Recent Developments of Cobalt-Catalyzed Hydrofunctionalization of Olefins

radical R Me

III Co Ln alkylcobalt R Me Co + silane R olefin

carbocation R Me

carbanion R Me

Yufan Liang MacMillan Group Meeting February 5th, 2020 Outline

III Co Ln

R Me R Me Co + silane Co radical alkylcobalt R R Me regioselective olefin alkyl radical R Me R Me

carbocation carbanion

Selected examples from these research groups will be discussed in detail

Prof. Erick Carreira (ETH Zürich) Prof. Seth Herzon (Yale) Prof. Ryan Shenvi (Scripps) Prof. Hiroki Shigehisa (Musashino University, Japan) Prof. Sergey Pronin (UC Irvine) Prof. Rong Zhu (Peking University, China) Mukaiyama Hydration

5 mol% Co(acac)2 2 equiv PhSiH3 OH O BzO BzO Me BzO Me O2, THF, r.t., 18 h

84% yield 14% yield

III LnCo –H BzO BzO Me II – LnCo Generating a stable radical

+ O2

Highly regioselective process II O OH + LnCo O

BzO Me + silane BzO Me

Teruaki Mukaiyama et al., Chem. Lett. 1989, 449; 1989, 569; 1989, 573; 1989, 1071. Quenching Alkyl Radicals with Radicalophiles: Summary of Carreira’s Work

III LnCo –H radicalophile R R Me R Me olefin alkyl radical

OBn N Ph t-BuO2C N Ts N3 Ts CN Ts Cl S X N CO2t-Bu O O (X = H or CN)

H Boc N X N N Boc N3 CN Cl OBn

R Me R Me R Me R Me R Me

JACS 2004, 5676 JACS 2005, 8294 ACIE 2007, 4519 ACIE 2008, 5758 JACS 2009, 13214 Org. Lett. 2005, 4249 Synthesis 2007, 3839 Quenching Alkyl Radicals with Radicalophiles: Selected Examples

Me Boc Me N NH 2 75% yield NH Boc

Ph Ph Me Me 66% yield Me N3 Me

+ PhSiD3 Cl 54% yield Ph D Ph

H N H O OBn 82% yield Ph (over 2 steps) Ph Me Ph Me Quenching Alkyl Radicals with Radicalophiles: Important Findings

Ligand Me Me Me Me Ph Ph Me Me t-Bu O N N O N N OK t-Bu OH HO t-Bu ONa OH OH t-Bu t-Bu t-Bu

Silane ◉ Most commonly used solvent: EtOH PhSiH3 ◉ In some cases, addition of t-BuOOH improves efficiency, especially when Co(II) catalyst was used: Me H H Me Si Si Me O Me t-BuOOH II III LnCo LnCo –H (TMDSO) silane

For a full article (including a SAR study of the ): Waser, J.; Gasper, B.; Nambu, H.; Carreira, E. M. J. Am. Chem. Soc. 2006, 128, 11693. Quenching Alkyl Radicals with Radicalophiles: Hydroheteroarylation

N 1 equiv Co(acac)2 (MeO)SO3 R2 1 equiv t-BuOOH R1 N R3 5 equiv Et SiH, DCM, r.t. MeO 3 R1 R2 R3 N-methoxy salt olefin

Me Me Cbz N Me Me Me

OH Me

Me Cbz Me N Me Me Me Me Me Me Me OH N

Me N Me Me N Me N Me CF3 Me N Me

71% yield 71% yield 79% yield 52% yield 60% yield

Ma, X.; Herzon, S. B. J. Am. Chem. Soc. 2016, 138, 8718 Ma, X.; Dang, H.; Rose, J. A.; Rablen, P.; Herzon, S. B. J. Am. Chem. Soc. 2017, 139, 5998 (full article) Quenching Alkyl Radicals with Radicalophiles: Hydroheteroarylation

N 1 equiv Co(acac)2 (MeO)SO3 R2 1 equiv t-BuOOH R1 N R3 5 equiv Et SiH, DCM, r.t. MeO 3 R1 R2 R3 N-methoxy salt olefin

R2 R1 t-BuOOH 3 R 1 2 III R R Co(acac)2 LnCo –H 3 II R Et3SiH – LnCo Me

N MeO Me

OMe

Me N Me II Me N Me + LnCo SET H 1 2 III 1 2 R R – LnCo , – MeOH R R R3 R3

Ma, X.; Herzon, S. B. J. Am. Chem. Soc. 2016, 138, 8718 Ma, X.; Dang, H.; Rose, J. A.; Rablen, P.; Herzon, S. B. J. Am. Chem. Soc. 2017, 139, 5998 (full article) Quenching Alkyl Radicals with Radicalophiles: A Versatile Strategy

