1,2-Metallate Rearrangements - Boston College - Metallate Rearrangements.pdf25 ͦC RB(OR) 2 THF-78...

1

1,2-Metallate Rearrangements

By Gabriel Lovinger

Morken Group

09/25/2015

2

Outline

Introduction

Seminal Examples

Other Metals

Chirality Control

Conclusion

1) Sp3 Centers: α-Halo boronic esters,

2) Sp2 Centers: α-halo boranes and boronic esters: unactivated and

electrophile-triggered

3) Sp Centers: trialkyl boranes unactivated

1) Cu

2) All the rest

1) Substrate Control: α-halo boronic esters and chiral diols

2) Reagent Control: sulfur ylides, Lithiated Carbamates, Various

Applications

3) Catalyst Control: α-unsaturated boronic esters

• Focus:

Metal = Boron

Migrating Terminus = Carbon sp3 Centers

Asymmetric Reactions

3

Mechanism of 1,2-Metallate Rearrangements

• What is 1,2-metallate rearrangement?

4


5


6


7

Outline

Introduction

Seminal Examples

Other Metals

Chirality Control

Conclusion

1) Sp3 Centers: α-Halo boronic esters,




1) Cu

2) All the rest



Applications


• Focus:

Metal = Boron



7

Seminal Examples: Sp3 Centers

α-Halo boronic esters

• The role of boron demonstrated over direct SN2

• Concerted transition state supported

• Seminal example of α-Halo boronic esters 1,2-metallate rearrangement

• “Neighboring Boron in Nucleophilic Displacement”

Matteson, D. S. J. Am. Chem. Soc. 1960, 4228.

Matteson, D. S.; Mah, R. W. H. J. Am. Chem. Soc. 1963, 2599.

.

-78 ͦͦC

25 ͦͦC

Vs

8Stevens, C. I.; Farkas, E., J. Am Chem. Soc. 74, 5352, 1952.

53% yield 25% yield

Xylene

reflux



• Matteson cites this as the closes previously reported analogues reaction

9Hawthorne, M. F.; Dupont, J. A. J. Am. Chem. Soc. 1958, 5830.

Pasto, D. J.; Snyder, Sr. R. J. Org. Chem. 1966, 2773.

• Hawthorn and Dupont proposed β-hydroboration/decomposition of vinyl chloride

• Pasto and Snyder observed predominantly α-hydroboration of vinyl halides

• Likely initial α- and β-haloborane decomposed exothermically

< 5% yield

79% yield< 0.5% yield

< 1.0% yield0 ͦCTHF

-70 ͦCTHF

• Other early examples ( before 1963 ) exist


α-Halo boronic esters• Unrecognized earlier example

Very low yields

10

AIBN

Cl3CBr105 ͦͦC

HI

Cl3CBr-34 ͦͦC

45 % yield

37 % yield 23 % yield

B2H6

THF25 ͦͦC

H2O

hv, Br2

Pentane25 ͦͦC

96 % yield

Matteson, D. S. J. Am. Chem. Soc. 1960, 4228

.

Pasto, D. J.; Hickman, J.; Cheng, T.-C. J. Am. Chem. Soc. 1968, 6259.

Matteson, D. S.; Schaumberg, G.D. J. Org. Chem. 1966, 726.

Brown, H. C.; De Lue, N. R.; Yamamoto, Y.; Maruyama, K. J. Org. Chem. 1977, 3252.

85-100 % yield

R = Me, Bu, iPr, Ph, nBuC=C

RM

M = Li or MgBr

Et2O-78 ͦͦC

Seminal Examples: Sp3 Centersα-Halo Boronic Esters: Synthesis

• Radical bromination

• Hydrohalogenation

• Hydroboration

• Radical

bromination

11

Matteson, D. S.; Cheng, T.-S. J. Organomet. Chem. 1966, 6, 100.

Matteson, D. S.; Cheng, T.-S. J. Org. Chem. 1968, 33, 3055.

BBr3, rt, 24 h

40 % yield

BuOH

-70 ͦͦC

NaI

50 % yieldYield N.R.

Phillion, D. P.; Neubauer, R. ; Andrew, S. S. J. Org. Chem. 1986, 51, 1610.

