Lithium Compounds in Organic Synthesis E-Book
178,99 €
Mehr erfahren.
- Herausgeber: Wiley-VCH
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
This unique book covers fundamentals of organolithium compounds and gives a comprehensive overview of the latest synthetic advances and developments in the field. Part I covers computational and spectroscopic aspects as well as structure-reactivity relationships of organolithiums, whereas Part II deals with new lithium-based synthetic methodologies as well as novel synthetic applications of functionalized lithium compounds. A useful resource for newcomers and active researchers involved in organic synthesis, whether working in academia or industry!
Sie lesen das E-Book in den Legimi-Apps auf:
Seitenzahl: 843
Veröffentlichungsjahr: 2014
Ähnliche
Table of Contents
Cover
Related Titles
Title Page
Copyright
Dedication
List of Contributors
Foreword
Preface
Part I: New Structural Aspects of Lithium Compounds
Chapter 1: Structure–Reactivity Relationship in Organolithium Compounds
1.1 Structural Principles in Organolithium Compounds
1.2 Donor-Base-Free Structures
1.3 Disaggregation with Lewis Bases
1.4 Donor-Base-Induced Dimers and Monomers
1.5 Heterobimetallic Organolithium Compounds
1.6 Conclusion and Outlook
References
Further Reading
Chapter 2: Computational Perspectives on Organolithiums
2.1 Introduction
2.2 The Nature of Bonds to Lithium
2.3 Aggregation of Lithium Organic Compounds
2.4 Solvation Effects
2.5 Lithium Alkoxides and Lithium Amides
2.6 Computational Studies on Various Organolithium Applications
2.7 Conclusion and Outlook
References
Further Reading
Chapter 3: Spectroscopic Advances in Organolithium Reactivity: The Contribution of Rapid-Injection NMR (RINMR)
3.1 Introduction
3.2 The Curtin–Hammett Principle
3.3 Organolithium NMR
3.4 Features of RINMR
3.5 Use of RINMR to Study Organometallic Reactions
3.6 Conclusion and Outlook
References
Further Reading
Chapter 4: Spectroscopic Advances in Structural Lithium Chemistry: Diffusion-Ordered Spectroscopy and Solid-State NMR
4.1 General Introduction
4.2 Application of Solution NMR to the Structural Characterization of Organolithium Compounds
4.3 Solid-State NMR
References
Further Reading
Chapter 5: Mixed Lithium Complexes: Structure and Applicationin Synthesis
5.1 Introduction
5.2 Structural Chemistry of Heterometallic Lithium Complexes
5.3 Structural Chemistry of Heteroanionic Lithium Complexes
5.4 Synthetic Applications of Lithium Magnesiates: Turbo-Grignard Reagents
5.5 Conclusion and Outlook
References
Further Reading
Part II: New Synthetic Methodologies Based on Lithium Compounds
Chapter 6: Oxygen-Bearing Lithium Compounds in Modern Synthesis
6.1 Introduction
6.2 α-Lithiated Oxygen-Substituted Compounds
6.3
ortho
-Lithiated Oxygen-Bearing Aromatic Compounds
6.4 Remote Lithiated Oxygen-Bearing Compounds
6.5 Conclusion and Outlook
References
Further Reading
Chapter 7: Nitrogen-Bearing Lithium Compounds in Modern Synthesis
7.1 Introduction
7.2 Lithiation of Cyclic Amines
7.3 Lithiation of Acyclic Amines
7.4 Conclusion and Outlook
References
Further Reading
Chapter 8: Sulfur-Bearing Lithium Compounds in Modern Synthesis
8.1 Introduction
8.2 α-Lithiation
8.3 β-Lithiation (ortho-Directed Lithiation)
8.4 γ-Lithiation
8.5 Conclusion and Outlook
References
Further Reading
Chapter 9: Phosphorus-Bearing Lithium Compounds in Modern Synthesis
9.1 Introduction
9.2 Carbanions Directly Linked to a Phosphorus Atom: PC
1
Li
9.3 Carbanions Separated by One Atom from the Phosphorus: PC
2
Li
9.4 Carbanions Separated by Three Bonds from a Phosphorus Atom: PC
3
Li
9.5 Conclusion and Outlook
References
Further Reading
Chapter 10: Advances in the Chemistry of Chiral Lithium Amides
10.1 Introduction
10.2 Chiral Lithium Amides as Bases
10.3 Chiral Lithium Amides as Nucleophiles
10.4 Chiral Lithium Amides as Ligands
10.5 Chiral Lithium Amides Structures
10.6 Conclusion and Outlook
References
Chapter 11: Advances in Carbolithiation
11.1 Introduction: The Definition of the Carbolithiation Reaction
11.2 Intermolecular Carbolithiation of Alkenes
11.3 Intramolecular Carbolithiation of Alkenes
11.4 Intermolecular Carbolithiation of Alkynes
11.5 Intramolecular Carbolithiation of Alkynes
11.6 Conclusion and Outlook
References
Further Reading
Chapter 12: Reductive Lithiation and Multilithiated Compounds in Synthesis
12.1 Introduction
12.2 Alternative Solvents for Reductive Lithiation Reactions
12.3 Reductive Lithiation of Heterocyclic Compounds
12.4 Reductive Lithiation via C–C Bond Cleavage
12.5 Ammonia-Free Birch Reductions
12.6 Silyl-Lithium Derivatives
References
Further Reading
Chapter 13: Dearomatization and Aryl Migration in Organolithium Chemistry
13.1 Introduction
13.2 Intermolecular Dearomatizing Addition Reactions
13.3 Intramolecular Dearomatizing Cyclization Reactions
13.4 Aryl Migrations
13.5 Alkenyl Migrations
13.6 Conclusion and Outlook
References
Chapter 14: Lithium–Boron Chemistry: A Synergistic Strategy in Modern Synthesis
14.1 Reagent-Controlled Lithiation-Borylation
14.2 α-Halogen-Stabilized Lithium Carbenoids
14.3 Alkylidene-Type Carbenoids
14.4 α-Oxygen-Stabilized Organolithiums
14.5 α-Nitrogen-Stabilized Organolithiums
14.6 Conclusion and Outlook
References
Further Reading
Chapter 15: Lithiated Aza-Heterocycles in Modern Synthesis
15.1 Introduction
15.2 Direct Metallation with Lithiated Bases versus Nucleophilic Addition to Bare Pyridines and Analogs
15.3 Metallation of Dipolar Adducts of Pyridines (
