Tandem Prins/pinacol reaction for the synthesis of oxaspiro[4.5]decan-1-one scaffolds

Reddy, B. V. Subba; Reddy, S. Gopal; Reddy, M. Ramana; Bhadra, Manika Pal; Sarma, Akella V. S.

doi:10.1039/c4ob01188k

Cited by 20 publications

(5 citation statements)

References 35 publications

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“…In this context, we identified a Prins-semipinacol rearrangement as a stringent test that involves structurally distinct reactive intermediates and bond forming steps to produce stereochemically dense spirocycles. In accord with previous studies, − we surmised that upon exposure of an aldehyde with a homoallylic alcohol an acid-catalyzed cyclocondensation would generate a carbocation and trigger a stereoselective skeletal rearrangement through the migration of the σ-bond. Central to the utility of this reaction sequence is the mechanistic requirement that any selectivity imparted in the semipinacol step is reinforced not eroded by the catalyst structure.…”

Section: Results and Discussionsupporting

confidence: 85%

A Bulky Imidodiphosphorimidate Brønsted Acid Enables Highly Enantioselective Prins-semipinacol Rearrangements

Lai,

Reid

2024

ACS Catal.

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The development of BINOL-derived Brønsted acid catalysts has been profoundly guided by rational design, with carefully implemented structural changes leading to generations of catalysts with enhanced reaction capabilities. This approach to catalyst optimization has promoted the integration of knowledge gathered in optimizing prior eras of Brønsted acids, and ultimately, the molecular features that have contributed to the success of previous designs are preserved. Of these, the large substituents at the 3 and 3′ positions of the BINOL backbone are the most critical with almost every developed structure possessing this feature. However, imidodiphosphorimidate (IDPi) catalysts are not synthetically well-suited to contain the same sterically bulky groups associated with the high selectivity imparted by previously implemented catalyst structures. Herein, we have leveraged the moderate size of the 9-phenanthryl substituent to synthesize an IDPi with sizable steric demands. The applicability of the catalyst was evaluated in the construction of stereochemically dense spirocycles generated via an asymmetric Prins-semipinacol reaction sequence. Transition state calculations were deployed to interrogate the origins of the high enantioselectivity, and these demonstrate the mechanistic hallmarks of the 9-phenanthryl substituent can be generalized to a genuinely different class of Brønsted acid catalyst. Ultimately, this work provides the basis for the development of general catalyst design principles and the translation of "privileged" substituents across prior eras of Brønsted acid catalysts structures.

show abstract

Section: Results and Discussionsupporting

confidence: 85%

A Bulky Imidodiphosphorimidate Brønsted Acid Enables Highly Enantioselective Prins-semipinacol Rearrangements

Lai,

Reid

2024

ACS Catal.

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show abstract

“…In this context, we identified a Prins-semipinacol rearrangement as a stringent test that involves structurally unique reactive intermediates and bond forming steps to produce stereochemically dense spirocycles. In accord with previous studies, [20][21][22] we surmised that upon exposure of an aldehyde with a homoallylic alcohol an acid-catalyzed cyclocondensation would generate a carbocation and trigger a stereoselective skeletal rearrangement through the migration of the s-bond. Central to the utility of this reaction sequence is the mechanistic requirement that any selectivity imparted in the semipinacol step is reinforced not eroded by the catalyst structure.…”

Section: Catalytic Applicationsupporting

confidence: 86%

A Bulky Imidodiphosphorimidate Brønsted Acid Enables Highly Enantioselective Prins-semipinacol Rearrangements