Phillion, D. P. U.S. Patent 4734517, March 29, 1988.

1) nBuLi, TMEDA

20 ͦC

2) B(Ome)3, THF

, -78 ͦC3) AcOH, Pinicol

THF, -30 ͦC

BuOH/Aceton

CH3I, NaI,

ACN, rt, 72 h

41 % yield 90 % yield 74 % yield

Patented Herbicide

60 % yield 100 % yield 75 % yield 85-30 % yield

R= nBu, Ph, tBuRathke, M. W.; Chao, E,; Wu, G. J. Organomet. Chem. 1976, 122, 145.

Wuts, P. G. M.Thompson, P. A. J. Organomet. Chem. 1982, 234, 137.

1) nBuLi, THF,

-100 ͦC

2) B(OiPr)3, -78 ͦCThen HCl

1) Pinicol, THF

rt, 48 h

2) Bu3SnH, C6H6

rt, 48 h

Seminal Examples: Sp3 Centersα-Halo Boronic Esters: Synthesis

12Sadhu, K. M. ; Matteson, D. S. Organometallics 1985, 4,1687.

nBuLi

THF, -78 ͦC

B(OR)3

-78 to 10 ͦCHCl

• One Synthetic steps, 85% yield for B(OR)2 = B(OiPr)2

• Readily available and relatively low-cost starting materials

• No Sn or Hg



12

nBuLi

THF, -78 ͦC

RLi, THF

-78 ͦC25 ͦC

B(OR)3

-78 to 10 ͦCHCl

• Two synthetic steps to homologate R

Sadhu, K. M. ; Matteson, D. S. Organometallics 1985, 4,1687.



12

nBuLi

THF, -78 ͦC

RLi, THF

-78 ͦC25 ͦC

RB(OR)2

THF

-78 ͦC

B(OR)3

-78 to 10 ͦCHCl

• One synthetic steps to homologate R

R =

yield = 93 % 90 % 94 % 96 % 95 % 90 %

nBuLi

THF, -78 ͦC




12

nBuLi

THF, -78 ͦC

25 ͦC

RB(OR)2

THF

-78 ͦC

RLi, THF

-78 ͦC

B(OR)3

-78 to 10 ͦCHCl




12

nBuLi

THF, -78 ͦC

25 ͦC

RB(OR)2

THF

-78 ͦC

25 ͦC

nBuLi, ICH2Cl

THF, -78 ͦCRLi, THF

-78 ͦC

B(OR)3

-78 to 10 ͦCHCl




13Matteson, D. S.; Majumdar, D. J. Am. Chem. Soc. 1980, 102, 7588.

Matteson, D. S.; Majumdar, D. Organometallics 1983, 2, 1529.

nBuLi

THF, -78 ͦC

CH2Cl2, nBuLi

THF, -100 ͦCThen 20 ͦC

R’M


CH2Cl2, nBuLi


R’’MTHF, -78 ͦCThen 20 ͦC



93 % yield

94 % yield

80 % yield

71 % yield

• Possible to homologate and substitute

• Access to secondary alcohols

• Previously demonstrated R homologation with ICH2



21

Outline

Introduction

Seminal Examples

Other Metals

Chirality Control

Conclusion

1) Sp3 Centers: α-Halo boronic esters




1) Cu

2) All the rest



Applications


• Focus:

Metal = Boron



.

Köbrich, G.; Merkle, H. R. Angew. Chem. Int. Ed. 1967, 6, 1, 74.

Zweifel, G.; Steele, R. B. J. Am. Chem. Soc. 1967,89, 5086.

• Köbrich and Merkle, first reported sp-centered 1,2-

metallate rearrangement

• Zweifel independently reports similar reaction

Seminal Examples: sp2 Centers

Unactivated Boranes

14


.Zweifel, G.; Arzoumanian, H.; White, C.C. J. Am. Chem. Soc. 1967, 89, 6352.

• Very high Z selectivity observed

• Seminal Electrophile-triggered 1,2-metallate rearrangement

Electrophile-Triggered.

15


.Zweifel, G.; Arzoumanian, H.; White, C.C. J. Am. Chem. Soc. 1967, 89, 6352.

