Organic Reactions, Volume 110 E-Book
326,99 €
Mehr erfahren.
- Herausgeber: John Wiley & Sons
- Kategorie: Wissenschaft und neue Technologien
- Serie: Organic Reactions
- Sprache: Englisch
A carefully curated review of the scientific literature on selected organic reactions, Volume 110 of the Organic Reactions series delivers insightful invited reviews of primary research material in the field of organic chemistry. The latest volume explores the practical and theoretical aspects of the reaction under discussion. The Organic Reactions series is a renowned, peer-reviewed reference in publication since 1942. It is one of the leading secondary- and tertiary-level sources in organic chemistry today.
Sie lesen das E-Book in den Legimi-Apps auf:
Seitenzahl: 528
Veröffentlichungsjahr: 2022
Ähnliche
Table of Contents
COVER
TITLE PAGE
COPYRIGHT
INTRODUCTION TO THE SERIES BY ROGER ADAMS, 1942
INTRODUCTION TO THE SERIES BY SCOTT E. DENMARK, 2008
PREFACE TO VOLUME 110
PETER BEAK JANUARY 12, 1936 – FEBRUARY 21, 2021
CHAPTER 1: RADICAL ALLYLATION, VINYLATION, ALLENYLATION, ALKYNYLATION, AND PROPARGYLATION REACTIONS USING TIN REAGENTS
ACKNOWLEDGEMENTS
INTRODUCTION
MECHANISM AND STEREOCHEMISTRY
SCOPE AND LIMITATIONS
APPLICATIONS TO SYNTHESIS
COMPARISON WITH OTHER METHODS
EXPERIMENTAL CONDITIONS
EXPERIMENTAL PROCEDURES
TABULAR SURVEY
REFERENCES
SUPPLEMENTAL REFERENCES
ENANTIOSELECTIVE EPOXIDE OPENING
ACKNOWLEDGMENTS
INTRODUCTION
MECHANISM AND STEREOCHEMISTRY
SCOPE AND LIMITATIONS
APPLICATIONS TO SYNTHESIS
COMPARISON WITH OTHER METHODS
EXPERIMENTAL CONDITIONS
EXPERIMENTAL PROCEDURES
TABULAR SURVEY
REFERENCES
CUMULATIVE CHAPTER TITLES BY VOLUMECUMULATIVE CHAPTER TITLES BY VOLUME
AUTHOR INDEX, VOLUMES 1–110
CHAPTER AND TOPIC INDEX, VOLUMES 1–110
END USER LICENSE AGREEMENT
List of Illustrations
Chapter 1
Scheme 1
Scheme 2
Scheme 3
Scheme 4
Scheme 5
Scheme 6
Figure 1 Most stable conformation of the 2‐stannylethyl radical.
Scheme 7
Scheme 8
Scheme 9
Scheme 10
Scheme 11
Scheme 12
Scheme 13
Scheme 14
Figure 2 Examples of substituted allylstannanes synthesized via Grignard rea...
Scheme 15
Scheme 16
Scheme 17
Figure 3 Examples of substituted allylstannanes synthesized by the addition ...
Scheme 18
Scheme 19
Scheme 20
Figure 4 Examples of substituted allylstannanes prepared by addition of a tr...
Scheme 21
Scheme 22
Scheme 23
Scheme 24
Scheme 25
Scheme 26
Scheme 27
Scheme 28
Scheme 29
Figure 5 Example substrates showing the diversity of functional groups toler...
Scheme 30
Scheme 31
Scheme 32
Scheme 33
Scheme 34
Scheme 35
Scheme 36
Scheme 37
Scheme 38
Scheme 39
Scheme 40
Figure 6 Yields for allylation of simple primary, secondary, and tertiary α‐...
Scheme 41
Scheme 42
Scheme 43
Scheme 44
Figure 7 Successfully allylated chlorodifluoromethyl pyridine, pyrimidine, a...
Figure 8 Yields for allylation of perfluoroalkyl iodide substrates.
Scheme 45
Scheme 46
Scheme 47
Scheme 48
Scheme 49
Scheme 50
Scheme 51
Scheme 52
Scheme 53
Scheme 54
Scheme 55
Scheme 56
Scheme 57
Scheme 58
Scheme 59
Figure 9 Allylstannane
51
contains a polar substituent that facilitates bypr...
Figure 10 Allylstannane
52
contains fluorinated substituents that facilitate...
Scheme 60
Figure 11 Allylstannane
54
produces an inorganic tin byproduct, which facili...
Scheme 61
Scheme 62
Scheme 63
Figure 12 2‐Substituted allylstannanes incorporating stannyl or silyl groups...
Scheme 64
Scheme 65
Scheme 66
Figure 13 Tributylstannyl‐radical‐mediated isomerization of (1‐methyl‐2‐prop...
Scheme 67
Scheme 68
Scheme 69
Scheme 70
Scheme 71
Scheme 72
Scheme 73
Scheme 74
Scheme 75
Scheme 76
Scheme 77
Scheme 78
Scheme 79
Scheme 80
Scheme 81
Scheme 82
Scheme 83
Scheme 84
Scheme 85
Scheme 86
Figure 14 Steroid‐based templates for controlling telomer length.
Scheme 87
Scheme 88
Scheme 89
Scheme 90
Scheme 91
Scheme 92
Scheme 93
Scheme 94
Scheme 95
Scheme 96
Scheme 97
Scheme 98
Scheme 99
Scheme 100
Scheme 101
Scheme 102
Scheme 103
Scheme 104
Figure 15 The preferred conformations of conformationally mobile carbohydrat...
Scheme 105
Scheme 106
Scheme 107
Scheme 108
Scheme 109
Scheme 110
Scheme 111
Scheme 112
Figure 16 The lowest‐energy conformations of radicals derived from selenides...
Scheme 113
Scheme 114
Figure 17 Preferred ground‐state conformation of the radical derived from io...
Scheme 115
Figure 18 The preferred conformation of the radical derived from iodide
113
...
Scheme 116
Figure 19 Substrates that generate radicals α to a cyclic ether.
Scheme 117
Scheme 118
Scheme 119
Scheme 120
Scheme 121
Figure 20 Conformations of the radical derived from bromide
120
.
Scheme 122
Scheme 123
Figure 21 The preferred Felkin–Anh transition state for allylation of an α‐o...
Scheme 124
Figure 22 The preferred ground‐state conformation (left) and Felkin–Anh tran...
Scheme 125
Figure 23 The preferred conformation of the radical formed from bromide
125
...
Scheme 126
Figure 24 The preferred (
s
‐
trans
) and disfavored (
s‐cis
) conformations...
Scheme 127
Figure 25 The preferred
s‐cis
conformation of alkyl substituted α‐aryl...
