Levoglucosenone and Its Dimer - ACS Publications - American

Chapter 21

Downloaded by UNIV OF GUELPH LIBRARY on August 6, 2012 | http://pubs.acs.org Publication Date: April 16, 2007 | doi: 10.1021/bk-2007-0954.ch021

New Stereoselective Functionalization of CelluloseDerived Pyrolysis Derivatives: Levoglucosenone and Its Dimer Zbigniew J. Witczak Department of Pharmaceutical Sciences, School of Pharmacy, Wilkes University, Wilkes-Barre, PA 18766

As a part of a study to develop methods to obtain high-value nonracemic chiral building blocks from waste cellulosic materials and biomass, a convenient modification method to pyrolyze these materials to produce levoglucosenone is presented in this chapter. Its functionalized dimer has been obtained by base catalyzed oligomerization of levoglucosenone. Both chiral bicyclic enones are convenient precursors for the synthesis of many attractive synthons and are generating steady interest due to their rigidity and stereoselective functionalization in many synthetic organic methodologies. Some of the examples of steroselective functionalization of these enones are presented in this chapter.

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© 2007 American Chemical Society In Materials, Chemicals, and Energy from Forest Biomass; Argyropoulos, D.; ACS Symposium Series; American Chemical Society: Washington, DC, 2007.

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Historical Background Practical methods for deriving economically useful chemicals from renewable biomass such as plant material, are highly desirable making possible the use biomass instead of petroleum as a source of chemicals and fuels. A major component of biomass is cellulose and the major products from the pyrolysis of cellulose are small saturated chiral molecules. Since biomass is chiral, these saturated molecules could also be chiral and could be useful chiral synthetic building blocks called chirons. Levoglucosenone (1), is a classical representative of this class and with unique rigidity with several important functional groups including a ketone group double bond conjugated with ketone, a protected aldehyde and two protected hydroxyl groups by 1,6-anhydro ring. The enone an attractive chiral carbohydrate building block, is produced by the pyrolysis of cellulose composed materials. Despite the disadvantages of its low yield and the amount of solid cellulosic material necessary for pyrolysis, the efficiency and the economy of the pyrolysis process makes it an effective method. In addition, pyrolysis reduces the amount of waste cellulosic materials, which is clearly beneficial to the environment. Although levoglucosenone has been known for more than 30 years (2), it continues to have only limited applications in organic synthesis. This can be attributed to the rather conservative opinion regarding the process, purification and stability, etc. This simple and small bicyclic enone molecule is an important and efficient chiral starting material for the synthesis of many analogs of complex natural products (Fig. 1). Despite the efforts of various laboratories (1,3-6) to promote the chemistry of levoglucosenone, the interest of chemical and pharmaceutical industries in this chemical remains low. We hope continuous promotion of this remarkable molecule will make levoglucosenone a commodity product, a status that should have been granted to this molecule long ago. Thus, the goal of this chapter is to put levoglucosenone and its fiinctionalized analogs on the map as a valuable chiral building block to the synthesis of value added products.

Structural Studies and Physicochemical Properties This small molecule (M.W. 126), with remarkable potential applications in synthetic organic chemistry, first attracted the attention of the chemists in the early 1970s. Since then, detailed structural studies have been published (1-5) and the revision of the previously published data for the M S and *H N M R spectra by Broido and coworkers (6-7) clearly established its structure as l,6-anhydro-3,4dideoxy-a-D-g/vc^AO-hex-3-enopyranose-2-ulose. These studies were based on the combined G C / M S using both electron impact (EI) and chemical ionization (CI) techniques and allowed for the determination of the correct molecular ion at m/z 126.

In Materials, Chemicals, and Energy from Forest Biomass; Argyropoulos, D.; ACS Symposium Series; American Chemical Society: Washington, DC, 2007.

334 Among the first attempts to elucidate the structure of levoglucosenone through H and C N M R spectral analysis was with Broido data. The C N M R chemical shifts are shown in Scheme 1. Relevant data on optical rotatory dispersion and circular dichroism were reported by Ohnishi (8) whereas Domburg (9,10) reported conformational and structural studies. Halpern and Hoppech conducted a detailed N M R study of the levoglucosenone and its functionalized derivatives (11) and 1,4 adducts.