• Very high Z selectivity observed

• Seminal Electrophile-triggered 1,2-metallate rearrangement


15

• The nature of the 1,2-metallate rearrangement step was not fully understood

• Electrophilic I2 triggers 1,2-metallate rearrangement

• High Z selectivity suggest concerted 1,2-migration TS


.Zweifel, G.; Polston, N. L.; White, C.C. J. Am. Chem. Soc. 1968, 90, 6243.

Evans, D. A.; Crawford, T. C.; Thomas, R. C.; Walker, J. A. J. Org. Chem. 1976, 41, 3947.

• Evans’ modification (use of boronic esters) early sp3-sp2 coupling

• Vinyl-vinyl coupling, early sp2-sp2 coupling


16

.Utimoto, K.; Uchida, K.; Nozaki. H. Tetrahedron. Lett. 1973, 45, 4527.



17

• Epoxide electrophile trapping

.

• Epoxide electrophile trapping

• Aldehyde electrophile trappingUtimoto, K.; Uchida, K.; Nozaki. H. Tetrahedron. Lett. 1973, 45, 4527.

Utimoto, K.; Uchida, K.; Nozaki. H. Tetrahedron, 1977, 33, 1949.



17

28

Outline

Introduction

Seminal Examples

Other Metals

Chirality Control

Conclusion





1) Cu

2) All the rest



Applications


• Focus:

Metal = Boron



.

Hillman, M. E. D. J. Am. Chem. Soc. 1962, 84, 4715.

• Very Early 1,2-metallate rearrangement to a Csp (1962)

• Predates Matteson (1963)

Seminal Examples: sp CentersUnactivated.

18

.




• Very Early 1,2-metallate rearrangement to a Csp (1962)

• Predates Matteson (1963)


18

.Leung, T.; Zweifel, G. J. Am. Chem. Soc. 1974, 96, 5620.

Zweifel, G.; Backlund, S. J.; Leung, T. J. Am. Chem. Soc. 1978, 100, 5561.


19

.


19Leung, T.; Zweifel, G. J. Am. Chem. Soc. 1974, 96, 5620.

Zweifel, G.; Backlund, S. J.; Leung, T. J. Am. Chem. Soc. 1978, 100, 5561.

33

Outline

Introduction

Seminal Examples

Other Metals

Chirality Control

Conclusion





1) Cu

2) All the rest



Applications


• Focus:

Metal = Boron



Other Metals: Cu and All The Rest

20

Fujisawa, T. Kurita, Y. Kawashima, M.; Sato, T. Chemistry Letters, 1982, 1641.

Kocienski, P.; Wadman, S. J. Am. Chem. Soc. 1989, 11, 2363.

Kocienski, P.; Barber, C.; Pure Appl. Chem. 1990, 62, 10, 1933.

Negishi, E.-I.; Akiyoshi, K.; J. Am. Chem. Soc. 1988, 110, 646.

• First observation of Cu-based 1,2-metallate rearrangement (Sato)

• Rendered catalytic in copper (Kocienski)

• Nigishi then demonstrated 1,2-metallate

rearrangements with Al, Zn, Cd, and Mg

35

Outline

Introduction

Seminal Examples

Other Metals

Chirality Control

Conclusion





1) Cu

2) All the rest



Applications


• Focus:

Metal = Boron



21.

Substrate

control

R2M.

*

* *

LiCHCl2

• Chiral diols can be used as chiral directors

Chirality Control: α-Halo Boronic EstersChiral Diols

Matteson, D. S. Majumdar, D. J. Am. Chem. Soc. 1980, 102, 7590.

MeMgBr ,

THF, -78 ͦCto 20 ͦCovernight

CH2Cl2 ,

nBuLi

THF, -100 ͦCto 0, 1h

a = b =

a b

94 % yield

97 % dr

94 % ee


22

22Matteson, D. S. Majumdar, D. J. Am. Chem. Soc. 1980, 102, 7590.

MeMgBr ,


CH2Cl2 ,

nBuLi


a = b =

a b a

b

96 % yield

88 % yield

90 % dr

94 % yield

97 % dr

94 % ee

7 h at ͦC


22Matteson, D. S. Majumdar, D. J. Am. Chem. Soc. 1980, 102, 7590.