Figure 26 Potential conformations of chiral‐auxiliary‐substituted radicals....
Scheme 128
Scheme 129
Scheme 130
Scheme 131
Figure 27 The preferred conformation of the radical derived from iodide
135
....
Scheme 132
Figure 28 The preferred conformation of the metal‐complexed radical derived ...
Scheme 133
Figure 29 Conformations of oxazolidinone‐substituted substrates and radicals...
Scheme 134
Scheme 135
Figure 30 The preferred reactive conformation of the radical formed from add...
Scheme 136
Scheme 137
Figure 31 Preferred reactive conformation of the radical formed from bromogl...
Scheme 138
Scheme 139
Figure 32 The preferred reactive conformation of the radical formed by addit...
Figure 33 The structures of ligands
lig.2
and
lig.3
, which can be used for e...
Scheme 140
Scheme 141
Figure 34 The conformations of the radical derived from bromide
149
when com...
Scheme 142
Scheme 143
Figure 35 The preferred reactive conformation of the radical derived from α‐...
Figure 36 The structure of
C
2
‐symmetric sulfonamide ligand
lig.7
.
Scheme 144
Figure 37 Phosphoric‐ester‐substituted cinnamate
151
.
Scheme 145
Scheme 146
Scheme 147
Scheme 148
Scheme 149
Scheme 150
Scheme 151
Scheme 152
Scheme 153
Scheme 154
Scheme 155
Scheme 156
Scheme 157
Figure 38 Substrate
158
generates an acyl radical by S
H
2 substitution. The r...
Scheme 158
Scheme 159
Scheme 160
Scheme 161
Scheme 162
Scheme 163
Scheme 164
Scheme 165
Scheme 166
Scheme 167
Scheme 168
Scheme 169
Scheme 170
Scheme 171
Scheme 172
Scheme 173
Scheme 174
Scheme 175
Scheme 176
Scheme 177
Scheme 178
Scheme 179
Scheme 180
Scheme 181
Scheme 182
Scheme 183
Scheme 184
Scheme 185
Scheme 186
Scheme 187
Scheme 188
Scheme 189
Scheme 190
Scheme 191
Scheme 192
Scheme 193
Scheme 194
Scheme 195
Scheme 196
Figure 39 The structure of poly(dichlorophosphazene)
194
.
Scheme 197
Scheme 198
Figure 40 The structures of vinylstannanes that have been used in radical vi...
Scheme 199
Scheme 200
Scheme 201
Scheme 202
Scheme 203
Scheme 204
Scheme 205
Scheme 206
Scheme 207
Scheme 208
Scheme 209
Scheme 210
Scheme 211
Scheme 212
Scheme 213
Scheme 214
Scheme 215
Scheme 216
Scheme 217
Scheme 218
Scheme 219
Scheme 220
Scheme 221
Scheme 222
Scheme 223
Scheme 224
Scheme 225
Scheme 226
Scheme 227
Scheme 228
Scheme 229
Scheme 230
Scheme 231
Scheme 232
Scheme 233
Scheme 234
Scheme 235
Scheme 236
Scheme 237
Scheme 238
Scheme 239
Scheme 240
Scheme 241
Scheme 242
Scheme 243
Scheme 244
Scheme 245
Scheme 246
Scheme 247
Scheme 248
Scheme 249
Scheme 250
Scheme 251
Scheme 252
Scheme 253
Scheme 254
Scheme 255
Scheme 226
Scheme 257
Scheme 258
Chapter 2
Scheme 1
Scheme 2
Scheme 3
Scheme 4
Scheme 5
Scheme 6
Scheme 7
Scheme 8
Scheme 9
Scheme 10
Scheme 11
Scheme 12
Scheme 13
Scheme 14
Figure 1 The structures of Cr(salen) complex
15
and Co(salen) complex
16
.
Scheme 15
Scheme 16
Figure 2 The proposed intermediate in the zirconium-mediated azidolysis and ...
Scheme 17
Scheme 18
Figure 3 Possible transition states for the samarium-mediated aminolysis of ...
Scheme 19
Scheme 20
Scheme 21
Scheme 22
Scheme 23
Scheme 24
Scheme 25
Scheme 26
Scheme 27
Scheme 28
Scheme 29
Scheme 30
Scheme 31
Scheme 32
Scheme 33
Scheme 34
Scheme 35
Scheme 36
Scheme 37
Scheme 38
Scheme 39
Scheme 40
Scheme 41
Scheme 42
Scheme 43
Scheme 44
Scheme 45
Scheme 46
Scheme 47
Scheme 48
Scheme 49
Scheme 50
Scheme 51
Scheme 52
Scheme 53
Scheme 54
Scheme 55
Scheme 56
Scheme 57
Scheme 58
Scheme 59
Scheme 60
Scheme 61
Scheme 62
Scheme 63
Scheme 64
Scheme 65
Scheme 66
Scheme 67
Scheme 68
Scheme 69
Scheme 70
Scheme 71
Scheme 72
Scheme 73
Scheme 74
Scheme 75
Scheme 76
Scheme 77
Scheme 78
Scheme 79
Scheme 80
Scheme 81
Scheme 82
Scheme 83
Figure 4 The structure of nelfinavir.
Scheme 84
Scheme 85
Scheme 86
Scheme 87
Scheme 88
Scheme 89
Scheme 90
Scheme 91
Scheme 92
Scheme 93
Scheme 94
Scheme 95
Scheme 96
Scheme 97
Scheme 98
Scheme 99
Scheme 100
Scheme 101
Scheme 102
Scheme 103
Scheme 104
Guide
Cover
Table of Contents
Title Page
Copyright
Introduction to the Series By Roger Adams, 1942
Introduction to the Series By Scott E. Denmark, 2008
Preface to Volume 110
Peter Beak January 12, 1936 – February 21, 2021
Begin Reading
Cumulative Chapter Titles by Volume
Author Index, Volumes 1–110
CHAPTER AND TOPIC INDEX, VOLUMES 1–110
END USER LICENSE AGREEMENT
Pages
ii
iii
iv
v
vi
vii
viii
ix
x
xi
xii
xiii
1
2
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
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
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
122
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
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
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
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
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
276
277
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
314
315
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
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
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
490
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
518
519
520
521
522
523
524
525
526
527
528
529
530
531
532
533
534
535
536
537
538
539
540
541
542
543
544
545
546
547
548
549
550
551
552
553
554
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
570
571
572
573
574
575
576
577
578
579
580
581
582
583
584
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
603
604
605
606
607
608
609
610
611
612
613
614
615
616
617
618
619
620
621
622
623
624
625
626
627
628
629
630
631
632
633
634
635
636
637
638
639
640
641
642
643
644
645
646
647
648
649
650
651
652
653
655
656
657
658
659
660
661
662
663
664
665
666
667
668
669
670
671
672
673
674
675
676
677
678
679
680
681
682
683
684
685
686
687
688
689
690
691
692
693
694
695
696
697
698
699
700
701
702
703
704
705
706
707
708
709
710
711
712
713
714
715
716
717
718
719
720
721
722
723
724
725
726
727
728
729
730
731
732
733
734
735
736
737
738
739
740
741
742
743
744
745
746
747
748
749
750
751
752
753
754
755
756
757
758
759
760
761
762
763
764
765
766
767
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
821
822
823
824
825
826
827
828
829
830
831
832
833
834
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
865
866
867
868
869
870
871
872
873
874
875
876
877
878
879
880
881
882
883
884
885
886
887
888
889
890
891
892
893
894
895
896
897
898
899
900
901
902
903
904
905
906
907
908
909
910
911
912
913
914
915
916
917
918
919
920
921
922
923
924
925
926
927
928
929
931
932
933
934
935
936
937
938
939
940
941
942
943
944
945
946
947
948
949
FORMER MEMBERS OF THE BOARDOF EDITORS AND DIRECTORS
JEFFREY
AUBÉ
LAURA
KIESSLING
JOHN
E.
