Barton’s base

As expected from a Barton s base (2), the guanidine skeleton can be widely and easily modified to a chiral base by introducing chirality into the molecule, in which five chiral centres can be theoretically incorporated in the three nitrogen atoms, indicating that the TMG (1) participating organic reactions could be theoretically expanded to asymmetric... 

Figure 4.1 Structures of TMG (1), Barton s bases (2) and bicyclic guanidines 3...

There are many reports on the synthetic uses of TMG (1) and its analogues such as Barton s base (2). In this section, their synthetic roles in organic synthesis will be discussed according to their tentative classification into three categories [addition (catalytic reaction), substimtion (stoichiometric reaction) and others] from the view points of a landmark for guanidine mediated asymmetric synthesis. 

Alkylative esterification of carboxylic acids with alkyl halides are effected by action with TMG (1) [65]. An ester is given by the TMG (1) mediated reaction of y-hydroxy-a,p-unsaturated carboxylic acid with methyl iodide without lactone formation after isomerization [65a]. Barton s base effectively works in the alkylation of sterically hindered carboxylic acid [3]. Ethanolysis of the acetate of tertiary alcohol occurred easily in 86% yield in the presence of BTMG (2) [66] (Scheme 4.24). 

Barton s bases are used for the formation of diaryl ether by SnAt reactions [73]. In the comparison of several bases BTMG (2) was found to be an excellent and mild alternative for promoting SnAt reactions [73a] (Table 4.11). 

The intramolecular Michael addition reaction of ketone enolate to p-alkoxyacrylate proceeded selectively (in a ratio of 5.9 1) with Barton s base (5) to give tetrahydrofuran 36 [8]. In a model smdy, LDA was much less effective than Barton s base (28 5% versus 96% yield). The diester 36 was converted into 38, which corresponds to the A-D ring system for lactonamycin (39) (Scheme 7.6). 

Corey and Kania reported an enantioselective Claisen rearrangement reaction of macrocychc lactone for the synthesis of (-l-)-dollabellatrienone (56) [13], Reaction of the lactone 53 with chiral (5,5)-diazaborolidine L2BBr 54 and Barton s base (6) resulted in Claisen rearrangement to give carboxylic acid 55 in 86% yield with >98% ee (diastereos-electivity >98 2) (Scheme 7.10). In this reaction, rapid deprotonation by sterically hindered guanidine base is the key to suppress side reactions. 

Wipf, P. and Lynch, S.M. (2003) Synthesis of highly oxygenated dinaphthyl ethers via SNAr reactions promoted by Barton s base. Organic Letters, 5, 1155-1158. 

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