MeMgBr ,


CH2Cl2 ,

nBuLi


a = b =

a b a

b

1) a

2) b 96 % yield

88 % yield

90 % dr

93 % yield

94 % dr

91 % yield

59 % yield

Over 2 steps

94 % yield

97 % dr

94 % ee

NaBO3

1) BCl3,

2) PhCH2B(OH)2

3) HCl

7 h at ͦC


23Matteson, D. S.; Sadhu, K. M. J. Am. Chem. Soc. 1983, 105, 2077.

Matteson, D. S.; Erdik, E. Organometallics 1983, 2, 1083.

b

Cl-

LiCHCl2

-100 ͦC

ZnCl2

• Without ZnCl2:15-33 % yield

77 % de

• With ZnCl2: 90 % yield

99 % de

At rt in THF:

20 % epimerization/hour for phenylboron

1 % epimerization/hour for alkylboron

58-63 % yield

99 % dr

78 % yield

97 % dr

H2/Pd

exo-brevicomin

• Insect pheromone

components


24.

a = LiCHCl2

b = ZnCl2

c = RM

a b

c


Matteson, D. S.; Sadhu, K. M. J. Am. Chem. Soc. 1983, 105, 2077.


25.

LiCHCl2

LiCHCl2

RLi

RLi

High dr

Low dr

• C2 symmetric chiral directors (equivalent boron ate intermediate)

• Non-C2 symmetric chiral directors

(match case)


(mismatch case)




25.

LiCHCl2

LiCHCl2

RLi

RLi

High dr

Low dr


(match case)


(mismatch case)

• C2 symmetric chiral directors (equivalent boron ate intermediate)




26.Tripathy, P. B.; Matteson, D. S. Synthesis 1990, 200.

• Mismatch


27.

1) Boron ate complexes do not rearrange at low temperature

2) Electrophilic boron promotes clean ate formation; low side reactivity (beta-elimination)

3) Cations such as Zn, Li, and Mg accelerate rate of 1,2-metallate rearrangement

4) Boronic esters with beta-halides or weakly basic groups are unstable (beta-elimination)

5) C2-symmetric boronic esters are generally more selective in 1,2-metallate rearrangements

( only one diasteriameric TS) than those derived from pinanediol (two diasteriameric Ts)

6) Alkoxy groups (Obn, OPMB, OCPh3), CΞN, are tolerated at alph and beta position

7) To prevent beta-elimination halides, carbonyl, thioether, and cyano substituents

must be at least two carbons from boron

8) RMgX, RLi, RO-, RS-, R2N-, N3

-, and LiCH2CN are effective nucleophiles

9) General utility hampered by the need to exchange chiral diol to invert chiral direction

Alph-Chloro Boronic Ester 1,2-Metallate

Rearangment: Key Principles

Matteson, D. S. Chem. Rev. 1989, 89, 1535.

28.

Applications of Matteson-Type Homologation

Hiscox, W. C.; Matteson, D. S. J. Organomet Chem. 2000, 614-615, 314.

94 % yield. 79 % yield.

97 % yield.

40 % yield.

(1.2 eq), THF, -78 ͦC.

LiCHCl2-100 to

then -78 ͦZnCl2

1) H2O2/NaOH

2) pTsOH

3) Lindlar/H2

29.

Applications of Matteson-Type Homologation

Matteson, D. S.; Man, H.-W.; Ho, O. C. J. Am. Chem. Soc. 1996,118, 4560.

13 % overall yield

1) LiHCCl2/ZnCl2

2) NaOBn

1) LiCCl2/ZnCl22) MeMgBr

H2O2

Ph 8-9

1) NaOH

2) H2/Pd

3) H3O+

4) pinicol

1) (PyH+)CrO7

2) 9BBNOTf1) A

1) (PyH+)CrO7

2) H2O2 pH

3) CF3CO2H

1) MeSO3H

CH3Cl, 25 ͦC

A

2) NMO/TPAP

CH2Cl2 25 ͦC

49

Outline

Introduction

Seminal Examples

Other Metals

Chirality Control

Conclusion





1) Cu

2) All the rest



Applications


• Focus:

Metal = Boron



30.