N
-Oxides or BF
3
Adducts)
15.4 Halogen–Metal Exchange in Aza-Heterocyclic Series
15.5 Directed Ortho-Metallation (DoM) of Aza-Heterocycles
15.6 Halogen Dance: A Useful Side Reaction
15.7 Lateral and Remote Metallations
15.8 Lithiation Investigations of the Nicotinic Unit
15.9 Miscellaneous Examples of Various Heteroaryllithium Reagents as Key Intermediates in Organic Synthesis
15.10 Conclusion and Outlook
References
Chapter 16: Lithium Compounds in Cross-Coupling Reactions
16.1 Introduction
16.2 Cross-Coupling Reactions of Organolithium Reagents
16.3 Cross-Coupling Reactions of Lithium Enolates
16.4 Cross-Coupling Reactions of Lithium Amides
16.5 Cross-Coupling Reactions of Lithium Thiolates
16.6 Conclusion and Outlook
References
Chapter 17: Microreactor Technology in Lithium Chemistry
17.1 Introduction
17.2 Characteristic Features of Flow Microreactors
17.3 Control of Unstable Organolithiums Using Flow Microreactors
17.4 Protecting-Group-Free Synthesis Using Flow Microreactors
17.5 Stereoselective Reactions Based on Control of Configurationally Unstable Organollithiums Using Flow Microreactors
17.6 Switching Reaction Pathways of Organolithiums Using Flow Microreactors
17.7 Reaction Integration Using Flow Microreactors
17.8 Controlled/Living Anionic Polymerization of Vinyl Monomers Using Organolithium Initiators in Flow Microreactors
17.9 Conclusion and Outlook
References
Chapter 18: Practical Aspects of Organolithium Chemistry
18.1 Introduction
18.2 General Preparations of Organolithium Compounds
18.3 Practical Aspects Related to the Use of Organolithiums
18.4 NMR Analysis of Organolithium Reagents
18.5 Hazards Associated with Organolithium Compounds
18.6 Setting up of Experiments Using Organolithiums
18.7 Transferring Organolithiums
References
Further Reading
Index
End User License Agreement
Pages
XV
XVI
XVII
XVIII
XIX
XXI
XXII
XXIII
XXIV
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
177
176
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
204
203
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
277
276
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
315
314
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
393
392
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
412
413
414
415
416
417
418
419
420
421
422
423
424
425
426
427
428
429
430
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
465
466
467
468
469
470
471
472
473
474
475
476
477
478
479
480
481
482
483
484
485
486
487
488
489
491
492
493
494
495
496
497
498
499
500
501
502
503
504
505
506
507
508
509
510
511
512
513
514
515
516
517
519
520
521
522
523
524
525
526
527
528
529
530
531
532
533
534
535
536
537
538
1
151
Guide
Cover
Table of Contents
Preface
Part I: New Structural Aspects of Lithium Compounds
Chapter 1: Structure–Reactivity Relationship in Organolithium Compounds
List of Illustrations
Figure 1.1
Figure 1.2
Figure 1.3
Figure 1.4
Figure 1.5
Figure 1.6
Figure 1.7
Figure 1.8
Figure 1.9
Figure 1.10
Figure 1.11
Scheme 1.1
Figure 1.12
Scheme 1.2
Figure 1.13
Figure 1.14
Figure 1.15
Scheme 1.3
Scheme 1.4
Scheme 1.5
Figure 1.16
Figure 1.17
Figure 1.18
Scheme 1.6
Figure 1.19
Scheme 1.7
Scheme 1.8
Figure 2.1
Scheme 2.1
Scheme 2.2
Scheme 2.3
Scheme 2.4
Scheme 2.5
Scheme 2.6
Scheme 2.7
Scheme 2.8
Figure 3.1
Figure 3.2
Figure 3.3
Figure 3.4
Scheme 3.1
Figure 3.5
Figure 3.6
Scheme 3.2
Figure 3.7
Figure 3.8
Scheme 3.3
Figure 3.9
Scheme 3.4
Scheme 3.5
Scheme 3.6
Figure 3.10
Scheme 3.7
Scheme 3.8
Figure 3.11
Figure 3.12
Figure 3.13
Scheme 3.9
Scheme 3.10
Figure 3.14
Figure 4.1
Figure 4.2
Figure 4.3
Scheme 4.1
Figure 4.4
Figure 4.5
Figure 4.6
Figure 4.7
Figure 4.8
Figure 4.9
Scheme 4.2
Figure 4.10
Scheme 4.3
Figure 4.11
Figure 4.12
Figure 4.13
Scheme 4.4
Figure 4.14
Figure 4.15
Figure 4.16
Figure 4.17
Figure 5.1
Figure 5.2
Figure 5.3
Figure 5.4
Figure 5.5
Figure 5.6
Figure 5.7
Scheme 5.1
Figure 5.8
Figure 5.9
Scheme 5.2
Figure 5.10
Figure 5.11
Figure 5.12
Figure 5.13
Figure 5.14
Figure 5.15
Figure 5.16
Scheme 5.3
Scheme 5.4
Scheme 5.5
Scheme 5.6
Scheme 5.7
Scheme 5.8
Scheme 5.9
Scheme 6.1
Scheme 6.2
Scheme 6.3
Scheme 6.4
Scheme 6.5
Scheme 6.6
Figure 6.1
Scheme 6.7
Scheme 6.8
Scheme 6.9
Scheme 6.10
Scheme 6.11
Scheme 6.12
Scheme 6.13
Scheme 6.14
Scheme 6.15
Figure 6.2
Scheme 6.16
Scheme 6.17
Figure 6.3
Figure 6.4
Scheme 6.18
Scheme 6.19
Scheme 6.20
Scheme 6.21
Scheme 6.22
Scheme 6.23
Scheme 6.24
Scheme 6.25
Scheme 6.26
Scheme 6.27
Scheme 6.28
Scheme 6.29
Scheme 6.30
Scheme 6.31
Scheme 6.32
Scheme 6.33
Scheme 6.34
Scheme 6.35
Scheme 6.36
Scheme 6.37
Scheme 6.38
Scheme 6.39
Scheme 6.40
Scheme 6.41
Scheme 6.42
Scheme 7.1
Scheme 7.2
Scheme 7.3
Scheme 7.4
Scheme 7.5
Scheme 7.6
Scheme 7.7
Scheme 7.8
Scheme 7.9
Scheme 7.10
Scheme 7.11
Scheme 7.12
Scheme 7.13
Scheme 7.14
Scheme 7.15
Scheme 7.16
Scheme 7.17
Scheme 7.18
Scheme 7.19
Scheme 7.20
Scheme 7.21
Scheme 7.22
Scheme 7.23
Scheme 7.24
Scheme 7.25
Scheme 7.26
Scheme 7.27
Scheme 7.28
Scheme 7.29
Scheme 7.30
Scheme 7.31
Scheme 7.32
Scheme 7.33
Scheme 7.34
Scheme 7.35
Scheme 7.36
Scheme 7.37
Scheme 7.38
Scheme 7.39
Scheme 7.40
Scheme 7.41
Scheme 7.42
Scheme 7.43
Scheme 7.44
Figure 8.1
Scheme 8.1
Scheme 8.2
Scheme 8.3
Scheme 8.4
Scheme 8.5
Scheme 8.6
Scheme 8.7
Scheme 8.8
Scheme 8.9
Scheme 8.10
Scheme 8.11
Scheme 8.12
Scheme 8.13
Scheme 8.14
Scheme 8.15
Scheme 8.16
Scheme 8.17
Scheme 8.18
Scheme 8.19
Scheme 8.20
Scheme 8.21
Scheme 8.22
Scheme 8.23
Scheme 8.24
Scheme 8.25
Scheme 8.26
Scheme 8.27
Scheme 8.28
Scheme 8.29
Scheme 8.30
