Acyclic stereogenic centers, control

Apart from cyclic or acyclic transition state geometry further distinctions of diastereoselec-tion have to be made with respect to the way in which the chiral center is attached to the reactive site. The term auxiliary control is used if a chiral subunit, e.g., an alcohol or an amine, is fixed covalently to the unsaturated substrate and then removed by bond cleavage after the addition. In contrast, if the stereogenic center remains part of the molecule after the addition, the term substrate control is applied (these definitions are given in Section A. 1.). 

The preceding discussion has demonstrated how the specificity inherent in the cyclic transition state may be used to fix structural elements in Cope products, establishing double bonds and other functional groups in definite relationships in a variety of acyclic and cyclic skeletons. This final section treats the remarkable consequences of cyclic transition states in stereochemical control, including alkene configuration and both relative and al olute configuration at stereogenic centers. ... 

An investigation into the preparation of n = 2 telomers was successful in showing that the ACT strategy with templates of type 14 is a viable means for producing isotactic 1,3 stereocenters as exemplified in the production of 16 (n=2) (Scheme 8-5). The oxazolidine unit has documented success as a stereocontrol element in acyclic radical reactions [35-37], and thus its incorporation into this template provides, in effect, a chiral auxiliary to control the configuration of new stereogenic centers formed in the sequence. 

The diastereoselectivity obtained for reactions on a ring makes it possible to use a cyclic molecule to fix a stereocenter in an acyclic target, as seen in the formation of 154 from 152. Diol 152 had been prepared by a multistep sequence, with control of the stereocenters. When this diol was subjected to oxidation with MCPBA lactone 153 was formed. Subsequent ring opening with methanolic potassium carbonate led to the acyclic fragment 154, with six contiguous stereogenic centers whose stereochemistry had been fixed in the cyclic... 

Also, it was demonstrated that acyclic radicals can react with high stereoselectivity [45]. In order for the reactions to be stereoselective, the radicals have to adopt preferred conformations where the two faces of the prochiral radical centers are shielded to different extents by the stereogenic centers. Giese and coworkers [49] demonstrated with the help of Electron Spin Resonance studies that ester-substituted radicals with stereogenic centers in (3-positions adopt preferred conformations that minimize allylic strain [49] (shown below). In these conformations, large (L) and medium sized substituents (M) shield the two faces. The attacks come preferentially from the less shielded sides of the radicals. Stereoselectivity, because of A-strain conformation, is not limited to ester-substituted radicals [50]. The strains and steric control in reactions of radicals with alkenes can be illustrated as follows [50] ... 

Introduction. (15,65)-2-(Phenylsulfonyl)-7-oxabicyclo[4.1.0] hept-2-ene (PhS02CHD-epoxide) is a versatile chiral scaffold for the elaboration of six-membered rings or six-carbon acyclic fragments with one to four chiral centers. The flexibility to control the relative and absolute stereochemistry of every stereogenic center makes PhS02CHD-epoxide as valuable tool in the synthesis of natural products and unnatural analogs. 

The diastereoselective construction of polycyclic structures such as linear triquinanes has been explored by the Malaciia group from acychc or macrocyclic precursors. Based on an acyclic (bromomethyl)dimethylsilyl precursor, the outcome of the sequence leading to the triquinane is remarkable five new C-C bonds, two contiguous quaternary centers, and four new stereogenic centers can be formed with almost complete control (eq 17). 3... 

This synthesis illustrates one strategy for the preparation of acyclic molecules containing multiple stereogenic centers — use cyclic structures to control stereochemistry and then liberate the acyclic structure. The strategy is not unlike several of the Cecropia juvenile hormone syntheses we examined, where stereoselective olefin synthesis was the goal. Whereas three pieces are ultimately assembled, the synthesis of the central fragment is linear and there was a price to pay for this approach. It is long. 

Bridged bicyclo[3.2.1]octenes and bicyclo[3.3.1]nonenes are obtained when this reaction is carried out in an intramolecular mode. The nucleophiles are generated in appropriately functionalized side chains at C5 of the tricarbonyl( n -cyclohexadiene)iron complexes. Acyclic (Ti -l,3-butadiene)Fe(CO)3 complexes with fimctionalized side chains at the terminal position of the diene ligands provide fused bicyclo[3.3.0]octanones and bicyclo[4.3.0]nonanones (Scheme 4-121). Up to four new stereogenic centers are established in a controlled way in the course of this reaction. ... 

Kishi described an elegant example of a bromoetherification reaction for effecting acyclic stereocontrol (Scheme 9.29) [162], In this case, bromide 219 was isolated as a single isomer in 57 % yield upon treatment of diolefin 218 with NBS. The presence of an allylic stereogenic center with two substituents of considerably different steric demands (Me versus 4-(3-methylbut-l-ene)) in 218 leads to a system in which interactions play a dominant role in controlling the stereochemical outcome of the cyclization. These synthetic efforts leading to intermediate 219 culminated in the total synthesis of the polyether antibiotic monensin (220) [163]. 

---