A major driving force for the intriguing developments in the field of total synthesis over the past century is the proficiency with which biological systems transform simple starting materials into complex molecular frameworks. Although necessary issues such as selectivity and synthetic efficiency to construct intricate biological structures can be addressed nowadays to a high degree, new aspects such as diversity and operational efficiency are becoming more important, because of the demand for making complex molecular architectures by effective and simple methodologies.[1] In this respect, catalytic cascade reactions involving two or more selective transformations in one pot are emerging as an attractive tool to overcome the operational limitations associated with traditional "Stop-and-Go" synthesis. [2] Organocatalysis has been shown to be a powerful tool for forming multiple stereocenters in a one-pot protocol by employing either a single catalyst [3a-k] or a combination of catalysts.[3i-l] We became interested in the 4,5-disubstituted isoxazoline-N-oxide motif, since it has the potential to serve as an important building block for diversity orientated total synthesis. Several approaches to isoxazoline-N-oxides are present in the literature either in a racemic fashion, [4] starting from enantiomerically pure compounds, [5] or by employing stoichiometric amounts of a chiral reagent.[6] We envisioned that 4,5-disubstituted isoxazoline-N-oxides having up to three stereocenters could be obtained through a highly stereoselective one-pot procedure using simple and commercially available starting materials in combination with one or two organocatalysts (Scheme 1).Herein, we report a new enantio-and diastereoselective one-pot protocol to access 4,5-disubstituted isoxazoline-Noxides, as well as demonstrate the use of this protocol for the de novo synthesis of b,g-dihydroxylated and b,g,d-trihydroxylated a-amino acid derivatives, phytosphingosines, and amino sugars.Recently, our group reported an efficient and highly enantioselective procedure for the formation of optically active a-bromo aldehydes. [7a,b] Encouraged by the size and leaving group ability of the bromine, we evaluated the possibility of an in situ entrapment, thereby, generating a new class of chiral 1,2-dielectrophiles to participate in multiple-bond-forming cascade sequences. To our delight, the chirality stored within this a-carbonyl sp 3 -carbon center, formed by the direct a-bromination of aldehydes 1 by the electrophilic bromination reagent 2 catalyzed by the TMSprotected diaryl-prolinol 3, is fully exploited by a basepromoted face-selective Henry addition of nitroacetates and subsequent stereospecific O-alkylation, furnishing the enantio-and diastereoselective synthesis of 4,5-disubstituted isoxazoline-N-oxides 4 in one pot (Table 1). The generality of this one-pot, three-step sequence was explored and the results are outlined in Table 1. It appears that b-branched aldehydes 1 a-c provided the 4,5-disubstituted isoxazoline-Noxides 4 a-c as s...