BALDWIN
MARISA
C.
KOZLOWSKI
DALE
L.
BOGER
STEVEN
V.
LEY
JIN
K.
CHA
JAMES
A.
MARSHALL
ANDRÉ
B.
CHARETTE
MICHAEL
J.
MARTINELLI
ENGELBERT
CIGANEK
SCOTT
J.
MILLER
DENNIS
CURRAN
JOHN
MONTGOMERY
SAMUEL
DANISHEFSKY
LARRY
E.
OVERMAN
HUW
M. L.
DAVIES
ALBERT
PADWA
SCOTT
E.
DENMARK
T. V.
RAJANBABU
VICTOR
FARINA
JAMES
H.
RIGBY
PAUL
FELDMAN
WILLIAM
R.
ROUSH
JOHN
FRIED
TOMISLAV
ROVIS
JACQUELYN
GERVAY
‐
HAGUE
SCOTT
D.
RYCHNOVSKY
STEPHEN
HANESSIAN
MARTIN
SEMMELHACK
LOUIS
HEGEDUS
CHARLES
SIH
PAUL
J.
HERGENROTHER
AMOS
B.
SMITH
, III
JEFFREY
S.
JOHNSON
BARRY
M.
TROST
ROBERT
C.
KELLY
PETER
WIPF
FORMER MEMBERS OF THE BOARDNOW DECEASED
ROGER
ADAMS
HERBERT
O.
HOUSE
HOMER
ADKINS
JOHN
R.
JOHNSON
WERNER
E.
BACHMANN
ROBERT
M.
JOYCE
PETER
BEAK
ANDREW
S.
KENDE
ROBERT
BITTMAN
WILLY
LEIMGRUBER
A. H.
BLATT
FRANK
C.
MC
GREW
VIRGIL
BOEKELHEIDE
BLAINE
C.
MC
KUSICK
GEORGE
A.
BOSWELL
,
JR
.
JERROLD
MEINWALD
THEODORE
L.
CAIRNS
CARL
NIEMANN
ARTHUR
C.
COPE
LEO
A.
PAQUETTE
DONALD
J.
CRAM
GARY
H.
POSNER
DAVID
Y.
CURTIN
HANS
J.
REICH
WILLIAM
G.
DAUBEN
HAROLD
R.
SNYDER
LOUIS
F.
FIESER
MILÁN
USKOKOVIC
HEINZ
W.
GSCHWEND
BORIS
WEINSTEIN
RICHARD
F.
HECK
JAMES
D.
WHITE
RALPH
F.
HIRSCHMANN
Organic Reactions
VOLUME 110
EDITORIAL BOARD
P. ANDREWEVANS, Editor‐in‐Chief
STEVEN M. WEINREB, Executive Editor
DAVID
B.
BERKOWITZ
STUART
W.
MCCOMBIE
PAUL
R.
BLAKEMORE
BO
QU
REBECCA
L.
GRANGE
JENNIFER
M.
SCHOMAKER
DENNIS
G.
HALL
KEVIN
H.
SHAUGHNESSY
DONNA
M.
HURYN
STEVEN
D.
TOWNSEND
JEFFREY
B.
JOHNSON
CHRISTOPHER
D.
VANDERWAL
JEFFREY
N.
JOHNSTON
MARY
P.
WATSON
STEFAN
LUTZ
BARRY B. SNIDER, Secretary
JEFFERY B. PRESS, Treasurer
DANIELLESOENEN, Editorial Coordinator
DENALINDSAY, Secretary and Processing Editor
LANDY K.BLASDEL, Processing Editor
TINAGRANT, Processing Editor
ENGELBERTCIGANEK,Editorial Advisor
ASSOCIATE EDITORS
SHUNSUKEKOTANI
MAKOTONAKAJIMA
IAN J. ROSENSTEIN
MASAHARUSUGIURA
Copyright © 2022 by Organic Reactions, Inc. All rights reserved.
Published by John Wiley & Sons, Inc., Hoboken, New Jersey
Published simultaneously in Canada
No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per‐copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750‐8400, fax (978) 750‐4470, or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) 748‐6011, fax (201) 748‐6008, or online at http://www.wiley.com/go/permission.
Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor author shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.
For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at (800) 762‐2974, outside the United States at (317) 572‐3993 or fax (317) 572‐4002.
Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic formats. For more information about Wiley products, visit our web site at www.wiley.com.
Library of Congress Cataloging‐in‐Publication Data:
ISBN: 978‐1‐119‐84166‐1
Printed in the United States of America
INTRODUCTION TO THE SERIES BY ROGER ADAMS, 1942
In the course of nearly every program of research in organic chemistry, the investigator finds it necessary to use several of the better‐known synthetic reactions. To discover the optimum conditions for the application of even the most familiar one to a compound not previously subjected to the reaction often requires an extensive search of the literature; even then a series of experiments may be necessary. When the results of the investigation are published, the synthesis, which may have required months of work, is usually described without comment. The background of knowledge and experience gained in the literature search and experimentation is thus lost to those who subsequently have occasion to apply the general method. The student of preparative organic chemistry faces similar difficulties. The textbooks and laboratory manuals furnish numerous examples of the application of various syntheses, but only rarely do they convey an accurate conception of the scope and usefulness of the processes.