Scheme 8.31
Scheme 8.32
Scheme 8.33
Scheme 8.34
Scheme 8.35
Figure 8.2
Scheme 8.36
Scheme 8.37
Scheme 8.38
Scheme 8.39
Scheme 8.40
Scheme 8.41
Scheme 8.42
Scheme 8.43
Scheme 8.44
Scheme 8.45
Scheme 8.46
Scheme 8.47
Scheme 8.48
Scheme 8.49
Scheme 8.50
Scheme 8.51
Scheme 8.52
Scheme 8.53
Scheme 8.54
Scheme 8.55
Scheme 8.56
Scheme 8.57
Scheme 8.58
Scheme 8.59
Scheme 8.60
Scheme 8.61
Scheme 8.62
Scheme 8.63
Scheme 9.1
Figure 9.1
Scheme 9.2
Scheme 9.3
Scheme 9.4
Scheme 9.5
Scheme 9.6
Scheme 9.7
Scheme 9.8
Scheme 9.9
Scheme 9.10
Scheme 9.11
Figure 9.2
Scheme 9.12
Scheme 9.13
Scheme 9.14
Scheme 9.15
Figure 10.1
Figure 10.2
Figure 10.3
Figure 10.4
Figure 10.5
Figure 10.6
Figure 10.7
Figure 10.8
Scheme 10.1
Scheme 10.2
Scheme 10.3
Scheme 10.4
Scheme 10.5
Scheme 10.6
Scheme 10.7
Scheme 10.8
Scheme 10.9
Scheme 10.10
Scheme 10.11
Scheme 10.12
Scheme 10.13
Scheme 10.14
Scheme 10.15
Scheme 10.16
Figure 10.9
Scheme 10.17
Scheme 10.18
Scheme 10.19
Scheme 11.1
Scheme 11.2
Scheme 11.3
Scheme 11.4
Scheme 11.5
Scheme 11.6
Scheme 11.7
Scheme 11.8
Scheme 11.9
Scheme 11.10
Scheme 11.11
Scheme 11.12
Scheme 11.13
Scheme 11.14
Scheme 11.15
Scheme 11.16
Scheme 11.17
Scheme 11.18
Scheme 11.19
Scheme 11.20
Scheme 11.21
Scheme 11.22
Scheme 11.23
Scheme 11.24
Scheme 11.25
Scheme 11.26
Scheme 11.27
Scheme 11.28
Scheme 11.29
Scheme 12.1
Scheme 12.2
Scheme 12.3
Scheme 12.4
Scheme 12.5
Scheme 12.6
Scheme 12.7
Scheme 12.8
Scheme 12.9
Scheme 12.10
Scheme 12.11
Scheme 12.12
Scheme 12.13
Scheme 12.14
Scheme 12.15
Scheme 12.16
Scheme 12.17
Scheme 12.18
Scheme 12.19
Scheme 12.20
Scheme 12.21
Scheme 12.22
Scheme 12.23
Scheme 12.24
Scheme 12.25
Scheme 12.26
Scheme 12.27
Scheme 12.28
Scheme 12.29
Scheme 12.30
Scheme 12.31
Scheme 12.32
Scheme 13.1
Scheme 13.2
Scheme 13.3
Scheme 13.4
Scheme 13.5
Scheme 13.6
Scheme 13.7
Scheme 13.8
Scheme 13.9
Scheme 13.10
Scheme 13.11
Scheme 13.12
Scheme 13.13
Scheme 13.14
Scheme 13.15
Scheme 13.16
Scheme 13.17
Scheme 13.18
Scheme 13.19
Scheme 13.20
Scheme 13.21
Scheme 13.22
Scheme 13.23
Scheme 13.24
Scheme 13.25
Scheme 13.26
Scheme 13.27
Scheme 13.28
Scheme 13.29
Scheme 14.1
Scheme 14.2
Scheme 14.3
Scheme 14.4
Scheme 14.5
Scheme 14.6
Figure 14.1
Scheme 14.7
Scheme 14.8
Scheme 14.9
Scheme 14.10
Scheme 14.11
Scheme 14.12
Scheme 14.13
Scheme 14.14
Figure 14.2
Scheme 14.15
Scheme 14.16
Scheme 14.17
Scheme 14.18
Scheme 14.19
Scheme 14.20
Scheme 14.21
Scheme 14.22
Scheme 14.23
Scheme 14.24
Scheme 14.25
Scheme 14.26
Scheme 15.1
Scheme 15.2
Scheme 15.3
Scheme 15.4
Scheme 15.5
Scheme 15.6
Scheme 15.7
Scheme 15.8
Figure 15.1
Figure 15.2
Figure 15.3
Scheme 15.9
Scheme 15.10
Figure 15.4
Figure 15.5
Scheme 15.11
Figure 15.6
Scheme 15.12
Scheme 15.13
Scheme 15.14
Scheme 15.15
Scheme 15.16
Scheme 15.17
Scheme 15.18
Figure 15.7
Scheme 15.19
Figure 15.8
Scheme 15.20
Scheme 15.21
Scheme 15.22
Scheme 15.23
Scheme 15.24
Figure 15.9
Scheme 15.25
Scheme 15.26
Scheme 15.27
Scheme 15.28
Scheme 15.29
Scheme 15.30
Scheme 15.31
Scheme 15.32
Scheme 15.33
Figure 15.10
Scheme 16.1
Scheme 16.2
Scheme 16.3
Scheme 16.4
Scheme 16.5
Scheme 16.6
Scheme 16.7
Scheme 16.8
Scheme 16.9
Scheme 16.10
Scheme 16.11
Scheme 16.12
Scheme 16.13
Scheme 16.14
Scheme 16.15
Scheme 16.16
Scheme 16.17
Scheme 16.18
Scheme 16.19
Scheme 16.20
Scheme 16.21
Scheme 16.22
Scheme 16.23
Scheme 16.24
Scheme 16.25
Scheme 16.26
Scheme 16.27
Scheme 16.28
Scheme 16.29
Scheme 16.30
Figure 17.1
Figure 17.2
Figure 17.3
Figure 17.4
Figure 17.5
Figure 17.6
Figure 17.7
Figure 17.8
Figure 17.9
Figure 17.10
Figure 17.11
Figure 17.12
Figure 17.13
Figure 17.14
Figure 17.15
Figure 17.16
Figure 17.17
Figure 17.18
Figure 17.19
Figure 17.20
Figure 17.21
Figure 17.22
Scheme 18.1
Scheme 18.2
Scheme 18.3
Scheme 18.4
Scheme 18.5
Scheme 18.6
Scheme 18.7
Scheme 18.8
Scheme 18.9
Scheme 18.10
Scheme 18.11
Scheme 18.12
Figure 18.1
Scheme 18.13
Scheme 18.14
Scheme 18.15
Scheme 18.16
Figure 18.2
Figure 18.3
Figure 18.4
List of Tables
Table 1.1
Table 1.2
Table 1.3
Table 1.4
Table 1.5
Table 1.6
Table 1.7
Table 1.8
Table 1.9
Table 1.10
Table 1.11
Table 4.1
Table 14.1
Table 14.2
Table 14.3
Table 14.4
Table 14.5
Table 18.1
Table 18.2
Table 18.3
Table 18.4
Table 18.5
Table 18.6
Table 18.7
Table 18.8
Related Titles
de Meijere, A., Bräse, S., Oestreich, M. (eds.)
Metal Catalyzed Cross-Coupling Reactions and More
2014
Print-ISBN: 978-3-527-33154-3, also available in digital formats
Alexakis, A., Krause, N., Woodward, S. (eds.)
Copper-Catalyzed Asymmetric Synthesis
2014
Print ISBN: 978-3-527-33204-5, also available in digital formats
Christmann, M., Bräse, S. (eds.)
Asymmetric Synthesis II
More Methods and Applications
2012
Print ISBN: 978-3-527-32921-2, also available in digital formats
Hall, D.G. (ed.)
Boronic Acids
Preparation and Applications in Organic Synthesis, Medicine and Materials 2nd Edition
2011
Print ISBN: 978-3-527-32598-6, also available in digital formats
Bäckvall, J. (ed.)
Modern Oxidation Methods
2nd Edition
2011
Print ISBN: 978-3-527-32320-3, also available in digital formats
Bullock, R.M. (ed.)
Catalysis without Precious Metals
2010
Print ISBN: 978-3-527-32354-8, also available in digital formats
Lithium Compounds in Organic Synthesis
From Fundamentals to Applications
Edited by
Renzo Luisi and Vito Capriati
Editors
Prof. Renzo Luisi
University of Bari “A. Moro”
Department of Pharmacy - Drug
Sciences
Consortium C.I.N.M.P.I.S.
Via E. Orabona 4
I-70125 Bari
Italy
Prof. Vito Capriati
University of Bari “A. Moro”
Department of Pharmacy - Drug
Sciences
Consortium C.I.N.M.P.I.S.
