Contact Info:

M. Christina White
Department of Chemistry
University of Illinois
270 Roger Adams Laboratory
600 South Mathews Ave.
Urbana, IL 61801
(217) 333-6173

Email: white@scs.uiuc.edu


Publication 16. SI.
"Total synthesis and study of 6-deoxyerythronolide B by late-stage C-H oxidation."
E.M. Stang and M.C. White
Nature Chemistry, 2009 DOI: 10.1038/NCHEM.351

Publication 16

A novel strategy for the synthesis of 6-deoxyerythronolide B is reported that uses a late-stage C–H oxidative macrocyclization reaction to forge the key macrocyclic core found in the erythromycins. Starting from a linear alkenoic acid intermediate lacking oxygen at C13, a PdII catalyzed C–H oxidation reaction generated the 14-memebred macrocycle with the natural configuration at C13 in >40:1 diastereoselectivity. Controlling the functionalization mechanism allowed for the alternative C13 diastereomer to be synthesized for the first time. By installing oxygen at a late-stage, this strategy improves synthetic efficiency by minimizing the "oxygen load" over lengthy linear sequences. Moreover, this work provides a new way to think about constructing macrolide natural products. Click here for photo of Erik and MCW
  • Follow link to comments on this paper by C&E News. [link]
  • Follow link to comments on this paper by the RSC. [link]
  • Follow link to comments on this paper in Nature Chemistry. [link]

Publication 15. SI.
"A Catalytic, Brønsted Base Strategy for Intermolecular Allylic C-H Amination."
S.A. Reed; A.R. Mazzotti; and M.C. White
JACS, 2009 DOI: 10.1021/ja903939k

Publication 15

In this article, a Brønsted base activation mode for oxidative, Pd(II)/sulfoxide-catalyzed, intermolecular C—H allylic amination is described. A catalytic amount of N,N-diisopropylethylamine was found to efficiently promote the linear allylic amination reaction with high levels of stereo-, regio-, and chemoselectivity. This departure from Lewis acid activation allows unprecedented functional group tolerance for a C—H amination method. For example, powerful synthetic building blocks and natural product derivatives containing reactive Lewis basic functionality such as epoxides, aldehydes, esters, nitriles, phenols, and even alcohols can be aminated without the use of protecting groups. Useful transformations of N-tosylcarbamate products as well as evidence to support this novel activation mode are discussed. Click here for photo of Sean, Anthony and MCW

Publication 14. SI.
"Allylic C-H Amination for Preparation of syn-1,3-Amino Alcohol Motifs."
G.T. Rice and M.C. White
JACS, 2009 DOI: 10.1021/ja9054959

Publication 14

We report a palladium/sulfoxide catalyzed allylic C—H amination to furnish syn-oxazinanone heterocycles en route to syn-1,3-amino alcohols. Key to the high reactivity observed under mild conditions (45°C, 24h) is the use of an electron deficient N-nosyl carbamate nitrogen nucleophile that enables high concentrations of the active anionic species to be reached using endogenous catalytic acetate base. The scope for this C—H amination reaction is very broad and orthogonal to both classical C—C bond forming/reduction sequences and metal nitrene-based C—H amination methods for furnishing this motif. The streamlining potential of this method is highlighted in the concise and high yielding total synthesis of (+)-allosedridine. Using this approach, significantly shorter reaction times (72h to 24h) could also be achieved for our previously reported allylic C—H amination reaction to furnish syn-1,2-amino alcohols. Click here for photo of Grant and MCW
  • For highlight of this paper see SynFacts 2009, 1262. [link]

Publication 13.
"The Fe(PDP)-catalyzed aliphatic C-H oxidation: a slow addition protocol."
N.A. Vermeulen; M.S. Chen; and M.C. White
Tetrahedron, 2009 DOI: 10.1016/j.tet.2008.11.082

Publication 13

A slow addition protocol for the Fe(PDP)-catalyzed aliphatic C—H oxidation reaction is described. Under this protocol, the reaction can be productively driven to higher conversions without the need for recycling.