For many years American organic chemists have discussed these problems. The plan of compiling critical discussions of the more important reactions thus was evolved. The volumes of Organic Reactions are collections of chapters each devoted to a single reaction, or a definite phase of a reaction, of wide applicability. The authors have had experience with the processes surveyed. The subjects are presented from the preparative viewpoint, and particular attention is given to limitations, interfering influences, effects of structure, and the selection of experimental techniques. Each chapter includes several detailed procedures illustrating the significant modifications of the method. Most of these procedures have been found satisfactory by the author or one of the editors, but unlike those in Organic Syntheses, they have not been subjected to careful testing in two or more laboratories. Each chapter contains tables that include all the examples of the reaction under consideration that the author has been able to find. It is inevitable, however, that in the search of the literature some examples will be missed, especially when the reaction is used as one step in an extended synthesis. Nevertheless, the investigator will be able to use the tables and their accompanying bibliographies in place of most or all of the literature search so often required. Because of the systematic arrangement of the material in the chapters and the entries in the tables, users of the books will be able to find information desired by reference to the table of contents of the appropriate chapter. In the interest of economy, the entries in the indices have been kept to a minimum, and, in particular, the compounds listed in the tables are not repeated in the indices.
The success of this publication, which will appear periodically, depends upon the cooperation of organic chemists and their willingness to devote time and effort to the preparation of the chapters. They have manifested their interest already by the almost unanimous acceptance of invitations to contribute to the work. The editors will welcome their continued interest and their suggestions for improvements in Organic Reactions.
INTRODUCTION TO THE SERIES BY SCOTT E. DENMARK, 2008
In the intervening years since “The Chief” wrote this introduction to the second of his publishing creations, much in the world of chemistry has changed. In particular, the last decade has witnessed a revolution in the generation, dissemination, and availability of the chemical literature with the advent of electronic publication and abstracting services. Although the exponential growth in the chemical literature was one of the motivations for the creation of Organic Reactions, Adams could never have anticipated the impact of electronic access to the literature. Yet, as often happens with visionary advances, the value of this critical resource is now even greater than at its inception.
From 1942 to the 1980's the challenge that Organic Reactions successfully addressed was the difficulty in compiling an authoritative summary of a preparatively useful organic reaction from the primary literature. Practitioners interested in executing such a reaction (or simply learning about the features, advantages, and limitations of this process) would have a valuable resource to guide their experimentation. As abstracting services, in particular Chemical Abstracts and later Beilstein, entered the electronic age, the challenge for the practitioner was no longer to locate all of the literature on the subject. However, Organic Reactions chapters are much more than a surfeit of primary references; they constitute a distillation of this avalanche of information into the knowledge needed to correctly implement a reaction. It is in this capacity, namely to provide focused, scholarly, and comprehensive overviews of a given transformation, that Organic Reactions takes on even greater significance for the practice of chemical experimentation in the 21st century.
Adams' description of the content of the intended chapters is still remarkably relevant today. The development of new chemical reactions over the past decades has greatly accelerated and has embraced more sophisticated reagents derived from elements representing all reaches of the Periodic Table. Accordingly, the successful implementation of these transformations requires more stringent adherence to important experimental details and conditions. The suitability of a given reaction for an unknown application is best judged from the informed vantage point provided by precedent and guidelines offered by a knowledgeable author.
As Adams clearly understood, the ultimate success of the enterprise depends on the willingness of organic chemists to devote their time and efforts to the preparation of chapters. The fact that, at the dawn of the 21st century, the series continues to thrive is fitting testimony to those chemists whose contributions serve as the foundation of this edifice. Chemists who are considering the preparation of a manuscript for submission to Organic Reactions are urged to contact the Editor‐in‐Chief.
PREFACE TO VOLUME 110
If you want to find the secrets of the universe, think in terms of energy, frequency, and vibration.
Nikola Tesla
Alchemy, a medieval protoscientific and philosophical endeavor that focused on producing precious metals from base materials and the discovery of the elixir of life, was ultimately unsuccessful. In contrast, advances in synthetic organic chemistry permit the preparation of valuable and functional materials in a safe and reproducible manner from readily available and inexpensive starting materials, which is the basis of the modern chemical industry that manufactures tons of pharmaceuticals, agrochemicals, and important materials. The enormous advances in our ability to prepare functional materials can, in part, be attributed to a greater understanding of the “energy, frequency, and vibrations” of chemical bonds. Indeed, our knowledge of reaction mechanisms offers insight into some of “the secrets of the universe” in the context of bond formation to permit the design of new reactions with increasing emphasis on challenging applications. Nevertheless, our ability to devise and execute a specific reaction in a new synthetic sequence is still fraught with problems, which stem from peripheral functionality that can interfere with the desired transformation and thus affect our ability to transfer the reaction into an array of new scenarios. The hallmark of Organic Reactions chapters is the marriage of the text and the tabular survey in a unique format to provide a detailed mechanistic picture of bond formation with the ability to analyze an array of examples to predict the outcome of a specific process with some degree of confidence. In essence, an Organic Reactions review offers a unique perspective that enables the reader to determine the feasibility of a proposed application and identify in advance any potential critical gaps in the reaction scope. The two chapters in this volume epitomize Tesla's notion by using “rate” and “strain” to orchestrate new bond formation. The first chapter focuses on radical allylation processes whose success relies heavily on relative reaction rates, whereas the second chapter employs ring strain to facilitate the enantioselective ring‐opening of epoxides.
The first chapter by Ian J. Rosenstein is an outstanding treatise on free‐radical allylation and vinylation reactions using organotin reagents. The Introduction provides a brief background on the independent discovery of the first radical allylation reaction with allyltrialkylstannanes by Kosugi and Grignon in 1973, which Keck further developed through applications to target‐directed synthesis. Hence, this reaction has evolved into a sophisticated and versatile approach to carbon‐carbon bond formation in the various incarnations outlined herein. The Mechanism and Stereochemistry section provides an insightful account of the establishment of the chain process and the characterization of the radical addition product by mass spectroscopy. Nevertheless, the question of whether the addition and subsequent β‐elimination follow a stepwise or concerted reaction remains unresolved. A particularly appealing feature of this section is the scholarly analysis of the many possible competing pathways and the origin of the selectivity for adding carbon radicals to allylstannanes. The stereochemical discussion is split into three sections that deal with the reactions of radicals derived from the scission of bonds directly attached to an enantioenriched stereocenter, prochiral radicals that undergo diastereoselective addition processes, and geometrical selectivity in vinylation reactions.
