Unprotected Amino Aldehydes

By: Dr. Mark Redlich, Chemfiles Volume 10 Article 1

         Dr. Mark Redlich

Dr. Mark Redlich
Product Manager
Email: mark.redlich@sial.com

Professor Andrei Yudin and his students have recently described the preparation of bench-stable, unprotected a-amino aldehydes.1 These kinetically amphoteric molecules exist as dimers (eq 1), and due to the strain of the aziridine ring, resist inter- and intramolecular iminium ion formation. Furthermore, the two functionalities remain orthogonal to each other throughout their transformations, allowing for the reaction of the aldehyde without the requirement of an additional protecting group.

(eq 1)

(eq 1)


Whereas the reductive amination of protected amino aldehydes has significant limitations due to epimerization or overalkylation, these Yudin amino aldehyde dimers do not suffer from either limitation, due to a negligible concentration of free aldehyde during the reaction. This allows the researcher facile access to a method for the creation of complex polycyclic skeletons2 or peptidomimetic conjugates3 with a high degree of stereocontrol. Nucleophilic additions,4 Wittig and related olefination reactions, can be carried out with high selectivities and yields.

More recently, the Yudin group has reported the use of the amino aldehydes as electrophiles in a domino aza-Michael/aldol reaction, which generated aminohydroxy a, b-unsaturated aldehydes in high yields (Scheme 1).5 The products from this transformation are not accessible through the more common Baylis–Hillman reaction due to the substitution pattern on the olefin.

Scheme 1

Scheme 1


Additionally, the Yudin amino aldehydes are also easily olefinated through a Wittig protocol in good to excellent yield (Scheme 2). These vinylaziridines can then be employed in the construction of azepines or heterobicycles though a ring-opening or a cascade ring-opening/ring-contraction route, respectively (Scheme 3).6

Scheme 2

Scheme 2


Scheme 3

Scheme 3


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Materials

     

References

  1. Hili, R.; Yudin, A. K. J. Am. Chem. Soc. 2006, 128, 14772.
  2. Yudin, A. K.; Hili, R. Chem.—Eur. J. 2007, 13, 6538.
  3. Li, X.; Yudin, A. K. J. Am. Chem. Soc. 2007, 129, 14152.
  4. Hili, R.; Yudin, A. K. Angew. Chem. Int. Ed. 2008, 47, 4188.
  5. Hili, R.; Yudin, A. K. J. Am. Chem. Soc. 2009, 131, 16404.
  6. Baktharaman, S. et al. Org. Lett. 2010,12, 240.

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