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Cu-Catalyzed Decarboxylative Borylation Phil S. Baran, Jie Wang, ming shang, Helena Lundberg, Karla S. Feu, Scott J. Hecker, Tian Qin, and Donna G. Blackmond ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b02928 • Publication Date (Web): 13 Sep 2018 Downloaded from http://pubs.acs.org on September 13, 2018
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ACS Catalysis
Cu-Catalyzed Decarboxylative Borylation Jie Wang‡,†, Ming Shang‡,†, Helena Lundberg‡, Karla S. Feu‡, Scott J. Hecker§, Tian Qin‡, Donna G. Blackmond*,‡ and Phil S. Baran*,‡ ‡
The Scripps Research Institute (TSRI), North Torrey Pines Road, La Jolla, California, 92037, United States
§
The Medicines Company, 3013 Science Park Road, San Diego, CA 92121, United States
1. [Ni]/L, B2pin2, MeLi ABSTRACT: A simple method for the conversion of carboxylic Science, 2017, 356, eaam7355 Me acids to boronic esters via redox-active esters (RAEs) is reportMe O 2. [hν], B2cat2; pinacol O O Me ed using copper catalysis. The scope of this transformation is Science, 2017, 356, aan3679 N R1 R1 B O Me O broad and compared to the known protocols available it repreO 3. [PET]/Ir, B2pin2 R2 R3 R2 R3 sents the most inexpensive, rapid, and operationally simple Org Lett, 2017, 19, 2770 derived from alkyl boronic ester carboxylic acid option. In addition to a full exploration of the scope, a kinetic Something better needed study was performed to elucidate substrate and reagent con- [Cu] decarboxylative borylation: • practical procedure (mix and stir) • short reaction time (finished in 30 examples • primary, secondary, tertiary acids • in situ activation • broad functional group tolerance • mild, scalable • natural products • drug molecules
[isolated] or [in situ]
A Primary Acids Bpin
Bpin
CO2Me Ph 6, 76%, 59%b, 11, 70%, 57%d b,c 55% e [Ni]e 52% [hν]f [Ni] 65% g 41% [PET]g 71% [PET] 54%
R = H, 12, 72%; [PET]g 54% BocN R = F, 13, 60%
Bpin
Bpin
MeO
RN
Bpin
15, 69%
BocHN
17, 40% [hν]f 16%, 42% (NMR)
Bpin 16, 56%
F
Bpin O
R = Ts, 21, 66% F 23, 75% R = Boc, 22, 68% [Ni]e 53% [hν]f 87% [hν]f 66%
24, 66%, [hν]f 32%
48%d
Bpin Me
Me Me Me
N
Bpin Me Ph
N Boc
BocHN 26, 56%
25, 62%
27, 59%, dr 10:1 28, 65% 54%,d dr 10:1 [Ni]e 58%,dr>15:1 OMe
Bu
C Natural Products and Drug Molecules Cl
O N
Bpin
from chlorambucil
Ph
34, 57 % [Ni]e 27%
Me
O
O
O
Bpin
Ph NH
from atorvastatin 36, 52% [Ni]e 57%
Bpin
O
F Me H
O from dehydrocholic acid H
Me Me
O H
H
Bpin 38, 69% [Ni]e 65% [PET]g 67%
D Limitations
from gabapentin 39, 83% [Ni]e 64%
Bpin Bpin
Br
4
from arachidonic acid 40, 35% [hν]f 58%
Br 44, 20:1 [hν]f 60%, 98:2 dr
Bpin
Bpin
MeO O
18, 70%, 54%d
B Secondary and Tertiary Acids Bpin
Bpin
Bpin
O
NHBoc 14, 55%
R
Bpin
Bpin
Bpin
Bpin N Boc 47,
