Intramolecular Huisgen-Type Cyclization of Platinum-Bound Pyrylium - - PowerPoint PPT Presentation

Intramolecular Huisgen-Type Cyclization of Platinum-Bound Pyrylium Ions with Alkenes and Subsequent Insertion into a Benzylic C-H Bond

Chang Ho Oh,* Ji Ho Lee, Su Jin Lee, Jae Il Kim, and Chang Seop Hong Angewandte Chemie International Addition, 2008, 47, early view.

Department of Chemistry, Hanyang University, Seoul, Korea DOI: 10.1002/anie.200802425

CHO

PtII

O PtII OBn OBn O Ph O H

Wipf Group Saturday Morning Meeting Current Literature Abstracts & Reports Rob Lettan August 30th, 2008

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Oxabicyclo[3.2.1]octanes in Natural Products

O O O O O Me O Me

corianlactone no remarkable inhibition towards K562 cells cytotoxic, IC50 > 50 µg/mL

O O N H OH HO2C OH O Me Me H

platensimycin broad spectrum Gram-positive antibiotic Synthesized by: Nicolaou (2006, racemic) (2007, 2008 asymmetric) Snider (2007, formal, racemic)

• E. Lee (2008, formal)

Me O OH HO

bruguierol C showed moderate activity against Gram-positive and Gram-negative bacteria Synthesized by: Jennings (2007) Ramana (2007, bruguierol A)

R Me RO RO RO H OR Me HO Me OR RO R

Taxane diterpenoids anti-cancer

O Rob Lettan @ Wipf Group Page 2 of 11 9/7/2008

Strategies for the Construction of 7-Membered Carbocycles:

[6C + 1C] Approach

MeO OMe OMe MeO OMe OMe

CH2=S(O)Me2

OH OMe MeO MeO MeO MeO MeO CO2Me OMe MeO MeO MeO MeO CO2Me OMe MeO MeO MeO O CO2Me OMe MeO MeO MeO OMe NHAc O

(±)-colchicine

TFA

O O

92%

Evans, D. A., et al. J. Am. Chem. Soc. 1981, 103, 5813-5821.

MeO Me O O H H H Me O Me O

harringtonolide

O N2 H MeO OMe ODEIPS Me CO2Me

RhII

MeO H MeO OMe ODEIPS Me CO2Me O Me H MeO OMe ODEIPS Me CO2Me O MeO Me

DBU

Mander, L. N., et al. Aust. J. Chem. 2000, 53, 819-830.

65% Rob Lettan @ Wipf Group Page 3 of 11 9/7/2008

Strategies for the Construction of 7-Membered Carbocycles:

[5C + 2C] Approach

O O OTBS AcO Me OAc H O O OTBS Me OAc

DBU MeCN

Me O OAc H OTBS O Me O OH OH Me Me OH HO Me OH H

phorbol

79%

Wender, P. A., et al. J. Am. Chem. Soc. 1997, 119, 7897-7898. This approach was also used by many others in natural product syntheses:

• P. Magnus (guanacastepene, taxanes), J. E. Baldwin (cordytropolone: alkyne trap), and Snider (cartorimine: unsat. ester)

Review: Wright, D. L., et al. Chem. Eur. J. 2006, 12, 3438-3447.

O O N2 R H H

Rh2(OHex)4

O O R H H H H O O R H

85%

tigliane skeleton McMills, M. C., et al. Tet. Lett. 1994, 35, 8311-8314. Dauben, W. G., et al. J. Org. Chem., 1993, 58, 7635-7637.

• Me

Me Me OBn Me Me

[Rh(CO)2Cl]2

RhLn Me Me H Me Me Me OBn Me Me H Me Ln Rh BnO Me Me H Me Me Me H Me Me O Me BnO HO Me Me

(+)-aphanamol I

90%

Wender, P. A., Zhang, L. Org. Lett. 2000, 2, 2323-2326.

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Strategies for the Construction of 7-Membered Carbocycles:

[4C + 3C] Approach

O O O Me H O O Me H Cl Cl O O Cl Cl O O O Me H O O Me O O O OH Me Me H Me OH OH

Zn-Cu

70% erinacine C Wright, D. L., et al. J. Org. Chem. 1999, 1, 1535-1538

O NHBoc MeO MeO OMe OTMS OMe OMe

TMSOTf

O NHBoc MeO MeO OMe TMSO MeO NHBoc MeO MeO OMe O OMe O

colchicine 45% Cha, J. K., Lee, J. C. Tetrahedron 2000, 56, 10176-10184.

