Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Mar 27;26(7):3065.
doi: 10.3390/ijms26073065.

Recent Developments in the [1,2]-Phospha-Brook Rearrangement Reaction

Ning Li  1 , Qian Wu  1 , Yu Huang  1 , Enxue Shi  1 , Junchen Li  1
Affiliations
Review

Recent Developments in the [1,2]-Phospha-Brook Rearrangement Reaction

Ning Li et al. Int J Mol Sci. .

Abstract

The [1,2]-phospha-Brook rearrangement serves as a powerful synthetic strategy that enables efficient carbonyl umpolung through phosphoryl group migration, providing direct access to α-hydroxyphosphoryl compounds-a privileged class of synthons with broad applications in organophosphorus chemistry, medicinal chemistry, and materials science. This review provides a comprehensive overview of recent progress in synthetic methodologies, possible mechanisms, and asymmetric transformations, highlighting key breakthroughs and future directions in this rapidly evolving field.

Keywords: [1,2]-phospha-Brook rearrangement; carbonyl compounds; phosphodiesters.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Brook rearrangement and [1,2]-phospha-Brook rearrangement. (a) Brook rearrangement. (b) [1,2]-phospha-Brook rearrangement.
Figure 2
Figure 2
DBU-catalyzed [1,2]-phospha-Brook rearrangement reported by Kaïm.
Figure 3
Figure 3
nBuLi-catalyzed [1,2]-phospha-Brook rearrangement reported by Manab. (A) Selected examples for 2a. (B) Plausible mechanism.
Figure 4
Figure 4
Pd-catalyzed [1,2]-phospha-Brook rearrangement reported by Wu. (A) Selected examples for 4 and 5. (B) Plausible mechanism.
Figure 5
Figure 5
PhOK-mediated [1,2]-phospha-Brook rearrangement reported by Petr.
Figure 6
Figure 6
Cu(OTf)2-catalyzed [1,2]-phospha-Brook rearrangement reported by Yang.
Figure 7
Figure 7
P2-tBu-catalyzed [1,2]-phospha-Brook rearrangement reported by Terda.
Figure 8
Figure 8
KCN-catalyzed [1,2]-phospha-Brook rearrangement reported by Eymur. (A) Selected examples for 12. (B) Plausible mechanism.
Figure 9
Figure 9
KCN/crown-catalyzed [1,2]-phospha-Brook rearrangement reported by Johnson and Saglam. (A) Johnson’s crown-KCN catalytic method. (B) Saglam’s crown/KCN catalytic method.
Figure 10
Figure 10
Et3N-catalyzed [1,2]-phospha-Brook rearrangement reported by Serebryakova and Makhaeva.
Figure 11
Figure 11
KOH-catalyzed [1,2]-phospha-Brook rearrangement reported by Zhao. (A) Selected examples for 20. (B) Plausible mechanism.
Figure 12
Figure 12
P2-tBu-catalyzed [1,2]-phospha-Brook rearrangement reported by Terada. (A) Selected examples for 22. (B) Plausible mechanism.
Figure 13
Figure 13
P(NMe2)3-catalyzed [1,2]-phospha-Brook rearrangement reported by Zi.
Figure 14
Figure 14
Quinine or quinidine-catalyzed [1,2]-phospha-Brook rearrangement reported by Nakamur.
Figure 15
Figure 15
Li(Na)HMDS-mediated [1,2]-phospha-Brook rearrangement reported by Xu. (A) Selected examples for 30 and 31. (B) Plausible mechanism.
Figure 16
Figure 16
LiHMDS-promoted [1,2]-phospha-Brook rearrangement reported by Xu.
Figure 17
Figure 17
tBuNa(Li)-catalyzed [1,2]-phospha-Brook rearrangement reported by Terada.
Figure 18
Figure 18
P2-tBu-catalyzed [1,2]-phospha-Brook rearrangement reported by Terada. (A) Selected examples for 43 and 44. (B) Plausible mechanism.
Figure 19
Figure 19
Iminophosphorane I-catalyzed [1,2]-phospha-Brook rearrangement reported by Johnson.
Figure 20
Figure 20
LiHMDS-mediated [1,2]-phospha-Brook rearrangement reported by Sigh.
Figure 21
Figure 21
Pd-catalyzed [1,2]-phospha-Brook rearrangement reported by Deng. (A) Selected examples for 52. (B) Plausible mechanism.
Figure 22
Figure 22
DBU-catalyzed [1,2]-phospha-Brook rearrangement reported by Yamaguchi.