Substrate

control.

Reagent

control

R2M.

*

*

* *

*

LiCHCl2

• Chiral nucleophiles can be used as the source of chirality

• Sense of chirality in every step tunable without need to exchanging chiral director

Chirality Control: Reagent Control

31.Aggarwal, V. K.; Fang, G. U.; Schmidt, A. T. J. Am. Chem. Soc. 2005, 127, 6, 1643.

Aggarwal, B. K.; Harvey, J. N; Robiette, R. Angew. Chem. Int. Ed. 2005, 44, 5468.

1.2 eq LIHMDS

THF/dioxane

5 ͦC

BBu3

78 % yield 74 % yield 76 % yield 77 % yield 87 % yield 17 % yield

67 % yield (with 10 eq BEt3)

1.2 eq LIHMDS

THF/dioxane, 5 ͦC

70 % yield

95 % ee72 % yield

97 % ee

73 % yield

96 % ee

68 % yield

97 % ee

87 % yield

95 % ee

68 % yield

96 % ee

Cetirizine

Neobenodine

Chirality Control: Reagent ControlSulfur Ylides

32.

1)1.2 eq LIHMDSTHF/dioxane, 5 ͦC

2) H2O2 or NH2OSO3H

BEt3

BEt3

ΔE = 4.37 kcal/mol

68-73 % yield

95-97 % ee

Major product

Minor product

Aggarwal, V. K.; Fang, G. U.; Schmidt, A. T. J. Am. Chem. Soc. 2005, 127, 6, 1643.


.

Entry R Yield Yield

1 Hexyl 56 % 41 %

2 Allyl 51 % 39 %

3 Benzyl 51 % 35 %

4 iPr Trace 77 %

5 Cyclopropyl 89 % Trace

6 Ph Trace 94 %

7 1-Hexenyl Trace 21 %

8 1-Hexynyl 92 % Trace

1) 1.2 eq LIHMDS

THF/CHCl2, -78 ͦC2) 9BBN-R, -100 ͦC to rt

3) H2O2, NaOH

Fang, G. Y.; Wallner, O. A.; Blasio, N. D.; Ginesta, X; Harvey, J. N.; Aggarwal, V. K. J. Am. Chem. Soc. 2007, 129, 14632.

Aggarwal, V. K.; Fang. G. Y.; Ginesta, X.; Howells, D. M.; Zaja, M. Pure Appl. Chem. 2006, 78, 2, 215.

• Both borocycle and R group migration depending on the nature of the R group

• 9-BBN identified as an easily migrated group


33

.

1) 1.2 eq LIHMDS

THF/CHCl2, -78 ͦC2) 9BBN-R, -100 ͦC to rt

3) H2O2, NaOH


33

Fang, G. Y.; Wallner, O. A.; Blasio, N. D.; Ginesta, X; Harvey, J. N.; Aggarwal, V. K. J. Am. Chem. Soc. 2007, 129, 14632.

Aggarwal, V. K.; Fang. G. Y.; Ginesta, X.; Howells, D. M.; Zaja, M. Pure Appl. Chem. 2006, 78, 2, 215.

55

Outline

Introduction

Seminal Examples

Other Metals

Chirality Control

Conclusion





1) Cu

2) All the rest



Applications


• Focus:

Metal = Boron



.Beckman, E.; Desai, V.; Hoppe, D. Synlett, 2004, 13, 2275.

sBuLi (1.2 eq)

(-)-sparteine (1.2 eq)

Et2O, -78 ͦC

1) B(OiPr)3 Et2O

Et2O, -78 ͦC

2) pinacol, p-TOH

MgSO4 CH2Cl2R1MgBr

-78 ͦC

1) Warm

2) H2O2/NaOH

50 % yield

> 95 % ee

70 % yield

> 95 % ee

61 % yield

> 95 % ee

56 % yield

> 95 % ee

64 % yield

> 95 % ee

• Separate steps: 1) form boronic ester

2)1,2-metallate rearrangement90 % yiels

Chirality Control: Reagent ControlLithiated Carbamates

35

.Besong, G.; Jarowicki, K.; Kocienski, P. J.; Sliwinski, E.; Boyle, T. F. Org. Biomol. Chem. 2006, 4, 2193.

