Structure, Reactivity, and Synthetic Applications of Sodium Diisopropylamide

Ryan A. Woltornist; Yun Ma; Russell F. Algera; Yuhui Zhou; Zirong Zhang; David B. Collum

doi:10.1055/s-0039-1690846

Synthesis, Table of Contents

Synthesis 2020; 52(10): 1478-1497
DOI: 10.1055/s-0039-1690846

short review

Structure, Reactivity, and Synthetic Applications of Sodium Diisopropylamide

Authors

Ryan A. Woltornist
Yun Ma
Russell F. Algera
Yuhui Zhou
Zirong Zhang
David B. Collum∗

Abstract

All articles of this category

Abstract

The 60-year history of sodium diisopropylamide (NaDA) is described herein. We review various preparations, solvent-dependent stabilities, and solution structures. Synthetic applications of NaDA reported to date are framed by a mechanism-driven approach, emphasizing selectivities when appropriate. We conclude with examples beyond metalation in which NaDA plays a central role and with a few thoughts on where future applications could be focused.

1 Introduction

2 Preparation and Physical Properties

3 Solution Structures

4 Reactivity and Mechanism

4.1 Solvent Decomposition

4.2 Alkene and Diene Metalation

4.3 Arene Metalations

4.4 Dehydrohalogenations

5 Selectivity and Applications in Synthesis

5.1 Picoline Metalations

5.2 C–H Metalation

5.3 Dehydrohalogenations

5.4 Triflate Alkylation

5.5 Allyl Ether Isomerizations

5.6 Cyclic Allene Synthesis

5.7 Epoxide Elimination

5.8 Enolization

5.9 Orthometalation

6 Flow

7 Catalysis

8 Organosodium Salts and Secondary Applications

9 Conclusion

Key words

sodium diisopropylamide - organosodium - selectivity - mechanism - metalation - structure

Full Text

References

References

1a Current address: Pfizer Worldwide Research and Development, Eastern Point Road, Groton, CT, 06340, USA
1b Current address: Frontage Laboratories, Inc., 75 E Uwchlan Avenue, Suite 100, Exton, PA, 19341, USA
1c Current address: Department of Chemistry, University of Michigan, CHEM 3614, 930 North University Ave, Ann Arbor, MI, 48109, USA.

2a Seyferth D. Organometallics 2006; 25: 2
2b Seyferth D. Organometallics 2009; 28: 2
2c Lochmann L, Janata M. Eur. J. Chem. 2014; 12: 537
2d Robertson SD, Uzelac M, Mulvey RE. Chem. Rev. 2019; 119: 8332

3a Schade C, Bauer W, Von Ragué Schleyer P. J. Organomet. Chem. 1985; 295: c25
3b Turner RR, Altenau AG, Cheng TC. Anal. Chem. 1970; 42: 1835
3c Mordini, A.; Valcchi, M.; In Science of Synthesis, Vol. 8b; Majewski, M.; Snieckus, V.; Eds.; Thieme: Stuttgart, 2005, 1215.
3d Lochmann L, Pospíšil J, Lím D. Tetrahedron Lett. 1966; 7: 257

4a Raynolds S, Levine R. J. Am. Chem. Soc. 1960; 82: 472
4b Lochmann L, Trekoval J. J. Organomet. Chem. 1979; 179: 123
4c Barr D, Dawson AJ, Wakefield BJ. J. Chem. Soc., Chem. Commun. 1992; 204

We examined the efficacy of 2-ethylhexylsodium as a hydrocarbon-soluble alkylsodium and found it functional but inconvenient to manipulate, see:

5a Eidt SH, Malpass DB. EP 0041306 A1, 1981
5b Sakharov SG, Pakuro NI, Arest-Yakubovich AA, Shcheglova LV, Petrovskii PV. J. Organomet. Chem. 1999; 580: 205
5c Maréchal J.-M, Carlotti S, Shcheglova L, Deffieux A. Polymer 2003; 44: 7601

