Thermally induced [3,3] sigmatropic rearrangement of N-allylhydrazones

Stevens, Roger; McEntire, Edward E.; Barnett, William E.; Wenkert, Ernest

doi:10.1039/c39730000662

“…The [3,3]‐sigmatropic rearrangement is a powerful tool for the construction of carbon–carbon bonds, and it has been used many times in organic synthesis 1. The Stevens rearrangement of N ‐allylhydrazones leads to a new carbon–carbon bond with loss of dinitrogen, but due to the very high temperatures required (up to 300 °C), this reaction is limited in its applications 2. Thomson and coworkers made significant improvements in 2010 when they introduced two modifications: the stability of the reaction substrates was greatly enhanced by using N ‐Boc‐ N ‐allylhydrazones ( A ; Boc = tert ‐butoxycarbonyl); and by using catalytic amounts (10 mol‐%) of the Brønsted acid triflimide (HNTf 2 ) to trigger the rearrangement, the reaction temperature could be lowered to 125 °C 3.…”

Section: Introductionmentioning

confidence: 99%

Triflimide‐Catalysed Rearrangement of N‐(1‐Trimethylsilyl)allylhydrazones Results in the Formation of Vinylsilanes and Cyclopropanes

Dittrich

¹

,

Bracher

²

2015

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“…A [3,3] sigmatropic rearrangement would afford diazonium ion 3, which would react with bromide to produce the benzylic bromide 4 (Nuc = Br).…”

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confidence: 99%

“…

Reliable bond-forming reactions that enable the union of two or more molecular fragments are essential for the efficient and convergent assembly of complex natural products or medicinal agents.[1] As part of a program aimed at developing such reactions, we have been investigating the utility of Nallylhydrazides as versatile chemical intermediates that allow for high yielding fragment coupling by way of hydrazone formation followed by a carbon-carbon bond-forming molecular rearrangement.[2] Most recently, we reported a triflimidecatalyzed rearrangement of N-allylhydrazones (the Stevens [3,3] rearrangement) [3] that allows for a "traceless" bond construction between two fragments.[2c] Prior to this development, we reported an N-bromosuccinimide (NBS)-initiated rearrangement that not only allowed for such fragment assembly but also incorporated an additional bromide atom (i.e., 1!4, Nuc = Br).[2b] We speculated that N-bromination, followed by loss of bromide, initiated the cascade sequence through diazoallene species 2 (Scheme 1). A [3,3] sigmatropic rearrangement would afford diazonium ion 3, which would react with bromide to produce the benzylic bromide 4 (Nuc = Br).

We wished to widen the scope of this cascade sequence to include other nucleophiles, and were especially intrigued by the possibility of initiating the hydrazone oxidation (i.e., 1!2 in Scheme 1) with hypervalent iodine compounds (i.e., PhIX 2 where X = OAc, OTFA, OTf, etc).

[4] We anticipated that the nucleophile in such a system might not necessarily be limited to the coordinated ligand on the iodine atom, providing a useful and powerful strategy to couple multiple species together (i.e., an aldehyde, an allylhydrazide, and the nucleophile).

We initiated our research efforts in this new area by investigating the effects of the commercially available hypervalent iodine compounds, PhI(OAc) 2 (PIDA) and PhI-(OTFA) 2 (PIFA; OTFA = trifluoroacetate), on the hydrazone derived from the condensation of 2-naphthaldehyde and methylallyl hydrazine (i.e., 5; Scheme 2).

…”

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confidence: 99%

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A Hypervalent Iodide‐Initiated Fragment Coupling Cascade of N‐Allylhydrazones

Lutz¹,

Thomson²

2011

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Reliable bond-forming reactions that enable the union of two or more molecular fragments are essential for the efficient and convergent assembly of complex natural products or medicinal agents.[1] As part of a program aimed at developing such reactions, we have been investigating the utility of Nallylhydrazides as versatile chemical intermediates that allow for high yielding fragment coupling by way of hydrazone formation followed by a carbon-carbon bond-forming molecular rearrangement.[2] Most recently, we reported a triflimidecatalyzed rearrangement of N-allylhydrazones (the Stevens [3,3] rearrangement) [3] that allows for a "traceless" bond construction between two fragments.[2c] Prior to this development, we reported an N-bromosuccinimide (NBS)-initiated rearrangement that not only allowed for such fragment assembly but also incorporated an additional bromide atom (i.e., 1!4, Nuc = Br).[2b] We speculated that N-bromination, followed by loss of bromide, initiated the cascade sequence through diazoallene species 2 (Scheme 1). A [3,3] sigmatropic rearrangement would afford diazonium ion 3, which would react with bromide to produce the benzylic bromide 4 (Nuc = Br).We wished to widen the scope of this cascade sequence to include other nucleophiles, and were especially intrigued by the possibility of initiating the hydrazone oxidation (i.e., 1!2 in Scheme 1) with hypervalent iodine compounds (i.e., PhIX 2 where X = OAc, OTFA, OTf, etc).[4] We anticipated that the nucleophile in such a system might not necessarily be limited to the coordinated ligand on the iodine atom, providing a useful and powerful strategy to couple multiple species together (i.e., an aldehyde, an allylhydrazide, and the nucleophile).We initiated our research efforts in this new area by investigating the effects of the commercially available hypervalent iodine compounds, PhI(OAc) 2 (PIDA) and PhI-(OTFA) 2 (PIFA; OTFA = trifluoroacetate), on the hydrazone derived from the condensation of 2-naphthaldehyde and methylallyl hydrazine (i.e., 5; Scheme 2). While PIDA gave no desired product under the conditions explored, PIFA provided trifluoroacetate 6 (X = OTFA) in 43 % yield (Scheme 2 A). This low-yielding result, which could not be improved upon, provided initial evidence that hypervalent iodides were able to promote rearrangements of N-allylhydrazones. It was during an investigation of various exogenous nucleophiles that we ran the reaction between hydrazone 5 and PIFA, in the presence of methanol (10 equiv), and observed formation of the ester 6, along with competitive formation of ether 7 (Scheme 2 B). While it was possible to favor generation of the ether adduct by using methanol as the solvent, this would limit the use of this method to readily available alcohols, and would preclude the use of solid alcohols or those that are part of a more complex fragment. Therefore, we explored the use of PhI(OTf) 2 as an initiator, [5] reasoning that the much less nucleophilic triflate would not compete with the alcohol for incorporation into the substrat...

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“…[6] In particular, we were interested in developing stereoselective fragment-coupling reactions that would allow the simultaneous introduction of the two requisite aryl groups along with the formation of the C7' and C8' stereocenters through a cascade process that involves N-allylhydrazones (Scheme 1). [7] We envisioned that hydrazine 8 would act as a linchpin for the reaction of aryl aldehyde 7 with arene 10 by initial formation of hydrazone 9, which is followed by a hypervalent-iodide-initiated one-pot oxidative [3,3] rearrangement/Friedel-Crafts arylation to afford benzhydryl derivative 11. Previous work from our laboratory has shown that a related oxidative rearrangement of aryl hydrazones (e.g., 15) in the presence of methanol led to the generation of ethers 17.…”

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confidence: 99%