sBuLi (1.2 eq)


Et2O, -78 ͦC

iPrOBpin

78 ͦC Et2O, rt

ii) MgBr (1.2 eq)

-78 ͦCiii) 80 ͦC

i) Et2O, rt

A 51 % yield (over 2 steps) 94:4 er

B 65 % yield 98:2 er

H2O2, K2CO3, H2O, rt

Path B

Path A Path A

• Synthetic application towards tubulin polymerization inhibitor

• First direct (one step) use of lithiated carbamates with boronic ester (path B)


36

.Stymiest, J. L.; Dutheuil, G.; Mahmood, A.; Aggarwal, V. K. Angew. Chem. Int. Ed. 2007, 46, 7491.

1)sBuLi (1.2 eq)


Et2O, -78 ͦC

2) R2B(R3)2

3) Lewis Acid

1) Warm

2) NaOH

H2O2

• Second direct (one step) use of lithiated carbamates with boronic ester • Convert ͦ1alcohol to ͦ2 alcohol


37

Structure R2 (R3)2 Lewis acid Yield er

A Et Et ̅ 91 98:2

nHex 9-BBN ̅ 90 98:2

iPr 9-BBN ̅ 81 98:2

Ph 9-BBN ̅ 85 88:12

Ph 9-BBN MgBr2 94 97:3

Et pinacol MgBr2 90 98:2

B Et Et ̅ 90 97:3


Et pinacol MgBr2 75 97:3

Ph pinacol MgBr2 73 98:2

C Et Et ̅ 67 95:5



D Ph 9-BBN MgBr2 68 96:4


E Ph pinacol MgBr2 70 97:3

.

A

B

C

D

E

1)sBuLi (1.2 eq)


Et2O, -78 ͦC

2) R2B(R3)2

3) Lewis Acid

1) Warm

2) NaOH

H2O2

Stymiest, J. L.; Dutheuil, G.; Mahmood, A.; Aggarwal, V. K. Angew. Chem. Int. Ed. 2007, 46, 7491.


37

.Stymiest, J. L.; Dutheuil, G.; Mahmood, A.; Aggarwal, V. K. Angew. Chem. Int. Ed. 2007, 46, 7491.


38

.Stymiest, J. L.; Bagutski, V..; French, R. S.; Aggarwal, V. K. Nature, 2008, 456, 778.


39



40



41

.

“Full Chirality Transfer”

Bagutski, V.; French, R. M.; Aggarwal, V. K. Angew. Chem. Int. Ed. 2010, 49, 5142

• Reactions previously in the 88-98 % ee range

• Where is the source of ee erosion?


42



• Observed yield and ee dependent on equivalents of boronic ester

• Implications for the mechanism?

.

“Full Chirality Transfer”





42

.

• Observed yield and ee dependent on equivalents of boronic ester

• Boron ate formation in equilibrium with dissociation

• Warming promotes 1,2-migration and boron ate dissociation

• Dissociation could be followed by racemization of lithium reagent

• High Rbpin concentration, fast recombination of dissociated boron ate

Proposed Mechanism



43

.

Trapping Experiment

• Sm indicates extent of lithiation of starting material

• Allylation (e1) indicates extent of boron ate formation

• Product (pdt) indicates extent of 1,2-metallate rearranging upon warming

• Deuteration (e2)indicates extent of boron ate dissociation upon warming



44

.

Trapping Experiment



44

.Bagutski, V.; French, R. M.; Aggarwal, V. K. Angew. Chem. Int. Ed. 2010, 49, 5142

Improved procedures

• Lewis acid additive for Bpin method

• MeOH trapping agent for Bpin method

• B(neo) found to be more reactive


45

.

Vedrenne, E.; Wallner, O. A. Vitale, M.: Schmidt, F.: Aggarwal, V. K. Angew. Org. Lett. 2009, 11, 165.

Schmidt, F.; Keller, F.; Vedrenne, E.; V. K. Angew. Angew. Chem. Int. Ed. 2009, 48, 1149.

