Glycosylmanganese Complexes and Anomeric Anomalies - ACS

Chapter 12

Glycosylmanganese Complexes and Anomeric Anomalies

Downloaded by UNIV OF MISSOURI COLUMBIA on June 5, 2013 | http://pubs.acs.org Publication Date: November 23, 1993 | doi: 10.1021/bk-1993-0539.ch012

The Next Generation? Philip DeShong1, Thomas A. Lessen1, Thuy X. Le1, Gary Anderson1, D. Rick Sidler1, Greg A. Slough2, Wolfgang von Philipsborn3, Markus Vöhler3, and Oliver Zerbe3 1Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742 2Department of Chemistry, Pennsylvania State University, University Park, PA 16802 3Organisch-chemisches Institut, University of Zurich, Zurich, Switzerland Sequential and migratory insertion processes involving pyranosyl and furanosylmanganese pentacarbonyl complexes have been performed to afford C-glycosyl derivatives. The rates of these insertion processes depends upon the configuration of the metal at the anomeric center. Kinetic analysis of the insertion reaction and determination of the solution conformation of the respective glycosyl complexes from 1D and 2 D - N M R analysis and molecular mechanics calculations demonstrates that the orientation of the carbon-metal bond with regard to the lone pairs of electrons on oxygen has an influence on the rates of the insertion process. In recent years, we have demonstrated that alkylmanganese pentacarbonyl complexes can be utilized for the synthesis of carbonyl derivatives via the intermediacy of manganacycles 1 and 2.(7) These processes are summarized in Scheme 1. In these sequential insertion reactions, a molecule of carbon monoxide and an alkene (or an alkyne) is incorporated into the manganese complex with the concomitant formation of at least two carbon-carbon bonds. Subsequent demetalation of manganacycle 1 or 2 results in the formation of a variety of carbonyl derivatives as indicated. The generality of the sequential insertion methodology with highly functionalized alkylmanganese complexes has been demonstrated(7) and the approach has been extended to the preparation of biologically relevant substances. One appealing feature of this methodology would involve the synthesis of C-glycosyl derivatives as outlined in Scheme 2. As originally conceived, glycosyl halide 3 and sodium 0097-6156/93/0539-0227$06.00/0 © 1993 American Chemical Society

In The Anomeric Effect and Associated Stereoelectronic Effects; Thatcher, G.; ACS Symposium Series; American Chemical Society: Washington, DC, 1993.

228

THE ANOMERIC EFFECT AND ASSOCIATED STEREOELECTRONIC EFFECTS

manganate pentacarbonyl (4) react to afford glycosylmanganese complex 5. Following the protocols established in the earlier studies, glycosyl complex 5 was expected to serve as the precursor for either ester 6 or ketone 7, respectively. The overall process results in formation of a carbon-carbon bond to the anomeric center, a reaction which is traditionally difficult to achieve with high stereoselectivity. Ο

Η

υ Τ


Me'^^XOOtBu Ο

Mn(CO)

4

COOtBu Me-Mn(CO)

5

Ph Ο

Mn(CO)

Me

4

Ph 2 Me

Scheme 1

Scheme 2


Ph

12.

DESHONG ET AL.

Glycosylmanganese Complexes & Anomeric Anomalies 229

One aspect of this process which deserved particular attention from the outset was the condensation of manganate anion 4 with halide 3 which could provide, in principle, a diastereomeric mixture of complexes 5 (at *). Since subsequent migratory insertion of carbon monoxide, the initial step in formation of 6 and 7, must occur with retention of configuration at the anomeric center, the configuration of the carbon-metal bond in complex 5 would be retained in the sequential insertion product. We were able to demonstrate subsequently that the anomeric configuration


