Methyl chemoselective deprotection

Hydroxylysine (328) was synthesized by chemoselective reaction of (Z)-4-acet-oxy-2-butenyl methyl carbonate (325) with two different nucleophiles first with At,(9-Boc-protected hydroxylamine (326) under neutral conditions and then with methyl (diphenylmethyleneamino)acetate (327) in the presence of BSA[202]. The primary allylic amine 331 is prepared by the highly selective monoallylation of 4,4 -dimethoxybenzhydrylamine (329). Deprotection of the allylated secondary amine 330 with 80% formic acid affords the primary ally-lamine 331. The reaction was applied to the total synthesis of gabaculine 332(203]. 

Elaboration of triol 88b to bryostatin 7 requires chemoselective hydrolysis of the Cl methyl ester in the presence of the C7 and C20 acetates, macrolide formation, installation of the C13 and C21 methyl enoates, and, finally, global deprotection. The sequencing of these transformations is critical, as attempts to introduce the C21 methyl enoate to form the fully functionalized C-ring pyran in advance of macrolide formation resulted in lactonization onto the C23 hydroxyl. In the event, trimethyltin hydroxide promoted hydrolysis [73] of the Cl carboxylate of triol 88b, and subsequent trie thy lsilylation of the C3 and C26 hydroxyls each occurs in a selective fashion, thus providing the seco-acid 89. Yamaguchi macrolacto-nization [39] proceeds uneventfully to provide the macrolide 67 in 66 % yield (Scheme 5.14). 

In addition, iodine snccessfnlly catalyzed the electrophilic snbstitntion reaction of indoles with aldehydes and ketones to bis(indonyl)methanes [225], the deprotection of aromatic acetates [226], esterifications [227], transesterifications [227], the chemoselective thioacetalization of carbon functions [228], the addition of mercaptans to a,P-nnsatnrated carboxylic acids [229], the imino-Diels-Alder reaction [230], the synthesis of iV-Boc protected amines [231], the preparation of alkynyl sngars from D-glycals [232], the preparation of methyl bisnlfate [233], and the synthesis of P-acetamido ketones from aromatic aldehydes, enolizable ketones or ketoesters and acetonitrile [234],... 

A keto group was extensively used in olefinations, providing a convenient access to natural-type oxonine products. Chemoselective formation of silyl enol ether of oxonine 171 (Scheme 34) followed by Wittig olefination, deprotection, and diastereoselective methylation afforded acetate 172 in good yield <2004JA1642>. 

Funk s synthesis in 2004 [28] of perophoramidine (Scheme 3), commenced with a base-catalyzed coupling reactiOTi between indole 19 and 3-bromoindolin-2-one 20. Boc protectiOTi of the resulting lactam 21 followed by reduction of the azido functionality led to transamidation and closure of the resulting carbamate upon the indolenine to deliver the aminal 22. Chemoselective chlorination and protection of the lactam followed by a two-step deprotection and conversion of the resulting alcohol to the azide afforded amide 23. A second transamidation reaction followed by selective methylation gave lactam 24. Treatment of lactam 24 with Meerwein s reagent gave imidate 25, which imderwent a Fukuyama deprotection of the sulfur... 

Reductive Etherifications and Acetal Reductions. Additional applications of triethylsilane in the reduction of C-0 bonds also continue to surface. The Kusanov-Pames dehydrative reduction of hemiacetals and acetals with trifluorosulfonic acid/EtsSiH has proven especially valuable. Under such conditions, 4,6-O-benzyli-dene acetal glucose derivatives can be asymmetrically deprotected to 6-0-benzyl-4-hydroxy derivatives (eq 28) and thioketone derivatives can be converted to syn-2,3-bisaryl (or heteroaryl) di-hydrobenzoxanthins with excellent stereo- and chemoselectivity (eq 29). Triethylsilane is also useful in a number of related acetal reductions, including those used for the formation of C-glycosides. For example, EtsSiH reductively opens 1,3-dioxolan-4-ones to 2-alkoxy carboxylic acids when catalyzed by HCU. Furthermore, functionalized tetrahydrofurans are generated in good yield from 1,2-0-isopropylidenefuranose derivatives with boron trifluoride etherate and EtsSiH (eq 30). These same conditions lead to 1,4- or 1,5-anhydroalditols when applied to methyl furanosides or pyranosides. ... 

Another way of achieving chemoselectivity is the use of catalytic amounts of chemically modified (methylated) /3-cyclodextrins as counterphase transfer agents (203). Such way the deprotection of neat, water insoluble allylic carbonates was achieved (without an organic solvent) with up to 300 times increase in the rate related to the cyclodextrin-free reactions. Furthermore, molecular recognition of the substrates by the cyclodextrin resulted in large differences between the rates of deprotection of the various substrates, for example, phenylbenzene allyl carbonates reacted considerably faster than naphtylmethyl allyl carbonates. 

Lee et al. succeeded in the total synthesis of (—)-amphidinolide E, whose side chain was constructed using ene-yne CM [30]. Alkyne 101 was first reacted with ethylene in the presence of catalyst [Ruj-II to give 102, which was further engaged in situ in a chemoselective CM with 2-methyl-l,4-pentadiene (103) to produce triene 104 in 65% yield along with diene 102 in 19% yield. The isolated diene 102 was recycled and further reacted with 103 in a similar manner to afford triene 104, which was finally converted to sulfone 105. Condensation of sulfone 105 and aldehyde 106 afforded compound 107, which was further elaborated to seco-add 108. Lactonization of 108 followed by deprotection completed the total synthesis of amphidinolide E (Scheme 6.25). 

---