Relay Deprotection

Some comprehensive reviews on enzymatic deprotection are given at the end of this chapter and further examples are given in Chapters 3, 6 and 8. 

PCB - p-chkKobenzyl l-(M,AMirnethylanttn -1 (dicyclohexylph08ph(no)blphenyl PBB = p4 romobenzyt o4 ipbenyl)P(Bu )2 

PPhs (2 equiv), DIAD (2 equrv) AcSH (2 equiv), 0 C to rt, 3 h 89% (0.43 mnwl scale) 

The three classes of relay deprotection strategies cited above are the most common but there are many other possibilities as in the rhodium(l)-catalysed isomerisation of a robust allyl ether to a hydrolytically labile enol ether discussed in section 1.2.11. 

---

An example of 3-fold relay deprotection in the second class depends on the selective conversion of a fairly inert p-halobenzyl ether to an activated p-ami-nobenzyl derivative by palladium (0)-catalysed animation.4 The subsequent deprotection is then achieved with Lewis or protic acids. Scheme 1.28 illustrates... 

Another significant application of the concept of relay deprotection comes from a synthesis of the antitumour macrolides Cryptophycins 1 and 8.644 The penultimate step required a mild method for the introduction of the epoxide ring in the side chain [Scheme 4.340]. A variant of a direct method for the conversion of diols to epoxides developed by Kolb and Sharpless645 was cleverly adapted to the case at hand. Thus diol 340.1 was treated with the 4-azido-1 1,1-tri-methoxybutane in the presence of chlorotrimethylsilane to give the cyclic orthoester 340.2, which decomposed under the reaction conditions with loss of Me SiOMe to give the chlorohydrin ester 3403 (inversion). Selective reduction... 

By 1903, Emil Fischer had already appreciated that a proximate nucleophile can accelerate the rate of cleavage of an otherwise unreactive amide. Adaptation of such neighbouring group participation to relay deprotection is easy all that is required is a protecting group with a latent hydroxyl or amino function within easy bonding distance of the amide carbonyl, as illustrated in Scheme 8.27 by the reduction of the o-nitrophenylacetamide 27,1. The theme is capable of extensive variation. For example, 2-((/er/-butyldiphenylsilyloxy)methyl]benz-amides (27.2), 2-(acetoxymethyl)benzamides (273) and 3-methyl-3-(2,4,5-tri-methyl-3,6-dioxo-cycIohexa-l,4-dienyl) butyramides (27.4) all have latent hydroxyl nucleophiles that are released by silyl ether cleavage, ester hydrolysis and quinone reduction, respectively. 

---