The Scope and Limitations section is organized by the type of stannane utilized as the primary rubric, mainly allyl, but also with vinyl, allenyl, alkynyl, and propargyl groups. The intermolecular allylation reaction traverses carbon radicals (alkyl, aryl, vinyl, and acyl) and heteroatom‐centered radicals, polymeric substrates and reagents, including the impact of the triorganostannane moiety on the rate of addition, elimination, and removal of the byproducts. The author defines the preferred methods for preparing allyl‐ and vinylstannanes and the optimal approaches for generating the free‐radical intermediate. Another important section outlines the impact of substitution at various positions on the allyl group, which identifies some of the remaining obstacles for extending the substrate scope. There is also a short section on adding alkyl radicals to tin enolates, which is formally the umpolung alkylation of a ketone enolate. The inclusion of multicomponent reactions illustrates the synthetic utility of this approach for forming multiple C‐C bonds in complex scenarios, including radical polymerization reactions and three‐component reactions involving carbon monoxide for the construction of unsymmetrical cyclic and acyclic ketones. The latter process is particularly attractive given the challenges associated with the regioselective alkylation of ketone enolates. A section on stereoselective reactions primarily focuses on cyclic and acyclic diastereocontrol, along with a short discussion on enantioselective reactions. Intramolecular allylations are described in the context of various three‐ and four‐component coupling reactions that result in the addition of carbonyl groups, fragmentations, and rearrangements. The section concludes with examples of allylation reactions involving heteroatom‐centered radicals, in addition to the extension of the general concept of β‐stannyl eliminations to other trialkyltin reagents to permit the installation of vinyl, allenyl, alkynyl, and propargyl groups.
The Applications to Synthesis section delineates several examples of utilizing the methodology for the total synthesis of natural products, including carbon‐linked disaccharides and amide‐linked dinucleotides. The Comparison with Other Methods section outlines the radical allylation and vinylation of reagents containing non‐stannyl groups that can also undergo β‐elimination (e.g., sulfides, sulfones, silanes, halides, ethers, and alcohols) and reagents containing alternative metals and metalloids (e.g., cobalt, mercury, zirconium, gallium, indium, and boron). The Tabular Survey incorporates reactions reported through the beginning of 2021. The table organization emulates the Scope and Limitations, making it simple to identify the C‐C bond‐forming process of interest and review the associated examples. Overall, this is an outstanding chapter on an important transformation that will be an exceptional resource to the synthetic community.
The second chapter by Makoto Nakajima, Shunsuke Kotani, and Masaharu Sugiura details the development of enantioselective epoxide ring‐opening reactions. The Introduction provides an excellent overview of the types of meso and centrosymmetric (prochiral) epoxides that undergo desymmetrization with a chiral reagent or catalyst to afford the requisite enantioenriched chiral nonracemic secondary alcohol derivatives that contain one or two stereogenic centers. The reagent or catalyst enhances the epoxide's inherent ring strain and bond polarization to mitigate the direct ring‐opening reaction to form racemic products. The Mechanism and Stereochemistry section subdivides the enantioselective epoxide ring‐opening reactions into three activation modes: epoxide activation, reagent activation, and dual activation. Each activation mode is further divided according to the mechanism, e.g., Lewis acid, Lewis base, electron transfer, chiral nucleophiles and bases, including dual processes that promote ring‐opening with monometallic, homo‐ and heterobimetallic, metal/hydrogen‐bond, and hydrogen‐bonding catalysts. Notably, the electron‐transfer process with low‐valent titanium reagents is fascinating since it represents the umpolung of the conventional ring‐opening reaction that proceeds via a prochiral radical intermediate and ultimately requires two modes of stereochemical induction.
The Scope and Limitations section is organized by the type of nucleophile deployed in the intermolecular ring‐opening reaction (e.g., halogen (including fluorine), carbon, nitrogen, oxygen (including intramolecular), sulfur, selenium, and hydrogen) using both fused and non‐fused epoxides. The specific transformation can be cross‐referenced by the type of activation and the mechanism (vide supra). Hence, the chapter organization permits the reader to quickly traverse the examples and identify gaps in knowledge within the reaction mechanism, catalyst/reagent, substrate, and nucleophile. For instance, the section on ring‐opening with carbon nucleophiles includes both organometallic and neutral species to illustrate the scope of this process. The ring‐opening process that incorporates carbon monoxide is particularly interesting, given that this variant provides a convenient route to enantiomerically enriched β‐lactones that can be challenging intermediates to access using more conventional methods. Additionally, the enantioselective ring‐opening with aryl and alkyl amines, azides, isocyanides, heterocycles, etc., is particularly important given the ubiquity and versatility of 1,2‐amino alcohols in target‐directed synthesis. The inclusion of oxygen, sulfur, selenium, and hydrogen pronucleophiles provides access to other important motifs, as exemplified by the reactions with alcohols that afford differentially‐protected diols that are challenging to prepare directly from the parent diol. The section concludes with ring‐opening reactions with chiral bases and a series of rearrangement and fragmentation reactions that furnish allylic and bicyclic alcohols.
The Applications to Synthesis section describes the application of some of these processes to the synthesis of natural products and an important synthetic intermediate present in an active pharmaceutical ingredient. The Comparison with Other Methods section provides a detailed picture of alternative methods for the enantioselective synthesis of 1,2‐halohydrins, β‐amino alcohols, 1,2‐diols, and allylic alcohols. The Tabular Survey mirrors the Scope and Limitations with the reactions organized by the product based on the type of nucleophile to allow the reader to identify the optimal method for preparing a specific product quickly. Overall, this is an excellent chapter on a fundamentally important reaction that permits the ring‐opening of meso and prochiral epoxides to form enantioenriched secondary alcohol derivatives bearing one or two stereocenters.
I would be remiss if I did not acknowledge the entire Organic Reactions Editorial Board for their collective efforts in steering this volume through the many stages of the editorial process. I thank Dr. Stuart W. McCombie, Dr. Steven M. Weinreb (Chapter 1), and Dr. Donna M. Huryn (Chapter 2), who served as the Responsible Editors to marshal the chapters through the various phases of development. I am also deeply indebted to Dr. Danielle Soenen for her continued and heroic efforts as the Editorial Coordinator; her knowledge of Organic Reactions is critical to maintaining consistency in the series. Dr. Dena Lindsay (Secretary to the Editorial Board) is thanked for coordinating the authors', editors', and publisher's contributions. In addition, the Organic Reactions enterprise could not maintain the quality of production without the efforts of Dr. Steven M. Weinreb (Executive Editor), Dr. Engelbert Ciganek (Editorial Advisor), Dr. Landy Blasdel (Processing Editor), and Dr. Tina Grant (Processing Editor). I would also like to acknowledge Dr. Barry B. Snider (Secretary) for keeping everyone on task and Dr. Jeffery Press (Treasurer) for his fiscal diligence.
I am also indebted to past and present members of the Board of Editors and Board of Directors for ensuring the enduring quality of Organic Reactions. The specific format of the chapters, in conjunction with the collated tables of examples, makes this series of reviews both unique and exceptionally valuable to the practicing synthetic organic chemist.