Via E. Orabona 4
I-70125 Bari
Italy
All books published by Wiley-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.
Library of Congress Card No.: applied for
British Library Cataloguing-in-Publication Data
A catalogue record for this book is available from the British Library.
Bibliographic information published by the Deutsche Nationalbibliothek
The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at <http://dnb.d-nb.de>.
© 2014 Wiley-VCH Verlag & Co. KGaA, Boschstr. 12, 69469 Weinheim, Germany
All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.
Print ISBN: 978-3-527-33343-1
ePDF ISBN: 978-3-527-66754-3
ePub ISBN: 978-3-527-66753-6
mobi ISBN: 978-3-527-66752-9
oBook ISBN: 978-3-527-66751-2
To my Mom and Dad, with love.
Renzo Luisi
This book is gratefully dedicated to my dear wife, Annalisa, for her constant care and loving support, and to our wonderful sons, Alessandro and Valerio, who are an endless source of great love, inspiration, energy, and joy in our lives.
Vito Capriati
List of Contributors
Varinder K. Aggarwal
University of Bristol
School of Chemistry
Cantock's Close
Bristol, BS8 1TS
UK
José Alemán
Universidad Autónoma de Madrid
Organic Chemistry Department
Cantoblanco
28049 Madrid
Spain
Ugo Azzena
University of Sassari
Department of Chemistry and Pharmacy
via Vienna 2
I-07100 Sassari
Italy
Vito Capriati
University of Bari “A. Moro”
Department of Pharmacy - Drug
Sciences
Consortium C.I.N.M.P.I.S.
Via E. Orabona 4
I-70125 Bari
Italy
Elena Carl
Georg-August Universität Göttingen
Institut für Anorganische Chemie
Tammannstraße 4
Göttingen
Germany
Laura Carroccia
University of Bari “A. Moro”
Department of Pharmacy - Drug
Sciences
Consortium C.I.N.M.P.I.S.
Via E. Orabona 4
I-70125 Bari
Italy
Jonathan Clayden
University of Manchester
School of Chemistry
Oxford Road
Manchester M13 9PL
UK
Corinne Comoy
Université de Lorraine
Groupe Hétérocycles: Réactivité et Interaction (HécRIn)
SRSMC UMR CNRS 7565
Vandoeuvre-lès-Nancy
France
Leonardo Degennaro
University of Bari “A. Moro”
Department of Pharmacy - Drug
Sciences
Consortium C.I.N.M.P.I.S.
Via E. Orabona 4
I-70125 Bari
Italy
Yves Fort
Université de Lorraine
Groupe Hétérocycles: Réactivité et Interaction (HécRIn)
SRSMC UMR CNRS 7565
Vandoeuvre-lès-Nancy
France
José Luis García Ruano
Universidad Autónoma de Madrid
Organic Chemistry Department
Cantoblanco
28049 Madrid
Spain
Arianna Giovine
University of Bari “A. Moro”
Department of Pharmacy - Drug
Sciences
Consortium C.I.N.M.P.I.S.
Via E. Orabona 4
I-70125 Bari
Italy
Laure Guilhaudis
Université de Rouen
CNRS
INSA de Rouen
UMR 6014 & FR 3038
IRCOF: Laboratoire COBRA
Mont Saint Aignan Cedex
France
Anne Harrison-Marchand
Université de Rouen
CNRS
INSA de Rouen
UMR 6014 & FR 3038
IRCOF: Laboratoire COBRA
Mont-Saint-Aignan Cedex
France
Amanda C. Jones
Wake Forest University
Chemistry Department
Salem Hall
Winston-Salem
NC 27109
USA
Daniele Leonori
University of Bristol
School of Chemistry
Cantock's Close
Bristol, BS8 1TS
UK
Fernando López Ortiz
University of Almería
Area of Organic Chemistry
Sacramento road s/n
Almería
Spain
Renzo Luisi
University of Bari “A. Moro”
Department of Pharmacy - Drug
Sciences
Consortium C.I.N.M.P.I.S.
Via E. Orabona 4
I-70125 Bari
Italy
Jacques Maddaluno
Université de Rouen
CNRS
INSA de Rouen
UMR 6014 & FR 3038
IRCOF: Laboratoire COBRA
Mont-Saint-Aignan Cedex
France
Ilan Marek
Technion-Israel Institute of Technology
Schulich Faculty of Chemistry and the Lise Meitner-Minerva Center for Computational Quantum Chemistry
Haifa 32000
Israel
Yury Minko
Technion-Israel Institute of Technology
Schulich Faculty of Chemistry and the Lise Meitner-Minerva Center for Computational Quantum Chemistry
Haifa 32000
Israel
Robert E. Mulvey
University of Strathclyde
WestCHEM
Department of Pure and Applied Chemistry
Thomas Graham Building
Cathedral Street
Glasgow, G1 1XL
UK
Biagia Musio
University of Bari “A. Moro”
Department of Pharmacy - Drug
Sciences
Consortium C.I.N.M.P.I.S.
Via E. Orabona 4
I-70125 Bari
Italy
Aiichiro Nagaki
Kyoto University
Department of Synthetic Chemistry and Biological Chemistry
Graduate School of Engineering
Kyotodaigaku-Katsura, Nishikyo-ku
Kyoto 615-8510
Japan
Sten O. Nilsson Lill
University of Gothenburg
Department of Chemistry and Molecular Biology
Kemivägen 10
SE-412 96 Göteborg
Sweden
Charles T. O'Hara
University of Strathclyde
WestCHEM
Department of Pure and Applied Chemistry
Thomas Graham Building
Cathedral Street
Glasgow, G1 1XL
UK
Hassan Oulyadi
Université de Rouen
CNRS
INSA de Rouen
UMR 6014 & FR 3038
IRCOF: Laboratoire COBRA
Mont Saint Aignan Cedex
France
Alejandro Parra
Universidad Autónoma de Madrid
Organic Chemistry Department
Cantoblanco
28049 Madrid
Spain
Filippo M. Perna
University of Bari “A. Moro”
Department of Pharmacy - Drug
Sciences
Consortium C.I.N.M.P.I.S.
Via E. Orabona 4
I-70125 Bari
Italy
Luisa Pisano
University of Sassari
Department of Chemistry and Pharmacy
via Vienna 2
I-07100 Sassari
Italy
Antonio Salomone
University of Bari “A. Moro”
Department of Pharmacy - Drug
Sciences
Consortium C.I.N.M.P.I.S.
Via E. Orabona 4
I-70125 Bari
Italy
Muriel Sebban
Université de Rouen
CNRS
INSA de Rouen
UMR 6014 & FR 3038
IRCOF: Laboratoire COBRA
Mont Saint Aignan Cedex
France
Masaki Shimizu
Kyoto Institute of Technology
Department of Biomolecular Engineering
Graduate School of Science and Technology
Hashikami-cho
Matsugasaki
Sakyo-ku
Kyoto 606-8585
Japan
Dietmar Stalke
Georg-August Universität Göttingen
Institut für Anorganische Chemie
Tammannstraße 4
Göttingen
Germany
Phillip J. Unsworth
University of Bristol
School of Chemistry
Cantock's Close
Bristol, BS8 1TS
UK
Charlotte G. Watson
University of Bristol
School of Chemistry
Cantock's Close
Bristol, BS8 1TS
UK
Jun-Ichi Yoshida
Kyoto University
Department of Synthetic Chemistry and Biological Chemistry
Graduate School of Engineering
Kyotodaigaku-Katsura, Nishikyo-ku
Kyoto 615-8510
Japan
Foreword
Since the pioneering work of Ziegler, Wittig, and Gilman in the 1930, the area of organolithium chemistry has undergone a vigorous and rich evolution, which has been described in papers, reviews, accounts, and books. Nonetheless, lithium compounds continue to advance in power and scope and to develop in new directions at a remarkable pace. Organic chemists are enticed to develop modern methods of generation and handling and new chemical instruments to study properties, stability, reactivity, structural features, as organolithiums are of paramount utility for practing synthetic chemists. Indeed, once generated by C-H deprotonation, C-halogen exchange, carbolithiation or reductive lithiation, they can be exposed to a broad range of carbon and heteroatom electrophilic reagents to provide products of varied complexity, intermediates and target substances on a small and large scale.
