Squarate esters

A further example of the utility of the cyclobuta[ >]chroman system in synthesis (see 6.4.1.3) is provided by the conversion of the cyclobutenedione derivatives (19) into substituted xanthones. Compounds (19) are obtained in high yield from salicylaldehydes and squarate esters and their reaction with alkenyl, aryl and heteroaryl li compounds is both facile and high yielding <96JA12473>. 

A domino process based on the twofold addition of alkenyl anions to a squarate ester was used by Paquette and coworkers [96] for the total synthesis of the triqui-nane sesquiterpene hypnophilin (4-284). The three-component reaction of 4-281,4-282 and vinyl lithium gave primarily the trans- and cis-adducts A and B, which furnished D either by an electrocyclic ring opening/ring closure via C or a dianionic oxy-Cope rearrangement (Scheme 4.60). Further transformations led to E and F, which resulted in the formation of 4-283 on treatment with acid. 

Polycycle Construction from Squarate Esters with Concomitant Elimination 5,6,7,7a,8,8a-Hexahydro-3a-hydroxy-2,3-diisopropoxy-8a-methylcyclopent[ajinden-1(3aH)-one. 

Linkers. Linkers mainly affect the attachment and detachment steps. Figure 7.7 gives data for the Stille reaction 18 with various chemical linkers. The characteristic carbonyl bands of the squarate moiety at 1780 and 1750 cm, and those of the ester or amide linkage bonds, allow facile monitoring... 

Methanol-0-4 methyl nitrite, and dimethyl disulfide have been examined as potential chemical probes for distinguishing between alkoxides and enolates in the gas phase.171 Methanol-0-d proved to be unsuitable and methyl nitrite reacts too slowly in contrast, the reactive ambident behaviour of dimethyl disulfide results in elimination across the C—S bond on reaction with alkoxides ( hard bases ) and attack at sulfur by enolates ( soft bases ). This probe has been applied to investigation of the anionic oxy-Cope rearrangement. The dianionic oxy-Cope rearrangement is a key step in a squarate ester cascade involving stereoinduced introduction of two alkenyllithium reagents cis to each other.172... 

Benzoquinones (13, 284). Full details of the use of a dialkyl squarate for a regioselective route to highly substituted benzoquinones are now available. The report includes a note of caution These esters show allerginicity comparable to that of the active principal of poison ivy.1... 

PREPARATION OP POLYQUINANES BY DOUBLE ADDITION OF VINYL ANIONS TO SQUARATE ESTERS 4,S,6,6a-TETRAHYDRO-3a-HYDROXY-2,3-DIISOPROPOXY-4,6a-DIMETHYL-1(3aH)-PENTALENONE... 

Twofold addition of the same or different vinyl anions to squarate esters leads to polyquinane products.4 The principal pathway involves trans-1,2-addition of the organometallic reagent to generate a cyclobutene dialkoxide such as 1. Ring strain and electrostatic factors promote the rapid conrotatory opening of 1 in that sense... 

The most dramatic synthetic achievement with cyclobutenediones is the synthesis of deltic acid derivatives. As illustrated below, photolysis43 of diethyl squarate (16 d) yielded, among other products, diethyl debate (21). The bis-trimethylsilyl ester (16 e) of squaric acid similarly furnished a deltate ester which was successfully hydrolysed to deltic acid itself (22), the lowest member of the series of oxocarbon acids48). 

Paquette, L. A. Feng Geng, F. A highly abbreviated synthesis of pentalenene by means of the squarate ester cascade, Org. Lett. 2002, 4, 4547-4549. 

Paquette, L. A. Cascade rearrangements following twofold addition of alkenyl anions to squarate esters. Eur. J. Org. Chem. 1998, 1709-... 

Hayashi, K.-L, Shinada, T., Sakaguchi, K., Horikawa, M., and Ohfune, Y., Olefination of dialkyl squarates by Wittig and Homer-Emmons reactions. A facile synthesis of 3,4-dioxo-l-cyclobutene-l-acetic acid esters. Tetrahedron Lett., 38, 7091, 1997. 

An unusual synthesis of ( )-septicine (866) from dimethyl squarate (878) exploits rearrangement of a 4-(l-pyrrolo)cyclobutenone 879 to the indolizine-5,8-dione 880, presumably via a ketene intermediate formed by electrocyclic ring opening of 879 (Scheme 113) (584). Partial reduction of 880 yielded the 4-hydroxypyridone 881, the triflate ester of which was deoxygenated with a palladium(II)-formic acid system to yield the l,2,3,5-tetrahyi oindolizin-5-one 882. Mild reduction with aluminum hydride completed the synthesis of ( )-866 in an excellent overall yield of 27% from 878. 

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