A Convenient Route to Synthesize
N-Protected α,α-Difluorohomoallylic Amines
by gem-Difluoroallylation of α-Amido
Sulfones

Zheng-Feng Xie; Zhuo Chai; Gang Zhao; Ji-De Wang

doi:10.1055/s-0028-1083220

PAPER

A Convenient Route to Synthesize N-Protected α,α-Difluorohomoallylic Amines by gem-Difluoroallylation of α-Amido Sulfones

Zheng-Feng Xie^a, Zhuo Chai^b, Gang Zhao*^b, Ji-De Wang*^a
^a Education Ministry Key Laboratory of Oil & Gas Fine Chemicals, Xinjiang University, Urumqi 830046, P. R. of China
e-Mail: awangjdl@xju.edu.cn;
^b Key Laboratory of Organofluorine Chemistry and Laboratory of Modern Synthetic Organic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, P. R. of China
Fax: +86(21)64166128; e-Mail: zhaog@mail.sioc.ac.cn;

Abstract

All articles of this category

Abstract

A simple, mild, and efficient synthesis of α,α-difluorohomoallylic amines was achieved by the gem-difluoroallylation of α-amido sulfones with zinc powder.

Key words

fluorine compounds - allylations - amines - amido sulfones - zinc - ring-closing metathesis

Full Text

References

<A NAME="RF13008SS-1A">1a</A> Groß U. Rüdiger S. In Houben-Weyl Vol. E10a: Baasner B. Hagemann H. Tatlow JC. Thieme; Stuttgart: 1999. p.18

<A NAME="RF13008SS-1B">1b</A> Hiyama T. Organofluorine Compounds: Chemistry and Properties Springer; Berlin: 2000.

<A NAME="RF13008SS-1C">1c</A> Welsch JT. Eswarakrishnan S. Fluorine in Bioorganic Chemistry John Wiley & Sons; New York: 1991.

<A NAME="RF13008SS-1D">1d</A> Organofluorine Chemistry: Principles and Commercial Applications Banks RE. Smart BE. Tatlow JC. Plenum Press; New York: 1994.

<A NAME="RF13008SS-2A">2a</A> Blackburn GM. England DA. Kolkmann F. J. Chem. Soc., Chem. Commun. 1981, 930

<A NAME="RF13008SS-2B">2b</A> Blackburn GM. Kent DE. Kolkmann F. J. Chem. Soc., Chem. Commun. 1981, 1188

<A NAME="RF13008SS-2C">2c</A> Blackburn GM. Ivory JA. Williamson MP. Bioorg. Med. Chem. Lett. 1994, 4: 2573

<A NAME="RF13008SS-2D">2d</A> Chambers RD. Jaouhari R. O’Hagan D. Tetrahedron 1989, 45: 5101

<A NAME="RF13008SS-2E">2e</A> Burke TR. Smyth MS. Otaka A. Nomizu M. Roller PP. Wolf G. Care R. Shoelson SE. Biochemistry 1994, 33: 6490

<A NAME="RF13008SS-2F">2f</A> Xu X.-H. Trunkfield AE. Bugg TDH. Qing FL. Org. Biomol. Chem. 2008, 6: 157

For reviews, see:

<A NAME="RF13008SS-3A">3a</A> Tozer MJ. Herpin TF. Tetrahedron 1996, 52: 8619

<A NAME="RF13008SS-3B">3b</A> Huang X.-H. Shi G.-Q. Youji Huaxue 1997, 17: 394

<A NAME="RF13008SS-3C">3c</A> Prakash GKS. Hu J. Acc. Chem. Res. 2007, 40: 921

For recent examples, see:

<A NAME="RF13008SS-3D">3d</A> Ramachandran PV. Chatterjee A. Org. Lett. 2008, 10: 1195

<A NAME="RF13008SS-3E">3e</A> Wang R.-W. Qiu X.-L. Bols M. Ortega-Caballero F. Qing F.-L. J. Med. Chem. 2006, 49: 2989

<A NAME="RF13008SS-3F">3f</A> Niida A. Tomita K. Mizumoto M. Tanigaki H. Terada T. Oishi S. Otaka A. Inui K. Fujii N. Org. Lett. 2006, 8: 613

<A NAME="RF13008SS-3G">3g</A> Wang R.-W. Qing F.-L. Org. Lett. 2005, 7: 2189

<A NAME="RF13008SS-3H">3h</A> Wu Y.-Y. Zhang X.-G. Meng W.-D. Qing F.-L. Org. Lett. 2004, 6: 3941

<A NAME="RF13008SS-3I">3i</A> Otaka A. Watanabe J. Yukimasa A. Sasaki Y. Watanabe H. Kinoshita T. Oishi S. Tamamura H. Fujii N. J. Org. Chem. 2004, 69: 1634

<A NAME="RF13008SS-3J">3j</A> Kirihara M. Kawasaki M. Katsumata H. Kakuda H. Shiro M. Kawabata S. Tetrahedron: Asymmetry 2002, 13: 2283

<A NAME="RF13008SS-3K">3k</A> Kirihara M. Takuwa T. Takizawa S. Momose T. Nemoto H. Tetrahedron 2000, 56: 8275

<A NAME="RF13008SS-3L">3l</A> Jeong IH. Kim MS. Kim BT. Synth. Commun. 1999, 29: 235

<A NAME="RF13008SS-3M">3m</A> Qing F. Wan D. Tetrahedron 1998, 54: 14189

<A NAME="RF13008SS-3N">3n</A> Kirihara M. Takuwa T. Takizawa S. Momose T. Tetrahedron Lett. 1997, 38: 2853

