Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• , forming a new C(sp3)–C(sp3) bond. The reaction can be performed in a phosphate-buffered saline (PBS) solution and shows post-functionalization prospects through pathways involving classical peptide chemistry. Keywords: dehydroalanine; Giese-type reaction; hydroalkylation; photocatalysis; water

• pathway for the functionalization of an electron-deficient olefin is the Giese reaction (Figure 1) [6][7]. This reaction involves the hydroalkylation of the olefin via radical addition (RA), followed by either hydrogen-atom transfer (HAT) or single-electron transfer (SET) and protonation. Traditionally

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• bond homolysis. In 2022, MacMillan and co-workers [56] outlined a comprehensive and direct deoxygenative hydroalkylation method for various types of electrophilic olefins (Scheme 20). This method involved primary, secondary, and tertiary alcohols and was facilitated by the use of a newly developed NHC

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• example, the NHPI ester derived from pivalic acid 58 and Hantzsch ester HE form EDA complex 59 which participates in radical mediated hydroalkylation reactions [60][61] (Scheme 13A). In the presence of electron deficient olefin 60, classic Giese-type addition takes place under photocatalyst-free

• hydrogen atom to terminate the radical reaction. The proposed mechanism of the hydroalkylation cascade is depicted in Scheme 13B. Upon excitation of complex 59 with blue light, intra-complex SET takes place from the HE to the NHPI ester, leading to the formation of tert-butyl radical 64 and radical cation

• Z-monofluoroalkene product 136 is achieved through anticoplanar elimination of fluoride. Shuhua Li and co-workers reported the generation of alkyl radicals from NHPI esters, mediated by a pyridine-boryl radical reductant species in the context of alkene hydroalkylation [104] and cross

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• method allows the efficient alkylation of aromatic rings, can directly afford pharmaceutically significant heterocycles, and the raw materials and iron catalysts are safe and readily available. In 2017, Xu, Loh, and co-workers, demonstrated an iron-catalyzed hydroalkylation reaction of α,β-unsaturated

• -catalyzed CDC reaction of N-methylaniline with ethers. Fe-catalyzed CDC of C(sp3)–H/C(sp3)–H bonds. Fe-catalyzed hydroalkylation of α,β-unsaturated ketones with ethers. Solvent-free Fe(NO3)3-catalyzed CDC of C(sp3)–H/C(sp2)–H bonds. Alkylation of disulfide compounds to afford tetrasubstituted alkenes. Fe

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• . Proposed catalytic cycle for the nickel/photoredox-catalyzed methylation of (hetero)aryl chlorides using trimethyl orthoformate. Proposed mechanism for the photoredox nickel-catalyzed hydroalkylation of internal alkynes. Proposed mechanism for the photoredox nickel-catalyzed acylation of α-amino C(sp3)–H

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• established as an excellent strategy for the construction of elaborate molecules. In particular, the hydroalkylation of olefins represents a straightforward strategy for the synthesis of new C(sp3)–C(sp3) bonds, with concomitant formation of challenging quaternary carbon centers. In the last 20 years

• , numerous hydroalkylation methodologies have emerged that have explored the diverse reactivity patterns of the olefin double bond. This review presents examples of olefins acting as electrophilic partners when coordinated with electrophilic transition-metal complexes or, in more recent approaches, when used

• as precursors of nucleophilic radical species in metal hydride hydrogen atom transfer reactions. This unique reactivity, combined with the wide availability of olefins as starting materials and the success reported in the construction of all-carbon C(sp3) quaternary centers, makes hydroalkylation

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

Copper-catalyzed stereoselective conjugate addition of alkylboranes to alkynoates

• Takamichi Wakamatsu,
• Kazunori Nagao,
• Hirohisa Ohmiya and
• Masaya Sawamura

Beilstein J. Org. Chem. 2015, 11, 2444–2450, doi:10.3762/bjoc.11.265

• alkenes with 9-BBN-H) to alkynoates to form β-disubstituted acrylates is reported. The addition occurred in a formal syn-hydroalkylation mode. The syn stereoselectivity was excellent regardless of the substrate structure. A variety of functional groups were compatible with the conjugate addition

