Spiroacetal amine

The alkylation of metalated imines, hydrazones, 4,5-dihydrooxazoles, 4,5-dihydroisoxazoles, 5,6-dihydro-4/7-1,2-oxazines and 2,5-dialkoxy-3,6-dihydropyrazines (i.e., azaenolates) is a commonly used method in asymmetric synthesis of enantiomerically enriched aldehydes, ketones, spiroacetals, amines, /J-oxo esters, carboxylic acids, lactones, 1,3-amino alcohols, /(-hydroxy ketones and amino acids. 

The spiroacetal morpholine work of Scheme 38 subsequently inspired research on the preparation of a novel family of morpholino-glycosides from sucrose via lead tetraacetate cleavage and reductive amination (Scheme 40). Significantly, the latter work, which was done with the present author, unveiled a completely new structural class of sweeteners, more intense than sucrose but having a similar taste profile. 

Having highlighted the different stereoselective metal-mediated MBFT approaches to reach aza- or oxa-spirocyclic compounds, we now review the different strategies to build, in a step-economical manner, spiroacetal and aminal derivatives. As stated earlier, the last part of this chapter is dedicated to the organometallic stereoselective... 

The main stereoselective MBFTs for the synthesis of spirocyclic acetals or aminals involve the activation of a C-C triple bond to form an intermediate cyclic enol ether. The method disclosed above for the synthesis of a-heteroatom-substituted spirocen-ter (see Section 9.3.3, Scheme 9.18) [34] was next extended by the same authors to the synthesis of spiroacetals. They simply used salicyladehyde as starting aldehyde, but the transformation was not diastereoselective anymore [43]. This problem of stereoselectivity was recently solved by Gong and coworkers, who employed a gold(I)/chiral Brpnsted acid catalysis to do so [44], The chroman spiroacetals were obtained in excellent yields (67-97%) and with high stereoselectivities (up to 95% ee, up to 25 1 dr) (Scheme 9.24). This reaction resulted in the formation of three new single bonds and two stereogenic centers. 

Section 3.5.2), was first communicated in 1996, and has since been published with full discussion and experimental details.This synthesis was presented in some detail in the previous review in this series. The key step was the triple reductive amination of the spiroacetal (+)-744 with... 

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