For studies of base-mediated solvent decomposition, see:

6a Holm T. Acta Chem. Scand. 1978; 32B: 162
6b Bates TF, Clarke MT, Thomas RD. J. Am. Chem. Soc. 1988; 110: 5109
6c Raposo ML, Fernández-Nieto F, Garcia-Rio L, Rodríguez-Dafonte P, Paleo MR, Sardina FJ. Chem. Eur. J. 2013; 19: 9677
6d Corset J, Castellà-Ventura M, Froment F, Strzalko T, Wartski L. J. Raman Spectrosc. 2002; 33: 652

7 Andrews PC, Barnett ND. R, Mulvey RE, Clegg W, O’Neil PA, Barr D, Cowton L, Dawson AJ, Wakefield BJ. J. Organomet. Chem. 1996; 518: 85
8 Clegg W, Conway B, Kennedy AR, Klett J, Mulvey RE, Russo L. Eur. J. Inorg. Chem. 2011; 721
9 Gilman H, Bebb RL. J. Am. Chem. Soc. 1939; 61: 109
10 Morton AA, Ward FK. J. Org. Chem. 1960; 25: 120
11 Ma Y, Algera RF, Collum DB. J. Org. Chem. 2016; 81: 11312
12 Mayr H, Ofial AR. Angew. Chem. Int. Ed. 2006; 45: 1844
13 Farina V, Reeves JT, Senanayake CH, Song JJ. Chem. Rev. 2006; 106: 2734

14a Hoppe D, Morgan BJ, Kozlowski MC. (–)-Sparteine . In e-EROS Encyclopedia of Reagents for Organic Synthesis . John Wiley & Sons; New York: 2007: 1-6
14b Kizirian J.-C. Top. Stereochem. 2010; 26: 189

15a Wong HN. C. Nat. Catal. 2019; 2: 282
15b Asako S, Nakajima H, Takai K. Nat. Catal. 2019; 2: 297

16 Zhou Y, Keresztes I, MacMillan SN, Collum DB. J. Am. Chem. Soc. 2019; 141: 16865
17 Algera RF, Ma Y, Collum DB. J. Am. Chem. Soc. 2017; 139: 7921

18a Border EC, Koutsaplis M, Andrews PC. Organometallics 2016; 35: 303
18b Andrews PC, Duggan PJ, Maguire M, Nichols PJ. Chem. Commun. 2001; 53

19a Collum DB. Acc. Chem. Res. 1993; 26: 227
19b Lucht BL, Collum DB. Acc. Chem. Res. 1999; 32: 1035
19c Mack KA, McClory A, Zhang H, Gosselin F, Collum DB. J. Am. Chem. Soc. 2017; 139: 12182

20 Renny JS, Tomasevich LL, Tallmadge EH, Collum DB. Angew. Chem. Int. Ed. 2013; 52: 11998

21a Eastham JF, Gibson GW. J. Am. Chem. Soc. 1963; 85: 2171
21b Bartlett PD, Goebel CV, Weber WP. J. Am. Chem. Soc. 1969; 91: 7425
21c Lewis HL, Brown TL. J. Am. Chem. Soc. 1970; 92: 4664
21d Popov AI. Pure Appl. Chem. 1975; 41: 275

22 Optimized protocols for DFT computations will be delineated in ref. 33.
23 Mulvey RE, Robertson SD. Angew. Chem. Int. Ed. 2013; 52: 11470
24 The TMEDA-solvated dimer has been characterized crystallographically.⁶
25 Zhang Z, Collum DB. J. Am. Chem. Soc. 2019; 141: 388
26 Ma Y, Woltornist RA, Algera RF, Collum DB. J. Org. Chem. 2019; 84: 9051

27a Gossage RA, Jastrzebski JT. B. H, van Koten G. Angew. Chem. Int. Ed. 2005; 44: 1448
27b Seebach D. Angew. Chem., Int. Ed. Engl. 1988; 27: 1624
27c Reich HJ. Chem. Rev. 2013; 113: 7130

