Unravelling Factors Affecting Directed Lithiation of Acylamino­aromatics

Keith Smith; Mohammed B. Alshammari; Gamal A. El-Hiti

doi:10.1055/s-0036-1591954

Synthesis, Table of Contents

Synthesis 2018; 50(18): 3634-3652
DOI: 10.1055/s-0036-1591954

short review

Unravelling Factors Affecting Directed Lithiation of Acylaminoaromatics

Keith Smith*

^aSchool of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, UK Email: smithk13@cardiff.ac.uk

,

Mohammed B. Alshammari

^bChemistry Department, College of Sciences and Humanities, Prince Sattam bin Abdulaziz University, P.O. Box 83, Al-Kharij 11942, Saudi Arabia

,

Gamal A. El-Hiti*

^cCornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia Email: gelhiti@ksu.edu.sa

› Author Affiliations

Abstract

All articles of this category

Published as part of the Special Section on the Main Group Metal Chemistry Symposium

Abstract

Ureas, pivalamides, and carbamates are widely used as directing metalation groups (DMGs) due to their good directing ability, low cost, ease of access, and ease of removal. Lithiation of substituted benzenes having such directing metalation groups using various alkyllithiums in anhydrous solvent at low temperature provides the corresponding lithium intermediates, but lithiation may take place at various sites. Reactions of the lithium reagents obtained in situ with various electrophiles give the corresponding derivatives, typically substituted at the site(s) where initial lithiation occurred, often in high yields. However, it is often difficult to predict what reagents and/or conditions might be needed to give specific products or to draw general conclusions about the factors that influence the reactions, especially when the reagents, temperature, and solvents used in reported reactions are not directly comparable. In this review, therefore, we attempt to unravel the various factors that influence the lithiation of various simple aromatic compounds containing urea, pivalamide, and carbamate groups.

1 Introduction

2 Lithiation with DMG Attached Directly to the Phenyl Ring

2.1 Influence of the DMG

2.2 Influence of Substitution on the Phenyl Ring

3 Lithiation with the DMG Separated by a CH₂ Group from the Phenyl Ring

3.1 Effect of the DMG

3.2 Influence of Substitution on the Phenyl Ring

4 Lithiation with the Phenyl Ring and DMG Separated by Two or More CH₂ Groups

4.1 Effect of the DMG and Its Distance from the Phenyl Group

4.2 Effect of Substituents on the Phenyl Ring

5 Conclusions

Keywords

lithium reagents - directed lithiation - ureas - pivalamides - carbamates - electrophiles - lateral lithiation

Full Text

References

References
1 Clayden J. Greeves N. Warren S. Wothers P. Organic Chemistry . Oxford University Press; Oxford: 2007
2 Smith K. El-Hiti GA. Green Chem. 2011; 13: 1579
3 Gschwend HW. Rodriguez HR. Org. React. 1979; 26: 1
4 Snieckus V. Chem. Rev. 1990; 90: 879
5 Clayden J. Organolithiums: Selectivity for Synthesis . Pergamon; Oxford: 2002
6 Schlosser M. Organoalkali Chemistry . In Organometallics in Synthesis: A Manual . 2nd ed.; Schlosser M. Wiley; Chichester: 2002: 1-352
7 Clayden J. In The Chemistry of Organolithium Compounds . Vol. 1. Rappoport Z. Marek I. Wiley; Chichester: 2004: 495-646
8 Schlenk W. Bergmann E. Justus Liebigs Ann. Chem. 1928; 463: 98
9 Gilman H. Bebb RL. J. Am. Chem. Soc. 1939; 61: 109
10 Wittig G. Fuhrman G. Chem. Ber. 1940; 73: 1197
11 Gilman H. Jacoby AL. J. Org. Chem. 1938; 03: 108
12 Wittig G. Pockels U. Dröge H. Chem. Ber. 1938; 71: 1903
13 Langer AW. Adv. Chem. Ser. 1974; 130: 1
14 Halesa AF. Schulz DN. Tate DP. Mochel VD. Adv. Organomet. Chem. 1980; 18: 55
15 Seyferth D. Organometallics 2006; 25: 2
16 Wakefield BJ. The Chemistry of Organolithium Compounds . Pergamon Press; Oxford: 1974
17 Schlosser M. Pure Appl. Chem. 1988; 60: 1627
18 Mallan JM. Bebb RL. Chem. Rev. 1969; 69: 693
19 Shirley DA. Letho EA. J. Am. Chem. Soc. 1957; 79: 3481
20 Slocum DW. Jennings CA. J. Org. Chem. 1976; 41: 3653

21a Simig G. Schlosser M. Tetrahedron Lett. 1991; 32: 1963
21b Schlosser M. Simig G. Tetrahedron Lett. 1991; 32: 1965