Publication 12.
"Catalytic Intermolecular Allylic C-H Alkylation."
A.J. Young and M.C. White
JACS, 2008 DOI: 10.1021/ja806867p

Publication 12

We report the first electrophilic Pd(II)-catalyzed allylic C—H alkylation. This method enables the direct conversion of allylic C—H bonds to C—C bonds. Using Pd(II)/bis-sulfoxide catalysts, α-olefin substrates can be alkylated with a series of weak carbon nucleophiles such as methyl nitroacetate, benzoylnitromethane, and (phenylsulfonyl)nitromethane. For example, allylated aromatic substrates and methyl nitroacetate yield a wide range of aromatic and heteroaromatic linear (E)-α-nitro-arylpentenoates as single olefin isomers in excellent yields. The π-acceptor ligand DMSO was found to play a crucial role in promoting functionalization of the π-allylPd intermediate. Products are readily transformed to amino esters via selective reduction and enantiomerically enriched α,α-disubstituted amino acid precursors via asymmetric conjugate addition. Click here for photo of Andrew and MCW

Publication 11.
"A General and Highly Selective Chelate-Controlled Intermolecular Oxidative Heck Reaction."
J.H. Delcamp; A.P. Brucks; and M.C. White
JACS, 2008 DOI: 10.1021/ja804120r

Publication 11

In this communication, we report a novel intermolecular Heck reaction that significantly expands the scope of the olefin in this classic cross-coupling method. A general Pd/bis-sulfoxide complex 1 catalyzes a chelate-controlled, oxidative Heck reaction with a wide range of non-stabilized -olefins and organoboron reagents in good yields and outstanding regio- and E:Z selectivities. Pd-H isomerization, a side-process deleterious to selectivities in many Heck reactions, is not observed under these mild, oxidative conditions. This is evidenced by a tolerance of unprotected alcohols, no erosion of optical purity for proximal stereogenic centers, and outstanding E:Z selectivities (>20:1 in all cases examined). We anticipate that this advance will bring the intermolecular Heck reaction a step closer to realizing its tremendous potential in streamlining complex molecule synthesis. Click here for photo of Jared, Alex and MCW

Publication 10.
"A Chiral Lewis Acid Strategy for Enantioselective Allylic C-H Oxidation."
D.J. Covell and M.C. White.
ACIEE, 2008 DOI: 10.1002/anie.200802106

Publication 10

Conventionally, enantioselective transition metal catalyzed processes use chiral metal ligands. A Lewis acid strategy for effecting asymmetric induction in oxidative systems not amenable to such chiral ligands is disclosed and its mechanism investigated. Addition of chiral Cr(III)(salen) catalyst to the Pd(II)/sulfoxide catalyzed branched allylic C-H oxidation achieves the highest levels of enantioselectivity for C-H oxidation of terminal olefins to date. When paired with enzymatic resolution, this method rapidly generates chiral building blocks in high yields. Click here for photo of MCW and Dustin
  • For highlight of this paper see SynFacts 2008, 1059. [link]

Publication 9.
"Catalytic Intermolecular Linear Allylic C-H Amination via Heterobimetallic Catalysis."
S.A. Reed and M.C. White.
JACS, 2008, 130, 3316.

Publication 9

Utilizing a heterobimetallic Pd/Cr(salen)Cl catalyst system, a wide variety of alpha olefins can be transformed directly into the corresponding allylic carbamates with good yields (50-72%), and excellent selectivity for E linear product (>20:1). This represents the first direct, general, intermolecular allylic C-H amination reaction for small molecule synthesis. To demonstrate its outstanding streamlining potential, the reaction was employed in a synthesis of an analogue of the antibiotic deoxynegamycin that proceeded in ca. half the number of steps from commercial starting materials and twice the overall yield when compared to a route employing oxygenated intermediates. It is noteworthy that 15N can now be installed directly into complex molecules using this method, as illustrated by its incorporation into an aminosugar precursor. Click here for photo of MCW and Sean
  • For commentary on this paper see Chemical & Engineering News Concentrates 2008, 86(11), 42. [link]
  • For a highlight of this paper in Synfacts please click here to see: Yamamoto, H.; Naodovic, M. Synfacts, 2008, 603.