O O Co(acac)2, t-BuOOH, Et3SiH Me PMP O PMP O 36–96% yield radicalophile Me Me

H F Cl Br

1,4-dihydrobenzene NFSI TsCl TsBr

I OH SPh SePh

CH2I2 O2 PhSO2SPh TsSePh

N3 N PMP OBn OBn N N N

+ H CN ArSO2N3 PMP–N2

Ma, X.; Herzon, S. B. Beilstein J. Org. Chem. 2018, 14, 2259 Outline

III Co Ln

R Me R Me Co + silane Co radical alkylcobalt R R Me regioselective olefin alkyl radical R Me R Me

carbocation carbanion Olefin Isomerization via Reversible HAT

1 mol% Co(SaltBu,tBu)Cl

2 mol% PhSiH3 Me

C8H17 C8H17 Me benzene, Ar, r.t., 3 h Me

1,1-disubstituted olefin 96% yield

silane III III LnCo –Cl LnCo –H

N N C8H17 CoIII Me t-Bu O O t-Bu Cl t-Bu t-Bu II Me Me + L Co Co(SaltBu,tBu)Cl n C8H17 C8H17 Me Me III – LnCo –H H

Crossley, S. W. M.; Barabé, F.; Shenvi, R. A. J. Am. Chem. Soc. 2014, 136, 16788 Olefin Isomerization via Reversible HAT

1–10 mol% Co(SaltBu,tBu)Cl

2–50 mol% PhSiH3 Me R1 R1 R benzene, Ar, r.t. R

1,1-disubstituted olefin

O Me Me Me H O Me Me H Ph Me Me Me Me 3

Me Me O Me Me O Me Me Me

Ph Me Me Me Me Me 3 Me

83% yield 74% yield 90% yield 95% yield

Crossley, S. W. M.; Barabé, F.; Shenvi, R. A. J. Am. Chem. Soc. 2014, 136, 16788 Diene Cycloisomerization via Reversible HAT

X X 3–6 mol% Co(SaltBu,tBu)Cl n n 6–12 mol% PhSiH3 R1 R2 R1 R2 benzene, Ar, r.t. H H R3 R3 diene

EtO2C CO2Et EtO C CO Et O 2 2

Me Me Me Ph Me Me

EtO C CO Et EtO2C CO2Et 2 2 H Me O H Me Me Me Me H Me Me Me H

94% yield 89% yield, >20:1 d.r. 92% yield 75% yield, >20:1 d.r.

Crossley, S. W. M.; Barabé, F.; Shenvi, R. A. J. Am. Chem. Soc. 2014, 136, 16788 Terminal Olefin as Substrate: Temperature Effect

5 mol% Co(SalOMe,tBu)Cl

50 mol% PhSiH3 Me C7H15 C7H15 benzene, r.t. terminal olefin 10% yield (3:1 E/Z)

5 mol% Co(SalOMe,tBu)Cl

50 mol% PhSiH3 Me C7H15 C7H15 benzene, 60 ºC terminal olefin 90% yield (3:1 E/Z)

N N CoIII MeO O O OMe Cl t-Bu t-Bu

Co(SalOMe,tBu)Cl

Crossley, S. W. M.; Barabé, F.; Shenvi, R. A. J. Am. Chem. Soc. 2014, 136, 16788 Terminal Olefin as Substrate: Temperature Effect

5 mol% Co(SalOMe,tBu)Cl

50 mol% PhSiH3 Me C7H15 C7H15 benzene, r.t. 10% yield

5 mol% Co(SalOMe,tBu)Cl

50 mol% PhSiH3 Me C7H15 C7H15 benzene, 60 ºC 90% yield

5 mol% Co(SalOMe,tBu)Cl

50 mol% PhSiH3 Me C8H17 C8H17 Me benzene, r.t. Me 95% yield

5 mol% Co(SalOMe,tBu)Cl

50 mol% PhSiH3 Me C8H17 C8H17 C7H15 Me benzene, r.t. Me trace

Crossley, S. W. M.; Barabé, F.; Shenvi, R. A. J. Am. Chem. Soc. 2014, 136, 16788 Proposed Mechanism: Off-Cycle Alkylcobalt Species

R Me

silane off-cycle pathway CoIIIL R n L CoIII–Cl L CoIII–H II n n Me + LnCo R Me H 60 ºC stable at r.t.

R

For 1,2-disubstituted olefin, formation of an alkylcobalt species with a tertiaryl alkyl is not favored.

Crossley, S. W. M.; Barabé, F.; Shenvi, R. A. J. Am. Chem. Soc. 2014, 136, 16788 Olefin Hydroarylation via Dual Nickel and Cobalt Catalysis

CF3 5 mol% NiBr2(dtbbpy) tBu,tBu CF3 20 mol% Co(Sal ) 75% yield C H 8 17 >20:1 b/l I 50 mol% oxidant 2 equiv Ph(i-PrO)SiH2 olefin aryl iodide C8H17 Me DMPU, r.t.

t-Bu Me BF N N N Br 4 NiII CoII N Br t-Bu O O t-Bu Me N Me t-Bu F t-Bu t-Bu

tBu,tBu Co(Sal ) NiBr2(dtbbpy) Oxidant

Green, S. A.; Matos, J. L. M.; Yagi, A.; Shenvi, R. A. J. Am. Chem. Soc. 2016, 138, 12779 Olefin Hydroarylation via Dual Nickel and Cobalt Catalysis

5 mol% NiBr2(dtbbpy) X 20 mol% Co(SaltBu,tBu) X hydroarylation R >20:1 b/l I 50 mol% oxidant

2 equiv Ph(i-PrO)SiH2 R Me olefin aryl iodide DMPU, r.t.