P. Andrew Evans
Kingston
Ontario, Canada
PETER BEAK
January 12, 1936 – February 21, 2021
Born in Syracuse, NY on January 12, 1936, Beak received a B.A. degree from Harvard University in 1957 and a Ph.D. from Iowa State University in 1961 under the direction of Professor Ernest Wenkert. That same year, Beak was hired as an Instructor at the University of Illinois at Urbana‐Champaign rising to Professor of Chemistry in 1970. Before retirement in 2008, Beak held numerous positions, including Jubilee Professor (LAS), Roger Adams Professor (Chemistry), James R. Eiszner Chair (Chemistry), and Professor in the Center for Advanced Study (UIUC). Among the many accolades he received for research, teaching, and service, the most notable include election to the National Academy of Sciences (2003), membership in the American Academy of Arts and Sciences (2004), and the Paul G. Gassman Award from the American Chemical Society (2000). Peter served on the Board of Editors of Organic Reactions from 1988–1997 and on the Board of Directors from 1998–2004. He was also a founding Associate Editor of Organic Letters from 1999–2003.
Over an illustrious career that spanned nearly five decades, Peter was recognized as a leader in the fields of physical organic and synthetic organic chemistry. His work was characterized by sustained excellence, creative insight, intelligent analyses, and a keen sense of practicality and impact. Peter's defining characteristic was his enduring dedication to the training and education of his coworkers. With characteristic modesty, Peter would always identify his most important contributions as the accomplishments of his current and former students. His was a difficult‐to‐emulate example, but one that all who knew him aspired to.
His early work on protomeric and alkylomeric equilibria related to the way in which carbon‐hydrogen and carbon‐carbon bonds are formed and broken, particularly in heterocyclic systems. Through elegant gas‐phase and solution studies, he showed that these reactions were dramatically dependent on the molecular environment, and he devised a phenomenological theory that rationalized these effects. This work fundamentally changed the way chemists think about chemical equilibria, one of the most important concepts in chemistry.
In work of fundamental significance in reaction mechanisms, Peter developed an insightful and general method to determine reaction trajectories at non‐stereogenic atoms called the “endocyclic restriction test.” The work entailed the combination of brilliant experimental design, sophisticated interpretation of reaction products, and the application of demanding synthetic methods to generate the substrates.
Peter had an enduring interest in the chemistry of carbanions, organic compounds in which one carbon center formally carries a negative charge and is associated with a metal ion, usually lithium. The advent of functional organolithium chemistry in the 1970's led to a revolution in the analysis and implementation of carbon‐carbon bond formation in organic synthesis, which simplified molecule building. Among the most notable contributions was his development of efficient methods for enantioselective synthesis through the use of chiral amines as asymmetric modifiers. Peter's asymmetric organolithium‐based methods and the variants they inspired enabled the production of many important chiral therapeutic agents. They also helped respond to the call for drug candidates that are rich in Csp3 stereogenic centers, to expand the types of biological functions that can be achieved with small‐molecule‐based therapeutics. Peter is recognized not only as one of the pioneers of this important field, but also as one of the most influential practitioners. Through his keen insights and guided by his sense for novelty, he invented new strategies and reactions for synthesizing organic compounds through the agency of these highly reactive species. As important as his contributions to synthetic methodology are, what distinguished Peter from his peers was his interest in and unparalleled ability to understand the fundamental structure‐reactivity and mechanistic underpinnings of these fascinating processes.
Perhaps Peter Beak's most lasting and influential legacy is his unwavering conviction that students should be empowered as active participants in their own education and in the intellectual ecosystem of the department. This vision became manifest in two unique and longstanding activities in the organic chemistry area, namely the annual Beak‐Pines Allerton Conference and the biennial Senter Symposium on Frontiers in Organic Chemistry. Peter developed the idea for the Allerton Conference in 1986 with the goal of encouraging graduate students to take the leadership in running a scientific retreat for the entire organic chemistry area. The students chair and organize the conference, give the presentations, participate in the discussions, and provide guidance to their successors. Although originally sponsored by gifts from Monsanto and Merck, a very generous gift from Peter and Sandy Beak in 2012 has provided a sustainable income stream to support the conference indefinitely into the future.
Similarly, the biennial Senter Symposium springs from the Beak philosophy of graduate education – enable the students to become the masters of their own professional development. By engaging the graduate student body in the planning, organization, and execution of a full‐day symposium, they become stakeholders in their own education. Moreover, they have the opportunity to compose a program of speakers of their own choosing and have the pleasure of interacting with them on a personal as well as a professional basis; excellent training for networking and building confidence. This symposium has been active since 1990 with sponsorship from many sources including Monsanto, Janssen, and alumni Peter Senter and Terry Balthazor.
Even more than his multidimensional contributions to chemistry, Peter Beak is remembered as the quintessential role model for collegiality and mentorship. His dedication to the notion of colleagues as partners and to the education and professional development of his students is legendary, as is evident in the heartfelt testimonials that followed his death.
Peter is survived by his wife of 61 years, Sandra Beak. Peter and Sandra met at age 14, married in 1959, and went on to spend a wonderful life together. They had two children who also survive, Bryan Beak, and Stacey Beatty, along with four grandchildren.
Peter was an avid and accomplished skier for most of his life, and his family will spread his ashes on a much‐loved helicopter skiing run in the Kootenay Mountains in British Columbia, Canada.
