347:
312:
134:
278:
911:); b) Teodoro S. Kaufman "Synthesis of Optically-Active Isoquinoline and Indole Alkaloids Employing the Pictet-Spengler Condensation with Removable Chiral Auxiliaries Bound to Nitrogen". in "New Methods for the Asymmetric Synthesis of Nitrogen Heterocycles"; Ed.: J. L. Vicario.
295:
Replacing an indole with a 3,4-dimethoxyphenyl group give the reaction named the Pictet–Spengler tetrahydroisoquinoline synthesis. Reaction conditions are generally harsher than the indole variant, and require refluxing conditions with strong acids like
965:
Ungemach, F.; Soerens, D.; Weber, R.; Dipierro, M.; Campos, O.; Mokry, P.; Cook, J. M.; Silverton, J. V. (1980). "General method for the assignment of stereochemistry of 1,3-disubstituted 1,2,3,4-tetrahydro-β-carbolines by carbon-13 spectroscopy".
125:
ion generated from the condensation of the aldehyde and amine under acid conditions. This explains the need for an acid catalyst in most cases, as the imine is not electrophilic enough for ring closure but the
693:
Yokoyama, Akihiro; Ohwada, Tomohiko; Shudo, Koichi (1999). "Prototype Pictet−Spengler
Reactions Catalyzed by Superacids. Involvement of Dicationic Superelectrophiles".
897:
The intermolecular Pictet-Spengler condensation with chiral carbonyl derivatives in the stereoselective syntheses of optically-active isoquinoline and indole alkaloids
490:
784:
Bonnet, D.; Ganesan, A. (2002). "Solid-Phase
Synthesis of Tetrahydro-β-carbolinehydantoins via the N-Acyliminium Pictet-Spengler Reaction and Cyclative Cleavage".
860:
Gremmen, C.; Willemse, B.; Wanner, M. J.; Koomen, G.-J. (2000). "Enantiopure
Tetrahydro-β-carbolines via Pictet-Spengler Reactions with N-Sulfinyl Tryptamines".
607:
Nielsen, T. E.; Diness, F.; Meldal, M. (2003). "Solid-Phase
Synthesis of Pyrroloisoquinolines via the Intramolecular N-Acyliminium Pictet-Spengler Reaction".
346:
311:
634:
Nielsen, T. E.; Meldal, M. (2005). "Solid-Phase
Synthesis of Pyrroloisoquinolines via the Intramolecular N-Acyliminium Pictet-Spengler Reaction".
670:
Larghi, E. L.; Kaufman, T. S. (2006). "The oxa-Pictet-Spengler
Cyclization. Synthesis of Isochromanes and Related Pyran-Type Heterocycles".
60:
141:
The Pictet–Spengler reaction is widespread in both industry and biosynthesis. It has remained an important reaction in the fields of
450:
controlled, i.e. it is performed at lower temperatures. At higher temperatures the reaction becomes reversible and usually favours
205:
group give poorer yields or require higher temperatures and strong acid. The original Pictet–Spengler reaction was the reaction of
1010:
558:
Whaley, W. M.; Govindachari, T. R. (1951). "The Pictet-Spengler synthesis of tetrahydroisoquinolines and related compounds".
748:
Maryanoff, B. E.; Zhang, H.-C.; Cohen, J. H.; Turchi, I. J.; Maryanoff, C. A. (2004). "Cyclizations of N-acyliminium ions".
529:"Über die Bildung von Isochinolin-derivaten durch Einwirkung von Methylal auf Phenyl-äthylamin, Phenyl-alanin und Tyrosin"
161:. Pictet–Spengler products can be isolated from many products initially derived from nature, including foodstuffs such as
277:
133:
916:
502:
1005:
1000:
507:
580:
Cox, E. D.; Cook, J. M. (1995). "The Pictet-Spengler condensation: a new direction for an old reaction".
721:
Quevedo, R.; Baquero, E.; Rodriguez, M. (2010). "Regioselectivity in isoquinoline alkaloid
Synthesis".
53:
908:
201:
give products in high yields and mild conditions, while less nucleophilic aromatic rings such as a
1015:
228:
255:
218:
158:
929:
Seayad, J.; Seayad, A. M.; List, B. (2006). "Catalytic
Asymmetric Pictet-Spengler Reaction".
422:
225:
82:
41:
301:
8:
470:
427:
267:
247:
117:, which follows a similar reaction pathway. The driving force for this reaction is the
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947:
931:
912:
878:
842:
802:
766:
652:
616:
447:
297:
214:
146:
78:
343:
and most aromatic ring systems will cyclize under mild conditions with good yields.
