Synthesis with Hypervalent Iodine

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Synthesis with Hypervalent Iodine
A presentation for the students of the Chemistry
Department of Penn State Erie, the Behrend College
by Dr. Michael W. Justik
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• Introduction What is Hypervalent Iodine
• Structure and Chemistry

While the structure may at first look complex,
the bonding model is familiar the allyl
anion This particular arrangement is referred to
as a 3-centered-4-electron bond 3c-4e It is
postulated that an orbital on each ligand
interacts with an unhybridized 5p orbital on
iodine These bonds are slightly longer than the
sum of covalent radii (in symmetrical
structures), yet substantially shorter than an
ionic bonding interaction It is the uniqueness
of this bond, from empirical observation of the
solid state, as well as the chemistry of these
compounds that is referred to when calling this
class of compounds hypervalent
axial
equatorial
axial
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• Introduction What is Hypervalent Iodine?
• Structure and Chemistry
• These hypervalent bonds are slightly weaker than
  covalent bonds
• Because iodine is in a higher oxidation state
  than normal the driving force for most
  reactions of this class of compounds is the
  reduction of iodine coupled with the oxidation of
  the substrate
• While there are a multitude of reaction pathways
  that have been observed, the greater majority of
  reaction pathways are of the following type

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• Introduction What is Hypervalent Iodine?
• These compounds are true reagents of organic
  chemistry
• To illustrate, since 1970

1 review 56 papers 7 patents
12 reviews 782 papers 50 patents
1 reviews 263 papers 15 patents
21 reviews 395 papers 269 patents
13 reviews 804 papers 146 patents
4 reviews 202 papers 32 patents
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• Introduction Hypervalent Iodine
• Bringing the functional group into the 21st
  century
• Engineer reagents to be amenable for
  combinatorial methods
• Reagents are refined to be environmentally
  benign/recyclable
• Reagents are engineered for broader synthetic
  application
• Incorporation of asymmetry

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• Project 1
• Oxidative rearrangements of arylalkenes to
  arylalkanones
• The purpose of this project is to make this known
  reaction green in two ways. First, replacing
  the original reagent hydroxyl(tosyloxy)iodobenze
  ne (HTIB) with an analog that allows the reduced
  by-product to be separated from the reaction
  mixture by simple aqueous extraction for
  re-oxidation and reuse. Second, because
  iodobenzene is no longer contaminating the
  organic by-products of the reaction, column
  chromatography can either be simplified or
  eliminated altogether.

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• Project 2
• The reaction of pyridine N-oxides with
  alkynyliodonium salts
• It is known that soft nucleophiles (phenoxides
  in particular) add as nucleophiles to
  alkynyliodonium salts to give a carbine
  intermediate (Eq. 1).

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• Project 2
• The reaction of pyridine N-oxides with
  alkynyliodonium salts
• This carbene can insert within the C-H bonds of
  the aromatic ring to form heterocycles (Eq. 2).
  Most nucleophiles have been studied in the
  literature, except pyridine N-oxides. The
  hypothesized products are known, isolable and
  stable materials. These products would be an
  important means of functionalizing pyridines, as
  well as creating new, possibly interesting
  heterocycles (Eq. 3).

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• Project 3
• Synthesis of diaryliodosyl salts
• These compounds are one of the most understudied
  moieties in hypervalent iodine chemistry. The
  original synthesis involves using two equivalents
  of iodylbenzene (iodoxybenzene) in conjunction
  with base (NaOH) to form a diaryliodosyl salt
  (Eq. 1). During my Ph.D. work, it was
  discovered that these compounds will undergo
  electrophilic aromatic substitution reactions via
  an intra-molecular process. If this also works
  on an intermolecular basis, the first examples of
  diaryliodosyl salts that are asymmetrical can be
  prepared, and their chemistry explored. Once
  more, no 1H or 13C NMR data is known of these
  compounds (the original papers pre-date the
  routine use of NMR).

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• Project 4
• Oxidative Rearrangement of alkynes with CHTIB
• HTIB can oxidize terminal and internal alkynes
  (terminal shown) in various solvents one of the
  more interesting oxidative rearrangements is
  observed when terminal alkynes are treated in an
  alcohol, to afford alkyl esters

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• Project 4
• Hoffmann degradation of N-alkylamides to
  N-alkylamines using hypervalent iodine
  catalytically in conjunction with a co-oxidant
• HTIB can perform the Hoffmann degradation better
  than the original Hoffmann reaction with regard
  to long chain amides (Eq. 1). This project will
  explore if the reaction can be made more green
  using the cyclic HTIB analog (Eq. 2). This can
  be accomplished by using cyclic HTIB in a
  stoichiometric amount, or by using it
  catalytically with a co-oxidant.