• methoxide to form trisubstituted alkenylstannanes [15]. The latter reaction pathway involved Sn-trapping of an alkenylcopper intermediate that was formed through syn-carbocupration of an alkylcopper(I) species across the C–C triple bond of the alkynoate. We envisioned that 1,2-hydroalkylation of the

• alkynoates might be possible through proton-trapping of an alkenylcopper intermediate. Herein, we report a copper-catalyzed conjugate addition of alkylboranes to alkynoates, providing a versatile approach to β-disubstituted acrylates [16][17][18][19]. The addition occurred in a formal syn-hydroalkylation

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• . 4.1 Alkylation of active methylene compounds Hydroalkylation of styrenes, indene and norbornene with 1,3-diketones was firstly reported in 2004 by using AuCl3 and AgOTf in 1:3 ratio as the catalyst (Scheme 15) [51]. The addition took place with Markovnikov selectivity in good yields, however optimal

• inactivated alkenes was also exploited for the synthesis of highly substituted lactams 59, also in a preparative scale [53]. When alkenyl β-keto amides 60 were reacted with a 1:1 mixture of phosphine-gold complex 20a and AgOTf (toluene, 50–90 °C), exo-trig hydroalkylation of the C–C double bond took place

• processes through gold activated olefins allowed expanding the scope of the reaction to other carbon nucleophiles. For examples Che and co-workers reported on the hydroalkylation of alkenes with simple ketones [57]. Reaction of alkenyl ketones with IPrAuCl/AgClO4 (5 mol %) afforded functionalized

Metal–ligand multiple bonds as frustrated Lewis pairs for C–H functionalization

• Matthew T. Whited

Beilstein J. Org. Chem. 2012, 8, 1554–1563, doi:10.3762/bjoc.8.177

• , followed by insertion of an unsaturated substrate (olefin, alkyne) and either a 1,2-elimination (to afford a hydroalkylation or hydroarylation product) or reductive elimination as described above. However, to the best of our knowledge, this type of reactivity has not been observed at early metal imido or

Efficient gold(I)/silver(I)-cocatalyzed cascade intermolecular N-Michael addition/intramolecular hydroalkylation of unactivated alkenes with α-ketones

• Ya-Ping Xiao,
• Xin-Yuan Liu and
• Chi-Ming Che

Beilstein J. Org. Chem. 2011, 7, 1100–1107, doi:10.3762/bjoc.7.126

• hydroalkylation reaction offers a simple and efficient method for the synthesis of pyrrolidine derivatives in moderate to excellent product yields and with moderate to good diastereoselectivities. The reaction conditions and the substrate scope of this reaction are examined, and a possible mechanism involving

• AgClO4 catalyzed intermolecular N-Michael addition and the subsequent gold(I)-catalyzed hydroalkylation is proposed. Keywords: cascade; cocatalyzed; gold(I)-catalyzed; intramolecular hydroalkylation; intermolecular N-Michael addition; pyrrolidine; silver(I)-catalyzed; Introduction Gold complexes are

• cascade intermolecular N-Michael addition/intramolecular hydroalkylation process. A variety of pyrrolidine compounds were conveniently prepared in moderate to excellent yields and with moderate to good diastereoselectivities from the simple starting materials. More recently, we have reported that gold(I

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

• Magnus Rueping and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

• –Crafts alkylation; green chemistry; hydroalkylation; hydroarylation; Lewis-acid catalysis; propargyl alcohols; Introduction In 1887 Charles Friedel and James Mason Crafts isolated amylbenzene after the treatment of amyl chloride with AlCl3 in benzene (Scheme 1) [1]. This was not only one of the first

• para-substituted product 36 was highly preferred. Interestingly, the hydroalkylation of anisole with citral (37) did not result in the expected alkyl-substituted anisole derivative. Instead, the diarylalkane 38 was obtained in 44% yield, most likely through a FC alkylation, cationic cyclization

• “on water”. Reductive FC alkylation of arenes with benzaldehyde and acetophenone catalyzed by the Ir-carbene complex 33. Formal synthesis of 1,1-diarylalkanes from benzyl alcohols and styrenes. (A) Mo-catalyzed hydroarylation of styrenes and cyclohexenes. (B) Hydroalkylation–cyclization cascade