22 Gilman H. Cheney LC. Willis HB. J. Am. Chem. Soc. 1939; 61: 951
23 Gilman H. Langham W. Willis HB. J. Am. Chem. Soc. 1940; 62: 346
24 Hillis LR. Gould SJ. J. Org. Chem. 1985; 50: 718
25 Cho IS. Gong L. Muchowski JM. J. Org. Chem. 1991; 56: 7288
26 Stanetty P. Koller H. Mihovilovic M. J. Org. Chem. 1992; 57: 6833
27 Takagishi S. Katsoulos G. Schlosser M. Synlett 1992; 360
28 Ubeda JI. Villacampa M. Avendaño C. Synlett 1997; 285
29 Bellezza F. Cipiciani A. Ruzziconi R. Spizzichino S. J. Fluorine Chem. 2008; 129: 97
30 Muchowski JM. Venuti MC. J. Org. Chem. 1980; 45: 4798
31 Gomez-Bengoa E. Echavarren AM. J. Org. Chem. 1991; 56: 3497
32 Salituro FC. McDonald IA. J. Org. Chem. 1988; 53: 6138
33 Clark RD. Caroon JM. Kluge AF. Repke DB. Roszkowski AP. Strosberg AM. Baker S. Bitter SM. Okadaf MD. J. Med. Chem. 1986; 26: 657
34 Sato N. Tetrahedron Lett. 2002; 43: 6403
35 Hoffmann RW. Kemper B. Tetrahedron Lett. 1981; 22: 5263
36 Derdau V. J. Labelled Compd. Radiopharm. 2004; 47: 19
37 Rajapakse HA. Young MB. Zhu H. Charlton S. Tsou NN. Tetrahedron Lett. 2005; 46: 8909
38 Führer W. Gschwend HW. J. Org. Chem. 1979; 44: 1133
39 Smith K. Pritchard GJ. Angew. Chem., Int. Ed. Engl. 1990; 29: 282
40 Smith K. El-Hiti GA. Pritchard GJ. Hamilton A. J. Chem. Soc., Perkin Trans. 1 1999; 2299
41 Spitznerd R. Mielke D. Scholz D. Schroth W. Preiss A. Tetrahedron 1982; 38: 927
42 Smith K. El-Hiti GA. Shukla AP. J. Chem. Soc., Perkin Trans. 1 1999; 2305
43 Schlosser M. Eur. J. Org. Chem. 2001; 3975
44 Lizos DE. Murphy JA. Org. Biomol. Chem. 2003; 1: 117
45 Kondo Y. Kojima S. Sakamoto T. J. Org. Chem. 1997; 62: 6507
46 Reuter DC. Flippin LA. McIntosh J. Caroon JM. Hammaker J. Tetrahedron Lett. 1994; 35: 4899
47 Smith K. El-Hiti GA. Fekri A. Alshammari MB. Heterocycles 2012; 86: 391
48 Hansch C. Leo A. Taft RW. Chem. Rev. 1991; 91: 165
49 Leroux F. Castagnetti E. Schlosser M. J. Org. Chem. 2003; 68: 4693
50 Rauf W. Brown JM. Angew. Chem. Int. Ed. 2008; 47: 4228
51 Guilarte V. Castroviejo MP. García-García P. Fernandez-Rodríguez MA. Sanz R. J. Org. Chem. 2011; 76: 3416
52 Sedelmeier J. Lima F. Litzler A. Martin B. Venturoni F. Org. Lett. 2013; 15: 5546
53 Rescigno A. Bruyneel F. Padiglia A. Sollai F. Salis A. Marchand-Brynaert J. Sanjust E. Biochim. Biophys. Acta 2011; 1810: 799
54 Mulhem TA. Davis M. Krikke JJ. Thomas JA. J. Org. Chem. 1993; 58: 5537
55 Clark RD. Jahangir A. Org. React. 1995; 47: 1
56 Clark DR. Muchowski MJ. Souchet M. Repke BD. Synlett 1990; 207
57 Clark RD. Muchowski JM. Flippin LA. Repke DB. Souchet M. Synthesis 1991; 871
58 Cervantes A. Contreras CA. Guzman A. Vale EE. Velarde E. Berthiaume SL. Muchowski JM. Can. J. Chem. 1995; 73: 336
59 Smith K. El-Hiti GA. Al-Mansury SA. Alshammari MB. Balakit AA. ARKIVOC 2014; v: 365 ; http://www.arkat-usa.org/home
60 Schmid M. Waldner B. Schnurch M. Mihovilovic DM. Stanetty P. Tetrahedron 2011; 67: 2895
61 Aurrecoechea JM. Suero R. de Torres E. J. Org. Chem. 2006; 71: 8767
62 Van der Veken P. Senten K. Kertesz I. De Meester I. Lambeir A.-M. Maes M.-B. Scharpé S. Haemers A. Augustyns K. J. Med. Chem. 2005; 48: 1768
63 Katsoulos G. Schlosser M. Tetrahedron Lett. 1993; 34: 6263
64 Smith K. El-Hiti GA. Hegazy AS. Fekri A. Kariuki BM. ARKIVOC 2009; xiv: 266 ; http://www.arkat-usa.org/home
65 Simig G. Schlosser M. Tetrahedron Lett. 1988; 29: 4277
66 Barberis C. Voyer N. Roby J. Chenard S. Tremblay M. Labrie P. Tetrahedron 2001; 57: 2965
67 Hoppe D. Hense T. Angew. Chem. Int. Ed. 1997; 36: 2282
68 Park YS. Beak P. Bull. Korean Chem. Soc. 1998; 19: 1253
69 Kanazawa AM. Correa A. Denis J.-N. Luche M.-J. Greene AE. J. Org. Chem. 1993; 58: 255
70 Keller L. Beaumont S. Liu J.-M. Thoret S. Bignon JS. Wdzieczak-Bakala J. Dauban P. Dodd RH. J. Med. Chem. 2008; 51: 3414
71 Smith K. El-Hiti GA. Hegazy AS. Synthesis 2010; 1371
72 Smith K. El-Hiti GA. Alshammari MB. Synthesis 2012; 44: 2013
73 Clark DR. Jahangir A. Tetrahedron 1993; 49: 1351
74 Smith K. El-Hiti GA. Alshammari MB. Synthesis 2014; 46: 394
75 Smith K. El-Hiti GA. Alshammari MB. Synlett 2013; 24: 117
76 Smith K. El-Hiti GA. Alshammari MB. J. Org. Chem. 2012; 77: 11210

Unravelling Factors Affecting Directed Lithiation of Acylamino­aromatics

Unravelling Factors Affecting Directed Lithiation of Acylaminoaromatics