Often depicted as simple monomeric species, the real structure of organolithiums is much more complicated making it possible for them to exist as dimers, tetramers, hexamers, and complex aggregates. The identification of their real molecular structure is then vital to deduce the structure–reactivity relationship which is essential to optimize reactions. Efforts are made to this end by matching experiments and modern technologies. By using modern and powerful chemical instruments the potential of organolithiums has increased dramatically in recent years. Indeed, the combination of computational chemistry with multinuclear magnetic resonance techniques, rapid injection NMR, diffusion-ordered spectroscopy, solid state NMR, and X-Ray diffraction analysis, has had a significant impact on organolithiums shedding light on their “true structure”, reactivity, and contributing to explain enantio- and diastereoselectivities of their reactions.
Within the large family of organolithium reagents, α-heterosubstituted organolithiums, including oxygen, nitrogen, boron, phosphorus, sulfur derivatives, have today been attracting particular attention as the heteroatom may significantly affect the properties of the related lithiated intermediate, its chemical and configurational stability, and the stereochemistry of its reactions. The carbenoid character of such heterosubstituted organolithiums is expected to bring improvements in organic synthesis.
The introduction of flow microreactors is causing a revolutionary change in organometallic chemistry. In fact, extensive studies on organolithiums using flow microreactors have opened up new possibilities in organic synthesis. This new technology is also expected to get more insights into the chemistry of organolithiums toward more successful synthetic applications.
Luisi and Capriati's “Lithium Compounds in Organic Synthesis: from Fundamentals to Applications” provides the readers with the state of the art of organolithiums and lets them to foresee further exciting developments in this area. I anticipate that this quite readable book will give all those interested in organolithium chemistry the inspiration to start new projects in this field.
Saverio Florio
Preface
Since the first discovery of organolithium compounds by Schlenk and Holtz in 1917, lithiation chemistry has grown more and more into a well-established and useful methodology for the selective construction of C–C bonds. The possibility of preparing functionalized lithiated compounds and of controlling their reactivity has set the stage for new surgical applications in organic synthesis especially in sterocontrolled processes, thereby transforming these intermediates into powerful reagents.
Advances in spectroscopic techniques in computational chemistry and the development of new crystallographic methods, now permit to identify also the most reactive fleeting intermediates both in solution and in the solid state, to study their stereodynamics, aggregation states, and to calculate their energies. Owing to the strong structure-reactivity relationship, these synergistic investigations are central to an understanding and to a modulation of the reactivity of organolithium compounds, and allow the optimization of the reaction conditions.
Lithium Compounds in Organic Synthesis – From Fundamentals to Applications provides new structural insights into organolithiums and covers the most innovative synthetic methodologies based on lithium compounds over the past decade according to the author's selection. The book is divided into two parts. Part I, New Structural Aspects of Lithium Compounds, describes recent structural features of organolithiums and mixed lithium complexes, and their impact on synthesis and reactivity; computational and spectroscopic aspects (in particular, contributions from rapid-injection NMR, diffusion-ordered spectroscopy, and solid state NMR) are also discussed. Part II, New Synthetic Methodologies Based on Lithium Compounds, is dedicated to synthetic strategies involving (stereodefined) oxygen-, nitrogen-, sulfur-, boron-, aza-heterocycle-, and phosphorus-bearing lithium compounds. Recent advances in the chemistry of chiral lithium amides, carbolithiation, and reductive lithiation have also been addressed. This latter part also features the importance of dearomatisation and aryl migration as well as catalytic cross-coupling reactions of lithium compounds. The benefit of microreactor technology in organolithium chemistry has been highlighted as well. Finally, a special chapter details practical aspects of working with lithium compounds. Each chapter has a concluding section summarizing the current status of the described chemistry, with an eye towards new challenging research directions.
We would like to thank all the contributors for their great support in preparing this book that, hopefully, may serve as a source of inspiration for major breakthroughs in this exciting field!
December 30, 2013
Renzo LuisiVito Capriati
Part I
New Structural Aspects of Lithium Compounds
Chapter 1Structure–Reactivity Relationship in Organolithium Compounds
Elena Carl and Dietmar Stalke
1.1 Structural Principles in Organolithium Compounds
Owing to the versatile application of organolithiums compounds in syntheses, the identification of their molecular structure is vital to deduce structure–reactivity relationships. In reaction schemes, the organolithium compounds are often depicted as monomeric species although it is known since 1963 that the real structure of these compounds is much more complicated. Back then, Dietrich [1] determined the first solid-state structure of soluble ethyllithium from single crystals (and the first solid-state structure of a lithium compound that was determined via experimental X-ray diffraction analyses ever). In the solid state, basic organolithium reagents such as n-BuLi, i-PrLi, and LiCH2SiMe3 form hexameric aggregates, while t-BuLi and MeLi aggregate to tetramers [2]. The basic building principle in these deltahedra is the arrangement of the lithium cations in a Li3 triangle capped by a carbanionic Cα atom (Figure 1.1). The Li3 triangle is the building block for deltahedral metal cores, and further aggregation leads to tetramers or hexamers where the lithium cation reaches its preferred coordination number of four [3].
Figure 1.1Aggregation of the μ3-Cα-capped Li3 triangle to give deltahedral metal cores.
The molecular structure in organolithium compounds is not only defined by the electrostatic interactions between the counter charged atoms (Li+ and −CH2R). The choice of the used solvent or co-solvent also has an immense effect on the molecular structure [4]. Our focus is on the disaggregation of lithium oligomers by adding Lewis donor bases and on the structural differences in organolithium compounds with a silicon next to the Cα carbon anion (Li–Cα–R3, Li–Cα–SiR3). We present experiments that demonstrate the enhanced reactivity of smaller disaggregated fragments as, for example, the benzylic deprotonation of toluene employing n-BuLi, which is only feasible on the addition of tetramethylethylenediamine (TMEDA) [5]. Alkyllithium compounds such as MeLi and n-BuLi are the most famous and commonly used representatives and their disaggregation has been investigated thoroughly for many years [6]. In addition, LiCH2SiMe3 is a commonly used reagent in syntheses [7] and interesting studies about its disaggregation and reactivity with different donor bases have been published recently.
1.2 Donor-Base-Free Structures
1.2.1 Tetramers
[MeLi]4 [8] (1), [EtLi]4 [9] (2), and [t-BuLi]4 [2a] (3) are the only donor-base-free tetrameric structures of organolithium compounds known so far. The characteristic core of these structures is built by four of the Li3 triangles joining together to create the tetrahedron. Each of the four Li3 triangles is μ3-capped by a Cα atom above the center of the equilateral metal triangle. In this way, each carbanion coordinates to three lithium atoms so that every lithium cation reaches at least its preferred coordination number of four. Even in the solid state, none of the three tetramers adopts ideal Td symmetry (Figure 1.2).
Figure 1.2 Solid-state structures of the basic [RLi]4 tetramers [MeLi]4 (1), [EtLi]4 (2), and [t-BuLi]4 (3).