Me Me Ph S C8H17 C8H17 Me

NBoc CF3 CF3 Ts N N

Me Me Ph Me Me S Me C8H17 Me C8H17 Me

70% yield 55% yield 61% yield 80% yield

Green, S. A.; Matos, J. L. M.; Yagi, A.; Shenvi, R. A. J. Am. Chem. Soc. 2016, 138, 12779 Mechanistic Studies: Roles of the Oxidant

Me OTf N N N N CoII OTf CoIII t-Bu O O t-Bu t-Bu O O t-Bu Me N Me t-Bu t-Bu F t-Bu t-Bu

Co(SaltBu,tBu) X-ray

III oxidant silane R Co Ln II III + III LnCo [LnCo ] LnCo –H R Me

Shevick, S. L.; Obradors, C.; Shenvi, R. A. J. Am. Chem. Soc. 2018, 140, 12056 Mechanistic Studies: Roles of the Oxidant

CF3 5 mol% NiBr2(dOMe-bpy) CF3 20 mol% Cobalt Bn

I oxidant 2 equiv Ph(i-PrO)SiH2 Bn 1.3 equiv 1 equiv Me DMPU, r.t.

20 mol% CoII(SaltBu,tBu), 50 mol% oxidant 82% yield

III tBu,tBu 20 mol% Co (Sal )(BF4), no oxidant 56% yield

III tBu,tBu 20 mol% Co (Sal )(BF4), 30 mol% oxidant 70% yield

Roles of oxidant: ◉ Generating CoIII to initiate the reaction ◉ Reoxidizing CoII to the active CoIII oxidation state

Shevick, S. L.; Obradors, C.; Shenvi, R. A. J. Am. Chem. Soc. 2018, 140, 12056 Mechanistic Studies: Cobalt to Nickel Alkyl Transfer

Me Me

N N II 1. Na(Hg), N N Co CoIII t-Bu O O t-Bu t-Bu O O t-Bu 2. i-PrBr, THF t-Bu t-Bu t-Bu t-Bu Py

CoII(SaltBu,tBu) (Py)(SaltBu,tBu)CoIII i-Pr

t-Bu t-Bu Me N THF, r.t. N I I NiII Ni(COD)2 N N t-Bu Me t-Bu NiII(dtbbpy)(o-Tol)I

Shevick, S. L.; Obradors, C.; Shenvi, R. A. J. Am. Chem. Soc. 2018, 140, 12056 Mechanistic Studies: Cobalt to Nickel Alkyl Transfer

t-Bu Me Me Me N I Me THF/DMPU II I Ni (Py)(SaltBu,tBu)CoIII Me N Me r.t. t-Bu Me 1 equiv

NiII(dtbbpy)(o-Tol)I 10% yield 25% yield

Me 5 mol% NiBr2(dtbbpy) Me Me III tBu,tBu 20 mol% Co (Sal )(BF4) Bn I Bn

2 equiv Ph(i-PrO)SiH2 DMPU, r.t. 1.3 equiv 1 equiv 25% yield

Shevick, S. L.; Obradors, C.; Shenvi, R. A. J. Am. Chem. Soc. 2018, 140, 12056 Mechanistic Studies: Cobalt to Nickel Alkyl Transfer

t-Bu Me Me Me tBu,tBu III N I oxidant 1 equiv (Py)(Sal )Co i-Pr II I Ni Me N DMPU, r.t., 3 h THF/DMPU, r.t., 18 h t-Bu Me

NiII(dtbbpy)(o-Tol)I

oxidant yield yield

none 10% 25%

Me

BF4 1 equiv 17% 78% Me N Me F

III 1 equiv AcFcBF4 (Fe as oxidant) 18% 18%

III 2 equiv AcFcBF4 (Fe as oxidant) 41% 44%

Shevick, S. L.; Obradors, C.; Shenvi, R. A. J. Am. Chem. Soc. 2018, 140, 12056 Mechanistic Studies: Cobalt(III) to Nickel(III) Alkyl Transfer

Me Me

III II X2(dtbbpy)Ni X(dtbbpy)Ni SET Me Me (solvent)(SaltBu,tBu)CoIII X(solvent)(SaltBu,tBu)CoIV Me Me

1. CoIII to NiIII alkyl transfer C–Co homolysis 2. NiIII reductive elimination (within solvent cage)

Me

NiI(dtbbpy)X Me X(dtbbpy)NiII

Me Me X(dtbbpy)NiIII reductive radical trapping Me Me Me Me elimination (within solvent cage) Me CoIII(SaltBu,tBu)(solvent)X

CoIII(SaltBu,tBu)(solvent)X CoIII(SaltBu,tBu)(solvent)X

Shevick, S. L.; Obradors, C.; Shenvi, R. A. J. Am. Chem. Soc. 2018, 140, 12056 Cobalt(III) to Nickel Alkyl Transfer: Literature Precedents