Scott E. Denmark
University of Illinois at Urbana‐Champaign
CHAPTER 1RADICAL ALLYLATION, VINYLATION, ALLENYLATION, ALKYNYLATION, AND PROPARGYLATION REACTIONS USING TIN REAGENTS
IAN J. ROSENSTEIN
Department of Chemistry, Hamilton College, Clinton, NY 13323
Edited by STUART McCOMBIEAND STEVEN M. WEINREB
CONTENTS
ACKNOWLEDGEMENTS
INTRODUCTION
MECHANISM AND STEREOCHEMISTRY
Mechanism
Stereochemistry
Allylation Reactions
Vinylation Reactions
SCOPE AND LIMITATIONS
Preparation of Allyl and Vinyl Stannanes
Methods for Radical Generation
Direct Allylation Reactions Using Allyltributylstannane
Alkyl Radicals
Aryl and Vinyl Radicals
Acyl Radicals
Polymer‐Bound Substrates and Reagents
Direct Additions to Substituted Allylstannanes
Effect of Changing the Non‐Allylic Substituents on Tin
Alternative Alkyl/Aryl Groups
Reagents that Form Easily Separable Byproducts
Substitution at C‐2
Substitution at C‐1 or C‐3
Cyclic Allylstannanes
Radical Additions to Tin Enolates
Multicomponent Reactions
Reactions of a Radical Precursor, Alkene, and Allylstannane
Reactions Involving Carbon Monoxide
Stereoselective Allylation Reactions
Diastereoselective Reactions of Cyclic Substrates
Diastereoselective Reactions of Acyclic Substrates
1,2‐ and 1,3‐Induction
Acyclic α‐Sulfoxide Radicals
Chiral Auxiliary Control
Enantioselective Reactions
Reactions Involving Intramolecular Processes
Reactions Involving a Radical–Alkene Cyclization Followed by Trapping with an Allylstannane
Reactions Involving Allylation Following Other Intramolecular Processes
Cyclization Reactions Involving Intramolecular Trapping by an Allylstannane
Allylstannylation Reactions
Allylation Reactions of Heteroatom‐Centered Radicals
Vinylation Reactions
Allenylation Reactions
Alkynylation and Propargylation Reactions
APPLICATIONS TO SYNTHESIS
(±)‐Perhydrohistrionicotoxin
(+)‐
ent
‐Debromoflustramine B
(−)‐Stenine and (−)‐Tuberostemonine
(±)‐Ryanodol
Carbon‐Linked Disaccharides
Amide‐Linked Dinucleotides
(+)‐Resiniferatoxin
(−)‐Magellanine
(+)‐Scholarisine A
COMPARISON WITH OTHER METHODS
Sulfides
Sulfones
Silanes
Halides
Ethers and Alcohols
Non‐Tin Metals and Metalloids
EXPERIMENTAL CONDITIONS
Hazards
Reaction Conditions
Isolation of Products
EXPERIMENTAL PROCEDURES
(2′
R
*,3′
S
*)‐4‐[3′‐(
tert
‐Butyldimethylsiloxy)‐2′‐oxepanyl]‐1‐butene [Direct Allylation with Thermal Initiation].
422
Phenylmethyl 4‐Deoxy‐2,3‐
O
‐(1‐methylethylidene)‐4‐(2‐propen‐1‐yl)‐
L
‐lyxopyranoside (Mixture of Anomers) [Direct Allylation with Photochemical Initiation].
423
1‐Phenylpent‐4‐en‐1‐one [Direct Allylation Using a Photoredox Catalyst].
47
3‐Methyl‐α‐2‐propen‐1‐yl‐2,4,10‐trioxatricyclo[3.3.1.1
3,7
]decane‐1‐propanoic Acid Methyl Ester [Three‐Component Reaction of a Radical Precursor, Alkene, and Allyltributylstannane].
144
4‐Cyano‐1‐tetradecen‐6‐one [Four‐Component Reaction of a Radical Precursor, Carbon Monoxide, Alkene, and Allyltributylstannane].
155
(±)‐(2
S
*)‐2‐[(2
S
*)‐Tetrahydropyran‐2‐yl]‐2‐[propen‐3‐yl]‐2‐methylpropanoic Acid Ethyl Ester [Allylation with 1,2‐Asymmetric Induction Mediated by a Lewis Acid].
179
(2
S
,4
R
)‐3‐(2‐Propyl‐4‐pentenoyl)‐4‐diphenylmethyl‐2‐oxazolidinone [Three‐Component Diastereoselective Reaction Using a Chiral Auxiliary].
204
3‐[(2
R
)‐2‐(2,2‐Dimethylpropyl)‐1‐oxo‐4‐penten‐1‐yl]‐2‐oxazolidinone [Three‐Component Enantioselective Reaction].
209
(3
S
,3a
S
,5
R
,6
R
,6a
R
)‐5,6‐Bis(acetyloxy)hexahydro‐3‐(2‐propen‐1‐yl)‐2
H
‐cyclopenta[
b
]furan‐2‐one [Allylation Following Radical–Alkene Cyclization].
224
2‐Methylene‐4‐[(tributylstannyl)methyl]pentanedioic Acid 1,5‐Dimethyl Ester [Allylstannylation Reaction].
265
(7
E
)‐[6,7,8‐Trideoxy‐1,2,3,4‐bis‐
O
‐(1‐methylethylidene)]‐α‐
D
‐
galacto
‐non‐7‐enopyranuronic Acid Ethyl Ester [Vinylation Reaction].
293
TABULAR SURVEY
Chart 1. Chiral Ligands and Additives Used in the Tables
Table 1. Direct Allylations
A. Acyclic Substrates
B. Cyclic Substrates
C. Carbohydrates and Related Substrates
D. Nucleosides and Related Substrates
Table 2. Multicomponent Reactions
A. Three-Component Processes
B. Four-Component Processes
Table 3. Allylations Following Cyclizations
Table 4. Allylations Following Other Rearrangements
Table 5. Intramolecular Trapping by a Stannane
A. Simple Cyclizations
B. Two-Component Processes
Table 6. Allylstannylation Reactions
Table 7. Additions to Stannyl Enolates
Table 8. Vinylation Reactions
Table 9. Allenylation Reactions
Table 10. Alkynylation and Propargylation Reactions
Table 11. Reactions of Heteroatom-Centered Radicals
A. Allylations
B. Vinylations
C. Allenylations and Alkynylations
REFERENCES
SUPPLEMENTAL REFERENCES
ACKNOWLEDGEMENTS
The author is grateful for the assistance of four members of the editorial board: Dr. Stuart McCombie was critical in helping to organize the chapter and with work on the tables, Dr. Paul Feldman helped to keep things moving forward through the middle of the project, Dr. Engelbert Ciganek kindly reordered the table entries, and Prof. Steven Weinreb provided thoughtful feedback and editing of the complete manuscript. The author also gratefully acknowledges the contributions of Dr. Danielle Soenen, who was always quick to provide helpful guidance on formatting and technical issues, Dr. Landy Blasdel, for improving the text through careful copy editing, and Dr. Dena Lindsay, for final editing of the tables.
INTRODUCTION
Over the past thirty years, radical allylation using allyltin reagents has been developed to provide a useful synthetic method. Kosugi and Grignon reported the first examples of these reactions in 19731,2 and, beginning about a decade later, Keck began to systematically explore the application of the reaction to target‐directed synthesis.3,4 In its simplest form, the reaction involves the generation of a carbon‐based radical from an appropriate precursor, followed by the addition of this radical to an allyltrialkyltin reagent to form the allylated product (Scheme 1).
Scheme 1
Direct allylations are possible with a variety of carbon‐centered radicals. Most examples involve alkyl radicals (primary, secondary, or tertiary), and the reaction is compatible with substituents located at the radical center. Reactions of vinyl, aryl, and acyl radicals are well‐studied, and allylations of heteroatom‐substituted radicals are also known. Some substituents on the tin reagent are tolerated, further expanding the scope of the simple transformation shown above. In addition, the radical precursor and the allyltrialkyltin moiety can be incorporated into the same molecule, leading to intramolecular trapping of the radical.