Lithiated epoxides and Azirdines for boronic ester

homologation

• Access to chiral diols ad amino alcohols

Chirality Control: Reagent ControlVarious Applications

46

.

Roesner, Stefan, Brown, C. A.; Mohiti, M.; Pulis, A. P.: Rasppan, R.; Blair, D. J.: Essafi, S.: Leonori, D.:

Aggarwal, V. K. Chem. Commun. 2014, 50, 4053.

Alcohol to pinacol ester


47

.

Burns, M.; Essafi, S.; Bame, R. J.; Bull, S. P.; Webster, M. P.; Balieu, S.; Dale, J. W.; Butts, C. P.; Harvey, J. N.:

Aggarwal, V. K. Nature, 2014, 513, 183..

Towards Ideality/Assembly-line Synthesis

Balieu, S.; Hallett, G. E.; Burns, M.; Bootwicha, Teerawut, B. Studley, J.; Aggarwal, V. K.

J. Am. Chem. Soc. 2015, 137, 4398.


48

.

Transition-Metal-Free Enantiospecific sp2-sp3 Coupling:

Electron-Rich Aromatics

Bonet, A.; Odachowski, M.; Leonori, D.; Essafi, S.; Aggarwal, V. K. Nature. Chem. 2014, 6, 584.


49

.

Transition-Metal-Free Enantiospecific sp2-sp3 Coupling:

Electron-Rich Aromatics

Llaveria, J.: Leonori, D.; Aggarwal, V. K. J. Am. Chem. Soc. 2015, 137, 10958.


50

84

Outline

Introduction

Seminal Examples

Other Metals

Chirality Control

Conclusion





1) Cu

2) All the rest



Applications


• Focus:

Metal = Boron



51.

Substrate

control.

Reagent

control

R2M.

• What about catalyst control?

Chirality Control: Catalyst Control

*

*

*

**

51.

Substrate

control.

Reagent

control

R2M.

• Only one known example of asymmetric catalyst-controlled 1,2-metallate rearrangement

• Only one known example of transition-metal-triggered 1,2-metallate rearrangement

• What about catalyst control?

Chirality Control: Catalyst Control

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*

*

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52. Jadhav, P. K.; Man, H.-W. J. Am. Chem. Soc. 1997, 119, 846.

• Only known example of 1,2-metallate rearrangement employing a chiral catalyst

• Catalytic in Yb(OTf)3 0.3 eq

• 5 eq of 2b required for 88 % ee

• 0.5 eq of 2b results in 55 % ee

Chirality Control: Catalyst ControlChiral Catalyst

52. Jadhav, P. K.; Man, H.-W. J. Am. Chem. Soc. 1997, 119, 846.

• Only known example of 1,2-metallate rearrangement employing a chiral catalyst

• LiCl and free Yb(OTf)3 promote non-selective reaction (path 1)

• Catalytic in Yb(OTf)3 0.3 eq

• 5 eq of 2b required for 88 % ee

• 0.5 eq of 2b results in 55 % ee

Chirality Control: Catalyst ControlChiral Catalyst

53.

Sebald, A.; Wrackmeyer, B. J. Chem. Soc. Chem. Commun. 1983, 309.

• Only known example of a transition-metal triggered 1,2-metallate rearrangement

Chirality Control: Catalyst ControlTransition-Metal-Triggered

54.

Chirality Control: Chiral Catalysts

Substrate

control.

Reagent

control

R2M.

Catalyst

control

α-Unsaturated Boronic Esters

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54.

Chirality Control: Chiral Catalystsα-Unsaturated Boronic Esters

• Representative products

• Readily accessed targets

• New reactivity can be programmed into known

reactions to design new transformations

92

Outline

Introduction

Seminal Examples

Other Metals

Chirality Control

Conclusion





1) Cu

2) All the rest



Applications


• Focus:

Metal = Boron



55.

Conclusion

• 1,2-metallate rearrangement reactions have a long and rich history

• The reactivity mode is very versatile and can be rendered asymmetric

• 1,2-metallate rearrangements are known for a large number of metals

• 1,2-metallate rearrangement reactions have a bight future ahead

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