of glycosylmanganese complexes can be controlled in the condensation reaction. For example, condensation of potassium manganate (9) and glucopyranosyl bromide 8 in THF at low temperature leads exclusively to β-complex 10 in high yield. On the other hand, if the condensation of 8 and 9 is performed at higher temperatures and in the presence of tetrabutylammonium bromide, a mixture of α-anomer 11 and βanomer 10 is obtained with the α-anomer predominating.(2,3) This protocol has been applied to the preparation of a variety of pyranosyl- and furanosylmanganese complexes. In this paper, we shall focus on four families of glycosyl derivatives: permethylated glucopyranosyl (12), mannopyranosyl (13), arabinofuranosyl (14), and ribofuranosyl (15) complexes. In each glycosyl family, both the a- and βanomers can be prepared in anomerically pure form.(2,3) See Scheme 3.

BnO^V^°v

THF, -78 °C 90%

BnO BnO BnO

5

BnO

ΒηΟ-^^νή B n

Mn(CO)

10

°Br

8

THF, Bu NBr -78 °C to r.t. 70% 4

KMn(CO) 9

5

BnO^V^-°v + β-anomer ΒηΟ-^Γή W(CO) 11 B n (

B

10:11 = 3:1

Scheme 3 As the sequential insertion processes were studied for each of these compounds, it was observed that the rate at which the respective anomers underwent sequential insertion was very different. For instance, sequential insertion of methyl acrylate with the α-anomer of arabinosylmanganese pentacarbonyl (Cc-14) occurred readily and in high yield to afford manganacycle 16 (see Scheme 4). However, anomer β-14 was inert to manganacycle formation under identical conditions. Other glycosyl derivatives displayed qualitatively analogous


230


MeO-

MeO

MeO~ MeO-

MeO MeO MeO

Mn(CO)

Mn(CO)

5

Glucopyranosyl (12)

Ι/°Ν~Μη(00)

OMe Ο 5

Mannopyranosyl (13)

Β


\MeO/

MeO

MeO OMe

Arabinofuranosy 1 ( 14)

Rlbofuranosyl ( 15)

behavior. Employing control experiments which cannot be discussed at this time,(3) we were able to demonstrate that it was the migratory insertion of carbon monoxide into the anomeric carbon-metal bond of complex 12, and not the alkene insertion step, which was responsible for the differential rates of manganacycle production. Accordingly, a preliminary kinetic study of the migratory insertion of carbon monoxide into glycosyl complexes 12-15 was perfrmed to investigate this phenomenon. The results of this study are the subject of this presentation. MeO^

MeO.

- ° \

,r

^MeOyl MeO^ Mn(CO)

C

O

O

M

e

II

\ MeO/

B

MeO

MeO a-14

MeO^

λ Γ * MeGy

Ο

COOMe Mn(CO)

4

16

if

.COOMe

•

No Reaction

MeO

^

1

4

Scheme 4

The preliminary results of this kinetic investigation are summarized in the Table. (4) In each case, the relative rate of migratory insertion promoted by carbon monoxide to afford the acyl derivative (i.e., 17) was determined. The kinetics of this process were complicated by the reversibility of the insertion reaction (17 slowly


12.

DESHONG ET AL.

Glycosylmanganese Complexes & Anomeric Anomalies

reverts to 16); however, under pseudo first-order conditions with excess carbon monoxide, the rates of the forward reaction could be measured. Several trends are apparent. First, the relative rates of migratory insertion of the anomers are remarkably different in each glycosyl family. For example, the α-anomers of the glucopyranosyl (12) and ribofuranosylmanganese (15) complexes are approximately an order of magnitude more reactive than the corresponding β-anomers. The difference in the relative rates of mannopyranosyl (13) and arabinofuranosyl (14)


derivatives is even greater (see Table I). This extreme difference in insertion proclivity suggests to us that electronic features are influencing the rates of migratory insertion (vide infra).

