Mapping the Chemical Reactivity of Polyquinanes Produced by 2-fold Addition of Vinyl Anions to Squarate Esters. A Bicyclic Case Study

Abstract

A highly oxygenated diquinane representative of the product class obtained from the condensation of squarate esters with a pair of vinyl anions has been subjected to a battery of chemical reactions for the purpose of achieving utilitarian functional group transformations. Reduction with lithium aluminum hydride proceeds predominantly, but not exclusively, by 1,4-reduction. Dehydration of the γ-hydroxy-α,β-(bisalkoxy)cyclopentenone to extend conjugation into the B ring was achieved via chlorination and subsequent removal of HCl. Access to dienone 12 in this manner has opened the door to reductive removal of the γ-hydroxyl substituent, to angular methylation, and to allied chemical changes. The global results disclose that the previously unknown functional group array present in 5 and its congeners is amenable to convenient modification, thereby providing the backdrop for more advanced annulation and structural elaboration. The prospects for utilization of the several new compound types as serviceable building blocks are considered to be numerous.

Cascade Rearrangements Following Twofold Addition of Alkenyl Anions to Squarate Esters

“…Selected examples of chemical transformhad to materialize from the two possible diastereomeric cis adducts. This dominance of one mode of addition to ations that have been performed on 164 [48] can be found in Scheme 26 [49] . Noteworthy is the ability to remove one the squarate ester is not shared by 150 which delivers a mixture of 153 and 156 (1.1:1).…”

Total Synthesis of Spiromamakone A and Structure Revision of Spiropreussione A

“…6, 193.4, 192.7, 192.6, 170.99, 170.98, 146.50, 146.49, 146.45, 134.0, 127.59, 127.54, 127.53, 127.47, 120.75, 120.72, 120.70, 120.66, 119.84, 119.78, 113.19, 113.16, 109.9, 109.78, 109.75, 109.71, 108.93, 108.89, 100.9, 100.8, 78.7, 78.6, 76.51, 76.48, 67.1, 67.0, 64.60, 64.57, 54.0, 53.9, 40.3, 40.2, 26.4, 26.3, 25.92, 25.90, 25.35, 25.32, 21.15, 21.13, 21.04, 21.02, 18.08, 18.06, −4.48, −4.51, −4.52, −4.60. LRMS (EI) m/z (relative intensity): 582 [M] + (0.9), 567 (5), 525 (23) (1S,3′S,4′S)-and (1R,3′S,4′S)-4′-((tert-Butyldimethylsilyl)oxy)-3isopropoxy-3′-(methoxymethoxy)dispiro[cyclopentane-1,2′-cyclopentane-1′,2′′-naphtho[1,8-de][1,3]dioxin]-3-ene-2,5-diones (18a and 18b). To a stirred solution of 16a•b (3.91 g, 6.71 mmol) in anhydrous EtOAc (34 mL) was added orthoperiodic acid (2.29 g, 10.0 mmol) at room temperature.…”

“…The final step was the reductive removal of the isopropoxy group from 20a – b . Lithium aluminum hydride can reduce 4-hydroxy or acetoxy-3-alkoxy-2-cyclopenten-1-one to 4-hydroxycyclopentanone, , which is transformed into 4-cyclopentene-1,3-dione by a two-step oxidation through 1,3-cyclopentanedione. The reduction proceeds through formation of aluminate at C-4, intramolecular 1,4-addition of hydride, elimination of the alkoxy group from C-3, and a second 1,4-reduction to give 4-hydroxycyclo­pentanone after hydrolytic workup.…”

Theoretical study of the molecular mechanism of the domino pathways for squarate ester sequential reactions

“…This type of chemical reaction has been systematically studied by Paquette and co-workers [10][11][12] and can be considered as a useful synthetic transformation in organic chemistry. 13,14 A schematic representation of the stages of the overall process is presented in Scheme 1.…”

“…Although the sequence of the major steps is known from experimental work, [10][11][12][13][14] there have been no theoretical investigations on the detailed molecular mechanism. As a part of our ongoing research program to study the family of consecutive inter-and intramolecular domino reactions, [15][16][17] in this paper we report on a first theoretical study in which all stationary points related to the co-addition of a chiral alkyl-substituted and an achiral cyclopentenyllithium to a squarate ester were characterized on model compounds having the essential group elements intervening in the chemistry of this system.…”