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The Silver-Promoted Phosphonation/Alkynylation of Alkene Proceeding with Radical 1,2- Alkynyl Migration Shengnan Jin, Song Sun, Jin-Tao Yu, and Jiang Cheng J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01088 • Publication Date (Web): 19 Aug 2019 Downloaded from pubs.acs.org on August 19, 2019
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The Journal of Organic Chemistry
The Silver-Promoted Phosphonation/Alkynylation Proceeding with Radical 1,2- Alkynyl Migration
of
Alkene
Shengnan Jin, Song Sun, Jin-Tao Yu, and Jiang Cheng* School of Petrochemical Engineering, Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, Jiangsu Province Key Laboratory of Fine Petrochemical Engineering, Changzhou University, Changzhou 213164, P. R. China
[email protected] RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required according to the journal that you are submitting your paper to)
ABSTRACT O Ar OH R2P(O)H Ar'
Ag2O (2.0 equiv)
Ar
EtOH, 120 oC, 24 h, air
R
P
O R
Ar'
The silver-promoted phosphonation/alkynylation of vinyl in α-aryl α-alkynyl allylic alcohols with phosphine oxide was developed, affording a series of α-alkynyl γ-ketophosphine oxides in moderate to good yields. This procedure involved the radical 3-exo-dig cyclization, proceeding with the radical 1,2-alkynyl migration rather than the aryl migration. The radical-mediated difunctionalization of alkenes represents one of continuously hot topics in organic chemistry.1 Among which, the difunctionalization of unactivated alkenes by means of intramolecular functional-group migrations is particularly appealing.2-5 Pioneered by Li,6 the difunctionalization of vinyl in α,α-diaryl allylic alcohol proceeding with radical 1,2-aryl migration provides a mechanistically different pathway to access functionalized ketone (Scheme 1, eq 1).7 For example, Ji,8 Li,9 Tu10 and Pan11 independently reported oxidative direct C(sp3)-H bonds functionalization of α,α-diaryl allylic alcohols involving concomitant 1,2-aryl migration. Ji also demonstrateded radical phosphonation/arylation of α, α-diaryl allylic alcohols proceeding with the similar procedure (Scheme 1, eq 2).12 One the other hand, Zhu and co-workers pioneered to extend this strategy to the intramolecular distal alkynyl migration, thus realizing the elusive alkynylation of unactivated olefins.13 Later on, Studer and coworkers reported a ACS Paragon Plus Environment
The Journal of Organic Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Page 2 of 24
visible-light promoted α-perfluoroalkyl-β-alkynylation of alkenes via an alkyne radical migration.14 Zhu presented a photocatalytic protocol for the dicarbofunctionalization of unactivated alkenes via tandem radical difluoroalkylation and 1,4-alkynyl migration.15 However, these examples restricted in distal 1,4- or 1,5-alkynyl migration, the radical 1,2alkynyl migration has been rarely studied.16 Recently, Jiang realized the dicarbofunctionalization of 1,4-enynes with simple cycloalkanes via intramolecular 1,2-alkynyl migration by the modification of the vinyl moiety with an isopropenyl group (Scheme 1, eq 3).16a Thus, difunctionalization of 1,4-enynes with other radical precursors by means of 1,2-alkynyl migration remains an area of synthetic interest. Meanwhile, the phosphonation of alkenes17 allows the construction of new C-P bond toward products with diversity and complexity. Herein, we wish to report the silver-promoted phosphonation/alkynylation of alkenyl in αaryl α-alkynyl allylic alcohols by phosphine oxide, proceeding with sequential addition of P-centered radical18 to vinyl, 3-exo-dig cyclization, and radical 1,2-alkynyl migration toward α-alkynyl γ-ketophosphine oxides (Scheme 1, eq 4). Notably, the target γ-ketophosphine oxides show wide-ranging biological activities and unique properties.19 Ar OH
O
1,2- aryl migration
Ar
Ar
dicarbonation of alkene
Ar
FG = C-centered functional group Ar OH Ar'
1,2- aryl migration
FG eq 1
O Ar
phosphonation/arylation of alkene
Ar'
P(O)R2 eq 2
O Ar OH
Ar
1,2- alkynyl migration Ar'
FG
carbonation/alkynylation of alkene FG = C-centered functional group
Ar'
eq 3
O Ar OH
1,2- alkynyl migration Ar'
Ar P(O)R2
phosphonation/alkynylation of alkene this work Ag2O (2.0 equiv), EtOH, 120 oC,24 h
Ar'
eq 4
Scheme 1. The Radical 1,2- Migration in α-Aryl Allylic Alcohols We initially tested the reaction of diphenylphosphine oxide with α-aryl α-alkynyl allylic alcohol 1a (0.2 mmol, 49.6 mg) in the presence of AgOAc (0.4 mmol, 66.8 mg) in 1,4-dioxane (3 mL) under 120 oC. To our delight, the desired product 3aa proceeded with sequential radical addition and 1,2- alkynyl migration was isolated in 32% yield (Table 1, ACS Paragon Plus Environment
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The Journal of Organic Chemistry
entry 1). Replacing Ag2CO3 with AgOAc, the yield increased to 37% (Table 1, entry 2). When Ag2O (65%) and AgO (57%) were used, the yields increased significantly (Table 1, entries 3 and 4). Reducing the equivalent of silver decreased the reaction efficiency and no reaction took place in the absence of silver (Table 1, entries 5 and 6). Some solvents were tested, among which, ethanol was the best (68%, Table 1, entries 7 and 8). The reaction efficiency slightly decreased under higher or lower temperature resulted (110 oC, 63%; 130 oC, 59%, entries 9 and 10). Additionally, increasing the equivalents of silver oxide was not beneficial to the reaction efficiency (entry 11). Table 1. Selected Results for Screening the Optimized Reaction Conditionsa O Ar
Ph OH Ph2P(O)H
Ph
Ph 1a
a
2a
Ar'
O
P
3aa
Ph
entry
additive (x equiv)
solvent
temp (oC)
Yield (%)b
1
AgOAc (2.0)
1,4-dioxane
120
32
2
Ag2CO3 (2.0)
1,4-dioxane
120
37
3
Ag2O (2.0)
1,4-dioxane
120
65
4
AgO (2.0)
1,4-dioxane
120
57
5
Ag2O (0)
1,4-dioxane
120