Table I. Relative Rates of Migratory Insertion

MeO

MeO

Mn(CO)

5

OMe


231

232


A second trend was noted for the pyranosyl derivatives - the glucosyl (12) and mannosyl (13) series, respectively. While in each family the α-anomer was more reactive toward migratory insertion of carbon monoxide than the β-anomer (see Table I), the relative difference was ca. 10 in the glucosyl derivatives, but ca. 100 in the mannosyl complexes. We attribute the "hyper"-reactivity of the amannosyl complex to anchimeric stabilization of the transition state by the C-2 alkoxy substituent in the migratory insertion reaction (see Figure 1). An analogous


anchimeric assistance has been proposed to explain the preference for α-anomer formation in glycosidic coupling of mannosyl halides. (5)

Figure 1 Based upon our preliminary kinetic data we hypothesized that the orientation of the lone pairs of the ring (or glycosidic) oxygen and the carbon-metal bond dramatically influenced the rate of migratory insertion of the complexes. The hypothesis is summarized in Scheme 5 for the glucopyranosyl complexes. For example, glucopyranosyl complex β-12 should exist in the chair conformation with the carbon-metal bond gauche to the pyranosidic lone pairs on oxygen. In this conformation, migratory insertion is slow. On the other hand, for the α-anomer in the chair conformation, the carbon-metal bond lies antiperiplanar to one lone pair of the pyranosidic oxygen and undergoes migratory insertion more rapidly. A similar situation can be envisioned for the other glycosyl derivatives studied.


12.

DESHONG

Glycosylmanganese Complexes & Anomeric Anomalies 233

ET A L .

β-Anomer

cc-Anomer MeO-^, MeO--*\^ °

MeO MeO MeO

Mn(CO)

Me

MeO

β-12

°an(CO)

5

a-12

III Downloaded by UNIV OF MISSOURI COLUMBIA on June 5, 2013 | http://pubs.acs.org Publication Date: November 23, 1993 | doi: 10.1021/bk-1993-0539.ch012

x

ΜβΟ-^Ύή

5

•Il

G§C

1C0

*

0&

Mn(CO)

H

5

CO

CO

fast migratory insertion

slow migratory insertion

Scheme 5 One assumption implicit in this hypothesis is that the pyranosyl derivatives exist in chair conformations with the orientation of lone pairs of electrons and bonds as indicated in Scheme 5. To provide support for this hypothesis, we were, accordingly, compelled to unambiguously determine the preferred solution conformations of the respective glycosyl derivatives. As indicated in Schemes 6 and 7, the solution conformations of the anomers of the glucopyranosyl (12) and mannopyranosyl (13) complexes were established by ID TOCS Y and 2D NOES Y N M R experiments. (6) These experiments conclusively demonstrated that as anticipated the β-anomers in each series adopted the chair conformation of the pyranosidic ring. As such, the carbon-manganese bond in question was gauche to the lone pairs on the pyranosidic oxygen in accord with the hypothesis outlined in Scheme 5. However, the α-anomers of the glucopyranosyl (a-12, Scheme 6) and mannopyranosyl derivatives (a-13, Scheme 7) did not adopt the anticipated chair conformations in solution. Analysis of the N M R data for gluco-complex a-12 was consistent with an approximately 1:1 mixture of boat conformer 18 and chair conformer 19. Similarly, the α-anomer of the mannosyl complex (a-13) exists in conformation 20.


234


MeO—χ

MeO MeO MeO

Mn(CO)

MeO— MeO— MeO J , Mn(CO)

5

MeO

5

a-12

β-12

(28.8)

NOB


( Me

Η

^NOE îï

*

ν

°r\ Λ

Mn(CO)

MeO^r

^

5

loMe ?

|^^7^Mn(CO)

MeO-\W*°

MeO

OMe

OMe 19

18

(24.8)

(24.4)

Mn(CO)

Mn(CO)

B

Scheme 6 MeO—ν

Y

Me

Me0^4°\

M e O — ν OMe

a-13 Mn(CO)

5

(25.6) β-13

NOE

Mn(CO)

B

MeO-^Γ

^

loMe ? O-TLOMC

Η

Mn(CO) MeO 20 (23.6)

III Mn(CO)

B

Scheme 7


B

5

5

12.

