Synlett 2009(10): 1690-1691  
DOI: 10.1055/s-0029-1217323
SPOTLIGHT
© Georg Thieme Verlag Stuttgart ˙ New York

Simmons-Smith Reagent (Et2Zn, CH2I2): An Efficient Reagent in Organic Synthesis

Ali Maleki*
Department of Chemistry, Shahid Beheshti University, P.O. Box 19396-4716, Tehran, Iran
e-Mail: a_maleki@sbu.ac.ir;

Further Information

Publication History

Publication Date:
02 June 2009 (online)

Biographical Sketches

Ali Maleki was born in Mianeh, Iran, in 1980. He received his ­B.Sc. in Chemistry from Imam Khomeini International University, Qazvin, in 2003 and his M.Sc. in Organic Chemistry from Shahid Beheshti University in 2005. Presently he is a Ph.D. student at Shahid Beheshti University under the supervision of Professor Ahmad Shaabani. His research interests focus on the design and development of novel isocyanide-based multicomponent reactions, combinatorial chemistry, green chemistry, heterocyclic compounds and catalytic reactions.

Introduction

The diethylzinc/diiodomethane or zinc-diiodomethane (Et2Zn, CH2I2 or Zn, CH2I2 = ICH2ZnI) known as Simmons-Smith reagent is probably the best known carbenoid reagent in organic syntheses. [¹] This ether soluble reagent has been used mainly for the conversion of al­kenes into cyclopropanes [¹] via stereospecific and supra­facial CH2 addition using chiral auxiliaries, [²] reagents [³] and catalysts. [4]

Due to the presence of cyclopropanes in many biologically and medicinally important molecules, [5] natural products, [6] essential oils [7] and the marine cyanobacteriums, [8] some recent applications of Simmons-Smith reagent are reported herein.

Abstracts

(A) Asymmetric reaction of allylic alcohols with Al Lewis acid/N Lewis base bifunctional Al(salalen) catalyst in the presence of Simmons-Smith reagent has been reported by Katsuki and Shitama in quantitative yields with high enantiomeric excess. The hydroxyl group is a prerequisite serving as an anchor for zinc. [9]

(B) A catalytic asymmetric Simmons-Smith cyclopropan­ation of silyl enol ethers 1 using dipeptide 2 as a ligand has been described. A variety of optically active cyclopropyl silyl ethers 3 can be obtained in high yields and with an ee up to 96%. The dipeptide can be recovered after the reaction in good yield and reused without the loss of reactivity or enantioselectivity. [¹0]

(C) White et al. have reported asymmetric total syntheses of solandelactones. The key step in these syntheses ­involved directed Simmons-Smith cyclopropanation which this reaction preceded in quantitative yield (97%). [¹¹]

(D) A highly diastereoselective cyclopropanation protocol for allylic amines 1 has been demonstrated by Davies et al. giving access to complete conversion into syn-2 in 98% de with Simmons-Smith reagent, and anti-3 in 98% de in the presence of TFA. [¹²]

(E) Recently, an efficient asymmetric synthesis of conformationally constrained (2S,3S)-piperidinedicarboxylic acid derivatives has been reported by Zhuo et al. This was the first successful example of cyclopropanation of an allylic amine by masking the amine as a carbamate without the presence of a chelating group (OH or OR) ­using Simmons-Smith reagent. [¹³]

(F) A highly stereoselective synthesis of chiral amino­cyclopropanes through cyclopropanation of chiral enamides using the Simmons-Smith reagent has been explored by Hsung et al. Various substrates are transformed with moderate to good diastereoselectivity to cyclopropane products. The method includes the synthesis of the cyclopropane fragment of the nucleoside. [¹4]

(G) A series of novel fluorocyclopropyl nucleosides with antiviral activity has been synthesized starting from acetol using the Simmons-Smith reagent. All the synthesized nucleosides were assayed against several viruses. [¹5]

(H) The Simmons-Smith reagent has been applied to prepare a new class of haloalkylzinc compounds leading to transition metal carbenes. Halomethylzinc and ­halobenzylzinc compounds react with ruthenium and iridium complexes to form methylene and benzylidene complexes including the Grubbs catalyst. [¹6]

(I) The total synthesis of the natural metabolite (+/-)-cascarillic acid 3 has been achieved by a sequential cross-metathesis and Simmons-Smith cyclopropanation between 1-octene 1 with an appropriate unsaturated carboxylic acid 2. Interestingly, the smooth conditions required for both the cross-metathesis and the cyclopropanation allow the combination of the two processes in one single pot. Compared to other racemic syntheses, this high yielding (up to 90%), selective (the E/Z ratio near 80:20) and shorter procedure is expected to be generalized to other naturally occurring trans-cyclopropane derivatives. [¹7]