However, the crystallographically independent Li···Li distances within the individual tetramers are similar within the estimated standard deviations (esds). They decrease from 256 pm in 1 to 253 pm in 2 and 241 pm in 3. One would expect the opposite considering the increasing steric demand of the organic groups. But along this line, the t-butyl group has the highest electron-releasing capability and provides the most charge to the single lithium cations so that they can get in closer proximity than in methyl lithium with a considerably higher positive charge and hence higher repulsion.
The Li–Cα bond lengths are almost invariant at 226 ± 2 pm and close to the mean Li–C bond distance of 230 pm from the CCDC (The Cambridge Crystallographic Data Centre) [10] (Table 1.1). [EtLi]4 and [t-BuLi]4 display relatively short Li···Cβ distances so that by the arrangement of the methyl groups in close proximity to a lithium cation some extra charge density can be provided to the lithium cation. In the [t-BuLi]4 tetramer, the t-butyl groups are even arranged ecliptically relative to the Li3 triangle. Because there is no Cβ atom in [MeLi]4, this gives rise to long-range interactions of the methyl groups of adjacent tetramers (Figure 1.3). As both the apical lithium cation and the basal lithium atoms point toward a nearby methanide group, the sum of all long-range interactions give the unit cell a tetramer in the center and the centroid of a tetramer at each corner. The related Li···“Cβ” distances (236 pm) are only 10 pm longer than the Li–Cα bonds. Their considerable contribution to the overall lattice energy leaves [MeLi]4,∞ insoluble in non-donating solvents while [EtLi]4 and [t-BuLi]4 are soluble even in nonpolar hydrocarbons such as hexane [3].
Table 1.1Distances in the alkyllithium tetramers (pm).
Compounds
Li···Li
Li–C
α
Li–C
β
References
[MeLi]
4
1
259
226
236
[8]
[EtLi]
4
2
253
228
250
[9]
[
t
-BuLi]
4
3
241
225
237
[2a]
Figure 1.3 Long-range interactions between the [MeLi]4 tetramers.
1.2.2 Hexamers
The most important and prominent representatives of the octahedral Li6 structural motif are [Me3SiCH2Li]6 [11] (4) and [n-BuLi]6 [2a] (5), followed by others such as [i-PrLi]6 [12] (6), [c-HexLi]6 [13] (7), and [(t-Bu)2C6H3Li]6 [14] (8) (Figure 1.4). In the Li6 octahedra, only six of the eight Li3 triangles are μ3-capped by Cα atoms. The two remaining uncapped Li3 triangles are arranged oppositely and show elongated Li···Li distances of 294–318 pm. This elongation is due to a stronger electrostatic repulsion of the uncapped lithium cations because the attraction and electron density of a capped anion is missing. The six carbanions of the octahedron form a “paddle-wheel” along the noncrystallographic threefold axis through the midpoint of these uncapped triangles.
Figure 1.4 Solid-state structures of [RLi]6 hexamers: [Me3SiCH2Li]6 (4), [n-BuLi]6 (5), [i-PrLi]6 (6), and [c-HexLi]6 (7).
On average, the bond distances of the capped Li3 triangles in the hexamers are equal to those of the tetramers (240–251 pm vs 240–246 pm) (Table 1.2). As in the tetramers, in all structures 5–7, secondary electron donation exists by the methyl group in β position to the metallated carbon atom or in γ position for [Me3SiCH2Li]6 (4), respectively.
Table 1.2Distances in the alkyllithium hexamers (pm).
Compounds
Li···Li
Li–C
α
Li–C
β
References
[Me
3
SiCH
2
Li]
6
4
246(318)
a
219(227)
267
b
[11]
[
n
-BuLi]
6
5
243(294)
216(227)
229
[2a]
[
i
-PrLi]
6
6
240(296)
218(231)
231
[12]
[
c
-HexLi]
6
7
240(297)
218(230)
249
[13]
[(
t
-Bu)
2
C
6
H
3
Li]
6
8
251(314)
215(221)
—
[14]
a Values in brackets represent the Li···Li distances in the unoccupied Li3 triangles.
b Li–Cγ distance.
1.2.3 Comparison of [Me3SiCH2Li]6 and [n-BuLi]6
Both compounds 4 and 5 have the same central structural motif, the hexameric Li6 octahedron capped by six carbanions. A closer look reveals small but appreciable structural differences between 4 and 5 due to the different types of carbanions. Structures 4 and 5 vary in the position of the Cα carbon atoms relative to the triangles. In [n-BuLi]6, the Cα is located more in the center of the lithium triangle while in [Me3SiCH2Li]6, the carbon atom is shifted to one side (Figure 1.5a) [15]. The Si–Cα bond is almost parallel to the closely approached Li···Li vector. This is reflected in a Si–C–Li bond angle close to 180° (175°) building an almost straight line. The corresponding C–Cα–Li angle in 5 is only 148°. The C–C bond is rotated to facilitate an interaction between the Cβ and the Li atom (Li–Cβ distance: 229 pm). It can be distinguished between longer and shorter Li–Cα bonds. Interestingly, the Li–Cα shortage is less pronounced in [LiCH2SiMe3]6 (219 pm vs 216 pm in [n-BuLi]6) while the longer Li–Cα distances are of the same length in both complexes. The similarity of the longer Li–Cα contacts in the uncapped triangles might be explained by electrostatic interactions of the lithium cation with the negatively charged carbanions without orbital control. A plausible explanation for the length difference in the shorter Li–C bonds of the capped Li3 triangles would be the stabilization of the carbanion in [LiCH2SiMe3]6 by increased negative hyperconjugation. The lone pairs at the carbanions (sp3 orbital mimicking electron density facing the Li3 triangle) interact with the σ* molecular orbital of the silicon–carbon bond in trans position (Figure 1.5b) [15].
Figure 1.5 (a) Exemplary position of the carbon anion relative to the Li3 triangle in (4) and (5). (b) Graphical representation of the supposed hyperconjugation in (4).
Hence, the anion is stabilized by negative hyperconjugation. Further evidence for this effect can be found in the Si–C bond lengths. In comparison to a standard Si–C bond length of 187 pm [16], shortened Si–Cα bonds are detected (184.5–185.7 pm) while the Si–C bonds of the methyl groups are elongated (186.7–189.0 pm). The concept of negative hyperconjugation implies that the Si–Ctrans bonds in trans position to the Li–C bond are more elongated than the Si–Ccis bonds because the σ* molecular orbital is stabilized. Such a tendency is not observed in [LiCH2SiMe3]6. Here, the Si–Ccis bonds are slightly longer in comparison to the Si–Ctrans bonds (Si–Ccis: 187.9(av.) and Si–Ctrans: 186.6(av.)).
An alternative explanation to the negative hyperconjugation is the contraction of the Cα–Si bond lengths due to strong electrostatic interactions between the negatively charged carbanion and positively charged silicon atom. According to a charge density investigation, the electrostatic attraction between two highly charged atoms dominates the negative hyperconjugation [15].
1.3 Disaggregation with Lewis Bases
Neutral Lewis bases are added to the organolithium compounds to decrease the degree of aggregation [17]. The Li–Cα and Li–Cβ interactions in the oligomeric structures are partly replaced by N–Li or O–Li donor bonds. Disaggregation increases the solubility and can also cause a drastic increase in reactivity because the rate-determining step is normally the reaction of the monomer [18]. The commonly used donor bases can be the solvent itself, such as diethyl ether (Et2O) and tetrahydrofuran (THF). The alternative choice is to add chelating or bridging ligands such as TMEDA, N,N,N′,N′′,N′′-pentamethylethylenetriamine (PMDETA), or dimethoxyethane (DME) (Figure 1.6).
Figure 1.6 Lewis bases frequently employed for disaggregation and discussed here.