DESHONG E T AL.


235

Molecular mechanics calculations on these derivatives employing the augmented force field parameters of the CAChe molecular modeling system (7) were consistent with the results from the NMR experiments. The calculated energies of the respective global and local minima of the glycosyl conformers are indicated in Schemes 6 and 7 in parantheses. Once the solution conformations of the pyranosyl complexes had been determined, it was clear that the original hypothesis for the differences in rate of


migratory insertion was not tenable. As originally proposed, the β-anomers of 12 and 13 adopt the gauche orientation of lone pairs and carbon-manganese bond. However, the α-anomer of gluco-complex 12 exists as conformers 18 and 19 in which the orientation of lone pairs and carbon-manganese bonds are also gauche (see Scheme 6)! Therefore, by the original hypothesis (Scheme 5), migratory insertion of carbon monoxide in this anomer should not be increased in comparison to the β-anomer. An analogous situation exists for the mannosyl anomers (see Scheme 7). A revision of the hypothesis was required to accomodate the new data. Careful analysis of the conformational situation has allowed us to retain the basic tenet of the hypothesis developed in Scheme 5: if the carbon-manganese bond is gauche to the lone pairs, the migratory insertion reaction is not enhanced. However, when the carbon-metal bond is either antiperiplanar or synperiplanar to a lone pair, the migratory aptitude in increased. Application of this hypothesis to the results in the gluco and manno series are summarized in Schemes 8 and 9. For the β-anomer of glucopyanosylmanganese pentacarbonyl, the ground state conformation (β-12) is unreactive according to the hypothesis. One can envision that conformational mobility of the pyranosidic ring would provide either conformers 21 or 22, both of which should display "enhanced" reactivity. However, molecular mechanics calculations (7) indicate that neither 21 nor 22 is accessible energetically (ΔΔΕ vs β-12 > 6 kcal/mole in each instance). Accordingly, the insertion reaction is not accelerated, and anomer β-12 is assigned a relative insertion rate of 1. The situation for the α-anomer is that conformers 18 and 19 (Scheme 6) are the predominant solution conformers and by the hypothesis are "unenhanced" due to the gauche orientation of lone pairs and bonds. However, conformer α-12, an "enhanced" orientation, lies only 4.4 kcal/mole above 18 and 19 and is conformationally accessible. It is the small amount of conformer α-12 in the equilibrium (Curtin-Hammett principle) that is responsible for the increased reactivity of the α-anomer. Analogous reasoning can be applied to the situation in the mannosyl series.


236



β-12 (O.O) Unreactlve

~ i

21 (>6.0) Reactive

22 (>8.0) Reactive

c$L»r ^ ° S o , 18 (0.0) Unreactlve

19 (0.4) Unreactlve

ot-12 (4.8) Reactive

Conclusion: α-anomer undergoes migratory insertion of C O with slight preference Experimental Result: k /kp = ca. 10 a

Scheme 8

> \ ofr*— K: β-13 Unreactlve

23 (>8.0) Reactive

24 (>8.0) Reactive

Conclusion: α-anomer undergoes migratory insertion of CO with strong preference Experimental Result: k /kp = ca. 100 a

Scheme 9


12.

DESHONG

ET A L .