F F B Me Me O O Me N N [Me–CoII(dmgBF ) py]– Me N N Me 2 2 CoIII NiI OTf SET Me N N Me N N II Py [Ni (tmc)OTf]+ O O Me Me B F F

III I Me–Co (dmgBF2)2py [Ni (tmc)]OTf

C–Co homolysis II – I – [Me–Co (dmgBF2)2py] Me• [Co (dmgBF2)2py]

radical trapping Me• [NiI(tmc)]OTf [Me–NiII(tmc)]OTf

Ram, M. S.; Riordan, C. G.; Yap, G. P. A.; Liable-Sands, L.; Rheingold, A. L.; Marchaj, A.; Norton, J. R. J. Am.Chem. Soc. 1997, 119, 1648 Cobalt(III) to Nickel Alkyl Transfer: Literature Precedents

10 mol% NiCl2(dtbbpy) Br 10 mol% Vitamin B12 PhthN PhthN OTs 2 equiv Mn, DMF, 30 ºC

1º alkyl OTs 2º alkyl bromide 83% yield 1.5 equiv without VB12: 0% yield

NPhth

Mn CoI PhthN OTs VB III 12 Co OTs L SN2 oxidation addition L

NPhth Co(III) to Ni(0) alkyl transfer NPhth CoI III Ni0(dtbbpy) Co OTs NiII(dtbbpy)(OTs) L L

Alternatively, Co(III) to Ni(I)–R alkyl transfer is also feasible

Komeyama, K.; Michiyuki, T.; Osaka, T. ACS Catalysis 2019, 9, 9285 Outline

III Co Ln

R Me R Me Co + silane Co radical alkylcobalt R R Me regioselective olefin alkyl radical R Me R Me

carbocation carbanion Hydrofluorination of Olefin via Radical Fluorination

2 equiv Fe2(ox)3 O 6.5 equiv NaBH4 O F Selectfluor HO MeCN/H2O, 0.0125 M HO Me 0 ºC, 30 min olefin 2 equiv 73% yield

Barker, T. J.; Boger, D. L. J. Am. Chem. Soc. 2012, 134, 13588 Hydrofluorination of Olefin via Radical Fluorination

III LnCo –H radical fluorination F R R Me II R Me – LnCo

Me 3 mol% CoII Catalyst A MeO MeO Me BF4 4 equiv (Me2SiH)2O (TMDSO)

F MeO Me N Me PhCF3, 0 ºC MeO F 2 equiv 81% yield

Me Me Me Me

N N CoII t-Bu O O t-Bu

t-Bu t-Bu

CoII Catalyst A

Shigehisa, H.; Nishi, E.; Fujisawa, M.; Hiroya, K. Org. Lett. 2013, 15, 5158 Hydrofluorination of Olefin: An Happy Accident

1 mol% CoII Catalyst A 1.1 equiv NFSI MeO MeO Me MeO Me 1 equiv PhSiH3 F OEt MeO EtOH, 0 ºC, 22 h MeO MeO

0% yield 93% yield

Me Me Me Me

N N CoII t-Bu O O t-Bu

t-Bu t-Bu

CoII Catalyst A

1 mol% CoII Catalyst A

1.1 equiv N-F Me3-pyridinium BF4 MeO MeO Me 1 equiv PhSiH3 96% yield OEt MeO EtOH, 0 ºC, 0.5 h MeO

Shigehisa, H. Chem. Pharm. Bull. 2018, 66, 339 Shigehisa, H.; Aoki, T.; Yamaguchi, S.; Shimizu, N.; Hiroya, K. J. Am. Chem. Soc. 2013, 135, 10306 Hydroalkoxylation of Olefin: Scope

1– 5 mol% CoII Catalyst A

1.1–3 equiv N-F Me3-pyridinium (BF4) or (OTf) 1–2 equiv PhSiH3 or (Me2SiH)2O R1 Me R1 OR ROH or ROH/PhCF3, 0 ºC

Ot-Bu O MeO Me Me Me Me HO O 7 7 Ot-Bu OMe S Ot-Bu MeO Cl

92% yield 88% yield 76% yield 42% yield

O O O

Me Me H2N Me O O O 7 7 7 Ot-Bu OMe Ot-Bu N O2N Ph

7% yield 55% yield 9% yield with MeOH: 33% yield with MeOH: 55% yield

Shigehisa, H.; Aoki, T.; Yamaguchi, S.; Shimizu, N.; Hiroya, K. J. Am. Chem. Soc. 2013, 135, 10306 Hydroalkoxylation of Olefin: Tertiary Alkyl C–O Formation

MeO Co MeO OR

Me Me Me MeO MeOH or t-BuOH/PhCF3 MeO

R = Me, 71% yield R = t-Bu, 34% yield

Co BzO BzO OR

Me Me Me MeOH or t-BuOH/PhCF3

R = Me, 51% yield R = t-Bu, 34% yield

Co BzO Me BzO OR

Me Me Me MeOH or t-BuOH/PhCF3

R = Me, 57% yield R = t-Bu, 24% yield

Shigehisa, H.; Aoki, T.; Yamaguchi, S.; Shimizu, N.; Hiroya, K. J. Am. Chem. Soc. 2013, 135, 10306 Hydroalkoxylation of Olefin: not as Solvent

