A one-pot synthesis of allenes by the 2-nitrobenzenesulfonylhydrazide-mediated coupling of hydroxyaldehydes or ketones with alkynyl trifluoroborate salts is reported. This mild process involves in situ formation of a sulfonylhydrazone that reacts with alkynyl trifluoroborates to generate a transient propargylic hydrazide species. Decomposition of this unstable hydrazide via an intermediate monoalkyldiazine produces the allene products through an alkene walk mechanism.

The development of a stereoselective one-pot oxidative [3,3] sigmatropic rearrangement/Friedel-Crafts arylation that provides enantioenriched benzhydryl compounds is reported. The utility of this new transformation is demonstrated by the concise synthesis of several tetralone- and naphthyl-type lignan natural products, many of which display anti-malarial activity.

A new method for the stereoselective synthesis of dienes from aldehydes and N-allylhydrazine derivatives has been developed. High levels of (E)-stereoselectivity are obtained for a variety of substrates. Addition of a dienophile to the reaction mixture allows a one-flask diene synthesis-cycloaddition sequence.

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...

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).