<A NAME="RF13008SS-3O">3o</A> Arnone A. Bravo P. Viani F. Zanda M. Cavicchio G. Crucianelli M. J. Fluorine Chem. 1996, 76: 169

<A NAME="RF13008SS-3P">3p</A> Patel ST. Percy JM. Wilkes RD. J. Org. Chem. 1996, 61: 166

<A NAME="RF13008SS-3Q">3q</A> Morikawa T. Uejima M. Kobayashi Y. Chem. Lett. 1988, 1407

<A NAME="RF13008SS-3R">3r</A> Hiyama T. Obayashi M. Sawahata M. Tetrahedron Lett. 1983, 24: 4113

<A NAME="RF13008SS-3S">3s</A> Seyferth D. Simon RM. Sepelak DJ. Klein HA. J. Am. Chem. Soc. 1983, 105: 4634

<A NAME="RF13008SS-4">4</A> Yang Z. Burton DJ. J. Org. Chem. 1991, 56: 1037

<A NAME="RF13008SS-5">5</A> Ohba T. Ikeda E. Takei H. Bioorg. Med. Chem. Lett. 1996, 6: 1875

For a recent review, see:

<A NAME="RF13008SS-6A">6a</A> Petrini M. Chem. Rev. 2005, 105: 3949

For recent examples, see:

<A NAME="RF13008SS-6B">6b</A> Lombardo M. Mosconi E. Pasi F. Petrini M. Trombini C. J. Org. Chem. 2007, 72: 1834

<A NAME="RF13008SS-6C">6c</A> Mizuta S. Shibata N. Goto Y. Furukawa T. Nakamura S. Toru T. J. Am. Chem. Soc. 2007, 129: 6394

<A NAME="RF13008SS-6D">6d</A> Song J. Shih H.-W. Deng L. Org. Lett. 2007, 9: 603

<A NAME="RF13008SS-6E">6e</A> Shibasaki M. Matsunaga S. J. Organomet. Chem. 2006, 691: 2089

<A NAME="RF13008SS-6F">6f</A> Marques MMB. Angew. Chem. Int. Ed. 2006, 45: 348

<A NAME="RF13008SS-6G">6g</A> Fini F. Bernardi L. Herrera RP. Pettersen D. Ricci A. Sgarzania V. Adv. Synth. Catal. 2006, 348: 2043

<A NAME="RF13008SS-6H">6h</A> Herrera RP. Bernardi L. Fini F. Pettersen D. Ricci A. J. Org. Chem. 2006, 71: 9869

For reviews, see:

<A NAME="RF13008SS-7A">7a</A> Enders D. Thiebes T. Pure Appl. Chem. 2001, 73: 573

<A NAME="RF13008SS-7B">7b</A> Laschat S. Dickner T. Synthesis 2000, 1781

For examples, see:

<A NAME="RF13008SS-7C">7c</A> Agami C. Couty F. Evano G. Tetrahedron: Asymmetry 2000, 11: 4639

<A NAME="RF13008SS-7D">7d</A> De Matteis V. van Delft FL. Tiebes J. Rutjes FPJT. Eur. J. Org. Chem. 2006, 1166

<A NAME="RF13008SS-7E">7e</A> Petukhov PA. Zhang J. Wang CZ. Ye YP. Johnson KM. Kozikowski AP. J. Med. Chem. 2004, 47: 3009

<A NAME="RF13008SS-7F">7f</A> Amat M. Lozano O. Escolano C. Molins E. Bosch J. J. Org. Chem. 2007, 72: 4431 ; and references cited therein

Characterization data for 5: colorless crystals; mp 96-97 ˚C. IR (film): 2925, 2855, 1707, 1456, 1408, 1393, 1168, 1092, 698 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 7.32 (m, 5 H), 6.26 (m, 1 H), 6.09 (m, 1 H), 5.74 (m, 1 H), 4.48-4.38 (m, 1 H), 3.56-3.47 (m, 13 H), 1.49 (s, 9 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 154.1, 134.9, 133.6, 128.4, 128.2, 128.0, 122.1 (dd, J = 17.3, 25.1 Hz), 115.9 (t, J = 9 Hz), 120.6 (t, J = 177.5 Hz), 81.2, 59.1, 40.6, 27.2 (3 C). ^¹9F NMR (282 MHz, CDCl₃): δ = -79.56 (d, J _F,F = 279.2 Hz), -103.24 (d, J _F,F = 297.2 Hz). MS (ESI): m/z = 318 [M + Na]⁺. HRMS (EI): m/z calcd for C₁₁H₁₀NF₂ [M⁺-Boc]: 194.0781; found: 194.0777.

For recent examples of the application of RCM in olefins bearing fluorine substituents, see:

<A NAME="RF13008SS-9A">9a</A> Fustero S. Fernández B. Sanz-Cervera JF. Mateu N. Mosulén S. Carbajo RJ. Pineda-Lucena A. de Arellano CR. J. Org. Chem. 2007, 72: 8716

<A NAME="RF13008SS-9B">9b</A> Miles JAL. Mitchell L. Percy JM. Singh K. Uneyama E. J. Org. Chem. 2007, 72: 1575

<A NAME="RF13008SS-9C">9c</A> Yang Y.-Y. Xu J. You Z.-W. Xu X.-H. Qiu X.-L. Qing F.-L. Org. Lett. 2007, 9: 5437

<A NAME="RF13008SS-9D">9d</A> You Z.-W. Wu Y.-Y. Qing FL. Synthesis 2006, 2535