28a Collum DB, McNeil AJ, Ramírez A. Angew. Chem. Int. Ed. 2007; 46: 3002
28b Algera RF, Gupta L, Hoepker AC, Liang J, Ma Y, Singh KJ, Collum DB. J. Org. Chem. 2017; 82: 4513
28c Meek SJ, Pitman CL, Miller AJ. M. J. Chem. Educ. 2016; 93: 275
28d Simmons EM, Hartwig JF. Angew. Chem. Int. Ed. 2012; 51: 3066

29 LDA does not appear to isomerize simple alkenes.
30 Although unreported, cyclohexa-1,4-diene can be metalated slowly with LDA.
31 Algera RF, Ma Y, Collum DB. J. Am. Chem. Soc. 2017; 139: 11544
32 Yamada S. Chem. Rev. 2018; 118: 11353
33 Ma, Y.; Woltornist, R. A.; Algera, R. F.; Collum, D. B. manuscript in preparation.
34 Snieckus V. Chem. Rev. 1990; 90: 879
35 Ma Y, Algera RF, Woltornist RA, Collum DB. J. Org. Chem. 2019; 84: 10860

For a recent application of NaDA-mediated 3-picoline functionalization, see:

36a LaMontagne MP, Ao MS, Markovac A, Menke JR. J. Med. Chem. 1976; 19: 363
36b Bond JL, Krottinger D, Schumacher RM, Sund EH, Weaver TJ. J. Chem. Eng. Data 1973; 18: 349
36c Mamane V, Louërat F, Iehl J, Abboud M, Fort YA. Tetrahedron 2008; 64: 10699

37 Baum BM, Levine R. J. Heterocycl. Chem. 1966; 3: 272
38 Ma Y, Breslin S, Keresztes I, Lobkovsky E, Collum DB. J. Org. Chem. 2008; 73: 9610
39 Munguia T, Bakir ZA, Cervantes-Lee F, Metta-Magana A, Pannell KH. Organometallics 2009; 28: 5777
40 Han Z, Chen S, Tu Y, Lian X, Li G. Eur. J. Org. Chem. 2019; 4658
41 Mohamadi F, Collum DB. Tetrahedron Lett. 1984; 25: 271
42 The elimination of halo ethers to acetylenes is facile with NaNH₂, see: Matovic N, Matthias A, Gertsch J, Raduner S, Bone KM, Lehmann RP, DeVoss JJ. Org. Biomol. Chem. 2007; 5: 169
43 Jakubec P, Muratore ME, Aillaud I, Thompson AL, Dixon DJ. Tetrahedron: Asymmetry 2015; 26: 251
44 For the substitution of an alkyl triflate by a sodium amide, see: Cruciani G, Valeri A, Goracci L, Pellegrino RM, Buonerba F, Baroni M. J. Med. Chem. 2014; 57: 6183
45 Su C, Williard PG. Org. Lett. 2010; 12: 5378

46a Pietruszka J, Konig WA, Maelgerb H, Kopf J. Chem. Ber. 1993; 126: 159 ; and references cited therein
46b Ball WJ, Landor SR. J. Chem. Soc. 1962; 2298
46c Caubere P, Coudert G. Bull. Soc. Chim. Fr. 1973; 3067
46d Christl M, Groetsch S, Gunther K. Angew. Chem. Int. Ed. 2000; 39: 3261

47a Ramírez A, Collum DB. J. Am. Chem. Soc. 1999; 121: 11114
47b Apparu M, Barrelle M. Tetrahedron 1978; 34: 1541
47c Whitesell JK, White PD. Synthesis 1975; 602

48 Boeckman RK, Boehmler DJ, Musselman RA. Org. Lett. 2001; 3: 3777

49a Plutschack MB, Bartholomäus P, Gilmore K, Seeberger PH. Chem. Rev. 2017; 117: 11796
49b Bogdan AR, Dombrowski AW. J. Med. Chem. 2019; 62: 6422