Lai,

Reid

2023

Preprint

View full text Add to dashboard Cite

The development of BINOL-derived Brønsted acid catalysts has been profoundly guided by rational design, with carefully implemented structural changes leading to unique generations of catalysts with enhanced reaction capabilities. This approach to catalyst optimization has promoted the integration of knowledge gathered in optimizing prior eras of Brønsted acids and ultimately, the molecular features that have contributed to the success of previous designs are preserved. Of these, the large substituents at the 3 and 3’ positions of the BINOL backbone are the most critical with almost every newly developed structure possessing this feature. However, imidodiphosphorimidate (IDPi) catalysts are not synthetically well-suited to contain the same sterically bulky groups associated with the high selectivity imparted by previously implemented catalyst structures. Herein, we have leveraged the moderate size (as compared to TRIP and 9-anthryl) but high applicability of the 9-phenanthryl substituent to synthesize a sterically demanding IDPi. Using computed descriptors, we survey the catalyst properties of known structures to demonstrate this catalyst to be both unique and one of the bulkiest IDPi yet synthesized. The applicability of the catalyst was evaluated in the construction of stereochemically dense spirocycles generated via an asymmetric Prins-semipinacol reaction sequence. Transition state calculations were deployed to interrogate the origins of the superior enantioselectivity and these demonstrate the mechanistic hallmarks of the 9-phenanthryl substituent can be generalized to a genuinely different class of Brønsted acid catalyst. Ultimately, providing the basis for the development of general catalyst design principles and the translation of “privileged” substituents across unique eras of Brønsted acid catalyst structures.

show abstract

“…In this context, we identified a Prins-semipinacol rearrangement as a stringent test that involves structurally unique reactive intermediates and bond forming steps to produce stereochemically dense spirocycles. In accord with previous studies, [18][19][20] we surmised that upon exposure of an aldehyde with a homoallylic alcohol an acid-catalyzed cyclocondensation would generate a carbocation and trigger a stereoselective skeletal rearrangement through the migration of the s-bond. Central to the utility of this reaction sequence is the mechanistic requirement that any selectivity imparted in the semipinacol step is reinforced not eroded by the catalyst structure.…”

Section: Catalytic Applicationsupporting

confidence: 86%

The Synthesis and Application of the Bulkiest Imidodiphosphorimidate Brønsted Acid Catalyst

Lai

Reid

2023

Preprint

View full text Add to dashboard Cite

The development of BINOL-derived Brønsted acid catalysts has been profoundly guided by rational design, with carefully implemented structural changes leading to unique generations of catalysts with enhanced reaction capabilities. This approach to catalyst optimization has promoted the integration of knowledge gathered in optimizing prior eras of Brønsted acids and ultimately, the molecular features that have contributed to the success of previous designs are preserved. Of these, the large substituents at the 3 and 3’ positions of the BINOL backbone are the most critical with almost every newly developed structure possessing this feature. However, imidodiphosphorimidate (IDPi) catalysts are not synthetically well-suited to contain the same sterically bulky groups associated with the high selectivity imparted by previously implemented catalyst structures. Herein, we have leveraged the moderate size (as compared to TRIP and 9-anthryl) but the high applicability of the 9-phenanthryl substituent to synthesize an extremely sterically demanding IDPi. Using computed descriptors, we survey the catalyst properties of known structures to demonstrate this catalyst to be both unique and to the best of our knowledge, the bulkiest IDPi yet synthesized. The applicability of the catalyst was evaluated in the construction of stereochemically dense spirocycles generated via an asymmetric Prins-semipinacol reaction sequence. Transition state calculations were deployed to interrogate the origins of the superior enantioselectivity and these demonstrate the mechanistic hallmarks of the 9-phenanthryl substituent can be generalized to a genuinely different class of Brønsted acid catalyst.

show abstract

Tandem Prins/pinacol reaction for the synthesis of oxaspiro[4.5]decan-1-one scaffolds

Cited by 20 publications

References 35 publications

A Bulky Imidodiphosphorimidate Brønsted Acid Enables Highly Enantioselective Prins-semipinacol Rearrangements

A Bulky Imidodiphosphorimidate Brønsted Acid Enables Highly Enantioselective Prins-semipinacol Rearrangements

A Bulky Imidodiphosphorimidate Brønsted Acid Enables Highly Enantioselective Prins-semipinacol Rearrangements

The Synthesis and Application of the Bulkiest Imidodiphosphorimidate Brønsted Acid Catalyst

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