Andreea Argintaru 11.22.

2011
Br Li R

t-BuLi (2 equiv) THF, -78 C, 1h

B2Pin2 (1 equiv) THF, -78 C, 1 h

O B B O O

Best conditions from previous subgroup

Br BPin 85 C, 24 h 53% Li 2. 1.

O Li

O B B O

O O

PhLi -78 C, THF

Ph O B B O O O

Br

85 C, 24 h

R = OMe, ~40% R = H, ~20% R = CF3, traces

Mass corresponding to C4H9BPin was detected (different retention time then n-BuBPin. BPin BPin F3C BPin

BPin

1. The yield was obtained using 1 equiv of B2Pin2, 1 equiv of PhLi and 1 equiv of alkyl bromide. 2. Propyl benzene (probably by protodeboronation) was the major side product.
3.

were formed during the reaction !!! MeO

3. Using MeLi instead of PhLi provided the product in slightly lower yield.

Try other aryl lithium reagents to determine if the EWG and EDG substituents on the aryl lithium make a diference.
Ar-Br that can be converted to Ar-Li:
Br MeO Br F3C Br

Try copper additives in combination with lithium reagents.

O R B B O

O O

RLi (1 equiv) -78 C, THF

R O [Cu] - 78 -> 0 C, THF, 24 h Br O B Cu O

B B O O Li

1 equiv Br R n-BuLi (2 equiv) THF, -78 C, 1h R Li B2Pin2 (1 equiv) THF, -78 C, 1 h O O B B O O Li

85 C, 24 h

BPin

Br

85 C, 24 h

[Cu]: CuCl, CuBr, CuI, CuCN, CuTC, CuSO4, CuBr2. Amount [Cu]: 0.25, 0.5, 1, or 2 equiv. Conclusion: The yield was not imporved by addition of copper (best yield obtained was ~25% using 0.5 equiv CuCl). Potential problem: [Cu] was added from the beginning of the reaction together with B2Pin2, before forming the lithium-B2Pin2 complex.

1.

R = OMe, ~20% R = H, ~5% R = CF3, traces

BPin was detected in a signicant amount. BPin BPin F3C BPin

BPin

2.

Future plans: HTE screening using PhLi or MeLi and various copper species and solvents.
were formed during the reaction !!!

3. MeO

Possible mechanisms
Br O

Test path D
O B B O RLi (1 equiv) -78 C, THF O R O

OH O H or rt and 85 C OH Me

BPin SET Br BPin SN2 boryl anion Li Br + Ph O B B O O O BPin

B B O O Li

1 equiv R = Me or Ph

B
B2Pin2 1 equiv PhLi (1 equiv) -78 C, THF Ph O B B O O O Li

Detected: PhBPin and MeBPin

Conclusion: The complex between B2Pin2 and RLi seems to be stable and irreversible. The stability of the complex was conformed by calculations (Ioana Aron), the complex is ~30 kcalmole more stable than the B2Pin2.

2 SET

Reaction with other alkyl bromides

Br BPin Br 85 C Li + PhLi BPin Br B2Pin2 RLi (1 equiv) 1 equiv -78 C, THF O R B O O R Li + O B B O O R O B B O O O + B Li O MeLi or PhLi O O R B B O O 85 C 35% No toluene (by protodeboronation) was detected. I will test if lowering the temperature will diminish the homocoupling. No product or SM detected by GC/MS. BPin + B2Pin2

37% Decane was the major side product and SM decylbromide was still left.

Li

Br 85 C

Li O

O B B O O

O Li 85 C Br Two peaks that have the mass of the desired product and reasonable bp detected by GC/MS, but I couldn't isolate any product by column chromatography

Importance of: - nature of R : to favor the attack - solvatation of Li : to trigger the second step