Preparation of 3-Alkyl-Substituted 1-Alkoxyallenes – Synthetic and Mechanistic Aspects

Dedicated to Professor Manfred Braun on the occasion of his 70^th birthday

Abstract

Two routes to 3-alkyl-substituted 1-alkoxyallenes are investigated. The deprotonation and alkylation at C-3 of methoxyallene requires prior silylation at C-1 and provides mixtures of the expected products and 1-alkyl-substituted methyl propargyl ethers as minor component. The desilylation of these mixtures affords the desired 3-alkyl-substituted 1-methoxyallenes together with the 1-alkyl-substituted isomers in moderate overall yields. Following the second route, the disadvantages of this three-step method are avoided. In analogy to Brandsma, C-3 alkylation of methyl propargyl ether and subsequent isomerization under basic conditions affords two of the desired 3-alkyl-substituted methoxyallenes in good yields. This method is also applied to propargyl ethers bearing a diacetone-fructose-derived auxiliary. Two diastereomeric 3-alkyl-substituted 1-alkoxyallenes are formed during the isomerization, the ratio being strongly dependent on the reaction conditions. The mechanistic aspects of these observations are discussed on the basis of deuteration experiments and the configurational stability of the ambident propargyl-allenyl carbanion involved.

Key words

alkoxyallenes - alkynes - lithiation - alkylation - carbohydrate derivatives

• References


For general reviews on the chemistry of alkoxyallenes, see:
• 1a Zimmer R. Synthesis 1993; 165
• 1b Reissig H.-U. Hormuth S. Schade W. Okala Amombo M. Watanabe T. Pulz R. Hausherr A. Zimmer R. J. Heterocycl. Chem. 2000; 37: 597
• 1c Reissig H.-U. Zimmer R. Donor-Substituted Allenes . In Modern Allene Chemistry . Krause N. Hashmi AS. K. Wiley-VCH; Weinheim: 2004: 425
• 1d Brasholz M. Reissig H.-U. Zimmer R. Acc. Chem. Res. 2009; 42: 45
• 1e Zimmer R. Reissig H.-U. Chem. Soc. Rev. 2014; 43: 2888
• 1f Reissig H.-U. Zimmer R. Synthesis 2017; 49: 3291

For reviews on lithiated alkoxyallenes summarizing the work of other groups, see:
• 1g Nedolya A. Tarasova O. Volostnykh OG. Albanov AL. Klyba LV. Trofimov BA. Synthesis 2011; 2192
• 1h Tius MA. Chem. Soc. Rev. 2014; 43: 2979
• 2a Flögel O. Okala Amombo MG. Reissig H.-U. Zahn G. Brüdgam I. Hartl H. Chem. Eur. J. 2003; 9: 1405
• 2b Kaden S. Brockmann M. Reissig H.-U. Helv. Chim. Acta 2005; 88: 1826
• 2c Chowdhury MA. Reissig H.-U. Synlett 2006; 2383
• 2d Kaden S. Reissig H.-U. Org. Lett. 2006; 8: 4763
• 2e Brasholz M. Reissig H.-U. Angew. Chem Int. Ed. 2007; 46: 1634 ; Angew. Chem. 2007, 119, 1659
• 2f Brasholz M. Reissig H.-U. Eur. J. Org. Chem. 2009; 3595
• 2g Bressel B. Reissig H.-U. Org. Lett. 2009; 11: 527
• 2h Parmeggiani C. Cardona F. Giusti L. Reissig H.-U. Goti A. Chem. Eur. J. 2013; 19: 10595
• 2i Schmiedel VM. Stefani S. Reissig H.-U. Beilstein J. Org. Chem. 2013; 9: 2564
• 2j Pecchioli T. Cardona F. Reissig H.-U. Zimmer R. Goti A. J. Org. Chem. 2017; 83: 5835
• 3 Hoff S. Brandsma L. Arens JF. Recl. Trav. Chim. Pays-Bas 1969; 88: 609
• 4a Gange D. Magnus P. J. Am. Chem. Soc. 1978; 100: 7746
• 4b Gange D. Magnus P. Bass L. Arnold EV. Clardy J. J. Am. Chem. Soc. 1980; 102: 2134
• 4c Magnus P. Albaugh-Robertson P. J. Chem. Soc., Chem. Commun. 1984; 804
• 4d Hormuth S. Reissig H.-U. J. Org. Chem. 1994; 59: 67
• 4e Hormuth S. Schade W. Reissig H.-U. Liebigs Ann. 1996; 2001
• 4f Cumine F. Young A. Reissig H.-U. Tuttle T. Murphy JA. Eur. J. Org. Chem. 2017; 6867
• 5 Jasiński M. Mlostoń G. Stolarski M. Costa W. Dominguez M. Reissig H.-U. Chem. Asian J. 2014; 9: 2641
• 6a Okala Amombo M. Hausherr A. Reissig H.-U. Synlett 1999; 1871
• 6b Flögel O. Reissig H.-U. Synlett 2004; 895
• 6c Okala Amombo MG. Flögel O. Kord Daoroun Kalai S. Schoder S. Warzok U. Reissig H.-U. Eur. J. Org. Chem. 2017; 1965
• 7a Breuil-Desvergnes V. Compain P. Vatèle J.-M. Goré J. Tetrahedron Lett. 1999; 40: 5009
• 7b Breuil-Desvergnes V. Compain P. Vatèle J.-M. Goré J. Tetrahedron Lett. 1999; 40: 8789
• 7c Breuil-Desvergnes V. Goré J. Tetrahedron 2001; 57: 1939
• 7d Breuil-Desvergnes V. Goré J. Tetrahedron 2001; 57: 1951