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1 3

1 3

Naphtopyranqui^

3

- y h

d r o

^" - y 4

h

c , r o x

y

m e t h

y * " ,

4

b u t a n o , i d e

Figure 1.

189.8

i.5

Scheme 1.


335 Yamada and Matsumoto (12,13) reported the photochemical α-cleavage of levoglucosenone and pointed out the general pathway of photolysis and its application to the synthesis of intermediates as convenient chiral building blocks.

Mechanism of the Formation of Levoglucosenone


A mechanism for acid catalysed thermal decomposition of cellulose (15-26) is a 1,2-hydride shift from the C-3 to the carbenium center at C-2 with the formation of a more stable hydroxycarbenium ion.

σ

6 Scheme 2.

The intermediate levoglucosan is formed first via formation of a 1,6anhydro ring. A n alternative 1,2-hydride shift leading to a hydroxycarbenium ion at C-4 does not occur since the corresponding levoglucosenone isomer known as isoievoglucosenone was not found in the pyrolysate (Scheme 2). The hypothetical mechanism of the formation of levoglucosenone via three alternative routes is depicted in Scheme 3 (21). The new modified method produces levoglucosenone in a relatively pure form (ca. 85%) and can be further purified by fractional distillation to give a pure 98% fraction. In this procedure, waste cellulosic materials such as paper and fibers from paper mill waste were pretreated with methanolic solution of phosphoric acid (1.5 wt %) and pyrolyzed by fast pyrolysis under reduced pressure (30-40mm Hg) in the Kugehohr apparatus. The yellow distillate containing water and levoglucosenone was quickly neutralized with solid sodium bicarbonate (with very small portions) to a pH of 7.0, and extracted with


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methylene chloride. The extract was dried over anhydrous magnesium sulfate and evaporated to an oily syrup. The yield was ca. 8-10% based on the weight of cellulosic material and the purity of levoglucosenone was ca. 85%.

Levoglucosenone )

Scheme 3.

Synthesis of Levoglucosenone The traditional method of cellulose pyrolysis for the production of levoglucosenone is still a viable and economically feasible procedure, however, the synthetic methods utilizing various and cheap starting carbohydrate precursors are highly competitive and cost-effective alternatives. K o l l and coworkers (27) reported the first practical synthesis of levoglucosenone as part of a study on the utilization of 1,6-anhydrosugars in the synthesis of convenient derivatives of 1,6-anhydrosugars (Scheme 4). The key step proceeds via rearrangement of one of the Cerny epoxides to the intermediate


337


allyl alcohol which upon oxidation, produces levoglucosenone. The most efficient approach uses a cheap 1,6-anhydrogalactopyranose precursor through functionalization with thiocarbonyldiimidazole (TCDI) followed by desulfurization to the previously prepared allyl alcohol, which upon oxidation with manganese dioxide produces levoglucosenone in moderate 46% yield.

Shibagaki's Approach

Gallagher's Approach

Scheme 4.

Shibagaki and coworkers (28) reported an alternative practical and efficient approach to the synthesis of levoglucosenone utilizing a galactose derivative as a starting material. This route (Scheme 4) utilizes oxidative decarboxylation of 2,3-functionalized orthoesters with zirconium dioxide as a critically important key step. In Gallagher's herbicidin synthesis, (29) an interesting and serendipitous discovery presented a possible alternative route to levoglucosenone. A bicyclic


338 ketone (prepared from 1,5-anhydro-D-mannitol) underwent efficient silylation and gave the silyl enol ether, which when treated with Lewis acid promoters (TiCl , ZnBr , T M S O S 0 C F or LiC10 ) gave levoglucosenone. In the examination of the crude reaction mixtures by H - N M R , it was evident that in all cases extensive rearrangement of silyl enol ether had always taken place. The researchers were able to isolate and characterize levoglucosenone as the major product. 4

2

2

3

4

!

A cleaner process was observed when the silyl enol ether was treated with L i C 1 0 in the absence of an additional electrophilic component, and levoglucosenone was isolated in moderate 40% yield (Scheme 4). Earlier efforts (30) pioneered the synthesisis of the (+)-enantiomer of levoglucosenone and its new 5-hydroxymethyl analog, starting from the known precursor, 5-hydroxymethyl- l,6-anhydro-a-

Levoglucosenone and Its Dimer - ACS Publications - American

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