Journal of the American Chemical Society
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(5) For selected reviews, see: (a) Seebach, D.; Enders, D.
Advances in Chromium(II)- and Chromium(III)-Mediated Organic
Synthesis. Synthesis 1999, 1, 1–36. (c) Hargaden, G. C.; Guiry, P. J.
The Development of the Asymmetric Nozaki–Hiyama–Kishi
Reaction. Adv. Synth. Catal. 2007, 349, 2407–2424. (d) Tian, Q.;
Zhang, G. Recent Advances in the Asymmetric Nozaki–Hiyama–
Kishi Reaction. Synthesis 2016, 48, 4038–4049.
Umpolung of Amine Reactivity. Nucleophilic α-(Secondary Amino)-
alkylation via Metalated Nitrosamines. Angew. Chem., Int. Ed. 1975,
14, 15–32. (b) Beak, P.; Zajdel, W. J.; Reitz, D. B. Metalation and
electrophilic substitution of amine derivatives adjacent to
nitrogen: α-metallo amine synthetic equivalents. Chem. Rev. 1984,
84, 471–523. (c) Peterson, D. J. N,N-Disubstituted
Aminomethyllithium Compounds. J. Am. Chem. Soc. 1971, 93,
4027–4031. Alternatively, α-amino carbanions can be generated
from the corresponding silanes mediated by fluoride. However,
this approach is limited to protected amines or an additional arene
is needed to stabilize the generated carbanion. For seminal
publications, see: (d) Tsuge, O.; Tanaka, J.; Kanemasa, S.
Nucleophilic Aminomethylation of Aldehydes with α-Amino
Alkylsilanes. Bull. Chem. Soc. Jpn. 1985, 58, 1991–1999. (e)
Shimizu, S.; Ogata, M. Fluoride- or Alkoxide-Induced Reaction of 1-
[Trimethylsilyl)methyl]azoles with Carbonyl Compounds. J. Org.
Chem. 1986, 51, 3897–3900. (f) Katritzky, A. R.; Sengupta, S. Facile
Desilylative Hydroxyalkylation and Acylation of 1-Trimethylsilyl-
2-pyridone. Tetrahedron Lett. 1987, 28, 5419–5422. (g) Cuevas, J.-
C.; Snieckus, V. α’-Silylated Tertiary Benzamides as Dual Ortho- and
α’-Carbanion Synthons. Carbodesilylative Routes to Isoquinoline
and Dibenzoquinolizidine Derivatives. Tetrahedron Lett. 1989, 30,
5837–5840.
(6) A similar retrosynthetic disconnection can be achieved
using other methods. For selected photochemical examples, see:
(a) Yoon, U. C.; Kim, D. U.; Lee, C. W.; Choi, Y. S.; Lee, Y.-J.; Ammon,
H. L.; Mariano, P. S. Novel and Efficient Azomethine Ylide Forming
Photoreactions of N-(Silylmethyl)phthalimides and Related Acid
and Alcohol Derivatives. J. Am. Chem. Soc. 1995, 117, 2698–2710.
(b) Ma, J.; Harms, K.; Meggers, E. Enantioselective
rhodium/ruthenium photoredox catalysis en route to chiral 1,2-
aminoalcohols. Chem. Commun. 2016, 52, 10183–10186. (c) Ding,
W.; Lu, L.-Q.; Liu, J.; Liu, D.; Song, H.-T.; Xiao, W.-J. Visible Light
Photocatalytic Radical–Radical Cross-Coupling Reactions of
Amines and Carbonyls: A Route to 1,2-Amino Alcohols. J. Org. Chem.
2016, 81, 7237–7243. (d) Wang, C.; Qin, J.; Shen, X.; Riedel, R.;
Harms, K.; Meggers, E. Asymmetric Radical–Radical Cross-
Coupling through Visible-Light-Activated Iridium Catalysis. Angew.
Chem., Int. Ed. 2016, 55, 685–688. (e) Ye, C.-X.; Melcamu, Y. Y.; Li,
H.-H.; Cheng, J.-T,; Zhang, T.-T.; Ruan, Y.-P.; Zheng, X.; Lu, X.; Huang,
P.-Q. Dual Catalysis for Enantioselective Convergent Synthesis of
Enantiopure Vicinal Amino Alcohols. Nature Commun. 2018, 9,
Article Nr. 410. (f) Rono, L. J.; Yayla, H. G.; Wang, D. Y.; Armstrong,
M. F.; Knowles, R. R. Enantioselective Photoredox Catalysis Enabled
by Proton-Coupled Electron Transfer: Development of an
Asymmetric Azo-Pinacol Cyclization. J. Am. Chem. Soc. 2013, 135,
17735–17738. (g) Chen, Q.; Yang, H. Photoredox-Catalyzed Direct
Aminoalkylation of Isatins: Diastereoselective Access to 3-
Hydroxy-3-aminoalkylindolin-2-ones Analogues. Org. Chem. Front.
2018, 5, 1608–1612. For selected examples using low-valent
transition metals, see: (h) Roskamp, E. J.; Pedersen, S. F. The First
Practical Niobium(III) Reagent in Organic Synthesis. A Convenient
Route to 2-Amino Alcohols via the Coupling of Imines with
Aldehydes or Ketones Promoted by NbCl3(DME). J. Am. Chem. Soc.
1987, 109, 6551–6553. (i) Zhong, Y.-W.; Dong, Y.-Z.; Fang, K.; Izumi,
K.; Xu, M.-H.; Lin, G.-Q. A Highly Efficient and Direct Approach for
Synthesis of Enantiopure ß-Amino Alcohols by Reductive Cross-
Coupling of Chiral N-tert-Butanesulfinyl Imines with Aldehydes. J.