This analysis also allows us to rationalize why the difference in rates in the gluco complexes (ka/kp = ca. 10) is less than in the manno derivatives (ko/kp = ca. 100). The energy difference between the ground state conformers of the oc-gluco anomer (18 and 19) and the "reactive" conformers (a-12) is ca. A A kcal/mole; while the ΔΔΕ between the "unreactive" conformer 20 and the "reactive" conformer 25 in the mannose family is only 2.0 kcal/mole. Conformer 25 assumes a more dominant role in the conformation equilibrium of the mannosyl series than conformer α-12 has


in the glucose system. Accordingly, the difference in rates (ka/kfi ) for the mannopyranosyl derivatives is greater than in the glucose derivatives. The important question that is inherent in the hypothesis presented above is why is it that antiperiplanar and synperiplanar orientations lead to "enhanced" rates of migratory insertion? We propose that the rate enhancements are the result of electronic interactions between the lone pairs on oxygen and the carbon-metal bond. In the antiperiplanar arrangement, the predominant orbital interaction is between the filled η-orbital of oxygen and the empty a*-orbital of the carbon-manganese bond. This interaction results in population of the a*-orbital and weakening of the carbonmanganese bond. Since this bond is broken during migratory insertion, the net result is a lowered energy in the transition state for CO insertion.


237

238


The situation is altered for the synperiplanar orientation. In this case, interaction between the filled η-orbital on oxygen and the filled, high-lying σcarbon-metal orbital results in destabilization of the system. In the transition state for migratory insertion in which the carbon-manganese bond is being broken, this destabilizing interaction with the synperiplanar lone pair on oxygen is diminished. Accordingly, the overall activation energy for migratory insertion is reduced.(8) The kinetic and computational results presented in this forum are preliminary


and require refinement. Migratory insertion reactions in these arnd related derivatives 26-29 under conditions in which precise kinetic data can be obtained are underway and shall be reported when complete. To date, the results from these experiments are qualitatively identical to those presented above and are consistent with the hypothesis outlined in Scheme 5. Acknowledgments. We thank the National Institutes of Health (P. D.) and the Swiss National Science Foundation (W. v. P.) for generous financial support of this program. We also acknowledge numerous discussions with our colleagues, especially Bryan Eichhorn and Rinaldo Poli. Finally, P. D. wishes to thank CAChe Scientific, Inc. for the generous donation of software, hardware, advice, and intellectual stimulation during the course of this investigation. References and Notes 1. (a) DeShong, P.; Slough, G.A. Organometallics 1984, 3, 636. (b) DeShong, P.; Slough, G. Α.; Rheingold, A. L. TetrahedronLett.1987, 28, 2229. (c) DeShong, P.; Slough, G.A.; Sidler, D. R. Tetrahedron Lett. 1987, 28, 2233. (d) DeShong, P.; Sidler, D.R.; Rybczynski, P. J.; Slough, G. Α.; Rheingold, A. L. J. Am. Chem. Soc. 1988, 110, 2575. (e) DeShong, P.; Sidler, D. R. J. Org. Chem. 1988, 53, 4892. (f) DeShong, P.; Slough, G. Α.; Sidler, D. R.; Rybczynski, P. J.; von Philipsborn, W.; Kunz, R.; Bursten, Β. E.; Clayton, T. W. Jr. Organometallics 1989, 8, 1381. 2. (a) DeShong, P.; Slough, G. Α.; Trainor, G. J. Am. Chem. Soc. 1985,107,7788. (b) DeShong, P.; Slough, G.A.; Elango, V. Carbohydr. Res. 1987, 171, 342. 3. Unpublished results of T.L. Lessen and T. X. Le. 4. Unpublished results of G. Anderson and T.X. Le. 5. Bochkov, A. F.; Zaikov, G. E. "Chemistry of the O-Glycosidic Bond". New York: Pergamon Press, 1979, pp. 5-80; and references cited therein. 6. Unpublished results of M. Vöhler, O. Zerbe, and W. von Philipsborn.


12.

DESHONG E T AL.


7. CAChe Scientific, Inc.; Beaverton, Oregon 97077. 8. Preliminary extended Hückel and ZNDO calculations (7) on model systems of related manganese complexes have provided results consistent with this interpretation. Unpublished results by P. DeShong. 1993


RECEIVED June 25,


239

Glycosylmanganese Complexes and Anomeric Anomalies - ACS

Recommend Documents