    References

  • 1a Simmons HE. Smith RD. J. Am. Chem. Soc.  1959,  81:  4256 
  • 1b Simmons HE. Smith RD. J. Am. Chem. Soc.  1958,  80:  5322 
  • 1c Charette AB. Beauchemin A. Simmons-Smith Cyclopropanation Reaction In Organic Reactions   John Wiley & Sons; New York: 2001.  58:  p.1-415  
  • 2 Kang J. Lim GJ. Yoon SK. Kim MY. J. Org. Chem.  1995,  60:  564 
  • 3 Charette AB. Juteau H. Lebel H. Molinaro C. J. Am. Chem. Soc.   1998,  120 :  11943 
  • 4 Balsells J. Walsh PJ. J. Org. Chem.  2000,  65:  5005 
  • 5 Lebel H. Marcoux J.-F. Molinaro C. Charette AB. Chem. Rev.  2003,  103:  977 
  • 6 Wessjohann LA. Brandt W. Thiemann T. Chem. Rev.  2003,  103:  1625 
  • 7a Roberts IO. Baird MS. Liu Y. Tetrahedron Lett.  2004,  45:  8685 
  • 7b Cheeseman M. Bull SD. Synlett  2006,  1119 
  • 8 Avery TD. Culbert JA. Taylor DK. Org. Biomol. Chem.   2006,  4:  323 
  • 9 Shitama H. Katsuki T. Angew. Chem. Int. Ed.  2008,  47:  2450 
  • 10 Du H. Long J. Shi Y. Org. Lett.  2006,  8:  2827 
  • 11 White JD. Martin WHC. Lincoln C. Yang J. Org. Lett.  2007,  9:  3481 
  • 12 Davies SG. Ling KB. Roberts PM. Russell AJ. Thomson JE. Chem. Commun.  2007,   4029 
  • 13 Zhuo J. Burns DM. Zhang C. Xu M. Weng L. Qian D.-Q. He C. Lin Q. Li Y.-L. Shi E. Agrios C. Metcalf B. Yao W. Synlett  2007,  460 
  • 14 Song Z. Lu T. Hsung RP. Al-Rashid ZF. Ko C. Tang Y. Angew. Chem. Int. Ed.  2007,  46:  4069 
  • 15 Kim A. Hong JH. Eur. J. Med. Chem.  2007,  42:  487 
  • 16 Poverenov E. Milstein D. Chem. Commun.  2007,   3189 
  • 17 Salim H. Piva O. Tetrahedron Lett.  2007,  48:  2059 

    References

  • 1a Simmons HE. Smith RD. J. Am. Chem. Soc.  1959,  81:  4256 
  • 1b Simmons HE. Smith RD. J. Am. Chem. Soc.  1958,  80:  5322 
  • 1c Charette AB. Beauchemin A. Simmons-Smith Cyclopropanation Reaction In Organic Reactions   John Wiley & Sons; New York: 2001.  58:  p.1-415  
  • 2 Kang J. Lim GJ. Yoon SK. Kim MY. J. Org. Chem.  1995,  60:  564 
  • 3 Charette AB. Juteau H. Lebel H. Molinaro C. J. Am. Chem. Soc.   1998,  120 :  11943 
  • 4 Balsells J. Walsh PJ. J. Org. Chem.  2000,  65:  5005 
  • 5 Lebel H. Marcoux J.-F. Molinaro C. Charette AB. Chem. Rev.  2003,  103:  977 
  • 6 Wessjohann LA. Brandt W. Thiemann T. Chem. Rev.  2003,  103:  1625 
  • 7a Roberts IO. Baird MS. Liu Y. Tetrahedron Lett.  2004,  45:  8685 
  • 7b Cheeseman M. Bull SD. Synlett  2006,  1119 
  • 8 Avery TD. Culbert JA. Taylor DK. Org. Biomol. Chem.   2006,  4:  323 
  • 9 Shitama H. Katsuki T. Angew. Chem. Int. Ed.  2008,  47:  2450 
  • 10 Du H. Long J. Shi Y. Org. Lett.  2006,  8:  2827 
  • 11 White JD. Martin WHC. Lincoln C. Yang J. Org. Lett.  2007,  9:  3481 
  • 12 Davies SG. Ling KB. Roberts PM. Russell AJ. Thomson JE. Chem. Commun.  2007,   4029 
  • 13 Zhuo J. Burns DM. Zhang C. Xu M. Weng L. Qian D.-Q. He C. Lin Q. Li Y.-L. Shi E. Agrios C. Metcalf B. Yao W. Synlett  2007,  460 
  • 14 Song Z. Lu T. Hsung RP. Al-Rashid ZF. Ko C. Tang Y. Angew. Chem. Int. Ed.  2007,  46:  4069 
  • 15 Kim A. Hong JH. Eur. J. Med. Chem.  2007,  42:  487 
  • 16 Poverenov E. Milstein D. Chem. Commun.  2007,   3189 
  • 17 Salim H. Piva O. Tetrahedron Lett.  2007,  48:  2059