Addition of metalated pyrones to β-alkoxy aldehydes: Synthesis of hydroxylated spiroketals

Crimmins, Michael T.; Washburn, David G.; Katz, Jason D.; Zawacki, Frank J.

doi:10.1016/s0040-4039(98)00566-8

Cited by 12 publications

(5 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To prepare substituted pyrone 8 , we envisioned that treatment of 11 with trimethylsilyl triflate (TMSOTf) should afford a siloxypyrylium intermediate [9] that may be deprotonated under basic conditions. Accordingly, 11 was consecutively treated with TMSOTf and 2,6-lutidine, followed by addition of quinone 9 .…”

mentioning

confidence: 99%

Total Synthesis of Aurofusarin: Studies on the Atropisomeric Stability of Bis‐Naphthoquinones

Wang

Reichl

et al. 2018

Angew Chem Int Ed

View full text Add to dashboard Cite

An efficient annulation involving pyrone addition to a quinone and Dieckmann condensation was developed for rapid assembly of a γ-naphthopyrone monomeric precursor to the bis-naphthoquinone natural product aurofusarin. Dimerization was achieved through Pd -catalyzed dehydrogenative coupling. Further studies employing asymmetric nucleophilic epoxidation indicate that the atropisomers of aurofusarin and derivatives are not configurationally stable at ambient temperature.

show abstract

mentioning

confidence: 99%

Total Synthesis of Aurofusarin: Studies on the Atropisomeric Stability of Bis‐Naphthoquinones

Wang

Reichl

et al. 2018

Angew Chem Int Ed

View full text Add to dashboard Cite

show abstract

“…Compound 10 may be accessed from the commercially available dimethyl -pyrone 11. To prepare substituted pyrone 8, we envisioned that treatment of 11 with trimethylsilyl triflate (TMSOTf) should afford a siloxypyrylium intermediate [9] which may be deprotonated under basic conditions. Accordingly, 11 was consecutively treated with TMSOTf and 2,6-lutidine, which was followed by addition of quinone 9.…”

mentioning

confidence: 99%

Total Synthesis of Aurofusarin: Studies on the Atropisomeric Stability of Bis‐Naphthoquinones

Wang

Reichl

et al. 2018

Angewandte Chemie

View full text Add to dashboard Cite

An efficient annulation involving pyrone addition to a quinone and Dieckmann condensation was developed for rapid assembly of a γ‐naphthopyrone monomeric precursor to the bis‐naphthoquinone natural product aurofusarin. Dimerization was achieved through PdII‐catalyzed dehydrogenative coupling. Further studies employing asymmetric nucleophilic epoxidation indicate that the atropisomers of aurofusarin and derivatives are not configurationally stable at ambient temperature.

show abstract

“…As shown in Scheme , deprotonation of pyrone 5 with LiHMDS followed by addition of aldehyde 6 led to the generation of a 1:1 mixture of diastereomers. All attempts to improve the diastereoselection of the addition by changing the counterion, solvents, and additives were unsatisfactory . Additionally, attempts to prepare the enol silyl ether of pyrone 5 to investigate Mukaiyama-type additions to aldehyde 6 were thwarted since all silylating conditions led to C-silylation of pyrone 5 .…”

mentioning

confidence: 99%

A Hetero-Diels−Alder Approach to Complex Pyrones: An Improved Synthesis of the Spongistatin AB Spiroketal

Crimmins

Smith

2006

Org. Lett.

Self Cite

View full text Add to dashboard Cite

The conversion of a substituted dioxinone to a pyrone was used in an improved synthesis of the AB spiroketal subunit of the spongistatins. This transformation occurred via a hetero-Diels-Alder reaction of an acyl ketene with butyl vinyl ether. A double diastereoselective Mukaiyama aldol reaction is used to provide the hetero-Diels-Alder precursor.The spongistatins (Figure 1) are potent antitumor agents 1 initially isolated in 1993 from marine sponges of the genus Spongia. 2 The potenial clinical importance of the spongistatins has created substantial interest in their synthesis, and several total syntheses have been accomplished. 3 The total synthesis of spongistatins 1 and 2 (1, 2) from our laboratory was based on the assembly of three fragments including the C1-13 AB spiroketal 3 (Figure 1). 4Our original synthesis of the AB spiroketal (Scheme 1) centered on the preparation of pyrone 4 through addition of a metallated pyrone to an aldehyde. As shown in Scheme 1, deprotonation of pyrone 5 with LiHMDS followed by addition of aldehyde 6 led to the generation of a 1:1 mixture of diastereomers. All attempts to improve the diastereoselection of the addition by changing the counterion, solvents and additives were unsatisfactory. 5 Additionally, attempts to prepare the enol silyl ether of pyrone 5 to investigate Mukaiyama type additions to aldehyde 6 were thwarted since all silylating conditions led to C-silylation of pyrone 5. The lack of stereocontrol at C5 required a four-step sequence to correct and could not be accomplished until after the spiroketalization event, thus requiring that both diastereomers be carried forward several steps prior to convergence. An improvement in the preparation of the pyrone precursor to the spiroketal which overcomes this stereochemical shortcoming is reported herein.Retrosynthetically, the AB spiroketal subunit was envisioned to come from an acid-catalyzed cyclization 6 of pyrone 9 (Scheme 2), which would be formed through a hetero-Diels-Alder cycloaddition-elimination sequence from dioxinone 10. The dioxinone would derive from a selective Mukaiyama aldol addition of silyl dienolate 11 to aldehyde 6.To improve the synthesis of the AB spiroketal, a general method to selectively access the Mukaiyama aldol adduct of silyl dienolate 11 with aldehyde 6 was needed. First attempts to achieve this goal focused on the use of different Lewis acids to take advantage of the potential directing ability of the β-alkoxyaldehyde. The use of a common Lewis acid, BF 3 -OEt 2 (Table

show abstract

Addition of metalated pyrones to β-alkoxy aldehydes: Synthesis of hydroxylated spiroketals

Cited by 12 publications

References 23 publications

Total Synthesis of Aurofusarin: Studies on the Atropisomeric Stability of Bis‐Naphthoquinones

Total Synthesis of Aurofusarin: Studies on the Atropisomeric Stability of Bis‐Naphthoquinones

Total Synthesis of Aurofusarin: Studies on the Atropisomeric Stability of Bis‐Naphthoquinones

A Hetero-Diels−Alder Approach to Complex Pyrones: An Improved Synthesis of the Spongistatin AB Spiroketal

Contact Info

Product

Resources

About