Indium-Induced Addition of Bromomethylacrylates to Phthaloyl-Protected Amino Aldehydes

Abstract

The indium-mediated reaction of phthaloyl-protected α-amino aldehydes 1-4 with methyl 2-(bromomethyl)acrylate in aqueous solvents was investigated. The homoallyl alcohols 5-8 were formed in 72-89% yields, the anti-isomers being the major diastereoisomers (dr 45:55-18:82). Acid-catalyzed esterification (H₂SO₄ in Et₂O) led to α-methylene γ-butyrolactones 9,10 with yields ranging from 88 to 99%. Conjugate addition of cyanide and thiophenolate led to the addition products with improved selectivities compared with additions to carbamate-protected substrates. During the conjugate addition of a cuprate, a trapping of the intermediate enolate by a phthaloyl carbonyl group occurred, leading to tetracycle 11 in 57% yield. The configuration of all diastereo­isomers could be established by three X-ray crystallographic analyses and by NMR spectroscopy.

allylation - indium - Michael additions - α-amino aldehydes - α-methylene γ-butyrolactones

References

<A NAME="RC00802SS-1">1</A> Blomberg C. The Barbier Reaction and Related One-Step Processes   Springer; Heidelberg: 1994. 

<A NAME="RC00802SS-2A">2a</A> Lubineau A. Augé J. Queneau Y. Synthesis  1994,  741 

<A NAME="RC00802SS-2B">2b</A> Cintas P. Synlett  1995,  1087 

<A NAME="RC00802SS-2C">2c</A> Li C.-J. Tetrahedron  1996,  52:  5643 

<A NAME="RC00802SS-2D">2d</A> Li C.-J. Chan T.-H. Organic Reactions in Aqueous Media   Wiley-Interscience; New York: 1997. 

<A NAME="RC00802SS-2E">2e</A> Lubineau A. Augé J. Queneau Y. In Organic Synthesis in Water   Grieco PA. Blackie Academic; London: 1998.  p.102 

<A NAME="RC00802SS-2F">2f</A> Paquette LA. In Green Chemistry. Frontiers in Benign Chemical Syntheses and Processes   Anastas PT. Williamson TC. Oxford University Press; Oxford: 1998.  p.250 

<A NAME="RC00802SS-2G">2g</A> Hashmi ASK. J. Prakt. Chem.  1998,  340:  84 

<A NAME="RC00802SS-2H">2h</A> Lainé D. Synlett  1999,  1331 

<A NAME="RC00802SS-2I">2i</A> Lubineau A. Augé J. Top. Curr. Chem.  1999,  206:  1 

<A NAME="RC00802SS-2J">2j</A> Loh T.-P. Huang J.-M. Xu K.-C. Goh S.-H. Vittal JJ. Tetrahedron Lett.  2000,  41:  6511 

<A NAME="RC00802SS-3A">3a</A> Steurer S. Podlech J. Eur. J. Org. Chem.  1999,  1551 

<A NAME="RC00802SS-3B">3b</A> Steurer S. Podlech J. Org. Lett.  1999,  1:  481 

<A NAME="RC00802SS-3C">3c</A> Steurer S. Podlech J. Adv. Synth. Catal.  2001,  343:  251 

<A NAME="RC00802SS-3D">3d</A> Steurer S. Podlech J. Eur. J. Org. Chem.  2002,  899 

<A NAME="RC00802SS-3E">3e</A> For the original publication of this method see: Öhler E. Reininger K. Schmidt U. Angew. Chem., Int. Ed. Engl.  1970,  9:  457 ; Angew.Chem. 1970, 82, 480

<A NAME="RC00802SS-3F">3f</A> Independent work was published by: Paquette LA. Mitzel TM. Isaac MB. Crasto CF. Schomer WW. J. Org. Chem.  1997,  62:  4293 

<A NAME="RC00802SS-4A">4a</A> Hanessian S. Park H. Yang R.-Y. Synlett  1997,  351 

<A NAME="RC00802SS-4B">4b</A> Hanessian S. Park H. Yang R.-Y. Synlett  1997,  353 

<A NAME="RC00802SS-4C">4c</A> See also: Kurihara K. Sugimoto T. Saitoh Y. Igarashi Y. Hirota H. Moriyama Y. Tsuyuki T. Takahashi T. Khuong-Huu Q. Bull. Chem. Soc. Jpn.  1985,  58:  3337 