Publication 8.
"A Predictably Selective Aliphatic C-H Oxidation Reaction for Complex Molecule Synthesis."
M.S. Chen and M.C. White.
Science, 2007, 318, 783.

Publication 8

We report an iron-based small molecule catalyst that uses hydrogen peroxide to oxidize a broad range of substrates. Predictable selectivity is achieved solely based on the electronic and steric properties of the C-H bonds, without the need for directing groups. Additionally, carboxylate directing groups may be used to furnish 5-membered ring lactone products. We demonstrate that these three modes of selectivity enable the predictable oxidation of complex natural products and their derivatives at specific C-H bonds with preparatively useful yields. This type of general and predictable reactivity stands to enable aliphatic C-H oxidation to streamline the process of complex molecule synthesis. Click here for photo of MCW and Mark   Alt Photo
  • This paper has been selected as one of the top ten "Breakthroughs of the Year" in science by Science, 2007.
  • This paper has been selected as Chem. & Eng. News Highlights 2007, 85 (52), 17-18; and Chemistry World Highlight, 2007.
  • For a perspective on this paper in Science please click here to see: R.H. Crabtree, "No Protection Required." Science, 2007, 318, 756.
  • For a Research Highlight of this paper in Nature please click here to see: "Green Cleaver." Nature, 2007, 450 (8), 139.
  • For a "News of the Week" article of this paper in Chemical & Engineering News please click here to see: Jyllian Kemsley "Catalyst Oxidizes Selectively." Chem. Eng. News, 2007, 85 (45) 8.
  • For a highlight of this paper in Chemistry & Industry please click here to see: Patrick Walter "Green Catalyst Could Clean Up in Drug Production." Chemistry & Industry, 2007, 21, 7.
  • For a highlight of this paper in Chemistry World please click here to see: Richard Van Noorden, "Step Change for Organic Synthesis." Chemistry World, 2007.
  • For a highlight of this paper in Technology Review please click here to see: Kevin Bullis, "Drugs That Are Easier on the Environment." Technology Review, 2007.

Publication 7.
"syn-1,2-Amino Alcohols via Diastereoselective Allylic C—H Amination."
K.J. Fraunhoffer and M.C. White.
JACS 2007, 129, 7274-7276.

Publication 7

This communication describes the first general, stereoselective allylic C—H amination reaction for synthesis. The key to solving this problem in chemical reactivity was the discovery that a bis-sulfoxide/Pd(II) catalyst can divert aminopalladation pathways to allylic C—H cleavage. The acetate counterion associated with Pd(II) is demonstrated to activate the weak nitrogen nucleophile towards intramolecular attack of the pi-allylPd. The ability to skip the oxygen required in conventional allylic amine forming reactions is shown to result in a significant streamlining effect on their synthesis. Click here for photo of MCW and Ken
  • For a "News of the Week" article of this paper in Chemical & Engineering News please click here to see: Stu Borman "Amination Advance: New Reaction is first to catalytically convert allylic C—H to C—N." Chem. Eng. News, 2007, 85 (23) 7.
  • This article is the most-accessed web article in JACS for April-June 2007.

Publication 6.
"Sequential Hydrocarbon Functionalization: Allylic C—H Oxidation/Vinylic C—H Arylation".
J.H. Delcamp and M.C. White.
JACS 2006, 128, 15076-15077.

