Letter Cite This: Org. Lett. 2018, 20, 5709−5713
pubs.acs.org/OrgLett
Nickel/Copper Dual Catalysis for Sequential Nazarov Cyclization/ Decarboxylative Aldol Reaction Heyi Zhang and Zhan Lu* Department of Chemistry, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China
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ABSTRACT: A nickel/copper cocatalyzed sequential Nazarov cyclization/decarboxylative aldol reaction is reported. Various βhydroxycyclopentenones containing three contiguous stereocenters were prepared in good yields with high diastereoselectivities. A gram-scale reaction and further derivatizations were easily achieved to highlight the synthetic utility of this transformation. Preliminary attempts for sequential asymmetric transformation were also conducted.
T
methane. These protocols not only provided convenient synthetic approaches but also expanded the applications of the sequential Nazarov reaction. Thus, the development of sequential Nazarov cyclizations/further functionalizations with other electrophiles is still highly attractive to achieve novel trapping processes. The decarboxylative aldol reaction has attracted considerable interest over the years because it has emerged as a powerful tool for the formation of new carbon−carbon bonds.7 A general model of catalytic decarboxylative aldol reactions was conducted by using β-carbonyl acids and aldehydes to afford various β-hydroxycarbonyls (Scheme 1b). To date, to the best of our knowledge, creating compounds with three contiguous stereocenters through a catalytic decarboxylative aldol reaction has not been explored. Based on our recent works on sequential Nazarov cyclization/decarboxylation8 (Scheme 1c) and electrophilic fluorination,4d we envisaged that aldehyde, a versatile electrophile, could participate in sequential Nazarov cyclization/decarboxylative functionalization. Herein, we report a nickel/copper cocatalyzed sequential Nazarov cyclization/decarboxylative aldol reaction of α-tertbutyl ester divinyl ketones with aldehydes to deliver various βhydroxycyclopentenones with three contiguous stereocenters and good to excellent diastereoselectivities (Scheme 1c).9 We initially investigated the catalytic sequential Nazarov cyclization/decarboxylative aldol reaction of α-tert-butyl ester divinyl ketone 1a with 4-nitrobenzaldehyde 2a (Table 1). Under the conditions using 10 mol % of Ni(ClO4)2·6H2O and 12 mol % of oxazoline iminopyridine (OIP) L1 at 100 °C for 12 h in chlorobenzene, the reaction unfortunately did not provide the desired aldol product, and the major byproduct was from Nazarov cyclization/decarboxylation8 of 1a (Table 1,
he catalytic Nazarov reaction has received tremendous attention in the field of organic synthesis for its ability to form functionalized five-membered carbocycles, which are prevalent in numerous natural products.1 It is well-known that the Nazarov reaction of α-ester divinyl ketones2 could generate cyclopentadienolate intermediates which could be captured by other electrophiles, other than protons (Scheme 1a). However, Scheme 1. Sequential Nazarov Cyclization/Electrophilic Reactions and Decarboxylative Aldol Reactions
to the best of our knowledge, there are only a few examples of this sequential Nazarov cyclization/electrophilic reaction with different electrophiles, including nitrostyrenes for Michael addition,3 NFSI for electrophilic fluorinations,4 and alkynes for Conia-ene reaction.5 Recently, the concept of a dual nucleophilic/electrophilic trapping Nazarov reaction has been established by West and co-workers6 by employing an added external electrophile, such as oxygen, bromine, or diiodo© 2018 American Chemical Society
Received: July 30, 2018 Published: August 30, 2018 5709
DOI: 10.1021/acs.orglett.8b02426 Org. Lett. 2018, 20, 5709−5713
Letter
Organic Letters Table 1. Optimization of Reaction Conditionsa
entry
L
3a/4ab (%)
c
L1 L1 L1 L2 L3 L4 L5 L6 L7 L1
