New chiral molybdenum metathesis catalysts : application to the enantioselective preparation of cyclic amines
Author(s)Dolman, Sarah Jennifer, 1977-
Massachusetts Institute of Technology. Dept. of Chemistry.
Richard R. Schrock.
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Optically pure (R)-5,5',6,6',7,7',8,8'-octahydro-1,1'-bi-2-napthol was derivatized with mesityl groups in the 3 and 3' positions to give (R)-MES₂BitetH₂ 1.43. Addition of the di-potassium salt of 1.43 to (Ar[sub]prN)Mo(CHCMe₂Ph)(OTf)₂(DME) yielded [(Ar[sub]prN)Mo((R)-MES₂Bitet)(CHCMe₂Ph)(THF), (R)-1.44a. This material was studied in detail by variable temperature ¹H NMR spectroscopy with and without solvent additives (THF, DMF and MeCN). An X-ray study of (R)-1.44a showed it to crystallize as the THF adduct of an anti-alkylidene, in a distorted trigonal bipyramid. Complex (R)-1.44a was shown to be an active and selective catalyst for olefin metathesis for representative ARCM transformations to form dihydrofurans. CHAPTER 2: The first catalytic asymmetric ring-closing metathesis (ARCM) method for the synthesis of nitrogen-containing heterocycles was developed; this was accomplished via Mo-catalyzed desymmetrization of unsaturated prochiral amines to afford tetrahydropyridines (2.68a-e). The selectivity of this transformation was sensitive to the olefin substitution pattern of the prochiral amine. However, this novel method was also applicable for the formation seven-(2.84), and eight-membered (2.84) rings in high yield, with exceptional enantioselectivity. Importantly, this method remained highly effective when performed without solvent. Several chiral benzoazepines (2.95a-c) were also prepared via Mo- catalyzed ARCM. In these latter cases, the steric size of groups attached to the prochiral carbon was observed to affect both the rate and selectivity of ARCM. Related benzoazocine precursors (2.97 and 2.100) could not be successfully desymmetrized to cyclic amines.(cont.) A prochiral tetraene (2.101) was rapidly transformed into a spirocyclic-benzazepine (2.103) by tandem ARCM/RCM with good enantioselectivity. Carbocyclic amines (2.105a-f) were also efficiently synthesized via ARCM with good enantioselectivity. Several of these enantioselective transformations were equally effective when catalyzed by catalysts prepared in situ. Three new poly(styrene) supported chiral Mo-based catalysts were prepared. Two of the supported complexes were biphenolate-based ((S)-3.75 and (S)-3.76) while the third was binapnatholate-based ((R)-3.77). Additionally, a new support was developed, wherein the Mo-alkylidene could be supported in tandem with polymer generation. Several poly(norbornene) supported catalysts were also prepared, with various cross- linking levels. It was found that the activity and selectivity of these poly(norbornene) supported systems was greatest with low cross-linking levels (8 %), such as for (S)-3.88d. Two more lightly cross-linked poly(norbornene) complexes were prepared with distinct imido groups, (S)-3.89 and (S)-3.90. The ability of these polymer-bound chiral complexes to promote an assortment of asymmetric ring-closing (ARCM) and ring-opening (AROM) metathesis reactions was studied. In many instances, the levels of reactivity and enantioselectivity observed were competitive with the analogous homogeneous catalysts. In all cases, the optically enriched products obtained through the use of the above supported complexes, after simple filtration and removal of the polymeric chiral Mo complexes, were found to contain significantly lower levels of metal impurities ...
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2004.Vita.Includes bibliographical references (leaves 222-230).
DepartmentMassachusetts Institute of Technology. Dept. of Chemistry.
Massachusetts Institute of Technology