<A NAME="RC00802SS-4D">4d</A> An overview over dibenzyl-protected amino aldehydes is given in: Reetz MT. Chem. Rev.  1999,  99:  1121 

<A NAME="RC00802SS-5">5</A> Podlech J. Gurrath M. Müller G. Lohof E. In Houben-Weyl   E22:  Goodman M. Felix A. Moroder L. Toniolo C. Georg Thieme Verlag; Stuttgart: 2001.  p.41 

<A NAME="RC00802SS-6">6</A> Lewis N. McKillop A. Taylor RJK. Watson RJ. Synth. Commun.  1995,  25:  561 

<A NAME="RC00802SS-7">7</A> Karrer P. Portmann P. Suter M. Helv. Chim. Acta  1948,  31:  1617 

<A NAME="RC00802SS-8">8</A> Neidlein R. Greulich P. Kramer W. Helv. Chim. Acta  1993,  76:  2407 

<A NAME="RC00802SS-9A">9a</A> Dess DB. Martin JC. J. Am. Chem. Soc.  1991,  113:  7277 

<A NAME="RC00802SS-9B">9b</A> Soucek M. Urban J. Collect. Czech. Chem. Commun.  1995,  60:  693 

<A NAME="RC00802SS-9C">9c</A>

A detailed procedure is given in Ref. [3a]

<A NAME="RC00802SS-10">10</A> Cassady JM. Howie GA. Robinson JM. Stamos IK. Organic Syntheses, Coll. Vol. 7   Wiley; New York: 1990.  p.319 

<A NAME="RC00802SS-11">11</A>

The respective isomers could be separated by medium pressure liquid chromatography (MPLC). All new compounds gave satisfactory spectroscopic data (NMR, IR, MS, [α]_D ²⁰ and elemental analyses).

<A NAME="RC00802SS-12">12</A> Roush WR. In Comprehensive Organic Synthesis   Vol. 2:  Trost BM. Fleming I. Heathcock CH. Pergamon; Oxford: 1991.  p.1 

<A NAME="RC00802SS-13">13</A>

Crystal data for 11a: C₂₄H₃₅NO₄Si, M = 429.62 g/mol, orthorhombic, space group P2₁2₁2₁. a = 10.009(2), b = 12.223(2), c = 20.057(3) Å, V = 2453.8(7) ų, Z = 4, D_c = 1.163 Mg/m³, µ (Mo-K_α) = 0.123 mm^-1, F(000) = 928. Data (2735 collected reflections, and 2063 unique reflections [I > 2σ(I)]) were measured on a Nicolet P3 diffractometer with Mo-K_α radiation (graphite monochromator) using 2θ-ω-scans at 293(2) K. The structure was solved by direct methods and the non-hydrogen atoms were refined anisotropically by full-matrix least-squares based on F² to give the agreement factors R₁ = 0.0597, ωR₂ = 0.1289. Computations were carried out using the SHELXTL^TM program. Crystallographic data have been deposited at the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-179132 (8a), CCDC-179133 (9a), and CCDC-179131 (11a). Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, (UK), fax:[phone] or email: [e-mail].

<A NAME="RC00802SS-14">14</A> Fürstner A. Shi N. J. Am. Chem. Soc.  1996,  118:  2533 

<A NAME="RC00802SS-15">15</A> Baldwin JE. Adlington RM. Sweeney JB. Tetrahedron Lett.  1986,  27:  5423 

<A NAME="RC00802SS-16">16</A> Ciapetti P. Taddei M. Ulivi P. Tetrahedron Lett.  1994,  35:  3183 

<A NAME="RC00802SS-17">17</A> Kempf DJ. J. Org. Chem.  1986,  51:  3921 

<A NAME="RC00802SS-18A">18a</A> Griesbeck AG. Kramer W. Bartoschek A. Schmickler H. Org. Lett.  2001,  3:  537 

<A NAME="RC00802SS-18B">18b</A> See also: Viscontini M. Kaiser W. Helv. Chim. Acta  1965,  48:  1927 

<A NAME="RC00802SS-19">19</A> Mertens A. Zilch H. König B. Schäfer W. Poll T. Kampe W. Seidel H. Leser U. Leinert H. J. Med. Chem.  1993,  36:  2526