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939:
870:
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758:
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703:
675:
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589:
540:
362:
210:
118:
114:
820:
Youn, S. W. (2006). "Development of the Pictet-Spengler
Reaction Catalyzed by AuCl
393:
899:
Enrique L. Larghi, Marcela
Amongero, Andrea B. J. Bracca, and Teodoro S. Kaufman
859:
734:
385:
369:
106:
327:
Instead of catalyzing the Pictet–Spengler cyclization with strong acid, one can
786:
636:
474:
206:
150:
110:
102:
98:
361:-acyliminium Pictet–Spengler reaction. This reaction can also be catalyzed by
994:
826:
695:
544:
478:
415:
384:, a new chiral center is created. Several substrate- or auxiliary-controlled
97:
and Theodor Spengler (22 February 1886 – 18 August 1965). Traditionally, an
94:
29:
951:
882:
846:
806:
770:
656:
620:
451:
381:
380:
When the Pictet–Spengler reaction is performed with an aldehyde other than
340:
187:
149:
since its inception, where it has been employed in the development of many
105:
was employed with heating; however, the reaction has been shown to work in
679:
404:
980:
593:
862:
750:
435:
407:
173:
170:
113:. The Pictet–Spengler reaction can be considered a special case of the
93:
followed by ring closure. The reaction was first discovered in 1911 by
943:
874:
838:
798:
762:
707:
648:
258:
at the 3-position, in accordance with the expected nucleophilicity of
354:
328:
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181:
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919:. Research SignPost, Trivandrum, India. 2005. Chapter 4, pp. 99–147.
528:
439:
290:
190:
142:
86:
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Pictet–Spengler reactions have been developed. Additionally, List
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198:
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127:
122:
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259:
202:
194:
177:
154:
90:
411:
319:
964:
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234:
An analogous reaction with an aryl-β-ethanol is called
153:. Natural Pictet–Spengler reaction typically employ an
375:
396:
that catalyzes asymmetric Pictet–Spengler reactions.
692:
606:
557:
224:The Pictet–Spengler reaction has been applied to
992:
928:
291:Pictet–Spengler tetrahydroisoquinoline synthesis
481:signals for C1 and C3 are downfield shifted in
250:occurs by initial formation of an iminium ion (
533:Berichte der Deutschen Chemischen Gesellschaft
526:
783:
669:
633:
281:The mechanism of the Pictet–Spengler reaction
350:The N-acyliminium Pictet–Spengler reaction
315:The Pictet–Spengler isoquinoline synthesis
575:
573:
400:Tryptophans: diastereocontrolled reaction
331:the iminium ion forming the intermediate
323:-acyliminium ion Pictet–Spengler reaction
169:. In such cases it is common to find the
109:in superior yields and sometimes without
458:dominated products can be obtained with
579:
130:is capable of undergoing the reaction.
993:
570:
81:in which a β-arylethylamine undergoes
469:tryptophans, which are accessible by
241:
819:
339:-acyliminium ion is a very powerful
376:Asymmetric Pictet–Spengler reaction
270:, deprotonation gives the product (
13:
473:. The benzyl group can be removed
345:
310:
276:
132:
14:
1027:
527:Pictet, A.; Spengler, T. (1911).
958:
922:
889:
853:
813:
777:
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714:
686:
663:
627:
600:
551:
520:
425:center at C-1 adopts either a
266:. After migration of the best
1:
1011:Heterocycle forming reactions
513:
503:Bischler–Napieralski reaction
477:afterwards. As a rough rule,
285:
735:10.1016/j.tetlet.2010.01.115
609:Curr. Opin. Drug Discov. Dev
414:leads to 1,2,3,4-tetrahydro-
236:oxa-Pictet–Spengler reaction
137:The Pictet–Spengler reaction
7:
496:
10:
1032:
508:Pomeranz–Fritsch reaction
491:steric compression effect
262:, to give the spirocycle
67:
47:
21:Pictet-Spengler reaction
20:
545:10.1002/cber.19110440309
410:or its short-chain alkyl
392:have published a chiral
75:Pictet–Spengler reaction
357:is synthesized via the
229:combinatorial chemistry
180:used as the biological
1006:Condensation reactions
1001:Ring forming reactions
351:
335:-acyliminium ion. The
316:
282:
256:electrophilic addition
219:tetrahydroisoquinoline
159:strictosidine synthase
138:
903:(RL-1554K) pp 98–153
680:10.1055/s-2005-918502
485:products relative to
349:
314:
280:
136:
42:Ring forming reaction
302:trifluoroacetic acid
231:with great success.