Publication 6

This communication describes a method that rapidly converts inexpensive and abundant hydrocarbon, carboxylic acid and boronic acid starting materials to densely functionalized fragments for complex molecule synthesis. The Pd(II)/bis-sulfoxide complex catalyzes vinylic C—H arylation of electronically unbiased allylic ester intermediates with a wide range of aryl boronic acids under acidic, oxidative conditions and mild temperatures (rt to 45°C). Click here for photo   Alt Photo



Publication 5.
"Polyol Synthesis through Hydrocarbon Oxidation: De Novo Synthesis of L-Galactose".
D.J. Covell; N.A. Vermeulen; N.A. Labenz; and M.C. White.
ACIEE 2006, 45, 8217-8220.

Publication 5

This communication describes a strategy for rapidly building chiral polyol structures starting with readily accessible chiral building blocks (1 & 2). Key to the effciency of this strategy is the ability to convert chiral homoallylic ethers (3) directly to 4-methoxybenzoate allylic esters (4). These compounds undergo reagent controlled asymmetric dihydroxylations (AD) with high diastereoselectivities and no acyl transfer. We describe conditions that allow p-anisic acid to act as a nucleophile for the linear allylic oxidation reaction to directly generate (4) with good yields (70%) and outstanding selectivities (E:Z = 97:3). Click here for photo   Alt Photo



Publication 4.
"Macrolactonization via Hydrocarbon Oxidation".
K.F. Fraunhoffer; N. Prabagaran; L.E. Sirois; and M.C. White.
JACS 2006, 128, 9032-9033.

Publication 4


Click here for photo of the macrolactonization group.   Alt Photo



Publication 3.
"Serial Ligand Catalysis: A Highly Selective Allylic C—H Oxidation".
M.S. Chen; N. Prabagaran; N.A. Labenz; and M.C. White.
JACS 2005, 127, 6970-6971.

Publication 3


In this communication, we show that replacing DMSO with a catalytic amount of polydentate sulfoxide ligand results in an unexpected reversal in regioselectivities favoring the branched allylic ester product. Together, the branched and linear allylic C—H oxidation reactions are rare examples of highly selective, intermolecular C—H oxidation processes. By studying the mechanism of the branched allylic C—H oxidation reaction, we demonstrate for the first time the concept of serial ligand catalysis: two (or more) different ligands binding reversibly to one metal to promote different product forming steps in a catalytic cycle. Click here for photo of serial ligand catalysis group.
  • For Commentary click here to see: Science and Technology Concentrate in Chem. & Eng. News 2005, 83, (18), 31.

Publication 2.
"Hydrocarbon Oxidation vs C-C Bond-Forming Approaches for Efficient Synthesis of Oxygenated Molecules".
K. J. Fraunhoffer; D. A. Bachovchin; and M.C. White.
Org. Lett. 2005, 7, 223-226.

Publication 2


The discovery of regio-, chemo- and stereoselective C-H oxidation reactions stands to significantly impact the ways in which small molecules are constructed. Specifically, such reactions enable oxygenated functionality to be installed late in a synthetic sequence, thereby eliminating functional group manipulations (FGMs) required to carry it throughout a synthesis. In this communication, we test this strategy for streamlining synthesis for the first time. Click here for photo.
  • Selected by Organic Letters Editorial board as one of nine best papers in 2004. Please click here to see.
  • For an excellent review highlighting this strategy see: R.H. Hoffmann"Protecting-Group-Free Synthesis."
    Synthesis 2006, 3561.

Publication 1.
" A Sulfoxide-Promoted, Catalytic Method for the Regioselective Synthesis of Allylic Acetates from Monosubstituted Olefins via C—H Oxidation".
M.S. Chen; M.C. White
J. Am. Chem. Soc. 2004, 126, 1346-1347.

Publication 1

In this communication we disclose that addition of sulfoxide to Pd(OAc)2/benzoquinone (BQ)/AcOH diverts oxidation away from the olefin to the allylic C—H bond resulting in the first allylic C—H oxidation system for alpha-olefins. This reaction has very broad scope (R = esters, amides, ketals, silyl and benzyl ethers, etc.) and proceeds with high regio- and stereoselectivities to furnish linear E-allylic esters in preparatively useful yields. Click here for photo.

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