Additions of Carbohydrate-Derived Alkoxyallenes to Imines and Subsequent Reactions to Enantiopure 2,5-Dihydropyrrole Derivatives

Abstract

The additions of six alkoxyallenes bearing carbohydrate-derived chiral auxiliaries to imines were systematically studied. The reactions of three lithiated 1-alkoxypropa-1,2-dienes with an N-tosyl imine revealed that the diacetone fructose-derived auxiliary provided the highest diastereoselectivity of 91:9. The preferred absolute configuration of the newly formed stereogenic center was determined by subsequent ozonolysis of the allene moiety, transesterification and comparison with literature data. The analogous reactions of three axially chiral 3-nonyl-substituted 1-alkoxyallenes with these auxiliaries confirm these results and also prove that the configuration of the generated stereogenic center was only steered by the auxiliaries, whereas the chiral axis has essentially no influence. In general, four diastereomers were obtained in various portions, depending on the ratio of the two precursor allene diastereomers and on the auxiliary employed. The obtained dia­stereomeric allenyl amines were cyclized under different conditions. As expected, under basic conditions, a stereospecific cyclization occurred, whereas under silver nitrate catalysis partial isomerization at the allene stage was observed. Under both conditions the 2,5-cis-disubstituted dihydropyrroles were formed faster than the trans-isomers. Several of the 2-substituted or 2,5-disubstituted dihydropyrrole derivatives could be isolated in diastereomerically pure form and were subsequently converted into the expected pyrrolidin-3-ones by removal of the carbohydrate-derived auxiliary under acidic conditions. The desired products were obtained in good yield and with high enantiopurity. They are suitable starting materials for the synthesis of enantiopure pyrrolidine natural products.

Key words

alkoxyallenes - axial chirality - carbohydrate derivatives - imines - lithiation - nitrogen heterocycles - pyrrolidines

• References


Early reports:
• 1a Tius MA. Zhou X.-m. Tetrahedron Lett. 1989; 30: 5629
• 1b Tius MA. Busch-Petersen J. Yamashita M. Tetrahedron Lett. 1998; 39: 4219
• 1c For a review on Nazarov cyclizations: Tius MA. Chem. Soc. Rev. 2014; 43: 2979
• 1d Synthesis of pentasubstituted pyridines: Lechel T. Dash J. Hommes P. Lentz D. Reissig H.-U. J. Org. Chem. 2010; 75: 726
• 1e Synthesis of pyrrolizidine alkaloids: Pecchioli T. Cardona F. Reissig H.-U. Zimmer R. Goti A. J. Org. Chem. 2017; 83: 5835

General reviews on the chemistry of alkoxyallenes:
• 2a Zimmer R. Synthesis 1993; 165
• 2b Reissig H.-U. Hormuth S. Schade W. Okala Amombo M. Watanabe T. Pulz R. Hausherr A. Zimmer R. J. Heterocycl. Chem. 2000; 37: 597
• 2c Reissig H.-U. Zimmer R. Donor-Substituted Allenes . In Modern Allene Chemistry . Krause N. Hashmi AS. K. Wiley-VCH; Weinheim: 2004: 425
• 2d Brasholz M. Reissig H.-U. Zimmer R. Acc. Chem. Res. 2009; 42: 45
• 2e Zimmer R. Reissig H.-U. Chem. Soc. Rev. 2014; 43: 2888
• 2f Reissig H.-U. Zimmer R. Synthesis 2017; 49: 3291
• 2g For reviews on lithiated alkoxyallenes summarizing the work of other groups, see: Nedolya A. Tarasova O. Volostnykh OG. Albanov AL. Klyba LV. Trofimov BA. Synthesis 2011; 2192
• 3 Hausherr A. Reissig H.-U. Synthesis 2018; 50: 2546
• 4 Hausherr A. Reissig H.-U. Eur. J. Org. Chem. 2018; 4071
• 5a Flögel O. Okala Amombo MG. Reissig H.-U. Zahn G. Brüdgam I. Hartl H. Chem. Eur. J. 2003; 9: 1405
• 5b Chowdhury MA. Reissig H.-U. Synlett 2006; 2383
• 6a Arnold T. Orschel B. Reissig H.-U. Angew. Chem. Int. Ed. Engl. 1992; 31: 1033 ; Angew. Chem. 1992, 104, 1084
• 6b Zimmer R. Orschel B. Scherer S. Reissig H.-U. Synthesis 2002; 1553
• 7a Rochet P. Vatèle J.-M. Goré J. Synthesis 1994; 795
• 7b Surivet JP. Goré J. Vatèle JM. Tetrahedron 1996; 47: 14877
• 7c Kaden S. Brockmann M. Reissig H.-U. Helv. Chim. Acta 2005; 88: 1826
• 7d Banaag AR. Tius MA. J. Org. Chem. 2008; 73: 8133 ; and other publications of this group collected in ref. 1c
• 7e After completion of this work (ref. 9a), a report on diastereoselective additions of lithiated alkoxyallenes bearing carbohydrate-derived auxiliaries to N-tosyl imines was published, see: Cai S. Gorityala BK. Ma J. Leow ML. Liu X.-W. Org. Lett. 2011; 13: 1072
• 8 Hausherr A. Orschel B. Scherer S. Reissig H.-U. Synthesis 2001; 1377
• 9a Hausherr A. Dissertation . Freie Universität Berlin; 2001
• 9b Hausherr A., Reissig H.-U. publication in preparation.
• 10a Hormuth S. Reissig H.-U. Dorsch D. Liebigs Ann. Chem. 1994; 121
• 10b Schade W. Reissig H.-U. J. Prakt. Chem. 1999; 341: 685
• 10c Okala Amombo M. Hausherr A. Reissig H.-U. Synlett 1999; 1871
• 10d Taszarek M. Zimmer R. Schefzig L. Reissig H.-U. Synlett 2008; 2046
• 10e Prisyazhnyuk V. Jachan M. Brüdgam I. Zimmer R. Reissig H.-U. Collect. Czech. Chem. Commun. 2009; 74: 1069
• 11 Bressel B. Reissig H.-U. Org. Lett. 2009; 11: 527
• 12 Kobayashi K. Okamoto T. Oida T. Tanimoto S. Chem. Lett. 1986; 2031

