Helen's enthusiasm for science is great, and Dan is a great person to talk about science with. I'm also grateful that I gave Helen the cleanest and most organized couch in the group. Shortly after they left the group, I had the opportunity to get to know other people in the group.
I also had the pleasure of working with some great people in my early days of 130 Church with Sheldon Okaka, Prof. I spent a lot of time working with them, talking about science and going to Koreatown with them. John Morgan has also been a good person to talk science with and I enjoyed working with him.
He was a good friend, a keen scientist and I really enjoyed working with him and getting to know his large family. I also want to thank the members of my committee for being part of this journey, including Prof.
Introduction to Olefin Cross-Metathesis (CM)
Furthermore, asymmetric variants of RCM17 and ROX18 have been reported with related sets of ligands, illustrating another example of functional group tolerance in the generation of chirally functionalized olefinic compounds. Moreover, both unwanted homocoupling products would also be obtained as mass balance in the reaction. Furthermore, recent work by Taylor and co-workers has demonstrated CM kinetic control in the CM of substituted homoallylic alcohols with allylsilanes using ruthenium catalyst 3 (Scheme 8).24 These authors demonstrate that secondary metathesis of the.
The relay of stereochemistry at the allylic and homoallylic position to the newly formed olefin is unprecedented. However, at this point, a general model for product selectivity in CM is lacking despite some important discoveries made in the area. Using ruthenium-based catalyst 2 , terminal olefin dimerization was cleanly accomplished in the presence of a cis styrenyl bond ( Scheme 15 ).
However, Diver and Schreiber achieved an important application of CM in the dimerization of immunosuppressive drug FK506.41 The functional group compatibility was a central highlight in this work using ruthenium catalyst 2 albeit in moderate yields. However, recent reports in the area have focused on two classes of CM utility: dimerization strategies and chain extension.
Ruthenium (bis)-phosphine Catalysts in CM
However, CM has recently been re-investigated by the Grubbs group, starting with the use of disubstituted olefins as chain transfer agents in the formation of telehelical polymers in the tandem ROMP/CM process (Scheme 2).7 The use of these chain transfer agents allows for excellent control above. The CM addition reaction was used in a remarkably convergent manner to accommodate one of the two olefins into the natural product. The reaction mixture was then reduced in volume to 0.5 ml and purified directly on a silica gel column (2x10 cm) by elution with 5:1 hexane:ethyl acetate.
The reaction mixture was then reduced in volume to 0.5 ml and purified directly on a silica gel column (2x10 cm), eluting with 20:1 hexane:ethyl acetate. The reaction mixture was then reduced in volume to 0.5 ml and purified directly on a silica gel column (2x10 cm), eluting with 10:1 hexane:ethyl acetate. The reaction mixture was then purified directly on a silica gel column (2x10 cm), eluting with 15:1 hexane:ethyl acetate.
The reaction mixture was then purified directly on a silica gel column (2x10 cm), eluting with 2:1 hexane:ethyl. The reaction mixture was then reduced in volume to 0.5 ml and purified directly on a silica gel column (2x10 cm), eluting with 2:1 hexane:ethyl acetate.
Synthesis of Trisubstituted Olefins by CM
Unfortunately, the use of 1,1-disubstituted vinyl boronate containing a homoallyl silyl ether did not provide significant amounts of CM product, so the reaction appears to be sensitive to steric bulk in addition to methyl groups as a second geminal substituent. Our initial work in 1,1-symmetrically disubstituted olefins began with the cross metathesis of isobutylene with α-olefins (Table 2). For example, the reaction works well with simple α-olefins (entry 1) as well as with 1,2-disubstituted olefin starting materials (entry 2).
In fact, we were pleased to find that this method was applied in an allyl-to-prenyl conversion in the synthesis of the nucleus of Garsubellin A.21 In all these reactions in Table 3, we were able to obtain a small amount of the methyl -CM product, but noted that this material is consumed in the course of the reaction to provide the more thermodynamically stable tri-substituted olefin. For example, in the reaction of n-butyl acrylate with 2-methyl-2-butene, we were able to detect only a small amount (< 5%) of the senesioic acid derivative, but observed that most material after n has been converted. -butyl crotonate (Scheme 5). The reaction mixture was then reduced in volume to 0.5 ml and purified directly on a silica gel column (2x10 cm), eluted with 9:1 hexane:ethyl acetate.
The reaction mixture was then reduced in volume to 0.5 mL and purified directly on a silica gel column (2x10 cm), eluting with 9:1 hexane:ethyl acetate (500 mL). The reaction mixture was then reduced in volume to 0.5 mL and purified directly on a silica gel column (2x10 cm) eluting with 9:1 hexane:ethyl acetate (500 mL). The reaction mixture was then reduced in volume to 0.5 mL and purified directly on a silica gel column (2x10 cm) eluting with 20:1 hexane:ethyl acetate (500 mL).
