Enol carbamates deprotection

Another approach for the deprotection of highly functionalized enol carbamates is based on hydroboration (equation 96) . 

The first total synthesis of the intricate Stemona alkaloid (+ /—)-isostemofoline (224) was reported by Kende and coworkers 81) starting from 1,2-hexanediol (225) which was straightforwardly converted to 227 (Scheme 22) 82). Reductive cycUzation with sodium hydrosulfite in refluxing aqueous ethanol, and protection of the unstable pyrrole as tert-butyl carbamate, afforded 228 in five steps with 12% overall )deld. The key bicyclic ketone 231 was assembled by [4 + 3] cycloaddition of pyrrole 228 and diazoester 229 promoted by rhodium octanoate dimer, followed by enol silane deprotection, exo-specific hydrogenation, and nucleophilic decarboxylation (47% overall yield). Sodium methoxide-catalyzed aldol condensation of ketone 231 and furfural provided the Q-j/i-unsaturated ketone 232 whose olefin configuration was established by nOe studies. Allylation of 232 provided a 2.4 1 mixture of ketone 234 and the corresponding allylic enol ether 233, which could be converted to the former via a stereoselective Claisen rearrangement. 

Further alkylation of the lithium (Z)-enolate of 25 with methyl iodide gave 26, introducing the C16 stereocentre (3 1 dr) and completing the carbon backbone. Oxidation at Cl and carbamate formation gave 27 which underwent a chelation-controlled reduction at C17 (30 1 dr). Finally, global deprotection completed the synthesis of discodermolide (1), with an overall yield of 4.3% achieved over 24 steps in the longest linear sequence. 

A concise and practical synthesis of HIV-1 protease inhibitor 2 was developed by Askin and coworkers, using the rigid tricyclic aminoindanol acetonide as a chiral platform.11 The diastereo-selective alkylation of (Z)-lithium enolate of amide 48 with amino epoxide 49 gave intermediate 50 in >90% yield and >98% de (Scheme 24.9). Lithium carbamate salt of 49 presumably activated the epoxide toward electrophilic epoxide opening, and alkylation of the (Z)-enolate occurred from the less hindered (3-face. The amino alcohol was deprotected by treatment with camphorsulfonic acid and gave 2 in good yield. 

The enolate formed in this process then condenses irreversibly with the r -allylpalladium species. At the outset, dimedone and A,A-dimethylbarbituric acid had been more specifically devisedP for the deprotection of allyl carbamates in solution or in solid-phaseP chemistry in which case the enolate species also forms by proton transfer from the (3-dicarbonyl allyl scavenger to the liberated amine but since then it has also been used for the deprotection of allyl carboxylic esters (see Section 2.2.1.1.3).P 1... 

The only asymmetric synthesis of the Nuphar indolizidine to date is due to Barluenga and co-workers (615). Their route to the (5S,8 ,8aS)-( -) enantiomer of 944 commenced with cycloaddition between the proline-derived 2-amino-butadiene 957 and imine 958 (Scheme 125). Hydrolysis of the adduct 959 gave piperidinone 960 in 51% yield and an ee of better than 99%. Once the alcohol and amine groups had been mutually protected as the cyclic carbamate 961, defimctionalization of the ketone was accomplished via an enol triflate. Chain-extension of the deprotected piperidine 962 at the hydroxymethyl substituent afforded 963, which was cyclized to the bicyclic lactam 964 simply by heating in toluene. Reduction with lithium aluminum hydride completed the synthesis of ( - )-944 ([a]n -99°, c 1.3, CH2CI2). 

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