For gas-phase and solution studies of lithiated methoxyallene and the influence of additives, see:
• 13a Dixon DD. Tius MA. Pratt LM. J. Org. Chem. 2009; 74: 5881
• 13b Pratt LM. Dixon DD. Tius MA. ChemistryOpen 2014; 3: 250
• 14 Chemla F. Hebbe M. Normant J.-F. Synthesis 2000; 75
• 15 Verkruijsse HD. Verboom W. Van Rijn PE. Brandsma L. J. Organomet. Chem. 1982; 232: C1

For cyclizations of allenyl amines under basic conditions, see:
• 16a ref. 5a.
• 16b Flögel O. Reissig H.-U. Synlett 2004; 895
• 16c Okala Amombo MG. Flögel O. Kord Daoroun Kalai S. Schoder S. Warzok U. Reissig H.-U. Eur. J. Org. Chem. 2017; 1965
• 16d For a theoretical study of this reaction, see: Cumine F. Young A. Reissig H.-U. Tuttle T. Murphy JA. Eur. J. Org. Chem. 2017; 6867

For silver nitrate-promoted reactions of allenyl alcohols and amines, see:
• 17a Leandri G. Monti M. Bertrand M. Tetrahedron 1974; 30: 289
• 17b Olsson L.-I. Claesson A. Synthesis 1979; 743
• 17c Claesson A. Sahlberg S. Luthman K. Acta Chem. Scand., Ser. B 1979; 33: 309
• 17d Arseniyadis S. Goré J. Tetrahedron Lett. 1983; 24: 3997
• 17e Prasad JS. Liebeskind LS. Tetrahedron Lett. 1988; 29: 4253
• 17f Shaw RW. Lathbury D. Gallagher T. Synlett 1993; 710
• 17g Schierle K. Vahle R. Steckhan E. Eur. J. Org. Chem. 1998; 509 ; see also refs. 16a–c

The presented investigations were performed (ref. 9a) before gold compounds were discovered to be superior catalysts for many cyclization reactions: For selected examples, see:
• 18a Hashmi AS. K. Schwarz I. Choi J.-H. Frost TM. Angew. Chem. Int. Ed. 2000; 39: 2285 ; Angew. Chem. 2000, 112, 2382
• 18b Gockel B. Krause N. Org. Lett. 2006; 8: 4485
• 18c Tao S. Deutsch C. Krause N. Org. Biomol. Chem. 2012; 10: 5965

For reviews on gold-catalyzed allene cyclizations, see:
• 18d Krause N. Winter C. Chem. Rev. 2011; 111: 1994
• 18e Alcaide B. Almendros P. Acc. Chem. Res. 2014; 47: 939 . For our results employing gold catalysis in allenyl amine cyclizations, see ref. 16c
• 19 Flögel O. Reissig H.-U. Eur. J. Org. Chem. 2004; 2797
• 20a Breuil-Desvergnes V. Compain P. Vatèle J.-M. Goré J. Tetrahedron Lett. 1999; 40: 5009
• 20b Breuil-Desvergnes V. Goré J. Tetrahedron 2001; 57: 1951
• 21 For a review, see: Job A. Janeck CF. Bettray W. Peters R. Enders D. Tetrahedron 2002; 58: 2253
• 22 We assume that the relatively high acidity of the benzylic position of this hydrazone is responsible for a protonation of the fairly basic lithiated allenes.

For reviews on the use of carbohydrate derivatives as auxiliaries in organic synthesis, see:
• 23a Reissig H.-U. Angew. Chem. Int. Ed. Engl. 1992; 31: 288 ; Angew. Chem. 1992, 104, 295
• 23b Kunz H. Rück K. Angew. Chem. Int. Ed. Engl. 1993; 32: 336 ; Angew. Chem. 1992, 105, 355
• 23c Kunz H. Rück-Braun K. Chiral Auxiliaries in Cycloadditions . Wiley-VCH; Weinheim: 1999
• 23d Hultin PG. Earle MA. Sudharshan M. Tetrahedron 1997; 53: 14823
• 23e Lehnert T. Özüduru G. Grugel H. Albrecht F. Telligmann SM. Boysen MM. K. Synthesis 2011; 2685
• 24 Albrecht R. Kresze G. Mlakar B. Chem. Ber. 1964; 97: 483
• 25 Paterson W. Proctor GR. J. Chem. Soc. 1965; 485
• 26 Hojo M. Hojo M. Inoue Y. Tanimoto S. Bull. Chem. Soc. Jpn. 1990; 63: 2588