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Volumn 133, Issue 8, 2011, Pages 2714-2720

Organocatalytic Functionalization of carboxylic acids: Isothiourea- catalyzed asymmetric intra- and intermolecular Michael addition-lactonizations

Author keywords

[No Author keywords available]

Indexed keywords

ARYLACETIC ACIDS; DIHYDROPYRANONES; ENANTIOCONTROL; FUNCTIONALIZATIONS; FUNCTIONALIZED; INTRAMOLECULAR MICHAEL ADDITION; ISOTHIOUREA; LACTONIZATION; MICHAEL ADDITIONS; ORGANOCATALYTIC; UNSATURATED ESTERS;

EID: 79952269315     PISSN: 00027863     EISSN: 15205126     Source Type: Journal    
DOI: 10.1021/ja109975c     Document Type: Article
Times cited : (230)

References (97)
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    • The absolute configuration of 2 was assigned by comparison of the HPLC and specific rotation data with that contained in ref 24a. Ring opening of 2 with MeOH to give 14, and comparison of its specific rotation contained in ref 24b, also confirmed the absolute configuration and stereochemical integrity of the products of this transformation (see SI for full details).
    • The absolute configuration of 2 was assigned by comparison of the HPLC and specific rotation data with that contained in ref 24a. Ring opening of 2 with MeOH to give 14, and comparison of its specific rotation contained in ref 24b, also confirmed the absolute configuration and stereochemical integrity of the products of this transformation (see SI for full details).
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    • See SI for full experimental details.
    • See SI for full experimental details.
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    • The relative and absolute configuration of 21 was confirmed by X-ray crystal structure analysis, with all other dihydrobenzofuran derivatives assigned by analogy. See SI for further details. Crystallographic data for 21 have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 799331.
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    • Preliminary unoptimized experiments show only modest conversion (around 30%) using hydrocinnamic acid as the acid component.
    • Preliminary unoptimized experiments show only modest conversion (around 30%) using hydrocinnamic acid as the acid component.
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    • The relative and absolute configuration of 32 was confirmed by X-ray crystal structure analysis, with all other derivatives assigned by analogy. See SI for further details. Crystallographic data for 32 have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 799871.
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    • Although this intermolecular process was routinely carried out on an analytical scale (0.2 mmol), this reaction process has been scaled to a 2 mmol scale, giving 26 in 66% yield and 99% ee. This reaction can also be performed in an open flask using bench-grade solvents without degradation of reactivity and enantioselectivity.
    • Although this intermolecular process was routinely carried out on an analytical scale (0.2 mmol), this reaction process has been scaled to a 2 mmol scale, giving 26 in 66% yield and 99% ee. This reaction can also be performed in an open flask using bench-grade solvents without degradation of reactivity and enantioselectivity.
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    • We have considered the possibility that these reaction processes proceed via the enol tautomer of the acyl ammonium species, rather than the ammonium enolate, although we currently favor the enolate pathway due to the assumed attenuated nucleophilicity of the enol. An alternative reaction process, involving the in situ generation of a ketene from the mixed anhydride, followed by nucleophilic addition of an isothiourea to generate the ammonium enolate, cannot be ruled out at this time, although we favor the mechanisms depicted in Figure 2. Further mechanistic investigations of these reaction pathways are currently under investigation. We thank a reviewer for helpful comments on this matter.
    • We have considered the possibility that these reaction processes proceed via the enol tautomer of the acyl ammonium species, rather than the ammonium enolate, although we currently favor the enolate pathway due to the assumed attenuated nucleophilicity of the enol. An alternative reaction process, involving the in situ generation of a ketene from the mixed anhydride, followed by nucleophilic addition of an isothiourea to generate the ammonium enolate, cannot be ruled out at this time, although we favor the mechanisms depicted in Figure 2. Further mechanistic investigations of these reaction pathways are currently under investigation. We thank a reviewer for helpful comments on this matter.
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    • Using the assumption of a stepwise Michael addition-lactonization pathway over a concerted [4+2] hetero-Diels-Alder reaction manifold, the high observed diastereoselectivity in these processes may arise due to reversible Michael addition, followed by an irreversible lactonization process occurring preferentially through one diastereoisomer.
    • Using the assumption of a stepwise Michael addition-lactonization pathway over a concerted [4+2] hetero-Diels-Alder reaction manifold, the high observed diastereoselectivity in these processes may arise due to reversible Michael addition, followed by an irreversible lactonization process occurring preferentially through one diastereoisomer.
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    • For a recent computational investigation of intermolecular Michael reactions see: Kwan, E. E.; Evans, D. A. Org. Lett. 2010, 12, 5124-5127
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    • Kwan, E.E.1    Evans, D.A.2


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.