981:10.1021/ja00543a012
723:Tetrahedron Letters
594:10.1021/cr00038a004
471:reductive amination
475:hydrogenolytically
386:diastereoselective
352:
317:
283:
248:reaction mechanism
242:Reaction mechanism
139:
975:(23): 6976–6984.
969:J. Am. Chem. Soc.
944:10.1021/ja057444l
932:J. Am. Chem. Soc.
875:10.1021/ol006034t
869:(13): 1955–1958.
839:10.1021/jo0524775
799:10.1021/cc020026h
763:10.1021/cr0306182
729:(13): 1774–1778.
708:10.1021/jo982019e
649:10.1021/cc050008a
298:hydrochloric acid
215:hydrochloric acid
147:organic synthesis
79:chemical reaction
71:
70:
33:Theodor Spengler
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956:
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938:(4): 1086–1087.
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833:(6): 2521–2523.
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588:(6): 1797–1842.
582:Chemical Reviews
577:
568:
567:
555:
549:
548:
539:(3): 2030–2036.
524:
438:towards the C-3
403:The reaction of
211:dimethoxymethane
119:electrophilicity
115:Mannich reaction
63:
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421:in which a new
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268:migrating group
244:
213:, catalysed by
151:beta-carbolines
99:acidic catalyst
59:
32:
12:
11:
5:
1029:
1019:
1018:
1016:Name reactions
1013:
1008:
1003:
987:
986:
957:
921:
888:
852:
821:
812:
793:(6): 546–548.
787:J. Comb. Chem.
776:
740:
713:
702:(2): 611–617.
685:
674:(2): 187–210.
662:
643:(4): 599–610.
637:J. Comb. Chem.
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615:(6): 801–814.
599:
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489:products (see
461:
446:conduction is
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324:
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292:
289:
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254:) followed by
243:
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207:phenethylamine
193:rings such as
111:acid catalysis
103:protic solvent
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38:Reaction type
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917:81-7736-278-X
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909:Online Review
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436:configuration
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394:Brønsted acid
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452:racemisation
443:
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382:formaldehyde
379:
358:
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341:electrophile
336:
332:
326:
320:
294:
271:
263:
251:
245:
235:
233:
223:
188:Nucleophilic
186:
176:and various
140:
83:condensation
74:
72:
61:RXNO:0000059
56:ontology ID
48:Identifiers
26:Named after
15:
448:kinetically
442:group. The
419:-carbolines
405:enantiopure
226:solid-phase
128:iminium ion
995:Categories
863:Org. Lett.
751:Chem. Rev.
560:Org. React
514:References
467:benzylated
408:tryptophan
306:superacids
286:Variations
217:forming a
174:tryptophan
171:amino acid
157:, such as
95:Amé Pictet
30:Amé Pictet
824:/AgOTf".
672:Synthesis
355:Tadalafil
182:feedstock
163:soy sauce
952:16433519
883:10891200
847:16526809
807:12425597
771:15008627
657:16004504
621:14758752
497:See also
440:carboxyl
191:aromatic
143:alkaloid
87:aldehyde
85:with an
901:Arkivoc
329:acylate
260:indoles
199:pyrrole
178:aldoses
167:ketchup
123:iminium
121:of the
950:
915:
881:
845:
805:
769:
655:
619:
454:. 1,3-
423:chiral
412:esters
390:et al.
203:phenyl
195:indole
155:enzyme
91:ketone
566:: 74.
487:trans
479:C NMR
456:trans
433:trans
370:AgOTf
77:is a
948:PMID
913:ISBN
905:2005
879:PMID
843:PMID
803:PMID
767:PMID
653:PMID
617:PMID
368:and
363:AuCl
246:The
209:and
165:and
145:and
73:The
977:doi
973:102
940:doi
936:128
871:doi
835:doi
795:doi
759:doi
755:104
731:doi
704:doi
676:doi
645:doi
590:doi
541:doi
493:).
483:cis
444:cis
431:or
428:cis
304:or
274:).
197:or
101:in
89:or
54:RSC
997::
946:.
895:a)
877:.
841:.
831:71
801:.
765:.
727:51
725:.
700:64
651:.
611:.
586:95
584:.
572:^
562:.
537:44
535:.
531:.
372:.
308:.
300:,
238:.
221:.
184:.
983:.
979::
954:.
942::
907:(
885:.
873::
867:2
849:.
837::
822:3
809:.
797::
791:4
773:.
761::
737:.
733::
710:.
706::
682:.
678::
659:.
647::
641:7
623:.
613:6
596:.
592::
564:6
547:.
543::
465:-
462:b
460:N
417:β
365:3
359:N
337:N
333:N
321:N
272:5
264:3
252:2
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