OMe MeO MeO Co OH MeO O OMe MeO MeO PhCF3 Me MeO x equiv y equiv

x equiv y equiv yield

1 equiv 2 equiv 79% yield

2 equiv 1 equiv 80% yield

1 equiv 1 equiv 67% yield

Shigehisa, H.; Aoki, T.; Yamaguchi, S.; Shimizu, N.; Hiroya, K. J. Am. Chem. Soc. 2013, 135, 10306 Hydroalkoxylation of Olefin: Proposed Mechanism

Me Me BF4 step A II III III 2 LnCo LnCo –F [LnCo ](BF4) Me N Me Me N Me F

step B III III LnCo –F PhSiH3 LnCo –H PhSiH2F

step C III II L Co –H R L Co n R Me n

step D III II [L Co ](BF ) BF L Co R Me n 4 R Me 4 n

Me Me step E OR1 BF4 BF R1OH R Me 4 R Me Me N Me Me N Me H

Shigehisa, H.; Aoki, T.; Yamaguchi, S.; Shimizu, N.; Hiroya, K. J. Am. Chem. Soc. 2013, 135, 10306 Hydroalkoxylation of Olefin: Mechanistic Studies

Dueterium labeling

MeO Me Co MeO Co MeO D

OCD3 OMe MeO PhSiH3 MeO PhSiD3 MeO CD3OD MeOH 90% yield 92% yield

Radical Clock

Co Me Me MeOH

OMe Me Me

33% yield

Shigehisa, H.; Aoki, T.; Yamaguchi, S.; Shimizu, N.; Hiroya, K. J. Am. Chem. Soc. 2013, 135, 10306 Hydroalkoxylation of Olefin: Mechanistic Studies

Ph Ph Co Ph Ph Ph Ph HO HO Me MeOH O Me

92% yield

Ph Ph Co Ph Ph Ph Ph – TBS+ TBSO TBSO Me MeOH O Me

89% yield

Shigehisa, H.; Aoki, T.; Yamaguchi, S.; Shimizu, N.; Hiroya, K. J. Am. Chem. Soc. 2013, 135, 10306 Intramolecular Hydroalkoxylation of Olefin with Protected Alcohol

3 mol% CoII Catalyst A

2 equiv N-F Me3-pyridinium (OTf) Ph Ph Ph Ph 2 equiv (Me2SiH)2O O PG toluene, r.t. O Me

PG time (h) yield

TBS 0.5 99% Me

MOM 0.5 99% OTf

MEM 0.5 97% Me N Me PG BOM 0.5 99% PG = MOM, Bn, Me Bn 1.5 93% major by-product Me 1.5 87% (>80% yield)

Ac 6.5 27%

Shigehisa, H. et. al., J. Am. Chem. Soc. 2016, 138, 10597 Intramolecular Hydroalkoxylation of Olefin with Protected Alcohol

3 mol% CoII Catalyst A

2 equiv N-F Me3-pyridinium (OTf) 2 equiv (Me2SiH)2O n n PG Me toluene, r.t. O R O R

Bn OMOM Ph Bn OH OMOM HO Me HO Me OMe

Bn OMOM Me Ph Bn Me O Me O Me O Me O Me OMe

91% yield 91% yield 55% yield 90% yield

Shigehisa, H. et. al., J. Am. Chem. Soc. 2016, 138, 10597 Intramolecular Hydroalkoxylation of Olefin with Acid and

3 mol% CoII Catalyst A

2 equiv N-F Me3-pyridinium (OTf) Ph Ph Ph Ph 2 equiv (Me SiH) O 2 2 O O PG toluene, r.t. O O Me

PG time (h) yield

H 21 84%

Me 0.5 99%

Et 1 99%

Bn 19 97%

PMB 3 99%

t-Bu 19 93%

Shigehisa, H. et. al., J. Am. Chem. Soc. 2016, 138, 10597 Intramolecular Hydroalkoxylation of Olefin with Acid and Esters

3 mol% CoII Catalyst A

2 equiv N-F Me3-pyridinium (OTf) 2 equiv (Me2SiH)2O n n

PG toluene, r.t. O O Me O O

O O OH OMe OMe OH MeO Ph O OH O

O Me Me

Ph O O O O MeO Me O Me O OH O

96% yield 76% yield 88% yield 86% yield

Shigehisa, H. et. al., J. Am. Chem. Soc. 2016, 138, 10597 Intramolecular Hydroalkoxylation of Olefin with Acid and Esters

3 mol% CoII Catalyst 2 equiv N-F Me -pyridinium (OTf) 3 Ph Ph Ph 2 equiv (Me SiH) O 2 2 Ph O OH 7 toluene, r.t. Me