50 Wiedmann N, Ketels M, Knochel P. Angew. Chem. Int. Ed. 2018; 57: 10748
51 Gros PC, Fort Y. Eur. J. Org. Chem. 2009; 4199

52a Barozzino-Consiglio G, Yuan Y, Fressigné C, Harrison-Marchand A, Oulyadi H, Maddaluno J. Organometallics 2015; 34: 4441
52b Steffen P, Unkelbach C, Christmann M, Hiller W, Strohmann C. Angew. Chem. 2013; 52: 9836
52c Harrison-Marchand A, Gerard H, Maddaluno J. New J. Chem. 2012; 36: 2441
52d Denmark SE, Nakajima N, Stiff CM, Nicaise OJ.-C, Kranz M. Adv. Synth. Catal. 2008; 350: 1023
52e Gammon JJ, Canipa SJ, O’Brien P, Kelly B, Taylor S. Chem. Commun. 2008; 3750
52f Ramírez A, Sun X, Collum DB. J. Am. Chem. Soc. 2006; 128: 10326 ; and references cited therein

For reviews on phase-transfer catalysis, see:

53a Dehmlow EV, Dehmlow SS. Phase Transfer Catalysis, 3rd ed. Wiley-VCH; Weinheim: 1993
53b Starks CM, Liotta CL, Halpern M. Phase-Transfer Catalysis. Chapman & Hall; New York: 1994
53c Sasson Y, Neumann R. Handbook of Phase-Transfer Catalysis . Blackie Academic & Professional; London: 1997
53d Phase-Transfer Catalysis Mechanisms and Synthesis, ACS Symposium Series 659. Halpern ME. American Chemical Society; Washington DC: 1997

54a Naik SD, Doraiswamy LK. AIChE J. 1998; 44: 612
54b Liotta CL, Berkner J, Wright J, Fair B. Mechanisms and Applications of Solid–Liquid Phase-Transfer Catalysis . In Phase-Transfer Catalysis Mechanisms and Synthesis, ACS Symposium Series 659. Halpern ME. American Chemical Society; Washington DC: 1997. Chap. 3

55 Majhi J, Turnbull BW. H, Ryu H, Park J, Baik M.-H, Evans PA. J. Am. Chem. Soc. 2019; 141: 11770

Inorganic chemists have found NaDA useful for installing the diisopropylamido moiety into transition-metal coordination spheres, see:

56a Spallek T, Heß O, Meermann-Zimmermann M, Meermann C, Klimpel MG, Estler F, Schneider D, Scherer W, Tafipolsky M, Törnroos KW, Maichle-Mössmer C, Sirsch P, Anwander R. Dalton Trans. 2016; 45: 13750
56b Clegg W, García-Álvarez J, García-Álvarez P, Graham DV, Harrington RW, Hevia E, Kennedy AR, Mulvey RE, Russo L. Organometallics 2008; 27: 2654

57a Lipshutz BH, Ellsworth EL. Tetrahedron Lett. 1988; 29: 893
57b Bertz SH, Gibson CP, Dabbagh G. Organometallics 1988; 7: 227
57c Eaborn C, Hill MS, Hitchcock PB, Smith JD. Organometallics 2000; 19: 5780

58a Mangelinckx S, Giubellina N, De Kimpe N. Chem. Rev. 2004; 104: 2353
58b Caine D. Product Subclass 17: α-Lithio Aldehydes, α-Lithio Ketones, and Related Compounds. In Science of Synthesis, Vol. 8a. Snieckus V. Georg Thieme Verlag; Stuttgart: 2005

59 For NaDA-initiated polymerization of styrene, see: Nagasaki Y, Ito H, Tsuruta T. Makromol. Chem. 1986; 187: 23
60 Tsuruta T. Makromol. Chem. 1985; 13: 33