title: Evaluating cis-2,6-dimethylpiperidide (cis-DMP) as a base component in lithium-mediated zincation chemistry.
abstract: Most recent advances in metallation chemistry have centred on the bulky secondary amide 2,2,6,6-tetramethylpiperidide (TMP) within mixed metal, often ate, compositions. However, the precursor amine TMP(H) is rather expensive so a cheaper substitute would be welcome. Thus this study was aimed towards developing cheaper non-TMP based mixed-metal bases and, as cis-2,6-dimethylpiperidide (cis-DMP) was chosen as the alternative amide, developing cis-DMP zincate chemistry which has received meagre attention compared to that of its methyl-rich counterpart TMP. A new lithium diethylzincate, [(TMEDA)LiZn(cis-DMP)Et2] (TMEDA=N,N,N',N'-tetramethylethylenediamine) has been synthesised by co-complexation of Li(cis-DMP), Et2Zn and TMEDA, and characterised by NMR (including DOSY) spectroscopy and X-ray crystallography, which revealed a dinuclear contact ion pair arrangement. By using N,N-diisopropylbenzamide as a test aromatic substrate, the deprotonative reactivity of [(TMEDA)LiZn(cis-DMP)Et2] has been probed and contrasted with that of the known but previously uninvestigated di-tert-butylzincate, [(TMEDA)LiZn(cis-DMP)tBu2]. The former was found to be the superior base (for example, producing the ortho-deuteriated product in respective yields of 78% and 48% following D2O quenching of zincated benzamide intermediates). An 88% yield of 2-iodo-N,N-diisopropylbenzamide was obtained on reaction of two equivalents of the diethylzincate with the benzamide followed by iodination. Comparisons are also drawn using 1,1,1,3,3,3-hexamethyldisilazide (HMDS), diisopropylamide and TMP as the amide component in the lithium amide, Et2Zn and TMEDA system. Under certain conditions, the cis-DMP base system was found to give improved results in comparison to HMDS and diisopropylamide (DA), and comparable results to a TMP system. Two novel complexes isolated from reactions of the di-tert-butylzincate and crystallographically characterised, namely the pre-metallation complex [{(iPr)2N(Ph)C=O}LiZn(cis-DMP)tBu2] and the post-metallation complex [(TMEDA)Li(cis-DMP){2-[1-C(=O)N(iPr)2]C6H4}Zn(tBu)], shed valuable light on the structures and mechanisms involved in these alkali-metal-mediated zincation reactions. Aspects of these reactions are also modelled by DFT calculations.
authors: WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow, G1 1XL (UK).
authors: David R
authors: DR
authors: Armstrong
authors: Jennifer A
authors: JA
authors: Garden
authors: Alan R
authors: AR
authors: Kennedy
authors: Sarah M
authors: SM
authors: Leenhouts
authors: Robert E
authors: RE
authors: Mulvey
authors: Philip
authors: P
authors: O'Keefe
authors: Charles T
authors: CT
authors: O'Hara
authors: Alan
authors: A
authors: Steven
mesh_terms: D018360:Crystallography, X-Ray; D008094:Lithium / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry*; D011789:Quantum Theory; D015032:Zinc / Q000737:chemistry*
chemical_list: D009942:Organometallic Compounds; D010880:Piperidines; C000588712:cis-2,6-dimethylpiperidide; C450681:phenyllithium; D008094:Lithium; D015032:Zinc
keywords: amides; lithium; metallation; structural elucidation; zincates
references: Angew Chem Int Ed Engl. 2007;46(21):3802-24
references: 17444540
references: Angew Chem Int Ed Engl. 2009;48(34):6350-3
references: 19621406
references: Chem Commun (Camb). 2007 Jun 21;(23):2402-4
references: 17844760
references: Angew Chem Int Ed Engl. 2006 Apr 3;45(15):2370-4
references: 16511891
references: Angew Chem Int Ed Engl. 2008;47(36):6802-6
references: 18663703
references: J Am Chem Soc. 2007 Feb 21;129(7):1921-30
references: 17263527
references: Phys Rev A Gen Phys. 1988 Sep 15;38(6):3098-3100
references: 9900728
references: J Am Chem Soc. 2007 Oct 24;129(42):12734-8
references: 17910445
references: Chem Commun (Camb). 2001 Dec 7;(23):2450-1
references: 12240009
references: Chem Commun (Camb). 2008 Nov 14;(42):5375-7
references: 18985215
references: Acc Chem Res. 2009 Jun 16;42(6):743-55
references: 19348412
references: J Am Chem Soc. 2005 May 4;127(17):6184-5
references: 15853319
references: Angew Chem Int Ed Engl. 2004 Jun 21;43(25):3333-6
references: 15213967
references: Science. 2009 Oct 30;326(5953):706-8
references: 19900927
references: J Org Chem. 2010 May 7;75(9):3117-20
references: 20387865
references: Angew Chem Int Ed Engl. 2011 Oct 10;50(42):9794-824
references: 21953742
references: Dalton Trans. 2006 Oct 28;(40):4755-68
references: 17033700
references: J Am Chem Soc. 2007 Dec 12;129(49):15102-3
references: 18004847
references: Acc Chem Res. 2009 Feb 17;42(2):270-80
references: 19105594
references: Phys Rev B Condens Matter. 1988 Jan 15;37(2):785-789
references: 9944570
references: Acta Crystallogr B. 2002 Jun;58(Pt 3 Pt 1):380-8
references: 12037359
references: J Am Chem Soc. 2008 Dec 3;130(48):16193-200
references: 18989965
references: Angew Chem Int Ed Engl. 2011 Oct 4;50(41):9668-71
references: 21938760
references: J Am Chem Soc. 2002 Jul 24;124(29):8514-5
references: 12121077
references: J Org Chem. 2001 Oct 19;66(21):7078-83
references: 11597233
references: Angew Chem Int Ed Engl. 2010 Dec 3;49(49):9388-91
references: 20979075
references: J Org Chem. 2012 Jan 20;77(2):985-90
references: 22200186
references: Chemistry. 2008;14(1):65-72
references: 18033708
references: Chemistry. 2011 Jun 6;17(24):6725-30
references: 21538621
references: Angew Chem Int Ed Engl. 2006 Apr 3;45(15):2374-7
references: 16511892
references: J Am Chem Soc. 2006 Jun 14;128(23):7434-5
references: 16756285
references: Dalton Trans. 2010 Jan 14;(2):511-9
references: 20023988
references: Chem Commun (Camb). 2006 Aug 14;(30):3208-10
references: 17028745
references: Acta Crystallogr A. 2008 Jan;64(Pt 1):112-22
references: 18156677
references: J Am Chem Soc. 2004 Sep 1;126(34):10526-7
references: 15327295
references: Angew Chem Int Ed Engl. 2001 Apr 1;40(7):1238-1240
references: 11301436
references: J Am Chem Soc. 2009 Feb 18;131(6):2375-84
references: 19199628
references: Angew Chem Int Ed Engl. 2006 Oct 6;45(39):6548-50
references: 16952186
references: Inorg Chem. 2011 Dec 19;50(24):12241-51
references: 21520928
references: Org Lett. 2010 Mar 19;12(6):1200-3
references: 20192197