Figure 23
Figure 23
Quinine-catalyzed [1,2]-phospha-Brook rearrangement reported by Wang.
Figure 24
Figure 24
P2-tBu-catalyzed [1,2]-phospha-Brook rearrangement reported by Terada. (A) Selected examples for 59. (B) Plausible mechanism.
Figure 25
Figure 25
DBU-catalyzed [1,2]-phospha-Brook rearrangement reported by Wu.
Figure 26
Figure 26
LiHMDS-mediated [1,2]-phospha-Brook rearrangement reported by Xu.
Figure 27
Figure 27
KHMDS-promoted [1,2]-phospha-Brook rearrangement reported by Xu.
Figure 28
Figure 28
iPr2NEt-catalyzed [1,2]-phospha-Brook rearrangement reported by Terada.
Figure 29
Figure 29
Iminophosphorane II-catalyzed [1,2]-phospha-Brook rearrangement reported by Oil. (A) Selected examples for 69. (B) Plausible mechanism.
Figure 30
Figure 30
LDA/alkaloid-catalyzed [1,2]-phospha-Brook rearrangement reported by Johnson.
Figure 31
Figure 31
L-PiEt2Me/Sc-catalyzed [1,2]-phospha-Brook rearrangement reported by Feng. (A) Selected examples for 72. (B) Plausible mechanism.
Figure 32
Figure 32
Cinchona alkaloid-catalyzed [1,2]-phospha-Brook rearrangement reported by Sigh.
Figure 33
Figure 33
TMG-catalyzed [1,2]-phospha-Brook rearrangement reported by Xiao.
Figure 34
Figure 34
DBU-catalyzed [1,2]-phospha-Brook rearrangement reported by Liu. (A) Selected examples for 78. (B) Plausible mechanism.
Figure 35
Figure 35
Cs2CO3-mediated [1,2]-phospha-Brook rearrangement reported by Kanai.
Figure 36
Figure 36
P1-tBu/Au-catalyzed [1,2]-phospha-Brook rearrangement reported by Terada. (A) Selected examples for 82. (B) Plausible mechanism.
Figure 37
Figure 37
P2-tBu/acid-catalyzed [1,2]-phospha-Brook rearrangement reported by Terada.
Figure 38
Figure 38
L-PiEt2Me/Sc-catalyzed [1,2]-phospha-Brook rearrangement reported by Feng. (A) Selected examples for 85. (B) Plausible mechanism.
Figure 39
Figure 39
PPS-catalyzed [1,2]-phospha-Brook rearrangement reported by Wang.
Figure 40
Figure 40
Et3N or P1-tBu-mediated [1,2]-phospha-Brook rearrangement reported by Hammerschmidt.
Figure 41
Figure 41
Iminophosphorane II-catalyzed [1,2]-phospha-Brook rearrangement reported by Johnson. (A) Selected examples for 93. (B) Plausible mechanism.
Figure 42
Figure 42
P2-tBu-catalyzed [1,2]-phospha-Brook rearrangement reported by Terada.
Figure 43
Figure 43
tBuOK-catalyzed [1,2]-phospha-Brook rearrangement reported by Terada.
Figure 44
Figure 44
tBuOK-catalyzed [1,2]-phospha-Brook rearrangement reported by Terada.
Figure 45
Figure 45
P2-tBu-catalyzed [1,2]-phospha-Brook rearrangement reported by Terada.
Figure 46
Figure 46
P2-tBu-catalyzed [1,2]-phospha-Brook rearrangement reported by Terada.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Brook A.G. Isomerism of Some α-Hydroxysilanes to Silyl Ethers. J. Am. Chem. Soc. 1958;80:1886–1889. doi: 10.1021/ja01541a026. - DOI
    1. Yang F., Wang J., Dong Y., Zhang N., Zhang C. Transition Metal Promoted Brook Rearrangement and Its Related Reactions. Tetrahedron. 2024;168:134351. doi: 10.1016/j.tet.2024.134351. - DOI
    1. Kondoh A., Terada M. Development of Molecular Transformations on the Basis of Catalytic Generation of Anionic Species by Organosuperbase. Bull. Chem. Soc. Jpn. 2021;94:339–356. doi: 10.1246/bcsj.20200308. - DOI
    1. Kondoh A., Terada M. [1,2]-Phospha-Brook Rearrangement as Tool for Generation of Anionic Nucleophiles in Addition Reactions under Bronsted Base Catalysis. Asian. J. Org. Chem. 2023;12:e202300003.
    1. Kaur R., Singh R.P. Stereoselective Reductive Coupling Reactions Utilizing 1,2-Phospha-Brook Rearrangement: A Powerful Umpolung Approach. J. Org. Chem. 2023;88:10325–10338. - PubMed

MeSH terms

Substances

LinkOut - more resources