Enol carbamates, asymmetric

Z)-awh-4-Hydroxy-l-aIkenyl carbamates 363, when subjected to substrate-directed, vanadyl-catalysed epoxidation , lead to diastereomerically pure epoxides of type 364 (equation 99)247,252,269 qqjggg epoxides are highly reactive in the presence of Lewis or Brpnsted acids to form -hydroxylactol ethers 366 in some cases the intermediate lactol carbamates 365 could be isolated . However, most epoxides 364 survive purification by silica gel chromatography . The asymmetric homoaldol reaction, coupled with directed epoxidation, and solvolysis rapidly leads to high stereochemical complexity. Some examples are collected in equation 99. The furanosides 368 and 370, readily available from (/f)-0-benzyl lactaldehyde via the corresponding enol carbamates 367 and 369, respectively, have been employed in a short synthesis of the key intermediates of the Kinoshita rifamycin S synthesis . 1,5-Dienyl carbamates such as 371, obtained from 2-substituted enals, provide a facile access to branched carbohydrate analogues . 

Monodentate phosphoramidites, in particular (9) and its octahydro analogue, are found to be excellent ligands for the rhodium-catalysed asymmetric hydrogenation of aromatic enol acetates, enol carbamates, and 2-dienol carbamates with up to 98%... 

The Merck group has applied the electrophilic amination using lithium terf-butyl N-(tosyloxy)carbamate 9a to the chiral amide derived from (lS,2/ )-cw-amino-indanol [10] (Scheme 4). Treatment of 10 with n-Buli in THF at -78 °C gave the lithium enolate which was reacted with CuCN. The resulting amide cuprate was allowed to react with 9a. The authors found that a single diastereomer of a-Boc-protected amino amide 11 was formed. The sense of asymmetric induction observed was consistent with preferential approach of 9a from the least hindered face of the enolate. The removal of the chiral auxiliary with refluxing 6N HC1 afforded a-amino acids 12 in good yields and optical purities. 

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). 

A simple application is the asymmetric alkylation of carbamates 155 of cyclic amines. Removal of one of the diastereotopic protons from 155 gives a more stable sparteine chelate 156. This is not an enolate but has a C-Li bond stabilised by coordination to the carbonyl group. Alkylation occurs with retention of configuration to give, after hydrolysis, one enantiomer of the secondary alcohol28 158. 

Hydrogenation. The phosphepin ligands 1 and 2, constituting with Rh and Pd respectively, mediate asymmetric hydrogenation of enol carbamates and cyclic sulfamidates. ... 

Allylic substitutions. The catalyt preparation of (V-protected allylic amio cyclic carbamates. Asymmetric a-allj ried out by treating the enamines d (Ph3P)4Pd and subsequent hydrolysis. 1 bonates to l-allyl-2(l//)-pyrimidinonei peptides through ester enolate Claisci set. l-Arylprop-2-enols are suitable fa allyl ether cleavage treatment with a < suffices. 

A 1-benzyl analogue of the preceeding structure was obtained by way of an asymmetric Pictet-Spengler ring closure of the chiral carbamate shown (a derivative of (-)-8-phenylmenthol) with an enol methyl ether of... 

In the search for new ligands for asymmetric catalysis Ben L. Feringa and coworkers developed the synthesis of chiral monodentate phosphoramidites (PipPhos) (Figure 3.20) which were excellent ligands for asymmetric hydrogenation of aromatic enol acetates, and enol carbamates with high ee values up to 98%. 

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