The reaction mixture was then reduced in volume to 0.5 mL and purified directly on a silica gel column (2x10 cm), eluted with 9:1 hexane:ethyl acetate (500 mL) and then eluted with 4:1 hexane:ethyl acetate. The reaction mixture was then reduced in volume to 0.5 mL and purified directly on a silica gel column (2x10 cm) eluting with hexane:ethyl acetate 25:1 to give the cross metathesis product (244 mg, 1.43 mmol, 97% yield) as a light brown oil. The reaction mixture was then reduced in volume to 0.5 mL and purified directly on a silica gel column (2x10 cm) eluting with 10:1 hexane:ethyl acetate to give the cross metathesis product (229 mg, 1.29 mmol, 95% yield) as a light brown oil.
The reaction mixture was then reduced in volume to 0.5 mL and purified directly on a silica gel column (2x10 cm) eluting with 10:1 hexane:ethyl acetate to give the cross metathesis product (231 mg, 1.18 mmol, 91% yield) as clear oil. The reaction mixture was then reduced in volume to 0.5 mL and purified directly on a silica gel column (2x10 cm) eluting with 20:1 hexane:ethyl acetate to give the cross metathesis product (316 mg, 1.34 mmol, 91% yield). ) as clear oil. The volume of the reaction mixture was then reduced to 0.5 mL and purified directly on a silica gel column (2x10 cm) eluting with 10:1 hexane:ethyl acetate to give the cross metathesis product (290 mg, 1.05 mmol, 99% yield) as clear oil.
Synthesis of Functionalized Olefins by CM
The reaction mixture was then reduced in volume to 0.5 mL and purified directly on a silica gel column (2x10 cm), eluting with 4:1 hexane:ethyl acetate + 2% Et3N. The reaction mixture was then reduced in volume to 0.5 ml and purified directly on a silica gel column (2x10 cm), eluting with 4:1 hexane:ethyl acetate. The reaction mixture was then reduced in volume to 0.5 ml and purified directly on a silica gel column (2x10 cm), eluting with 5:1 hexane:ethyl acetate + 2% Et3N.
The reaction mixture was then reduced in volume to 0.5 ml and purified directly on a silica gel column (2x10 cm), eluted with 9:1 hexane:ethyl acetate (500 ml) followed by 3:1 hexane:ethyl acetate (1000 ml). The reaction mixture was then reduced in volume to 0.5 ml and purified directly on a silica gel column (2x10 cm), eluted with 8:1 hexane:ethyl acetate (500 ml) followed by 4:1 hexane:ethyl acetate (300 ml). The reaction mixture was then reduced in volume to 0.5 ml and purified directly on a silica gel column (2x10 cm), eluted with 3:1 hexane:ethyl acetate (500 ml) followed by ethyl acetate (500 ml).
The reaction mixture was then reduced in volume to 0.5 ml and purified directly on a silica gel column (2 x 10 cm), eluting with 2:1 hexane:ethyl acetate (500 ml), followed by 1:1 hexane:ethyl acetate (700 ml). ml). . The reaction mixture was then reduced in volume to 0.5 ml and purified directly on a silica gel column (2 x 10 cm), eluting with 1:1 hexane:ethyl acetate (400 ml), followed by 1:4 hexane:ethyl acetate (500 ml). ml). . The reaction mixture was then reduced in volume to 0.5 ml and purified directly on a silica gel column (2 x 10 cm), eluting with 1:1 hexane:ethyl acetate (400 ml), followed by 1:3 hexane:ethyl acetate (500 ml). ml). .
The reaction mixture was then reduced in volume to 0.5 ml and purified directly on a silica gel column (2 x 10 cm), eluting with 3:2 hexane:ethyl acetate (500 ml), followed by 1:1 hexane:ethyl acetate (200 ml). ml). . The reaction mixture was then reduced in volume to 0.5 ml and purified directly on a silica gel column (2x10 cm), eluting at 2:1. The reaction mixture was then reduced in volume to 0.5 ml and purified directly on a silica gel column (2 x 10 cm), eluting with 3:1 hexane:ethyl acetate (500 ml).
The reaction mixture was then reduced in volume to 0.5 ml and purified directly on a silica gel column (2x10 cm), eluted with 9:1 hexane:ethyl acetate (500 ml), followed by 3:1 hexane:ethyl acetate (500 ml ). The reaction mixture was then reduced in volume to 0.5 ml and purified directly on a silica gel column (2x10 cm) by elution with 3:1 hexane:ethyl acetate. The reaction mixture was then reduced in volume to 0.5 ml and purified directly on silica gel.
The reaction mixture was then reduced in volume to 0.5 mL and purified directly on a silica gel column (2x10 cm) eluting with 9:1 hexane:ethyl acetate (500 mL) followed by 3:1 hexane:ethyl acetate (300 ml). The reaction mixture was then reduced in volume to 0.5 ml and purified directly on a silica gel column (2x10 cm) by elution with 9:1 pentane:ethyl acetate. The reaction mixture was then reduced in volume to 0.5 mL and purified directly on a silica gel column (2 x 10 cm) eluting with 20:1 hexane:ethyl acetate (300 mL) followed by 3:1 hexane:ethyl acetate (500 ml) .
The reaction mixture was then reduced in volume to 0.5 ml and purified directly on a silica gel column (2x10 cm) eluting with
A Model for Selectivity in CM