Selected references:
• 8a Schade W. Reissig H.-U. Synlett 1999; 632
• 8b Pulz R. Cicchi S. Brandi A. Reissig H.-U. Eur. J. Org. Chem. 2003; 1153
• 8c Helms M. Schade W. Pulz R. Watanabe T. Al-Harrasi A. Fišera L. Hlobilová I. Zahn G. Reissig H.-U. Eur. J. Org. Chem. 2005; 1003

Reviews:
• 8d Pfrengle F. Reissig H.-U. Chem. Soc. Rev. 2010; 39: 549
• 8e Bouché L. Reissig H.-U. Pure Appl. Chem. 2012; 84: 23

Selected references:
• 9a Flögel O. Dash J. Brüdgam I. Hartl H. Reissig H.-U. Chem. Eur. J. 2004; 10: 4283
• 9b Dash J. Lechel T. Reissig H.-U. Org. Lett. 2007; 9: 5541
• 9c Lechel T. Dash J. Brüdgam I. Reissig H.-U. Eur. J. Org. Chem. 2008; 3647
• 9d Lechel T. Dash J. Eidamshaus C. Brüdgam I. Lentz D. Reissig H.-U. Org. Biomol. Chem. 2010; 8: 3007
• 9e Lechel T. Dash J. Hommes P. Lentz D. Reissig H.-U. J. Org. Chem. 2010; 75: 726

For reviews, see:
• 9f Lechel T. Reissig H.-U. Pure Appl. Chem. 2010; 82: 1835
• 9g Lechel T. Reissig H.-U. In Targets in Heterocyclic Systems - Chemistry and Properties . Vol. 20. Attanasi OA. Merino P. Spinelli D. Italian Society of Chemistry; Rome: 2016: 1
• 10 For examples, see ref. 2c, ref. 9e and Lechel, T.; Gerhard, M.; Trawny, D.; Brusilowskij, B.; Schefzig, L.; Zimmer, R.; Rabe, J. P.; Lentz, D.; Schalley, C. A.; Reissig, H.-U. Chem. Eur. J. 2011, 17, 7480.
• 11 For examples, see ref. 2j; 3-alkyl-substituted 1-alkoxyallenes were mainly employed in allene ether Nazarov cyclizations, for a review, see ref. 1h. Also see: Deagostino, A.; Prandi, C.; Toppino­, A.; Venturello P. Tetrahedron 2008, 64, 10344.