Am. Chem. Soc. 2005, 127, 11956–11957. For a recent copper-
catalyzed coupling between aromatic carbonyls and imines see: (j)
Takeda, M.; Mitsui, A.; Nagao, K.; Ohmiya, H. J. Am. Chem. Soc. 2019,
141, 3664–3669.
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5
6
7
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(8) For selected reviews on the use of the Nozaki-Hiyama-
Kishi reaction in total synthesis, see: (a) Andrushko, V.; Andrushko,
N. Stereoselective Synthesis of Drugs and Natural Products; John
Wiley & Sons, Inc.: Hoboken, NJ, USA, 2013. (b) Gil, A.; Albericio, F.;
Álvarez, M. Role of the Nozaki-Hiyama-Takai-Kishi Reaction in the
Synthesis of Natural Products. Chem. Rev. 2017, 117, 8420–8446.
(9) For selected seminal publications of the Nozaki-Hiyama-
Kishi reaction, see: (a) Okude, Y.; Hirano, S.; Hiyama, T.; Nozaki, H.
Grignard-type carbonyl addition of allyl halides by means of
chromous salt. A chemospecific synthesis of homoallyl alcohols. J.
Am. Chem. Soc. 1977, 99, 3179–3181. (b) Jin, H.; Uenishi, J.; Christ,
W. J.; Kishi, Y. Catalytic effect of nickel(II) chloride and
palladium(II) acetate on chromium(II)-mediated coupling reaction
of iodo olefins with aldehydes. J. Am. Chem. Soc. 1986, 108, 5644–
5646. (c) Takai, K.; Tagashira, M.; Kuroda, T.; Oshima, K.; Utimoto,
K.; Nozaki, H. Reactions of alkenylchromium reagents prepared
from alkenyl trifluoromethanesulfonates (triflates) with
chromium(II) chloride under nickel catalysis. J. Am. Chem. Soc.
1986, 108, 6048–6050. (d) Fürstner, A.; Shi, N.
Nozaki−Hiyama−Kishi Reactions Catalytic in Chromium. J. Am.
Chem. Soc. 1996, 118, 12349–12357. (e) Fürstner, A.; Shi, N. A
Multicomponent Redox System Accounts for the First
Nozaki−Hiyama−Kishi Reactions Catalytic in Chromium. J. Am.
Chem. Soc. 1996, 118, 2533–2534. (f) Bandini, M.; Cozzi, P. G.;
Melchiorre, P.; Umani-Ronchi, A. The First Catalytic
Enantioselective Nozaki-Hiyama Reaction. Angew. Chem., Int. Ed.
1999, 38, 3357–3359.
(10) (a) Takai, K.; Nitta, K.; Fujimura, O.; Utimoto, K.
Preparation of alkylchromium reagents by reduction of alkyl
halides with chromium(II) chloride under cobalt catalysis. J. Org.
Chem. 1989, 54, 4732–4734. (b) Matos, J. L. M.; Vásquez-Céspedes,
S.; Gu, J.; Oguma, T.; Shenvi, R. A. Branch-Selective Addition of
Unactivated Olefins into Imines and Aldehydes. J. Am. Chem. Soc.
2018, 140, 16976–16981. (c) Ni, S.; Padial, N. M.; Kingston, C.;
Vantourout, J. C.; Schmitt, D. C.; Edwards, J. T.; Kruszyk, M. M.;
Merchant, R. R.; Mykhailiuk, P. K.; Sanchez, B. B.; Yang, S.; Perry, M.
A.; Gallego, G. M.; Mousseau, J. J.; Collins, M. R.; Cherney, R. J.; Lebed,
P. S.; Chen, J. S.; Qin, T.; Baran, P. S. A Radical Approach to Anionic
Chemistry: Synthesis of Ketones, Alcohols, and Amines. J. Am. Chem.
Soc. 2019, 141, 6726–6739.
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57
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(11) (a) Knochel reported on one exception if the amine is
protected as
a succinimide or phthalimide to reduce the
destabilizing interaction of the lone pairs. This strategy, however,
cannot be employed for unprotected tertiary amines. Knochel, P.;
Chou, T. S.; Jubert, C.; Rajagopal, D. Preparation and reactivity of
highly functionalized organometallics at the α position of oxygen
or nitrogen. J. Org. Chem. 1993, 58, 588–599. (b) Steinborn
reported on the isolation of one α-aminoalkyl–CrIII complex. The
reactivity of this complex, however, was not studied. Becke, F.;
Wiegeleben, P.; Rüffer, T.; Wagner, C.; Boese, R.; Bläser, D.;
Steinborn, D. Organometallics 1998, 17, 475–478.
(12) (a) Schwarz, J. L.; Schäfers, F.; Tlahuext-Aca, A.;
Lückemeier, L.; Glorius, F. Diastereoselective Allylation of
Aldehydes by Dual Photoredox and Chromium Catalysis. J. Am.
Chem. Soc. 2018, 140, 12705–12709. (b) Mitsunuma, H.; Tanabe, S.;
Fuse, H.; Ohkubo, K.; Kanai, M. Catalytic asymmetric allylation of
aldehydes with alkenes through allylic C(sp3)–H functionalization
mediated by organophotoredox and chiral chromium hybrid
catalysis. Chem. Sci. 2019, 10, 3459–3465.
(7) For selected reviews on Cr-mediated carbonyl
functionalization, see: (a) Fürstner, A. Carbon−Carbon Bond
Formations Involving Organochromium(III) Reagents. Chem. Rev.
1999, 99, 991–1046. (b) Wessjohann, L. A.; Scheid, G. Recent
(13) For selected reviews about photoredox catalysis, see: (a)
Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Visible light
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