O O O O

75 °C

MeO MeO OMe O O

73%

MeO MeO OMe O O O CO MeO MeO MeO OMe NHAc O

(±)-colchicine Boger, D. L., Brotherton, C.E. J. Am. Chem. Soc. 1986, 108, 6713-6719.

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Strategies for the Construction of 7-Membered Carbocycles:

Alternative Approaches

N O TMS O Me O N2

Rh2(OAc)4

N Me O O O N O O TMS Me O TMS Me N Me O

ferruginine

• 1. (PPh3)3RhCl, H2
• 2. nBu4F
• 3. CH2O, Na(CN)BH3

73% 70%, 3 steps

Davies, H. M. L., et al. J. Org. Chem. 1991, 56, 5696-5700.

O N2 Me Me Me Me Me O Me O O Me Me O H H Me O Me Me O H H Me

tremulenolide

H2, ClRh(PPh3)3 76% Rh2(S-DOSP)4 140 °C 85% 90% ee

Davies, H. M. L., Doan, B. D. Tet. Lett. 1996, 37, 3967-3970.

O O O PMP Me Me O O PMP Me O Me O O PMP Me O Me OH CHO Me O Me AcO Me Me

guanacastepene

h

• 1. SmI2
• 2. PhSeBr
• 3. mCPBA

37%, 3 steps 76%

Sorenson, E. J., Shipe, W. D. Org. Lett. 2002, 4, 2063-2066.

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Transition-Metal Catalyzed Cyclization of Pyrylium Ions with Alkenes/Alkynes

O Me Me O Me Me W(CO)5 O Me Me W(CO)5 OEt OCH2CH3 O i-Pr O OEt H H H Me

C-H insertion —W(CO)5·THF

OEt OEt

W(CO)5·THF THF, rt 20 mol% 76%

Iwasawa, N. et al. J. Am. Chem. Soc. 2001, 123, 5814-5815.

CHO

10 mol% AuCl3

O AuCl3 Ph Ph Ph O Ph AuCl3 O Ph Ph Ph

Yamamoto, Y., et al. J. Am. Chem. Soc. 2002, 124, 12650-12651. 96% yield >99:1 regioselectivity

TsN CHO

[Rh(COD)Cl]2, dppp 80 °C, 8 h

TsN O Rh TsN O TsN O O

[5+2] H2O

87%

Rh H H

Oh, C. H., et al. Chem. Commun. 2005, 4429-4431.

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Intramolecular Platinum Catalyzed Cyclization of Pyrylium Ions with Alkenes and Subsequent C-H Insertion

CHO

5 mol% PtII

O PtII OBn OBn O Ph O H O O H Ph H H PtII H H PhO2C O

2a 3a 4a

toluene 120 °C, 1h

Catalyst 2a 3a 4a PtCl2 PtCl4 Pt(PPh3)4 PtCl2(PPh3)2 PtCl2(dppe) 25% 35% — 20% 40% — 77% 61% 10% 20% — — — — —

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Mechanistic Proposal

CHO

PtII

O PtII OBn OBn O Ph O H O O H PtII H H PhOCO O

2a 3a 4a

Ph O O H PtII Ph O Ph O H Pt H O H Pt O Ph H O H Pt O Ph

a b

a b

H H H O

• 1. NaOH
• 2. PCC

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Reaction Scope

CHO OBn O Ph O H H

SM Product

CHO OBn O Ph O H H

SM Product

80% 74%

CHO OBn O Ph O H H

66%

CHO OBn O Ph O H H

88%

CHO OBn H

86%

PhOCO CHO

80%

BnO BnO O CHO OBn O Ph O H H OTBS OH O Ph O H H O

76% PDC Rob Lettan @ Wipf Group Page 10 of 11 9/7/2008

Summary

Methods for the synthesis of 7-membered carbocycles are necessary due to their prevelance in natural products. Several tactics for the formation of 7-membered carbocycles have been developed, including strategies that employ, [6C + 1C], [5C + 2C], [4C + 3C], and other alternatives. Oh and coworkers have published a platinum-catalyzed cyclization of pyrylium ions with alkenes to give a tetracyclic platinum-carbene complex, which immediately undergoes insertion into a benzylic C-H bond to give a highly complex ring system. The power of transition metal-catalyzed pyrylium ion formation and subsequent cyclization has been demonstrated to access various multi-cyclic scaffolds, and lends to possibility of utilization of these methods for the future development of other sophisticated carbon frameworks.

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