For the synthesis of 1-trimethylsilyl-substituted alkoxyallenes, see:
• 12a Clinet J.-C. Linstrumelle G. Tetrahedron Lett. 1980; 21: 3987
• 12b Papparlardo P. Magnus P. Tetrahedron Lett. 1982; 23: 309
• 12c Tius MA. Zhou X.-M. Tetrahedron Lett. 1989; 30: 4629
• 12d Tius MA. Busch-Petersen J. Yamashita M. Tetrahedron Lett. 1998; 39: 4219
• 12e For the synthesis of 1-tert-butyldimethylsilyl-substituted alkoxyallenes, see: Reich HJ. Kelly MJ. Olson RE. Holtan RC. Tetrahedron 1983; 39: 949
• 13 Clinet C. Linstrumelle G. Tetrahedron Lett. 1978; 19: 1137
• 14 Compounds 3 generally undergo isomerization to give 1,3-dienes in the presence of acid (e.g., DCl in CDCl₃) or during longer storage at room temperature. They should be used for subsequent reactions as soon as possible.
• 15 Verkruijsse HD. Verboom W. Van Rijn PE. Brandsma L. J. Organomet. Chem. 1982; 232: C1
• 16a McDonald C. Ramsey JD. Sampsell DG. Butler JA. Cecchini MR. Org. Lett. 2010; 12: 5178
• 16b Berndt M. Hölemann A. Niermann A. Bentz C. Zimmer R. Reissig H.-U. Eur. J. Org. Chem. 2012; 1299
• 17 Mukhopadhyay T. Seebach D. Helv. Chim. Acta 1982; 65: 385
• 18 Hausherr A. Orschel B. Scherer S. Reissig H.-U. Synthesis 2001; 1377
• 19a Arnold T. Orschel B. Reissig H.-U. Angew. Chem., Int. Ed. Engl. 1992; 31: 1033 ; Angew. Chem. 1992, 104, 1084
• 19b Zimmer R. Orschel B. Scherer S. Reissig H.-U. Synthesis 2002; 1553
• 20 See ref. 2i and ref. 1h.
• 21a Rochet P. Vatèle J.-M. Goré J. Synthesis 1994; 795
• 21b Surivet JP. Goré J. Vatèle JM. Tetrahedron 1996; 47: 14877

The configurational assignment is based on the transfer of these compounds into subsequent cyclization products and their analysis:
• 22a Hausherr A. Dissertation. Freie Universität Berlin; Germany: 2001
• 22b Hausherr A., Reissig H.-U. manuscript submitted to Eur. J. Org. Chem.
• 23a Tius MA. Hu H. Kawakami JK. Busch-Petersen J. J. Org. Chem. 1998; 63: 5971
• 23b Harrington PE. Tius MA. Org. Lett. 2000; 2: 2447
• 24 Schultz-Fademrecht C. Wibbeling B. Fröhlich R. Hoppe D. Org. Lett. 2001; 3: 1221
• 25 For a review, see: Hoppe D. Hense T. Angew. Chem. Int. Ed. 1997; 36: 2282 ; Angew. Chem. 1997, 109, 2376
• 26a Reich HJ. Holladay JE. J. Am. Chem. Soc. 1995; 117: 8470
• 26b Reich HJ. Thompson JL. Org. Lett. 2000; 2: 783
• 26c Reich HJ. J. Org. Chem. 2012; 77: 5471

For gas phase and solution studies of lithiated methoxyallene, see:
• 27a Dixon DD. Tius MA. Pratt LM. J. Org. Chem. 2009; 74: 5881
• 27b Pratt LM. Dixon DD. Tius MA. ChemistryOpen 2014; 3: 250
• 28 For a review on heteroatom-substituted alkenyl lithium reagents, see: Braun M. Angew. Chem. Int. Ed. 1998; 37: 430 ; Angew. Chem. 1998, 110, 444
• 29 Hoff S. Brandsma L. Arens JF. Recl. Trav. Chim. Pays-Bas 1968; 87: 916
• 30 Jackson WR. Perlmutter P. Smallridge AJ. Aust. J. Chem. 1988; 41: 251