1.3.1 Tetramers of Alkyllithium Compounds
The state of disaggregation depends on the added donor base and on the organolithium compound. The monodentate donor base THF, for example, is able to reduce the polymeric structure of [MeLi]4,∞ to the tetrameric molecular [(thf)MeLi]4 [19] (9) and the parent hexamer of [n-BuLi]6 to the tetramer [(thf)n-BuLi]4 [20] (10). In these oligomeric structures, each Li3 triangle is μ3-capped by a Cα carbanion. In addition, each lithium atom is apically coordinated by the THF oxygen atom to prevent long-range interactions (Figure 1.7).
Figure 1.7 Solid-state structures of (a) [(thf)MeLi]4 (9) and (b) [(thf)n-BuLi]4 (10).
Bidentate donor bases such as the (N,N) chelating TMEDA or the (O,O) chelating DME tend to link the tetrameric units to form polymeric arrays as in [(tmeda)2(MeLi)4]∞ [21] (11), [(tmeda)(n-BuLi)4]∞ [20, 22] (12), and [(dme)2(n-BuLi)4]∞ [20] (13). The nitrogen atoms coordinate lithium atoms of two adjacent tetramers. In compound 11, the lithium cations of the tetrahedra are μ3-capped by the methanide anions. Each nitrogen atom of the TMEDA molecule coordinates to one lithium cation of different tetrahedra. The TMEDA molecules act as bridges between the Li4 units, resulting in a polymeric network structure where all the Li···C long-range interactions observed in 1 are replaced by Li···N coordination. Compound 11 is insoluble and precipitates even out of a diethyl ether solution. Probably the bite of TMEDA is flexible enough to build such a dense network structure that no other solvent molecule fits in [3]. In 12, only two lithium cations of the tetramers are connected by the donor base so that ribbon-like polymers are built (Figure 1.8). Disaggregation of [n-BuLi]6 with DME results in the polymeric [(dme)2(n-BuLi)4]∞ (13), which is more reminiscent of 11 with each lithium cation solvated by one oxygen atom of a DME molecule. The DME molecules link tetramers in a polymer network. For the synthetic chemists, it is important to know that the disadvantageous properties of the solvated aggregates 9, 11, and 12 are their reduced reactivity and solubility [3].
Figure 1.8[(tmeda)2(MeLi)4]∞ (11) and [(tmeda)(n-BuLi)4]∞ (12) [3].
In comparison to TMEDA and DME, the bite of diethoxymethane (DEM) is smaller because the oxygen atoms are linked by just one methylene bridge. The disaggregation of [MeLi]4,∞ gives [(dem)1.5(MeLi)4]∞ [23] (14) where only one methyl group is exposed to inter-tetrameric long-range Li···C interactions. The remaining three methyl groups cap a single Li3 face, each without further coordination. The three lithium atoms of the Li3 basal face are coordinated to a single oxygen atom of the DEM donor each. The second provides linkage to another [(MeLi)4]∞ rod. The fourth lithium cation supplies long-range Li3CH3···Li interactions of 244 pm. Space group symmetry constitutes a hexagonal channel along the six rods of a more than 720 pm wide diameter (Figure 1.9). The microporous structure of [(dem)1.5(LiMe)4]∞ improves solubility even in nonpolar hydrocarbons.
Figure 1.9 Solid-state structures of [(dem)1.5(MeLi)4]∞ (14) [3].
On average, the metal–metal distances in the donor-base-coordinated tetrahedra 10–14 are about 7 pm longer than the short Li···Li distances of the capped Li3 triangles in the octahedra of the hexamers (Table 1.3). However, the obtained distances of 248–257 pm are always considerably smaller than the long Li···Li distances in the hexamers of just below 300 pm. The lithium cation gets additional electron density from the N/O donor atoms and the electrostatic attraction between the high positively charged Li+ and the negatively charged −CH2R decreases. Consequently, the Li–Cα distances in the donor-base-coordinated compounds are elongated in comparison to the nonsolvated hexamers. Moreover, the addition of the donor bases causes the absence of any Li···Cβ interactions in 10–14 because the secondary electron donation is substituted by the heteroatom of the donor base. The N → Li and O → Li donor bonds obtained are typical.
Table 1.3Distances in the donor-base-coordinated alkylithium compounds (pm).
Compounds
Li···Li
Li–C
α
Li–O/
N
(av.)
References
[(thf)MeLi]
4
9
251
224
196
[19]
[(thf)
n
-BuLi]
4
10
254
224
197
[20]
[(tmeda)
2
(MeLi)
4
]
∞
11
257
226
221
[21]
[(tmeda)(
n
-BuLi)
4
]
∞
12
248
225
213
[20, 22]
[(dme)
2
(
n
-BuLi)
4
]
∞
13
252
227
201
[20]
[(dem)
1.5
(MeLi)
4
]
∞
14
254
226
199
[23]
1.3.2 Asymmetric Aggregates of [Me3SiCH2Li] (4)
In 2010, Stalke et al. [24] reported the hexameric aggregate of trimethylsilylmethyllithium 4 to be reduced by simple ether donors such as diethyl ether (Et2O) and tert-butylmethylether (t-BuOMe) to give the unprecedented asymmetric tetramers [(Et2O)2(LiCH2SiMe3)4] (15) and [(t-BuOMe)2(LiCH2SiMe3)4] (16) (Figure 1.10).
Figure 1.10 Solid-state structures of the asymmetric tetramers [(Et2O)2(LiCH2SiMe3)4] (15) (a) and [(t-BuOMe)2(LiCH2SiMe3)4] (16) (b).
As in the alkyllithium compounds, the structural key feature is the distorted tetrahedral lithium core with averaged Li···Li distance of 256 pm, which is shorter than those in [Me3SiCH2Li]6 but longer than those in 9–14. Surprisingly, only two lithium atoms are apically coordinated by the oxygen atom of the ether donor base. The other two lithium atoms are only threefold coordinated by the carbanions associated with a shorter metal–metal distance compared to their donor-base-coordinated counterparts (Li1 and Li2). This seems to be surprising as the more pronounced electrostatic repulsion without the additional supply of electron density from a donor base should result in longer distances. The missing electron density is compensated by shorter Li–Cα distances of the solvent uncoordinated lithium cations (15: 222 pm vs 230 pm) and by a secondary electron donation to the solvent uncoordinated lithium cores by Cγ atom (Table 1.4). There are two different Li–Cγ bond lengths (284.1 and 254.2 pm), which are on average akin to those in 4 (267 pm).
Table 1.4Selected bond lengths in the asymmetric tetramers 15 and 16 (pm).
Compounds
Li···Li
(av.)
Li–C
α
Li–O
(av.)
C
α
–Si
Li–C
γ
References
[(Et
2
O)
2
(LiCH
2
SiMe
3
)
4
]
15
255
223/230
a
197
184
254/284
[24]
[(
t
-BuOMe)
2
(LiCH
2
SiMe
3
)
4
]
16
257
209–239
b
201
188
—
[24]
a Li–C distance of the solvent coordinated lithium cations.
b Bond lengths and angles are not discussed in detail because parts of the molecule are highly disordered.
The unsymmetrical coordination of the donor base molecules in 15 and 16 is untypical for tetrameric aggregates and is not observed in the structures of [(thf)LiMe]4 (9) and [(thf)n-BuLi]4 (10) where all lithium atoms are apically coordinated. The bulky SiMe3 group shields the coordination sphere of the lithium cation and gives no further access to solvent molecules. Owing to the longer Si–C bond lengths (in comparison to the C–C bond lengths), the SiMe3 groups are more flexible and can elude the lithium core.