Me Me Me Me N N N N CoII II Co t-Hex O O t-Hex t-Bu O O t-Bu

t-Hex t-Hex t-Bu t-Bu CoII Catalyst B CoII Catalyst A

30% yield 60% yield

O Ts PMP O Me N Me O 7 O 69% yield 8 59% yield 9 33% yield O Me O Me Me Me

Shigehisa, H. et. al., J. Am. Chem. Soc. 2016, 138, 10597 Intramolecular Hydroamination of Olefin

3–6 mol% CoII Catalyst A

2 equiv N-F Me3-pyridinium (BF4) or (OTf) n n 2 equiv (Me2SiH)2O 1 Me R N R N toluene, r.t. R H R1

Ph Ph Me H N HN Me HN NH Ts HN Ns Me Cbz Ns Ns

Ph Ph Ts Me Me Me N Me N N Me N Me N Me Me Cbz Ns Ns Ns

90% yield 55% yield 68% yield 42% yield 56% yield

Shigehisa, H.; Koseki, N.; Shimizu, N.; Fujisawa, M.; Niitsu, M.; Hiroya, K. J. Am. Chem. Soc. 2014, 136, 13534 Intramolecular Hydroamination of Olefin: Oxygen v.s. Nitrogen

3 mol% CoII Catalyst A

PG 2 equiv N-F Me3-pyridinium (BF4) OPG NHNs 2 equiv (Me SiH) O Ns O 2 2 N O H N toluene, r.t. Ns Me Me

C–N product C–O product

PG C–N product C–O product

H 0% 67%

MOM 24% 54%

TBS 43% 50%

Ac 89% 0%

Shigehisa, H.; Koseki, N.; Shimizu, N.; Fujisawa, M.; Niitsu, M.; Hiroya, K. J. Am. Chem. Soc. 2014, 136, 13534 Other Applications: Arenes and Thioester as

MeO O O Co MeO O O

Boc Boc 74% yield N N-F Me -pyridinium (OTf) N H 3 H Me Me Me (Me2SiH)2O, PhCF3, r.t.

NTs

NTs Co S 92% yield N-F Me -pyridinium (OTf) 3 Me O S (Me2SiH)2O, PhCF3, r.t.

OMe

Shigehisa, H.; Ano, T.; Honma, H.; Ebisawa, K.; Hiroya, K. Org. Lett. 2016, 18, 3622 Date, S.; Hamasaki, K.; Sunagawa, K.; Koyama, H.; Sebe, C.; Hiroya, K.; Shigehisa, H. ACS Catal. 2020, 10, 2039 Alternative Pathway to Generate Carbocations: Alkylcobalt(IV)

step C III II L Co –H R L Co n R Me n

step D III II [L Co ](BF ) BF L Co R Me n 4 R Me 4 n

III step C’ Co Ln III LnCo –H R R Me

III IV Nu Co Ln step D’ Co Ln step E’ oxidant II LnCo R Me R Me Nu R Me

III oxidant = N-F pyridinium salt or [Co Ln](BF4) Generation of Alkylcobalt(IV) and Reacting with Nucleophiles: Literature Precedents

H O O Bn Me N N Me III IV 2– IV + III 3– Co Ir Cl6 SET [Bn–Co (dmgH)2(H2O)] Ir Cl6 Me N N Me O2H O O H

III Bn–Co (dmgH)2(H2O)

ox R E1/2 (v.s. SCE, in HClO4 aq.) H O O R Me 0.902 V Me N N Me CoIII Me N N Me Et 0.878 V O2H O O n-Pr 0.867 V H

III i-Pr 0.856 V R–Co (dmgH)2(H2O) Bn 0.859 V

Abley, P.; Dockal, E. R.; Halpern, J. J. Am. Chem. Soc. 1972, 94, 659 Halpern, J.; Chan, M. S.; Hanson, J.; Roche, T. S.; Topich, J. A. J. Am. Chem. Soc. 1975, 97, 1606 Generation of Alkylcobalt(IV) and Reacting with Nucleophiles: Literature Precedents

Me C6H13 SN2 nucleophilic substitution Me C6H13 I – [Co (dmgH)2(py)] III Br inversion Co (dmgH)2(py)

+ Me C H CeIV, MeOH/H O, H+, – HPy+ 6 13 2 Me C6H13

CoIII(dmgH) (py) IV 2 oxidation Co (dmgH)2(H2O)

+ S 2 nucleophilic substitution Me C6H13 N Me C6H13 – II Cl Co (dmgH)2(H2O) IV Cl Co (dmgH)2(H2O) inversion

The cobalt part of an alkylcobalt(IV) species is functioning as a great in SN2 reactions

Anderson, S. N.; Ballard, D. H.; Chrzastowski, J. Z.; Dodd, D.; Johnson, M. D. J. Chem. Soc. Chem. Commun. 1972, 685 Magnuson, R. H.; Halpern, J.; Levitin, I. Y.; Vol’pin, M. E. J. Chem. Soc. Chem. Commun. 1978, 44 Divergent Pathways of Alkylcobalt(IV) Generated from Allylic

III IV III Me Co Ln Me Co L LnCo –H oxidation n OH OH OH R 1 1 R R R R R1

intramolecular C–O formation Me O R R1

IV Me Co Ln OH R R1

O semipinacol rearrangement R R1 Me

The ligands can serve as a controlling factor for achieving divergent and selective transformations.

