Science of Synthesis

Collier, S. J., Science of Synthesis, (2007) 20, 702.

Di-tert-butyl dicarbonate, otherwise known as di-tert-butyl pyrocarbonate or tert-butoxycarbonyl anhydride, is most commonly used as a tert-butoxycarbonylation reagent for heteroatoms, particularly with amines or alcohols (giving tert-butyl carbamates or carbonates, respectively). In such products the newly formed function often plays the role of a protecting group.[‌260‌,‌261‌] However, under certain conditions, di-tert-butyl dicarbonate also reacts with carbon nucleophiles giving net addition of a tert-butyl ester group. In the simplest example a carbanion nucleophile reacts with the dicarbonate to give a substituted ester with loss of carbon dioxide and tert-butyl alcohol. Both alkylmagnesium halides[‌262‌] and organolithium[‌263‌] nucleophiles prove effective; so that tert-butyl pent-4-enoate (‌62‌), for example, is obtained, albeit in modest yield, by the interaction of the reagent and but-3-enylmagnesium bromide (‌Scheme 25‌).[‌262‌] Similarly, tert-butyl (2-methylphenyl)carbamates ‌63‌ can be deprotonated with sec-butyllithium (when R1 = H), or tert-butyllithium (when R1 = Cl) and the dianions generated may then be alkoxycarbonylated to afford tert-butyl {2-[(tert-butoxycarbonyl)amino]phenyl}acetates ‌64‌ (‌Scheme 25‌).[‌262‌] Chiral tert-butyl esters can also be prepared from chiral benzyl thiocarbamates and tert-butyl dicarbonate using N,N,N′,N′-tetramethylethylenediamine-stabilized lithium derivatives.[‌156‌] Less reactive carbon nucleophiles such as ester enolates[‌264‌] and amide enolates[‌265‌,‌266‌] can also be used in similar reactions, and with amide enolates both N- and C-oxycarbonylation may be observed. Thus, the tetracyclic indole ‌65‌, when reacted with 3 equivalents of sodium hydride, and then with di-tert-butyl dicarbonate, affords the ester ‌66‌, in which the indolic nitrogen atom is also tert-butoxycarbonylated (‌Scheme 25‌).[‌265‌] However, when the sodium hydride is replaced by 4-(dimethylamino)pyridine only the two nitrogen functions of the tetracyclic indole ‌65‌ undergo this reaction.[‌265‌] In a related reaction diethyl dicarbonate undergoes a titanium-mediated reaction with ester-derived silyl enol ethers to give malonate diesters.[‌267‌]

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