N-Boc-α-amino aldehydes are shown to be excellent partners in cross-benzoin reactions with aliphatic or heteroaromatic aldehydes. The chemoselectivity of the reaction and the facial selectivity on the amino aldehyde allow cross-benzoin products to be obtained in good yields and good diastereomeric ratios. The developed method is utilized as the key step in a concise total synthesis of d-arabino-phytosphingosine.
The effectiveness of utilizing N-Bn-N-Boc-α-amino aldehydes in cross-benzoin reactions with heteroaromatic aldehydes is demonstrated. The reaction is both chemoselective and syn-selective, making it complementary to the anti-selective cross-benzoin reaction of NHBoc-α-amino aldehydes. Good diastereoselectivity is obtained for a variety of amino aldehydes, including nonhindered ones. A Felkin-Anh model can be used to rationalize the observed diastereoselectivity.
An efficient, one-pot and multicomponent synthesis of dialkyl 5,5-dicyano-3-aryl-2-cyclopentene-1,2-dicarboxylates is described. A mixture of a phenacyl bromide, malononitrile, and a dialkyl acetylenedicarboxylate in the presence of triphenylphosphine and triethylamine undergo a smooth addition reaction in absolute ethanol at ambient temperature to afford the highly functionalized cyclopentenes in good to excellent yields.
We report the shortest synthesis of glycosidase inhibitor (+)-hyacinthacine A 1 using a highly chemoselective N-heterocyclic carbene-catalyzed crossbenzoin reaction as well as a furan photooxygenation−amine cyclization strategy. This is the first such cyclization on a furylic alcohol, an unprecedented reaction due to the notorious instability of the formed intermediates. The photooxygenation strategy was eventually incorporated into a three-step one-pot process that formed the requisite pyrrolizidine framework of (+)-hyacinthacine A 1 .(+)-Hyacinthacine A 1 [7 (Figure 1)] is a member of a large class of polyhydroxylated pyrrolizidine and indolizidine structures that act as glycosidase inhibitors. 1 These belong to the broader class of amino sugars, a group of compounds that have found significant use in glycobiology as tools and as frameworks for potential pharmaceuticals. 1,2 Important amino sugars include the various deoxynojirimycin derivatives, 3 Celgosivir, 4 and other neuraminidase inhibitors such as zanamivir. 5 (+)-Hyacinthacine A 1 ( 7) is especially interesting due to its low micromolar range inhibition, making it an important target for further study. 6 It is also one of the more challenging hyacinthacine derivatives to access, highlighting the need to develop more efficient methods for its preparation. 6,7 Previously, in attempting to solve the chemoselectivity issues that plagued cross-benzoin reactions, 8 our group discovered that two aldehydes could be coupled catalytically with Nheterocyclic carbenes (NHCs) when one of the reactants was a protected amino aldehyde. 9,10 The reaction generates an αhydroxy-β-aminoketone [3 (Figure 1)] with good yields and diastereoselectivities. We believed that incorporating a furan ring into this structure would make it more amenable to useful transformations, 11 thereby allowing us to target a variety of natural products. 12−15 The high availability and versatility of furans from biomass emphasize the importance of furthering our understanding of these transformations. 16
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