Synthesis proton sponges

With the reaction between [arachno-6-SB9H11], PhPCl2, and proton sponge a high yield synthesis for the phos-phathiaborane [OTV/o-lO-PhT.lO-SPBgHg] was reported.133... 

Majetich reports a general intramolecular Lewis acid allylation protocol for the synthesis of bicy-clo[5.4.0]undecen-3-ones (168) and bicyclo[4.4.0]decen-3-ones (170), which are 1,6-addition products (Scheme 27). The same precursors, (167) and (169), when submitted to the fluoride ion cyclization protocol, also afford 1,2- and 1,4-addition products.73 Typically, ethylaluminum dichloride, a proton sponge Lewis acid, is used in order to minimize adventitious protonic desilylation. Other 0,y-unsatu-rated silanes also undergo similar intramolecular Lewis acid catalyzed additions for example, the si-lylpropargylic enones (171) undergo intramolecular cyclization to the allenylspiro system (172).74... 

Under optimized reaction conditions this two step synthesis for asymmetric preparation of /1-lactams is performed as follows. First, the organocatalyst 46 is added as a shuttle base to a solution of the acid chloride, 47, and the proton sponge , 49, at low temperature. Within a few minutes the soluble ketene and the hydrochloride salt, 49 HC1, as a white precipitate, are formed. Subsequently, the imino ester 44 is added to this solution at —78 °C, which results in the asymmetric formation of the /Mactam. Thus, the alkaloid 46 acts both as a dehydrohalogena-tion agent and as an organocatalyst for subsequent lactam formation [49, 52]. 

Scheme 16. Synthesis of 1.8-bis(dimethylamino)-2-(4-methoxyphenyl)naphthalene from proton sponge (1.8-bis(dimethylamino)naphthalene. (a) N-bromosuccinimide. THFand -78 °C. (b) Pd(OAc)2. PPha. NaC03H and mixture of n-propanol with water. Reflux 12h [92. ...

During a synthesis of the polyether antibiotic X-206. Evans and co-workers503 accomplished the protection of a hindered secondary alcohol with benzyl bro momethyl ether (BOMBr) in the presence of proton sponge [l,8-bis(dimethyl-amino )naphthalene], without racemising the two stereogenic centres adjacent to the ketone function [Scheme 4.281],... 

Some kinds of proton sponges are best prepared starting from accessible l,8-bis(methyl-amino)naphthalene (4) or its derivatives2,40-43. For example, the optimal synthesis of l,8-bis(dimethylamino)-4,5-dinitronaphthalene (51) consists in methylation of compound 50, which in turn can be prepared from perimidone 49 (Scheme 2)44,45. 

Recently, there has been research activity in the area of chiral proton sponges, in particular, those containing nitrogens with pairs of different substituents. The molecular asymmetry of such sponges, especially well pronounced in the cationic forms, arises as a result of the arrangement of bulkier functions at opposite sides of the naphthalene ring plane. Synthesis of these compounds, e.g. 5248, 5333 and 5449, is also achieved via alkylation of the corresponding A,A -dialkyl- or A,A,A -trialkyl-l,8-diaminonaphthalenes (Scheme 3). 

TABLE 2. Synthesis of proton sponges by exhaustive N-alkylation of the corresponding 1,8-diaminonaphthalenes... 

Proton sponge halides play an important role in organometallic synthesis of many valuable derivatives of this series. This can be illustrated by Scheme 36, showing the... 

The main area of application of proton sponges, primarily compound 1, is in organic synthesis as strong but low-nucleophilicity bases. Besides, the proton sponges and their salts are a favourite model of physical chemists and theoreticians for investigating hydrogen bonds and a number of other interesting phenomena. 

Phosgene-free synthesis of isocyanates directly from carboxylic acids and diphenylphos-phonic azide (PhO)2P(0)N3 in combination with proton sponge 1 followed by Curtius rearrangement has been also described222. 

In conjunction with proton sponge, the activated phosphate 256 turned out to be an effective reagent in the direct synthesis of peptides and branched amides from carboxylic acids (equation 21). In this process, diamine 1 surpassed in its efficiency for such bases as triethylamine, V,iV-dimethylaniline, 2,6-lutidine and Hiinig bases225. 

Dehydrochlorination of acid chlorides of type RCH2COCI by proton sponge 1 in order to produce monoketenes is not directly realized232,233, but proceeds in the presence of benzoylquinine (BQ) as a shuttle base . The in situ generated ketenes were used further for the synthesis of optically active /3-lactams 258 (Scheme 48). Additionally, a method providing fraws-isomers of 258 with the help of diamine 1 has recently been elaborated234. 

The 1/BQ system alone or with Lewis acid additives was also employed for asymmetric catalysis in the synthesis of /3-amino acids235. During an elaboration of the tandem catalytic asymmetric chlorination/esterification process, Lectka and coworkers found that proton sponge 1 competes with ketenes in the reaction with halogenating agents, such... 

Until recently, there had been no reports on the application of 2,7-disubstituted proton sponges like 44 and 65 in organic synthesis. Their advantage in comparison with compound 1 is their increased basicity coupled with their extremely low C-nucleophilicity. Lately, the 2,7-dimethoxy compound 44 was used for deprotonation of salts of other proton sponges, in particular of 88 and 89 (Section n.C.2)67. In another example, when the proton sponge 1 participated in the azo-coupling reaction, the addition of base 44 increased the degree of interaction (equation 30)56. The yield of the azo compound 269 was nearly quantitative, and the base 44 could be easily recovered. 

Recently, proton sponge was used as a fluorescent indicator for protons257. By incorporating the residue of 1 into the structure of the known fluorophore, 4-aminonaphthalimide, the researchers designed the fluorescent switch 274, whose synthesis was conducted in 5 steps with overall yield ca 10%. 

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