The great versatility of this allylation reaction lies in the fact that it can be coupled with other radical transformations to enable formation of two or more carbon–carbon bonds in a single reaction sequence. The initial radical that is generated from a radical precursor can undergo either inter‐ or intramolecular addition to an alkene (Schemes 2 and 3, respectively), followed by trapping with an allyltrialkyltin; longer sequences that combine multiple intermolecular addition or cyclization events can build significant complexity in a one‐pot process.
Scheme 2
Scheme 3
Further variations on the basic allylation reaction use vinyl‐, propargyl‐, alkynyl‐, and allenyltrialkyltin reagents to effect vinylation, allenylation, alkynylation, and propargylation reactions, respectively, and these transformations are also discussed in the chapter.
The literature on the deployment of tin reagents for radical allylation and vinylation reactions has not previously been reviewed in depth, although some aspects of this chemistry have been described.5–8 This chapter and the accompanying Tabular Survey provide a comprehensive review of the literature up to the beginning of 2021. Note that all available diastereomeric and enantiomeric ratios are provided if they were available in the primary literature.
MECHANISM AND STEREOCHEMISTRY
Mechanism
Scheme 4 illustrates the major mechanistic steps in the simple allylation reaction of a generic alkyl halide substrate with allyltributylstannane. This chain process involves initial generation of an alkyl radical by abstraction of a halogen by the tributyltin radical (typically formed by reaction of a radical initiator with the allylstannane). This alkyl radical then adds to the terminal end of the allylstannane to produce an intermediate radical 1, which undergoes rapid β‐fragmentation to afford the allylated product and regenerate the chain‐carrying tributyltin radical.
Scheme 4
Early work on the allylation reaction established that the mechanism is a radical‐chain process. For instance, the reaction is promoted by radical initiators, it is inhibited by radical scavengers, it results in the racemization of enantioenriched halides, and it is subject to well‐known radical rearrangements.1,2 In a later study, the initial alkyl intermediate radical formed in an allylation reaction of diethyl 2‐iodoadipate was observed directly by mass spectrometry as a complex with scandium triflate.9 One question that has not been carefully investigated is whether adduct radical 1 is a distinct intermediate or if the addition of the alkyl radical and loss of tributyltin radical is a concerted process, although a recent report concludes that the analogous reaction of allyl chloride is consistent with a concerted process.10 If radical 1 is a distinct intermediate, it must be short‐lived since other processes are not known to compete with β‐elimination of the trialkylstannyl radical.
The rapid rate of the unimolecular β‐elimination is a critical aspect of the effectiveness of this reaction. As with any radical process, competition between different pathways available to each intermediate radical in the mechanism can lead to multiple products. For the initial tin radical, the alternatives to abstracting a halogen atom from the alkyl halide substrate are either addition to allyltributylstannane or addition to the alkene of the allylation product. Addition to the allylstannane is degenerate, reforming the allylstannane and tin radical by β‐elimination (Scheme 5), and addition to the allylation product is reversible, favoring the starting materials (Scheme 6).11 The lack of productive alternatives for the tin radical means that relatively unreactive radical precursors such as chlorides and sulfides can be used. Once formed, radical 1 could also add to either allyltributylstannane or a product alkene; however these bimolecular addition processes are too slow to compete with the rapid unimolecular β‐elimination. As a result, the relatively slow rate constants for addition of alkyl radicals to allylstannanes can be offset by carrying out the reactions at high concentrations. The alkyl radical can also add to either the allylstannane, as desired, or to a product alkene. Kinetic experiments demonstrate that the rate of addition of a primary radical to allyltributylstannane is approximately 3 × 104 M–1s–1 at 50°, and the rate of addition of a secondary radical to allyltributylstannane is approximately 1 × 105 M–1s–1 at 80°.12 These rates are about an order of magnitude faster than the rates of the analogous additions of alkyl radicals to propene, so there is a small but decided preference for the addition to the allylstannane over addition to the product alkene.
Scheme 5
Scheme 6
The origin of the rate acceleration for the addition of simple alkyl radicals to the allylstannane, relative to propene, is not definitively established. It is well known that the rates of addition of alkyl radicals to alkenes are affected primarily by a combination of electronic and steric effects.13,14 For electron‐rich, nucleophilic radicals like alkyl radicals, the rate of addition is accelerated by the presence of electron‐withdrawing groups on the alkene, especially at the β‐carbon, but the stannylmethyl group does not provide this sort of electron‐withdrawing activation. However, EPR studies indicate that the most stable conformation of the 2‐stannylethyl radical places the carbon–tin bond in a position eclipsing the singly occupied p‐orbital (Figure 1).15,16 The resulting hyperconjugative interaction is estimated to stabilize the radical by approximately 2 kcal⋅mol–1, and thus, the developing hyperconjugation in the transition state of the radical addition is likely responsible for the rate acceleration.
Figure 1 Most stable conformation of the 2‐stannylethyl radical.
Because the addition of an alkyl radical to an allylstannane is generally (albeit only marginally) faster than addition to an unactivated alkene, allylstannane‐trapping reactions can be incorporated into multistep cascade processes. For example, carbohydrate iodide 2 reacts with tributyltin radical to form a primary radical, which undergoes a rapid 5‐exo‐trig cyclization before trapping with allyltributylstannane (Scheme 7).17,18 Similarly, in the reaction of iodobutane with 1,1‐dicyano‐2‐phenylethene (3) in the presence of allyltributylstannane, the initially formed butyl radical intermolecularly adds more rapidly to the electron‐poor, activated alkene 3 than to the allylstannane. The resulting adduct radical is now electron poor, so it reacts faster with allyltributylstannane than with the activated alkene 3, and the three‐component product is generated in high yield (Scheme 8).19
Scheme 7
Scheme 8
While most reactions involving β‐fragmentation of stannyl radicals are allylation reactions, numerous examples of vinylation, allenylation, alkynylation, and propargylation reactions (occurring by closely related mechanisms) have also been reported. Of these processes, vinylations are the most common. In these reactions, radical addition must occur at the carbon bearing the stannyl group to form a β‐stannyl radical adduct that can then fragment and generate the final product. An efficient reaction is only possible when the vinylstannane substrate bears an activating substituent, (Y), at the 2‐position to increase the rate of radical addition to C‐1. Suitable substituents include phenyl groups and strongly electron‐withdrawing substituents such as carbonyl or sulfonyl groups. After the initial addition, β‐fragmentation occurs rapidly to form the vinylated product (Scheme 9). For vinylation reactions, it is clearly established from the stereochemical outcome of reactions (vide infra) that the addition–elimination is a two‐step process wherein intermediate radical 4 has a short but distinct lifetime.20
Scheme 9
Stereochemistry
Allylation Reactions.
