitals. If all things are equal then CC and C sigma bonds should be the least reactive type of nucleophiles but if we replace C with to make a C bond then the bonds became exquisitely reactive. σ* π* E E M p n π B E E σ We need to discuss the nucleophilicity of sigma bonds more broadly.

3 Periodic Trends Electronegativity ere are some periodic trends you should know electronegative rapid atom transfer pi character weaker, more nucleophilic bonds electropositive

4 Frontier Molecular rbital Energies Predict eactivity What happens when you replace carbon with an electropositive atom? Bonds to electropositive atoms can be highly nucleophilic. n () E faster E M σ C σ CBe faster 3 C E E M n (Be) n (B) n (C) E slower C 3 σ CB σ CC E σ C 3 C C 3 σ E For bonds to and, the nonbonding FM (i.e., the lone pair) is still more reactive than the sigma bond FM.

5 Alkyllithiums: Frontside vs. Backside Attack Frontside attack is most common for. 3 C S C 3 Bn C 3 Bn Still, W. C.; Sreekumar, C. JACS 1980, 102, owever, electrons in the M of also spend time on the back side of the carbonlithium bond. X C X C X C Ashweek,. et. al. JACS 2005, 127, 449 With 2, k rac [] not [] 2 Backside attack of the bond is important for [2,3]Wittig rearrangement [2,3] Verner, E. J.; Cohen, T. JACS 1992, 114, 375.

6 ucleophilic ydrides ucleophilic hydrides are generally attached to ate complexes with electropositive elements. Bonds to anionic atoms are more nucleophilic than comparable bonds to neutral atoms. > >> Al B Si Ac C 3 TMEDA C 3 2 lithiate better u ab 4 and Al 4 change with each hydride addition Al Al : Al etc. less reactive Al than Al 4 Cheap, simple reagents rarely involve simple reaction mechanisms.

7 ucleophilic ydrides and Selectivity atoms generally move faster than C atoms. ydrido groups undergo [1,2] migrations faster than. Bases attack faster than. faster slower 2 : Cl 2 : 3 C Cl B Ketone reduction is fast (S 2 on Br isn't fast) 3 B JeanClaude, B. J.; Just, G. Syn. Comm. 1994, 24, a ab 4 Br Me rt, 1 h Br 100% Alkyl groups increase reactivity of anionic ates versus hydrogen. 3 B is 10 4 more nucleophlic than B 4. 3 B = "Super ydride" Br B 3 TF 25 C, 3 h Brown,. C.; Krishnamurthy, S. JACS 1973, 95.

8 Selectivity of ydride Donor eagents Selectivity of hydride reagents toward π* react fastest react slowest 2 Al 4 /TF ab 4 /Me B Si C or Sodium cyanoborohydride doesn t react with carbonyls unless they are protonated. a C B Cl (slow addn, p 3) C 3 23 C, 1 h Borch,.F., et. al. JACS 1971, 93, 2897.

9 ydridostannates and ydridosiliconates 3 Sn and 3 Si form nucleophilic hydride reagents in situ Me Bu 4 F nbu 3 Sn 0 C, 5 h Bu Bu Sn Bu F Me 81% Shibata, I.; Yoshida, T.; Baba, A.; Matsuda,. Chem. Lett. 1991, 307. acb 3 reduces enamines, indoles, and pyrroles via iminium ions. This reduction works with hydridosiliconates. CF 3 Si : CF 3 3 Si CF 3 C 2 2 CCF 3 Si 2 CCF 3 Si Usually with acb 3 /CF 3 C 2 Lanzilotti, A. E., et. al. JC 1979, 44, 4809.

10 Electrophilic ydride eagents B 3 and ibu 2 Al reduce ketones. They are not nucleophilic UTIL after they coordinate to the carbonyl B B B Al DIBAL DIBAL reduces esters to aldehydes because it only delivers one hydride : ibu 2 Al toluene Al Al workup 2 2 Al, 2 B, and 3 Si groups reduce the nucleophilicity of oxygen l.p. Al 4 reduces esters to alcohols via electrophilic alane (Al 3 ). Al 4 : TF 3 Al 3 Al Al 3 Al

11 C Weakening by Lone Pair Donation Bohlmann bands occur ~ cm 1 in the I spectrum. Bohlmann bands are due to donation of nitrogen lone pairs into σ* C Ferdinand Bohlmann Chem. Ber. 1958, Vapor phase I spectrum Daly, J. W., et.al. JC 2000, 65, An extreme example of nitrogen lone pair donation affecting spectroscopy and chemical reactivity 2450 cm 1 Bohlmann bands cm 1 ~2900 cm 1 aliphatic C Wuest, J. JACS 1980, Watkins, T. JACS 1980, 6363 X 23 h 110 C X X n donate into σ* C

12 ydride Transfer from Carbon Aldehydes without αhydrogens can t undergo aldol reactions. Instead, they disproportionate via hydride transfer (Cannizzaro reaction). 2 a a a Geissman, T. rg. eact. 1944, 2, 94. Formaldehyde and formate are particularly good hydride donors EschweilerClark methylation 2 C 2 2 C 2 Eschweiler, W. Chem. Ber. 1905, 38, 880. Clarke,. T., et. al. JACS 1933, 55, Moore, rg. eact. 1949, 5, 301. Daio, G., Mariano, P. S. JC 1988, 53, Awachie, P.I.; Vagwanda, V.C. Tetrahedron 1990, 46, 1899

13 ppenauer and MeerweinPondorffVerley eactions ppenauer oxidation: (ipr) 3 Al catalyzes hydride transfer to acetone solvent cat. Al(iPr) 3 acetone = oxidation! Djerassi, C. rg. eact. 1951, 26, 207 Al Al Al The reaction is reversible and is driven by the use of solvent as a reagent MeerweinPondorffVerley eduction (MPV): un the reaction in ipr cat. Al(iPr) 3 isopropanol Wilds, A. L. rg. eact. 1944, 2, 178.