Reaction of the Acetals with TESOTf−Base Combination; Speculation of the Intermediates and Efficient Mixed Acetal Formation

Fujioka, Hiromichi; Okitsu, Takashi; Sawama, Yoshinari; Murata, Nobutaka; Li, Ruichuan; Kita, Yasuyuki

doi:10.1021/ja060328d

Cited by 117 publications

(70 citation statements)

References 19 publications

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“…In previous work, we observed that acetal-selective deprotection of substrates containing both an acetal and ketal group can be carried out using a combination of 2,4,6-collidine and triethylsilyl trifluoromethansulfonate (TESOTf). 21,22) In this effort, we found that excess amounts of reagents (3 eq of 2,4,6-collidine and 2 eq of TESOTf) are required in order to promote complete reaction. We also observed that acetals can be deprotected using a combination of TESOTf and a phosphine.…”

Section: Resultsmentioning

confidence: 99%

Methodology for in Situ Protection of Aldehydes and Ketones Using Trimethylsilyl Trifluoromethanesulfonate and Phosphines: Selective Alkylation and Reduction of Ketones, Esters, Amides, and Nitriles

et al. 2013

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A methodology for selective transformations of ketones, esters, Weinreb amides, and nitriles in the presence of aldehydes has been developed. The use of a combination of PPh 3 -trimethylsilyl trifluoromethanesulfonate (TMSOTf) promotes selective transformation of aldehydes to their corresponding, temporarily protected, O,P-acetal type phosphonium salts. Because, hydrolytic work-up following ensuing reactions of other carbonyl moieties in the substrates liberates the aldehyde moiety, a sequence involving aldehyde protection, transformation of other carbonyl groups, and deprotection can be accomplished in a one-pot manner. Furthermore, the use of PEt 3 instead of PPh 3 enables ketones to be converted in situ to their corresponding O,Pketal type phosphonium salts and, consequently, selective transformations of esters, Weinreb amides, and nitriles in the presence of ketones can be performed. This methodology is applicable to various dicarbonyl compounds, including substrates that possess heteroaromatic skeletons and hydroxyl protecting groups.Key words carbonyl group; selectivity; one-pot; reversing reactivity; in situ protection From a synthetic perspective, carbonyl groups are among the most important functional groups in organic substances because they participate in simultaneous C-C bond and hydroxyl forming reactions. So they are frequently utilized in organic synthesis and their reactivity is well investigated. It is well known that the reactivity of different types of carbonyl groups towards nucleophiles falls in the following order: aldehydes>ketones>esters>amides and nitriles. By using this reactivity profile, numerous selective transformations of more reactive carbonyl groups in the presence of less reactive counterparts have been developed. 1) In contrast, multiple-step sequences, which include often complicated protection and deprotection steps, are required for selective conversion of less reactive carbonyl groups in substrates that also contain more reactive carbonyl moieties. Moreover, the few methods that have been devised to reverse the reactivity order of carbonyl groups [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] have drawbacks that include low substrate scope and reactions that require strict stoichiometry control and use of expensive reagents. Thus, in spite of their ability to simplify preparative sequences, these methods have rarely been used in synthetic organic chemistry.Previously, we have developed a concise and practical method, which utilizes a combination of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and PPh 3 or PEt 3 , for selective transformation of ketones and esters in the presence of aldehydes and ketones 20) (Chart 1). Unique advantages of this method, which involves in situ generation of O,P-acetal or -ketal type phosphonium salts, are that commercially available reagents can be utilized and that PPh 3 can be employed to form salts with aldehydes rather than ketones even when it is used in excess. Consequently, the method is simple to execute and no n...

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Section: Resultsmentioning

confidence: 99%

Methodology for in Situ Protection of Aldehydes and Ketones Using Trimethylsilyl Trifluoromethanesulfonate and Phosphines: Selective Alkylation and Reduction of Ketones, Esters, Amides, and Nitriles

et al. 2013

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“…We developed a new chemoselective method for the deprotection of acetals in the presence of ketals using a combination of 2,4,6-collidine and triethylsilyl trifluoromethanesulfonate (TESOTf) [23][24][25] (Chart 1, Eq. 1).…”

Section: Selective Transformations Of Less Reactive Carbonyl Groups Imentioning

confidence: 99%

Chemoselective Reduction and Alkylation of Carbonyl Functions Using Phosphonium Salts as an in Situ Protecting Groups

Ohta

Fujioka

2017

Chem. Pharm. Bull.

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Recent progress in the chemoselective reduction and alkylation of carbonyl functions using our in situ protection method is described. Methods that enable reversal or control of the reactivity of a carbonyl functional group are potentially useful. They open up new areas of synthetic organic chemistry and change the concept of retrosynthesis because they remove the need for complicated protection/deprotection sequences. In this account, we discuss the strategy and applications of our in situ protection method using phosphonium salts.

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“…21) In addition, only one method exists for selective deprotection of acetals in the presence of ketals. 22,23) In 1992, Kim et al described a ketone selective dioxolanation reaction that takes place in the presence of an aldehyde. 24) A combination of dimethyl sulfide and trimethylsilyl trifluoromethanesulfonate (TMSOTf) (Chart 15) was used to selectively protect aldehydes by formation of the corresponding O,S-acetal type sulfonium salts in the presence of ketones, and after carrying out selective ketalization of the remaining ketones using Noyori's conditions, rebirth of aldehydes with alkaline work-up gives ketal aldehydes 25) ( Table 8).…”

Section: Lewis Acid and Lewis Base Pairmentioning

confidence: 99%

In Situ Protection Methodology in Carbonyl Chemistry

Yahata

Fujioka

2014

CHEMICAL & PHARMACEUTICAL BULLETIN

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Reaction of the Acetals with TESOTf−Base Combination; Speculation of the Intermediates and Efficient Mixed Acetal Formation

Cited by 117 publications

References 19 publications

Methodology for <i>in Situ</i> Protection of Aldehydes and Ketones Using Trimethylsilyl Trifluoromethanesulfonate and Phosphines: Selective Alkylation and Reduction of Ketones, Esters, Amides, and Nitriles

Methodology for <i>in Situ</i> Protection of Aldehydes and Ketones Using Trimethylsilyl Trifluoromethanesulfonate and Phosphines: Selective Alkylation and Reduction of Ketones, Esters, Amides, and Nitriles

Chemoselective Reduction and Alkylation of Carbonyl Functions Using Phosphonium Salts as an <i>in Situ</i> Protecting Groups

<i>In Situ</i> Protection Methodology in Carbonyl Chemistry

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