Touney, E. E.; Foy, N. J.; Pronin, S. V. J. Am. Chem. Soc. 2018, 140, 16982 Divergent Functionalization of Allylic Alcohols

5 mol% CoII Catalyst O Me 2 equiv N-F Me -pyridinium (OTf) HO 3 Me O 2 equiv PhMeSiH2 or acetone, 0 ºC or –40 ºC N N N Boc Boc Boc

Me Me Ph Ph Me Me

N N N N CoII CoII t-Bu O O t-Bu t-Bu O O t-Bu

t-Bu t-Bu t-Bu t-Bu

CoII Catalyst A CoII Catalyst C

63% yield ketone 84% epoxide (14% epoxide) (9% ketone)

Touney, E. E.; Foy, N. J.; Pronin, S. V. J. Am. Chem. Soc. 2018, 140, 16982 Divergent Functionalization of Allylic Alcohols

With CoII Catalyst C With CoII Catalyst A

Me O O HO Me 56% yield 66% yield

d.r. = 18:1

t-Bu t-Bu t-Bu

Me Me O HO O 56% yield 32% yield

S S S O O O O O O

O O 90% yield HO 70% yield Me Me

Touney, E. E.; Foy, N. J.; Pronin, S. V. J. Am. Chem. Soc. 2018, 140, 16982 Asymmetric Catalysis for sp3 C–O Formation using Chiral Salen Ligands

Me Ph Ph OH O Ph Ph Catalyst D Catalyst E

HO O N N Me Cbz Cbz 71% yield 77% yield 89% ee 94% ee

O O N N CoII N N O O Ph Ph t-Bu CoII t-Bu O O

t-Bu t-Bu

CoII Catalyst D CoII Catalyst E

Discolo, C. A.; Touney, E. E.; Pronin, S. V. J. Am. Chem. Soc. 2019, 141, 17527 Shigehisa, H. et. al., Chemrxiv doi: 10.26434/chemrxiv.9981395.v1 How to develope intermolecular sp3 C–O and sp3 C–N formation reactions? Intermolecular Hydrofunctionalization using Oxygen and Nitrogen Nucleophiles

II 3.3 mol% Co Catalyst A Me C H I 2 equiv oxidant 9 19 O O 2 equiv (Me2SiH)2O (TMDSO) OH C9H19 solvent, r.t. I O

Me Me Me Me Me

N N BF4 PhO2S SO2Ph CoII N t-Bu O O t-Bu Me N Me F F t-Bu t-Bu

CoII Catalyst A Oxidant 1 Oxidant 2

<10% yield, under a variety of conditions using either oxidant 1 or 2

Zhou, X.-L.; Yang, F.; Sun, H.-L.; Yin, Y.-N.; Ye, W.-T.; Zhu, R. J. Am. Chem. Soc. 2019, 141, 7250 Zhu, R. Synlett 2019, 30, 2015 Intermolecular Hydrofunctionalization using Oxygen and Nitrogen Nucleophiles

3.3 mol% CoII Catalyst A

2 equiv (Me2SiH)2O (TMDSO) R Me R PhIO EtOAc, r.t. Nu

2 equiv 4 equiv Nu = oxidant acid, phenol, (Nu activator) sulfonimide

MeO

PMP PMP C10H21 MeO

NO2 O Ph MeO NTs O O NTs2 2 O PMP Me PMP Me MeO Me C10H21 Me

70% yield 59% yield 76% yield 47% yield

Zhou, X.-L.; Yang, F.; Sun, H.-L.; Yin, Y.-N.; Ye, W.-T.; Zhu, R. J. Am. Chem. Soc. 2019, 141, 7250 Intermolecular Hydrofunctionalization using Oxygen and Nitrogen Nucleophiles

3.3 mol% CoII Catalyst A

2 equiv (Me2SiH)2O (TMDSO) R Me R PhIO Nucleophile EtOAc, r.t. Nu

2 equiv 4 equiv Nu = oxidant acid, phenol, (Nu activator) sulfonimide

OH activated Nucleophile PhIO Nu–H Ph I & Nu oxidant

II OH 2 LnCo III III Ph I R3Si–H LnCo –H LnCo –Nu R3Si–OH PhI Nu

Zhou, X.-L.; Yang, F.; Sun, H.-L.; Yin, Y.-N.; Ye, W.-T.; Zhu, R. J. Am. Chem. Soc. 2019, 141, 7250 Intermolecular Hydrofunctionalization using Oxygen and Nitrogen Nucleophiles

R Me O 3.3 mol% Co(SaltBu,tBu)

2 equiv (Me2SiH)2O (TMDSO) O O R O I DCM, r.t. I OH 2 equiv oxidant & Nu

MeO F PMP

83% yield 71% yield 77% yield 75% yield

O Me Me Ph HO C H Ph 8 10 21

Not applicable (<5% yield) 65% yield

Zhou, X.-L.; Yang, F.; Sun, H.-L.; Yin, Y.-N.; Ye, W.-T.; Zhu, R. J. Am. Chem. Soc. 2019, 141, 7250 Optimization: Some Interesting Findings

