Amines, cyclic aldehydes, synthesis

As shown in the table, chiral substrale.s, amines, or aldehydes are employed in synthesis. Cyclic derivatives can also be obtained according to the reaction schemes reported in Sec. C.4. 

With the aim of developing new analogues of the cyclic AMP phosphodiesterase inhibitor lixazinone (554), the synthesis of agents 553 and 555-557 was undertaken (Scheme 167) (88JMC2136). Thus, all possible 1,2-related N-r-Boc aldehydes 551 were prepared by directed metalation on isomers 549, with the exception of that which required the use of a metal-halogen exchange reaction on the bromo precursor 550 (attempts to metalate 4-TMS-3-N-f-Boc pyridine proved inefficient). As exemplified for one particular isomer, conversion of 551 into 552 by reductive amination... 

The silatropic ene pathway, that is, direct silyl transfer from an silyl enol ether to an aldehyde, may be involved as a possible mechanism in the Mukaiyama aldol-type reaction. Indeed, ab initio calculations show that the silatropic ene pathway involving the cyclic (boat and chair) transition states for the BH3-promoted aldol reaction of the trihydrosilyl enol ether derived from acetaldehyde with formaldehyde is favored [60], Recently, we have reported the possible intervention of a silatropic ene pathway in the catalytic asymmetric aldol-type reaction of silyl enol ethers of thioesters [61 ]. Chlorine- and amine-containing products thus obtained are useful intermediates for the synthesis of carnitine and GABOB (Scheme 8C.26) [62],... 

The formylation of phenols with the electron-rich olefin to give imidazolidin-2-yl-phenols is very selective and avoids mixtures of o- and p-isomers which are frequently obtained by methods commonly employed for the synthesis of phenolaldehydes. Para substitution of the cyclic aminal group in the phenol is preferred. If the p-position is blocked or sterically hindered, the reaction proceeds via the ortho- aminals to salicylaldehydes. Incorporation of more than one aldehyde group in the benzene nucleus is often achieved with hydroxy- and aminophenols. 

In another application, PEG-bound a-aminoaldehydes served as a starting point for the combinatorial synthesis of polyamines [154], Reductive amination with an amine of type 5, followed by alkylation of the formed secondary amine (via reductive amination) and cleavage of the cyclic aminal yielded the starting aldehyde for the next cycle. 

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