Aza-Wittig rearrangement of N,N-dipropargylic α-amino alkyllithiums: Periselectivity and steric course

Synlett

Volumn , Issue 11, 2004, Pages 1925-1928

  Tomoyasu, Takahiro ^a   Tomooka, Katsuhiko ^a  

^a TOKYO INSTITUTE OF TECHNOLOGY   (Japan)

Author keywords

Amines; Asymmetric; Carbanions; Periselectivity; Wittig rearrangements

Indexed keywords

CARBON; LITHIUM DERIVATIVE; TIN;

ARTICLE; CHEMICAL STRUCTURE; ENANTIOSELECTIVITY; STEREOCHEMISTRY; WITTIG REARRANGEMENT;

EID: 4544253639     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2004-830854     Document Type: Article

References (19)

1. Reviews: (a) Vogel, C. Synthesis 1997, 497. (b) Tomooka, K. In The Chemistry of Organolithium Compounds; Rappoport, Z.; Marek, I., Eds.; Wiley: New York, 2004, Chap. 12.
2. Reviews: (a) Vogel, C. Synthesis 1997, 497. (b) Tomooka, K. In The Chemistry of Organolithium Compounds; Rappoport, Z.; Marek, I., Eds.; Wiley: New York, 2004, Chap. 12.
3. For recent examples of synthetic applications of the aza-Wittig rearrangement, see: (a) Broka, C. A.; Shen, T. J. Am. Chem. Soc. 1989, 111, 2981. (b) Coldham, I. J. Chem. Soc., Perkin Trans. 1 1993, 1275. (c) Åhman, J.; Somfai, P. Tetrahedron Lett. 1996, 37, 2495. (d) Anderson, J. C.; Whiting, M. J. Org. Chem. 2003, 68, 6160.
4. For recent examples of synthetic applications of the aza-Wittig rearrangement, see: (a) Broka, C. A.; Shen, T. J. Am. Chem. Soc. 1989, 111, 2981. (b) Coldham, I. J. Chem. Soc., Perkin Trans. 1 1993, 1275. (c) Åhman, J.; Somfai, P. Tetrahedron Lett. 1996, 37, 2495. (d) Anderson, J. C.; Whiting, M. J. Org. Chem. 2003, 68, 6160.
5. For recent examples of synthetic applications of the aza-Wittig rearrangement, see: (a) Broka, C. A.; Shen, T. J. Am. Chem. Soc. 1989, 111, 2981. (b) Coldham, I. J. Chem. Soc., Perkin Trans. 1 1993, 1275. (c) Åhman, J.; Somfai, P. Tetrahedron Lett. 1996, 37, 2495. (d) Anderson, J. C.; Whiting, M. J. Org. Chem. 2003, 68, 6160.
6. For recent examples of synthetic applications of the aza-Wittig rearrangement, see: (a) Broka, C. A.; Shen, T. J. Am. Chem. Soc. 1989, 111, 2981. (b) Coldham, I. J. Chem. Soc., Perkin Trans. 1 1993, 1275. (c) Åhman, J.; Somfai, P. Tetrahedron Lett. 1996, 37, 2495. (d) Anderson, J. C.; Whiting, M. J. Org. Chem. 2003, 68, 6160.
7. Tomoyasu, T.; Tomooka, K.; Nakai, T. Tetrahedron Lett. 2003, 44, 1239.
8. 3 (Chemical Equation Presented) (5) Gawley' s group has reported the first experimental evidence for the inversion course in the aza-[2,3]-Wittig rearrangement of (S)-N-allyl-2-lithiopyrrolidine, which considerably competes with the [1,2]-Wittig rearrangement process. However, no systematic study has been made on the steric course at the Li-bearing terminus of the aza-[1,2]-Wittig rearrangement. See: Gawley, R. E.; Zhang, Q.; Campagna, S. J. Am. Chem. Soc. 1995, 117, 11817. (Chemical Equation Presented)
9. For the preparation of N,N-dipropargyl alkylstannane (R)-1a, N,N-diisopropylethylamine was utilized as a base instead of NaH.
10. 3).
11. 2O = 5:1) to give the [1,2]-product 3c (10 mg, 10%), [2,3]-product 4c (35 mg, 36%) and allene 6c (14 mg, 15%).
12. 3): δ = 12.4, 13.4, 14.1, 22.1, 32.3, 36.3, 37.9, 56.9, 77.4, 84.9, 86.7, 93.9, 125.7, 128.3, 128.5, 142.2, 203.8. (Chemical Equation Presented)
13. The formation of 6c can be explained by two possible pathways. The first is the conversion of the alkynyl group into an allenyl group by deprotonation at the propargylic position of 2c, followed by [1,2]-allenyl migration (path A). The second is the deprotonation of [1,2]-shifted product (path B). However, the exact mechanism is unclear at present.
14. The periselectivity of the Wittig rearrangement of propargylic ethers also depends upon the kind of substituents at the acetylenic terminus, see: Tomooka, K.; Komine, N.; Nakai, T. Synlett 1997, 1045.
15. Attempts to separate the enantiomers of rearrangement products 3 and 4 at this stage using chiral HPLC (OD-H, AD) failed. Also, attempts to determine the diastereomer ratio of 7 and 9 using achiral HPLC analysis (ODS) failed.
16. Non-stereospecificity of the rearrangement of 2a is understandable if the electronic repulsion between the radical pairs prevents radical recombination. In that case, the radical recombination proceeds at a slow rate; thus, the chiral migrating radical can be racemized during the reaction.
17. HPLC analysis was carried out on a Chiralcel OD-H (0.46 x 25 cm) using heptane:i-PrOH:MeOH = 99.8:0.15:0.05 v/v (0.5 mL/min) as the mobile phase.
18. Low enantiopurity of (R,S)-8 is attributed to the racemization of chiral α-oxy lithium which generated via Sn-Li exchange.
19. Retention of stereochemistry in tin-lithium exchange reactions is well-known for the generation of α-hetero alkyllithiums, see: Pearson, W. H.; Lindbeck, A. C.; Kampf, J. W. J. Am. Chem. Soc. 1993, 115, 2622; and references cited therein.