1.3.3 An Octameric Aggregate of [Me3SiCH2Li]6
An interesting and quite novel structural motif can be created by adding the ligand DABCO (1,4-diazabicylo[2.2.2]octane) to a solution of [Me3SiCH2Li]6 in n-heptane [25]. The resulting molecule [(DABCO)7(LiCH2SiMe3)8] [25] (17) crystallizes in the triclinic space group P (Figure 3.6). The asymmetric unit contains half of the molecule and the other half is generated by an inversion center. DABCO is a bidentate donor base with two nitrogen atoms arranged at opposite sites, providing a 180° linker. It is able to break the hexameric structure but instead of reducing the aggregation state the two nitrogen atoms of one DABCO molecule create a bridge between two [DABCO3(LiCH2SiMe3)4] strands. Surprisingly, this ends up in an octameric lithium compound although one would rather expect an infinite coordination polymer. The whole [(DABCO)7(LiCH2SiMe3)8] complex consists of four (LiC)2 four-membered rings, two of them symmetry independent and each in a different conformation. The conformation of the methyl groups bound to the silicon atom varies relative to the position of the virtual lone pair at the Cα (Figure 1.11, right; different arrangement highlighted in red and green). The (LiC)2 four-membered ring in the peripheries adopt a staggered conformation of the methyl groups relative to the freely refined hydrogen atom positions at Cα. As a result, one methyl group at the silicon atom is oriented trans to the position of the virtual lone pair at Cα. This is the conformation that would be expected from considerations concerning a negative hyperconjugation as described in Section 1.2.3.
Figure 1.11Molecular structures of the octameric [(DABCO)7(LiCH2SiMe3)8] (17) in the crystal (a) and different confirmation of the methyl group relative to virtual lone pair (view along the Cα–SiMe3 bond) (b).
In contrast, the methyl groups of the silicon atom of the inner part of the molecule are arranged ecliptically to the freely refined hydrogen atom positions at Cα. This results in a cis conformation of one methyl group relative to the virtual lone pair position. A contracted Si–Cα bond (183 pm) is observed in both conformations and both conformations show Si–CH3 distances in the range of 188–189 pm (Table 1.5). Hence, the trend of an elongated bond trans to the lone pair is not observed and the geometry of the SiMe3 groups gives no evidence of a negative hyperconjugation as mentioned above for [Me3SiCH2Li]6 (4). Consequently, the reason for the different conformations has to be attributed more to steric than to orbital-controlled interactions. The SiMe3 groups located at the outer part of the chain in the trans conformation have more space than those close to the bridging DABCO molecules. The SiMe3 groups at the inner part of the chain are forced into the sterically less demanding cis conformation. The significant contraction of the Si–Cα is just due to electrostatic interactions between the highly positively charged Si- and the negatively charged Cα atom and is not caused by a negative hyperconjugation.
Table 1.5Selected bond lengths (pm).
Compounds
Li–C
α(av.)
Li–O/
N
(av.)
Si–C
α
Li–C
ipso
References
[(DABCO)
7
(LiCH
2
SiMe
3
)
8
]
17
217
a
/221
207
a
/215
183
—
[25]
[(DABCO) (LiCH
2
Ph)]
∞
18
219
210
—
236
[25, 26]
[(Me
2
N(CH
2
)
2
OMe)(LiCH
2
SiMe
3
)]
2
19
224
206/
21
5
182
—
[27]
[(Me
2
N(CH
2
)
2
OMe)(LiCH
2
C
6
H
5
)]
4
20
231
202/
214
—
—
[27]
a Distances in the trans conformation.
The coordination number of lithium in 17 varies between three and four, and because of the unsaturated coordination sphere of the threefold coordinated lithium cations, an enhanced reactivity can be expected. This was proven by an experiment according to Scheme 1.1. DABCO and [Me3SiCH2Li]6 were dissolved in a mixture of toluene and n-hexane.
Scheme 1.1 Reaction scheme of the synthesis of [(DABCO)(LiCH2Ph)]∞.
By storing the reaction mixture at −3 °C, two different types of crystals could be obtained, differentiated by their colorlessness and yellow color. The amount of the yellow crystals increases at the expense of the colorless ones. The colorless crystals turned out to be compound 17 and the yellow crystals were formed in a single-crystal-to-single-crystal transition by a reaction of 17 with toluene to give the polymeric benzyllithium structure [(DABCO)(LiCH2Ph)]∞ (18). Deprotonation of toluene by 4 without additional activation by a Lewis donor base is not observed. Stucky and coworkers [26] have published the crystal structure of [(DABCO)(LiCH2Ph)]∞ in 1970, synthesized by deprotonation of toluene with n-BuLi in the presence of DABCO. The compound is published in the orthorhombic space group P212121 but the noticed disorder could not be refinement appropriately because of the limited quality of data. Stalke and coworkers [25] could solve that problem with higher resolved data and published a differently refined structure of 18 in the space group P21 in 2012. The asymmetric unit of 18 contains two segments of the chain with four independent benzyllithium molecules (Figure 1.12). Every lithium atom is fourfold coordinated by two nitrogen atoms of the bridging ligand and the Cα/Cipso carbon atoms. Weak Li–Cortho interactions are indicated by a distance range between 250 and 266 pm length and a Cortho–Cipso–Cα–Li torsion angle that decreases from 64.5° to 56.4° while simultaneously the Li–Cortho bond length increases. Hence, the lithium cation is clearly attracted by the same Cortho ring atom in all independent benzyllithium molecules causing a η3-coordination. So far, [(DABCO)(LiCH2Ph)]∞ is the only aggregate of benzyllithium, which shows an η3-coordination coordination mode [28, 29]. The question of why [(DABCO)(LiCH2Ph)]∞ gives infinite polymeric chains rather than chains of a definitive length such as [(DABCO)7(LiCH2SiMe3)8] can easily be answered by paying attention to the size of the organic groups. The spherical Me3Si groups shield the lithium atom more efficiently and prevent further aggregation by the bridging DABCO molecule. The planar benzyl anion can be arranged in such a way that two carbon atoms (Cα and Cispo) are in close proximity to the lithium cation so that either can provide electron density. In 17, spatial proximity between one lithium cation and two carbon atoms is just possible to form (LiC)2 four-membered rings.
Figure 1.12Excerpt from the coordination polymer of the infinite chains of [(DABCO)(LiCH2Ph)]∞ (18) in the solid state. Constrained hydrogen atoms are omitted for clarity.
By an exchange of the donor base, the phenomena of a single-crystal-to-single-crystal transition can be observed as well but the resulting oligomers are different. On addition of a mixture of toluene and the ligand donor base Me2N(CH2)2OMe to a solution of 4 in hexane at −25 °C, colorless crystals are obtained after several hours (Scheme 1.2) [27].
Scheme 1.2The transformation from [(Me2N(CH2)2OMe)(LiCH2SiMe3)]2 (19) to [(Me2N(CH2)2OMe)(LiCH2C6H5)]4 (20).
After some days, those colorless crystals disappear in favor of newly growing yellow crystals. In the structure analysis, the colorless crystals turned out to be the dimeric adduct [(Me2N(CH2)2OMe)(LiCH2SiMe3)]2 (19) (Figure 1.13a) with a planar (LiC)2 four-membered rhombic ring as the central structural motif. The yellow crystals were identified to be the tetrameric benzyllithium complex [(Me2N(CH2)2OMe)(LiCH2C6H5)]4 (20) (Figure 1.13b; for bond distances see Table 1.5). The central structural motif is a planar (LiC)4 eight-membered ring although an octameric ring structure complexed by a bidentate ligand is normally sterically forbidden in homometallic lithium tetramers [28b]. The structure of 20 is even more remarkable as, until today, only two benzyl alkali-metal compounds with an eight-membered ring of alternating metal and carbon atoms are known. Both compounds [(tmeda)4(Li1.67Na2.33(CH2C6H5)4)] [28b] and [(tmeda)(NaCH2C6H5)]4
