Science - USA (2021-11-05)

Stimulated by this challenge, we conceived
an alternative enone-based strategy (Fig. 4B).
Conjugate addition of alkyl nucleophiles to
cyclohexenone substrates, followed by quench-

ing with Comins’reagent, generated the

desired alkenyl triflates in moderate to good

yields ( 32 ). Next, considering theb-steric

hindrance, we postulated that a less bulky

amineelectrophileshouldbebeneficialfor

the C–H amination step. The use of an

azetidine-derived electrophile (R10), which is

expected to be even smaller than dimethylamine,

SCIENCEscience.org 5 NOVEMBER 2021•VOL 374 ISSUE 6568 739

Fig. 5. Synthetic applications.

(A) Synthesis of Diels-Alder

products with inverse regioselec-

tivity was achieved by the regio-

selective ketone 1,2-migration.

TMS, trimethylsilyl. (B) Alkylative

1,2-carbonyl migration was

accomplished by trapping the

enamine intermediate with allyl

bromide. (C) Rapid access to

g-stereocenters was realized

through asymmetric conjugate

addition that was followed by the

carbonyl 1,2-transposition, which

led to a formal enantioselective

synthesis of an antagonist of the

orexin receptor 50. dr, diastereo-

meric ratio; es, enantiomeric

specificity; L, ligand; M, metal.

(D)“C2-oxo”analogs of three

steroids were synthesized

with this method, which shows

substantially improved efficiency

and selectivity. (E) Synthesis

oftrans-decalone 54 was

achieved in a much-shortened

sequence, representing a concise

formal synthesis of pallescensin A.

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