Me O 3.3 mol% Co(SaltBu,tBu) C9H19 2 equiv (Me SiH) O (TMDSO) O O 2 2 Me O C9H19 C9H19 I DCM (0.3 M), r.t. I OH B 2 equiv A

2nd order in [Co] 1st order in [Co]

entry deviation from above A (%) B (%)

1 none 84 16 N N 2 24 10 CoII 0.1 M instead of 0.3 M t-Bu O O t-Bu 3 0.1 M, with 10 mol% Co 73 24

t-Bu t-Bu 4 (S,S) cobalt catalyst 81 17 (R,R)-Co(SaltBu,tBu) 5 racemic cobalt catalyst 36 15

Zhou, X.-L.; Yang, F.; Sun, H.-L.; Yin, Y.-N.; Ye, W.-T.; Zhu, R. J. Am. Chem. Soc. 2019, 141, 7250 Proposed Mechanism: Bimetallic C–O Formation

Nu H R Me R CoIII Me

Me R Bimetallic C–O III formation Co isomerization side reaction

R Nu H Me

2 CoII CoIII + CoIII CoII

PhIO

R3SiH NuH

PhI

R3Si–OH R

Zhou, X.-L.; Yang, F.; Sun, H.-L.; Yin, Y.-N.; Ye, W.-T.; Zhu, R. J. Am. Chem. Soc. 2019, 141, 7250 Outline

III Co Ln

R Me R Me Co + silane Co radical alkylcobalt R R Me regioselective olefin alkyl radical R Me R Me

carbocation carbanion Olefins as Carbanion Precursors

O OH L CoIII–H CoIIIL H R1 n n R R or 1 R Me R R Me Me

O OH III III Co to Cr L Co –H Co Ln Cr H R1 n R R R1 R Me transmetallation R Me Me anion surrogate

Matos, J. L. M.; Vásquez-Céspedes, S.; Gu, J.; Oguma, T.; Shenvi, R. A. J. Am. Chem. Soc. 2018, 140, 16976 Olefins as Carbanion Precursors

10 mol% Co(SaltBu,tBu)

10 mol% N-F Me3-pyridinium BF4 1 equiv CrCl3 Me 2 equiv PhSiH3 Bn Bn CF3 THF/MeCN or DME, r.t. OHC CF3 OH 70% yield (1:1 d.r.) without Cr: 0% yield without CrCl2: 0% yield

S Me Me Me Me Bn Bn N Bn Me

OH OH OH Me Me

68% yield 90% yield 62% yield

Me Me Me Bn Me Me OH Me OH OH

84% yield 52% yield 33% yield

Matos, J. L. M.; Vásquez-Céspedes, S.; Gu, J.; Oguma, T.; Shenvi, R. A. J. Am. Chem. Soc. 2018, 140, 16976 Olefins as Carbanion Precursors: Mechanistic Studies

MHAT add Cr Me Bn Bn ◉ ◉ CF3 OHC CF time 3 OH

time yield

0 s 90%

10 s 90%

10 min 71%

60 min 86%

L CoIII–H CoIIIL n n stable species at r.t. in solution R R Me

Matos, J. L. M.; Vásquez-Céspedes, S.; Gu, J.; Oguma, T.; Shenvi, R. A. J. Am. Chem. Soc. 2018, 140, 16976 Olefins as Carbanion Precursors: Mechanistic Studies

Me Me

Me 2 equiv CrCl3(THF)3 N N Me CF CoIII 3 OHC CF3 THF, r.t. t-Bu O O t-Bu OH

t-Bu t-Bu 2 equiv L 0% yield

Me Me

Me 2 equiv CrCl2 N N Me CF CoIII 3 OHC CF3 THF, r.t. t-Bu O O t-Bu OH

t-Bu t-Bu 2 equiv L 50% yield

◉ CoIII to CrII transmetallation (alkyl transfer) ◉ CrII was generated through reduction using silane

Matos, J. L. M.; Vásquez-Céspedes, S.; Gu, J.; Oguma, T.; Shenvi, R. A. J. Am. Chem. Soc. 2018, 140, 16976 Summary

III Co Ln

R Me R Me Co + silane Co radical alkylcobalt R R Me regioselective olefin alkyl radical R Me R Me

carbocation carbanion

Reviews for further reading:

Shenvi, R. A. et. al., Chem. Rev. 2016, 116, 8912 Shenvi, R. A. et. al., Acc. Chem. Soc. 2018, 51, 2628 Shenvi, R. A. et. al., Chapter 7. Markovnikov Functionalization by Hydrogen Atom Transfer Organic Reactions, 2019, 100, 383 Shigehisa, H. Chem. Pharm. Bull. 2018, 66, 339 Zhu, R. Synlett 2019, 30, 2015

Michiyuki, T.; Komeyama, K. Asian J. Org. Chem. 2020, 9, 1 “Recent Advances in Four-Coordinated Planar Cobalt Catalysis in